An M1-like macrophage polarization in decidual tissue during spontaneous preterm labor that is attenuated by rosiglitazone treatment1

PubMed Central

Kadam, Leena; Mial, Tara N.; Plazyo, Olesya; Garcia-Flores, Valeria; Hassan, Sonia S.; Xu, Zhonghui; Tarca, Adi L.; Drewlo, Sascha; Gomez-Lopez, Nardhy

2016-01-01

Macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo an M1 polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. Herein, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) M2-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared to term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL12, but low levels of PPARγ, during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1↔M2 polarization in vitro; 6) incubation with rosiglitazone reduces the expression of TNF and IL12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with rosiglitazone reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic pro-inflammatory response in B6 mice and down-regulating mRNA and protein expression of NFκB, TNF, and IL10 in decidual and myometrial macrophages. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor, and that PPARγ activation via rosiglitazone can attenuate the macrophage-mediated pro-inflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth. PMID:26889045

The quality of preterm infants' spontaneous movements: an early indicator of intelligence and behaviour at school age.

PubMed

Butcher, Phillipa R; van Braeckel, Koen; Bouma, Anke; Einspieler, Christa; Stremmelaar, Elisabeth F; Bos, Arend F

2009-08-01

The quality of very preterm infants' spontaneous movements at 11 to 16 weeks post-term age is a powerful predictor of their later neurological status. This study investigated whether early spontaneous movements also have predictive value for the intellectual and behavioural problems that children born very preterm often experience. Spontaneous movement quality was assessed, using Prechtl's method, at 11 to 16 weeks post-term in 65 infants born at

Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor.

PubMed

van Baaren, Gert-Jan; Vis, Jolande Y; Wilms, Femke F; Oudijk, Martijn A; Kwee, Anneke; Porath, Martina M; Oei, Guid; Scheepers, Hubertina C J; Spaanderman, Marc E A; Bloemenkamp, Kitty W M; Haak, Monique C; Bolte, Antoinette C; Bax, Caroline J; Cornette, Jérôme M J; Duvekot, Johannes J; Nij Bijvanck, Bas W A; van Eyck, Jim; Franssen, Maureen T M; Sollie, Krystyna M; Vandenbussche, Frank P H A; Woiski, Mallory; Grobman, William A; van der Post, Joris A M; Bossuyt, Patrick M M; Opmeer, Brent C; Mol, Ben W J

2014-06-01

To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor. We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk. Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk. Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days. II.

Epidemiology and causes of preterm birth.

PubMed

Goldenberg, Robert L; Culhane, Jennifer F; Iams, Jay D; Romero, Roberto

2008-01-05

This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.

Predicting preeclampsia from a history of preterm birth

PubMed Central

Ebbing, Cathrine; Irgens, Lorentz M.

2017-01-01

Objective To assess whether women with a history of preterm birth, independent on the presence of prelabour rupture of the membranes (PROM) and growth deviation of the newborn, are more likely to develop preeclampsia with preterm or preterm birth in a subsequent pregnancy. Methods We conducted a population-based cohort study, based on Medical Birth Registry of Norway between 1967 and 2012, including 742,980 women with singleton pregnancies who were followed up from their 1st to 2nd pregnancy. In the analyses we included 712,511 women after excluding 30,469 women with preeclampsia in the first pregnancy. Results After preterm birth without preeclampsia in the first pregnancy, the risk of preterm preeclampsia in the second pregnancy was 4–7 fold higher than after term birth (odds ratios 3.5; 95% confidence interval (CI) 3.0–4.0 to 6.5; 95% CI 5.1–8.2). The risk of term preeclampsia in the pregnancy following a preterm birth was 2–3 times higher than after term birth (odds ratios 1.6; 95% CI 1.5–1.8 to 2.6; 95% CI 2.0–3.4). After spontaneous non-PROM preterm birth and preterm PROM, the risk of preterm preeclampsia was 3.3–3.6 fold higher than after spontaneous term birth. Corresponding risks of term preeclampsia was 1.6–1.8 fold higher. No significant time trends were found in the effect of spontaneous preterm birth in the first pregnancy on preterm or term preeclampsia in the second pregnancy. Conclusions The results suggest that preterm birth, regardless of the presence of PROM, and preeclampsia share pathophysiologic mechanisms. These mechanisms may cause preterm birth in one pregnancy and preeclampsia in a subsequent pregnancy in the same woman. The association was particularly evident with preterm preeclampsia. PMID:28738075

An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment.

PubMed

Xu, Yi; Romero, Roberto; Miller, Derek; Kadam, Leena; Mial, Tara N; Plazyo, Olesya; Garcia-Flores, Valeria; Hassan, Sonia S; Xu, Zhonghui; Tarca, Adi L; Drewlo, Sascha; Gomez-Lopez, Nardhy

2016-03-15

Decidual macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo a proinflammatory (M1) polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone (RSG) would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. In this study, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) anti-inflammatory (M2)-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared with term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL-12 but low levels of peroxisome proliferator-activated receptor γ (PPARγ) during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1↔M2 polarization in vitro; 6) incubation with RSG reduces the expression of TNF and IL-12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with RSG reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic proinflammatory response and downregulating mRNA and protein expression of NF-κB, TNF, and IL-10 in decidual and myometrial macrophages in C57BL/6J mice. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor and that PPARγ activation via RSG can attenuate the macrophage-mediated proinflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth. Copyright © 2016 by The American Association of Immunologists, Inc.

Sleep duration, vital exhaustion, and odds of spontaneous preterm birth: a case-control study.

PubMed

Kajeepeta, Sandhya; Sanchez, Sixto E; Gelaye, Bizu; Qiu, Chunfang; Barrios, Yasmin V; Enquobahrie, Daniel A; Williams, Michelle A

2014-09-27

Preterm birth is a leading cause of perinatal morbidity and mortality worldwide, resulting in a pressing need to identify risk factors leading to effective interventions. Limited evidence suggests potential relationships between maternal sleep or vital exhaustion and preterm birth, yet the literature is generally inconclusive. We examined the relationship between maternal sleep duration and vital exhaustion in the first six months of pregnancy and spontaneous (non-medically indicated) preterm birth among 479 Peruvian women who delivered a preterm singleton infant (<37 weeks gestation) and 480 term controls who delivered a singleton infant at term (≥37 weeks gestation). Maternal nightly sleep and reports of vital exhaustion were ascertained through in-person interviews. Spontaneous preterm birth cases were further categorized as those following either spontaneous preterm labor or preterm premature rupture of membranes. In addition, cases were categorized as very (<32 weeks), moderate (32-33 weeks), and late (34- <37 weeks) preterm birth for additional analyses. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). After adjusting for confounders, we found that short sleep duration (≤6 hours) was significantly associated with preterm birth (aOR = 1.56; 95% CI 1.11-2.19) compared to 7-8 hours of sleep. Vital exhaustion was also associated with increased odds of preterm birth (aOR = 2.41; 95% CI 1.79-3.23) compared to no exhaustion (Ptrend <0.001). These associations remained significant for spontaneous preterm labor and preterm premature rupture of membranes. We also found evidence of joint effects of sleep duration and vital exhaustion on the odds of spontaneous preterm birth. The results of this case-control study suggest maternal sleep duration, particularly short sleep duration, and vital exhaustion may be risk factors for spontaneous preterm birth. These findings call for increased clinical attention to maternal sleep and the study of potential intervention strategies to improve sleep in early pregnancy with the aim of decreasing risk of preterm birth.

Role of Cervical Length Measurement for Preterm Delivery Prediction in Women With Threatened Preterm Labor and Cervical Dilatation.

PubMed

Hiersch, Liran; Melamed, Nir; Aviram, Amir; Bardin, Ron; Yogev, Yariv; Ashwal, Eran

2016-12-01

To compare the accuracy and cutoff points for cervical length for predicting preterm delivery in women with threatened preterm labor between those with a closed cervix and cervical dilatation. We conducted a retrospective cohort study of women with singleton pregnancies with threatened preterm labor before 34 weeks. The accuracy of cervical length for predicting preterm delivery was compared between women with cervical dilatation (0.5-3 cm) and those with a closed cervix. The predictive accuracy of cervical length for spontaneous preterm delivery was analyzed with several outcome-specific thresholds. Overall, 1068 women with threatened preterm labor met the inclusion criteria; of them, 276 (25.8%) had cervical dilatation, and 792 (74.2%) had a closed cervix. The risk of preterm delivery before 37 weeks was significantly higher in the cervical dilatation group than the closed cervix group, as well as a shorter assessment-to-delivery interval of within 14 days (P = .001 and .004, respectively). On a multivariable analysis, cervical length was independently associated with the risk of preterm delivery in both groups. There was no significant difference between women with cervical dilatation and those with a closed cervix regarding the area under the receiver operating characteristic curves of cervical length for prediction of preterm delivery before 37 (0.674 versus 0.618; P = .18) and 34 (0.628 versus 0.640; P = .88) weeks and an assessment-to-delivery interval of 14 days (0.686 versus 0.660; P= .72). The negative predictive value of cervical length ranged from 77.4% to 95.7% depending on the different thresholds used. Cervical length was significantly associated with the risk of preterm delivery in women presenting with threatened preterm labor and cervical dilatation of less than 3 cm. However, the predictive accuracy of cervical length as a single measure was relatively limited. © 2016 by the American Institute of Ultrasound in Medicine.

Cervical pessary to reduce preterm birth before 34 weeks of gestation after an episode of preterm labor and a short cervix: a randomized controlled trial.

PubMed

Pratcorona, Laia; Goya, Maria; Merced, Carme; Rodó, Carlota; Llurba, Elisa; Higueras, Teresa; Cabero, Luis; Carreras, Elena

2018-04-25

To date, no intervention has proved effective in reducing the spontaneous preterm birth rate in singleton pregnancies following an episode of threatened preterm labor and short cervix remaining. This study was designed to ascertain whether cervical pessaries could be useful in preventing spontaneous preterm birth in women with singleton pregnancies and a short cervix after a threatened preterm labor episode. This open randomized controlled trial was conducted in 357 pregnant women (between 24 0 and 33 6 weeks) who had not delivered 48h after a threatened preterm labor episode and had a short cervix remaining (≤25 mm at 24 0 -29 6 weeks; ≤15mm at 30 0 -33 6 weeks). Patients were randomly assigned to cervical pessary (179) or routine management (178). The primary outcome was the spontaneous preterm birth rate before 34 weeks. Spontaneous preterm birth before 28 and 37 weeks and neonatal morbidity and mortality were also evaluated in an intention-to-treat analysis. No significant differences between the pessary and routine management groups were observed in the spontaneous preterm birth rate before 34 weeks (19/177 [10.7%] in the pessary group vs. 24/175 [13.7%] in the control group; relative risk, 0.78; 95% confidence interval, 0.45-1.38). Spontaneous preterm birth before 37 weeks occurred less frequently in the pessary group (26/175 [14.7%] vs 44/175 [25.1%]; relative risk, 0.58; 95% confidence interval 0.38-0.90; p=0.01). The preterm premature rupture of membranes rate was significantly lower in pessary carriers (4/177 [2.3%] vs. 14/175 [8.0%]; relative risk, 0.28; 95% confidence interval 0.09-0.84; p=0.01). The pessary group less frequently required readmission for new threatened preterm labor episodes (8/177 [4.5%] vs. 35/175 [20.0%]; relative risk, 0.23; 95% confidence interval, 0.11-0.47; p<0.0001. No serious adverse maternal events occurred; neonatal morbidity and mortality were similar in both groups. Pessary use did not significantly lower the spontaneous preterm birth rate before 34 weeks in women with a short cervix remaining after a threatened preterm labor episode but did significantly reduce the spontaneous preterm birth rate before 37 weeks, threatened preterm labor recurrence and the preterm premature rupture of membranes rate. Copyright © 2018 Elsevier Inc. All rights reserved.

Preterm birth time trends in Europe: a study of 19 countries

PubMed Central

Zeitlin, J; Szamotulska, K; Drewniak, N; Mohangoo, AD; Chalmers, J; Sakkeus, L; Irgens, L; Gatt, M; Gissler, M; Blondel, B

2013-01-01

Objective To investigate time trends in preterm birth in Europe by multiplicity, gestational age, and onset of delivery. Design Analysis of aggregate data from routine sources. Setting Nineteen European countries. Population Live births in 1996, 2000, 2004, and 2008. Methods Annual risk ratios of preterm birth in each country were estimated with year as a continuous variable for all births and by subgroup using log-binomial regression models. Main outcome measures Overall preterm birth rate and rate by multiplicity, gestational age group, and spontaneous versus non-spontaneous (induced or prelabour caesarean section) onset of labour. Results Preterm birth rates rose in most countries, but the magnitude of these increases varied. Rises in the multiple birth rate as well as in the preterm birth rate for multiple births contributed to increases in the overall preterm birth rate. About half of countries experienced no change or decreases in the rates of singleton preterm birth. Where preterm birth rates rose, increases were no more prominent at 35–36 weeks of gestation than at 32–34 weeks of gestation. Variable trends were observed for spontaneous and non-spontaneous preterm births in the 13 countries with mode of onset data; increases were not solely attributed to non-spontaneous preterm births. Conclusions There was a wide variation in preterm birth trends in European countries. Many countries maintained or reduced rates of singleton preterm birth over the past 15 years, challenging a widespread belief that rising rates are the norm. Understanding these cross-country differences could inform strategies for the prevention of preterm birth. PMID:23700966

Progesterone to prevent spontaneous preterm birth

PubMed Central

Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

2014-01-01

Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth <33 weeks of gestation, 12 patients with a short cervix would need to be treated. Vaginal progesterone reduces the rate of spontaneous preterm birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

Posttraumatic stress disorder and risk of spontaneous preterm birth.

PubMed

Shaw, Jonathan G; Asch, Steven M; Kimerling, Rachel; Frayne, Susan M; Shaw, Kate A; Phibbs, Ciaran S

2014-12-01

To evaluate the association between antenatal posttraumatic stress disorder (PTSD) and spontaneous preterm delivery. We identified antenatal PTSD status and spontaneous preterm delivery in a retrospective cohort of 16,334 deliveries covered by the Veterans Health Administration from 2000 to 2012. We divided mothers with PTSD into those with diagnoses present the year before delivery (active PTSD) and those only with earlier diagnoses (historical PTSD). We identified spontaneous preterm birth and potential confounders including age, race, military deployment, twins, hypertension, substance use, depression, and results of military sexual trauma screening and then performed multivariate regression to estimate adjusted odds ratio (OR) of spontaneous preterm delivery as a function of PTSD status. Of 16,334 births, 3,049 (19%) were to mothers with PTSD diagnoses, of whom 1,921 (12%) had active PTSD. Spontaneous preterm delivery was higher in those with active PTSD (9.2%, n=176) than those with historical (8.0%, n=90) or no PTSD (7.4%, n=982) before adjustment (P=.02). The association between PTSD and preterm birth persisted, when adjusting for covariates, only in those with active PTSD (adjusted OR 1.35, 95% confidence interval [CI] 1.14-1.61). Analyses adjusting for comorbid psychiatric and medical diagnoses revealed the association with active PTSD to be robust. In this cohort, containing an unprecedented number of PTSD-affected pregnancies, mothers with active PTSD were significantly more likely to suffer spontaneous preterm birth with an attributable two excess preterm births per 100 deliveries (95% CI 1-4). Posttraumatic stress disorder's health effects may extend, through birth outcomes, into the next generation.

Comparative Evaluation of Arabin Pessary and Cervical Cerclage for the Prevention of Preterm Labor in Asymptomatic Women with High Risk Factors

PubMed Central

Tsikouras, Panagiotis; Anastasopoulos, George; Maroulis, Vasileios; Bothou, Anastasia; Chalkidou, Anna; Deuteraiou, Dorelia; Anthoulaki, Xanthoula; Bourazan, Arzou Halil; Iatrakis, George; Zervoudis, Stefanos; Galazios, Georgios; Inagamova, Lola-Katerina; Csorba, Roland; Teichmann, Alexander-Tobias

2018-01-01

Objective: Preterm labor is one of the most significant obstetric problems associated with high rate of actual and long-term perinatal complications. Despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers, the prediction and prevention of preterm labor is still a matter of concern. The aim of this study was to examine cervical findings for the prediction and the comparative use of Arabin pessary or cerclage for the prevention of preterm birth in asymptomatic women with high risk factors for preterm labor. Material and methods: The study group was composed of singleton pregnancies (spontaneously conceived) with high risk factors for preterm labor. Cervical length, dilatation of the internal cervical os and funneling, were estimated with transvaginal ultrasound during the first and the second trimesters of pregnancy. Results: Cervical funneling, during the second trimester of pregnancy, was the most significant factor for the prediction of preterm labor. The use of Arabin cervical pessary was found to be more effective than cerclage in the prolongation of pregnancy. Conclusion: In women at risk for preterm labor, the detection of cervical funneling in the second trimester of pregnancy may help to predict preterm labor and to apply the appropriate treatment for its prevention. Although the use of cervical pessary was found to be more effective than cerclage, more studies are needed to classify the effectiveness of different methods for such prevention. PMID:29670041

Preterm birth time trends in Europe: a study of 19 countries.

PubMed

Zeitlin, J; Szamotulska, K; Drewniak, N; Mohangoo, A D; Chalmers, J; Sakkeus, L; Irgens, L; Gatt, M; Gissler, M; Blondel, B

2013-10-01

To investigate time trends in preterm birth in Europe by multiplicity, gestational age, and onset of delivery. Analysis of aggregate data from routine sources. Nineteen European countries. Live births in 1996, 2000, 2004, and 2008. Annual risk ratios of preterm birth in each country were estimated with year as a continuous variable for all births and by subgroup using log-binomial regression models. Overall preterm birth rate and rate by multiplicity, gestational age group, and spontaneous versus non-spontaneous (induced or prelabour caesarean section) onset of labour. Preterm birth rates rose in most countries, but the magnitude of these increases varied. Rises in the multiple birth rate as well as in the preterm birth rate for multiple births contributed to increases in the overall preterm birth rate. About half of countries experienced no change or decreases in the rates of singleton preterm birth. Where preterm birth rates rose, increases were no more prominent at 35-36 weeks of gestation than at 32-34 weeks of gestation. Variable trends were observed for spontaneous and non-spontaneous preterm births in the 13 countries with mode of onset data; increases were not solely attributed to non-spontaneous preterm births. There was a wide variation in preterm birth trends in European countries. Many countries maintained or reduced rates of singleton preterm birth over the past 15 years, challenging a widespread belief that rising rates are the norm. Understanding these cross-country differences could inform strategies for the prevention of preterm birth. © 2013 The Authors. BJOG: An International Journal of Obstetrics & Gynaecology published by John Wiley and Sons on behalf of the Royal College of Obstetricians and Gynaecologists.

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

PubMed

Visser, Laura; de Boer, Marjon A; de Groot, Christianne J M; Nijman, Tobias A J; Hemels, Marieke A C; Bloemenkamp, Kitty W M; Bosmans, Judith E; Kok, Marjolein; van Laar, Judith O; Sueters, Marieke; Scheepers, Hubertina; van Drongelen, Joris; Franssen, Maureen T M; Sikkema, J Marko; Duvekot, Hans J J; Bekker, Mireille N; van der Post, Joris A M; Naaktgeboren, Christiana; Mol, Ben W J; Oudijk, Martijn A

2017-07-14

Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

Intake of probiotic food and risk of spontaneous preterm delivery123

PubMed Central

Myhre, Ronny; Brantsæter, Anne Lise; Myking, Solveig; Gjessing, Håkon Kristian; Sengpiel, Verena; Meltzer, Helle Margrete; Haugen, Margaretha; Jacobsson, Bo

2011-01-01

Background: Preterm delivery represents a substantial problem in perinatal medicine worldwide. Current knowledge on potential influences of probiotics in food on pregnancy complications caused by microbes is limited. Objective: We hypothesized that intake of food with probiotics might reduce pregnancy complications caused by pathogenic microorganisms and, through this, reduce the risk of spontaneous preterm delivery. Design: This study was performed in the Norwegian Mother and Child Cohort on the basis of answers to a food-frequency questionnaire. We studied intake of milk-based products containing probiotic lactobacilli and spontaneous preterm delivery by using a prospective cohort study design (n = 950 cases and 17,938 controls) for the pregnancy outcome of spontaneous preterm delivery (<37 gestational weeks). Analyses were adjusted for the covariates of parity, maternal educational level, and physical activity. Results: Pregnancies that resulted in spontaneous preterm delivery were associated with any intake of milk-based probiotic products in an adjusted model [odds ratio (OR): 0.857; 95% CI: 0.741, 0.992]. By categorizing intake into none, low, and high intakes of the milk-based probiotic products, a significant association was observed for high intake (OR: 0.820; 95% CI: 0.681, 0.986). Conclusion: Women who reported habitual intake of probiotic dairy products had a reduced risk of spontaneous preterm delivery. PMID:20980489

Umbilical cord CD71+ erythroid cells are reduced in neonates born to women in spontaneous preterm labor.

PubMed

Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; C MacKenzie, Tippi; Frascoli, Michela; Hassan, Sonia S

2016-10-01

Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+CD71+ cells by flow cytometry. (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who underwent spontaneous preterm labor and those born to women who delivered at term with labor. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Relationship between 17-alpha hydroxyprogesterone caproate concentration and spontaneous preterm birth.

PubMed

Caritis, Steve N; Venkataramanan, Raman; Thom, Elizabeth; Harper, Margaret; Klebanoff, Mark A; Sorokin, Yoram; Thorp, John M; Varner, Michael W; Wapner, Ronald J; Iams, Jay D; Carpenter, Marshall W; Grobman, William A; Mercer, Brian M; Sciscione, Anthony; Rouse, Dwight J; Ramin, Susan

2014-02-01

17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation. A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration. There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P = .03) and delivered at significantly earlier gestational ages (P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL. Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage. Copyright © 2014 Mosby, Inc. All rights reserved.

Trends in preterm birth and perinatal mortality among singletons: United States, 1989 through 2000.

PubMed

Ananth, Cande V; Joseph, K S; Oyelese, Yinka; Demissie, Kitaw; Vintzileos, Anthony M

2005-05-01

Despite the recent increase in preterm birth in the United States, trends in preterm birth subtypes have not been adequately examined. We examined trends in preterm birth among singletons following ruptured membranes, medical indications, and spontaneous preterm birth and evaluated the impact of these trends on perinatal mortality. A population-based, retrospective cohort study comprising 46,375,578 women (16% blacks) who delivered singleton births in the United States, 1989 through 2000, was performed. Rates of preterm birth (< 37 weeks), their subtypes, and associated perinatal mortality (stillbirths at >/= 22 weeks plus neonatal deaths within 28 days), before and after adjustment for potential confounders, were derived from ecological logistic regression models. Preterm birth rates increased by 14% (95% confidence interval 13-15%) among whites from 8.3% to 9.4% and decreased by 15% (95% confidence interval 14-16%) among blacks from 18.5% to 16.2% between 1989 and 2000. Among whites, preterm birth following ruptured membranes declined by 23%, medically indicated preterm birth increased by 55%, and spontaneous preterm birth increased by 3%. Among blacks, preterm birth following ruptured membranes declined by 37%, medically indicated preterm birth increased by 32%, and spontaneous preterm birth decreased by 27%. The largest decline in perinatal mortality among whites was associated with increases in medically indicated preterm birth, whereas the largest decline in perinatal mortality among blacks was associated with declines in preterm birth following ruptured membranes and spontaneous preterm birth. Temporal trends in preterm birth varied substantially based on underlying subtype and maternal race. The recent increase in medically indicated preterm birth was associated with a favorable reduction in perinatal mortality.

Early preterm delivery due to placenta previa is an independent risk factor for a subsequent spontaneous preterm birth

PubMed Central

2012-01-01

Background To determine whether patients with placenta previa who delivered preterm have an increased risk for recurrent spontaneous preterm birth. Methods This retrospective population based cohort study included patients who delivered after a primary cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were determined. Results Patients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence [crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS pregnancy was 55.9%; and these patients had a higher rate of recurrent preterm delivery than the rest of the study population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent preterm birth [OR of 3.6 (95% CI 1.5-8.5)]. Conclusions Women with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended. PMID:22876799

Enrichment of clinically relevant organisms in spontaneous preterm delivered placenta and reagent contamination across all clinical groups in a large UK pregnancy cohort.

PubMed

Leon, Lydia J; Doyle, Ronan; Diez-Benavente, Ernest; Clark, Taane G; Klein, Nigel; Stanier, Philip; Moore, Gudrun E

2018-05-18

In this study differences in the placental microbiota of term and preterm deliveries from a large UK pregnancy cohort were studied using 16S targeted amplicon sequencing. The impact of contamination from DNA extraction, PCR reagents, as well as those from delivery itself were also examined. A total of 400 placental samples from 256 singleton pregnancies were analysed and differences investigated between spontaneous preterm, non-spontaneous preterm, and term delivered placenta. DNA from recently delivered placenta was extracted, and screening for bacterial DNA was carried out using targeted sequencing of the 16S rRNA gene on the Illumina MiSeq platform. Sequenced reads were analysed for presence of contaminating operational taxonomic units (OTUs) identified via sequencing of negative extraction and PCR blank samples. Differential abundance and between sample (beta) diversity metrics were then compared. A large proportion of the reads sequenced from the extracted placental samples mapped to OTUs that were also found in negative extractions. Striking differences in the composition of samples were also observed, according to whether the placenta was delivered abdominally or vaginally, providing strong circumstantial evidence for delivery contamination as an important contributor to observed microbial profiles. When OTU and genus level abundances were compared between the groups of interest, a number of organisms were enriched in the spontaneous preterm cohort, including organisms that have been previously associated with adverse pregnancy outcomes, specifically Mycoplasma spp., and Ureaplasma spp.. However, analyses of overall community structure did not reveal convincing evidence for the existence of a reproducible 'preterm placental microbiome'. IMPORTANCE Preterm birth is associated with both psychological and physical disabilities and is the leading cause of infant morbidity and mortality worldwide. Infection is known to be an important cause of spontaneous preterm birth, and recent research has implicated variation in the 'placental microbiome' with preterm birth risk. Consistent with previous studies, the abundance of certain clinically relevant species differed between spontaneous preterm and non-spontaneous preterm or term delivered placenta. These results support the view that a proportion of spontaneous preterm births have an intra-uterine infection component. However, an additional observation from this study was that a substantial proportion of reads sequenced were contaminating reads, rather than DNA from endogenous, clinically relevant species. This observation warrants caution in the interpretation of sequencing output from such low biomass samples as the placenta. Copyright © 2018 Leon et al.

Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.

PubMed

Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

2001-03-31

Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

Prevalence and risk factors related to preterm birth in Brazil.

PubMed

Leal, Maria do Carmo; Esteves-Pereira, Ana Paula; Nakamura-Pereira, Marcos; Torres, Jacqueline Alves; Theme-Filha, Mariza; Domingues, Rosa Maria Soares Madeira; Dias, Marcos Augusto Bastos; Moreira, Maria Elizabeth; Gama, Silvana Granado

2016-10-17

The rate of preterm birth has been increasing worldwide, including in Brazil. This constitutes a significant public health challenge because of the higher levels of morbidity and mortality and long-term health effects associated with preterm birth. This study describes and quantifies factors affecting spontaneous and provider-initiated preterm birth in Brazil. Data are from the 2011-2012 "Birth in Brazil" study, which used a national population-based sample of 23,940 women. We analyzed the variables following a three-level hierarchical methodology. For each level, we performed non-conditional multiple logistic regression for both spontaneous and provider-initiated preterm birth. The rate of preterm birth was 11.5 %, (95 % confidence 10.3 % to 12.9 %) 60.7 % spontaneous - with spontaneous onset of labor or premature preterm rupture of membranes - and 39.3 % provider-initiated, with more than 90 % of the last group being pre-labor cesarean deliveries. Socio-demographic factors associated with spontaneous preterm birth were adolescent pregnancy, low total years of schooling, and inadequate prenatal care. Other risk factors were previous preterm birth (OR 3.74; 95 % CI 2.92-4.79), multiple pregnancy (OR 16.42; 95 % CI 10.56-25.53), abruptio placentae (OR 2.38; 95 % CI 1.27-4.47) and infections (OR 4.89; 95 % CI 1.72-13.88). In contrast, provider-initiated preterm birth was associated with private childbirth healthcare (OR 1.47; 95 % CI 1.09-1.97), advanced-age pregnancy (OR 1.27; 95 % CI 1.01-1.59), two or more prior cesarean deliveries (OR 1.64; 95 % CI 1.19-2.26), multiple pregnancy (OR 20.29; 95 % CI 12.58-32.72) and any maternal or fetal pathology (OR 6.84; 95 % CI 5.56-8.42). The high proportion of provider-initiated preterm birth and its association with prior cesarean deliveries and all of the studied maternal/fetal pathologies suggest that a reduction of this type of prematurity may be possible. The association of spontaneous preterm birth with socially-disadvantaged groups reaffirms that the reduction of social and health inequalities should continue to be a national priority.

Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days.

PubMed

Hermans, Frederik J R; Bruijn, Merel M C; Vis, Jolande Y; Wilms, Femke F; Oudijk, Martijn A; Porath, Martina M; Scheepers, Hubertina C J; Bloemenkamp, Kitty W M; Bax, Caroline J; Cornette, Jérôme M J; Nij Bijvanck, Bas W A; Franssen, Maureen T M; Vandenbussche, Frank P H A; Kok, Marjolein; Grobman, William A; Van Der Post, Joris A M; Bossuyt, Patrick M M; Opmeer, Brent C; Mol, Ben Willem J; Schuit, Ewoud; Van Baaren, Gert-Jan

2015-07-01

To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days. Prospective observational study. Nationwide cohort of women with threatened preterm labor from the Netherlands. Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission. Kaplan-Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery. Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks. The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL ≥15 to <30 mm and a positive fFN, compared with women with a CL ≥30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL ≥15 to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR 3.0 (95% CI 1.2-7.1)] compared with women with a CL ≥ 30 mm. In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Obstetric History and Likelihood of Preterm Birth of Twins.

PubMed

Easter, Sarah Rae; Little, Sarah E; Robinson, Julian N; Mendez-Figueroa, Hector; Chauhan, Suneet P

2018-01-05

 The objective of this study was to investigate the relationship between preterm birth in a prior pregnancy and preterm birth in a twin pregnancy.  We performed a secondary analysis of a randomized controlled trial evaluating 17-α-hydroxyprogesterone caproate in twins. Women were classified as nulliparous, multiparous with a prior term birth, or multiparous with a prior preterm birth. We used logistic regression to examine the odds of spontaneous preterm birth of twins before 35 weeks according to past obstetric history.  Of the 653 women analyzed, 294 were nulliparas, 310 had a prior term birth, and 49 had a prior preterm birth. Prior preterm birth increased the likelihood of spontaneous delivery before 35 weeks (adjusted odds ratio [aOR]: 2.44, 95% confidence interval [CI]: 1.28-4.66), whereas prior term delivery decreased these odds (aOR: 0.55, 95% CI: 0.38-0.78) in the current twin pregnancy compared with the nulliparous reference group. This translated into a lower odds of composite neonatal morbidity (aOR: 0.38, 95% CI: 0.27-0.53) for women with a prior term delivery.  For women carrying twins, a history of preterm birth increases the odds of spontaneous preterm birth, whereas a prior term birth decreases odds of spontaneous preterm birth and neonatal morbidity for the current twin pregnancy. These results offer risk stratification and reassurance for clinicians. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth.

PubMed

D'Silva, Arlene M; Hyett, Jon A; Coorssen, Jens R

2018-04-30

Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder. Identifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare preterm (<37 weeks) and preterm (≥37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a clinical setting as well as for future investigation of underlying aetiological processes. Copyright © 2018 Elsevier B.V. All rights reserved.

The impact of low-dose aspirin on preterm birth: secondary analysis of a randomized controlled trial.

PubMed

Allshouse, A A; Jessel, R H; Heyborne, K D

2016-06-01

The objective of this study is to determine whether low-dose aspirin (LDA) reduced the rate of preterm birth (PTB) in a cohort of women at high risk for preeclampsia. Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin trial. Preterm births were categorized by phenotype: indicated, spontaneous or due to preterm premature rupture of membranes (PPROMs). Of 1789 randomized women, 30.5% delivered before 37 weeks (18.5% indicated, 5.8% spontaneous and 6.2% following preterm PPROMs). Among women randomized to LDA, we observed a trend favoring fewer PTBs due to spontaneous preterm labor and preterm PPROMs, odds ratio (OR: 0.826 (0.620, 1.099)); the incidence of indicated PTBs appeared unchanged, OR: 0.999 (0.787, 1.268). Although not reaching significance, we observed an effect size similar to other studies of both low- and high-risk women. These results support findings from other studies assessing LDA as a PTB prevention strategy.

Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor.

PubMed

Ambühl, Lea M M; Leonhard, Anne K; Widen Zakhary, Carina; Jørgensen, Annemette; Blaakaer, Jan; Dybkaer, Karen; Baandrup, Ulrik; Uldbjerg, Niels; Sørensen, Suzette

2017-10-01

Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

PubMed Central

Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen; Blaakær, Jan; Uldbjerg, Niels; Sørensen, Suzette

2016-01-01

Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3–17.7) for cervix, 8.3% (95% CI; 7.6–9.1) for placental tissue, 5.7% (95% CI; 5.1–6.3) for amniotic fluid, and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding. PMID:27110088

Trends in preterm birth: singleton and multiple pregnancies in the Netherlands, 2000-2007.

PubMed

Schaaf, J M; Mol, B W J; Abu-Hanna, A; Ravelli, A C J

2011-09-01

Several studies have reported increasing trends in preterm birth in developed countries, mainly attributable to an increase in medically indicated preterm births. Our aim was to describe trends in preterm birth among singleton and multiple pregnancies in the Netherlands. Prospective cohort study. Nationwide study. We studied 1,451,246 pregnant women from 2000 to 2007. We assessed trends in preterm birth. We subdivided preterm birth into spontaneous preterm birth after premature prelabour rupture of membranes (pPROM), medically indicated preterm birth and spontaneous preterm birth without pPROM. We performed analyses separately for singletons and multiples. The primary outcome was preterm birth, defined as birth before 37 weeks of gestation, with very preterm birth (<32 weeks of gestation) being a secondary outcome. The risk of preterm birth was 7.7% and the risk of very preterm birth was 1.3%. In singleton pregnancies, the preterm birth risk decreased significantly from 6.4% to 6.0% (P < 0.0001), mainly as a result of the decrease in spontaneous preterm birth without pPROM (3.6-3.1%, P < 0.0001). In multiple pregnancies, the preterm birth risk increased significantly (47.3-47.7%, P = 0.047), mainly as a result of medically indicated preterm birth, which increased from 15.0% to 17.9% (P < 0.0001). In the Netherlands, the preterm birth risk in singleton pregnancies decreased significantly over the years. The trend of increasing preterm birth risk reported in other countries was only observed in (medically indicated) preterm birth in multiple pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Transvaginal cervical length and tobacco use in Appalachian women: association with increased risk for spontaneous preterm birth.

PubMed

Findley, Joseph; Seybold, Dara J; Broce, Mike; Yadav, Dolly; Calhoun, Byron C

2015-01-01

Currently ACOG recommends that a mid-term screening strategy may be considered to identify short cervix in low risk populations in an effort to prevent preterm birth. Vaginal progesterone is recommended for women with a cervical length ≤20 mm. Cerclage is recommended for women with prior spontaneous preterm birth who are already receiving progesterone supplementition and CL is <25 mm. This study examined risk factors for spontaneous preterm birth (SPB) <35 weeks among a general obstetrical population prior to these ACOG recommendations. However, cervical cerclage was a possible intervention. Study population included 1,074 patients from 1 Jan 2007-30 Jun 2008 receiving mid-trimester transvaginal ultrasounds during prenatal care at a tertiary medical center clinic. Receiver operator characteristic (ROC) curve cutoff optimal value was ≤34 mm, (n=224), corresponding to 8.9% SPB with shortened cervices compared to 1.4% in patients with normal cervices (>34 mm; n=850; p<0.001 (Area Under the Curve (AUC) 76.6, p<0.001). Cervical lengths <30 mm had 12 times the risk of SPB (p<0.001) while 30-34 mm had 5 times (p=0.005). Tobacco use (≥10 cigarettes per day), p=0.030, and low BMI, p=0.034, had additive effect. Shortened cervical length during routine screening independently predicted SPB while heavy smoking with shortened cervix during pregnancy doubled risk compared to shortened cervix alone.

Transvaginal Cervical Length and Tobacco Use in Appalachian Women: Association with Increased Risk for Spontaneous Preterm Birth

PubMed Central

Findley, Joseph; Seybold, Dara J.; Broce, Mike; Yadav, Dolly; Calhoun, Byron C.

2015-01-01

Currently ACOG recommends that a mid-term screening strategy may be considered to identify short cervix in low risk populations in an effort to prevent preterm birth. Vaginal progesterone is recommended for women with a cervical length ≤20 mm. Cerclage is recommended for women with prior spontaneous preterm birth who are already receiving progesterone supplementation and CL is <25 mm. This study examined risk factors for spontaneous preterm birth (SPB) <35 weeks among a general obstetrical population prior to these ACOG recommendations. However, cervical cerclage was a possible intervention. Study population included 1,074 patients from 1 Jan 2007-30 Jun 2008 receiving mid-trimester transvaginal ultrasounds during prenatal care at a tertiary medical center clinic. Receiver operator characteristic (ROC) curve cutoff optimal value was ≤34 mm, (n=224), corresponding to 8.9% SPB with shortened cervices compared to 1.4% in patients with normal cervices (>34 mm; n=850; p<0.001 (Area Under the Curve (AUC) 76.6, p<0.001). Cervical lengths <30 mm had 12 times the risk of SPB (p<0.001) while 30-34 mm had 5 times (p=0.005). Tobacco use (≥10 cigarettes per day), p=0.030, and low BMI, p=0.034, had additive effect. Shortened cervical length during routine screening independently predicted SPB while heavy smoking with shortened cervix during pregnancy doubled risk compared to shortened cervix alone. PMID:26050294

Spontaneous movements of preterm infants is associated with outcome of gross motor development.

PubMed

Miyagishima, Saori; Asaka, Tadayoshi; Kamatsuka, Kaori; Kozuka, Naoki; Kobayashi, Masaki; Igarashi, Lisa; Hori, Tsukasa; Tsutsumi, Hiroyuki

2018-04-30

We conducted a longitudinal cohort study to analyze the relationship between outcome of gross motor development in preterm infants and factors that might affect their development. Preterm infants with a birth weight of <1500 g were recruited. We measured spontaneous antigravity limbs movements by 3D motion capture system at 3 months corrected age. Gross motor developmental outcomes at 6 and 12 months corrected age were evaluated using the Alberta Infant Motor Scale (AIMS). Statistical analysis was carried out by canonical correlation analysis. Eighteen preterm infants were included. In the 6 months corrected age analysis, spontaneous movement had a major effect on Prone and Sitting at 6 months corrected age of AIMS. In the 12 months corrected age analysis, spontaneous movement had a major effect on Sitting and Standing at 12 months corrected age of AIMS. In preterm infants, better antigravity spontaneous movements at 3 months corrected age were significantly correlated with better gross motor development at 6 or 12 months corrected age. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Maternal Vitamin D Insufficiency Early in Pregnancy Is Associated with Increased Risk of Preterm Birth in Ethnic Minority Women in Canada.

PubMed

Tabatabaei, Negar; Auger, Nathalie; Herba, Catherine M; Wei, Shuqin; Allard, Catherine; Fink, Guy D; Fraser, William D

2017-06-01

Background: Maternal vitamin D insufficiency (plasma 25-hydroxyvitamin D [25(OH)D] <75 nmol/L) may play a role in ethnic disparities in rates of preterm and spontaneous preterm births. Objective: We explored the relation between maternal plasma 25(OH)D concentration in the first trimester (8-14 wk of gestation) and the risk of preterm and spontaneous preterm births (<37 wk of gestation) by ethnicity. Methods: We designed a case-control study that included 120 cases of preterm birth (<37 wk of gestation) and 360 term controls (≥37 wk of gestation) of singleton pregnancies from the 3D cohort, a multicenter study in 2456 pregnant women in Quebec, Canada. Plasma 25(OH)D was measured by LC-mass spectrometry. We compared the distribution of vitamin D status between cases and controls for 8 ethnic minority subgroups. We explored the association between maternal plasma 25(OH)D concentration and preterm and spontaneous preterm births with the use of splines in logistic regression by ethnicity. Results: The distributions of maternal vitamin D status (<50, 50-75, and >75 nmol/L) were different in preterm and spontaneous preterm birth cases compared with controls but only in women of ethnic minority ( P- trend = 0.003 and 0.024, respectively). Among ethnic subgroups, sub-Saharan Africans ( P -trend = 0.030) and Arab-West Asians ( P -trend = 0.045) showed an inverse relation between maternal vitamin D status and the risk of preterm birth. Maternal plasma 25(OH)D concentrations of 30 nmol/L were associated with 4.05 times the risk of preterm birth in the total ethnic minority population (95% CI: 1.16, 14.12; P = 0.028) relative to participants with a concentration of 75 nmol/L. In contrast, there was no such association among nonethnic women (OR: 0.94; 95% CI: 0.48, 1.82; P = 0.85). There was no association when we considered only spontaneous preterm births in the total ethnic minority population (OR: 1.75; 95% CI: 0.39, 7.79; P = 0.46). Conclusion: Vitamin D insufficiency is associated with an increased risk of preterm birth in ethnic minority women in Canada. © 2017 American Society for Nutrition.

The value of oral micronized progesterone in the prevention of recurrent spontaneous preterm birth: a randomized controlled trial.

PubMed

Ashoush, Sherif; El-Kady, Osama; Al-Hawwary, Gehan; Othman, Ahmed

2017-12-01

Progesterone is becoming universally accepted for preventing recurrent spontaneous preterm delivery. There is, however, poor consensus on the effective types and doses of progesterone to be used. Despite the encouraging available research, the role of oral micronized progesterone has not yet been thoroughly investigated. We randomized 212 singleton pregnancies with past history of spontaneous preterm delivery at <37 weeks, into a progesterone group (receiving 100 mg oral micronized progesterone, six-hourly, starting at 14-18 weeks until 37 weeks or delivery) and an identical placebo group. The rate of spontaneous preterm delivery was the primary outcome. Secondary outcomes included gestational age at birth and admission to neonatal intensive care units. The progesterone group delivered at a later gestational age, and needed longer tocolysis-to-delivery intervals (35.4 weeks vs. 33.9 weeks, p = 0.01, and 87 days vs. 36 days, p < 0.001, respectively). The relative risk of spontaneous preterm delivery was 0.7 (95% confidence interval 0.54-0.92, p = 0.01), and the number needed-to-treat to prevent one case of spontaneous preterm delivery was 5 (95% confidence interval 3-20). The two groups had similar rates of operative delivery and postpartum complications. Progesterone was associated with mild maternal dizziness (29.1% vs. 9.8%, p = 0.002), somnolence (41.6% vs. 19.7%, p = 0.002), and vaginal dryness (20.8% vs. 8.7%, p = 0.03), lower neonatal mortality rates (7.3% vs. 25.2%, p < 0.001), and shorter neonatal intensive care unit admissions (p = 0.008). Oral micronized progesterone is effective in preventing spontaneous preterm delivery. The additional advantages of oral administration, affordability, and high safety profile make it worth recommending, at least for further research. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Multivariate adaptive regression splines analysis to predict biomarkers of spontaneous preterm birth.

PubMed

Menon, Ramkumar; Bhat, Geeta; Saade, George R; Spratt, Heidi

2014-04-01

To develop classification models of demographic/clinical factors and biomarker data from spontaneous preterm birth in African Americans and Caucasians. Secondary analysis of biomarker data using multivariate adaptive regression splines (MARS), a supervised machine learning algorithm method. Analysis of data on 36 biomarkers from 191 women was reduced by MARS to develop predictive models for preterm birth in African Americans and Caucasians. Maternal plasma, cord plasma collected at admission for preterm or term labor and amniotic fluid at delivery. Data were partitioned into training and testing sets. Variable importance, a relative indicator (0-100%) and area under the receiver operating characteristic curve (AUC) characterized results. Multivariate adaptive regression splines generated models for combined and racially stratified biomarker data. Clinical and demographic data did not contribute to the model. Racial stratification of data produced distinct models in all three compartments. In African Americans maternal plasma samples IL-1RA, TNF-α, angiopoietin 2, TNFRI, IL-5, MIP1α, IL-1β and TGF-α modeled preterm birth (AUC train: 0.98, AUC test: 0.86). In Caucasians TNFR1, ICAM-1 and IL-1RA contributed to the model (AUC train: 0.84, AUC test: 0.68). African Americans cord plasma samples produced IL-12P70, IL-8 (AUC train: 0.82, AUC test: 0.66). Cord plasma in Caucasians modeled IGFII, PDGFBB, TGF-β1 , IL-12P70, and TIMP1 (AUC train: 0.99, AUC test: 0.82). Amniotic fluid in African Americans modeled FasL, TNFRII, RANTES, KGF, IGFI (AUC train: 0.95, AUC test: 0.89) and in Caucasians, TNF-α, MCP3, TGF-β3 , TNFR1 and angiopoietin 2 (AUC train: 0.94 AUC test: 0.79). Multivariate adaptive regression splines models multiple biomarkers associated with preterm birth and demonstrated racial disparity. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Has publication of the results of the ORACLE Children Study changed practice in the UK?

PubMed

Kenyon, S; Pike, K; Jones, D; Brocklehurst, P; Marlow, N; Salt, A; Taylor, D

2010-10-01

  To investigate whether publication of the results of the ORACLE Children's Study, a 7-year follow-up of the ORACLE trial, changed practice with regard to the routine prescription of antibiotics to women with preterm rupture of membranes or spontaneous preterm labour (intact membranes).   A comparative questionnaire survey of clinical practice in November 2007 (before publication) and March 2009 (after publication).   Lead obstetricians for labour wards of all maternity units in the UK.   Self-administered questionnaires requested information about the routine prescription of antibiotics to women with either preterm rupture of membranes or spontaneous preterm labour (intact membranes).   Change in practice for prescription of antibiotics.   The response rate was 166/214 (78%) in 2007 and 158/209 (76%) in 2009. In total, 120 maternity units responded on both occasions. For women with preterm rupture of membranes, 162/214 (98%) in 2007 and 151/158 (96%) in 2009 maternity units reported that they prescribed antibiotics, with the majority using erythromycin (98%). For women with spontaneous preterm labour (intact membranes), 35/166 (21%) in 2007 and 25/158 (16%) in 2009 maternity units reported that they routinely prescribed antibiotics. The findings from units who responded on both occasions are similar.   There has been little change in the reported prescription of antibiotics to women with either preterm rupture of membranes or spontaneous preterm labour following publication of the ORACLE Children's Study. This suggests that current practice may require updated guidance.

Activation of the Alternative Pathway of Complement is a Feature of Preterm Parturition but Not of Spontaneous Labor at Term

PubMed Central

Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Soto, Eleazar; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Ogge, Giovanna; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.

2012-01-01

Problem Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous preterm delivery <34 weeks of gestation. The study aim was to determine whether spontaneous preterm labor with intact membranes (PTL), intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. Method of Study This cross-sectional study included women in the following groups: 1) non-pregnant (n=40); 2) normal pregnancy (gestational age range 20-36 6/7 weeks, n=63); 2) women at term not in labor (n=70); 3) women at term in spontaneous labor (n=59); 4) patients with an episode of PTL who delivered at term (n=62); 5) PTL without IAI who delivered preterm (n=30); and 6) PTL with IAI who delivered preterm (n=67). Maternal plasma FBb concentrations were determined by ELISA. Results 1) Among patients with PTL, those who had a preterm delivery either with IAI (1.21 μg/ml, IQR 0.77-2.16) or without IAI (1.13 μg/ml, IQR 0.92-2.08;) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 μg/ml, IQR 0.64-1.57; p=0.007 and p=0.026, respectively); 2) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered preterm (p=0.9); 3) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (p=0.8); 4) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls (p=0.8) and were not correlated with advancing gestational age (r −0.28, p=0.8). Conclusions 1) Preterm parturition is associated with activation of the alternative complement pathway in maternal circulation; 2) such activation is not detectable in spontaneous labor at term; 3) intra-amniotic infection/inflammation does not explain the activation of the alternative pathway of complement in preterm labor. Collectively, these observations suggest that preterm and term labor have fundamental differences in the regulation of innate immunity. PMID:20163401

[Relation Between Stress During Pregnancy and Spontaneous Preterm Birth].

PubMed

Ortiz Martínez, Roberth Alirio; Castillo, Alejandro

2016-01-01

Preterm birth occurs before 37 completed weeks, its causes are multifactorial and vary according to the gestational age, ethnicity and geographical context. Although several medical/social factors have been clearly identified, over 50% of cases are unknown or unclear; however, psychopathological components emerge as potentially important risk factors. To determine the relationship between the presence of stress during pregnancy and spontaneous preterm birth. Through a study of cases and controls in a level III hospital, with a sample of 360 patients during the period from March to November of 2013, where sociodemographic characteristics were collected. In addition, they were applied scales social adjustment, coping strategies and social support. Logistic regression models were developed; psychological, biological and social. Based on the significant variables in each of these generated a final one. The final model was found that stress during pregnancy increases the odds of spontaneous preterm birth 1.91 times (adjusted OR=2.91; 95%CI, 1.67-5.08; P<.05). Other significant variables were: history of preterm delivery, unplanned pregnancy, no emotional support, rural residence, inadequate prenatal care and non-stable partner. The findings support the hypothesis that stress during pregnancy is associated with spontaneous preterm delivery. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Biological determinants of spontaneous late preterm and early term birth: a retrospective cohort study.

PubMed

Brown, H K; Speechley, K N; Macnab, J; Natale, R; Campbell, M K

2015-03-01

Our aim was to examine the association between biological determinants of preterm birth (infection and inflammation, placental ischaemia and other hypoxia, diabetes mellitus, other) and spontaneous late preterm (34-36 weeks) and early term (37-38 weeks) birth. Retrospective cohort study. City of London and Middlesex County, Canada. Singleton live births, delivered at 34-41 weeks to London-Middlesex mothers following spontaneous labour. Data were obtained from a city-wide perinatal database on births between 2002 and 2011 (n = 17,678). Multivariable analyses used multinomial logistic regression. The outcome of interest was the occurrence of late preterm (34-36 weeks) and early term (37-38 weeks) birth, compared with full term birth (39-41 weeks). After controlling for covariates, there were associations between infection and inflammation and late preterm birth (aOR = 2.07, 95% CI 1.65, 2.60); between placental ischaemia and other hypoxia and late preterm (aOR = 2.21, 95% CI 1.88, 2.61) and early term (aOR = 1.25, 95% CI 1.13, 1.39) birth; between diabetes mellitus and late preterm (aOR = 3.89, 95% CI 2.90, 5.21) and early term (aOR = 2.66, 95% CI 2.19, 3.23) birth; and between other biological determinants (polyhydramnios, oligohydramnios) and late preterm (aOR = 2.81, 95% CI 1.70, 4.64) and early term (aOR = 1.89, 95% CI 1.32, 2.70) birth. Our findings show that delivery following spontaneous labour even close to full term may be a result of pathological processes. Because these biological determinants of preterm birth contribute to an adverse intrauterine environment, they have important implications for fetal and neonatal health. © 2014 Royal College of Obstetricians and Gynaecologists.

Prepregnancy Depressive Symptoms and Preterm Birth in the Black Women’s Health Study

PubMed Central

Phillips, Ghasi S.; Wise, Lauren A.; Rich-Edwards, Janet W.; Stampfer, Meir J.; Rosenberg, Lynn

2009-01-01

PURPOSE To examine the association between prepregnancy depressive symptoms and preterm birth. METHODS The present study is a prospective investigation of prepregnancy depressive symptoms—measured by the Center for Epidemiologic Studies Depression Scale (CES-D)—and risk of preterm birth reported in the Black Women’s Health Study. With data on 2,627 singleton births (175 spontaneous and 163 medically-indicated preterm births and 2,289 term births), we used generalized estimating equation models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for potential confounders. RESULTS Relative to mothers with CES-D scores <16, the multivariable ORs of spontaneous preterm birth for mothers with CES-D scores of 16-22, 23-32, and ≥33 were 1.17 (95% CI=0.78-1.80), 1.20 (95% CI=0.69-2.10), and 2.00 (95% CI=0.94-4.25), respectively (P-trend=0.09). There was little evidence of an association between prepregnancy depressive symptoms and medically-indicated preterm birth. CONCLUSIONS Our data provide some evidence of an increased risk of spontaneous preterm birth among women with high prepregnancy depressive symptoms. PMID:20006271

Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety

PubMed Central

How, Helen Y; Sibai, Baha M

2009-01-01

Preterm birth is the leading cause of neonatal mortality and morbidity and long-term disability of non-anomalous infants. Previous studies have identified a prior early spontaneous preterm birth as the risk factor with the highest predictive value for recurrence. Two recent double blind randomized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate (IM 17OHP-C) or intravaginal micronized progesterone suppositories in women at risk for preterm delivery. However, it is still unclear which high-risk women would truly benefit from this treatment in a general clinical setting and whether socio-cultural, racial and genetic differences play a role in patient’s response to supplemental progesterone. In addition the patient’s acceptance of such recommendation is also in question. More research is still required on identification of at risk group, the optimal gestational age at initiation, mode of administration, dose of progesterone and long-term safety. PMID:19436604

[Bacterial vaginosis and spontaneous preterm birth].

PubMed

Brabant, G

2016-12-01

To determine if bacterial vaginosis is a marker for risk of spontaneous preterm delivery and if its detection and treatment can reduce this risk. Consultation of the database Pubmed/Medline, Science Direct, and international guidelines of medical societies. Bacterial vaginosis (BV) is a dysbiosis resulting in an imbalance in the vaginal flora through the multiplication of anaerobic bacteria and jointly of a disappearance of well-known protective Lactobacilli. His diagnosis is based on clinical Amsel criteria and/or a Gram stain with establishment of the Nugent score. The prevalence of the BV extraordinarily varies according to ethnic and/or geographical origin (4-58 %), in France, it is close to 7 % in the first trimester of pregnancy (EL2). The link between BV and spontaneous premature delivery is low with an odds ratio between 1.5 and 2 in the most recent studies (EL3). Metronidazole or clindamycin is effective to treat BV (EL3). It is recommended to prescribe one of these antibiotics in the case of symptomatic BV (Professional Consensus). The testing associated with the treatment of BV in the global population showed no benefit in the prevention of the risk of spontaneous preterm delivery (EL2). Concerning low-risk asymptomatic population (defined by the absence of antecedent of premature delivery), it has been failed profit to track and treat the BV in the prevention of the risk of spontaneous preterm delivery (EL1). Concerning the high-risk population (defined by a history of preterm delivery), it has been failed profit to track and treat the VB in the prevention of the risk of spontaneous preterm delivery (EL3). However, in the sub population of patients with a history of preterm delivery occurred in a context of materno-fetal bacterial infection, there may be a benefit to detect and treat early and systematically genital infection, and in particular the BV (Professional Consensus). The screening and treatment of BV during pregnancy in asymptomatic low-risk population is not recommended in the prevention of the risk of spontaneous preterm delivery (grade A). In the population at high risk with the only notion of antecedent of premature delivery, screening and treatment of the BV is not recommended (grade C). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Longitudinal profiling of inflammatory cytokines and C-reactive protein during uncomplicated and preterm pregnancy.

PubMed

Ferguson, Kelly K; McElrath, Thomas F; Chen, Yin-Hsiu; Mukherjee, Bhramar; Meeker, John D

2014-09-01

Previous studies have investigated the utility of inflammation markers as predictors of preterm birth, but none have compared trends in levels between uncomplicated and preterm pregnancy. We explored longitudinal changes in plasma cytokines, including IL-1β, IL-6, IL-10, and TNF-α, as well as C-reactive protein in pregnant women from a nested case-control study. IL-6 was associated with increased odds of spontaneous preterm birth, defined by presentation of spontaneous preterm labor and/or preterm premature rupture of the membranes. Associations were strongest later in pregnancy. IL-10 was associated with increased odds of placentally mediated preterm birth, defined by presentation with preeclampsia or intrauterine growth restriction, and odds ratios were also highest near the end of pregnancy. Maternal inflammation markers were associated with increased risk of preterm birth, and relationships differed by etiology of preterm delivery and gestational age at sample collection. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Trends in provider-initiated versus spontaneous preterm deliveries, 2004–2013

PubMed Central

Ada, Melissa L.; Hacker, Michele R.; Golen, Toni H.; Haviland, Miriam J.; Shainker, Scott A.; Burris, Heather H.

2017-01-01

Objectives 1) To estimate the proportion of preterm deliveries at a tertiary perinatal center that were provider-initiated vs. spontaneous before and after a 2009 policy to reduce elective early-term deliveries. 2) To evaluate if shifts in type of preterm delivery varied by race/ethnicity. Methods We performed a retrospective cohort study of preterm deliveries over a 10-year period, 2004–2013, including detailed review of 929 of 5,566 preterm deliveries to designate each delivery as provider-initiated or spontaneous. We dichotomized the time period into early (2004–2009) and late (2010–2013). We used log-binomial regression to calculate adjusted risk ratios. Results Of the 46,981 deliveries, 5,566 (11.8%) were preterm, with a significant reduction in the overall incidence of preterm delivery from 12.3% to 11.2% (P=0.0003). Among the 929 preterm deliveries analyzed, there was a reduction in the proportion of provider-initiated deliveries from 48.3% to 41.8% that was not statistically significant. The proportion of provider-initiated preterm deliveries among black, but not white, women declined from 50.8% to 39.7% (adjusted RR: 0.66; 95%CI: 0.45–0.97). This coincided with a larger reduction in overall preterm deliveries among black women (16.2% to 12.8%) vs. white women (12.3% to 11.2%) (P interaction=0.038). By 2013, the incidence of preterm deliveries had decreased for both black (12.1%) and white women (11.4%) and the difference was no longer statistically significant (P=0.7). Conclusion We found a reduction in preterm deliveries after a policy targeted at reducing elective early-term deliveries in 2009 that coincided with reductions in the proportion of provider-initiated preterm deliveries, especially among black women. PMID:28749488

Combination antiretroviral use and preterm birth.

PubMed

Watts, D Heather; Williams, Paige L; Kacanek, Deborah; Griner, Raymond; Rich, Kenneth; Hazra, Rohan; Mofenson, Lynne M; Mendez, Hermann A

2013-02-15

Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)-exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.

Associations of neighborhood-level racial residential segregation with adverse pregnancy outcomes.

PubMed

Salow, Arturo D; Pool, Lindsay R; Grobman, William A; Kershaw, Kiarri N

2018-03-01

Previous analyses utilizing birth certificate data have shown environmental factors such as racial residential segregation may contribute to disparities in adverse pregnancy outcomes. However, birth certificate data are ill equipped to reliably differentiate among small for gestational age, spontaneous preterm birth, and medically indicated preterm birth. We sought to utilize data from electronic medical records to determine whether residential segregation among Black women is associated with an increased risk of adverse pregnancy outcomes. The study population was composed of 4770 non-Hispanic Black women who delivered during the years 2009 through 2013 at a single urban medical center. Addresses were geocoded at the level of census tract, and this tract was used to determine the degree of residential segregation for an individual's neighborhood. Residential segregation was measured using the Gi* statistic, a z-score that measures the extent to which the neighborhood racial composition deviates from the composition of the larger surrounding area. The Gi* statistic z-scores were categorized as follows: low (z < 0), medium (z = 0-1.96), and high (z > 1.96). Adverse pregnancy outcomes included overall preterm birth, spontaneous preterm birth, medically indicated preterm birth, and small for gestational age. Hierarchical logistic regression models accounting for clustering by census tract and repeated births among mothers were used to estimate odds ratios of adverse pregnancy outcomes associated with segregation. In high segregation areas, the prevalence of overall preterm birth was significantly higher than that in low segregation areas (15.5% vs 10.7%, respectively; P < .001). Likewise, the prevalence of spontaneous preterm birth and medically indicated preterm birth were higher in high (9.5% and 6.0%) vs low (6.2% and 4.6%) segregation neighborhoods (P < .001 and P = .046, respectively). The associations of high segregation with overall preterm birth (odds ratio, 1.31; 95% confidence interval, 1.02-1.69) and spontaneous preterm birth (odds ratio, 1.37; 95% confidence interval, 1.02-1.85) remained significant with adjustment for neighborhood poverty, insurance status, parity, and maternal medical conditions. Among non-Hispanic Black women in an urban area, high levels of segregation were independently associated with the higher odds of spontaneous preterm birth. These findings highlight one aspect of social determinants (ie, segregation) through which adverse pregnancy outcomes may be influenced and points to a potential target for intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Spontaneous prematurity in fetuses with congenital diaphragmatic hernia: a retrospective cohort study about prenatal predictive factors.

PubMed

Barbosa, Bruna Maria Lopes; Rodrigues, Agatha S; Carvalho, Mario Henrique Burlacchini; Bittar, Roberto Eduardo; Francisco, Rossana Pulcineli Vieira; Bernardes, Lisandra Stein

2018-01-12

To evaluate possible predictive factors of spontaneous prematurity in fetuses with congenital diaphragmatic hernia (CDH). A retrospective cohort study was performed. Inclusion criteria were presence of CDH; absence of fetoscopy; absence of karyotype abnormality; maximum of one major malformation associated with diaphragmatic hernia; ultrasound monitoring at the Obstetrics Clinic of Clinicas Hospital at the University of São Paulo School of Medicine, from January 2001 to October 2014. The data were obtained through the electronic records and ultrasound system of our fetal medicine service. The following variables were analyzed: maternal age, primiparity, associated maternal diseases, smoking, previous spontaneous preterm birth, fetal malformation associated with hernia, polyhydramnios, fetal growth restriction, presence of intrathoracic liver, invasive procedures performed, side of hernia and observed-to- expected lung to head ratio (o/e LHR). On individual analysis, variables were assessed using the Chi-square test and the Mann-Whitney test. A multiple logistic regression model was applied to select variables independently influencing the prediction of preterm delivery. A ROC curve was constructed with the significant variable, identifying the values with best sensitivity and specificity to be suggested for use in clinical practice. Eighty fetuses were evaluated, of which, 21 (26.25%) were premature. O/e LHR was the only factor associated with prematurity (p = 0.020). The ROC curve showed 93% sensitivity with 48.4% specificity for the cutoff of 40%. O/e LHR was the only predictor of prematurity in this sample.

Predictors of response to 17-alpha hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth.

PubMed

Manuck, Tracy A; Esplin, M Sean; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Varner, Michael W; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M; Ilekis, John

2016-03-01

Prematurity is the leading cause of neonatal morbidity and death among nonanomalous neonates in the United States. Intramuscular 17-alpha hydroxyprogesterone caproate injections reduce the risk of recurrent prematurity by approximately one third. Unfortunately, prophylactic 17-alpha hydroxyprogesterone caproate is not always effective, and one-third of high-risk women will have a recurrent preterm birth, despite 17-alpha hydroxyprogesterone caproate therapy. The reasons for this variability in response are unknown. Previous investigators have examined the influence of a variety of factors on 17-alpha hydroxyprogesterone caproate response but have analyzed data that used a fixed outcome of term delivery to define progesterone response. We hypothesized that the demographics, history, and pregnancy course among women who deliver at a similar gestational age with 17-alpha hydroxyprogesterone caproate for recurrent spontaneous preterm birth prevention differs when compared with those women who deliver later with 17-alpha hydroxyprogesterone caproate and that these associations could be refined by the use of a contemporary definition of 17-alpha hydroxyprogesterone caproate "responder." This was a planned secondary analysis of a prospective, multicenter, longitudinal study of women with ≥1 previous documented singleton spontaneous preterm birth at <37 weeks gestation. Data were collected at 3 prespecified gestational age epochs during pregnancy. All women who were included in this analysis received 17-alpha hydroxyprogesterone caproate during the studied pregnancy. We classified women as a 17-alpha hydroxyprogesterone caproate responder or nonresponder by calculating the difference in delivery gestational age between the 17-alpha hydroxyprogesterone caproate-treated pregnancy and her earliest spontaneous preterm birth. Responders were defined as those with pregnancy that extended ≥3 weeks later with 17-alpha hydroxyprogesterone caproate, compared with the delivery gestational age of their earliest previous spontaneous preterm birth. Data were analyzed with the use of chi-square test, t-test, and logistic regression. One hundred fifty-five women met the inclusion criteria. The 118 responders delivered later on average (37.7 weeks gestation) than the 37 nonresponders (33.5 weeks gestation; P < .001). Among responders, 32% (38/118 women) had a recurrent spontaneous preterm birth. Demographics (age, race/ethnicity, education, and parity) were similar between groups. In the regression model, the gestational age of the previous spontaneous preterm birth (odds ratio, 0.68; 95% confidence interval, 0.56-0.82; P < .001), vaginal bleeding/abruption in the current pregnancy (odds ratio, 0.24; 95% confidence interval, 0.06-0.88; P = .031), and first-degree family history of spontaneous preterm birth (odds ratio, 0.37; 95% confidence interval, 0.15-0.88; P = .024) were associated with response to 17-alpha hydroxyprogesterone caproate. Because women with a penultimate preterm pregnancy were more likely to be 17-alpha hydroxyprogesterone caproate nonresponders, we performed an additional limited analysis examining only the 130 women whose penultimate pregnancy was preterm. In regression models, the results were similar to those in the main cohort. Several historic and current pregnancy characteristics define women who are at risk for recurrent preterm birth at a similar gestational age, despite 17-alpha hydroxyprogesterone caproate therapy. These data should be studied prospectively in larger cohorts and combined with genetic and environmental data to identify women who are most likely to benefit from this intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Whole Blood Gene Expression Profile Associated with Spontaneous Preterm Birth in Women with Threatened Preterm Labor

PubMed Central

Heng, Yujing Jan; Pennell, Craig Edward; Chua, Hon Nian; Perkins, Jonathan Edward; Lye, Stephen James

2014-01-01

Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB. PMID:24828675

Combination Antiretroviral Use and Preterm Birth

PubMed Central

Watts, D. Heather; Williams, Paige L.; Kacanek, Deborah; Griner, Raymond; Rich, Kenneth; Hazra, Rohan; Mofenson, Lynne M.; Mendez, Hermann A.

2013-01-01

Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)–exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics. Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens. Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity. PMID:23204173

Preterm labor in the absence of acute histologic chorioamnionitis is characterized by cellular senescence of the chorioamniotic membranes.

PubMed

Gomez-Lopez, Nardhy; Romero, Roberto; Plazyo, Olesya; Schwenkel, George; Garcia-Flores, Valeria; Unkel, Ronald; Xu, Yi; Leng, Yaozhu; Hassan, Sonia S; Panaitescu, Bogdan; Cha, Jeeyeon; Dey, Sudhansu K

2017-11-01

Decidual senescence has been considered a mechanism of disease for spontaneous preterm labor in the absence of severe acute inflammation. Yet, signs of cellular senescence have also been observed in the chorioamniotic membranes from women who underwent the physiological process of labor at term. We aimed to investigate whether, in the absence of acute histologic chorioamnionitis, the chorioamniotic membranes from women who underwent spontaneous preterm labor or labor at term exhibit signs of cellular senescence. Chorioamniotic membrane samples were collected from women who underwent spontaneous preterm labor or labor at term. Gestational age-matched nonlabor controls were also included. Senescence-associated genes/proteins were determined using reverse transcription quantitative polymerase chain reaction analysis (n = 7-9 each for array; n = 26-28 each for validation), enzyme-linked immunosorbent assays (n = 7-9 each), immunoblotting (n = 6-7 each), and immunohistochemistry (n = 7-8 each). Senescence-associated β-galactosidase activity (n = 7-11 each) and telomere length (n = 15-22 each) were also evaluated. In the chorioamniotic membranes without acute histologic chorioamnionitis: (1) the expression profile of senescence-associated genes was different between the labor groups (term in labor and preterm in labor) and the nonlabor groups (term no labor and preterm no labor), yet there were differences between the term in labor and preterm in labor groups; (2) most of the differentially expressed genes among the groups were closely related to the tumor suppressor protein (TP53) pathway; (3) the expression of TP53 was down-regulated in the term in labor and preterm in labor groups compared to their nonlabor counterparts; (4) the expression of CDKN1A (gene coding for p21) was up-regulated in the term in labor and preterm in labor groups compared to their nonlabor counterparts; (5) the expression of the cyclin kinase CDK2 and cyclins CCNA2, CCNB1, and CCNE1 was down-regulated in the preterm in labor group compared to the preterm no labor group; (6) the concentration of TP53 was lower in the preterm in labor group than in the preterm no labor and term in labor groups; (7) the senescence-associated β-galactosidase activity was greater in the preterm in labor group than in the preterm no labor and term in labor groups; (8) the concentration of phospho-S6 ribosomal protein was reduced in the term in labor group compared to its nonlabor counterpart, but no differences were observed between the preterm in labor and preterm no labor groups; and (9) no significant differences were observed in relative telomere length among the study groups (term no labor, term in labor, preterm no labor, and preterm in labor). In the absence of acute histologic chorioamnionitis, signs of cellular senescence are present in the chorioamniotic membranes from women who underwent spontaneous preterm labor compared to those who delivered preterm in the absence of labor. However, the chorioamniotic membranes from women who underwent spontaneous labor at term did not show consistent signs of cellular senescence in the absence of histologic chorioamnionitis. These results suggest that different pathways are implicated in the pathological and physiological processes of labor. Published by Elsevier Inc.

The relationship of the subtypes of preterm birth with retinopathy of prematurity.

PubMed

Lynch, Anne M; Wagner, Brandie D; Hodges, Jennifer K; Thevarajah, Tamara S; McCourt, Emily A; Cerda, Ashlee M; Mandava, Naresh; Gibbs, Ronald S; Palestine, Alan G

2017-09-01

Retinopathy of prematurity is an adverse outcome of preterm birth and is a leading cause of childhood blindness. The relationship between the subtypes of preterm birth with retinopathy of prematurity is understudied. To investigate whether there is a difference in the incidence of type 1 or type 2 retinopathy of prematurity in infants with preterm birth resulting from spontaneous preterm labor, a medical indication of preterm birth, or preterm premature rupture of the membranes. A retrospective cohort study was conducted of 827 infants screened for retinopathy of prematurity who were delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for retinopathy of prematurity defined as "infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for retinopathy of prematurity." Two independent reviewers masked to retinopathy of prematurity outcomes determined whether preterm birth resulted from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes. Discrepancies were resolved by a third reviewer. Data were analyzed with univariate and multivariable logistic regression. In our cohort, the frequency of preterm birth resulting from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes was 34%, 40%, and 26%, respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the preterm birth subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days - 36 weeks, 4 days); spontaneous preterm labor, 28 weeks 1 day ± 2 weeks, 3 days (23 weeks, 3 days - 33 weeks, 4 days); medical indication of preterm birth, 29 weeks, 1 day ± 2 weeks, 2 days (24-36 weeks, 4 days); preterm premature rupture of the membranes, 28 weeks, 4 days ± 2 weeks, 1 day (24-33 weeks, 1 day). Among infants with type 1, type 2, or no retinopathy of prematurity, the incidence of type 1 or type 2 retinopathy of prematurity in births from spontaneous preterm labor, medical indication of preterm birth, and preterm premature rupture of the membranes was 37 of 218 (17%), 27 of 272 (10%), and 10 of 164 (6%), respectively. Adjusted for gestational age, birth weight, and multiparity and compared with the preterm premature rupture of the membranes group, the odds ratios of spontaneous preterm labor and medical indication of preterm birth for type 1 or type 2 retinopathy of prematurity were 6.1 (95% confidence interval, 1.8 to 20, P = .003) and 5.5 (95% confidence interval, 1.4 to 21, P = .01), respectively. Among neonates born after preterm premature rupture of the membranes, the probability of developing type 1 or type 2 retinopathy of prematurity was greatest in infants with rupture of membrane duration of up to 24 hours. After 24 hours, the probability of developing type 1 or type 2 retinopathy of prematurity declined. The odds of developing type 1 or type 2 retinopathy of prematurity was 9.0 (95% confidence interval 2.3 to 34, P = .002) in infants who had preterm premature rupture of the membranes ≤ 24 hours compared with infants who had preterm premature rupture of the membranes > 24 hours. Type 1 or type 2 retinopathy of prematurity are adverse ocular outcomes linked with not only lower gestational age and birth weight at delivery but also with events in the intrauterine environment that trigger a preterm birth. The reduced incidence of type 1 or type 2 retinopathy of prematurity in the preterm premature rupture of the membranes group compared with other causes of preterm birth may be related to the perinatal therapies associated with preterm premature rupture of the membranes (such as corticosteroids, antibiotics, maternal-fetal surveillance), which may have an inhibitory effect on the development of retinopathy of prematurity. We suggest that the physiologic events that predispose infants to type 1 or type 2 retinopathy of prematurity begin before delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Morbidity and mortality among very preterm singletons following fertility treatment in Australia and New Zealand, a population cohort study.

PubMed

Wang, Alex Y; Chughtai, Abrar A; Lui, Kei; Sullivan, Elizabeth A

2017-02-02

Due to high rates of multiple birth and preterm birth following fertility treatment, the rates of mortality and morbidity among births following fertility treatment were higher than those conceived spontaneously. However, it is unclear whether the rates of adverse neonatal outcomes remain higher for very preterm (<32 weeks gestational age) singletons born after fertility treatment. This study aims to compare adverse neonatal outcomes among very preterm singletons born after fertility treatment including assisted reproductive technology (ART) hyper-ovulution (HO) and artificial insemination (AI) to those following spontaneous conception. The population cohort study included 24069 liveborn very preterm singletons who were admitted to Neonatal Intensive Care Unit (NICU) in Australia and New Zealand from 2000 to 2010. The in-hospital neonatal mortality and morbidity among 21753 liveborn very preterm singletons were compared by maternal mode of conceptions: spontaneous conception, HO, ART and AI. Univariate and multivariate binary logistic regression analysis was used to examine the association between mode of conception and various outcome factors. Odds ratio (OR) and adjusted odds ratio (AOR) and 95% confidence interval (CI) were calculated. The rate of small for gestational age was significantly higher in HO group (AOR 1.52, 95% CI 1.02-2.67) and AI group (AOR 2.98, 95% CI 1.53-5.81) than spontaneous group. The rate of birth defect was significantly higher in ART group (AOR 1.71, 95% CI 1.36-2.16) and AI group (AOR 3.01, 95% CI 1.47-6.19) compared to spontaneous group. Singletons following ART had 43% increased odds of necrotizing enterocolitis (AOR 1.43, 95% CI 1.04-1.97) and 71% increased odds of major surgery (AOR 1.71, 95% CI 1.37-2.13) compared to singletons conceived spontaneously. Other birth and NICU outcomes were not different among the comparison groups. Compared to the spontaneous conception group, risk of congenital abnormality significantly increases after ART and AI; the risk of morbidities increases after ART, HO and AI. Preconception planning should include comprehensive information about the benefits and risks of fertility treatment on the neonatal outcomes.

What Interventions Are Being Used to Prevent Preterm Birth and When?

PubMed

Feng, Yu Yang; Jarde, Alexander; Seo, Ye Rin; Powell, Anne; Nwebube, Nwachukwu; McDonald, Sarah D

2018-05-01

This study sought to determine the proportions of women at risk of preterm birth who received progesterone, elective and rescue cerclage, or pessary to prevent preterm birth, by using medical records. The authors also sought to determine whether these proportions differed among primary-, secondary-, and tertiary-level centres. The authors conducted a retrospective cohort study and extracted data from consecutive medical charts of women with an estimated date of confinement over 3 months in primary-, secondary-, and tertiary-level centres in Southern Ontario. The study identified women with a previous spontaneous preterm birth or a short cervix and determined whether they were offered and whether they received a preventive intervention for preterm birth. Descriptive statistics and Fisher exact tests were calculated. The authors reviewed 1024 consecutive charts at primary, secondary, and tertiary centres and identified 31 women with a previous spontaneous preterm birth or a short cervix. Of these women, less than one half (42%) received progesterone or cerclage for prevention of preterm birth, and none received pessary. One in four women (26%) were not referred to an obstetrician or maternal-fetal medicine specialist in time for an intervention, and among those referred before 24 weeks of gestation, an intervention was offered to 57% of the women. Less than half of women at risk of spontaneous preterm birth received progesterone, cerclage, or pessary, attesting to the importance of improving knowledge translation methods to encourage timely referral and use of progesterone for the prevention of preterm birth. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt.

PubMed

Mosbah, Alaa; Barakat, Rafik; Nabiel, Yasmin; Barakat, Ghada

2018-03-01

This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

Is it possible to predict the infant's neurodevelopmental outcome at 14 months of age by means of a single preterm assessment of General Movements?

PubMed Central

Manacero, Sonia Aparecida; Marschik, Peter B.; Nunes, Magda Lahorgue; Einspieler, Christa

2012-01-01

Background It continues to be a challenge for clinicians to identify preterm infants likely to experience subsequent neurodevelopmental deficits. The Test of Infant Motor Performance (TIMP) and the assessment of spontaneous general movements (GMs) are the only reliable diagnostic and predictive tools for the functionality of the developing nervous system, if applied before term. Aim To determine to what extent singular preterm assessments of motor performance can predict the neurodevelopmental outcome in 14-month olds. Methods Thirty-seven preterm infants born < 34 weeks gestational age were recruited for the study at the NICU of the São Lucas University Hospital, Porto Alegre, RS, Brazil. At 34 weeks, their GMs were assessed; and the Test of Infant Motor Performance (TIMP) was applied. A prospective design was used to examine (A) the association between the GM assessment and the TIMP; and (B) the relation between GMs or the TIMP and the developmental status at 14 months, assessed by means of Alberta Infant Motor Scales (AIMS) and the Pediatric Evaluation of Disability Inventory (PEDI). Results Nineteen infants (41%) had abnormal GMs; only one scored within the TIMP average range. Hence, GMs and TIMP were not related. Children with cramped-synchronized GMs at 34 weeks preterm had a lower AIMS centile rank than those with poor repertoire or normal GMs. There was a marginal association between cramped-synchronized GMs and a lower PEDI mobility score. Conclusions A single preterm GM assessment is only fairly to moderately associated with the 14-month motor development. The TIMP is not suitable as a complementary assessment tool at such a young age. PMID:21775078

Cell-free fetal DNA and spontaneous preterm birth

PubMed Central

Davidson, Donald J; Norman, Jane E

2018-01-01

Inflammation is known to play a key role in preterm and term parturition. Cell-free fetal DNA (cff-DNA) is present in the maternal circulation and increases with gestational age and some pregnancy complications (e.g. preterm birth, preeclampsia). Microbial DNA and adult cell-free DNA can be pro-inflammatory through DNA-sensing mechanisms such as Toll-like receptor 9 and the Stimulator of Interferon Genes (STING) pathway. However, the pro-inflammatory properties of cff-DNA, and the possible effects of this on pregnancy and parturition are unknown. Clinical studies have quantified cff-DNA levels in the maternal circulation in women who deliver preterm and women who deliver at term and show an association between preterm labor and higher cff-DNA levels in the 2nd, 3rd trimester and at onset of preterm birth symptoms. Together with potential pro-inflammatory properties of cff-DNA, this rise suggests a potential mechanistic role in the pathogenesis of spontaneous preterm birth. In this review, we discuss the evidence linking cff-DNA to adverse pregnancy outcomes, including preterm birth, obtained from preclinical and clinical studies. PMID:29269517

Single Fasting Plasma Glucose Versus 75-g Oral Glucose-Tolerance Test in Prediction of Adverse Perinatal Outcomes: A Cohort Study.

PubMed

Shen, Songying; Lu, Jinhua; Zhang, Lifang; He, Jianrong; Li, Weidong; Chen, Niannian; Wen, Xingxuan; Xiao, Wanqing; Yuan, Mingyang; Qiu, Lan; Cheng, Kar Keung; Xia, Huimin; Mol, Ben Willem J; Qiu, Xiu

2017-02-01

There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes. We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22-28weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT. 1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30-1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1h, and 2h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P=0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥5.1mmol/l), irrespective of 1h or 2h glucose levels. A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Human cervicovaginal fluid biomarkers to predict term and preterm labor

PubMed Central

Heng, Yujing J.; Liong, Stella; Permezel, Michael; Rice, Gregory E.; Di Quinzio, Megan K. W.; Georgiou, Harry M.

2015-01-01

Preterm birth (PTB; birth before 37 completed weeks of gestation) remains the major cause of neonatal morbidity and mortality. The current generation of biomarkers predictive of PTB have limited utility. In pregnancy, the human cervicovaginal fluid (CVF) proteome is a reflection of the local biochemical milieu and is influenced by the physical changes occurring in the vagina, cervix and adjacent overlying fetal membranes. Term and preterm labor (PTL) share common pathways of cervical ripening, myometrial activation and fetal membranes rupture leading to birth. We therefore hypothesize that CVF biomarkers predictive of labor may be similar in both the term and preterm labor setting. In this review, we summarize some of the existing published literature as well as our team's breadth of work utilizing the CVF for the discovery and validation of putative CVF biomarkers predictive of human labor. Our team established an efficient method for collecting serial CVF samples for optimal 2-dimensional gel electrophoresis resolution and analysis. We first embarked on CVF biomarker discovery for the prediction of spontaneous onset of term labor using 2D-electrophoresis and solution array multiple analyte profiling. 2D-electrophoretic analyses were subsequently performed on CVF samples associated with PTB. Several proteins have been successfully validated and demonstrate that these biomarkers are associated with term and PTL and may be predictive of both term and PTL. In addition, the measurement of these putative biomarkers was found to be robust to the influences of vaginal microflora and/or semen. The future development of a multiple biomarker bed-side test would help improve the prediction of PTB and the clinical management of patients. PMID:26029118

The predictive value of quantitative fibronectin testing in combination with cervical length measurement in symptomatic women.

PubMed

Bruijn, Merel M C; Kamphuis, Esme I; Hoesli, Irene M; Martinez de Tejada, Begoña; Loccufier, Anne R; Kühnert, Maritta; Helmer, Hanns; Franz, Marie; Porath, Martina M; Oudijk, Martijn A; Jacquemyn, Yves; Schulzke, Sven M; Vetter, Grit; Hoste, Griet; Vis, Jolande Y; Kok, Marjolein; Mol, Ben W J; van Baaren, Gert-Jan

2016-12-01

The combination of the qualitative fetal fibronectin test and cervical length measurement has a high negative predictive value for preterm birth within 7 days; however, positive prediction is poor. A new bedside quantitative fetal fibronectin test showed potential additional value over the conventional qualitative test, but there is limited evidence on the combination with cervical length measurement. The purpose of this study was to compare quantitative fetal fibronectin and qualitative fetal fibronectin testing in the prediction of spontaneous preterm birth within 7 days in symptomatic women who undergo cervical length measurement. We performed a European multicenter cohort study in 10 perinatal centers in 5 countries. Women between 24 and 34 weeks of gestation with signs of active labor and intact membranes underwent quantitative fibronectin testing and cervical length measurement. We assessed the risk of preterm birth within 7 days in predefined strata based on fibronectin concentration and cervical length. Of 455 women who were included in the study, 48 women (11%) delivered within 7 days. A combination of cervical length and qualitative fibronectin resulted in the identification of 246 women who were at low risk: 164 women with a cervix between 15 and 30 mm and a negative fibronectin test (<50 ng/mL; preterm birth rate, 2%) and 82 women with a cervix at >30 mm (preterm birth rate, 2%). Use of quantitative fibronectin alone resulted in a predicted risk of preterm birth within 7 days that ranged from 2% in the group with the lowest fibronectin level (<10 ng/mL) to 38% in the group with the highest fibronectin level (>500 ng/mL), with similar accuracy as that of the combination of cervical length and qualitative fibronectin. Combining cervical length and quantitative fibronectin resulted in the identification of an additional 19 women at low risk (preterm birth rate, 5%), using a threshold of 10 ng/mL in women with a cervix at <15 mm, and 6 women at high risk (preterm birth rate, 33%) using a threshold of >500 ng/mL in women with a cervix at >30 mm. In women with threatened preterm birth, quantitative fibronectin testing alone performs equal to the combination of cervical length and qualitative fibronectin. Possibly, the combination of quantitative fibronectin testing and cervical length increases this predictive capacity. Cost-effectiveness analysis and the availability of these tests in a local setting should determine the final choice. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of maternal omentin-1 levels and genetic variability between spontaneous term and preterm births.

PubMed

Šplíchal, Zbyněk; Zlámal, Filip; Máchal, Jan; Lipková, Jolana; Pavlová, Tereza; Hodická, Zuzana; Ventruba, Pavel; Vašků, Anna; Bienertová-Vašků, Julie

2018-07-01

To determine maternal omentin-1 levels and genetic variability in the omentin-1 gene in women with spontaneous term and preterm births (PTBs). Maternal serum omentin-1 levels and the role of the omentin-1 Val109Asp (rs2274907) polymorphism were evaluated in 32 women with spontaneous term birth (sTB) and 30 women with spontaneous preterm birth (sPTB) including women with (n = 16) and without (n = 14) preterm premature rupture of membranes (PPROM). Maternal omentin-1 levels were significantly lower in women with sPTBs compared to term births during the hospitalization period (p = .015). However, maternal omentin-1 levels were similar in women with sPTBs with and without PPROM (p = .990). Furthermore, the omentin-1 Val109Asp polymorphism was found to have no significant effect on omentin-1 serum levels. In addition, no significant differences in genotype distributions and allelic frequencies between sTB and sPTB were established. High omentin-1 levels in normal sTBs compared to PTBs without significant differences between cases with and without PPROM suggest that omentin-1 plays a potential role in the pathophysiology of PTB but not in the PPROM mechanism itself.

Neonatal outcome in preterm deliveries before 34-week gestation - the influence of the mechanism of labor onset.

PubMed

Pinto, Sara; Malheiro, Maria Filipa; Vaz, Ana; Rodrigues, Teresa; Montenegro, Nuno; Guimarães, Hercília

2018-06-21

To evaluate neonatal outcomes in preterm infants with less than 34 weeks after spontaneous labor, preterm premature rupture of membranes (PPROM) or iatrogenic delivery and to clarify whether the mechanism of labor onset is a risk factor for adverse short-term neonatal outcome. We performed a retrospective case-control study, which included 266 preterm newborns with less than 34-week gestation, between 2011 and 2015. Neonatal outcomes were compared according to the mechanism of labor onset. Our primary outcomes were neonatal death, sequelae on hospital discharge and a composite of these two variables (combined neonatal outcome). Compared to spontaneous preterm labor, iatrogenic preterm newborns were at increased risk of respiratory distress syndrome (RDS) [Odds Ratio (OR) 3.05 (95%CI 1.31; 7.12)], and need of exogenous surfactant administration [OR 3.87 (95%CI 1.60; 9.35)]. PPROM was associated with higher risk of neonatal sepsis [OR 12.96 (95%CI 1.18; 142.67)]. There were no differences regarding the combined outcome for iatrogenic [OR 0.94 (95%CI 0.33; 2.71)] or PPROM [OR 1.11 (95%CI 0.35; 3.49)] groups. In our study, the different mechanisms of labor onset are associated with different neonatal outcomes. Iatrogenic preterm birth was associated with an increased risk of RDS and a higher need of exogenous surfactant administration than spontaneous group. The rate of neonatal sepsis was significantly higher in PPROM group along with a higher prevalence of histological chorioamnionitis.

Can the Assessment of Spontaneous Oscillations by Near Infrared Spectrophotometry Predict Neurological Outcome of Preterm Infants?

PubMed

Stammwitz, André; von Siebenthal, Kurt; Bucher, Hans U; Wolf, Martin

2016-01-01

The aim was to assess the correlation between cerebral autoregulation and outcome. Included were 31 preterm infants, gestational age 26 1/7 to 32 2/7 and <24 h life. Coherence between cerebral total haemoglobin (tHb) or oxygenation index (OI) measured by near-infrared spectrophotometry (NIRS) and systemic heart rate (HR) or arterial blood pressure (MAP) was calculated as a measure of autoregulation. In contrast to previous studies, low coherences in the first 24 h were significantly associated with intraventricular haemorrhage, death or abnormal neurodevelopmental outcome at 18 months or later. We suggest that our results can be explained by the concept of a multi-oscillatory-functions-order.

Short and inflamed cervix predicts spontaneous preterm birth (COLIBRI study).

PubMed

Raiche, Evelyne; Ouellet, Annie; Berthiaume, Maryse; Rousseau, Éric; Pasquier, Jean-Charles

2014-07-01

To develop a new strategy of predicting spontaneous preterm birth (sPTB) by combination of transvaginal ultrasound (TVUS) assessment and inflammatory proteins detection in vaginal secretions. Prospective study of 87 women referred for cervical length assessment with a standardized TVUS combined to vaginal secretions sampling. Samples were analyzed for presence of 10 cytokines. Main outcome was sPTB (<37 weeks of gestation). Associations were assessed with the chi-square, Fisher's exact test (p < 0.05) and Wald's logistic regression. sPTB occurred in 25.3% of women at a median gestational age of 35.6 weeks of gestation. Short cervix (<25 mm) (n = 24) was associated with sPTB (p < 0.01) as interleukine (IL)-1β, IL-8 and IL-10 in vaginal secretions (p < 0.05). In multivariate analysis, short cervix and IL-8 in vaginal secretions were independently associated with sPTB (OR 3.58 (95%CI 1.02; 12.61) and 14.55 (95%CI 1.64; 128.83), respectively) as their combination (OR 4.33 (95%CI 1.25; 14.95)). By categorizing cervical length by presence of IL-8, sPTB occurred in 55.6% of women with a short inflamed cervix. COLIBRI study used a novel, single-step method of vaginal secretions sampling during TVUS and demonstrated that combination of short cervix and IL-8 in vaginal secretions is a promising sPTB predictive test.

Factors that influence the timing of spontaneous labor at term.

PubMed

Fogleman, Kelly A; Herring, Amy H; Kaczor, Diane; Pusek, Susan N; Jo, Hyejin; Thorp, John M

2007-11-01

Whether pre-term birth culminates as a result of a de novo pathologic process or is more simply early activation of physiologic mechanisms is unknown. Exploration of the onset of labor in term women with classical risk factors for early delivery might provide insights into the mechanisms leading to pre-term birth. This study examines whether sociodemographic factors known to increase the risk of pre-term birth also affect the length of term gestations. From a large prospective cohort composed of women delivering from 1995-2000, a sample was selected of 441 women from Central North Carolina, US, who delivered singletons after 37 weeks gestation. An algorithm was designed to identify induced labors and gestational age was censored at the time of induction. Gestational age was assigned by sonography and menstrual dating. Data were analysed using the Cox proportional hazards model. The main outcome measure was time to spontaneous labor. Women with 12 years of education had longer periods of gestation than women with less than 12 years of education, HR = 0.57 [0.39, 0.84]. Shorter gestational periods were found for women with pre-term premature rupture of membranes (PPROM) in a previous pregnancy, HR = 3.70 [1.60, 8.52], even after adjusting for confounders. Smoking was not associated (p > 0.1) with the timing of labor at term. By studying the timing of spontaneous parturition at term we identified that there is little overlap in risk factors that affect timing of delivery between spontaneous term and pre-term births.

Maternal and neonatal interleukin-1 receptor antagonist genotype and pregnancy outcome in a population with a high rate of pre-term birth.

PubMed

Chaves, José Humberto Belmino; Babayan, Arthur; Bezerra, Cledna de Melo; Linhares, Iara M; Witkin, Steven S

2008-10-01

We evaluated associations between a length polymorphism in intron 2 of the gene coding for IL-1ra (gene symbol IL1RN) and pregnancy outcome in a population with a high rate of preterm birth. Subjects were pregnant women in Maceio, Brazil and their newborns. DNA was tested for IL1RN genotypes and alleles by gene amplification using primer pairs that spanned the polymorphic region. Every subject completed a detailed questionnaire. The frequency of allele 2 (IL1RN*2) carriage was elevated in mothers with a spontaneous preterm birth (SPTB) in the current pregnancy (P = 0.02) and also with a prior preterm delivery (P = .01). Both SPTB with intact membranes (P = 0.01) and SPTB preceded by pre-term premature rupture of membranes (P = .03) were associated with ILlRN*2 carriage. A previous fetal demise was more than twice as prevalent in mothers positive for two copies of IL1RN*2. Maternal carriage of ILlRN*2 increases susceptibility to inflammation-triggered spontaneous pre-term birth.

Residential Agricultural Pesticide Exposures and Risks of Spontaneous Preterm Birth.

PubMed

Shaw, Gary M; Yang, Wei; Roberts, Eric M; Kegley, Susan E; Stevenson, David K; Carmichael, Suzan L; English, Paul B

2018-01-01

Pesticides exposures are aspects of the human exposome that have not been sufficiently studied for their contribution to risk for preterm birth. We investigated risks of spontaneous preterm birth from potential residential exposures to 543 individual chemicals and 69 physicochemical groupings that were applied in the San Joaquin Valley of California during the study period, 1998-2011. The study population was derived from birth certificate data linked with Office of Statewide Health Planning and Development maternal and infant hospital discharge data. After exclusions, the analytic study base included 197,461 term control births and 27,913 preterm case births. Preterm cases were more narrowly defined as 20-23 weeks (n = 515), 24-27 weeks (n = 1,792), 28-31 weeks (n = 3,098), or 32-36 weeks (n = 22,508). The frequency of any (versus none) pesticide exposure was uniformly lower in each preterm case group relative to the frequency in term controls, irrespective of gestational month of exposure. All odds ratios were below 1.0 for these any versus no exposure comparisons. The majority of odds ratios were below 1.0, many of them statistically precise, for preterm birth and exposures to specific chemical groups or chemicals. This study showed a general lack of increased risk of preterm birth associated with a range of agriculture pesticide exposures near women's residences.

A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

PubMed Central

Karjalainen, Minna K.; Huusko, Johanna M.; Ulvila, Johanna; Sotkasiira, Jenni; Luukkonen, Aino; Teramo, Kari; Plunkett, Jevon; Anttila, Verneri; Palotie, Aarno; Haataja, Ritva; Muglia, Louis J.; Hallman, Mikko

2012-01-01

Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD  = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB. PMID:23227263

Region-Specific Slowing of Alpha Oscillations is Associated with Visual-Perceptual Abilities in Children Born Very Preterm

PubMed Central

Doesburg, Sam M.; Moiseev, Alexander; Herdman, Anthony T.; Ribary, Urs; Grunau, Ruth E.

2013-01-01

Children born very preterm (≤32 weeks gestational age) without major intellectual or neurological impairments often express selective deficits in visual-perceptual abilities. The alterations in neurophysiological development underlying these problems, however, remain poorly understood. Recent research has indicated that spontaneous alpha oscillations are slowed in children born very preterm, and that atypical alpha-mediated functional network connectivity may underlie selective developmental difficulties in visual-perceptual ability in this group. The present study provides the first source-resolved analysis of slowing of spontaneous alpha oscillations in very preterm children, indicating alterations in a distributed set of brain regions concentrated in areas of posterior parietal and inferior temporal regions associated with visual perception, as well as prefrontal cortical regions and thalamus. We also uniquely demonstrate that slowing of alpha oscillations is associated with selective difficulties in visual-perceptual ability in very preterm children. These results indicate that region-specific slowing of alpha oscillations contribute to selective developmental difficulties prevalent in this population. PMID:24298250

Salivary progesterone and cervical length measurement as predictors of spontaneous preterm birth.

PubMed

Maged, Ahmed M; Mohesen, Mohamed; Elhalwagy, Ahmed; Abdelhafiz, Ali

2015-07-01

To evaluate the efficacy of salivary progesterone, cervical length measurement in predicting preterm birth (PTB). Prospective observational study included 240 pregnant women with gestational age (GA) 26-34 weeks classified into two equal groups; group one are high risk for PTB (those with symptoms of uterine contractions or history of one or more spontaneous preterm delivery or second trimester abortion) and group 2 are controls. There was a highly significant difference between the two study groups regarding GA at delivery (31.3 ± 3.75 in high risk versus 38.5 ± 1.3 in control), cervical length measured by transvaginal ultrasound (24.7 ± 8.6 in high risk versus 40.1 ± 4.67 in control) and salivary progesterone level (728.9 ± 222.3 in high risk versus 1099.9 ± 189.4 in control; p < 0.001). There was a statistically significant difference between levels of salivary progesterone at different GA among the high risk group (p value 0.035) but not in low risk group (p value 0.492). CL measurement showed a sensitivity of 71.5% with 100% specificity, 100% PPV, 69.97% NPV and accuracy of 83%, while salivary progesterone showed a sensitivity of 84% with 90% specificity, 89.8% PPV, 85.9% NPV and accuracy of 92.2%. The measurement of both salivary progesterone and cervical length are good predictors for development of PTB.

Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth.

PubMed

McCarthy, Fergus P; Khashan, Ali S; North, Robyn A; Rahma, Muna B; Walker, James J; Baker, Philip N; Dekker, Gus; Poston, Lucilla; McCowan, Lesley M E; O'Donoghue, Keelin; Kenny, Louise C

2013-12-01

Do women with a previous miscarriage or termination of pregnancy have an increased risk of spontaneous preterm birth and is this related to previous cervical dilatation and curettage? A single previous pregnancy loss (termination or miscarriage) managed by cervical dilatation and curettage is associated with a greater risk of SpPTB. Miscarriage affects ∼20% of pregnancies and as many as a further 20% of pregnancies undergo termination. We utilized data from 5575 healthy nulliparous women with singleton pregnancies recruited to the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study performed between November 2004 and January 2011. The primary outcome was spontaneous preterm birth (defined as spontaneous preterm labour or preterm premature rupture of membranes (PPROM) resulting in preterm birth <37 weeks' gestation). Secondary outcomes included PPROM, small for gestational age, birthweight, pre-eclampsia and placental abruption. Women with previous pregnancy loss (miscarriage or termination) were compared with those with no previous pregnancy loss. There were 4331 (78%) women who had no previous pregnancy loss, 974 (17.5%) who had one early previous pregnancy loss, 249 (4.5%) who had two and 21 (0.5%) who had three or four losses. Women with two to four previous losses, but not those with a single loss, had an increased risk of spontaneous preterm birth (adjusted OR 2.12; 95% CI 1.55, 2.90) and/or placental abruption (adjusted OR 2.30; 95% CI 1.36, 3.89) compared with those with no previous pregnancy. A single previous miscarriage or termination of pregnancy where the management involved cervical dilatation and curettage was associated with an increased risk of spontaneous preterm birth (adjusted OR 1.64; 95% CI 1.08, 2.50; 6% absolute risk and adjusted OR 1.83; 95% CI 1.35, 2.48; 7% absolute risk, respectively) compared with those with no previous pregnancy losses. This is in contrast with women with a single previous miscarriage or termination managed non-surgically who showed no increase risk (adjusted OR 0.86; 95% CI 0.38, 1.94; 3.4% absolute risk and adjusted OR 0.87; 95% CI 0.69, 1.12; 3.8% absolute risk, respectively). Although every effort was made to record accurate previous pregnancy data, it was not feasible to confirm the history and management of previous pregnancy loss by hospital records. This may have introduced recall bias. This large prospective cohort study of healthy nulliparous women has demonstrated that women with either a previous miscarriage or termination of pregnancy were at increased risk of spontaneous preterm birth if they were managed by procedures involving cervical dilatation and curettage. However, overall, women with a single pregnancy loss did not have an increased risk of having any other of the adverse pregnancy outcomes examined. In contrast, two to four previous pregnancy losses were associated with an increased risk of having a pregnancy complicated by spontaneous preterm birth and/or placental abruption. Research is required to determine whether non-surgical management of miscarriage or termination of pregnancy should be advocated over surgical treatment. New Zealand: New Enterprise Research Fund, Foundation for Research Science and Technology; Health Research Council; Evelyn Bond Fund, Auckland District Health Board Charitable Trust. Australia: Premier's Science and Research Fund, South Australian Government. Ireland: Health Research Board. Leeds: Cerebra Charity, Carmarthen. Manchester: National Health Service NEAT Grant; Manchester Biotechnology and Biological Sciences Research Council; University of Manchester Proof of Concept Funding. King's College London: Guy's and St Thomas' Charity. King's College London and Manchester: Tommy's-The Baby Charity. N/A.

Adverse Pregnancy Outcomes Among Women with Prior Spontaneous or Induced Abortions

PubMed Central

Makhlouf, Michel A; Clifton, Rebecca G.; Roberts, James M.; Myatt, Leslie; Hauth, John C.; Leveno, Kenneth J.; Varner, Michael W.; Thorp, John M.; Mercer, Brian M.; Peaceman, Alan M.; Ramin, Susan M.; Iams, Jay D.; Sciscione, Anthony; Tolosa, Jorge E.; Sorokin, Yoram

2014-01-01

OBJECTIVE To determine whether prior spontaneous (SAB) or induced (IAB) abortions, or the inter-pregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared to primigravid participants. RESULTS Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (OR 1.5; 95% CI 1.1–2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (OR 2.6, 95% CI 1.7–4.0), preterm PROM (OR 2.9, 95% CI 1.6–5.3) and perinatal death (OR 2.8, 95% CI 1.5–5.3). Women with one previous IAB had higher rates of spontaneous preterm birth (OR 1.4, 95% CI 1.0–1.9) and preterm PROM (OR 2.0, 95% CI 1.4–3.0). An inter-pregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. PMID:24347257

Fertility Treatment Is Associated with Stay in the Neonatal Intensive Care Unit and Respiratory Support in Late Preterm Infants.

PubMed

Wang, Erica T; Sundheimer, Lauren W; Spades, Carla; Quant, Cara; Simmons, Charles F; Pisarska, Margareta D

2017-08-01

Late preterm infants are at risk for short-term morbidities. We report that late preterm singletons conceived with fertility treatment have increased risk for admission to the neonatal intensive care unit and respiratory support compared with spontaneously conceived infants. Fertility treatment may be a risk factor to consider in managing late preterm infants. Copyright © 2017 Elsevier Inc. All rights reserved.

Basic vaginal pH, bacterial vaginosis and aerobic vaginitis: prevalence in early pregnancy and risk of spontaneous preterm delivery, a prospective study in a low socioeconomic and multiethnic South American population.

PubMed

Krauss-Silva, Leticia; Almada-Horta, Antonio; Alves, Mariane B; Camacho, Karla G; Moreira, Maria Elizabeth L; Braga, Alcione

2014-03-19

Bacterial vaginosis (BV) increases the risk of spontaneous preterm deliveries (PD) in developed countries. Its prevalence varies with ethnicity, socioeconomic conditions and gestational age. Aerobic vaginitis (AV) has also been implicated with spontaneous PD. The present study aimed to estimate the prevalence of asymptomatic BV, the accuracy of vaginal pH level to predict BV and to estimate the risk of spontaneous PD <34 and <37 weeks' gestation of BV and AV. Women attending prenatal public services in Rio de Janeiro were screened to select asymptomatic pregnant women, < 20 weeks' gestation, with no indication for elective PD and without risk factors of spontaneous PD. Vaginal smears of women with vaginal pH > = 4.5 were collected to determine the Nugent score; a sample of those smears was also classified according to a modified Donders' score. Primary outcomes were spontaneous PD < 34 and <37 weeks' gestation and abortion. Prevalence of asymptomatic BV was estimated in 28.1% (n = 1699); 42.4% of the smears were collected before 14 weeks' gestation. After an 8-week follow up, nearly 40% of the initially BV positive women became BV negative. The prevalence of BV among white and black women was 28.1% (95% CI: 24.6%-32.0%) and 32.5% (95% CI: 28.2%-37.2%), respectively. The sensitivity of vaginal pH= > 4.5 and = > 5.0 to predict BV status was 100% and 82%, correspondingly; the 5.0 cutoff value doubled the specificity, from 41% to 84%. The incidence of < 37 weeks' spontaneous PDs among BV pregnant women with a pH= > 4.5 was 3.8%. The RR of spontaneous PD < 34 and <37 weeks among BV women with pH > =4.5, as compared with those with intermediate state, were 1.24 and 1.86, respectively (Fisher's exact test, p value = 1; 0.52, respectively, both ns). No spontaneous case of PD or abortion was associated with severe or moderate AV. A high prevalence of asymptomatic BV was observed without statistically significant difference between black and white women. The RRs of spontaneous PD < 34 and <37 weeks among women with BV, as compared with those with intermediate state were not statistically significant but were consistent with those found in the literature.

Basic vaginal pH, bacterial vaginosis and aerobic vaginitis: prevalence in early pregnancy and risk of spontaneous preterm delivery, a prospective study in a low socioeconomic and multiethnic South American population

PubMed Central

2014-01-01

Background Bacterial vaginosis (BV) increases the risk of spontaneous preterm deliveries (PD) in developed countries. Its prevalence varies with ethnicity, socioeconomic conditions and gestational age. Aerobic vaginitis (AV) has also been implicated with spontaneous PD. The present study aimed to estimate the prevalence of asymptomatic BV, the accuracy of vaginal pH level to predict BV and to estimate the risk of spontaneous PD <34 and <37 weeks’ gestation of BV and AV. Methods Women attending prenatal public services in Rio de Janeiro were screened to select asymptomatic pregnant women, < 20 weeks’ gestation, with no indication for elective PD and without risk factors of spontaneous PD. Vaginal smears of women with vaginal pH > = 4.5 were collected to determine the Nugent score; a sample of those smears was also classified according to a modified Donders’ score. Primary outcomes were spontaneous PD < 34 and <37 weeks’ gestation and abortion. Results Prevalence of asymptomatic BV was estimated in 28.1% (n = 1699); 42.4% of the smears were collected before 14 weeks’ gestation. After an 8-week follow up, nearly 40% of the initially BV positive women became BV negative. The prevalence of BV among white and black women was 28.1% (95% CI: 24.6%-32.0%) and 32.5% (95% CI: 28.2%-37.2%), respectively. The sensitivity of vaginal pH= > 4.5 and = > 5.0 to predict BV status was 100% and 82%, correspondingly; the 5.0 cutoff value doubled the specificity, from 41% to 84%. The incidence of < 37 weeks’ spontaneous PDs among BV pregnant women with a pH= > 4.5 was 3.8%. The RR of spontaneous PD < 34 and <37 weeks among BV women with pH > =4.5, as compared with those with intermediate state, were 1.24 and 1.86, respectively (Fisher’s exact test, p value = 1; 0.52, respectively, both ns). No spontaneous case of PD or abortion was associated with severe or moderate AV. Conclusions A high prevalence of asymptomatic BV was observed without statistically significant difference between black and white women. The RRs of spontaneous PD < 34 and <37 weeks among women with BV, as compared with those with intermediate state were not statistically significant but were consistent with those found in the literature. PMID:24641730

Elevated maternal serum-free β-human chorionic gonadotropin (β-hCG) and reduced risk of spontaneous preterm delivery.

PubMed

Soni, Shelly; Krantz, David A; Blitz, Matthew J; Vohra, Nidhi; Rochelson, Burton

2018-04-12

To evaluate the relationship between first and second trimester maternal serum-free β-hCG and the risk of spontaneous preterm delivery (PTD). This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free β-hCG in one or both trimesters. High maternal first and/or second trimester free β-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free β-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free β-hCG in any trimester. Low free β-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free β-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. High free β-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

Transvaginal ultrasonographic measurement of cervical length in asymptomatic high-risk women with a short cervical length in the previous pregnancy.

PubMed

Crane, J M G; Hutchens, D

2011-07-01

To determine if asymptomatic women at high risk of preterm delivery who had a short cervical length in their previous pregnancy and delivered at term are at increased risk of having a short cervical length in their next pregnancy, and whether they are at increased risk of preterm birth. This retrospective cohort study included high-risk (those with a history of spontaneous preterm birth, uterine anomaly or excisional treatment for cervical dysplasia) asymptomatic women who were pregnant with a singleton gestation delivering between April 2003 and March 2010, who had had a previous pregnancy and who had transvaginal ultrasonographic cervical length measurement performed at 16-30 weeks' gestation in both pregnancies. Comparison was among women who had a short cervical length (< 3.0 cm) in their previous pregnancy but delivered at term in that pregnancy (Short Term Group), women with a history of a normal cervical length (≥ 3.0 cm) in their previous pregnancy delivering at term (Long Term Group), and women who had a short cervical length (< 3.0 cm) in their previous pregnancy delivering preterm (Short Preterm Group). Primary outcomes were spontaneous preterm birth at < 37 weeks' gestation and cervical length. Secondary outcomes were spontaneous preterm birth at < 35 weeks and < 32 weeks, low birth weight, maternal outcomes and neonatal morbidity. A total of 62 women were included. Women in the Short Term Group were more likely to have a short cervical length in their next pregnancy compared with those in the Long Term Group (10/23 (43.5%) vs. 4/26 (15.4%), respectively) but not as likely as women in the Short Preterm Group (9/13 (69.2%); P=0.003). Women in the Short Term Group were not at an increased risk of spontaneous preterm birth at < 37 weeks in the next pregnancy compared with women in the Long Term Group (2/23 (8.7%) vs. 2/26 (7.7%), respectively), but women in the Short Preterm Group were at an increased risk (6/13 (46.2%); P<0.0001). Compared with women in the Short Term and Long Term groups, women in the Short Preterm Group were also at an increased risk of threatened preterm labor (6/23 (26.1%) and 4/26 (15.4%) vs. 9/13 (69.2%), respectively; P=0.002) and of receiving corticosteroids for fetal lung maturation (6/23 (26.1%) and 4/26 (15.4%) vs. 11/13 (84.6%), respectively; P<0.0001). Although high-risk asymptomatic women with a short cervical length in their previous pregnancy who delivered at term are at increased risk of having a short cervix in their next pregnancy, they are not at increased risk of preterm birth. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Cervical dilatation thresholds for initiation of group B streptococcus antibiotic prophylaxis for women with spontaneous preterm labor.

PubMed

Fischer, Richard L; Parikh, Laura; Hansen, Clare; Hunter, Krystal M

2015-11-01

To determine the optimal time for initiating group B streptococcus (GBS) antibiotic prophylaxis for women in spontaneous preterm labor. In total, 227 women delivering singleton infants after presenting with spontaneous preterm labor and intact membranes at 24 0/7-36 6/7 weeks were evaluated, as well as 150 undelivered women with threatened preterm labor during the same time period. The date and time of each cervical examination throughout labor were recorded. We calculated the percentages who would have correctly received at least 4 h of GBS prophylaxis if antibiotics were routinely initiated for various cervical dilatation thresholds during labor, as well as the percentage of undelivered women who would have received unnecessary antibiotic exposure at each cervical dilatation cutoff. Delaying antibiotics until cervical dilatation reached 2 cm or greater would have resulted in 62.1% receiving four or more hours of antibiotics, compared to 66.5% if antibiotics were started on all women at admission (p = 0.33), while significantly reducing unnecessary antibiotic exposure in undelivered women from 100% to 62.0% (p < 0.001). The 2-cm threshold was applicable regardless of gestational age period or prior vaginal delivery ≥ 20 weeks. GBS antibiotic prophylaxis may reasonably be withheld for women with suspected preterm labor until the cervix reaches 2 cm or greater at any time during labor.

Reproductive outcomes following induced abortion: a national register-based cohort study in Scotland.

PubMed

Bhattacharya, Siladitya; Lowit, Alison; Bhattacharya, Sohinee; Raja, Edwin Amalraj; Lee, Amanda Jane; Mahmood, Tahir; Templeton, Allan

2012-01-01

To investigate reproductive outcomes in women following induced abortion (IA). Retrospective cohort study. Hospital admissions between 1981 and 2007 in Scotland. Data were extracted on all women who had an IA, a miscarriage or a live birth from the Scottish Morbidity Records. A total of 120 033, 457 477 and 47 355 women with a documented second pregnancy following an IA, live birth and miscarriage, respectively, were identified. Obstetric and perinatal outcomes, especially preterm delivery in a second ongoing pregnancy following an IA, were compared with those in primigravidae, as well as those who had a miscarriage or live birth in their first pregnancy. Outcomes after surgical and medical termination as well as after one or more consecutive IAs were compared. IA in a first pregnancy increased the risk of spontaneous preterm birth compared with that in primigravidae (adjusted RR (adj. RR) 1.37, 95% CI 1.32 to 1.42) or women with an initial live birth (adj. RR 1.66, 95% CI 1.58 to 1.74) but not in comparison with women with a previous miscarriage (adj. RR 0.85, 95% CI 0.79 to 0.91). Surgical abortion increased the risk of spontaneous preterm birth compared with medical abortion (adj. RR 1.25, 95% CI 1.07 to 1.45). The adjusted RRs (95% CI) for spontaneous preterm delivery following two, three and four consecutive IAs were 0.94 (0.81 to 1.10), 1.06 (0.76 to 1.47) and 0.92 (0.53 to 1.61), respectively. The risk of preterm birth after IA is lower than that after miscarriage but higher than that in a first pregnancy or after a previous live birth. This risk is not increased further in women who undergo two or more consecutive IAs. Surgical abortion appears to be associated with an increased risk of spontaneous preterm birth in comparison with medical termination of pregnancy. Medical termination was not associated with an increased risk of preterm delivery compared to primigravidae.

Breathing patterns in preterm and term infants immediately after birth.

PubMed

te Pas, Arjan B; Wong, Connie; Kamlin, C Omar F; Dawson, Jennifer A; Morley, Colin J; Davis, Peter G

2009-03-01

There is limited data describing how preterm and term infants breathe spontaneously immediately after birth. We studied spontaneously breathing infants >or=29 wk immediately after birth. Airway flow and tidal volume were measured for 90 s using a hot wire anemometer attached to a facemask. Twelve preterm and 13 term infants had recordings suitable for analysis. The median (interquartile range) proportion of expiratory braking was very high in both groups (preterm 90 [74-99] vs. term 87 [74-94]%; NS). Crying pattern was the predominant breathing pattern for both groups (62 [36-77]% vs. 64 [46-79]%; NS). Preterm infants showed a higher incidence of expiratory hold pattern (9 [4-17]% vs. 2 [0-6]%; p = 0.02). Both groups had large tidal volumes (6.7 [3.9] vs. 6.5 [4.1] mL/kg), high peak inspiratory flows (5.7 [3.8] vs. 8.0 [5] L/min), lower peak expiratory flow (3.6 [2.4] vs. 4.8 [3.2] L/min), short inspiration time (0.31 [0.13] vs. 0.32 [0.16] s) and long expiration time (0.93 [0.64] vs. 1.14 [0.86] s). Directly after birth, both preterm and term infants frequently brake their expiration, mostly by crying. Preterm infants use significantly more expiratory breath holds to defend their lung volume.

Maternal and neonatal epidemiological features in clinical subtypes of preterm-birth

PubMed Central

Gimenez, Lucas G.; Krupitzki, Hugo B.; Momany, Allison M.; Gili, Juan A.; Poletta, Fernando A.; Campaña, Hebe; Cosentino, Viviana R.; Saleme, César; Pawluk, Mariela; Murray, Jeffrey C.; Castilla, Eduardo E.; Gadow, Enrique C.; Lopez-Camelo, Jorge S.

2016-01-01

Objective This study was designed to characterize and compare the maternal and newborn epidemiological characteristics through analysis of environmental factors, socio-demographic characteristics, and clinical characteristics between the different clinical subtypes of preterm birth (PTB): Idiopathic (PTB-I), premature rupture of the membranes (PTB-PPROM) and medically indicated (PTB-M). The two subtypes PTB-I and PTB-PPROM grouped are called spontaneous preterm births (PTB-S). Methods A retrospective, observational study was conducted in 1.291 preterm non-malformed singleton live-born children to nulliparous and multiparous mother’s in Tucumán-Argentina between 2005 and 2010. Over 50 maternal variables and ten newborn variables were compared between the different clinical subtypes. The comparisons were done to identify heterogeneity between subtypes of preterm birth: (PTB-S) vs. (PTB-M), and within spontaneous subtype: (PTB-I) vs. (PTB-PPROM). In the same way, two conditional logistic multivariate regressions were used to compare the odds ratio (OR) between PTB-S and PTB-M, as well as PTB-I and PTB-PPROM. We matched for maternal age when comparing maternal variables and gestational age when comparing infant variables. Results The PTB-I subtype was characterized by younger mothers of lower socioeconomic status, PTB-PPROM was characterized by environmental factors resulting from inflammatory processes, and PTB-M was characterized by increased maternal or fetal risk pregnancies. Conclusions The main risk factor for PTB-I and PTB-M was having had a prior preterm delivery, however previous spontaneous abortion was not a risk factor, suggesting a reproductive selection mechanism. PMID:26701680

Maternal dental caries and pre-term birth: results from the EPIPAP study.

PubMed

Vergnes, Jean-Noel; Kaminski, Monique; Lelong, Nathalie; Musset, Anne-Marie; Sixou, Michel; Nabet, Cathy

2011-07-01

OBJECTIVE. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. MATERIALS AND METHODS. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. RESULTS. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01-1.45] and OR = 1.25 [1.01-1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91-1.32] and aOR = 1.14 [0.91-1.42], respectively). CONCLUSIONS. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.

Examination of the association between male gender and preterm delivery.

PubMed

Brettell, Rachel; Yeh, Peter S; Impey, Lawrence W M

2008-12-01

To examine possible reasons why a male fetus constitutes a risk factor for preterm delivery. Retrospective study of deliveries from hospital database in a UK teaching hospital. The population comprised all deliveries >23 weeks over an 11-year period, excluding multiples, terminations and pregnancies with major abnormalities including indeterminate gender. Obstetric variables and outcomes were initially compared in male and female babies for preterm births in different gestation bands, extreme (<28 weeks), severe (29-32 weeks) and moderate (33-36 weeks). For each, the odds ratios with 95% confidence intervals for preterm delivery were calculated. Then, using binary logistic regression with adjusted odds ratios with 95% confidence intervals, putative causal pathways that might explain the male excess were tested. 75,725 deliveries occurred, of which 4003 (5.3%) were preterm. Males delivered preterm more frequently (OR 1.13, 95% CI 1.06-1.20). This was due to spontaneous (OR 1.30, 95% CI 1.19-1.42) but not iatrogenic (OR 0.96, 95% CI 0.87-1.05) preterm birth. There was an increased risk of pre eclampsia among preterm females. Although males were larger, and male pregnancies were more frequently nulliparous and affected by some other obstetric complications (abruption, urinary tract infection), these did not account for their increased risk. Any effect of growth restriction could not be properly determined. Being male carries an increased risk of spontaneous but not iatrogenic preterm birth. The reasons behind this remain obscure.

Randomized controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with intrauterine infection: study protocol

PubMed Central

2010-01-01

Background Spontaneous preterm deliveries that occur before the 34th week of gestation, and particularly before the 32nd week of gestation, have been strongly associated to intrauterine infection, ascending from vagina, and represent the largest portion of neonatal deaths and neurological problems. Bacterial vaginosis, characterized by a diminished or absent flora of lactobacilli and increased colonization of several anaerobic or facultative microorganisms, increases two times the risk of preterm delivery before the 34th week. Trials of antibiotics failed to show efficacy and effectiveness against spontaneous preterm birth related to bacterial vaginosis. Some studies indicate benefit from selected probiotics to treat genitourinary infections, including bacterial vaginosis. Objective The purpose of this study is to evaluate the effectiveness of the early administration of selected probiotics to pregnant women with asymptomatic bacterial vaginosis/intermediate degree infection to reduce the occurrence of spontaneous preterm delivery and related neonatal mortality and morbidity. Methods/Design Women attending public prenatal care services in Rio de Janeiro will be screened to select asymptomatic pregnant women, less than 20 weeks' gestation, with no indication of elective preterm delivery. Those with vaginal pH > = 4.5 and a Nugent score between 4 and 10 (intermediate degree infection or bacterial vaginosis) will be randomized to either the placebo or the intervention group, after written informed consent. Intervention consists in the use of probiotics, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, 2 capsules a day, each capsule containing more than one million bacilli of each strain, for 6-12 weeks, up to the 24th-25th wk of gestation. Ancillary analyses include quantification of selected cervicovaginal cytokines and genotyping of selected polymorphisms. The randomization process is stratified for history of preterm delivery and blocked. Allocation concealment was designed as well as blinding of women, caregivers and outcome evaluators. The study will be supervised by an independent monitoring committee. Outcomes under study are preterm delivery (< 34- < 32 weeks of gestation) and associated neonatal complications: early neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, and prematurity-related retinopathy; definitions were adapted from those recommended by the 2002 version of the Vermont-Oxford Network. Trial registration at NIH register: NCT00303082. PMID:20591191

Characteristics of antigravity spontaneous movements in preterm infants up to 3 months of corrected age.

PubMed

Miyagishima, Saori; Asaka, Tadayoshi; Kamatsuka, Kaori; Kozuka, Naoki; Kobayashi, Masaki; Igarashi, Risa; Hori, Tsukasa; Yoto, Yuko; Tsutsumi, Hiroyuki

2016-08-01

We investigated whether spontaneous antigravity limbs movements in very low birth weight preterm infants were insufficient compared to those in term infants. The relationship between the quality of general movements (GMs) and antigravity limbs movements was also examined. Preterm infants with very low birth weight without central nervous system disorders nor severe respiration disorders, and healthy term infants were recruited. The infants were set in a supine position. The distance between both hands and between both feet, and the height of both hands and feet from the floor were recorded at 1-3 corrected months for preterm infants, and at 1-3 months for term infants by a 3D motion capture system. The measurements were adjusted for body proportions. GMs in preterm and term infants were assessed similarly. Thirteen preterm and 15 term infants completed the study. In preterm infants, the distance between both hands and between both feet were longer, and the height of both hands and feet were lower than those in term infants in all measurements. In term infants, the height of both hands and feet increased as they developed, but no change was observed in preterm infants. In preterm infants with abnormal GMs, the distance between both hands was longer, and the height of both hands and feet was lower than that in those with normal GMs. There were no such differences between preterm infants with normal GMs and term infants with normal GMs. Antigravity limbs movements in preterm infants within the first 3 month of corrected age were insufficient compared with those in term infants. Furthermore, no improvement with development was observed in preterm infants. In addition, preterm infants with abnormal GMs showed worse antigravity limbs movements than preterm and term infants with normal GMs. The preterm infants with normal GMs could behave similar to the full term infants. Copyright © 2016 Elsevier Inc. All rights reserved.

The interaction between maternal race/ethnicity and chronic hypertension on preterm birth.

PubMed

Premkumar, Ashish; Henry, Dana E; Moghadassi, Michelle; Nakagawa, Sanae; Norton, Mary E

2016-12-01

In both the biomedical and public health literature, the risk for preterm birth has been linked to maternal racial/ethnic background, in particular African-American heritage. Despite this well-documented health disparity, the relationship of comorbid conditions, such as chronic hypertension, to maternal race/ethnicity and preterm birth has received relatively limited attention in the literature. The objective of the study was to evaluate the interaction between chronic hypertension and maternal racial/ethnic background on preterm birth. This is a retrospective cohort study of singleton pregnancies among women who delivered between 2002 and 2015 at the University of California, San Francisco. The associations of chronic hypertension with both spontaneous and medically indicated preterm birth were examined by univariate and multivariate logistical regression, adjusting for confounders including for maternal age, history of preterm birth, maternal body mass index, insurance type (public vs private), smoking, substance abuse, history of pregestational diabetes mellitus, and use of assisted reproductive technologies. The interaction effect of chronic hypertension and racial/ethnicity was also evaluated. All values are reported as odds ratios, with 95% confidence intervals and significance set at P = .05. In this cohort of 23,425 singleton pregnancies, 8.8% had preterm deliveries (3% were medically indicated preterm birth, whereas 5.5% were spontaneous preterm births), and 3.8% of women carried the diagnosis of chronic hypertension. Chronic hypertension was significantly associated with preterm birth in general (adjusted odds ratio, 2.74, P < .001) and medically indicated preterm birth specifically (adjusted odds ratio, 5.25, P < .001). When evaluating the effect of chronic hypertension within racial/ethnic groups, there was an increased odds of a preterm birth among hypertensive, African-American women (adjusted odds ratio, 3.91, P < .001) and hypertensive, Asian-American/Pacific Islander women (adjusted odds ratio, 3.51, P < .001) when compared with their nonhypertensive counterparts within the same racial/ethnic group. These significant effects were also noted with regard to medically indicated preterm birth for hypertensive African-American women (adjusted odds ratio, 6.85, P < .001) and Asian-American/Pacific Islander women (adjusted odds ratio, 9.87, P < .001). There was no significant association of chronic hypertension with spontaneous preterm birth (adjusted odds ratio, 0.87, P = .4). The effect of chronic hypertension on overall preterm birth and medically indicated preterm birth differs by racial/ethnic group. The larger effect of chronic hypertension among African-American and Asian/Pacific Islander women on medically indicated and total preterm birth rates raises the possibility of an independent variable that is not captured in the data analysis, although data regarding the indication for medically indicated preterm delivery was limited in this data set. Further investigation into both social-structural and biological predispositions to preterm birth should accompany research focusing on the effect of chronic hypertension on birth outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Cervical pessaries for prevention of spontaneous preterm birth: past, present and future

PubMed Central

Arabin, B; Alfirevic, Z

2013-01-01

This Review describes the rationale for the use of cervical pessaries to prevent spontaneous preterm birth and their gradual introduction into clinical practice, discusses technical aspects of the more commonly used designs and provides guidance for their use and future evaluation. Possible advantages of cervical pessaries include the easy, ‘one-off’ application, good side-effect profile, good patient tolerance and relatively low cost compared with current alternatives. Use of transvaginal sonography to assess cervical length in the second trimester allows much better selection of patients who may benefit from the use of a cervical pessary, but future clinical trials are needed to establish clearly the role of pessaries as a preterm birth prevention strategy worldwide. PMID:23775862

Evaluation of the quantitative fetal fibronectin test and PAMG-1 test for the prediction of spontaneous preterm birth in patients with signs and symptoms suggestive of preterm labor.

PubMed

Ravi, Mini; Beljorie, Mercy; El Masry, Karim

2018-05-28

The objective of this study is to compare the qualitative fFN test at 50 ng/ml threshold to novel methods for assessing risk of imminent sPTB in women with symptoms of preterm labor (PTL): (1) quantitative fetal fibronectin (qfFN) at four thresholds: 10, 50, 200, and 500 ng/ml; and (2) qualitative PAMG-1 test. Consecutive patients presenting with singleton pregnancies, signs of PTL, gestational age 23.1-34.6, intact membranes, no coitus within 24 h, and cervical dilation ≤3 cm. fFN was performed as standard of care, while clinicians were blinded to the qfFN and PAMG-1 test results. qfFN accuracy was evaluated at four thresholds of 10, 50, 200, and 500 ng/ml for its ability to predict imminent spontaneous preterm delivery (sPTD) ≤ 7 and ≤14 d from the time of sample collection. The PAMG-1 test was evaluated based on its qualitative result for the same delivery endpoints. Seventy-two patients were analyzed. Fifty-seven percent of patients had an fFN concentration of <10 ng/ml fFN; 75% < 50 ng/ml; 92% < 200 ng/ml; 97% < 500 ng/ml. The SN, SP, PPV, and NPV for fFN at each of the four cutoffs for sPTB ≤7 d: 10 ng/ml: 67%, 58%, 6%, 98%; 50 ng/ml: 67%, 77%, 11%, 98%; 200 ng/ml: 33%, 93%, 17%, 97%; 500 ng/ml: 0%, 97%, 0%, 96%. The PAMG-1 test was positive in 7% of patients. SN, SP, PPV, and NPV for PAMG-1 for sPTD ≤7 d were 67%, 96%, 40%, and 99%, respectively. Compared with qfFN, the PAMG-1 test is a better predictor of spontaneous delivery within 7 d while maintaining a very high negative predictive value. The PAMG-1 test is an easy-to-use bedside test that provides rapid results, does not require a speculum examination, can be used after vaginal exam and coitus and does not require specialized equipment to analyze results. As to be expected, compared with the conventional cutoff of fFN (50 ng/ml), a higher fFN cutoff of 200 ng/ml does seem to increase the PPV of the test, but this comes at a cost to the fFN test's SN and NPV, rendering it of little to no advantage in clinical practice.

Maternal drinking water arsenic exposure and perinatal outcomes in Inner Mongolia, China

EPA Science Inventory

Exposure to high levels of arsenic has been reported to increase adverse birth outcomes including spontaneous abortion, preterm birth, and low birthweight. This study evaluated the relationship between maternal arsenic exposure and perinatal endpoints (term birthweight, preterm ...

The effect of omega-3 supplementation on pregnancy outcomes by smoking status.

PubMed

Kuper, Spencer G; Abramovici, Adi R; Jauk, Victoria C; Harper, Lorie M; Biggio, Joseph R; Tita, Alan T

2017-10-01

Smoking during pregnancy is associated with adverse maternal and neonatal outcomes such as preterm delivery, intrauterine growth restriction, stillbirth, and low birth weight. Because smoking causes oxidative stress, some have suggested using antioxidants to counteract the effects of oxidative stress. Smokers have lower serum levels of omega-3 fatty acids, an important antioxidant, and thus, investigating whether omega-3 supplementation in smokers reduces adverse maternal and neonatal outcomes represents an important area of research. To investigate whether the antioxidant effect of omega-3 fatty acid supplementation on the incidence of adverse pregnancy outcomes differs between smokers and nonsmokers. Secondary analysis of a multicenter randomized controlled trial of omega-3 supplementation for preterm delivery prevention in women with a singleton pregnancy and a history of a previous singleton spontaneous preterm delivery. Subjects were randomized to begin omega-3 or placebo before 22 weeks, which was continued until delivery. All women received 17 alpha-hydroxyprogesterone caproate intramuscularly weekly beginning between 16 and 20 weeks of gestation and continued until 36 weeks of gestation or delivery, whichever occurred first. The primary outcome was spontaneous preterm delivery. Secondary outcomes were indicated preterm delivery, any preterm delivery (spontaneous and indicated), pregnancy-associated hypertension (gestational hypertension and preeclampsia), a neonatal composite (retinopathy of prematurity, intraventricular hemorrhage grade III or IV, patent ductus arteriosus, necrotizing enterocolitis, sepsis, respiratory morbidity, or perinatal death), low birth weight (<2500 g), small for gestational age (less than the 10th percentile), and neonatal intensive care unit or intermediate nursery admission. The study population was stratified into smokers and nonsmokers, and the incidence of each outcome was compared by omega-3 supplementation versus placebo in each subgroup. Zelen tests were performed to test for homogeneity of effect in smokers and nonsmokers. Of 851 subjects included in the analysis, 136 (16%) smoked. Baseline characteristics between omega-3 and placebo groups did not differ in smokers or nonsmokers. Omega-3 supplementation was associated with a lower risk of spontaneous preterm delivery in smokers (relative risk, 0.56, 95% confidence interval, 0.36-0.87) but not in nonsmokers (relative risk 1.04, 95% confidence interval 0.84-1.29); P value for interaction = 0.013. Low birth weight was also less frequent in smokers receiving omega-3 supplementation (relative risk 0.57, 95% confidence interval 0.36-0.90) compared with nonsmokers (relative risk 0.93, 95% confidence interval 0.71-1.24); P value for interaction = 0.047. The effect on other secondary outcomes did not differ significantly between smokers and nonsmokers. Omega-3 supplementation in smokers may have a protective effect against recurrent spontaneous preterm delivery and low birth weight. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of fertility treatment on adverse perinatal outcomes in women aged at least 40 years.

PubMed

Harlev, Avi; Walfisch, Asnat; Oran, Eynan; Har-Vardi, Iris; Friger, Michael; Lunenfeld, Eitan; Levitas, Eliahu

2018-01-01

To compare perinatal outcomes between spontaneous conception and assisted reproductive technologies (ART) among patients of advanced maternal age. The present retrospective study included data from singleton pregnancies of women aged at least 40 years who delivered between January 1, 1991, and December 31, 2013, at Soroka University Medical Center, Beer Sheva, Israel. Demographic, obstetric, and perinatal data were compared between pregnancies conceived with ART (in vitro fertilization [IVF] or ovulation induction) and those conceived spontaneously. Multiple regression models were used to define independent predictors of adverse outcomes. A total of 8244 singleton pregnancies were included; 229 (2.8%) following IVF, 86 (1.0%) following ovulation induction, and 7929 (96.2%) were spontaneous. Preterm delivery (P<0.001), fetal growth restriction (FGR) (P<0.001), and cesarean delivery (P<0.001) demonstrated linear associations with the conception mode; the highest rates for each were observed for IVF, with decreased rates for ovulation induction and spontaneous conception. The incidence of gestational diabetes and hypertensive disorders were highest among pregnancies following ART. No association was observed between conception mode and perinatal mortality. Multivariate logistic regression demonstrated that IVF was independently associated with increased odds of preterm delivery (P<0.001) and FGR (P=0.027) compared with spontaneous conception. Among patients of advanced maternal age, ART were independently associated with increased FGR and preterm delivery rates compared with spontaneous pregnancies; perinatal mortality was comparable. © 2017 International Federation of Gynecology and Obstetrics.

Combined value of placental alpha microglobulin-1 detection and cervical length via transvaginal ultrasound in the diagnosis of preterm labor in symptomatic patients.

PubMed

Bolotskikh, Vyacheslav; Borisova, Vera

2017-08-01

We aimed to evaluate the combined value of placental alpha microglobulin-1 (PAMG-1) and cervical length (CL) via transvaginal ultrasound for assessing risk of imminent spontaneous preterm delivery in patients presenting with threatened preterm labor (PTL). Clinical exam, PAMG-1 test, cardiotocography, and CL measurement via transvaginal ultrasound were performed on all patients meeting inclusion criteria. Ninety-nine patients at 22 +0 -36 +6 gestational weeks with the symptoms of PTL were included. The interval between sample collection and delivery was measured for each method. Performance metrics were calculated for PAMG-1 test, CL < 25 mm, and contractions ≥ 8/h. The sensitivity, specificity, positive predictive value, and negative predictive value for the PAMG-1 test were 100%, 95%, 75%, 100% and 100%, 98%, 88%, 100% for 7 and 14 days, respectively; the respective values for CL < 25 mm were 83%, 59%, 22%, 96% and 79%, 59%, 24%, 94% for 7 and 14 days; and those for contractions ≥ 8/h were 42%, 38%, 8%, 83% and 43%, 38%, 10%, 80% for 7 and 14 days. Specificity for the PAMG-1 test was statistically significant (P < 0.001) in pairwise comparisons for all other methods. Patients were divided into four groups for analysis of PAMG-1 test performance as follows: CL < 15 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively); CL < 25 mm (100%, 94%, 83%, 100% and 100%, 97%, 92%, 100% for 7 and 14 days, respectively); CL of 15-30 mm (100%, 95%, 64%, 100% and 100%, 97%, 82%, 100% for 7 and 14 days, respectively); and CL ≥ 30 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively). The use of the PAMG-1 test in patients with a CL of 15-30 mm is highly predictive of imminent spontaneous preterm delivery in women presenting with threatened PTL and could save hospital resources. © 2017 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.

Psychosocial Stress and Preterm Birth: The Impact of Parity and Race.

PubMed

Wheeler, Sarahn; Maxson, Pamela; Truong, Tracy; Swamy, Geeta

2018-03-29

Objectives Studies examining risk factors for preterm birth (PTB) such as psychosocial stress are often focused on women with a history of PTB; however, most preterm babies are born to women with no history of preterm birth. Our objective was to determine if the relationship between psychosocial stress and PTB is altered by parity. Non-Hispanic black (NHB) women have increased psychosocial stress and PTB; therefore, we further aimed to determine if race alters the relationship between psychosocial stress, parity, and PTB. Methods We performed a secondary analysis of the Healthy Pregnancy, Healthy Baby Study comparing pregnant women who were primiparous (first pregnancy), multiparous with history of preterm birth, or multiparous with history of term birth. Perceived stress, perceived racism, interpersonal support, John Henryism and self-efficacy were measured using validated instruments. Logistic regression was used to model the effect of psychosocial stress on PTB stratified by parity and race. Results The analysis entire cohort included 1606 subjects, 426 were primiparous, 268 had a history of presterm birth, and 912 had a history of term birth. In women with a history of term birth, higher self-efficacy was associated with lower odds of spontaneous PTB, and this association was amplified in NHB women. In women with a history of spontaneous PTB, John Henryism Active Coping was associated with lower odds of spontaneous PTB in the index pregnancy. Conclusions for Practice The relationship between psychosocial stress and PTB may be mediated by parity and race.

Does assisted reproduction technology, per se, increase the risk of preterm birth?

PubMed

Blickstein, I

2006-12-01

There is little doubt that all methods of assisted reproduction increase the likelihood of multiple pregnancy and, as a result, increase the likelihood of preterm birth. Data from the East Flanders Prospective Twin Study clearly show that the proportion of spontaneous to iatrogenic twins has changed from 25:1 to 1:1 over the past two decades. Data from the very low birthweight (VLBW) Infant Database of the Israel Neonatal Network showed that 10% of VLBW singletons were a result of assisted reproduction compared with 60% of the VLBW twins and 90% of the VLBW triplets. Irrespective of plurality, an association between preterm birth and assisted reproduction has long been suspected and was related to causes such as iatrogenic preterm birth (in the so-called 'premium' pregnancies), fertility history, past obstetric performance and to underlying medical conditions of the female partner. With more data available, a clearer picture is defined. Two different, recent meta-analyses showed that singleton pregnancies resulting from in vitro fertilisation (IVF) have increased rates of preterm birth at <33 weeks of gestation (OR 2.99; 95% CI 1.54-5.80), at <37 weeks of gestation (OR 1.93; 95% CI 1.36-2.74) and a relative risk of 1.98 (95% CI 1.77-2.22) for preterm birth in singleton pregnancies resulting from in vitro fertilisation embryo transfer/gamete intra fallopian transfer (IVF-ET/GIFT) compared with naturally conceived pregnancies. Since there is no way to predict which pregnant woman is at increased risk of preterm birth, it may be advisable to consider all pregnancies after assisted reproduction as being at risk. In any case, the most appropriate endpoint after assisted reproduction should also include preterm or term birth as measure of success.

Neutrophil chemotaxis in cord blood of term and preterm neonates is reduced in preterm neonates and influenced by the mode of delivery and anaesthesia.

PubMed

Birle, Alexandra; Nebe, C Thomas; Hill, Sandra; Hartmann, Karin; Poeschl, Johannes; Koch, Lutz

2015-01-01

Bacterial infections, even without any perinatal risk factors, are common in newborns, especially in preterm neonates. The aim of this study was to evaluate possible impairment of neutrophil chemotaxis in term and preterm neonates compared with adults as well as neonates with different modes of delivery and anaesthesia. We analysed the expression of the adhesion molecule L-Selectin as well as shape change, spontaneous and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced transmigration of neutrophils in a flow cytometric assay of chemotaxis after spontaneous delivery with Cesarian Section (CS) under spinal anaesthesia (mepivacaine, sufentanil), epidural anaesthesia (ropivacaine or bupivacaine, sufentanil) or general anaesthesia (ketamine, thiopental, succinylcholine). Chemokinesis was higher (p=0.008) in cord blood neutrophils than in the adult ones, whereas those could be more stimulated by fMLP (p=0.02). After vaginal delivery neutrophils showed a higher spontaneous and fMLP-stimulated chemotactic response compared to neonates after CS without labor. Comparing different types of anaesthesia for CS, spinal anaesthesia resulted in less impairment on chemotaxis than general anaesthesia or epidural anaesthesia. The new flow cytometric assay of neutrophil chemotaxis is an appropriate and objective method to analyse functional differences even in very small volumes of blood, essential in neonatology. Term neonates do not show reduced chemotaxis compared to adults. Preterm neonates present with reduced chemotaxis and chemokinesis, confirming the well known deficits in their neutrophil function. The side effects of maternal drugs on the neonatal immune system have to be considered especially when the immune response is already impaired, as in preterm infants.

Characteristics of Phonological Development as a Risk Factor for Language Development in Italian-Speaking Pre-Term Children: A Longitudinal Study

ERIC Educational Resources Information Center

D'Odorico, Laura; Majorano, Marinella; Fasolo, Mirco; Salerni, Nicoletta; Suttora, Chiara

2011-01-01

This study analysed the early linguistic development of Italian pre-term children. Samples of spontaneous pre-linguistic and verbal production were recorded at 12 and 18 months of age from two groups of children: 24 pre-term children and 15 full-term children. The Italian version of the MacArthur-Bates Questionnaire was administered at 24 months…

The impact of medically indicated and spontaneous preterm birth among hypertensive women.

PubMed

Kase, Benjamin A; Carreno, Carlos A; Blackwell, Sean C; Sibai, Baha M

2013-11-01

To (1) describe the frequency of spontaneous preterm birth (SPTB) and medically indicated preterm birth (PTB) among women with chronic hypertension (CHTN) and (2) to evaluate differences in neonatal outcomes according to SPTB or medically indicated PTB. Retrospective analysis of a previously conducted multicenter randomized trial. Deliveries were categorized as SPTB or medically indicated and stratified by gestational ages (<37 weeks, 34 to 366/7 weeks, 30 to 336/7 weeks, < 30 weeks). Rates of neonatal intensive care unit admission, composite respiratory morbidity, perinatal mortality, and small for gestational age (SGA) were evaluated. Of 765 women, 32.2% (n = 246) delivered at < 37 weeks, of which 10.5% (n = 80) were SPTB and 21.6% (n = 166) were medically indicated. Fifty-nine percent of PTBs occurred in the late preterm period (n = 146). SGA was significantly more frequent among those with medically indicated PTB at < 30 weeks (p = 0.03). There were no other differences in adverse neonatal outcomes between medically indicated versus SPTB at any gestational age (p > 0.05). Nearly one-third of women with CHTN delivered preterm. The majority of PTBs were medically indicated and late preterm, but approximately one-third were due to SPTB. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis

PubMed Central

Lamont, Ronald F.; Nhan-Chang, Chia-Ling; Sobel, Jack D.; Workowski, Kimberly; Conde-Agudelo, Agustin; Romero, Roberto

2011-01-01

The purpose of this study was to determine whether the administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation reduces the risk of preterm birth and late miscarriage. We conducted a systematic review and metaanalysis of randomized controlled trials of the early administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation. Five trials that comprised 2346 women were included. Clindamycin that was administered at <22 weeks of gestation was associated with a significantly reduced risk of preterm birth at <37 weeks of gestation and late miscarriage. There were no overall differences in the risk of preterm birth at <33 weeks of gestation, low birthweight, very low birthweight, admission to neonatal intensive care unit, stillbirth, peripartum infection, and adverse effects. Clindamycin in early pregnancy in women with abnormal vaginal flora reduces the risk of spontaneous preterm birth at <37 weeks of gestation and late miscarriage. There is evidence to justify further randomized controlled trials of clindamycin for the prevention of preterm birth. However, a deeper understanding of the vaginal microbiome, mucosal immunity, and the biology of bacterial vaginosis will be needed to inform the design of such trials. PMID:22071048

Spontaneous movements in the supine position of healthy term infants and preterm infants with or without periventricular leukomalacia.

PubMed

Kouwaki, Masanori; Yokochi, Mitsuko; Togawa, Yasuko; Kamiya, Takeshi; Yokochi, Kenji

2013-04-01

The individual motor elements presumed to be essential for motor development were determined from spontaneous movements involving the entire body of normal term and preterm infants. Then, diagnostic items for motor abnormality in infants with periventricular leukomalacia (PVL) were investigated. Video recordings of 24 healthy term infants, 21 normal preterm infants (8 males, 13 females; median gestational age 30 weeks; median birth weight 1216g) and 14 preterm infants with PVL (6 males, 8 females; median gestational age 30 weeks; median birth weight 1360g) were analyzed. In healthy term infants, predominant shoulder rotation was noticed until 1 month of age. After 2 months of age, isolated movements of the shoulder, elbow, hip, knee, and ankle frequently emerged. In preterm infants with PVL at the corrected age of 2 months, startle response and predominant shoulder rotation were more frequently seen and isolated neck, shoulder, elbow, hip, knee, and ankle movements were less frequently seen than in the normal preterm infants (Fisher's exact test, p<0.025). At 2 months of age, isolated movements evolve, and their failure to occur is suggested to be a useful sign for the diagnosis of cerebral motor disorders. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Amniotic Fluid Soluble HLA-G in Term and Preterm Parturition, and Intra-amniotic Infection/Inflammation

PubMed Central

Kusanovic, Juan Pedro; Romero, Roberto; Jodicke, Cristiano; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Edwin, Sam S.; Pacora, Percy; Hassan, Sonia S.

2012-01-01

Objective Circulating soluble HLA-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intraamniotic infection/inflammation (IAI). Study design This cross-sectional study included the following groups: 1) midtrimester (n=55); 2) normal pregnancy at term with (n=50) and without (n=50) labor; 3) spontaneous PTL with intact membranes divided into: a) PTL who delivered at term (n=153); b) PTL who delivered preterm without IAI (n=108); and c) PTL with IAI (n=84); and 4) preterm PROM with (n=46) and without (n=44) IAI. sHLA-G concentrations were determined by ELISA. Non-parametric statistics were used for analysis. Results 1) Among patients with PTL, the median AF sHLA-G concentration was higher in patients with IAI than in those without IAI or women that delivered at term (p<0.001 for both comparisons); 2) Similarly, patients with preterm PROM and IAI had higher median AF sHLA-G concentrations than those without IAI (p=0.004); 3) Among patients with PTL and delivery, those with histologic chorioamnionitis and/or funisitis had a higher median AF sHLA-G concentration than those without histologic inflammation (p<0.001); and 4) The median AF sHLA-G concentration did not change with advancing gestational age. Conclusions AF sHLA-G concentrations are elevated in preterm parturition associated to IAI as well as in histologic chorioamnionitis. We propose that sHLA-G may participate in the regulation of the host immune response against intra-amniotic infection. PMID:19916713

Visual and Cardiac Responses to Animate and Inanimate Faces by Young Term and Preterm Infants.

ERIC Educational Resources Information Center

Field, Tiffany Martini

1979-01-01

Infants' looking and looking-away behaviors, as well as cardiac responses to mothers' spontaneous and imitative faces and to dolls' animated and still faces, were recorded for 18 term and 19 preterm infants when they were three months old. (JMB)

Perinatal outcome of singleton siblings born after assisted reproductive technology and spontaneous conception: Danish national sibling-cohort study.

PubMed

Henningsen, Anna-Karina Aaris; Pinborg, Anja; Lidegaard, Øjvind; Vestergaard, Christina; Forman, Julie Lyng; Andersen, Anders Nyboe

2011-03-01

To compare the perinatal outcome of singleton siblings conceived differently. National population-based registry study. Denmark, from 1994 to 2008. Pairs of siblings (13,692 pairs; n = 27,384 children) conceived after IVF, intracytoplasmatic sperm injection (ICSI), frozen embryo replacement (FER), or spontaneous conception subcategorized into five groups according to succession: [1] IVF-ICSI vs. spontaneous conception (n = 7,758), [2] IVF-ICSI vs. FER (n = 716), [3] FER vs. FER (n = 34), [4] IVF-ICSI vs. IVF-ICSI (n = 2,876), and [5] spontaneous conception vs. spontaneous conception (n = 16,000). Observations were obtained from national registries. Birth weight, gestational age, low birth weight (<2,500 g), preterm birth (<37 weeks' gestation) and perinatal deaths. Mean birth weight was 65 g (95% confidence interval [CI], 41-89] lower in all assisted reproductive technology children compared with their spontaneously conceived siblings. FER children were 167 g (95% CI, 90-244] heavier than siblings born after replacement of fresh embryos. The difference in birth weight between firstborn and second born sibling depended on order of conception method. Higher risk of low birth weight with (odds ratio [OR], 1.4; 95%CI, 1.1-1.7] and preterm birth (OR, 1.3; 95% CI, 1.1-1.6] was observed in IVF/ICSI compared with spontaneous conception. When differentiating between order and mode of conception, it seems that assisted reproductive technology plays a role in mean birth weight and risk of low birth weight and preterm birth. Birth weight was higher in siblings born after FER compared with fresh embryos replacement. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Preterm labor: one syndrome, many causes.

PubMed

Romero, Roberto; Dey, Sudhansu K; Fisher, Susan J

2014-08-15

Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment. Copyright © 2014, American Association for the Advancement of Science.

Pregnant human peripheral leukocyte migration during several late pregnancy clinical conditions: a cross-sectional observational study.

PubMed

Takeda, Jun; Fang, Xin; Olson, David M

2017-01-10

Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating into stromal tissue. There they interact with resident immune and stromal cells to produce a mixture of matrix metalloproteinases, prostaglandins and cytokines including interleukin-1β (IL-1β) and IL-6 that in turn transform the uterus from pregnancy to parturition. Since migration is an early parturitional event our purpose was to study the migration of maternal peripheral blood leukocytes in response to a standard chemotactic signal during several different conditions of late pregnancy. We used a cross-sectional observational study design. Subjects were (sTL) spontaneous normal labour delivered vaginally at term, (TNL) elective caesarean section at term without labour, (PTL) preterm in labour, (PTNL) preterm not in labour, (TPTL) threatened preterm labour, and (pPROM) preterm with premature rupture of membranes. Leukocytes (100,000) obtained by venipuncture and chemotactic factor isolated from term labour fetal membranes were placed in the upper and lower halves, respectively, of a Boyden chamber separated by a filter with 3μm pores. Migrated leukocytes were assessed by flow cytometry. The number of leukocytes that migrated in 90 min was the primary outcome measure. Increased numbers of leukocytes from peripheral blood of women in labour (TL or PTL) or soon to go into labour (PPROM) migrated towards a chemotactic signal than did leukocytes from women not in labour (TNL, PTNL, or TPTL) (p < 0.0001). All pPROM delivered within 7d; TPTL delivered >30d. Receiver operating characteristic curve parameters indicated the cut-off point for delivery within 7d to be 37,082 leukocytes with sensitivity 78.1%, specificity 88.9%, positive predictive value 91.4%, negative predictive value 72.7%, and area under the curve 0.83. Leukocyte migration to a fetal membrane signal varies in a predictable fashion during various clinical situations of late gestation. This principle has the potential to be improved to become a clinical test to predict delivery.

Intakes of Garlic and Dried Fruits Are Associated with Lower Risk of Spontaneous Preterm Delivery12

PubMed Central

Myhre, Ronny; Brantsæter, Anne Lise; Myking, Solveig; Eggesbø, Merete; Meltzer, Helle Margrete; Haugen, Margaretha; Jacobsson, Bo

2013-01-01

Several studies have found associations between microbial infections during pregnancy and preterm delivery (PTD). We investigated the influence of food with antimicrobial and prebiotic components on the risk of spontaneous PTD. A literature search identified microbes associated with spontaneous PTD. Subsequently, 2 main food types (alliums and dried fruits) were identified to contain antimicrobial components that affect the microbes associated with spontaneous PTD; they also contained dietary fibers recognized as prebiotics. We investigated intake in 18,888 women in the Norwegian Mother and Child Cohort (MoBa), of whom 950 (5%) underwent spontaneous PTD (<37 gestational weeks). Alliums (garlic, onion, leek, and spring onion) [OR: 0.82 (95% CI: 0.72, 0.94), P = 0.005] and dried fruits (raisins, apricots, prunes, figs, and dates) [OR: 0.82 (95% CI: 0.72, 0.94); P = 0.005] were associated with a decreased risk of spontaneous PTD. Intake of alliums was related to a more pronounced risk reduction in early spontaneous PTD (gestational weeks 28–31) [OR: 0.39 (95% CI: 0.19, 0.80)]. The strongest association in this group was with garlic [OR: 0.47 (95% CI: 0.25–0.89)], followed by cooked onions. Intake of dried fruits showed an association with preterm prelabor rupture of membranes (PPROM) [OR: 0.74 (95% CI: 0.65, 0.95)]; the strongest association in this group was with raisins [OR: 0.71 (95% CI: 0.56, 0.92)]. The strongest association with PPROM in the allium group was with garlic [OR: 0.74 (95% CI: 0.56, 0.97)]. In conclusion, intake of food with antimicrobial and prebiotic compounds may be of importance to reduce the risk of spontaneous PTD. In particular, garlic was associated with overall lower risk of spontaneous PTD. Dried fruits, especially raisins, were associated with reduced risk of PPROM. PMID:23700347

Post-hemorrhagic hydrocephalus and diabetes insipidus in preterm infants.

PubMed

Borenstein-Levin, Liron; Koren, Ilana; Kugelman, Amir; Bader, David; Toropine, Arina; Riskin, Arieh

2014-11-01

We present two cases of transient central diabetes insipidus in preterm neonates with post-hemorrhagic hydrocephalus. Although the association between intraventricular hemorrhage and diabetes insipidus has been described in preterm infants, the association between diabetes insipidus and hydrocephalus, and the fact that such central diabetes insipidus could be reversible with the reduction of ventricular size, either because of spontaneous resolution or the placement of ventriculo-peritoneal shunt is first described here in neonates.

The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.

PubMed

Prince, Amanda L; Ma, Jun; Kannan, Paranthaman S; Alvarez, Manuel; Gisslen, Tate; Harris, R Alan; Sweeney, Emma L; Knox, Christine L; Lambers, Donna S; Jobe, Alan H; Chougnet, Claire A; Kallapur, Suhas G; Aagaard, Kjersti M

2016-05-01

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/or funisitis using state-of-the-science whole-genome shotgun metagenomics. This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either betamethasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative metagenomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis. Copyright © 2016. Published by Elsevier Inc.

The placental microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis

PubMed Central

Kannan, Paranthaman S.; Alvarez, Manuel; Gisslen, Tate; Harris, R. Alan; Sweeney, Emma L.; Knox, Christine L.; Lambers, Donna S.; Jobe, Alan H.; Chougnet, Claire A.; Kallapur, Suhas G.; Aagaard, Kjersti M.

2016-01-01

BACKGROUND Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. OBJECTIVE In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/ or funisitis using state-of-the-science whole-genome shotgun metagenomics. STUDY DESIGN This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9–15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. RESULTS Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either beta-methasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). CONCLUSION Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative meta-genomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis. PMID:26965447

Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial.

PubMed

Ugwumadu, Austin; Manyonda, Isaac; Reid, Fiona; Hay, Phillip

2003-03-22

Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat. Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.

Fragment Bb in Amniotic Fluid: Evidence for complement activation by the alternative pathway in women with Intra-amniotic Infection/Inflammation

PubMed Central

Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Tovi, Shali Mazaki; Pedro, Kusanovic Juan; Soto, Eleazar; Gotsch, Francesca; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Mittal, Pooja; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.

2013-01-01

Objective Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm), and in the presence of intra-amniotic infection/ inflammation (IAI). Study design This cross-sectional study included patients in the following groups: 1) midtrimester (n=64); 2) term in spontaneous labor (n=70); 3) term not in labor (n=43); 4) spontaneous preterm labor (PTL) who delivered at term (n=76); 5) PTL without IAI who delivered preterm (n=73); 6) PTL with IAI (n=76); 7) prelabor rupture of the membranes (preterm PROM) without IAI (n=71); and 8) preterm PROM with IAI (n=71). Fragment Bb concentration in amniotic fluid was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results 1) Fragment Bb was detected in all AF samples (n=544); 2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 μg/mL, interquartile range (IQR) 1.78-3.22 vs. 1.64 μg/mL, IQR 1.06-3.49; p<0.001]; 3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI who delivered preterm (4.82 μg/mL, IQR 3.32-6.08 vs. 3.67 μg/mL, IQR 2.35-4.57; p<0.001) and than that of women with an episode of PTL who delivered at term (3.21 μg/mL, IQR 2.39-4.16; p<0.001); 4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 μg/mL, IQR 2.58-5.79 vs. 2.79 μg/mL, IQR 2.09-3.89; p<0.001). 5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 μg/mL, IQR 1.86-3.22; p=0.97). Conclusions 1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the amniotic fluid, and its concentration increases with advancing gestational age; 2) Amniotic fluid concentrations of fragment Bb are higher in pregnancies complicated with IAI; and 3) Labor at term is not associated with changes in the amniotic fluid concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI. PMID:19603351

A Cross-Species Analysis of Animal Models for the Investigation of Preterm Birth Mechanisms

PubMed Central

Nielsen, Brian W.; Bonney, Elizabeth A.; Pearce, Bradley D.; Donahue, Leah Rae; Sarkar, Indra Neil

2015-01-01

Background: Spontaneous preterm birth is the leading cause of neonatal morbidity and mortality worldwide. The ability to examine the exact mechanisms underlying this syndrome in humans is limited. Therefore, the study of animal models is critical to unraveling the key physiologic mechanisms that control the timing of birth. The purpose of this review is to facilitate enhanced assimilation of the literature on animal models of preterm birth by a broad range of investigators. Methods: Using classical systematic and informatics search techniques of the available literature through 2012, a database of intact animal models was generated. Research librarians generated a list of articles using multiple databases. From these articles, a comprehensive list of Medical Subject Headings (MeSH) was created. Using mathematical modeling, significant MeSH descriptors were determined, and a MEDLINE search algorithm was created. The articles were reviewed for mechanism of labor induction categorized by species. Results: Existing animal models of preterm birth comprise specific interventions to induce preterm birth, as no animal model was identified that exhibits natural spontaneous preterm birth at an incidence comparable to that of the humans. A search algorithm was developed which when used results in a comprehensive list of agents used to induce preterm delivery in a host of animal species. The evolution of 3 specific animal models—sheep, mice, and rats—has demonstrated a clear shift in focus in the literature from endocrine to inflammatory agents of preterm birth induction. Conclusion: The process of developing a search algorithm to provide efficient access to information on animal models of preterm birth illustrates the need for a more precise organization of the literature to allow the investigator to focus on distinctly maternal versus fetal outcomes. PMID:26377998

Cold-knife conisation and large loop excision of transformation zone significantly increase the risk for spontaneous preterm birth: a population-based cohort study.

PubMed

Jančar, Nina; Mihevc Ponikvar, Barbara; Tomšič, Sonja

2016-08-01

Our aim was to explore the association between cold-knife conisation and large loop excision of transformation zone (LLETZ) with spontaneous preterm birth in a large 10-year national sample. We wanted to explore further the association of these procedures with preterm birth according to gestation. We conducted a population based retrospective cohort study, using data from national Medical Birth Registry. The study population consisted of all women giving birth to singletons in the period 2003-2012 in Slovenia, excluding all induced labors and elective cesarean sections before 37 weeks of gestation (N=192730). We compared the prevalence of spontaneous preterm births (before 28 weeks, before 32 weeks, before 34 weeks and before 37 weeks of gestation) in women with cold-knife conisation or LLETZ compared to women without history of conisation, calculating odds ratios (OR), adjusted for potential confounders. Chi-square test was used for descriptive analysis. Logistic regression analyses were performed to estimate crude odds ratio (OR) and adjusted odds ratio (aOR) and their 95% confidence intervals (95% CI) with two-sided probability (p) values. A total of 8420 (4.4%) women had a preterm birth before 37 weeks of gestation, 2250 (1.2%) before 34 weeks of gestation, 1333 (0.7%) before 32 weeks of gestation and 603 (0.3%) before 28 weeks of gestation. A total of 4580 (2.4%) women had some type of conisation in their medical history: 2083 (1.1%) had cold-knife conisation and 2498 (1.3%) had LLETZ. In women with history of cold-knife conisation, the adjusted OR for preterm birth before 37 weeks of gestation was 3.13 (95% CI; 2.74-3.57) and for preterm birth before 28 weeks of gestation 5.96 (95% CI; 4.3-8.3). In women with history of LLETZ, the adjusted OR was 1.95 (95% CI; 1.68-2.25) and 2.88 (95% CI; 1.87-4.43), respectively. Women with cervical excision procedure of any kind have significantly increased odds for preterm birth, especially for preterm birth before 28 weeks and before 32 weeks of gestation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor.

PubMed

Watson, H A; Carter, J; Seed, P T; Tribe, R M; Shennan, A H

2017-09-01

To evaluate the impact of triaging women at risk of spontaneous preterm birth (sPTB) using the QUiPP App, which incorporates a predictive model combining history of sPTB, gestational age and quantitative measurements of fetal fibronectin, compared with a treat-all policy (advocated by the UK National Institute for Health and Care Excellence) among women with threatened preterm labor before 30 weeks' gestation. Prospectively collected data of pregnant women presenting with symptoms of preterm labor (abdominal pain or tightening) at 24-34 weeks' gestation were retrieved from the research databases of the EQUIPP and PETRA studies for subanalysis. Each episode of threatened preterm labor was retrospectively assigned a risk for sPTB within 7 days using the QUiPP App. A primary outcome of delivery within 7 days was used to model the performance accuracy of the QUiPP App compared with a treat-all policy. Using a 5% risk of delivery within 7 days according to the QUiPP App as the threshold for intervention, 9/9 women who presented with threatened preterm labor < 34 weeks would have been treated correctly, giving a sensitivity of 100% (one-sided 97.5% CI, 66.4%) and a negative predictive value of 100% (97.5% CI, 98.9-100%). The positive predictive value for delivery within 7 days was 30.0% (95% CI, 11.9-54.3%) for women presenting before 30 weeks and 20.0% (95% CI, 12.7-30.1%) for women presenting between 30 + 0 and 34 + 0 weeks. If this 5% threshold had been used to triage women presenting between 24 + 0 and 29 + 6 weeks, 89.4% (n = 168) of admissions could have been safely avoided, compared with 0% for a treat-all strategy. No true case of preterm labor would have been missed, as no woman who was assigned a risk of < 10% delivered within 7 days. For women with threatened preterm labor, the QUiPP App can accurately guide management at risk thresholds for sPTB of 1%, 5% and 10%, allowing outpatient management in the vast majority of cases. A treat-all approach would not have avoided admission for any woman, and would have exposed 188 mothers and their babies to unnecessary hospitalization and steroid administration and increased the burden on network and transport services owing to unnecessary in-utero transfers. Prediction of sPTB should be performed before 30 weeks to determine management until there is evidence that such a high level of unnecessary intervention, as suggested by the treat-all strategy, does less harm than the occurrence of rare false negatives. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Is there an association between subclinical hypothyroidism and preterm uterine contractions? A prospective observational study.

PubMed

Nassie, Daniel I; Ashwal, Eran; Raban, Oded; Ben-Haroush, Avi; Wiznitzer, Arnon; Yogev, Yariv; Aviram, Amir

2017-04-01

To investigate the association between subclinical hypothyroidism and preterm contractions. Prospective observational study among women at 23 + 0/7 and 34 + 6/7 weeks of gestation, with no known thyroid function abnormality, and preterm uterine contractions (PTC). All patients underwent laboratory evaluation of Thyroid Stimulating Hormone (TSH) and Free Thyroxin (FT4). Patients with and without PTC were compared. No association was found between PTC and subclinical hypothyroidism. Rate of spontaneous preterm delivery (PTD) was comparable between women with abnormal and normal thyroid function tests. Excluding indicated PTD, patients in the study group had a higher rate of spontaneous PTD (24.7% versus 9.6%, p = 0.03). Patients with past PTD and preterm contractions had higher rates of hypothyroxinemia compared with patients without past PTD (54.6% versus 19.0% and 31.2%, p = 0.001), and patients with past PTD (regardless of the presence or absence of PTC) had higher rate of subclinical hypothyroidism compared with patients with PTC and without PTD (59.1% and 66.7% versus 31.6%, p = 0.017). No association was found between PTC and subclinical hypothyroidism in the entire cohort, except for patients with preterm contractions and a history of past PTD. This specific group of patients might benefit from thyroid function evaluation.

A randomised controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results

PubMed Central

2011-01-01

Background Bacterial vaginosis increases the risk of spontaneous preterm delivery at less than 34 weeks of gestation. Objective The purpose of this study was to evaluate the efficacy of the early administration of selected lactobacilli strains (probiotics) to pregnant women with asymptomatic bacterial vaginosis/intermediate-degree infections to prevent spontaneous premature delivery and associated neonatal morbidity. Methods/Design Asymptomatic pregnant women at less than 20 weeks of gestation, with no indication of elective preterm delivery, with a vaginal pH ≥ 4.5 and Nugent score > 3 were randomly assigned to the placebo or intervention group (oral administration of selected lactobacilli up to the 24th to 26th week of gestation). The randomisation was stratified for the history of premature delivery (HPD) and blocked. The allocation was concealed, and the participating health professionals and patients were blinded. The primary outcome was preterm delivery (<34 to <32 weeks), and the secondary outcomes were associated neonatal complications. Results In total, 4,204 pregnant women were screened; 320 and 324 individuals were respectively randomly assigned to the placebo and intervention groups, and 62% finished the trial. None of the randomised patients were lost to follow-up. For the non-HPD stratum, the intent-to-treat relative risks of spontaneous premature birth at < 34 and < 37 weeks' gestation were 0.33 (0.03, 3.16) and 0.49 (0.17, 1.44), respectively, and they were non-significant (ns) with p = 0.31 and 0.14. The corresponding actual treatment figures were zero and 0.32 (0.09, 1.19), which were ns with p = 0.12 and 0.06. The intent-to-treat relative risk of spontaneous premature birth at < 37 weeks of gestation for the trial as a whole, including HPD and non-HPD participants, was 0.69 (0.26, 1.78), p = 0.30 (ns). The neonatal complications under evaluation occurred in only one infant (< 34 weeks; placebo group) who presented with respiratory distress syndrome and suspected early neonatal sepsis. The recorded adverse events were minor and relatively non-specific. Conclusions The efficacy of the tested probiotics to prevent preterm delivery among women without a history of preterm delivery was not determined because the study sample was insufficient to estimate statistically significant intent-to-treat effects; additional studies are needed to evaluate this intervention among these women. Trial registration Trial registration at NIH register: NCT00303082. Sources of funding: the Brazilian Health Ministry and the State of Rio de Janeiro Research Foundation. PMID:22059409

Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study

PubMed Central

2011-01-01

Background Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. Methods We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Québec, Canada, 1989-2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (< 28, 28-31, 32-36 completed weeks). Odds ratios (OR) of PTB by clinical subtype for systemic and localized maternal comorbidities were estimated using polytomous logistic regression, adjusting for maternal age, grand multiparity, and period. Attributable fractions were calculated. Results PTB rates were higher among mothers with comorbidity (10.9%) compared to those without comorbidity (4.7%). Several comorbidities were associated with greater odds of medically indicated PTB compared with no comorbidity, but only comorbidities localized to the reproductive system were associated with spontaneous PTB. Drug dependence and mental disorders were strongly associated with PPROM and spontaneous PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at < 32 weeks. Major systemic comorbidities (preeclampsia, anemia) were key contributors to PPROM and medically indicated PTBs. Conclusions The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system. PMID:21970736

Association between maternal comorbidity and preterm birth by severity and clinical subtype: retrospective cohort study.

PubMed

Auger, Nathalie; Le, Thi Uyen Nhi; Park, Alison L; Luo, Zhong-Cheng

2011-10-04

Preterm birth (PTB) is a major cause of infant morbidity and mortality, but the relationship between comorbidity and PTB by clinical subtype and severity of gestational age remains poorly understood. We evaluated associations between maternal comorbidities and PTB by clinical subtype and gestational age. We conducted a retrospective cohort study of 1,329,737 singleton births delivered in hospitals in the province of Québec, Canada, 1989-2006. PTB was classified by clinical subtype (medically indicated, preterm premature rupture of membranes (PPROM), spontaneous preterm labour) and gestational age (< 28, 28-31, 32-36 completed weeks). Odds ratios (OR) of PTB by clinical subtype for systemic and localized maternal comorbidities were estimated using polytomous logistic regression, adjusting for maternal age, grand multiparity, and period. Attributable fractions were calculated. PTB rates were higher among mothers with comorbidity (10.9%) compared to those without comorbidity (4.7%). Several comorbidities were associated with greater odds of medically indicated PTB compared with no comorbidity, but only comorbidities localized to the reproductive system were associated with spontaneous PTB. Drug dependence and mental disorders were strongly associated with PPROM and spontaneous PTBs across all gestational ages (OR > 2.0). At the population level, several major comorbidities (placental abruption, chorioamnionitis, oliogohydramnios, structural abnormality, cervical incompetence) were key contributors to all clinical subtypes of PTB, especially at < 32 weeks. Major systemic comorbidities (preeclampsia, anemia) were key contributors to PPROM and medically indicated PTBs. The relationship between comorbidity and clinical subtypes of PTB depends on gestational age. Prevention of PPROM and spontaneous PTB may benefit from greater attention to preeclampsia, anemia and comorbidities localized to the reproductive system.

Air travel and pregnancy outcomes: a review of pregnancy regulations and outcomes for passengers, flight attendants, and aviators.

PubMed

Magann, Everett F; Chauhan, Suneet P; Dahlke, Joshua D; McKelvey, Samantha S; Watson, Erin M; Morrison, John C

2010-06-01

To review flight regulations and gestational complications associated with air travel in pregnant passengers, flight attendants, and aviators. A literature search was undertaken on the relationship of air travel and spontaneous pregnancy losses, intrauterine fetal demise (IUFD), birth weight<10th percentile, preterm delivery, and neonatal intensive care unit admissions. The literature search identified 128 abstracts, of which 9 evaluated air travel and pregnancy outcomes. The risk of a pregnancy loss (spontaneous abortion or IUFD) was greater in flight attendants than controls (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.29, 2.04). The risk of preterm birth<37 weeks was greater in passengers than controls (OR: 1.44, 95% CI: 1.07, 1.93). However, the risk of preeclampsia (OR: 0.86, 95% CI: 0.58, 1.27), neonatal intensive care unit admissions (OR: 1.19, 95% CI: 0.78, 1.82), or birth weight<10th percentile (OR: 1.25, 95% CI: 0.62, 2.48) was not increased. Flight attendants did not have an increased risk of preterm birth compared to controls (OR: 1.37, 95% CI: 0.85, 2.22) or delivering infants with birth weight<10th percentile (OR: 1.57, 95% CI: 0.68, 3.74). The risks of spontaneous abortions and other adverse pregnancy outcomes have been poorly studied in a limited number of investigations. An analysis of the available information suggests a greater risk of spontaneous abortions or IUFD in flight attendants, and a greater risk of preterm birth<37 weeks in air passengers. However, the literature on which these findings are based is generally not of high methodologic quality.

Presentation to delivery interval in women with early preterm delivery presenting with preterm labor: the effect of gestational age.

PubMed

Ashwal, Eran; Shinar, Shiri; Wertheimer, Avital; Reina, Luciena; Miremberg, Hadas; Aviram, Amir; Yogev, Yariv; Hiersch, Liran

2017-10-01

To evaluate the association between gestational age at presentation and interval to delivery in women with early spontaneous preterm delivery (PTD). A retrospective cohort study of women who presented with threatened preterm labor (tPTL) and intact membranes and had a spontaneous PTD <34 weeks in a university-affiliated hospital (2009-2015). The interval from presentation to delivery was compared between different gestational age subgroups. Of 67 550 deliveries during the study period, 252 met inclusion criteria. This cohort was divided to three gestational age subgroups at presentation: 24-28 6/7 weeks (n = 83), 29-31 6/7 weeks (n = 61) and 32-33 6/7 weeks (n = 108). Median time from presentation to delivery was 24.5 h. An inverse relation was observed between gestational age at presentation and admission-delivery interval (group A: 74.7 h, group B: 21.0 h, group C: 14.0 h, p < 0.001). Gestational age at presentation is inversely related to admission-delivery interval in women with tPTL and intact membranes.

Paracetamol treatment of patent ductus arteriosus in preterm infants.

PubMed

Nadir, E; Kassem, E; Foldi, S; Hochberg, A; Feldman, M

2014-10-01

To determine the effectiveness of paracetamol in closing patent ductus arteriosus (PDA) in preterm infants of our population. Infants with symptomatic PDA who failed or could not get ibuprofen treatment, and who were candidates for surgical ligation, were administered oral paracetamol 15 mg kg⁻¹ every 6h, for up to 7 days and were monitored for clinical, echocardiographic and laboratorial courses. Seven infants, between 24-27 weeks' gestation, were included. In four the DA was closed while treated by paracetamol-in one of them the DA reopened, treated with paracetamol again, and closed. In one infant, the DA almost closed, symptoms disappeared, and the DA subsequently closed spontaneously later. Two needed surgical ligation. There were no hematologic or biochemical abnormalities. Although there is the possibility that PDA may have closed spontaneously, it is proposed that paracetamol could contribute to the closure of PDA in preterm infants.

Retained placenta is associated with pre-eclampsia, stillbirth, giving birth to a small-for-gestational-age infant, and spontaneous preterm birth: a national register-based study.

PubMed

Endler, M; Saltvedt, S; Cnattingius, S; Stephansson, O; Wikström, A-K

2014-11-01

To evaluate whether defective placentation disorders, i.e. pre-eclampsia, stillbirth, small for gestational age (SGA), and spontaneous preterm birth, are associated with risk of retained placenta. Population-based cohort study. Sweden. Primiparous women in Sweden with singleton vaginal deliveries between 1997 and 2009 at 32-41 weeks of gestation (n = 386,607), without placental abruption or infants with congenital malformations. Risks were calculated as odds ratios (ORs) by unconditional logistic regression with 95% confidence intervals (95% CIs) after adjustments for maternal, delivery, and infant characteristics. Retained placenta, defined by the presence of both a diagnostic code (of retained placenta) and a procedure code (for the manual removal of the placenta). The overall rate of retained placenta was 2.17%. The risk of retained placenta was increased for women with pre-eclampsia (adjusted OR, aOR, 1.37, 95% CI 1.21-1.54), stillbirth (aOR 1.71, 95% CI 1.28-2.29), SGA birth (aOR 1.47, 95% CI 1.28-1.70), and spontaneous preterm birth (32-34 weeks of gestation, aOR 2.35, 95% CI 1.97-2.81; 35-36 weeks of gestation, aOR 1.55, 95% CI 1.37-1.75). The risk was further increased for women with preterm pre-eclampsia (aOR 1.69, 95% CI 1.25-2.28) and preterm SGA birth (aOR 2.19, 95% CI 1.42-3.38). There was no association between preterm stillbirth (aOR 1.10, 95% CI 0.63-1.92) and retained placenta, but the exposed group comprised only 15 cases. Defective placentation disorders are associated with an increased risk of retained placenta. Whether these relationships indicate a common pathophysiology remains to be investigated. © 2014 Royal College of Obstetricians and Gynaecologists.

Urinary Bisphenol A Levels during Pregnancy and Risk of Preterm Birth

PubMed Central

Ferguson, Kelly K.; Mukherjee, Bhramar; McElrath, Thomas F.; Meeker, John D.

2015-01-01

Background Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB. Objectives In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB. Methods A nested case–control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women’s Hospital in Boston, Massachusetts, during 2006–2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as “spontaneous,” which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or “placental,” which was preceded by preeclampsia or intrauterine growth restriction. Results Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant’s sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males. Conclusions These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB. Citation Cantonwine DE, Ferguson KK, Mukherjee B, McElrath TF, Meeker JD. 2015. Urinary bisphenol A levels during pregnancy and risk of preterm birth. Environ Health Perspect 123:895–901; http://dx.doi.org/10.1289/ehp.1408126 PMID:25815860

Amniotic Fluid Eicosanoids in Preterm and Term Births: Effects of Risk Factors for Spontaneous Preterm Labor

PubMed Central

Menon, Ramkumar; Fortunato, Stephen J.; Milne, Ginger L.; Brou, Lina; Carnevale, Claudine; Sanchez, Stephanie C.; Hubbard, Leah; Lappas, Martha; Drobek, Cayce Owens; Taylor, Robert N.

2012-01-01

OBJECTIVE To evaluate amniotic fluid (AF) arachidonic acid metabolites using enzymatic and nonenzymatic (lipid peroxidation) pathways in spontaneous preterm birth and term births, and to estimate whether prostanoid concentrations correlate with risk factors (race, cigarette smoking, and microbial invasion of amniotic cavity) associated with preterm birth. METHODS In a case-control study, AF was collected at the time of labor or during cesarean delivery. AF samples were subjected to gas chromatography, negative ion chemical ionization, and mass spectrometry for prostaglandin (PG)E2, PGF2α, and PGD2, 6-keto-PGF1α (6-KPGF1α, thromboxane (TXB2), and F2-isoprostane (F2-IsoP). Primary analysis examined differences between prostanoid concentrations in preterm birth (n=133) compared with term births (n=189). Secondary stratified analyses (by race, cigarette smoking and microbial invasion of amniotic cavity) compared eicosanoid concentrations in three epidemiological risk factors. RESULTS AF F2-IsoP, PGE2, and PGD2 were significantly higher at term than in PTB, whereas PGF2 α was higher in PTB 6-KPGF1α and TXB2 concentrations were not different. Data stratified by race (African American or Caucasian) showed no significant disparity among prostanoid concentrations. Regardless of gestational age status, F2-IsoP was threefold higher in smokers, and other eicosanoids were also higher in smokers compared to non-smokers. Preterm birth with microbial invasion of amniotic cavity had significantly higher F2-IsoP compared to preterm birth without microbial invasion of amniotic cavity. CONCLUSIONS Most AF eicosanoid concentrations (F2-isoP PGE2 and PGD2), are higher at term than in preterm birth. The only AF eicosanoid that is not higher at term is PGF2α. PMID:21691170

Endoplasmic reticulum stress is increased after spontaneous labor in human fetal membranes and myometrium where it regulates the expression of prolabor mediators.

PubMed

Liong, Stella; Lappas, Martha

2014-09-01

Increasing evidence indicates that endoplasmic reticulum (ER) stress is involved in various diseases. In nongestational tissues, several markers of the unfolded protein response (UPR) have been shown to regulate the inflammatory response. Thus, the aim of this study was to determine the effect of human labor on markers of ER stress in fetal membranes and myometrium. In addition, the effect of ER stress inhibition on the expression and secretion of proinflammatory and prolabor mediators was also assessed. The markers of ER stress, GRP78, IRE1, and spliced XBP1 (XBP1s), were significantly increased in fetal membranes and myometrium after term and preterm labor compared to nonlaboring samples. Given that inflammation is considered to be one of the leading causes of spontaneous preterm birth, here we used bacterial endotoxin lipopolysaccharide (LPS) as a model for infection-induced preterm birth. In term nonlabored fetal membranes and myometrium, LPS induced UPR activation as evidenced by a significant increase in the expression of GRP78, IRE1, and XBP1s in fetal membranes and myometrium. The use of the chemical chaperones 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA) alleviated ER stress induced by LPS. 4-PBA and TUDCA also ameliorated the increase in LPS-induced prolabor mediators. Our data suggest that the UPR may regulate the inflammatory responses associated with labor or infection in fetal membranes and myometrium of pregnant term and preterm women. Thus, the use of ER stress inhibitors, in particular 4-PBA or TUDCA, may be a potential therapeutic strategy for the prevention of infection-mediated spontaneous preterm birth. © 2014 by the Society for the Study of Reproduction, Inc.

Effect of interpregnancy interval on risk of spontaneous preterm birth in Emirati women, United Arab Emirates.

PubMed Central

Al-Jasmi, Fatima; Al-Mansoor, Fatima; Alsheiba, Aisha; Carter, Anne O.; Carter, Thomas P.; Hossain, M. Moshaddeque

2002-01-01

OBJECTIVE: To investigate whether a short interpregnancy interval is a risk factor for preterm birth in Emirati women, where there is a wide range of interpregnancy intervals and uniformity in potentially confounding factors. METHODS: A case-control design based on medical records was used. A case was defined as a healthy multiparous Emirati woman delivering a healthy singleton spontaneously before 37 weeks of gestation between 1997 and 2000, and a control was defined as the next eligible similar woman delivering after 37 weeks of gestation. Women were excluded if there was no information available about their most recent previous pregnancy or if it had resulted in a multiple or preterm birth. Data collected from charts and delivery room records were analysed using the STATA statistical package. All variables found to be valid, stable and significant by univariate analysis were included in multivariate logistic regression analysis. FINDINGS: There were 128 cases who met the eligibility criteria; 128 controls were selected. Short interpregnancy intervals were significantly associated with case status (P<0.05). The multivariate adjusted odds ratios for the 1st, 2nd, and 4th quartiles of interpregnancy interval compared with the lowest-risk 3rd quartile were 8.2, 5.4, and 2.0 (95% confidence intervals: 3.5-19.2, 2.4-12.6, and 0.9- 4.5 respectively). CONCLUSION: A short interpregnancy interval is a risk factor for spontaneous preterm birth in Emirati women. The magnitude of the risk and the risk gradient between exposure quartiles suggest that the risk factor is causal and that its modification would reduce the risk of preterm birth. PMID:12481208

The association of gestational weight gain per institute of medicine guidelines and prepregnancy body mass index on outcomes of twin pregnancies.

PubMed

González-Quintero, Victor H; Kathiresan, Anupama S Q; Tudela, Felipe José; Rhea, Debbie; Desch, Cheryl; Istwan, Niki

2012-06-01

To determine if current recommendations for weight gain in twin pregnancies according to maternal prepregnancy body mass index (PPBMI) influence perinatal outcomes. We identified women with twins enrolled in a maternity risk screening and education program with initial screening and prenatal care initiated at <20 weeks and delivery at >23.9 weeks. Women with normal, overweight, or obese PPBMI were included (n = 5129). Pregnancy outcomes were compared between those women with weight gain meeting or exceeding 2009 Institute of Medicine recommendations and patients who did not meet weight gain guidelines. Rates of spontaneous preterm delivery at <35 weeks were higher in all PPBMI groups for those with weight gain below guidelines. In all PPBMI groups, numbers of pregnancies with both infants weighing >2500 g or >1500 g were significantly higher for women gaining weight at or above guidelines. Logistic regression analysis was utilized to assess multivariate impact on outcome of spontaneous preterm delivery at <35 weeks showing that regardless of PPBMI level, women who gain below recommended guidelines are 50% more likely to deliver spontaneously at <35 weeks. In twin pregnancies, weight gain below recommended guidelines determined by maternal PPBMI is associated with higher rates of spontaneous preterm delivery at <35 weeks. Copyright © 2012 Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Maternal exposure to heatwave and preterm birth in Brisbane, Australia.

PubMed

Wang, J; Williams, G; Guo, Y; Pan, X; Tong, S

2013-12-01

To quantify the short-term effects of maternal exposure to heatwave on preterm birth. An ecological study. A population-based study in Brisbane, Australia. All pregnant women who had a spontaneous singleton live birth in Brisbane between November and March in 2000-2010 were studied. Daily data on pregnancy outcomes, meteorological factors, and ambient air pollutants were obtained. The Cox proportional hazards regression model with time-dependent variables was used to examine the short-term impact of heatwave on preterm birth. A series of cut-off temperatures and durations were used to define heatwave. Multivariable analyses were also performed to adjust for socio-economic factors, demographic factors, meteorological factors, and ambient air pollutants. Spontaneous preterm births. The adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03-1.24) to 2.00 (95% CI 1.37-2.91) by using different heatwave definitions, after controlling for demographic, socio-economic, and meteorological factors, and air pollutants. Heatwave was significantly associated with preterm birth: the associations were robust to the definitions of heatwave. The threshold temperatures, instead of duration, could be more likely to influence the evaluation of birth-related heatwaves. The findings of this study may have significant public health implications as climate change progresses. © 2013 RCOG.

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births

PubMed Central

Ferrero, David M.; Jacobsson, Bo; Di Renzo, Gian Carlo; Norman, Jane E.; Martin, James N.; D’Alton, Mary; Castelazo, Ernesto; Howson, Chris P.; Sengpiel, Verena; Bottai, Matteo; Mayo, Jonathan A.; Shaw, Gary M.; Verdenik, Ivan; Tul, Nataša; Velebil, Petr; Cairns-Smith, Sarah; Rushwan, Hamid; Arulkumaran, Sabaratnam; Howse, Jennifer L.; Simpson, Joe Leigh

2016-01-01

Background Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. Methods We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. Findings Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6–6.0 and 2.8–5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25–50% and 11–16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. Conclusions We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions. PMID:27622562

Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

PubMed

Ferrero, David M; Larson, Jim; Jacobsson, Bo; Di Renzo, Gian Carlo; Norman, Jane E; Martin, James N; D'Alton, Mary; Castelazo, Ernesto; Howson, Chris P; Sengpiel, Verena; Bottai, Matteo; Mayo, Jonathan A; Shaw, Gary M; Verdenik, Ivan; Tul, Nataša; Velebil, Petr; Cairns-Smith, Sarah; Rushwan, Hamid; Arulkumaran, Sabaratnam; Howse, Jennifer L; Simpson, Joe Leigh

2016-01-01

Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6-6.0 and 2.8-5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25-50% and 11-16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.

Associations of maternal pre-pregnancy underweight with small-for-gestational-age and spontaneous preterm birth, and optimal gestational weight gain in Japanese women.

PubMed

Fujiwara, Kana; Aoki, Shigeru; Kurasawa, Kentaro; Okuda, Mika; Takahashi, Tsuneo; Hirahara, Fumiki

2014-04-01

To determine associations of maternal pre-pregnancy underweight with poor outcomes and evaluate how gestational weight gain affects risks for such outcomes in pre-pregnancy underweight Japanese women. By analyzing the January 2001-December 2012 hospital database, we retrospectively identified 6954 women with pre-pregnancy normal weights (body mass index, 18.5-24.9 kg/m²) and 1057 pre-pregnancy underweight women (body mass index, <18.5 kg/m²) who delivered at the Perinatal Maternity and Neonatal Center of Yokohama City University. These women were stratified by weekly weight gain during the second/third trimesters to investigate associations of gestational weight gain with spontaneous preterm birth and small for gestational age (SGA). Spontaneous preterm birth and SGA incidences were compared with those of women meeting Institute of Medicine (IO M) guidelines to determine optimal weight gain in Japanese women. Preterm birth and SGA incidences were significantly higher in pre-pregnancy underweight than in pre-pregnancy normal weight women (4.6% vs 2.4% [P=0.005] and 13.9% vs 9.7% [P = 0.003], respectively). For pre-pregnancy normal weight women, preterm birth incidence was significantly higher in those with weight gain of less than 0.2 kg/week than in those IOM guidelines. For pre-pregnancy underweight women, preterm birth and SGA incidences were significantly higher in those with weight gain of less than 0.3 kg/week than in those meeting IOM guidelines. Preterm birth and SGA incidences did not differ significantly between pre-pregnancy normal weight women with weight gain of 0.2 kg/week or more and pre-pregnancy underweight women with weight gain of 0.3 kg/week or more, as compared to women meeting IOM guidelines. These results suggest that IOM guidelines for gestational weight gain may lack external validity in Japanese women. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Second trimester serum cortisol and preterm birth: an analysis by timing and subtype.

PubMed

Bandoli, Gretchen; Jelliffe-Pawlowski, Laura L; Feuer, Sky K; Liang, Liang; Oltman, Scott P; Paynter, Randi; Ross, Kharah M; Schetter, Christine Dunkel; Ryckman, Kelli K; Chambers, Christina D

2018-05-24

We hypothesized second trimester serum cortisol would be higher in spontaneous preterm births compared to provider-initiated (previously termed 'medically indicated') preterm births. We used a nested case-control design with a sample of 993 women with live births. Cortisol was measured from serum samples collected as part of routine prenatal screening. We tested whether mean-adjusted cortisol fold-change differed by gestational age at delivery or preterm birth subtype using multivariable linear regression. An inverse association between cortisol and gestational age category (trend p = 0.09) was observed. Among deliveries prior to 37 weeks, the mean-adjusted cortisol fold-change values were highest for preterm premature rupture of the membranes (1.10), followed by premature labor (1.03) and provider-initiated preterm birth (1.01), although they did not differ statistically. Cortisol continues to be of interest as a marker of future preterm birth. Augmentation with additional biomarkers should be explored.

Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups.

PubMed

Parker, Margaret G; Ouyang, Fengxiu; Pearson, Colleen; Gillman, Matthew W; Belfort, Mandy B; Hong, Xiumei; Wang, Guoying; Heffner, Linda; Zuckerman, Barry; Wang, Xiaobin

2014-04-30

To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes. Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34-36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37-44 weeks) in multinomial regression. To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes. Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001). After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB. These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes. For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]). Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB. Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB.

[Risk factors for preterm labor].

PubMed

Rodrigues, T; Barros, H

1998-10-01

Most studies investigating preterm risk factors include medically induced preterm labor due to fetal or maternal complications and do not distinguish preterm labor from preterm premature rupture of membranes. Thus, the objective of this study was to determine the proportion of the three types of preterm birth and identify risk factors for spontaneous preterm labor in a sample of pregnant women who delivered at two level III units. From January to October 1996, we interviewed 385 women with live preterm newborns and, as controls, 357 mothers of term newborns. Preterm births were classified as preterm labor, preterm premature rupture of membranes and iathrogenic preterm. Independent associations between maternal sociodemographic, constitutional, nutritional and obstetric characteristics and preterm labor were identified using logistic regression analysis. In this sample of preterm births, 29% corresponded to preterm labor, 49% to preterm premature rupture of the membranes and 22% were iathrogenic preterm. The identified risk factors for preterm labor were multiple gestation, no paid work during pregnancy, less than six prenatal care visits, arm circumference less than 26 cm and previous preterm or low birth-weight. Gestational bleeding during the first or third trimester was significantly associated with preterm labor. As previously recognized, multiple gestation, prior preterm or low birthweight and gestational bleeding are established risk factors for preterm labor. However, prenatal care, maternal work and nutritional status have also been revealed as important issues in preterm risk, deserving special interest since they are susceptible to preventive intervention.

High bisphenol A (BPA) concentration in the maternal, but not fetal, compartment increases the risk of spontaneous preterm delivery.

PubMed

Behnia, Faranak; Peltier, Morgan; Getahun, Darios; Watson, Cheryl; Saade, George; Menon, Ramkumar

2016-11-01

The objective of this study is to determine if BPA exposure, as measured by maternal plasma (MP) and amniotic fluid (AF) BPA concentrations is associated with an increased risk of spontaneous preterm birth (PTB) and preterm premature rupture of membranes (pPROM). In this nested case-control study, MP samples from women in term labor (n = 30), preterm labor that ended with preterm delivery (n = 25), or who had pPROM (n = 30) and amniotic fluid samples from term labor (n= 45), preterm labor (n = 60), and pPROM (n = 35) were assayed for BPA by enzyme immunoassay. BPA was detectible in 100% of MP and AF samples. Women with MP BPA concentrations in the fourth quartile were at increased risk of PTB (cOR = 4.12, 95% CI = 1.32-12.87; aOR = 4.78, 95% CI = 1.14-20) but not pPROM. High (fourth quartile) AF BPA values also tended to increase the risk of pPROM (cOR = 2.47, 95% CI = 0.96-6.37) but results were not statistically significant. Increased BPA concentration is associated with an increased risk for PTB or pPROM depending on the maternal-fetal compartment(s) affected. High MP plasma BPA concentrations are associated with PTB with intact membranes but high AF BPA concentrations may weakly be associated with pPROM.

Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

PubMed

Kim, Sei Eun; Lee, Seul Yi; Blanco, Cynthia L; Kim, Jun Hee

2014-08-20

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse. Copyright © 2014 the authors 0270-6474/14/3411399-06$15.00/0.

DYSREGULATION OF MATERNAL SERUM ADIPONECTIN IN PRETERM LABOR

PubMed Central

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Nhan-Chang, Chia-Ling; Jodicke, Cristiano; Yoon, Bo Hyun; Hassan, Sonia S.; Kusanovic, Juan Pedro

2013-01-01

Objective Intra-amniotic and systemic infection/inflammation have been causally linked to preterm parturition and fetal injury. An emerging theme is that adipose tissue can orchestrate a metabolic response to insults, but also an inflammatory response via the production of adipocytokines, and that these two phenomenon are interrelated. Adiponectin, an insulin-sensitizing, anti-inflammatory adipocytokine, circulates in multimeric complexes including low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. Each of these complexes can exert differential biological effects. The aim of this study was to determine whether spontaneous preterm labor (PTL) with intact membranes and intra-amniotic infection/inflammation (IAI) is associated with changes in maternal serum circulating adiponectin multimers. Study design This cross-sectional study included patients in the following groups: 1) normal pregnant women (n=158); 2) patients with an episode of preterm labor and intact membranes without IAI who delivered at term (n=41); 3) preterm labor without IAI who delivered preterm (n=27); and 4) preterm labor with IAI who delivered preterm (n=36). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results 1) Preterm labor leading to preterm delivery or an episode of preterm labor which does not lead to preterm delivery, was associated with a lower median maternal serum concentration of total and HMW adiponectin, a lower median HMW/total adiponectin ratio, and a higher median LMW/total adiponectin ratio than normal pregnancy; 2) among patients with preterm labor, those with IAI had the lowest median concentration of total and HMW adiponectin, as well as the lowest median HMW/total adiponectin ratio; 3) The changes in maternal adiponectin and adiponectin multimers remained significant after adjusting for confounding factors such as maternal age, BMI, gestational age at sampling, and parity. Conclusion 1) Preterm labor is characterized by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation; 2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term; 3) The findings reported herein, provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organize the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not). PMID:19579094

White Matter Injury and General Movements in High-Risk Preterm Infants.

PubMed

Peyton, C; Yang, E; Msall, M E; Adde, L; Støen, R; Fjørtoft, T; Bos, A F; Einspieler, C; Zhou, Y; Schreiber, M D; Marks, J D; Drobyshevsky, A

2017-01-01

Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays. © 2017 by American Journal of Neuroradiology.

Preterm birth and inflammation-The role of genetic polymorphisms.

PubMed

Holst, Daniela; Garnier, Yves

2008-11-01

Spontaneous preterm labour and preterm births are still the leading cause of perinatal morbidity and mortality in the developed world. Previous efforts to prevent preterm birth have been hampered by a poor understanding of the underlying pathophysiology, inadequate diagnostic tools and generally ineffective therapies. Clinical, epidemiological and experimental studies indicate that genito-urinary tract infections play a critical role in the pathogenesis of preterm birth. Moreover, intrauterine infection increases perinatal mortality and morbidity, such as cerebral palsy and chronic lung disease, significantly. It has recently been suggested that gene-environment interactions play a significant role in determining the risk of preterm birth. Polymorphisms of certain critical genes may be responsible for a harmful inflammatory response in those who possess them. Accordingly, polymorphisms that increase the magnitude or the duration of the inflammatory response were associated with an increased risk of preterm birth. In contrast polymorphisms that decrease the inflammatory response were associated with a lower risk of preterm birth. This article will review the current understanding of pathogenetic pathways in the aetiology of preterm birth.

Tocolysis among Women with Preterm Birth: Associated Factors and Outcomes from a Multicenter Study in Brazil.

PubMed

Dias, Tabata Zumpano; Fava, Mariana Lacerda; Passini Júnior, Renato; Cecatti, Jose Guilherme; Tedesco, Ricardo Porto; Lajos, Giuliane Jesus; Rehder, Patricia Moretti; Nomura, Marcelo Luis; Oliveira, Paulo Fanti; Costa, Maria Laura

2018-04-01

 To evaluate the use of tocolysis in cases of preterm birth due to spontaneous preterm labor in a Brazilian sample.  A sample of 1,491 women with preterm birth due to spontaneous preterm labor were assessed, considering treatment with tocolysis or expectant management, according to gestational age at birth (< 34 weeks and 34 to 36 + 6 weeks) and drugs prescribed. The study took place in 20 Brazilian hospitals from April 2011 to July 2012. Bivariate analyses were conducted to evaluate associations with sociodemographic and obstetric characteristics and odds ratios with their respective 95% confidence intervals were estimated for maternal and neonatal outcomes.  A total of 1,491 cases of preterm birth were considered. Tocolysis was performed in 342 cases (23%), 233 of which (68.1%) were delivered before 34 weeks. Within the expectant management group, 73% was late preterm and with more advanced labor at the time of admission. The most used drugs were calcium channel blockers (62.3%), followed by betamimetics (33%). Among the subjects in the tocolysis group, there were more neonatal and maternal complications (majority non-severe) and an occurrence of corticosteroid use that was 29 higher than in the expectant management group.  Tocolysis is favored in cases of earlier labor and also among those with less than 34 weeks of gestation, using preferably calcium channel blockers, with success in achieving increased corticosteroid use. Tocolysis, in general, was related to higher maternal and neonatal complication rates, which may be due to the baseline difference between cases at admission. However, these results should raise awareness to tocolysis use. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

PubMed

Makhlouf, Michel A; Clifton, Rebecca G; Roberts, James M; Myatt, Leslie; Hauth, John C; Leveno, Kenneth J; Varner, Michael W; Thorp, John M; Mercer, Brian M; Peaceman, Alan M; Ramin, Susan M; Iams, Jay D; Sciscione, Anthony; Tolosa, Jorge E; Sorokin, Yoram

2014-10-01

The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Maternal c-reactive protein and oxidative stress markers as predictors of delivery latency in patients experiencing preterm premature rupture of membranes.

PubMed

Ryu, Hyun Kyung; Moon, Jong Ho; Heo, Hyun Ji; Kim, Jong Woon; Kim, Yoon Ha

2017-02-01

To evaluate the usefulness of maternal serum c-reactive protein (CRP), lipid peroxide, and oxygen radical absorbance capacity (ORAC), to predict the interval between membrane rupture and delivery in patients with preterm premature rupture of membranes (PPROM). The present prospective study included patients with singleton pregnancies experiencing PPROM at earlier than 34 weeks of pregnancy who underwent spontaneous vaginal delivery between August 1, 2010 and July 31, 2013 at Chonnam National University Hospital, Republic of Korea. Patients were categorized based on whether delivery occurred within 3 days of PPROM or after. CRP levels, lipid peroxide (using malondialdehyde levels), ORAC, protein carbonyl, and other potential risk factors were compared between the groups. There were 72 patients included. Maternal serum CRP levels, malondialdehyde levels, and Bishop Score were higher in patients who underwent delivery within 3 days (all P<0.05); ORAC levels were lower among these patients (P=0.002). A receiver operating characteristic curve analysis showed that CRP, malondialdehyde, and ORAC levels were predictive of delivery within 3 days after PPROM. Maternal serum CRP, malondialdehyde, and ORAC levels at admission were useful in predicting the latent period in patients with PPROM. © 2016 International Federation of Gynecology and Obstetrics.

Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery.

PubMed

Brantsæter, Anne Lise; Englund-Ögge, Linda; Haugen, Margareta; Birgisdottir, Bryndis Eva; Knutsen, Helle Katrine; Sengpiel, Verena; Myhre, Ronny; Alexander, Jan; Nilsen, Roy M; Jacobsson, Bo; Meltzer, Helle Margrete

2017-01-19

Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (>5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0.85) for ≥3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.

Prepregnancy body mass index and risk of preterm birth: association heterogeneity by preterm subgroups

PubMed Central

2014-01-01

Background To evaluate the association between prepregnancy body mass index (BMI) is associated with early vs. late and medically-induced vs. spontaneous preterm birth (PTB) subtypes. Methods Using data from the Boston Birth Cohort, we examined associations of prepregnancy BMI with 189 early (<34 completed weeks) and 277 late (34–36 completed weeks) medically-induced PTBs and 320 early and 610 late spontaneous PTBs vs. 3281 term births (37–44 weeks) in multinomial regression. To assess for mediation by important pregnancy complications, we performed sequential models with and without hypertensive disorders of pregnancy, chorioamnionitis, and gestational diabetes. Results Prevalence of prepregnancy obesity (BMI ≥ 30.0 kg/m2) was 28% among mothers with medically-induced PTBs, 18% among mothers with spontaneous PTBs, and 18% among mothers with term births (p = <0.001). After adjustment for demographic and known risk factors for PTB, prepregnancy obesity was associated with higher odds of both early [OR 1.78 (1.19, 2.66)] and late [OR 1.49 (1.09, 2.04)] medically-induced PTB. These effect estimates were attenuated with inclusion of hypertensive disorders of pregnancy and gestational diabetes. For spontaneous deliveries, prepregnancy obesity was associated with decreased odds of PTB (0.76 [0.58, 0.98]) and underweight was nearly associated with increased odds of PTB (1.46 [0.99, 2.16]). Conclusion Prepregnancy obesity is associated with higher risk of medically-induced, but not spontaneous PTB. Hypertensive disorders of pregnancy and gestational diabetes appear to partially explain the association between prepregnancy obesity and early and late medically-induced PTB. PMID:24779674

Preterm birth and maternal country of birth in a French district with a multiethnic population.

PubMed

Zeitlin, J; Bucourt, M; Rivera, L; Topuz, B; Papiernik, E

2004-08-01

This analysis explores the association between preterm birth and maternal country of birth in a French district with a multiethnic population. Prospective observational study. District of Seine-Saint-Denis in France 48,746 singleton live births from a population-based birth register between October 1998 and December 2000. We compare preterm birth rates by mother's country of birth controlling for demographic and obstetric factors as well as insurance coverage and timing of initiation of antenatal care. Overall preterm birth rates and preterm birth rates by timing of delivery (<33 weeks versus 33-36 weeks of gestation), mode of onset (spontaneous or indicated preterm birth) and the presence of hypertension in pregnancy. Women born in Northern Africa, Southern Europe and South/East Asia did not have higher preterm birth rates than women born in continental France. Rates were significantly higher for women born in the overseas French districts in the Caribbean and Indian Ocean and Sub-Saharan Africa. Excess risk was greatest for early preterm births, medically indicated births and preterm births associated with hypertension. Patterns of preterm birth with relation to timing, mode of onset and medical complications among of Afro-Caribbean origin should be confirmed in future research.

The distribution of clinical phenotypes of preterm birth syndrome: implications for prevention.

PubMed

Barros, Fernando C; Papageorghiou, Aris T; Victora, Cesar G; Noble, Julia A; Pang, Ruyan; Iams, Jay; Cheikh Ismail, Leila; Goldenberg, Robert L; Lambert, Ann; Kramer, Michael S; Carvalho, Maria; Conde-Agudelo, Agustin; Jaffer, Yasmin A; Bertino, Enrico; Gravett, Michael G; Altman, Doug G; Ohuma, Eric O; Purwar, Manorama; Frederick, Ihunnaya O; Bhutta, Zulfiqar A; Kennedy, Stephen H; Villar, José

2015-03-01

Preterm birth has been difficult to study and prevent because of its complex syndromic nature. To identify phenotypes of preterm delivery syndrome in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. A population-based, multiethnic, cross-sectional study conducted at 8 geographically demarcated sites in Brazil, China, India, Italy, Kenya, Oman, the United Kingdom, and the United States. A total of 60,058 births over a 12-month fixed period between April 27, 2009, and March 2, 2014. Of these, 53,871 had an ultrasonography estimate of gestational age, among which 5828 were preterm births (10.8%). Pregnancies were prospectively studied using a standardized data collection and online data management system. Newborns had anthropometric and clinical examinations using standardized methods and identical equipment and were followed up until hospital discharge. The main study outcomes were clusters of preterm phenotypes and for each cluster, we analyzed signs of presentation at hospital admission, admission rates for neonatal intensive care for 7 days or more, and neonatal mortality rates. Twelve preterm birth clusters were identified using our conceptual framework. Eleven consisted of combinations of conditions known to be associated with preterm birth, 10 of which were dominated by a single condition. However, the most common single cluster (30.0% of the total preterm cases; n = 1747) was not associated with any severe maternal, fetal, or placental condition that was clinically detectable based on the information available; within this cluster, many cases were caregiver initiated. Only 22% (n = 1284) of all the preterm births occurred spontaneously without any of these severe conditions. Maternal presentation on hospital admission, newborn anthropometry, and risk for death before hospital discharge or admission for 7 or more days to a neonatal intensive care unit, none of which were used to construct the clusters, also differed according to the identified phenotypes. The prevalence of preterm birth ranged from 8.2% in Muscat, Oman, and Oxford, England, to 16.6% in Seattle, Washington. We identified 12 preterm birth phenotypes associated with different patterns of neonatal outcomes. In 22% of all preterm births, parturition started spontaneously and was not associated with any of the phenotypic conditions considered. We believe these results contribute to an improved understanding of this complex syndrome and provide an empirical basis to focus research on a more homogenous set of phenotypes.

Kinematic analysis of preterm newborns' spontaneous movements for postural activity assessment.

PubMed

Halek, Jan; Muckova, Anita; Svoboda, Zdenek; Janura, Miroslav; Marikova, Jana; Horakova, Katerina; Kantor, Lumir; Nemcova, Nina

2015-12-01

The objectives of this pilot study were to assess the potential use of 3D videography for analyzing the motion of the body center of mass (COM) in newborns and to determine differences in spontaneous movements between preterm and full-term infants. The group comprised 10 preterm newborns (gestational age at birth between 26 and 37 weeks; birth weight 800 to 2960 g; gestational age at the time of examination 34 to 39 weeks) and 10 full-term infants (gestational week 38 to 41; birth weight 2810 to 4360 g). To determine the range of motion of the COM, 3D videography was used (2 cameras, 25 Hz). When recording their movements, the infants were in the supine position, calm and awake. The recordings were processed using the APAS software. Selected points on the body were marked to obtain data for calculating the basic parameters of COM trajectories. The range of motion of the COM in both craniocaudal and anteroposterior directions was significantly greater in premature infants (P < 0.05 and P < 0.01, respectively) than in full-term babies. The variability of motion of the COM was significantly greater in the craniocaudal (P < 0.01) and anteroposterior (P < 0.05) directions in preterm babies. This was also valid for the velocity of motion of the COM in the craniocaudal direction (P < 0.05). 3D videography can be used for experimental assessment of motor behavior in preterm infants. Basic kinematic characteristics of the motion of the COM (range, variability, velocity) are greater in preterm infants.

Human Uterine Wall Tension Trajectories and the Onset of Parturition

PubMed Central

Sokolowski, Peter; Saison, Francis; Giles, Warwick; McGrath, Shaun; Smith, David; Smith, Julia; Smith, Roger

2010-01-01

Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000–2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension. PMID:20585649

Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway

PubMed Central

Nordqvist, Mahsa; Jacobsson, Bo; Brantsæter, Anne-Lise; Myhre, Ronny; Nilsson, Staffan; Sengpiel, Verena

2018-01-01

Objectives To investigate whether the timing of probiotic milk intake before, during early or late pregnancy influences associations with preeclampsia and preterm delivery. Design Population based prospective cohort study. Setting Norway, between 1999 and 2008. Participants 70 149 singleton pregnancies resulting in live-born babies from the Norwegian Mother and Child Cohort Study (no chronic disease, answered questionnaires, no placenta previa/cerclage/serious malformation of fetus, first enrolment pregnancy). Only nulliparous women (n=37 050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term controls (between gestational weeks 39+0 and 40+6) were included in the preterm delivery analysis resulting in 34 458 cases. Main outcome measures Adjusted OR for preeclampsia and preterm delivery according to consumption of probiotic milk at three different time periods (before pregnancy, during early and late pregnancy). Results Probiotic milk intake in late pregnancy (but not before or in early pregnancy) was significantly associated with lower preeclampsia risk (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during early (but not before or during late pregnancy) was significantly associated with lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03). Conclusions In this observational study, we found an association between timing of probiotic milk consumption during pregnancy and the incidence of the adverse pregnancy outcomes preeclampsia and preterm delivery. If future randomised controlled trials could establish a causal association between probiotics consumption and reduced risk of preeclampsia and preterm delivery, recommending probiotics would be a promising public health measure to reduce these adverse pregnancy outcomes. PMID:29362253

Mapping a New Spontaneous Preterm Birth Susceptibility Gene, IGF1R, Using Linkage, Haplotype Sharing, and Association Analysis

PubMed Central

Luukkonen, Aino; Teramo, Kari; Puttonen, Hilkka; Ojaniemi, Marja; Varilo, Teppo; Chaudhari, Bimal P.; Plunkett, Jevon; Murray, Jeffrey C.; McCarroll, Steven A.; Muglia, Louis J.; Palotie, Aarno; Hallman, Mikko

2011-01-01

Preterm birth is the major cause of neonatal death and serious morbidity. Most preterm births are due to spontaneous onset of labor without a known cause or effective prevention. Both maternal and fetal genomes influence the predisposition to spontaneous preterm birth (SPTB), but the susceptibility loci remain to be defined. We utilized a combination of unique population structures, family-based linkage analysis, and subsequent case-control association to identify a susceptibility haplotype for SPTB. Clinically well-characterized SPTB families from northern Finland, a subisolate founded by a relatively small founder population that has subsequently experienced a number of bottlenecks, were selected for the initial discovery sample. Genome-wide linkage analysis using a high-density single-nucleotide polymorphism (SNP) array in seven large northern Finnish non-consanginous families identified a locus on 15q26.3 (HLOD 4.68). This region contains the IGF1R gene, which encodes the type 1 insulin-like growth factor receptor IGF-1R. Haplotype segregation analysis revealed that a 55 kb 12-SNP core segment within the IGF1R gene was shared identical-by-state (IBS) in five families. A follow-up case-control study in an independent sample representing the more general Finnish population showed an association of a 6-SNP IGF1R haplotype with SPTB in the fetuses, providing further evidence for IGF1R as a SPTB predisposition gene (frequency in cases versus controls 0.11 versus 0.05, P = 0.001, odds ratio 2.3). This study demonstrates the identification of a predisposing, low-frequency haplotype in a multifactorial trait using a well-characterized population and a combination of family and case-control designs. Our findings support the identification of the novel susceptibility gene IGF1R for predisposition by the fetal genome to being born preterm. PMID:21304894

Center variation in the delivery of indicated late preterm births

PubMed Central

Aliaga, Sofia; Zhang, Jun; Long, D. Leann; Herring, Amy H.; Laughon, Matthew; Boggess, Kim; Reddy, Uma M.; Grantz, Katherine Laughon

2016-01-01

Objective Evidence for optimal timing of delivery for some pregnancy complications at late preterm gestation is limited. The purpose of this study was to identify center variation of indicated late preterm births. Study design Analysis of singleton late preterm and term births from a large U.S. retrospective obstetrical cohort. Births associated with spontaneous preterm labor, major congenital anomalies, chorioamnionitis, and emergency cesarean were excluded. We used modified Poisson fixed effects logistic regression with interaction terms to assess center variation of indicated late preterm births associated with four medical/obstetric comorbidities after adjusting for socio-demographics, co-morbidities, and hospital/provider characteristics. Results We identified 150,055 births from 16 hospitals; 9218 were indicated late preterm births. We found wide variation of indicated late preterm births across hospitals. The extent of center variation was greater for births associated with preterm premature rupture of membranes (RR across sites: 0.45 – 3.05), hypertensive disorders of pregnancy (RR across sites: 0.36 – 1.27), and placenta previa/abruption (RR across sites: 0.48 – 1.82). We found less center variation for births associated with diabetes (RR across sites: 0.65 – 1.39). Conclusion Practice variation in the management of indicated late preterm deliveries might be a source of preventable late preterm birth. PMID:27120474

Evidence of perturbations of the cytokine network in preterm labor.

PubMed

Romero, Roberto; Grivel, Jean-Charles; Tarca, Adi L; Chaemsaithong, Piya; Xu, Zhonghui; Fitzgerald, Wendy; Hassan, Sonia S; Chaiworapongsa, Tinnakorn; Margolis, Leonid

2015-12-01

Intraamniotic inflammation/infection is the only mechanism of disease with persuasive evidence of causality for spontaneous preterm labor/delivery. Previous studies about the behavior of cytokines in preterm labor have been largely based on the analysis of the behavior of each protein independently. Emerging evidence indicates that the study of biologic networks can provide insight into the pathobiology of disease and improve biomarker discovery. The goal of this study was to characterize the inflammatory-related protein network in the amniotic fluid of patients with preterm labor. A retrospective cohort study was conducted that included women with singleton pregnancies who had spontaneous preterm labor and intact membranes (n = 135). These patients were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and amniotic fluid concentration of interleukin (IL)-6 into the following groups: (1) those without intraamniotic inflammation (n = 85), (2) those with microbial-associated intraamniotic inflammation (n = 15), and (3) those with intraamniotic inflammation without detectable bacteria (n = 35). Amniotic fluid concentrations of 33 inflammatory-related proteins were determined with the use of a multiplex bead array assay. Patients with preterm labor and intact membranes who had microbial-associated intraamniotic inflammation had a higher amniotic fluid inflammatory-related protein concentration correlation than those without intraamniotic inflammation (113 perturbed correlations). IL-1β, IL-6, macrophage inflammatory protein (MIP)-1α, and IL-1α were the most connected nodes (highest degree) in this differential correlation network (degrees of 20, 16, 12, and 12, respectively). Patients with sterile intraamniotic inflammation had correlation patterns of inflammatory-related proteins, both increased and decreased, when compared to those without intraamniotic inflammation (50 perturbed correlations). IL-1α, MIP-1α, and IL-1β were the most connected nodes in this differential correlation network (degrees of 12, 10, and 7, respectively). There were more coordinated inflammatory-related protein concentrations in the amniotic fluid of women with microbial-associated intraamniotic inflammation than in those with sterile intraamniotic inflammation (60 perturbed correlations), with IL-4 and IL-33 having the largest number of perturbed correlations (degrees of 15 and 13, respectively). We report for the first time an analysis of the inflammatory-related protein network in spontaneous preterm labor. Patients with preterm labor and microbial-associated intraamniotic inflammation had more coordinated amniotic fluid inflammatory-related proteins than either those with sterile intraamniotic inflammation or those without intraamniotic inflammation. The correlations were also stronger in patients with sterile intraamniotic inflammation than in those without intraamniotic inflammation. The findings herein could be of value in the development of biomarkers of preterm labor. Published by Elsevier Inc.

Preterm subtypes by immigrants’ length of residence in Norway: a population-based study

PubMed Central

2014-01-01

Background The reduction of the preterm delivery (PTD) rate is a maternal and child health target. Elevated rates have been found among several immigrant groups, but few studies have distinguished between PTD according to the mode of birth start. In addition, migrants’ birth outcomes have further been shown to be affected by the time in residence; however, the association to PTD subtypes has not previously been assessed. In this study we examined if the risk of spontaneous and non-spontaneous, or iatrogenic, PTD among immigrants in Norway varied according to the length of residence and the country of birth, and compared with the risks among the majority population. Methods We linked population-based birth and immigration data for 40 709 singletons born to immigrant women from Iraq, Pakistan, the Philippines, Somalia, Sri Lanka and Vietnam and 868 832 singletons born to non-immigrant women from 1990–2009. Associations between the length of residence and subtypes of PTD were estimated as relative risks (RRs) with 95% confidence intervals (CIs) from multivariable models. Results In total, 48 191 preterm births occurred. Both spontaneous and non-spontaneous PTD rates were higher among immigrants (4.8% and 2.0%) than among non-immigrants (3.6% and 1.6%). Only non-spontaneous PTD was associated with longer lengths of residence (p trend <0.001). Recent immigrants (<5 years of residence) and non-immigrants had a similar risk of non-spontaneous PTD, whereas immigrants with lengths of residence of 5–9 years, 10–14 years and ≥15 years had adjusted RRs of 1.18 [95% CI 1.03,1.35], 1.43 [95% CI 1.20,1.71] and 1.66 [95% CI 1.41,1.96]. The association was reduced after further adjustments for maternal and infant morbidity. Conversely, the risk of spontaneous PTD among immigrants was not mitigated by length of residence, but varied with country of birth according to the duration of pregnancy in term births. Conclusions Non-spontaneous PTD increased with the length of residence whereas spontaneous PTD remained elevated regardless of the length of residence. Policies to improve birth outcomes in ethnically mixed populations should address the modifiable causes of PTD rather than aiming to reduce absolute PTD rates. PMID:25048200

Recent pharmacological advances in the treatment of preterm membrane rupture, labour and delivery.

PubMed

Doggrell, Sheila A

2004-09-01

Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17alpha-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, beta2-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.

Seasonal Pattern of Preterm Births in Korea for 2000-2012.

PubMed

Woo, Yoonmi; Ouh, Yung Taek; Ahn, Ki Hoon; Cho, Geum Joon; Hong, Soon Cheol; Oh, Min Jeong; Kim, Hai Joong

2016-11-01

The aim of this study was to investigate a seasonal pattern of preterm births in Korea. Data were obtained from the national birth registry of the Korean Statistics Office and included all births in Korea during the period 2000-2012 (n = 6,310,800). Delivery dates were grouped by month of the year or by season (winter [December, January, February], spring [March, April, May], summer [June, July, August], and autumn [September, October, November]). The seasonal patterns of prevalence of preterm births were assessed. The rates of preterm births at 37 weeks were highest twice a year (once in winter and again in summer). The rates of preterm births increased by 13.9% in summer and 7.5% in winter, respectively, than in spring (OR, 1.139; 95% CI, 1.127-1.152, and OR, 1.075; 95% 1.064-1.087, respectively) after controlling for age, the educational level of the parents, maternal parity, and neonatal gender. The pattern for spontaneous preterm births < 34 weeks was similar. In Korea, a seasonal pattern of preterm births was observed, with peak prevalence in summer and winter. A seasonal pattern of preterm births may provide new insights for the pathophysiology of preterm births.

The Risk of Human Papillomavirus Infection for Spontaneous Abortion, Spontaneous Preterm Birth, and Pregnancy Rate of Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis.

PubMed

Xiong, Yi-Quan; Mo, Yun; Luo, Qiao-Ming; Huo, Shu-Ting; He, Wen-Qiao; Chen, Qing

2018-04-12

To estimate the impact of human papillomavirus (HPV) infection on spontaneous abortion, spontaneous preterm birth (sPTB), pregnancy rate of females undergoing assisted reproductive technologies (ART), and spontaneous abortion of ART pregnancy. PubMed, Medline, Embase, and the Cochrane Library were searched until December 16, 2016. The OR or relative risk (RR) with its corresponding 95% CI were selected as effect size. Subgroup analysis of HPV genotype infection (high-risk HPV [HR-HPV] or indiscriminate genotype) was performed. Statistical analysis was conducted using STATA 12.0. Eighteen studies were included. Eight studies revealed no significant association between HPV infection and spontaneous abortion (OR 1.40, 95% CI 0.56-3.50). However, subgroup analysis showed indiscriminate genotype HPV infection increased the ratio of spontaneous abortion with OR of 2.24 (95% CI 1.37-3.65), while HR-HPV infection had no significant effect (OR 0.65, 95% CI 0.21-1.98). The results indicated that HR-HPV infection was a risk for sPTB with a pooled OR of 2.84 (95% CI 1.95-4.14). HPV infection was found to be independent of the ART-based clinical pregnancy rate (RR 1.04, 95% CI 0.64-1.70) and spontaneous abortion of ART pregnancy (RR 1.47, 95% CI 0.86-2.50). Indiscriminate HPV genotype infection can increase the risk of spontaneous abortion and HR-HPV infection was a risk factor for sPTB. However, there was not enough evidence to indicate the association between HPV infection and pregnancy rate of ART, and spontaneous abortion of ART pregnancy. Different genotypes of HPV infection may play a discrepant role in adverse pregnancy outcomes. © 2018 S. Karger AG, Basel.

Chlamydia trachomatis and the risk of spontaneous preterm birth, babies who are born small for gestational age, and stillbirth: a population-based cohort study.

PubMed

Reekie, Joanne; Roberts, Christine; Preen, David; Hocking, Jane S; Donovan, Basil; Ward, James; Mak, Donna B; Liu, Bette

2018-04-01

Chlamydia trachomatis is one of the most commonly diagnosed sexually transmitted infections worldwide, but reports in the medical literature of an association between genital chlamydia infection and adverse obstetric outcomes are inconsistent. The Western Australia Data Linkage Branch created a cohort of women of reproductive age by linking records of birth registrations with the electoral roll for women in Western Australia who were born from 1974 to 1995. The cohort was then linked to both chlamydia testing records and the state perinatal registry for data on preterm births and other adverse obstetric outcomes. We determined associations between chlamydia testing, test positivity, and adverse obstetric outcomes using multivariate logistic regression analyses. From 2001 to 2012, 101 558 women aged 15 to 38 years had a singleton birth. Of these women, 3921 (3·9%) had a spontaneous preterm birth, 9762 (9·6% of 101 371 women with available data) had a baby who was small for gestational age, and 682 (0·7%) had a stillbirth. During their pregnancy, 21 267 (20·9%) of these women had at least one chlamydia test record, and 1365 (6·4%) of those tested were positive. Before pregnancy, 19 157 (18·9%) of these women were tested for chlamydia, of whom 1595 (8·3%) tested positive for chlamydia. Among all women with a test record, after adjusting for age, ethnicity, maternal smoking, and history of other infections, we found no significant association between a positive test for chlamydia and spontaneous preterm birth (adjusted odds ratio 1·08 [95% CI 0·91-1·28]; p=0·37), a baby who was small for gestational age (0·95 [0·85-1·07]; p=0·39), or stillbirth (0·93 [0·61-1·42]; p=0·74). A genital chlamydia infection that is diagnosed and, presumably, treated either during or before pregnancy does not substantially increase a woman's risk of having a spontaneous preterm birth, having a baby who is small for gestational age, or having a stillbirth. Australian National Health and Medical Research Council. Copyright © 2018 Elsevier Ltd. All rights reserved.

Age-specific preterm birth rates after exclusion of risk factors--an analysis of the german perinatal survey.

PubMed

Voigt, M; Briese, V; Carstensen, M; Wolterdorf, F; Hallier, E; Straube, S

2010-08-01

A description of preterm birth rates - specified according to maternal age - after the exclusion of anamnestic risk factors. Data for this study were taken from the German Perinatal Survey of 1998-2000. We analysed data from 492,576 singleton pregnancies and determined preterm birth rates according to maternal age after a stepwise exclusion of anamnestic risk factors. There was a U-shaped dependence of preterm birth rates on maternal age. The lowest preterm birth rate (without excluding women with anamnestic risk factors) was 5.6% at a maternal age of 29 years. The prevalence of some anamnestic risk factors for preterm birth, such as previous stillbirths, spontaneous and induced abortions, and ectopic pregnancies, increased with maternal age. Excluding women with anamnestic risk factors lowered the preterm birth rates substantially. The lowest preterm birth rates were found in women with one previous live birth, without any anamnestic risk factors, and with a body mass index (BMI) of 25.00-29.99. With these restrictions, we found preterm birth rates of under 2% for women aged 24-31 years. The magnitude and age-dependence of the preterm birth rate can to some extent be explained with the age-dependent prevalence of anamnestic risk factors for preterm birth. Excluding women with anamnestic risk factors from our study population lowered the preterm birth rates substantially. © Georg Thieme Verlag KG Stuttgart · New York.

Combination of three-dimensional ultrasound measurement of foetal adrenal gland enlargement and placental alpha microglobulin-1 for the prediction of the timing of delivery within seven days in women with threatened preterm labour and preterm labour.

PubMed

Santipap, Monchai; Phupong, Vorapong

2018-03-23

The aim of this study was to predict the timing of delivery within seven days in singleton pregnant women with threatened preterm labour and preterm labour by using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton pregnant women at 22-36 +6  weeks of gestation who presented with threatened preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement of the whole foetal adrenal gland and of the foetal adrenal zone were performed. Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One hundred and fifty-four pregnant women were included into the study. Eighty-four pregnant women had threatened preterm labour and seventy pregnant women had preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG-1 test in combination increased sensitivity; if one parameter was positive, the sensitivity, specificity, positive predictive value and negative predictive value were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing of delivery within seven days. The combination of foetal adrenal gland enlargement and PAMG-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. Impact Statement What is already known on this subject? An increased foetal adrenal gland volume is significantly correlated with the risk of preterm birth. What do the results of this study add? The combination of a foetal adrenal gland enlargement and a placental alpha microglobulin-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. What are the implications of these findings for clinical practice and/or further research? The combination of a foetal adrenal gland enlargement and placental alpha microglobulin-1 may be used for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and with preterm labour.

Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions

PubMed Central

Cha, Jeeyeon; Bartos, Amanda; Egashira, Mahiro; Haraguchi, Hirofumi; Saito-Fujita, Tomoko; Leishman, Emma; Bradshaw, Heather; Dey, Sudhansu K.; Hirota, Yasushi

2013-01-01

There are currently more than 15 million preterm births each year. We propose that gene-environment interaction is a major contributor to preterm birth. To address this experimentally, we generated a mouse model with uterine deletion of Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth due to premature decidual senescence with increased mTORC1 activity and COX2 signaling. Here we provide evidence that this predisposition provoked preterm birth in 100% of females exposed to a mild inflammatory insult with LPS, revealing the high significance of gene-environment interactions in preterm birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53-deficient mice when they were treated with a combination of rapamycin (mTORC1 inhibitor) and progesterone (P4), without adverse effects on maternal or fetal health. These results provide evidence for the cooperative contributions of two sites of action (decidua and ovary) toward preterm birth. Moreover, a similar signature of decidual senescence with increased mTORC1 and COX2 signaling was observed in women undergoing preterm birth. Collectively, our findings show that superimposition of inflammation on genetic predisposition results in high incidence of preterm birth and suggest that combined treatment with low doses of rapamycin and P4 may help reduce the incidence of preterm birth in high-risk women. PMID:23979163

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

PubMed

Yaron, Yuval; Heifetz, Sigal; Ochshorn, Yifat; Lehavi, Ofer; Orr-Urtreger, Avi

2002-09-01

Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome. Copyright 2002 John Wiley & Sons, Ltd.

Vaginal progesterone to prevent preterm birth in pregnant women with a sonographic short cervix: clinical and public health implications.

PubMed

Conde-Agudelo, Agustin; Romero, Roberto

2016-02-01

Vaginal progesterone administration to women with a sonographic short cervix is an efficacious and safe intervention used to prevent preterm birth and neonatal morbidity and mortality. The clinical and public health implications of this approach in the United States have been critically appraised and compared to other therapeutic interventions in obstetrics. Vaginal progesterone administration to women with a transvaginal sonographic cervical length (CL) ≤25 mm before 25 weeks of gestation is associated with a significant and substantial reduction of the risk for preterm birth from <28 to <35 weeks of gestation, respiratory distress syndrome, composite neonatal morbidity and mortality, admission to the neonatal intensive care unit, and mechanical ventilation. These beneficial effects have been achieved in women with a singleton gestation, with or without a history of spontaneous preterm birth, and did not differ significantly as a function of CL (<10 mm, 10-20 mm, or 21-25 mm). The number of patients required for treatment to prevent 1 case of preterm birth or adverse neonatal outcomes ranges from 10-19 women. The number needed to screen for the prevention of 1 case of preterm birth before 34 weeks of gestation is 125 women, and 225 for the prevention of 1 case of major neonatal morbidity or neonatal mortality. Several cost-effectiveness and decision analyses have shown that the combination of universal transvaginal CL screening and vaginal progesterone administration to women with a short cervix is a cost-effective intervention that prevents preterm birth and associated perinatal morbidity and mortality. Universal assessment of CL and treatment with vaginal progesterone for singleton gestations in the United States would result in an annual reduction of approximately 30,000 preterm births before 34 weeks of gestation and of 17,500 cases of major neonatal morbidity or neonatal mortality. In summary, there is compelling evidence to recommend universal transvaginal CL screening at 18-24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤25 mm, regardless of the history of spontaneous preterm birth, with the goal of preventing preterm birth and neonatal morbidity and mortality. Published by Elsevier Inc.

Role of perceived stress in the occurrence of preterm labor and preterm birth among urban women.

PubMed

Seravalli, Laura; Patterson, Freda; Nelson, Deborah B

2014-01-01

This study examined whether prenatal perceived stress levels during pregnancy were associated with preterm labor or preterm birth. Perceived stress levels were measured at 16 weeks' gestation or less and between 20 and 24 weeks' gestation in a sample of 1069 low-income pregnant women attending Temple University prenatal care clinics. Scores were averaged to create a single measure of prenatal stress. Preterm birth was defined as the occurrence of a spontaneous birth prior to 37 weeks' gestation. Preterm labor was defined as the occurrence of regular contractions between 20 and 37 weeks' gestation that were associated with changes in the cervix. Independent of potential confounding factors, prenatal perceived stress was not associated with preterm labor (odds ratio [OR], 1.10; 95% confidence interval [CI], 0.69-1.78; P = .66); however, prenatal stress trended toward an association with preterm birth (OR, 1.49; 95% CI, 1.00-2.23; P = .05). The strongest predictor of preterm labor was a history of preterm labor in a prior pregnancy. Women with a history of preterm labor were 2 times more likely to experience preterm labor in the current pregnancy than women who did not have a preterm labor history (OR, 2.16; 95% CI, 1.05-4.41; P = .04). Historical risk factors for preterm birth, such as African American race, a history of abortion, or a history of preterm birth, were not related to preterm labor. The strongest predictor of preterm birth was having a history of preterm birth in a prior pregnancy (OR, 2.55; 95% CI, 1.54-4.24; P < .001). Prenatal perceived stress levels may be a risk factor for preterm birth independent of preterm labor; however, prenatal stress was not associated with preterm labor. Risk factors for preterm labor may be different from those of preterm birth. © 2014 by the American College of Nurse-Midwives.

A SUBSET OF PATIENTS DESTINED TO DEVELOP SPONTANEOUS PRETERM LABOR HAS AN ABNORMAL ANGIOGENIC/ANTI-ANGIOGENIC PROFILE IN MATERNAL PLASMA: EVIDENCE IN SUPPORT OF PATHOPHYSIOLOGIC HETEROGENEITY OF PRETERM LABOR DERIVED FROM A LONGITUDINAL STUDY

PubMed Central

Chaiworapongsa, Tinnakorn; Romero, Roberto; Tarca, Adi; Kusanovic, Juan Pedro; Mittal, Pooja; Kim, Sun Kwon; Gotsch, Francesca; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi, Shali; Pacora, Percy; Ogge, Giovanna; Dong, Zhong; Kim, Chong Jai; Yeo, Lami; Hassan, Sonia S

2012-01-01

OBJECTIVE An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction, and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women. STUDY DESIGN This longitudinal nested case-control study included normal pregnant women (n=208) and patients with PTL leading to preterm delivery (n=52). Maternal blood samples were collected at 6 gestational age intervals from 6-36.9 weeks of gestation. The end point (time of diagnosis) of the study, “True PTL”, was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. RESULTS 1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of “true PTL”. 2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of “true PTL”; and 3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patents diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. CONCLUSION The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition. PMID:19916710

Exploration of preterm birth rates associated with different models of antenatal midwifery care in Scotland: Unmatched retrospective cohort analysis.

PubMed

Symon, Andrew; Winter, Clare; Cochrane, Lynda

2015-06-01

preterm birth represents a significant personal, clinical, organisational and financial burden. Strategies to reduce the preterm birth rate have had limited success. Limited evidence indicates that certain antenatal care models may offer some protection, although the causal mechanism is not understood. We sought to compare preterm birth rates for mixed-risk pregnant women accessing antenatal care organised at a freestanding midwifery unit (FMU) and mixed-risk pregnant women attending an obstetric unit (OU) with related community-based antenatal care. unmatched retrospective 4-year Scottish cohort analysis (2008-2011) of mixed-risk pregnant women accessing (i) FMU antenatal care (n=1107); (ii) combined community-based and OU antenatal care (n=7567). Data were accessed via the Information and Statistics Division of the NHS in Scotland. Aggregates analysis and binary logistic regression were used to compare the cohorts׳ rates of preterm birth; and of spontaneous labour onset, use of pharmacological analgesia, unassisted vertex birth, and low birth weight. Odds ratios were adjusted for age, parity, deprivation score and smoking status in pregnancy. after adjustment the 'mixed risk' FMU cohort had a statistically significantly reduced risk of preterm birth (5.1% [n=57] versus 7.7% [n=583]; AOR 0.73 [95% CI 0.55-0.98]; p=0.034). Differences in these secondary outcome measures were also statistically significant: spontaneous labour onset (FMU 83.9% versus OU 74.6%; AOR 1.74 [95% CI 1.46-2.08]; p<0.001); minimal intrapartum analgesia (FMU 53.7% versus OU 34.4%; AOR 2.17 [95% CI 1.90-2.49]; p<0.001); spontaneous vertex delivery (FMU 71.9% versus OU 63.5%; AOR 1.46 [95% CI 1.32-1.78]; p<0.001). Incidence of low birth weight was not statistically significant after adjustment for other variables. There was no significant difference in the rate of perinatal or neonatal death. given this study׳s methodological limitations, we can only claim associations between the care model and or chosen outcomes. Although both cohorts were mixed risk, differences in risk levels could have contributed to these findings. Nevertheless, the significant difference in preterm birth rates in this study resonates with other research, including the recent Cochrane review of midwife-led continuity models. Because of the multiplicity of risk factors for preterm birth we need to explore the salient features of the FMU model which may be contributing to this apparent protective effect. Because a randomised controlled trial would necessarily restrict choice to pregnant women, we feel that this option is problematic in exploring this further. We therefore plan to conduct a prospective matched cohort analysis together with a survey of unit practices and experiences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Absence of Circadian Rhythms of Preterm Premature Rupture of Membranes and Preterm Placental Abruption

PubMed Central

Luque-Fernandez, Miguel Angel; Ananth, Cande V.; Sanchez, Sixto E.; Qiu, Chun-fang; Hernandez-Diaz, Sonia; Valdimarsdottir, Unnur; Gelaye, Bizu; Williams, Michelle A.

2014-01-01

Purpose Data regarding circadian rhythm in the onset of spontaneous preterm premature rupture of membranes (PROM) and placental abruption (PA) cases are conflicting. We modeled the time of onset of preterm PROM and PA cases and examined if the circadian profiles varied based on the gestational age at delivery. Methods We used parametric and nonparametric methods, including trigonometric regression in the framework of generalized linear models, to test the presence of circadian rhythms in the time of onset of preterm PROM and PA cases, among 395 women who delivered a singleton between 2009 and 2010 in Lima, Peru. Results We found a diurnal circadian pattern, with a morning peak at 07h:32’ (95%CI:05h:46’ – 09h:18’) among moderate preterm PROM cases (P-value<0.001), and some evidence of a diurnal circadian periodicity among PA cases in term infants (P-value=0.067). However, we did not find evidence of circadian rhythms in the time of onset of extremely or very preterm PROM (P-value=0.259) and preterm PA (P-value=0.224). Conclusions The circadian rhythms of the time of onset of preterm PROM and PA cases varied based on gestational weeks at delivery. While circadian rhythms were presented among moderate preterm PROM and term PA cases, there was no evidence of circadian rhythms among preterm PA and very or extremely preterm PROM cases, underlying other mechanisms associated with the time of onset. PMID:25453346

[Low risk of reproductive disorders among female greenhouse workers--safe work conditions or health selection for the light work?].

PubMed

Jurewicz, Joanna; Hanke, Wojciech; Makowiec-Dabrowska, Teresa

2008-01-01

There are two major potential hazards typical of work in greenhouses: hard physical work or exposure to pesticides. The aim of the study was to investigate whether the work in greenhouse during pregnancy have an adverse effect on its outcome (preterm delivery, spontaneous abortion and birth defects). The study was performed in a group of 460 women employed in 14 greenhouses involved in growing vegetables and flowers. The rate of spontaneous abortions was much elbeit insignificantly higher in the women working in greenhouses during pregnancy than in those employed out of them; that applied mostly to the women performing light jobs in greenhouses. An increased risk of preterm delivery and spontaneous abortion was also observed in women performing greenhouse light jobs. No significantly increased risk of birth defects was observed in children born to women working in greenhouses. Neither was there any relationship between exposure to RD or ED pesticides exposure--and the occurrence of preterm delivery, spontaneous abortion and birth defects. No higher risk of pathological pregnancy that could be associated with hard physical work and pesticide exposure was observed. This may result from the fact that women themselves select an appropriate kind of job during pregnancy and a possible removal of women with pathological pregnancy from jobs involving pesticide exposure, as well as from the promotion of biological protection. The greenhouse workers should be aware of the two typical hazards found in greenhouses (hard work and exposure to pesticides) and their potential negative effects on the reproduction. The results of this study warrant the need for further study of the effect of pesticide exposure and work load on the pregnancy outcome.

Evidence of Perturbations of the Cytokine Network in Preterm Labor

PubMed Central

Romero, Roberto; Grivel, Jean-Charles; Tarca, Adi L.; Chaemsaithong, Piya; Xu, Zhonghui; Fitzgerald, Wendy; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Margolis, Leonid

2015-01-01

Objective Intra-amniotic infection/inflammation is the only mechanism of disease with persuasive evidence of causality for spontaneous preterm labor/delivery. Previous studies about the behavior of cytokines in preterm labor have been largely based on the analysis of the behavior of each protein independently. Emerging evidence indicates that the study of biological networks can provide insight into the pathobiology of disease, and improve biomarker discovery. The goal of this study is to characterize the inflammatory-related proteins network in the amniotic fluid in patients with preterm labor. Materials and Methods A retrospective cohort study was conducted, and included women with singleton pregnancies who presented with spontaneous preterm labor and intact membranes (n=135). These patients were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), and amniotic fluid concentration of interleukin (IL)-6 into the following groups: 1) those without intra-amniotic inflammation (n=85); 2) those with microbial-associated intra-amniotic inflammation (n=15); and 3) those with intra-amniotic inflammation without detectable bacteria (n=35). Amniotic fluid concentrations of 33 inflammatory-related proteins were determined using a multiplex bead array assay. Results 1) Patients with preterm labor and intact membranes who had microbial-associated intra-amniotic inflammation had a higher amniotic fluid inflammatory-related protein concentration correlation than those without intra-amniotic inflammation (113 perturbed correlations). IL-1β, IL-6, MIP-1α, and IL-1α were the most connected nodes (highest degree) in this differential correlation network (degree of 20, 16, 12, and 12, respectively); 2) patients with sterile intra-amniotic inflammation had correlation patterns of inflammatory-related proteins that were both increased and decreased when compared to those without intra-amniotic inflammation (50 perturbed correlations). IL-1α, MIP-1α, and IL-1β were the most connected nodes in this differential correlation network (degrees of 12, 10, and 7, respectively); and 3) there were more coordinated inflammatory-related protein concentrations in the amniotic fluid of women with microbial-associated intra-amniotic inflammation than in those with sterile intra-amniotic inflammation (60 perturbed correlations), with IL-4 and IL-33 having the largest number of perturbed correlations (degree of 15 and 13, respectively). Conclusion We report for the first time an analysis of the inflammatory-related protein network in spontaneous preterm labor. Patients with preterm labor who had microbial-associated intra-amniotic inflammation had more coordinated amniotic fluid inflammatory-related proteins than either those with sterile intra-amniotic inflammation or those without intra-amniotic inflammation. The correlations were also stronger in patients with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation. The findings herein could be of value in the development of biomarkers of preterm labor. PMID:26232508

Noninvasive Uterine Electromyography For Prediction of Preterm Delivery*

PubMed Central

UCOVNIK, Miha L; MANER, William L.; CHAMBLISS, Linda R.; BLUMRICK, Richard; BALDUCCI, James; NOVAK-ANTOLIC, Ziva; GARFIELD, Robert E.

2011-01-01

Objective Power spectrum (PS) of uterine electromyography (EMG) can identify true labor. EMG propagation velocity (PV) to diagnose labor has not been reported. The objective was to compare uterine EMG against current methods to predict preterm delivery. Study design EMG was recorded in 116 patients (preterm labor, n=20; preterm non-labor, n=68; term labor, n=22; term non-labor, n=6). Student’s t-test was used to compare EMG values for labor vs. non-labor (P<0.05 significant). Predictive values of EMG, Bishop-score, contractions on tocogram, and transvaginal cervical length were calculated using receiver-operator-characteristics analysis. Results PV was higher in preterm and term labor compared with non-labor (P<0.001). Combined PV and PS peak frequency predicted preterm delivery within 7 days with area-under-the-curve (AUC) = 0.96. Bishop score, contractions, and cervical length had AUC of 0.72, 0.67, and 0.54. Conclusions Uterine EMG PV and PS peak frequency more accurately identify true preterm labor than clinical methods. PMID:21145033

Safety of the 2010-11, 2011-12, 2012-13, and 2013-14 seasonal influenza vaccines in pregnancy: Birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants, a study from the cohort arm of VAMPSS.

PubMed

Chambers, Christina D; Johnson, Diana L; Xu, Ronghui; Luo, Yunjun J; Louik, Carol; Mitchell, Allen A; Schatz, Michael; Jones, Kenneth L

2016-08-17

There is a need for pregnancy safety information overall and for each seasonal formulation of the influenza vaccine. As part of the cohort arm of the Vaccines and Medications in Pregnancy Surveillance System, vaccine-exposed and unexposed women in the U.S. or Canada were recruited during pregnancy in the 2010-2014 vaccine seasons and followed to pregnancy outcome. For the four seasons combined, crude and adjusted relative risks (RRs) were estimated with 95% confidence intervals (CIs) for major birth defects overall and infants small for gestational age. Crude and adjusted hazard ratios (HRs) were estimated with 95% CIs for spontaneous abortion and preterm delivery. Specific influenza season subanalyses were also conducted. Of 1730 women, 1263 were exposed to an influenza vaccine and 467 were unexposed to any influenza vaccine. Among pregnancies with first-trimester exposure excluding lost-to-follow-up, 26/457 (5.7%) resulted in an infant with a major birth defect compared to 13/427 (3.0%) in the unexposed (RR 1.87, 95% CI 0.97, 3.59). No specific pattern of defects was evident in the vaccine-exposed cohort. The overall risk of spontaneous abortion was not elevated (HR 1.09, 95% CI 0.49, 2.40). Adjusted HRs for preterm delivery approximated 1.0 (adjusted HR 1.23, 95% CI 0.75, 2.02). RRs for small for gestational age infants on weight, length and head circumference ranged from 1.19 to 1.49 with all CIs including 1. Season-by-season analyses resulted in variation by season; however, estimates were based on small numbers. Combining the 2010-2014 influenza seasons, we found a moderately elevated RR for major birth defects overall, but no evidence of a specific pattern; 95% CIs included 1, and this finding could be due to chance. In the combined seasons, we found no meaningful evidence of an increased risk for spontaneous abortion or preterm delivery following exposure to the seasonal influenza vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ORACLE Children Study: educational outcomes at 11 years of age following antenatal prescription of erythromycin or co-amoxiclav

PubMed Central

Marlow, Neil; Bower, Hannah; Jones, David; Brocklehurst, Peter; Kenyon, Sara; Pike, Katie; Taylor, David; Salt, Alison

2017-01-01

Background Antibiotics used for women in spontaneous preterm labour without overt infection, in contrast to those with preterm rupture of membranes, are associated with altered functional outcomes in their children. Methods From the National Pupil Database, we used Key Stage 2 scores, national test scores in school year 6 at 11 years of age, to explore the hypothesis that erythromycin and co-amoxiclav were associated with poorer educational outcomes within the ORACLE Children Study. Results Anonymised scores for 97% of surviving children born to mothers recruited to ORACLE and resident in England were analysed against treatment group adjusting for key available socio-demographic potential confounders. No association with crude or with adjusted scores for English, mathematics or science was observed by maternal antibiotic group in either women with preterm rupture of membranes or spontaneous preterm labour with intact membranes. While the proportion receiving special educational needs was similar in each group (range 31.6–34.4%), it was higher than the national rate of 19%. Conclusions Despite evidence that antibiotics are associated with increased functional impairment at 7 years, educational test scores and special needs at 11 years of age show no differences between trial groups. Trial registration number ISCRT Number 52995660 (original ORACLE trial number). PMID:27515985

Meta-analysis of randomized controlled trials comparing 17α-hydroxyprogesterone caproate and vaginal progesterone for the prevention of recurrent spontaneous preterm delivery.

PubMed

Oler, Elizabeth; Eke, Ahizechukwu C; Hesson, Ashley

2017-07-01

Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed. To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD. Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery. Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included. Study data were extracted and meta-analyses were performed when outcomes were comparable. The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone. Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior. © 2017 International Federation of Gynecology and Obstetrics.

VAGINAL PROGESTERONE VERSUS CERVICAL CERCLAGE FOR THE PREVENTION OF PRETERM BIRTH IN WOMEN WITH A SONOGRAPHIC SHORT CERVIX, SINGLETON GESTATION, AND PREVIOUS PRETERM BIRTH: A SYSTEMATIC REVIEW AND INDIRECT COMPARISON META-ANALYSIS

PubMed Central

CONDE-AGUDELO, Agustin; ROMERO, Roberto; NICOLAIDES, Kypros; CHAIWORAPONGSA, Tinnakorn; O'BRIEN, John M.; CETINGOZ, Elcin; DA FONSECA, Eduardo; CREASY, George; SOMA-PILLAY, Priya; FUSEY, Shalini; CAM, Cetin; ALFIREVIC, Zarko; HASSAN, Sonia S.

2012-01-01

OBJECTIVE No randomized controlled trial has directly compared vaginal progesterone and cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone versus cerclage, using placebo/no cerclage as the common comparator. STUDY DESIGN Adjusted indirect meta-analysis of randomized controlled trials. RESULTS Four studies evaluating vaginal progesterone versus placebo (158 patients) and five evaluating cerclage versus no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in reducing preterm birth or adverse perinatal outcomes. CONCLUSION Based on state-of-the-art methodology for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the midtrimester, singleton gestation, and previous preterm birth. The selection of the optimal treatment may depend upon adverse events, cost and patient/clinician preferences. PMID:23157855

Placental heat shock proteins: no immunohistochemical evidence for a differential stress response in preterm labour.

PubMed

Divers, M J; Bulmer, J N; Miller, D; Lilford, R J

1995-01-01

The aetiology of idiopathic preterm labour remains obscure. The hypothesis that a stress response induced by low-grade bacterial infection in utero-placental tissues was investigated. Distribution of cognate and inducible isoforms of heat shock proteins (HSP) 70 kD, HSP 60 kD and HSP 90 kD were investigated in an immunohistochemical study of placental and decidual tissues before and after labour at varying gestations. Subjects were pregnant women undergoing singleton delivery after idiopathic preterm labour at less than 34 weeks' gestation (n = 23); spontaneous term labour at 37-42 weeks' gestation (n =24); preterm caesarean sections at less than 34 weeks' gestation for preeclampsia or intrauterine growth retardation (n=14); elective caesarean section at 37-42 weeks' gestation for cephalopelvic disproportion (n = 6). HSP expression was constant throughout the third trimester of pregnancy and did not change following the onset of labour, regardless of gestational age. A stress response in decidual tissues as determined by immunohistochemical analysis is apparently not associated with preterm labour.

Frequency of Respiratory Nursing Diagnoses and Accuracy of Clinical Indicators in Preterm Infants.

PubMed

Avena, Marta José; Pedreira, Mavilde da Luz Gonçalves; Bassolli de Oliveira Alves, Lucas; Herdman, T Heather; de Gutiérrez, Maria Gaby Rivero

2018-03-05

To identify the frequency of the nursing diagnoses, ineffective breathing pattern, impaired gas exchange and impaired spontaneous ventilation in newborns; and, to analyze the accuracy of diagnostic indicators identified for each of these diagnoses. This was a cross-sectional study conducted with a nonprobability sample of 92 infants. Data collected were represented by demographic and clinical variables, clinical indicators of the three respiratory nursing diagnoses from NANDA International, and were analyzed according to frequency and agreement between pairs of expert nurses (Kappa). Ineffective breathing pattern was identified in 74.5% of infants; impaired gas exchange was noted in 31.5%; impaired spontaneous ventilation was found in 16.8% of subjects. Use of accessory muscles to breathe showed the highest sensitivity for ineffective breathing pattern; abnormal blood gases had the best predictive value for impaired gas exchange. Use of accessory muscles to breathe had the highest sensitivity for impaired spontaneous ventilation. Ineffective breathing pattern was the most frequently identified; use of accessory muscles, alteration in depth of breathing, abnormal breathing, and dyspnea were the most representative signs/symptoms. Early recognition of respiratory conditions can support safe interventions to ensure appropriate outcomes. © 2018 NANDA International, Inc.

Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation

PubMed Central

Kusanovic, Juan Pedro; Romero, Roberto; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Gotsch, Francesca; Than, Nandor Gabor; Edwin, Sam S.; Pacora, Percy; Jodicke, Cristiano; Yeo, Lami; Hassan, Sonia S.

2010-01-01

Objective Intra-amniotic infection/inflammation (IAI) is one of the most important mechanisms of disease in preterm birth. Triggering receptor expressed on myeloid cells (TREM)-1 is a transmembrane glycoprotein expressed by neutrophils, macrophages and mature monocytes. TREM-1 is upregulated in biological fluids and tissues infected by Gram (+) and Gram (-) bacteria and fungi, amplifies the production of pro-inflammatory cytokines and chemokines, and its soluble form (sTREM-1) is released in the presence of infection. The aim of this study was to determine the effect of gestational age, parturition (term and preterm) and intra-amniotic infection/inflammation in the amniotic fluid (AF) concentrations of sTREM-1. Study design This cross-sectional study included 434 patients in the following groups: 1) mid-trimester of pregnancy (14-18 weeks, n=38); 2) normal pregnant women at term with (n=39) and without (n=39) labor; 3) patients with spontaneous preterm labor (PTL) and intact membranes classified into: a) PTL who delivered at term (n=99); b) PTL who delivered preterm (<37 weeks gestation) without IAI (n=80); and c) PTL with IAI (n=59); and 4) women with preterm prelabor rupture of membranes (PROM) with (n=40) and without (n=40) IAI. The AF concentration of sTREM-1 was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results 1) sTREM-1 was detected in all AF samples; 2) the median AF sTREM-1 concentration at term was higher than in the mid-trimester (4277.6 pg/mL vs. 1140.4 pg/mL; p<0.001); 3) among patients with PTL, the median AF sTREM-1 concentration was significantly higher in patients with IAI than in those without IAI (6154.4 pg/mL vs. 3282.8 pg/mL; p<0.001) and those with PTL who delivered at term (6154.4 pg/mL vs. 2794 pg/mL; p<0.001); 4) patients with preterm PROM with IAI had a higher median AF sTREM-1 concentration than those without IAI (7893.1 pg/mL vs. 3386.6 pg/mL; p<0.001); 5) no differences were observed in the median AF sTREM-1 concentration between patients with spontaneous labor at term and those at term not in labor (4712.4 pg/mL vs. 4277.6 pg/mL repectively; p=0.4); and 6) an AF sTREM-1 concentration ≥6,416 pg/mL (derived from a ROC curve) had a sensitivity of 72% and a specificity of 89% for the diagnosis of intra-amniotic infection. Conclusions sTREM-1 is a physiologic constituent of the AF, and its concentration: 1) is significantly elevated in the presence of IAI; 2) increases with advancing gestation; and 3) does not change in the presence of spontaneous labor at term. We propose that sTREM-1 play a role in the innate immune response against intra-amniotic infection. PMID:19591072

The Importance of Clinical Phenotype in Understanding and Preventing Spontaneous Preterm Birth.

PubMed

Esplin, M Sean

2016-02-01

Spontaneous preterm birth (SPTB) is a well-known cause of maternal and neonatal morbidity. The search for the underlying pathways, documentation of the genetic causes, and identification of markers of spontaneous PTB have been marginally successful due to the fact that it is highly complex, with numerous processes that lead to a final common pathway. There is a great need for a comprehensive, consistent, and uniform classification system, which will be useful in identifying mechanisms, assigning prognosis, aiding in clinical management, and can identify areas of interest for intervention and future study. Effective classification systems must overcome obstacles including the lack of widely accepted definitions and uncertainty about inclusion of classifying features (e.g., presentation at delivery and multiple gestations) and levels of detail of these features. The optimal classification system should be based on the clinical phenotype, including characteristics of the mother, fetus, placenta, and the presentation for delivery. We present a proposed phenotyping system for spontaneous PTB. Future classification systems must establish a universally accepted set of definitions and a standardized clinical workup for all PTBs including the minimum clinical data to be collected and the laboratory and pathologic evaluation that should be completed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Reproductive performance in the next pregnancy for nulliparous women with history of first trimester spontaneous abortion.

PubMed

El Behery, Manal M; Siam, Soha; Seksaka, Mahmoud A; Ibrahim, Zakia M

2013-10-01

To determine whether interpregnancy interval after the first spontaneous abortion has an effect on reproductive performance of women in their next pregnancy. A prospective cohort study was conducted on 4,619 women with history of spontaneous abortion in their first pregnancy. Of them 2,422 (52.4 %) conceived within 6 months of the miscarriage (group A) and 2,197 47.6 % after 12 months (group B). The primary outcome was abortion, live birth, termination, or ectopic pregnancy in the next pregnancy. Secondary outcomes were preterm delivery, low birth weight infants, caesarean section rate and occurrence of preeclampsia, placental abruption and induced labour in the second pregnancy. Women who conceived again within 6 months were less likely to have another abortion, termination, or ectopic pregnancy compared with women with interpregnancy interval more than 12 months. Women with an interpregnancy interval more than 12 months were less likely to have live birth in the second pregnancy and more likely to have a caesarean section, preterm delivery, or infant of low birth weight compared with women who conceived again within 6 months. Women who conceive within 6 months after their first spontaneous abortion have better reproductive outcomes and the lowest complication rates in their subsequent pregnancy.

Biochemical markers may identify preterm infants with a patent ductus arteriosus at high risk of death or severe intraventricular haemorrhage.

PubMed

El-Khuffash, A; Barry, D; Walsh, K; Davis, P G; Molloy, E J

2008-11-01

A patent ductus arteriosus (PDA) in preterm infants is associated with increased risk of intraventricular haemorrhage (IVH) and death. Cardiac troponin T (cTnT) and N-terminal-pro-B type natriuretic peptide (NTpBNP) are markers of cardiac function and can predict poor outcome in adults. To determine whether echocardiography and cTnT/NTpBNP levels at 48 h predict death before discharge or severe IVH in preterm infants with a PDA. Infants born <32 weeks' gestation or <1500 g underwent echocardiographic and cTnT/NTpBNP measurements at 12 and 48 h of life. Infants were divided according to their status at discharge: a closed PDA at 48 h, infants with a PDA at 48 h and IVH III/IV and/or death, and infants with a PDA at 48 h without IVH III/IV or death. Eighty infants with a median gestation of 28 weeks (IQR 26.1-29.5) and birth weight 1.06 kg (0.8-1.21) were included. At 48 h, infants with a PDA and IVH III/IV and/or death had significantly higher median cTnT/NTpBNP levels compared to infants with a PDA without IVH III/IV and/or death and those with spontaneous PDA closure (NTpBNP 9282, 5121 and 740 pmol/l, respectively, p = 0.008, and cTnT 0.66, 0.25 and 0.13 microg/l, respectively, p = 0.027). There were no differences in echocardiographic parameters of PDA size, left atrial to aortic ratio (LA:Ao), left and right ventricular outputs between the PDA groups. NTpBNP and cTnT in conjunction with echocardiography may provide a basis for trials of targeted medical treatment in infants with a PDA.

N-terminal pro-brain natriuretic peptide measurements in hemodynamically significant patent ductus arteriosus in preterm infants.

PubMed

Alenazi, Shehab Ahmed

2016-01-01

Evaluate the role of NT-proBNP levels in Preterm neonates suffering from PDA and used as a screening tool for predicting HsPDA and guiding physicians to consider early echocardiographic evaluation. This is a monocentric prospective blind study which was conducted at Arar Central Hospital, Ar'ar, Saudi Arabia, during the period between Jan 2014 to June 2014. Thirty-three (33) preterm infants born at less than 31 weeks of gestation or weighing less than 1200 g at birth infants were initially enrolled during a 6-month period. Blood samples were collected along with routine blood tests on days 1, 2, 3, and 7 of life for NT-proBNP analysis. Two echocardiographies were systematically performed on day two of life to ascertain about the status of Ductus Arteriosus. The Plasma NT-proBNP levels were high on day one of life and decline from day three to day seven of life except in those infants with significant hsPDA. Plasma NT-proNBP levels on day 2 of infants in the HsPDA group were significantly higher (<0.001) than those in non-HsPDA group. Echocardiogram parameters indicates the significant difference (p<0.002) in Left Atrial and Aortic ratio (LA/AO), Interventricular septum thickness (P<0.03), Left ventricular posterior wall thickness (p<0.05), diastole PDA gradient (p<0.005) between HsPDA and non-HsPDA. Plasma NT-proBNP level peaked during the first few days after birth and declined rapidly within a week. Therefore, its level may have a role as a screening tool to predict HsPDA and provide more information regarding its spontaneous closure or otherwise.

Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants

PubMed Central

Menon, Ramkumar; Pearce, Brad; Velez, Digna R; Merialdi, Mario; Williams, Scott M; Fortunato, Stephen J; Thorsen, Poul

2009-01-01

Objective To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools. Methods A large scale candidate gene association study was performed on 1442 SNPs in 130 genes in a case (preterm birth < 36 weeks) control study (term birth > 37 weeks). Both maternal and fetal DNA from Caucasians (172 cases and 198 controls) and 279 African-Americans (82 cases and 197 controls) were used. A single locus association (genotypic) analysis followed by hierarchical clustering was performed, where clustering was based on p values for significant associations within each race. Using Ingenuity Pathway Analysis (IPA) software, known pathophysiologic pathways in both races were determined. Results From all SNPs entered into the analysis, the IPA mapped genes to specific disease functions. Gene variants in Caucasians were implicated in disease functions shared with other known disorders; specifically, dermatopathy, inflammation, and hematological disorders. This may reflect abnormal cervical ripening and decidual hemorrhage. In African-Americans inflammatory pathways were the most prevalent. In Caucasians, maternal gene variants showed the most prominent role in disease functions, whereas in African Americans it was fetal variants. The IPA software was used to generate molecular interaction maps that differed between races and also between maternal and fetal genetic variants. Conclusion Differences at the genetic level revealed distinct disease functions and operational pathways in African Americans and Caucasians in spontaneous preterm birth. Differences in maternal and fetal contributions in pregnancy outcome are also different between African Americans and Caucasians. These results present a set of explicit testable hypotheses regarding genetic associations with preterm birth in African Americans and Caucasians PMID:19527514

Impact of IL1B gene polymorphisms and interleukin 1B levels on susceptibility to spontaneous preterm birth.

PubMed

Langmia, Immaculate M; Apalasamy, Yamunah D; Omar, Siti Z; Mohamed, Zahurin

2016-11-01

Genetic factors influence susceptibility to preterm birth (PTB) and the immune pathway of PTB that involves the production of cytokines such as interleukins has been implicated in PTB disease. The aim of this study is to investigate the association of interleukin 1β (IL1B) gene polymorphisms and IL1B levels with spontaneous PTB. Peripheral maternal blood from 495 women was used for extraction of DNA and genotyping was carried out using the Sequenom MassARRAY platform. Maternal plasma was used to measure IL1B levels. There was no significant association between the allelic and genotype distribution of IL1B single nucleotide polymorphism (SNP) (rs1143634, rs1143627, rs16944) and the risk of PTB among Malaysian Malay women (rs1143634, P=0.722; rs1143627, P=0.543; rs16944, P=0.615). However, IL1B levels were significantly different between women who delivered preterm compared with those who delivered at term (P=0.030); high mean levels were observed among Malay women who delivered at preterm (mean=32.52) compared with term (mean=21.68). IL1B SNPs were not associated with IL1B plasma levels. This study indicates a significant association between IL1B levels and reduced risk of PTB among the Malaysian Malay women. This study shows the impact of IL1B levels on susceptibility to PTB disease; however, the high levels of IL1B observed among women in the preterm group are not associated with IL1B SNPs investigated in this study; IL1B high levels may be because of other factors not explored in this study and therefore warrant further investigation.

Is routine transvaginal cervical length measurement cost-effective in a population where the risk of spontaneous preterm birth is low?

PubMed

Crosby, David A; Miletin, Jan; Semberova, Jana; Daly, Sean

2016-12-01

A recent meta-analysis has suggested that routine measurement of the cervical length should be performed in conjunction with the anomaly scan to identify a group of women at increased risk of preterm delivery. We decided to investigate whether this recommendation is justifiable in a population where the risk of preterm birth is low. We reviewed 12 years of obstetric data from the Coombe Women and Infants University Hospital. Relative risks of adverse outcomes from the randomized controlled trial were applied and we extrapolated the possible numbers of women requiring intervention. We then used published neonatal data to estimate the cost of neonatal care and estimated the costs of providing the service. Over 12 years from 2000 until 2011, there were 94 646 singleton deliveries, 1776 happening before 34 weeks. Spontaneous onset occurred in 882 (49.7%) of this group. These 882 births were studied. If we apply the figures from a randomized controlled trial, 1609 women (1.7% from our total population) would be expected to have a cervical length 15 mm. If we gave vaginal progesterone to all women with a sonographically short cervix, we would reduce the delivery rate before 34 weeks by 27.7%. The annual costs of providing the service were estimated to be €109 249 and the cost of immediate neonatal care was estimated to be €380 514. Given the implications associated with preterm delivery, routine measurement of cervical length at the time of the anomaly scan may be justifiable from a cost point of view in a population where the risk of preterm birth is low. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Impact of a stepwise introduction of smoke-free legislation on the rate of preterm births: analysis of routinely collected birth data.

PubMed

Cox, Bianca; Martens, Evelyne; Nemery, Benoit; Vangronsveld, Jaco; Nawrot, Tim S

2013-02-14

To investigate the incidence of preterm delivery in the Belgian population after implementation of smoke-free legislation in three phases (in public places and most workplaces January 2006, in restaurants January 2007, and in bars serving food January 2010). Logistic regression analyses on routinely collected birth data from January 2002 to December 2011. Flanders, Belgium. All live born singleton births delivered at 24-44 weeks of gestation (n = 606,877, with n = 448,520 spontaneous deliveries). Preterm birth (gestational age <37 weeks). We found reductions in the risk of preterm birth after the introduction of each phase of the smoking ban. No decreasing trend was evident in the years or months before the bans. We observed a step change in the risk of spontaneous preterm delivery of -3.13% (95% CI -4.37% to -1.87%; P<0.01) on 1 January 2007 (ban on smoking in restaurants), and an annual slope change of -2.65% (-5.11% to -0.13%; P=0.04) after 1 January 2010 (ban on smoking in bars serving food). The analysis for all births gave similar results: a step change of -3.18% (-5.38% to -0.94%; P<0.01) on 1 January 2007, and an annual slope change of -3.50% (-6.35% to -0.57%; P=0.02) after 1 January 2010. These changes could not be explained by personal factors (infant sex, maternal age, parity, socioeconomic status, national origin, level of urbanisation); time related factors (underlying trends, month of the year, day of the week); or population related factors (public holidays, influenza epidemics, and short term changes in apparent temperature and particulate air pollution). Our study shows a consistent pattern of reduction in the risk of preterm delivery with successive population interventions to restrict smoking. This finding is not definitive but it supports the notion that smoking bans have public health benefits from early life.

The Relationship between Chlamydia trachomatis Genital Infection and Spontaneous Abortion.

PubMed

Ahmadi, Amjad; Khodabandehloo, Mazaher; Ramazanzadeh, Rashid; Farhadifar, Fariba; Roshani, Daem; Ghaderi, Ebrahim; Farhangi, Niloofar

2016-01-01

Chlamydia trachomatis is the etiology of most of sexually transmitted diseases. Colonization of C. trachomatis in the genital tract during early gestation has been associated with preterm birth, and preterm premature rupture of the membranes. The role of C. trachomatis on spontaneous abortion has not yet been proved completely. The aim of this study was to evaluate the frequency of C. trachomatis infection among pregnant women and its association with spontaneous abortion. This case-control study was conducted from August 2012 until January 2013. Totally, 218 women were included; 109 women with spontaneous abortion with gestation age between 10-20 weeks (cases), and 109 women with normal pregnancy with gestation age between 20-30 weeks (controls) in Sanandaj, Iran. DNA was extracted from endocervical swabs and a PCR test was conducted for detection of C. trachomatis infection in women using specific primers. Independent T-test and Chi-square were used for comparison of quantitative and qualitative variables, respectively, and p<0.05 was considered significant. The total prevalence of C. trachomatis infection was 38(17.43%) in endocervical swabs of women. However, the number of cases with C. trachomatis infections was 25 out of 109(22.9%) in the case group and 13 out of 109(11.9%) in control group, respectively. Association between chlamydia infection and spontaneous abortion was statistically significant (OR=2.198, CI 95%: 1.058-4.56). Our study showed that C. trachomatis infection was associated with spontaneous abortion. Thus, screening and treatment of pregnant women may prevent this adverse pregnancy outcome.

Amniotic fluid angiopoietin-2 in term and preterm parturition, and intra-amniotic infection/inflammation

PubMed Central

Pacora, Percy; Romero, Roberto; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Erez, Offer; Vaisbuch, Edi; Mazaki-Tovi1, Shali; Gotsch, Francesca; Kim, Chong Jai; Than, Nandor Gabor; Yeo, Lami; Mittal1, Pooja; Hassan, Sonia S.

2012-01-01

Objective Recent observations have revealed an interaction between inflammation and angiogenesis, which may be mediated by angiopoietins and chemokines. Given the importance of inflammation in parturition, we sought to determine whether angiopoietin-2 (Ang-2) is present in amniotic fluid (AF) and if its concentration changes with gestational age, labor, and in intra-amniotic infection/inflammation (IAI) in patients with spontaneous preterm labor and intact membranes. Study design This cross-sectional study included 486 patients in the following groups: 1) women in the midtrimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=48) and without (n=45) spontaneous labor; 3) patients with an episode of spontaneous preterm labor (PTL) and intact membranes who were classified into: a) PTL without IAI who delivered at term (n=152); b) PTL without IAI who delivered preterm (<37 weeks gestation; n=107); and c) PTL with IAI (n=82). Ang-2 concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analysis. Results 1) Ang-2 was detected in all AF samples; 2) the median AF Ang-2 concentration at term was significantly lower than that in the mid-trimester (1877.4 pg/mL vs. 3525.2 pg/mL; P<0.001); 3) among patients with PTL, the median AF Ang-2 concentration was significantly higher in patients with IAI than in those without IAI (4031.3 pg/mL vs. 2599.4 pg/mL; P<0.001) and those with PTL without IAI who delivered at term (4031.3 pg/mL vs. 2707.3 pg/mL; P<0.001); and 4) no significant differences were observed in the median AF Ang-2 concentration between patients with spontaneous labor at term and those at term not in labor (1722.9 pg/mL vs. 1877.4 pg/mL; P=0.6). Conclusions 1) Ang-2, a protein involved in the process of vascular remodeling, is a physiologic constituent of the amniotic fluid and its concentration decreased with advancing gestation; 2) the median Ang-2 concentration in amniotic fluid is higher in patients with IAI than in those without; and 3) spontaneous parturition at term is not associated with changes in the AF concentration of Ang-2. These findings support the view of a link between angiopoietins and inflammation. PMID:19435449

Intellectual and Emotional Development and School Adjustment in Preterm Children at 6 and 7 Years of Age. Continuation of a Follow-Up Study.

ERIC Educational Resources Information Center

Grigoroiu-Serbanescu, Maria

1984-01-01

Continues a previous five-year follow-up of preterm and full-term children by studying the continuity in their intellectual and emotional development. Prematurity was predictive for school adjustment at ages six and seven only when regression was performed on the preterm group, but failed to be predictive when mixed groups of preterm and full-term…

The ORACLE Children Study: educational outcomes at 11 years of age following antenatal prescription of erythromycin or co-amoxiclav.

PubMed

Marlow, Neil; Bower, Hannah; Jones, David; Brocklehurst, Peter; Kenyon, Sara; Pike, Katie; Taylor, David; Salt, Alison

2017-03-01

Antibiotics used for women in spontaneous preterm labour without overt infection, in contrast to those with preterm rupture of membranes, are associated with altered functional outcomes in their children. From the National Pupil Database, we used Key Stage 2 scores, national test scores in school year 6 at 11 years of age, to explore the hypothesis that erythromycin and co-amoxiclav were associated with poorer educational outcomes within the ORACLE Children Study. Anonymised scores for 97% of surviving children born to mothers recruited to ORACLE and resident in England were analysed against treatment group adjusting for key available socio-demographic potential confounders. No association with crude or with adjusted scores for English, mathematics or science was observed by maternal antibiotic group in either women with preterm rupture of membranes or spontaneous preterm labour with intact membranes. While the proportion receiving special educational needs was similar in each group (range 31.6-34.4%), it was higher than the national rate of 19%. Despite evidence that antibiotics are associated with increased functional impairment at 7 years, educational test scores and special needs at 11 years of age show no differences between trial groups. ISCRT Number 52995660 (original ORACLE trial number). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Associations of maternal PLA2G4C and PLA2G4D polymorphisms with the risk of spontaneous preterm birth in a Chinese population

PubMed Central

Liu, Guang-Jian; He, Jian-Rong; Kuang, Ya-Shu; Fan, Xue-Jiao; Li, Wei-Dong; Lu, Jin-Hua; Xia, Xiao-Yan; Liu, Xiao-Dan; Chen, Nian-Nian; Mai, Wei-Bi; Xia, Hui-Min; Qiu, Xiu

2017-01-01

Preterm birth is the leading cause of mortality and morbidity in infants. Its etiology is multifactorial with genes and immune homeostasis. The authors investigated whether prostaglandin (PG) synthesis related single nucleotide polymorphisms (SNPs) PLA2G4C rs1366442 and PLA2G4D rs4924618 were associated with the risk of spontaneous preterm birth (SPTB) in a Chinese population of 114 cases of SPTB and 250 controls of term delivery. The risk associations were determined by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated using multivariate logistic regression. Homology modeling was performed to elucidate potential mechanism of the SNP function. The maternal AT/TT genotype of PLA2G4D rs4924618 was associated with a reduced risk of SPTB (OR, 0.61; 95% CI, 0.37–0.99), while no significant association between PLA2G4C rs1366442 and SPTB risk was identified. Structure and sequence analysis revealed that the amino acid substitution introduced by this SNP located at the conserved central core of the catalytic domain of cytosolic phospholipase A2 δ and was close to the active site. These findings suggested that the polymorphism of PLA2G4D rs4924618 may have a protective influence on the SPTB susceptibility in a Chinese population, supporting a role for genetics in the association between PG synthesis and preterm birth. PMID:28440406

Localization of spontaneous bursting neuronal activity in the preterm human brain with simultaneous EEG-fMRI.

PubMed

Arichi, Tomoki; Whitehead, Kimberley; Barone, Giovanni; Pressler, Ronit; Padormo, Francesco; Edwards, A David; Fabrizi, Lorenzo

2017-09-12

Electroencephalographic recordings from the developing human brain are characterized by spontaneous neuronal bursts, the most common of which is the delta brush. Although similar events in animal models are known to occur in areas of immature cortex and drive their development, their origin in humans has not yet been identified. Here, we use simultaneous EEG-fMRI to localise the source of delta brush events in 10 preterm infants aged 32-36 postmenstrual weeks. The most frequent patterns were left and right posterior-temporal delta brushes which were associated in the left hemisphere with ipsilateral BOLD activation in the insula only; and in the right hemisphere in both the insular and temporal cortices. This direct measure of neural and hemodynamic activity shows that the insula, one of the most densely connected hubs in the developing cortex, is a major source of the transient bursting events that are critical for brain maturation.

Ureaplasma parvum genotype, combined vaginal colonisation with Candida albicans, and spontaneous preterm birth in an Australian cohort of pregnant women.

PubMed

Payne, Matthew S; Ireland, Demelza J; Watts, Rory; Nathan, Elizabeth A; Furfaro, Lucy L; Kemp, Matthew W; Keelan, Jeffrey A; Newnham, John P

2016-10-18

Detection of Ureaplasma, Mycoplasma and Candida spp. in the vagina during pregnancy has previously been associated with preterm birth (PTB). However, the prevalence of these microorganisms and the associated obstetric risks (likely to be population-specific) have not been determined in Australian women; furthermore, in the case of Ureaplasma spp., very few studies have attempted characterisation at the species level and none have examined genotype/serovar status to further refine risk assessment. In order to address these issues we sampled the vaginal fluid of 191 pregnant Australian women at three time points in pregnancy. Culture methods were used for detection of Ureaplasma spp. and Candida spp., and real-time PCR was used for speciation of U. parvum and U. urealyticum, non-albicans Candida spp., Mycoplasma hominis and Mycoplasma genitalium. High-resolution melt PCR was used to genotype U. parvum. Data on various lifestyle factors (including sex during pregnancy and smoking), antimicrobial use and pregnancy outcome were collected on all participants. Chi-square tests were used to assess the association of vaginal microorganisms with PTB. Detection of Ureaplasma spp. was higher among spontaneous PTB cases, specifically in the presence of U. parvum [77 % preterm (95 % confidence interval (CI) 50-100 %) vs. 36 % term (CI: 29-43 %), p = 0.004], but not U. urealyticum. The association with PTB strengthened when U. parvum genotype SV6 was detected (54 % preterm (CI: 22-85 %) vs. 15 % term (CI: 10-20 %), p = 0.002); this genotype was also present in 80 % (4/5) of cases of PTB <34 weeks gestation. When present with Candida albicans in the same sample, the association with PTB remained strong for both U. parvum [46 % preterm (CI: 15-78 %) vs. 13 % term (CI: 8-18 %), p = 0.005] and U. parvum genotype SV6 [39 % preterm (CI: 8-69 %) vs. 7 % term (CI: 3-11 %), p = 0.003]. With the exception of Candida glabrata, vaginal colonisation status for all organisms was stable throughout pregnancy. Smoking significantly increased the likelihood of detection of all target organisms. These data suggest that the presence of different species and serovars of Ureaplasma spp. in the vagina confers an increased risk of spontaneous PTB, findings which may be useful in risk assessment for identifying women who would benefit from antimicrobial treatment.

Risk assessment and management to prevent preterm birth.

PubMed

Koullali, B; Oudijk, M A; Nijman, T A J; Mol, B W J; Pajkrt, E

2016-04-01

Preterm birth is the most important cause of neonatal mortality and morbidity worldwide. In this review, we review potential risk factors associated with preterm birth and the subsequent management to prevent preterm birth in low and high risk women with a singleton or multiple pregnancy. A history of preterm birth is considered the most important risk factor for preterm birth in subsequent pregnancy. General risk factors with a much lower impact include ethnicity, low socio-economic status, maternal weight, smoking, and periodontal status. Pregnancy-related characteristics, including bacterial vaginosis and asymptomatic bacteriuria, appear to be of limited value in the prediction of preterm birth. By contrast, a mid-pregnancy cervical length measurement is independently associated with preterm birth and could be used to identify women at risk of a premature delivery. A fetal fibronectin test may be of additional value in the prediction of preterm birth. The most effective methods to prevent preterm birth depend on the obstetric history, which makes the identification of women at risk of preterm birth an important task for clinical care providers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exposure to firework chemicals from production factories in pregnant women and risk of preterm birth occurrence in Liuyang, China.

PubMed

Li, Xun; Tan, Hongzhuan; Luo, Meiling; Wu, Xinrui; Huang, Xin; Zhou, Shujin; Shen, Lin; He, Yue; Liu, Yi; Hu, Li; Chen, Mengshi; Hu, Shimin; Wen, Shi Wu

2018-01-01

In the production of fireworks, various pollutants including particles of metals and organic compounds are released into the environment. Although the adverse effects of these air pollutants are known, the impact on pregnant women residing in this area remains to be determined. The aim of this study was to examine the association between maternal exposure to fireworks production chemicals and frequency of preterm birth in Liuyang, China. Maternal exposure to fireworks production was estimated at the residential district level and assessed using factory density, which was defined as the number of fireworks factories per 1000 residents in each district. The association of maternal exposure to particulates released from fireworks production plants with frequency of preterm birth was determined using data obtained from a cohort study conducted in Liuyang, China. Data were analyzed utilizing linear regression and logistic regression. There was no significant association between factory density and spontaneous preterm or medically induced preterm birth. Unexpectedly, pregnant women residing in areas with higher density of fireworks factories were at a reduced risk of preterm premature rupture of membranes (PPROM). Data demonstrated that residential density of fireworks factories appeared to be negatively correlated with preterm birth rate as evidenced by PPROM. At present, it is difficult to reconcile the inverse relationship between firework chemical exposure and frequency of preterm births as ambient particulate inhalation is known to adversely affect preterm birth occurrence.

Role of acoustic radiation force impulse and shear wave velocity in prediction of preterm birth: a prospective study.

PubMed

Agarwal, Arjit; Agarwal, Shubhra; Chandak, Shruti

2018-06-01

Background Preterm birth is one of the important causes of neonatal morbidity where we rely on subjective criteria such as modified Bishop's scoring and contemporary sonographic measurement of cervical length. Acoustic radiation force impulse (ARFI) is a technological advancement in elastography that can be employed in prediction of cervical softening and preterm labor. Purpose To evaluate the role of ARFI technique and shear wave velocity (SWV) estimates as a predictor of preterm birth and its comparison with other clinical and sono-elastographic measures. Material and Methods Thirty-four pregnant women (gestation age = 28-37 weeks age) showing features suggestive of preterm labor were included and evaluated with modified Bishop's score, cervical length by ultrasound (US), ARFI to derive Elastography index (EI), and SWV of the cervix. The patients were later divided into two groups, using the clinical outcome of preterm or term delivery. Results Twenty patients delivered at term (gestational age > 37 weeks) and 14 were preterm. Receiver operating characteristics (ROC) curves showed SWV with highest sensitivity and specificity (93% and 90%, respectively) for the prediction of preterm birth at a cutoff value of 2.83 m/s. EI and modified Bishop's score were comparable to each other, but were less sensitive techniques. Conclusion Elastographic assessment of antenatal cervix is a novel technique of virtual palpation of internal os and can be utilized as an objective criterion for preterm birth prediction.

AIR QUALITY AND SELECTED BIRTH DEFECTS, SEVEN COUNTY STUDY, TEXAS, 1997-2000

EPA Science Inventory

Introduction: A number of epidemiologic investigations have shown adverse effects of ambient air pollution on reproductive outcomes including spontaneous abortion, fetal growth, preterm delivery, and infant mortality. A southern California study found associations between carbon ...

Comparison of HFNC, bubble CPAP and SiPAP on aerosol delivery in neonates: An in-vitro study.

PubMed

Sunbul, Fatemah S; Fink, James B; Harwood, Robert; Sheard, Meryl M; Zimmerman, Ralph D; Ari, Arzu

2015-11-01

Aerosol drug delivery via high flow nasal cannula (HFNC), bubble continuous positive airway pressure (CPAP), and synchronized inspiratory positive airway pressure (SiPAP) has not been quantified in spontaneously breathing premature infants. The purpose of this study was to compare aerosol delivery via HFNC, bubble CPAP, and SiPAP in a model of a simulated spontaneously breathing preterm infant. The types of CPAP systems and nebulizer positions used during aerosol therapy will impact aerosol deposition in simulated spontaneously breathing infants. Quantitative, comparative, in-vitro study. A breath simulator was set to preterm infant settings (VT : 9 ml, RR: 50 bpm and Ti: 0.5 sec) and connected to the trachea of an anatomical upper airway model of a preterm infant via collecting filter distal to the trachea. The HFNC (Optiflow; Fisher & Paykel), Bubble CPAP (Fisher & Paykel), and SiPAP (Carefusion) were attached to the nares of the model via each device's proprietary nasal cannula and set to deliver a baseline of 5 cm H2 O pressure. Albuterol sulfate (2.5 mg/0.5 ml) was aerosolized with a mesh nebulizer (Aeroneb Solo) positioned(1) proximal to the patient and(2) prior to the humidifier (n = 5). The drug was eluted from the filter with 0.1 N HCl and analyzed via spectrophotometry (276 nm). Data were analyzed using descriptive statistics, t-tests, and one-way analysis of variance (ANOVA), with P < 0.05 significant. At position 1, the trend of lower deposition (mean ± SD%) across devices was not significant (0.90 ± 0.26, 0.70 ± 0.16 and 0.59 ± 0.19, respectively; P = 0.098); however, in position 2, drug delivery with SiPAP (0.79 ± 0.11) was lower compared to both HFNC (1.30 ± 0.17; P = 0.003) and bubble CPAP (1.24 ± 0.24; p = 0.008). Placement of the nebulizer prior to the humidifier increased deposition with all devices (P < 0.05). Aerosol can be delivered via all three devices used in this study. Device selection and nebulizer position impacted aerosol delivery in this simulated model of a spontaneously breathing preterm infant. © 2014 Wiley Periodicals, Inc.

Can stress biomarkers predict preterm birth in women with threatened preterm labor?

PubMed

García-Blanco, Ana; Diago, Vicente; Serrano De La Cruz, Verónica; Hervás, David; Cháfer-Pericás, Consuelo; Vento, Máximo

2017-09-01

Preterm birth is a major paediatric challenge difficult to prevent and with major adverse outcomes. Prenatal stress plays an important role on preterm birth; however, there are few stress-related models to predict preterm birth in women with Threatened Preterm Labor (TPL). The aim of this work is to study the influence of stress biomarkers on time until birth in TPL women. Eligible participants were pregnant women between 24 and 31 gestational weeks admitted to the hospital with TPL diagnosis (n=166). Stress-related biomarkers (α-amylase and cortisol) were determined in saliva samples after TPL diagnosis. Participants were followed-up until labor. A parametric survival model was constructed based on α-amylase, cortisol), TPL gestational week, age, parity, and multiple pregnancy. The model was adjusted using a logistic distribution and it was implemented as a nomogram to predict the labor probability at 7- and 14-day term. The time until labor was associated with cortisol (p=0.001), gestational week at TPL diagnosis (p=0.004), and age (p=0.02). Importantly, high cortisol levels at TPL diagnosis were predictive of latency to labor. Validation of the model yielded an optimum corrected AUC value of 0.63. High cortisol levels at TPL diagnosis may have an important role in the preterm birth prediction. Our statistical model implemented as a nomogram provided accurate predictions of individual prognosis of pregnant women. Copyright © 2017 Elsevier Ltd. All rights reserved.

Psychosocial stress in pregnancy and its relation to the onset of premature labour.

PubMed

Newton, R W; Webster, P A; Binu, P S; Maskrey, N; Phillips, A B

1979-08-18

A modified life events inventory was presented over a four-month period to 132 consecutive women going into spontaneous labour in Hull and Manchester. Three study groups were identified according to the duration of pregnancy. The levels of psychosocial stress in pregnancy were found to be particularly high in the mothers whose babies were born preterm. Stressful events may precipitate preterm labour in some women. The concept of antenatal care may have to be broadened if the incidence of premature labour and resulting perinatal mortality are to be reduced.

Global Incidence of Preterm Birth.

PubMed

Tielsch, James M

2015-01-01

Estimating the incidence of preterm birth depends on accurate assessment of gestational age and pregnancy outcomes. In many countries, such data are not routinely collected, making global estimates difficult. A recent systematic approach to this problem has estimated a worldwide incidence of 11.1 per 100 live births in 2010. Significant variation in rates by country and region of the world was noted, but this variation is smaller than observed for a number of other important reproductive outcomes. Rates range from approximately 5% in some northern European countries to over 15% in some countries in sub-Saharan Africa and Asia. Time trends suggest that preterm birth incidence is increasing, but much of this change may reflect changes in medically induced early delivery practices as improvements in survival of preterm infants has improved. Whether there have been major changes in spontaneous preterm birth is unknown. New approaches to classifying etiologic heterogeneity have been proposed and offer the promise of developing specific interventions to address the range of underlying causes of this important health problem. © 2015 Nestec Ltd., Vevey/S. Karger AG, Basel.

Threatened preterm labor is a risk factor for impaired cognitive development in early childhood.

PubMed

Paules, Cristina; Pueyo, Victoria; Martí, Elena; de Vilchez, Susana; Burd, Irina; Calvo, Pilar; Oros, Daniel

2017-02-01

Threatened preterm labor is a leading cause of hospital admission during pregnancy. Patients with an episode of threatened preterm labor who deliver at term are considered to have false preterm labor. However, threatened preterm labor has been proposed as a pathologic insult that is not always sufficient to induce irreversible spontaneous preterm birth but that could alter the normal course of pregnancy. The aim of this study was to evaluate threatened preterm labor during pregnancy as a risk factor of neurodevelopmental deficits of children at 2 years of age. Two-year-old children who were born late preterm (n=22) or at term after threatened preterm labor (n=23) were compared with at-term control children (n=42). Neurodevelopment was evaluated at a corrected age of 24-29 months with the use of the Merrill-Palmer-Revised Scales of Development. Children who were born at term after threatened preterm labor had lower scores than control children on global cognitive index (95.4 vs 104.2; P=.011), cognition (95.1 vs 103.1; P=.021), fine motor (95.2 vs 103.4; P=.003), gross motor (84.7 vs 99.8; P=.001), memory (92.9 vs 100.4; P=.015), receptive language (93.9 vs 102.9; P=.03), speed of processing (105.7 vs 113.3; P=.011), and visual motor coordination (98.8 vs 106.7; P=.003) subtests. Children born at term after threatened preterm labor had an increased risk of mild neurodevelopmental delay compared with control children (odds ratio for global cognitive index, 2.06; 95% confidence interval, 1.09-3.88; P=.033). There were no significant differences in any cognitive domain between children who were born late preterm and children who were born at term after threatened preterm labor. Threatened preterm labor is a risk factor for impaired cognitive development at 2 years of age, even if birth occurred at term. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of obesity on preterm delivery prediction by transabdominal recording of uterine electromyography.

PubMed

Lucovnik, Miha; Chambliss, Linda R; Blumrick, Richard; Balducci, James; Gersak, Ksenija; Garfield, Robert E

2016-10-01

It has been shown that noninvasive uterine electromyography (EMG) can identify true preterm labor more accurately than methods available to clinicians today. The objective of this study was to evaluate the effect of body mass index (BMI) on the accuracy of uterine EMG in predicting preterm delivery. Predictive values of uterine EMG for preterm delivery were compared in obese versus overweight/normal BMI patients. Hanley-McNeil test was used to compare receiver operator characteristics curves in these groups. Previously reported EMG cutoffs were used to determine groups with false positive/false negative and true positive/true negative EMG results. BMI in these groups was compared with Student t test (p < 0.05 significant). A total of 88 patients were included: 20 obese, 64 overweight, and four with normal BMI. EMG predicted preterm delivery within 7 days with area under the curve = 0.95 in the normal/overweight group, and with area under the curve = 1.00 in the obese group (p = 0.08). Six patients in true preterm labor (delivering within 7 days from EMG measurement) had low EMG values (false negative group). There were no false positive results. No significant differences in patient's BMI were noted between false negative group patients and preterm labor patients with high EMG values (true positive group) and nonlabor patients with low EMG values (true negative group; p = 0.32). Accuracy of noninvasive uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity. Copyright © 2016. Published by Elsevier B.V.

Micro RNA clusters in maternal plasma are associated with preterm birth and infant outcomes.

PubMed

Wommack, Joel C; Trzeciakowski, Jerome P; Miranda, Rajesh C; Stowe, Raymond P; Ruiz, R Jeanne

2018-01-01

The current study examined micro RNA (miRNAs) clusters from the maternal plasma to determine their association with preterm birth (PTB) and infant birth outcomes. A subsample of 42 participants who spontaneously delivered either preterm (≤37 weeks) or term was selected from a parent sample of 515 pregnant Mexican American women. Plasma samples and prenatal data were collected at a single mid-gestation time point (22-24 weeks' gestation) and birth outcomes were obtained from medical records after delivery. Circulating miRNAs were analyzed by qPCR. When miRNAs were grouped according to chromosomal cluster rather than expression level, individual miRNAs correlated strongly with other individual miRNAs within their respective genomic locus. miRNAs from the c19mc cluster negatively correlated with c14mc miRNAs, and this relationship was more pronounced in PTB. Clusters c14mc was negatively associated with length of gestation; while the c19mc was positively associated with length of gestation and infant head circumference. Together, these findings suggest that groups of miRNAs from common chromosomal clusters, rather than individual miRNAs, operate as co-regulated groups of signaling molecules to coordinate length of gestation and infant outcomes. From this evidence, differences in cluster-wide expression of miRNAs are involved in spontaneous PTB.

[Clinical evaluation of flomoxef in the treatment of chorioamnionitis and changes in the fetal fibronectin level in vaginal secretion].

PubMed

Chimura, T; Hirayama, T; Oda, T; Saitou, N; Morisaki, N

1993-02-01

Flomoxef (FMOX) was administered as an initial treatment for chorioamnionitis complicating possible spontaneous abortion or premature delivery and preterm PROM (premature rupture of the membranes), and the clinical effectiveness of the drug, and the usefulness of fetal fibronectin (FFN) as a diagnostic marker of premature delivery were evaluated. 1. Clinical effects of drip infusion of FMOX (2-4 g/day) with and without tocolysis for the treatment of chorioamnionitis were evaluated in 43 patients with possible spontaneous abortion or premature delivery and those with preterm PROM (n = 43). Changes in the FFN level in the vaginal secretion were also studied in 11 patients. 2. It was possible to prevent premature delivery in 7 (26.9%) of 26 patients, and the latent period of preterm PROM was longer than 8 days in 6 (46.2%) of 13 patients. 3. The FFN level decreased slightly in patients for whom FMOX was effective, and the outcome was satisfactory in those whose FFN levels were less than 200 ng/ml. However, the outcome was poor in those whose FFN levels were higher than 1,000 ng/ml. These findings suggest that changes in the FFN level in the vaginal secretion reflect the clinical course of chorioamnionitis as do changes in CRP.

Predicting School Readiness from Neurodevelopmental Assessments at Age 2 Years after Respiratory Distress Syndrome in Infants Born Preterm

ERIC Educational Resources Information Center

Patrianakos-Hoobler, Athena I.; Msall, Michael E.; Huo, Dezheng; Marks, Jeremy D.; Plesha-Troyke, Susan; Schreiber, Michael D.

2010-01-01

Aim: To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. Method: Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric…

Predictive accuracy of changes in transvaginal sonographic cervical length over time for preterm birth: a systematic review and metaanalysis.

PubMed

Conde-Agudelo, Agustin; Romero, Roberto

2015-12-01

To determine the accuracy of changes in transvaginal sonographic cervical length over time in predicting preterm birth in women with singleton and twin gestations. PubMed, Embase, Cinahl, Lilacs, and Medion (all from inception to June 30, 2015), bibliographies, Google scholar, and conference proceedings. Cohort or cross-sectional studies reporting on the predictive accuracy for preterm birth of changes in cervical length over time. Two reviewers independently selected studies, assessed the risk of bias, and extracted the data. Summary receiver-operating characteristic curves, pooled sensitivities and specificities, and summary likelihood ratios were generated. Fourteen studies met the inclusion criteria, of which 7 provided data on singleton gestations (3374 women) and 8 on twin gestations (1024 women). Among women with singleton gestations, the shortening of cervical length over time had a low predictive accuracy for preterm birth at <37 and <35 weeks of gestation with pooled sensitivities and specificities, and summary positive and negative likelihood ratios ranging from 49% to 74%, 44% to 85%, 1.3 to 4.1, and 0.3 to 0.7, respectively. In women with twin gestations, the shortening of cervical length over time had a low to moderate predictive accuracy for preterm birth at <34, <32, <30, and <28 weeks of gestation with pooled sensitivities and specificities, and summary positive and negative likelihood ratios ranging from 47% to 73%, 84% to 89%, 3.8 to 5.3, and 0.3 to 0.6, respectively. There were no statistically significant differences between the predictive accuracies for preterm birth of cervical length shortening over time and the single initial and/or final cervical length measurement in 8 of 11 studies that provided data for making these comparisons. In the largest and highest-quality study, a single measurement of cervical length obtained at 24 or 28 weeks of gestation was significantly more predictive of preterm birth than any decrease in cervical length between these gestational ages. Change in transvaginal sonographic cervical length over time is not a clinically useful test to predict preterm birth in women with singleton or twin gestations. A single cervical length measurement obtained between 18 and 24 weeks of gestation appears to be a better test to predict preterm birth than changes in cervical length over time. Published by Elsevier Inc.

Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update.

PubMed

Sheikh, Ishfaq A; Ahmad, Ejaz; Jamal, Mohammad S; Rehan, Mohd; Assidi, Mourad; Tayubi, Iftikhar A; AlBasri, Samera F; Bajouh, Osama S; Turki, Rola F; Abuzenadah, Adel M; Damanhouri, Ghazi A; Beg, Mohd A; Al-Qahtani, Mohammed

2016-10-17

Preterm birth (PTB), birth at <37 weeks of gestation, is a significant global public health problem. World-wide, about 15 million babies are born preterm each year resulting in more than a million deaths of children. Preterm neonates are more prone to problems and need intensive care hospitalization. Health issues may persist through early adulthood and even be carried on to the next generation. Majority (70 %) of PTBs are spontaneous with about a half without any apparent cause and the other half associated with a number of risk factors. Genetic factors are one of the significant risks for PTB. The focus of this review is on single nucleotide gene polymorphisms (SNPs) that are reported to be associated with PTB. A comprehensive evaluation of studies on SNPs known to confer potential risk of PTB was done by performing a targeted PubMed search for the years 2007-2015 and systematically reviewing all relevant studies. Evaluation of 92 studies identified 119 candidate genes with SNPs that had potential association with PTB. The genes were associated with functions of a wide spectrum of tissue and cell types such as endocrine, tissue remodeling, vascular, metabolic, and immune and inflammatory systems. A number of potential functional candidate gene variants have been reported that predispose women for PTB. Understanding the complex genomic landscape of PTB needs high-throughput genome sequencing methods such as whole-exome sequencing and whole-genome sequencing approaches that will significantly enhance the understanding of PTB. Identification of high risk women, avoidance of possible risk factors, and provision of personalized health care are important to manage PTB.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms

PubMed Central

Esplin, M Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

2015-01-01

Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design A secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks gestation. Each woman was assessed for the presence of underlying SPTB etiologies. A hierarchical cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

Maternal Circulating Lipid Profile during Early Pregnancy: Racial/Ethnic Differences and Association with Spontaneous Preterm Delivery.

PubMed

Chen, Xinhua; Scholl, Theresa O; Stein, Thomas P; Steer, Robert A; Williams, Keith P

2017-01-01

Prior reports on the association between altered maternal serum lipid levels with preterm delivery are inconsistent. Ethnic differences in serum lipids during pregnancy and their relation to preterm delivery have not been studied. We examined the relationships of six maternal lipids during early pregnancy with the risk of spontaneous preterm delivery (SPTD). The design represents a case-control study nested within a large prospective, multiethnic cohort of young, generally healthy pregnant women. SPTD cases ( n = 183) and controls who delivered at term ( n = 376) were included. SPTD is defined as delivery at <37 completed weeks of gestation without indicated conditions. We found that African-American women had significantly increased levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1), and lower triglyceride (TG) and apolipoprotein B (apoB) levels compared to Hispanic and non-Hispanic Caucasians combined. Elevated HDL-C and apoA1 concentrations were significantly associated with an increased odds of SPTD after controlling for potential confounding factors. The adjusted odds ratio (AOR) was 1.91 (95% confidence interval (CI) 1.15, 3.20) for the highest quartile of HDL-C relative to the lowest quartile, and for apoA1 the AOR was 1.94 (95% CI 1.16, 3.24). When controlling for ethnicity, the results remained comparable. These data suggest that pregnant African-American women had a more favorable lipid profile suggestive of a reduction in cardiovascular risk. Despite this, increased HDL-C and apoA1 were both found to be associated with SPTD.

Outcomes and predictive tests from a dedicated specialist clinic for women at high risk of preterm labour: A ten year audit.

PubMed

Hughes, Kelly; Sim, Shirlene; Roman, Alina; Michalak, Kasia; Kane, Stefan; Sheehan, Penelope

2017-08-01

Preterm birth continues to be a major cause of infant morbidity and mortality worldwide, but advances have recently been made in its prediction and prevention. A short cervix (<25 mm) in the second trimester on transvaginal ultrasound scan and fetal fibronectin are important predictive tests. For over ten years, the Preterm Labour Clinic at the Royal Women's Hospital, Melbourne, Australia has provided care for women at high risk of preterm birth, including those with a previous preterm birth, previous cervical surgery, uterine malformation or incidental finding of short cervix at routine ultrasound. The purpose of this study was to review this clinic's outcomes for the first decade. This was a retrospective cohort study of all referrals to the Preterm Labour Clinic during the period 2004-2013 inclusive. Seven hundred and fifty-six cases met the study inclusion criteria of appropriate risk factor, singleton pregnancy, surveillance undertaken and outcome data available. The preterm birth rate (<37 weeks) was 21.4%. The rate of preterm birth by year decreased significantly when adjusted for risk (P = 0.002). A short cervix was diagnosed in 32% of the sample, and positively correlated with lower gestational age at delivery. Fetal fibronectin and serum alkaline phosphatase were independent predictors of preterm birth <34 weeks and <37 weeks. The adjusted preterm birth rate at the Royal Women's Hospital's Preterm Labour Clinic has decreased significantly over the decade studied. Positive fetal fibronectin at 26 weeks and elevated serum alkaline phosphatase are independent predictors of preterm birth. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro.

PubMed

Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-06-01

Does proviral integration site for Moloney murine leukaemic virus (PIM)1 kinase play a role in regulating the inflammatory processes of human labour and delivery? PIM1 kinase plays a critical role in foetal membranes in regulating pro-inflammatory and pro-labour mediators. Infection and inflammation have strong causal links to preterm delivery by stimulating pro-inflammatory cytokines and collagen degrading enzymes, which can lead to rupture of membranes. PIM1 has been shown to have a role in immune regulation and inflammation in non-gestational tissues; however, its role has not been explored in the field of human labour. PIM1 expression was analysed in myometrium and/or foetal membranes obtained at term and preterm (n = 8-9 patients per group). Foetal membranes, freshly isolated amnion cells and primary myometrial cells were used to investigate the effect of PIM1 inhibition on pro-labour mediators (n = 5 patients per treatment group). Foetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and from preterm pre-labour rupture of membranes (PPROM) (n = 9 per group). Amnion was collected from women with and without preterm chorioamnionitis (n = 8 per group). Expression of PIM1 kinase was determined by qRT-PCR and western blotting. To determine the effect of PIM1 kinase inhibition on the expression of pro-inflammatory and pro-labour mediators induced by bacterial products lipopolysaccharide (LPS) (10 μg/ml) and flagellin (1 μg/ml) and pro-inflammatory cytokine tumour necrosis factor (TNF) (10 ng/ml), chemical inhibitors SMI-4a (20 μM) and AZD1208 (50 μM) were used in foetal membrane explants and siRNA against PIM1 was used in primary amnion cells. Statistical significance was set at P < 0.05. PIM1 expression was significantly increased in foetal membranes after spontaneous term labour compared to no labour at term and in amnion with preterm chorioamnionitis compared to preterm with no chorioamnionitis. There was no change in PIM1 expression with preterm labour or PPROM compared to preterm with no labour or PPROM. In human foetal membranes, PIM1 inhibitors SMI-4a and AZD1208 significantly decreased the expression of pro-inflammatory cytokine interleukin-6 (IL6) and chemokines CXCL8 and CCL2 mRNA and release, prostaglandin prostaglandin F2α (PGF2α) release, adhesion molecule intercellular adhesion molecule 1 mRNA expression and release, and oxidative stress marker 8-isoprostane release after stimulation with either LPS or flagellin. Primary amnion cells transfected with PIM1 siRNA also showed decreased expression of IL6, CXCL8 and CCL2, PTGS2 mRNA and PGF2α release, and matrix metalloproteinase-9 (MMP9) expression, when stimulated with TNF. None. The conclusions were drawn from in vitro experiments using foetal membrane explants and primary cells isolated from amnion. Animal models are necessary to determine whether PIM1 kinase inhibitors can prevent spontaneous preterm birth in vivo. PIM1 kinase inhibitors may provide a novel therapeutic approach for preventing spontaneous preterm birth. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Funding for this study was provided by the NHMRC (grant no. 1058786), Norman Beischer Medical Research Foundation and the Mercy Research Foundation. The authors have no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

International variations in the gestational age distribution of births: an ecological study in 34 high-income countries.

PubMed

Delnord, Marie; Mortensen, Laust; Hindori-Mohangoo, Ashna D; Blondel, Béatrice; Gissler, Mika; Kramer, Michael R; Richards, Jennifer L; Deb-Rinker, Paromita; Rouleau, Jocelyn; Morisaki, Naho; Nassar, Natasha; Bolumar, Francisco; Berrut, Sylvie; Nybo Andersen, Anne-Marie; Kramer, Michael S; Zeitlin, Jennifer

2018-04-01

Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset. We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses. Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset. Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.

Maternal tea consumption and the risk of preterm delivery in urban China: a birth cohort study.

PubMed

Huang, Lei; Lerro, Catherine; Yang, Tao; Li, Jing; Qiu, Jie; Qiu, Weitao; He, Xiaochun; Cui, Hongmei; Lv, Ling; Xu, Ruifeng; Xu, Xiaoying; Huang, Huang; Liu, Qing; Zhang, Yawei

2016-05-31

Studies investigating the relationship between maternal tea drinking and risk of preterm birth have reached inconsistent results. The present study analyzed data from a birth cohort study including 10,179 women who delivered a singleton live birth were conducted in Lanzhou, China between 2010 and 2012. Drinking tea (OR = 1.36, 95 % CI: 1.09-1.69), and specifically green (OR = 1.42, 95 % CI: 1.08-1.85) or scented tea (OR = 1.61, 95 % CI: 1.04-2.50), was associated with an increased risk of preterm birth. Drinking tea was associated with both moderate preterm (OR = 1.41, 95 % CI: 1.12-1.79) and spontaneous preterm birth (OR = 1.41, 95 % CI: 1.09-1.83). Risk of preterm birth increased with decreasing age of starting tea drinking (<20 years, OR = 1.60, 95 % CI: 1.17-2.20) and increasing duration (p for trend < 0.01). The relationship between tea drinking and preterm birth is modified by both maternal age (p < 0.05) and gestational weight gain (p < 0.05). Despite conflicting findings in the previous literature, we saw a significant association with maternal tea drinking and risk of preterm birth in our cohort. More studies are needed both to confirm this finding and to elucidate the mechanism behind this association.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

PubMed

Bruijn, Mmc; Vis, J Y; Wilms, F F; Oudijk, M A; Kwee, A; Porath, M M; Oei, G; Scheepers, Hcj; Spaanderman, Mea; Bloemenkamp, Kwm; Haak, M C; Bolte, A C; Vandenbussche, Fpha; Woiski, M D; Bax, C J; Cornette, Jmj; Duvekot, J J; Nij Bijvanck, Bwa; van Eyck, J; Franssen, Mtm; Sollie, K M; van der Post, Jam; Bossuyt, Pmm; Opmeer, B C; Kok, M; Mol, Bwj; van Baaren, G-J

2016-11-01

To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. Post hoc analysis of frozen fFN samples of a nationwide cohort study. Ten perinatal centres in the Netherlands. Symptomatic women between 24 and 34 weeks of gestation. The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. Spontaneous delivery within 7 days after study entry. We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD. © 2015 Royal College of Obstetricians and Gynaecologists.

RELATIONSHIP BETWEEN AMBIENT AIR QUALITY AND SELECTED BIRTH DEFECTS, SEVEN COUNTY STUDY, TEXAS, 1997-2000

EPA Science Inventory

Background and Objectives: A number of epidemiologic investigations have shown adverse effects of ambient air pollution on reproductive outcomes including spontaneous abortion, fetal growth, preterm delivery, and infant mortality. A southern California, population-based, case-c...

Ultrasonographic wall thickness measurement of the upper and lower uterine segments in the prediction of the progress of preterm labour.

PubMed

Sayed Ahmed, W A; Madny, E H; Habash, Y H; Ibrahim, Z M; Morsy, A G K; Said, M E

2015-01-01

To assess the role of ultrasonographic measurement of the upper and lower uterine segments wall thickness in predicting the progress of preterm labour in patients presenting with preterm labour pains. Fifty pregnant women presenting at Obstetrics Department - Suez Canal University, Egypt with regular lower abdominal pains and diagnosed as having preterm labour were enrolled in the study. Measurements of the upper and lower uterine segments wall thickness by transabdominal ultrasonography in-between contractions and with full bladder were taken. The upper/lower uterine wall thickness ratio was calculated and correlated to the progress of the preterm labour and to the response to tocolytics. The ultrasonographic upper/lower uterine wall thickness ratio was directly related to the progress of preterm delivery (PTD). The change in this ratio is correlated inversely with the response to tocolysis. Using the ROC curve, when the upper/lower uterine wall thickness ratio was ≤ 1.26 the sensitivity was 94.74 and the specificity was 100.00, and when the ratio was ≤ 1.52 the sensitivity was 100.00 and the specificity was 83.33. These data may serve as a baseline ultrasonographic reference values for further studies in prediction the progress of preterm labour in patients presenting with preterm labour pains.

p38 Mitogen Activated Protein Kinase (MAPK): A New Therapeutic Target for Reducing the Risk of Adverse Pregnancy Outcomes

PubMed Central

Menon, Ramkumar; Papaconstantinou, John

2016-01-01

Introduction Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert Opinion This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation and its functional effects. PMID:27459026

Preterm delivery and the severity of violence during pregnancy.

PubMed

Covington, D L; Hage, M; Hall, T; Mathis, M

2001-12-01

To determine the severity and consequences of physical violence during pregnancy among participants in a health department prenatal care coordination program. The prospective cohort study included all program participants from 1994 to 1996. Care coordinators screened participants for physical violence during pregnancy using a validated, systematic assessment protocol three times during prenatal care. The protocol was linked with prenatal records, delivery records and infant records to document complications and infant outcomes. Multiple logistic regression was used to assess the relationship between severe physical violence during pregnancy and pregnancy outcome while controlling for confounding factors. Among the 550 participants, 13.5% reported violence during pregnancy; it included 6.7% severe violence (hitting, kicking, injury with a weapon and abdominal injury) and 6.7% moderate violence (threats, slapping, shoving and sexual abuse). Severe physical prenatal violence was significantly associated with spontaneous preterm labor, preterm delivery, very preterm delivery, very low birth weight, preterm/low birth weight, mean birth weight, mean newborn hospital charges, five-minute Apgar < 7, neonatal intensive care unit admission, and fetal or neonatal death. Body site injured, timing of violence and number of violent incidents were significant factors associated with violence during pregnancy and preterm delivery. Because severe physical violence during pregnancy was a significant problem in this population, intervention programs are needed to reduce prenatal violence and its consequences.

Soluble ST2, a Modulator of the Inflammatory Response, in Preterm and Term Labor

PubMed Central

Stampalija, Tamara; Chaiworapongsa, Tinnakorn; Romero, Roberto; Tarca, Adi L.; Bhatti, Gaurav; Chiang, Po Jen; Than, Nandor Gabor; Ferrazzi, Enrico; Hassan, Sonia S.; Yeo, Lami

2014-01-01

Objective Intra-amniotic infection/inflammation (IAI) is causally linked with spontaneous preterm labor and delivery. The ST2L receptor and its soluble form (sST2) are capable of binding to interleukin (IL)-33, a member of the IL-1 superfamily. Members of this cytokine family have been implicated in the onset of spontaneous preterm labor in the context of infection. Soluble ST2 has anti-inflammatory properties, and plasma concentrations are elevated in systemic inflammation, such as sepsis, acute pyelonephritis in pregnancy and the fetal inflammatory response syndrome. The aims of this study were to examine: 1) whether amniotic fluid concentrations of sST2 change with IAI, preterm, and term parturition; and 2) if mRNA expression of ST2 in the chorioamniotic membranes changes with acute histologic chorioamnionitis in women who deliver preterm. Methods A cross-sectional study was conducted to determine amniotic fluid concentrations of sST2 in: 1) women with preterm labor (PTL) who delivered at term (n=49); 2) women with PTL who delivered preterm without IAI (n=21); 3) women with PTL who delivered preterm with IAI (n=31); 4) term pregnancies not in labor (n=13); and 5) term pregnancies in labor (n=43). The amniotic fluid concentration of sST2 was determined by ELISA. The mRNA expression of ST2 in the chorioamniotic membranes of women who delivered preterm with (n=24), and without acute histologic chorioamnionitis (n=19) was determined by qRT-PCR. Results 1) Patients with PTL who delivered preterm with IAI had a lower median amniotic fluid concentration of sST2 compared to those with PTL who delivered preterm without IAI [median 410 ng/mL, inter-quartile range (IQR) 152-699 ng/mL vs. median 825 ng/mL, IQR 493-1216 ng/mL; p=0.0003] and those with PTL who delivered at term [median 410 ng/mL, IQR 152-699 ng/mL vs. median 673 ng/mL, IQR 468-1045ng/mL; p=0.0003]; 2) no significant differences in the median amniotic fluid concentration of sST2 were observed between patients with PTL who delivered at term and those who delivered preterm without IAI (p=0.4), and between women at term in labor and those at term not in labor (p=0.9); 3) the mean mRNA expression of ST2 was 4-fold lower in women who delivered preterm with acute histologic chorioamnionitis than in those without this lesion (p=0.008). Conclusions The median sST2 amniotic fluid concentration and mRNA expression of ST2 by chorioamniotic membranes is lower in PTL associated with IAI and acute histologic chorioamnionitis than in PTL without these conditions. Changes in the median amniotic fluid sST2 concentration are not observed in preterm and term parturition without IAI. Thus, amniotic fluid sST2 in the presence of IAI behaves differently when compared to sST2 in the plasma of individuals affected by fetal inflammatory response syndrome, acute pyelonephritis in pregnancy, and adult sepsis. Decreased concentrations of sST2 in IAI are likely to promote a pro-inflammatory response, which is important for parturition in the context of infection. PMID:23688338

Relationships among neighborhood environment, racial discrimination, psychological distress, and preterm birth in African American women.

PubMed

Giurgescu, Carmen; Zenk, Shannon N; Dancy, Barbara L; Park, Chang G; Dieber, William; Block, Richard

2012-01-01

To (a) examine the relationships among objective and perceived indicators of neighborhood environment, racial discrimination, psychological distress, and gestational age at birth; (b) determine if neighborhood environment and racial discrimination predicted psychological distress; (c) determine if neighborhood environment, racial discrimination, and psychological distress predicted preterm birth; and (d) determine if psychological distress mediated the effects of neighborhood environment and racial discrimination on preterm birth. Descriptive correlational comparative. Postpartum unit of a medical center in Chicago. African American women (n(1)  = 33 with preterm birth; n(2)  = 39 with full-term birth). Women completed the instruments 24 to 72 hours after birth. Objective measures of the neighborhood were derived using geographic information systems (GIS). Women who reported higher levels of perceived social and physical disorder and perceived crime also reported higher levels of psychological distress. Women who reported more experiences of racial discrimination also had higher levels of psychological distress. Objective social disorder and perceived crime predicted psychological distress. Objective physical disorder and psychological distress predicted preterm birth. Psychological distress mediated the effect of objective social disorder and perceived crime on preterm birth. Women's neighborhood environments and racial discrimination were related to psychological distress, and these factors may increase the risk for preterm birth. © 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Psychosocial stress in pregnancy and its relation to the onset of premature labour.

PubMed Central

Newton, R W; Webster, P A; Binu, P S; Maskrey, N; Phillips, A B

1979-01-01

A modified life events inventory was presented over a four-month period to 132 consecutive women going into spontaneous labour in Hull and Manchester. Three study groups were identified according to the duration of pregnancy. The levels of psychosocial stress in pregnancy were found to be particularly high in the mothers whose babies were born preterm. Stressful events may precipitate preterm labour in some women. The concept of antenatal care may have to be broadened if the incidence of premature labour and resulting perinatal mortality are to be reduced. PMID:486966

The prevalence of short cervix between 20 and 24 weeks of gestation and vaginal progesterone for prolonging of gestation.

PubMed

Maerdan, Malipati; Shi, Chunyan; Zhang, Xiaoxiao; Fan, Lixin

2017-07-01

The objective of this study is to understand the prevalence of short cervical length between 20 and 24 weeks gestation in China and to evaluate the efficacy of micronized progesterone for prolonging gestation in nulliparous patients with a short cervix. From May 2010 to May 2015, a total of 25 328 asymptomatic women with singleton pregnancies at Peking University First Hospital had their cervical length routinely measured between 20 and 24 weeks of gestation. A cervical length of 25 mm or less was defined as a shortened cervical length. The therapies prescribed include vaginal micronized progesterone capsules (200 mg each night) or bed rest from 20 to 34 weeks of gestation. The primary outcome was spontaneous delivery before 33 weeks. (1) One hundred fourteen women had a cervical length of ≤25 mm (0.45%). (2) Twenty-nine of which with previous spontaneous preterm delivery or late pregnancy loss had cervical cerclage, the remaining 85 women by the use of vaginal progesterone or simply resting activity restriction to prevent preterm birth. (3) In 85 nulliparous women treated by progesterone or bed rest, progesterone use in cervical length between 10 and 20 mm was associated with a statistically significant reduction in the incidence of preterm birth at <33 weeks of gestation (9.5% versus 45.5%, p = 0.02) compared with bed rest. There were no significant differences in cervical length between 20 and 25 mm in their rates of spontaneous preterm delivery at <33 (5.3% versus 3.2%, p = 0.72), <37 (33.3% versus 54.5%, p = 0.25), or <35 weeks (14.3% versus 45.5, p = 0.06) of gestation between vaginal progesterone and bed rest. The rate of short cervical length was less than expected. Vaginal progesterone is efficacious for the prolonging of gestation in women with a cervical length of 10-20 mm in the mid-trimester for a singleton gestation and nulliparous women. For a cervical length of 20-25 mm in the mid trimester, vaginal progesterone compared with bed rest did not prolong pregnancy.

Prediction of Participation and Sensory Modulation of Late Preterm Infants at 12 Months: A Prospective Study

ERIC Educational Resources Information Center

Bart, O.; Shayevits, S.; Gabis, L. V.; Morag, I.

2011-01-01

The aim of the study was to prospectively assess the differences in participation and sensory modulation between late preterm infants (LPI) and term babies, and to predict it by LPI characteristics. The study population includes 124 late preterm infants at gestational age between 34 and 35 6/7 weeks who were born at the same medical center. The…

Comparison of CRP and ALK-P serum levels in prediction of preterm delivery

PubMed Central

Shahshahan, Zahra; Iravani, Hoda

2016-01-01

Background: Preterm birth, defined as birth occurring before 37 weeks of gestation, is a common complication of pregnancy and may lead to death or long-term disability in newborns. Accurate diagnosis is, therefore, crucial for identifying those women undergoing preterm labor who are at greatest risk of preterm delivery. This may allow transport to a regional obstetrical center and permit time for corticosteroid therapy. Recent study recommends several markers such as CRP (C-reactive protein) and ALK-P (alkaline phosphatase) to predict preterm delivery. Materials and Methods: We select a total of 300 pregnant women that had symptoms of premature birth. All of them were under treatment with tocolytic and serum sample were taken to assess the level of CRP-ALKp. Cervix length and the time of response to tocolytic were measured. 110 pregnant of them had preterm labor. 110 patient that had a term labor selected as a control group. Results: Qualitative evaluation of efficacy CRP level on preterm delivery showed a significant relationship with 27 as a cut of point of CRP (P < 0.00001 –OR = 7.5). Investigate of effect of ALK-P level on preterm delivery refers to a significant relationship with 399 as a cut of point of ALKP (P < 0.00001 –OR = 5). Inquire of efficacy of CRP level and ALK-P level on preterm delivery demonstrate a significant relationship (P < 0.0001 1OR = 9). Conclusions: Maternal concentrations of CRP and ALKP and cervix length can be used as appropriate biomarker for predicting preterm labor and response to tocolytic therapy in pregnant women. PMID:26962519

Infant sex, obstetric risk factors, and 2-year neurodevelopmental outcome among preterm infants.

PubMed

Spinillo, Arsenio; Montanari, Laura; Gardella, Barbara; Roccio, Marianna; Stronati, Mauro; Fazzi, Elisa

2009-07-01

To evaluate the effect of the interaction between fetal sex and obstetric variables on the risk of neurodevelopmental impairment among preterm infants. A cohort study of 394 male and 360 female surviving infants born at 24 to 33 completed weeks of gestational age. Neurological examination and cognitive assessment of the infants (Bayley Scales of Infant Development) were performed at 2 years corrected age. Mean gestational age was 30.4 weeks (SD 2.4). Rates of mild and moderate-to-severe neurodevelopmental impairment were 14.6% (110/754) and 7% (53/754) respectively. In logistic analysis, male sex was associated with an increased risk of neurodevelopmental impairment (odds ratio 1.8, 95% confidence interval 1.21-2.68) compared with females. The excess risk of neurodevelopmental impairment associated with male sex was higher among preeclamptic than normotensive pregnancies (p for interaction=0.004), among infants who were either small for gestational age or delivered to a mother with preeclampsia (p for interaction=0.001) and in iatrogenic as opposed to spontaneous preterm birth or preterm premature rupture of membranes (p for interaction=0.035). The excess risk of neurodevelopmental impairment associated with male sex among preterm infants is modulated by obstetric risk factors.

Prediction of preterm deliveries from EHG signals using machine learning.

PubMed

Fergus, Paul; Cheung, Pauline; Hussain, Abir; Al-Jumeily, Dhiya; Dobbins, Chelsea; Iram, Shamaila

2013-01-01

There has been some improvement in the treatment of preterm infants, which has helped to increase their chance of survival. However, the rate of premature births is still globally increasing. As a result, this group of infants are most at risk of developing severe medical conditions that can affect the respiratory, gastrointestinal, immune, central nervous, auditory and visual systems. In extreme cases, this can also lead to long-term conditions, such as cerebral palsy, mental retardation, learning difficulties, including poor health and growth. In the US alone, the societal and economic cost of preterm births, in 2005, was estimated to be $26.2 billion, per annum. In the UK, this value was close to £2.95 billion, in 2009. Many believe that a better understanding of why preterm births occur, and a strategic focus on prevention, will help to improve the health of children and reduce healthcare costs. At present, most methods of preterm birth prediction are subjective. However, a strong body of evidence suggests the analysis of uterine electrical signals (Electrohysterography), could provide a viable way of diagnosing true labour and predict preterm deliveries. Most Electrohysterography studies focus on true labour detection during the final seven days, before labour. The challenge is to utilise Electrohysterography techniques to predict preterm delivery earlier in the pregnancy. This paper explores this idea further and presents a supervised machine learning approach that classifies term and preterm records, using an open source dataset containing 300 records (38 preterm and 262 term). The synthetic minority oversampling technique is used to oversample the minority preterm class, and cross validation techniques, are used to evaluate the dataset against other similar studies. Our approach shows an improvement on existing studies with 96% sensitivity, 90% specificity, and a 95% area under the curve value with 8% global error using the polynomial classifier.

All Our Babies Cohort Study: recruitment of a cohort to predict women at risk of preterm birth through the examination of gene expression profiles and the environment

PubMed Central

2010-01-01

Background Preterm birth is the leading cause of perinatal morbidity and mortality. Risk factors for preterm birth include a personal or familial history of preterm delivery, ethnicity and low socioeconomic status yet the ability to predict preterm delivery before the onset of preterm labour evades clinical practice. Evidence suggests that genetics may play a role in the multi-factorial pathophysiology of preterm birth. The All Our Babies Study is an on-going community based longitudinal cohort study that was designed to establish a cohort of women to investigate how a women's genetics and environment contribute to the pathophysiology of preterm birth. Specifically this study will examine the predictive potential of maternal leukocytes for predicting preterm birth in non-labouring women through the examination of gene expression profiles and gene-environment interactions. Methods/Design Collaborations have been established between clinical lab services, the provincial health service provider and researchers to create an interdisciplinary study design for the All Our Babies Study. A birth cohort of 2000 women has been established to address this research question. Women provide informed consent for blood sample collection, linkage to medical records and complete questionnaires related to prenatal health, service utilization, social support, emotional and physical health, demographics, and breast and infant feeding. Maternal blood samples are collected in PAXgene™ RNA tubes between 18-22 and 28-32 weeks gestation for transcriptomic analyses. Discussion The All Our Babies Study is an example of how investment in clinical-academic-community partnerships can improve research efficiency and accelerate the recruitment and data collection phases of a study. Establishing these partnerships during the study design phase and maintaining these relationships through the duration of the study provides the unique opportunity to investigate the multi-causal factors of preterm birth. The overall All Our Babies Study results can potentially lead to healthier pregnancies, mothers, infants and children. PMID:21192811

Stress in parents of children born very preterm is predicted by child externalising behaviour and parent coping at age 7 years.

PubMed

Linden, Mark A; Cepeda, Ivan L; Synnes, Anne; Grunau, Ruth E

2015-06-01

To examine factors which predict parenting stress in a longitudinal cohort of children born very preterm, and seen at age 7 years. We recruited 100 very preterm (≤32 weeks gestational age) child-parent dyads and a control group of 50 term-born dyads born between 2001 and 2004 with follow-up at 7 years. Parents completed the Parenting Stress Index, Ways of Coping Questionnaire, Child Behavior Check List, Beck Depression Inventory and the State Trait Anxiety Inventory questionnaires. Child IQ was assessed using the Wechsler Intelligence Scale-IV. After controlling for maternal education, parents of preterm children (95% CI 111.1 to 121.4) scored higher (p=0.027) on the Parenting Stress Index than term-born controls (95% CI 97.8 to 113.2). Regression analyses showed that child externalising behaviour, sex and parent escape/avoidance coping style, predicted higher parenting stress in the preterm group. Parents of preterm girls expressed higher levels of stress than those of boys. Maladaptive coping strategies contribute to greater stress in parents of very preterm children. Our findings suggest that these parents need support for many years after birth of a very preterm infant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

GLYCOGEN PHOSPHORYLASE ISOENZYME BB PLASMA CONCENTRATION IS ELEVATED IN PREGNANCY AND PRETERM PREECLAMPSIA

PubMed Central

Lee, JoonHo; Romero, Roberto; Dong, Zhong; Lee, Deug-Chan; Dong, Yi; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai

2012-01-01

Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from six groups (n=396) were studied: non-pregnant women and pregnant women with normal term delivery, term preeclampsia, term small-for-gestational-age neonates, preterm preeclampsia, and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term cases were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in non-pregnant women (38.7 ng/ml versus 9.2 ng/mL, P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Preterm but not term preeclampsia cases had higher median plasma GPBB concentration than gestational-age-matched normal pregnancy cases (72.6 ng/ml versus 26.0 ng/ml, P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiologic elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin. PMID:22215716

Predicting high-risk preterm birth using artificial neural networks.

PubMed

Catley, Christina; Frize, Monique; Walker, C Robin; Petriu, Dorina C

2006-07-01

A reengineered approach to the early prediction of preterm birth is presented as a complimentary technique to the current procedure of using costly and invasive clinical testing on high-risk maternal populations. Artificial neural networks (ANNs) are employed as a screening tool for preterm birth on a heterogeneous maternal population; risk estimations use obstetrical variables available to physicians before 23 weeks gestation. The objective was to assess if ANNs have a potential use in obstetrical outcome estimations in low-risk maternal populations. The back-propagation feedforward ANN was trained and tested on cases with eight input variables describing the patient's obstetrical history; the output variables were: 1) preterm birth; 2) high-risk preterm birth; and 3) a refined high-risk preterm birth outcome excluding all cases where resuscitation was delivered in the form of free flow oxygen. Artificial training sets were created to increase the distribution of the underrepresented class to 20%. Training on the refined high-risk preterm birth model increased the network's sensitivity to 54.8%, compared to just over 20% for the nonartificially distributed preterm birth model.

Use of Non-invasive Uterine Electromyography in the Diagnosis of Preterm Labour

PubMed Central

Lucovnik, M.; Novak-Antolic, Z.; Garfield, R.E.

2012-01-01

Predictive values of methods currently used in the clinics to diagnose preterm labour are low. This leads to missed opportunities to improve neonatal outcomes and, on the other hand, to unnecessary hospitalizations and treatments. In addition, research of new and potentially more effective preterm labour treatments is hindered by the inability to include only patients in true preterm labour into studies. Uterine electromyography (EMG) detects changes in cell excitability and coupling required for labour and has higher predictive values for preterm delivery than currently available methods. This methodology could also provide a better means to evaluate various therapeutic interventions for preterm labour. Our manuscript presents a review of uterine EMG studies examining the potential clinical value that this technology possesses over what is available to physicians currently. We also evaluated the impact that uterine EMG could have on investigation of preterm labour treatments by calculating sample sizes for studies using EMG vs. current methods to enrol women. Besides helping clinicians to make safer and more cost-effective decisions when managing patients with preterm contractions, implementation of uterine EMG for diagnosis of preterm labour would also greatly reduce sample sizes required for studies of treatments. PMID:24753891

Placental hormone profiles as predictors of preterm birth in twin pregnancy: A prospective cohort study

PubMed Central

Lim, Hui; Powell, Sioned; Mcnamara, Helen C.; Howie, A. Forbes; Doust, Ann; Bowman, Maria E.; Smith, Roger; Norman, Jane E.

2017-01-01

Objective The objective of the study was to analyse placental hormone profiles in twin pregnancies to determine if they could be used to predict preterm birth. Study design Progesterone, estradiol, estriol and corticotropin-releasing hormone were measured using competitive immunoassay and radioimmunoassay in serum and saliva samples of 98 women with twin pregnancies,at 3 or more gestational timepoints. Hormone profiles throughout gestation were compared between very preterm (<34 weeks; n = 8), preterm (<37 weeks; n = 40) and term (37+ weeks; n = 50) deliveries. Results No significant differences were found between preterm and term deliveries in either absolute hormone concentrations or ratios. Estimated hormone concentrations and ratios at 26 weeks did not appear to predict preterm delivery. Salivary and serum hormone concentrations were generally poorly correlated. Conclusion Our results suggest that serial progesterone, estradiol, estriol and corticotropin-releasing hormone measurements in saliva and serum are not robust biomarkers for preterm birth in twin pregnancies. PMID:28278220

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

PubMed

Esplin, M Sean; Manuck, Tracy A; Varner, Michael W; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M; Ilekis, John

2015-09-01

We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ(2) analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P = .0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB. Copyright © 2015 Elsevier Inc. All rights reserved.

Affordability of programmes to prevent spontaneous preterm birth in Austria: a budget impact analysis.

PubMed

Zechmeister-Koss, Ingrid; Piso, Brigitte

2014-02-01

Preterm birth is a rising health problem in Europe generally, and in Austria specifically. Decision makers require objective information on the effects and costs of measures to prevent preterm birth. We undertook a budget impact analysis from a public payer perspective and for a 1-year and 5-year time horizon for five prevention approaches to reduce preterm birth. These were cervix screening + progesterone application, progesterone injection, smoking cessation, fish oil supplementation and infection screening. We analysed affordability in terms of programme costs and potential cost savings. Programme costs range from below €50 000 (cervix screening in high-risk pregnancy) to €500 000 (universal infection screening). The lowest health effects have been shown for smoking cessation programmes (-10 preterm births per year), whereas infection screening demonstrated the largest effect (-230 preterm births per year). In the base-case analysis, all programmes are potentially cost saving (-€500 000 to -€13 million per year). In the sensitivity analyses, preterm birth costs, target group size and (partly) unit costs of programme components have an influence on potential cost savings. However, except for two programmes, the results are robust concerning an overall economic net benefit of the programmes analysed compared with no programme. The study is mainly limited by the quality of some cost data and choice of the reference scenario. When considering potential cost savings, the five prevention programmes analysed seem affordable, with cervix screening and infection screening likely being the most promising in Austria.

T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants.

PubMed

Chen, L-W; Wang, S-T; Huang, C-C; Tu, Y-F; Tsai, Y-S

2018-01-18

T2-relaxometry brain MR imaging enables objective measurement of brain maturation based on the water-macromolecule ratio in white matter, but the outcome correlation is not established in preterm infants. Our study aimed to predict neurodevelopment with T2-relaxation values of brain MR imaging among preterm infants. From January 1, 2012, to May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation values were measured over the periventricular white matter, including sections through the frontal horns, midbody of the lateral ventricles, and centrum semiovale. Periventricular T2 relaxometry in relation to corrected age was analyzed with restricted cubic spline regression. Prediction of cerebral palsy was examined with the receiver operating characteristic curve. Thirty-eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had neurodevelopmental abnormalities, including 8 (21%) with developmental delay without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2-relaxation values in relation to age were curvilinear in preterm infants with normal development, linear in those with developmental delay without cerebral palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1 month corrected age, cerebral palsy could be predicted with T2 relaxometry of the periventricular white matter on sections through the midbody of the lateral ventricles (area under the receiver operating characteristic curve = 0.738; cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity). T2-relaxometry brain MR imaging could provide prognostic prediction of neurodevelopmental outcomes in premature infants. Age-dependent and area-selective interpretation in preterm brains should be emphasized. © 2018 by American Journal of Neuroradiology.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

PubMed Central

Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

2017-01-01

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

Risk factor for preterm labor in Haji Adam Malik General Hospital, Pirngadi General hospital and satellite hospitals in Medan from January 2014 to December 2016

NASA Astrophysics Data System (ADS)

Sukatendel, K.; Hasibuan, C. L.; Pasaribu, H. P.; Sihite, H.; Ardyansah, E.; Situmorang, M. F.

2018-03-01

In 2010, Indonesia was ranked fifth in the world for the number of premature birth. Prematurity is a multifactorial problem. Preterm Labor (PTL) can occur spontaneously without a clear cause. Preventing PTL, its associated risk factors must be recognized first. To analyze risk factors associated with the incidence of PTL. It is a cross sectional study using secondary data obtained from medical records in Haji Adam Malik general hospital, Pirngadi general hospital and satellite hospitals in Medan from January 2014 to December 2016. Data were analyzed using chi-square method and logistic regression test. 148 cases for each group of preterm labor and obtained term laborin this study. Using the logistic regression test, three factors with astrong association to the incidence of identifiedpreterm labor. Antenatal Care frequency (OR 2,326; CI 95%), leucorrhea (OR 6,291; 95%), and premature rupture of membrane (OR 9,755; CI 95%). In conclusion, antenatal care frequency, leucorrhea, and history of premature rupture of themembrane may increase the incidence of Preterm Labor (PTL).

Twins: prevalence, problems, and preterm births.

PubMed

Chauhan, Suneet P; Scardo, James A; Hayes, Edward; Abuhamad, Alfred Z; Berghella, Vincenzo

2010-10-01

The rate of twin pregnancies in the United States has stabilized at 32 per 1000 births in 2006. Aside from determining chorionicity, first-trimester screening and second-trimester ultrasound scanning should ascertain whether there are structural or chromosomal abnormalities. Compared with singleton births, genetic amniocentesis-related loss at <24 weeks of gestation for twin births is higher (0.9% vs 2.9%, respectively). Selective termination for an anomalous fetus is an option, although the pregnancy loss rate is 7% at experienced centers. For singleton and twin births for African American and white women, approximately 50% of preterm births are indicated; approximately one-third of these births are spontaneous, and 10% of the births occur after preterm premature rupture of membranes. From 1989-2000, the rate of preterm twin births increased, for African American and white women alike, although the perinatal mortality rate has actually decreased. As with singleton births, tocolytics should be used judiciously and only for a limited time (<48 hours) in twin births. Administration of antenatal corticosteroids is an evidence-based recommendation. Copyright © 2010 Mosby, Inc. All rights reserved.

Prediction of Cognitive Abilities at the Age of 5 Years Using Developmental Follow-Up Assessments at the Age of 2 and 3 Years in Very Preterm Children

ERIC Educational Resources Information Center

Potharst, Eva S.; Houtzager, Bregje A.; van Sonderen, Loekie; Tamminga, Pieter; Kok, Joke H.; Last, Bob F.; van Wassenaer, Aleid G.

2012-01-01

Aim: This study investigated prediction of separate cognitive abilities at the age of 5 years by cognitive development at the ages of both 2 and 3 years, and the agreement between these measurements, in very preterm children. Methods: Preterm children (n=102; 44 males; 58 females) with a gestational age less than 30 weeks and/or birthweight less…

Preterm or not--an evaluation of estimates of gestational age in a cohort of women from Rural Papua New Guinea.

PubMed

Karl, Stephan; Li Wai Suen, Connie S N; Unger, Holger W; Ome-Kaius, Maria; Mola, Glen; White, Lisa; Wangnapi, Regina A; Rogerson, Stephen J; Mueller, Ivo

2015-01-01

Knowledge of accurate gestational age is required for comprehensive pregnancy care and is an essential component of research evaluating causes of preterm birth. In industrialised countries gestational age is determined with the help of fetal biometry in early pregnancy. Lack of ultrasound and late presentation to antenatal clinic limits this practice in low-resource settings. Instead, clinical estimators of gestational age are used, but their accuracy remains a matter of debate. In a cohort of 688 singleton pregnancies from rural Papua New Guinea, delivery gestational age was calculated from Ballard score, last menstrual period, symphysis-pubis fundal height at first visit and quickening as well as mid- and late pregnancy fetal biometry. Published models using sequential fundal height measurements and corrected last menstrual period to estimate gestational age were also tested. Novel linear models that combined clinical measurements for gestational age estimation were developed. Predictions were compared with the reference early pregnancy ultrasound (<25 gestational weeks) using correlation, regression and Bland-Altman analyses and ranked for their capability to predict preterm birth using the harmonic mean of recall and precision (F-measure). Average bias between reference ultrasound and clinical methods ranged from 0-11 days (95% confidence levels: 14-42 days). Preterm birth was best predicted by mid-pregnancy ultrasound (F-measure: 0.72), and neuromuscular Ballard score provided the least reliable preterm birth prediction (F-measure: 0.17). The best clinical methods to predict gestational age and preterm birth were last menstrual period and fundal height (F-measures 0.35). A linear model combining both measures improved prediction of preterm birth (F-measure: 0.58). Estimation of gestational age without ultrasound is prone to significant error. In the absence of ultrasound facilities, last menstrual period and fundal height are among the more reliable clinical measures. This study underlines the importance of strengthening ultrasound facilities and developing novel ways to estimate gestational age.

Incidence and predictors of obstetric and fetal complications in women with structural heart disease.

PubMed

van Hagen, Iris M; Roos-Hesselink, Jolien W; Donvito, Valentina; Liptai, Csilla; Morissens, Marielle; Murphy, Daniel J; Galian, Laura; Bazargani, Nooshin Mohd; Cornette, Jérôme; Hall, Roger; Johnson, Mark R

2017-10-01

Women with cardiac disease becoming pregnant have an increased risk of obstetric and fetal events. The aim of this study was to study the incidence of events, to validate the modified WHO (mWHO) risk classification and to search for event-specific predictors. The Registry Of Pregnancy And Cardiac disease is a worldwide ongoing prospective registry that has enrolled 2742 pregnancies in women with known cardiac disease (mainly congenital and valvular disease) before pregnancy, from January 2008 up to April 2014. Mean age was 28.2±5.5 years, 45% were nulliparous and 33.3% came from emerging countries. Obstetric events occurred in 231 pregnancies (8.4%). Fetal events occurred in 651 pregnancies (23.7%). The mWHO classification performed poorly in predicting obstetric (c-statistic=0.601) and fetal events (c-statistic=0.561). In multivariable analysis, aortic valve disease was associated with pre-eclampsia (OR=2.6, 95%CI=1.3 to 5.5). Congenital heart disease (CHD) was associated with spontaneous preterm birth (OR=1.8, 95%CI=1.2 to 2.7). Complex CHD was associated with small-for-gestational-age neonates (OR=2.3, 95%CI=1.5 to 3.5). Multiple gestation was the strongest predictor of fetal events: fetal/neonatal death (OR=6.4, 95%CI=2.5 to 16), spontaneous preterm birth (OR=5.3, 95%CI=2.5 to 11) and small-for-gestational age (OR=5.0, 95%CI=2.5 to 9.8). The mWHO classification is not suitable for prediction of obstetric and fetal events in women with cardiac disease. Maternal complex CHD was independently associated with fetal growth restriction and aortic valve disease with pre-eclampsia, potentially offering an insight into the pathophysiology of these pregnancy complications. The increased rates of adverse obstetric and fetal outcomes in women with pre-existing heart disease should be highlighted during counselling. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Variability in urinary phthalate metabolite levels across pregnancy and sensitive windows of exposure for the risk of preterm birth

PubMed Central

Ferguson, Kelly K.; McElrath, Thomas F.; Ko, Yi-An; Mukherjee, Bhramar; Meeker, John D.

2014-01-01

Background Preterm birth is a significant public health problem, affecting over 1 in 10 live births and contributing largely to infant mortality and morbidity. Everyday exposure to environmental chemicals such as phthalates could contribute, and may be modifiable. In the present study we examine variability in phthalate exposure across gestation and identify windows of susceptibility for the relationship with preterm birth. Methods Women were recruited early in pregnancy as part of a prospective, longitudinal birth cohort at the Brigham and Women’s Hospital in Boston, Massachusetts. Urine samples were collected at up to 4 time points during gestation for phthalate measurement, and birth outcomes were recorded at delivery. From this population we selected all 130 cases of preterm birth, defined as delivery before 37 weeks completed gestation, as well as 352 random controls. Results Urinary phthalate metabolite levels were moderately variable over pregnancy, but levels measured at multiple time points were associated with increased odds of preterm birth. Adjusted odds ratios (aOR) for spontaneous preterm birth were strongest in association with phthalate metabolite concentrations measured at the beginning of the third trimester (aOR for summed di-2-ethylhexyl phthalate metabolites [∑DEHP]=1.33, 95% confidence interval [CI]=1.02, 1.73). Odds ratios for placental preterm birth, defined as delivery with presentation of preeclampsia or intrauterine growth restriction, were slightly elevated in the first trimester for DEHP metabolites (aOR for ∑DEHP=1.33, 95% CI=0.99, 1.78). Conclusions Pregnant women with exposure to phthalates both early and late in pregnancy are at increased risk of delivering preterm, but mechanisms may differ based on etiology. PMID:24934852

The impact of postpartum cervical tear on the occurrence of preterm birth in subsequent pregnancy.

PubMed

Zafran, Noah; Gerszman, Eden; Garmi, Gali; Zuaretz-Easton, Sivan; Salim, Raed

2017-08-01

To examine the occurrence of subsequent preterm birth (PTB) among women who experienced a cervical tear during prior delivery. A retrospective study conducted at a single teaching hospital on data from January 1994 to March 2014. The study group included all women who had a cervical tear detected at uterine and cervical examination, performed due to early postpartum hemorrhage. The control group consisted of women who delivered vaginally, experienced an early postpartum hemorrhage, and had an intact cervix at uterine and cervical examination. The control group was matched for maternal age and ethnicity at a ratio of 1:2. Women who had a cervical tear but then did not have a subsequent delivery, or had multiple fetal gestations or cervical cerclage at subsequent pregnancies were excluded. Primary outcome was spontaneous PTB rate (<37 weeks) in the subsequent pregnancy. Secondary outcomes included any PTBs in other subsequent pregnancies. Overall, 389 women were included. Of all cases of cervical tear, 129 were identified eligible and included in the final analysis. The control group included 260 women with an intact cervix. No significant differences were found between the study and control groups in the incidence of spontaneous PTB in the immediate subsequent pregnancy [1.6% (2/129) vs. 3.8% (10/260), respectively, p = 0.35]. The incidence of any spontaneous PTBs in all subsequent pregnancies did not differ also [4.7% (6/129) vs. 7.3% (19/260), respectively, p = 0.31]. Cervical tear detected after delivery does not increase the risk of spontaneous PTB in subsequent pregnancies.

Pregnancy outcomes in female hairdressers.

PubMed

Ronda, Elena; Moen, Bente E; García, Ana M; Sánchez-Paya, José; Baste, Valborg

2010-12-01

The hairdressing occupation may entail exposure to a wide range of chemical products, psychosocial and physical stress. All these factors may affect the health of a pregnant hairdresser and her offspring. Our aim was to analyse whether employment in this profession is associated with adverse reproductive effects. Female hairdressers working in the 248 hairdressing salons in Alicante (Spain), who became pregnant for the first time after 1990 were included (n = 94). The incidence of spontaneous abortions, number of children born and their birth weight and preterm delivery among hairdressers was compared with a control group of shop assistants and office workers (n = 138). Information was collected through personal interviews at their work place. A structured questionnaire was used gathering information concerning exposure variables including the use of chemical products, ventilation at the salons, work-related stress and hours of standing work. In addition, socio-demographic factors and smoking information were obtained. Crude and adjusted relative risks (RR) and 95% confidence intervals (95%CI) were calculated using logbinomial regression. Hairdressers showed a non-significant increased risk of spontaneous abortions (RR = 1.6, 95%CI 0.9-2.7). There were no differences in preterm delivery and birth weight of the children born of mothers in the two groups. Among hairdressers, the RR of spontaneous abortion among those with high perceived work-related stress was 2.4 (95%CI: 0.2-28.3) relative to those with low or normal perceived stress. A slightly increased risk of spontaneous abortion among hairdressers was found, mainly associated with perceived work-related stress. Observed results deserve further research.

Pregnancy outcome of threatened abortion with demonstrable fetal cardiac activity: a cohort study.

PubMed

Tongsong, T; Srisomboon, J; Wanapirak, C; Sirichotiyakul, S; Pongsatha, S; Polsrisuthikul, T

1995-08-01

Pregnancy with visible fetal heart beat complicated by first trimester threatened abortion had significant increased risk of subsequent spontaneous abortion compared with normal pregnancy. To compare pregnancy outcomes in cases complicated by first trimester threatened abortion with those that were not. Prospective cohort study of 255 cases of first trimester threatened abortions but with visible heart beat and 265 other normal pregnancies. Spontaneous abortion rates of 5.5% (with relative abortal risk of 2.91) was found for study group, compared to 1.88% for controls (p < 0.05). Preterm delivery was also higher, but was not statistically significant. First trimester bleeding with visible fetal heart beat appears to associate significantly with higher subsequent spontaneous abortion rate than those without.

The effects of maternal depression, anxiety, and perceived stress during pregnancy on preterm birth: A systematic review.

PubMed

Staneva, Aleksandra; Bogossian, Fiona; Pritchard, Margo; Wittkowski, Anja

2015-09-01

Experiencing psychological distress such as depression, anxiety, and/or perceived stress during pregnancy may increase the risk for adverse birth outcomes, including preterm birth. Clarifying the association between exposure and outcome may improve the understanding of risk factors for prematurity and guide future clinical and research practices. The aims of the present review were to outline the evidence on the risk of preterm associated with antenatal depression, anxiety, and stress. Four electronic database searches were conducted to identify quantitative population-based, multi-centre, cohort studies and randomised-controlled trial studies focusing on the association between antenatal depression, anxiety, and stress, and preterm birth published in English between 1980 and 2013. Of 1469 electronically retrieved articles, 39 peer-reviewed studies met the final selection criteria and were included in this review following the PRISMA and MOOSE review guidelines. Information was extracted on study characteristics; depression, anxiety and perceived stress were examined as separate and combined exposures. There is strong evidence that antenatal distress during the pregnancy increases the likelihood of preterm birth. Complex paths of significant interactions between depression, anxiety and stress, risk factors and preterm birth were indicated in both direct and indirect ways. The effects of pregnancy distress were associated with spontaneous but not with medically indicated preterm birth. Health practitioners engaged in providing perinatal care to women, such as obstetricians, midwives, nurses, and mental health specialists need to provide appropriate support to women experiencing psychological distress in order to improve outcomes for both mothers and infants. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Preterm birth--prediction, prevention, and consequences: an unmet challenge to perinatal medicine, science, and society: the declaration of Dubrovnik.

PubMed

Kurjak, Asim

2010-11-01

Preterm birth is the defining challenge to modern perinatal medicine. It is now clear that preterm birth is not caused by one pathologic process but many, some not identified. Prevention of preterm birth is possible if perinatal medicine, science, and society give the necessary priority to this most urgent problem of maternal, fetal, and neonatal patients.

Transabdominal amnioinfusion in preterm premature rupture of membranes.

PubMed

Singla, Anshuja; Yadav, Poonam; Vaid, Neelam B; Suneja, Amita; Faridi, Mohammad M A

2010-03-01

To evaluate the effect of transabdominal amnioinfusion on prolongation of pregnancy, and maternal and neonatal outcomes in preterm premature rupture of membranes (pPROM). We conducted a prospective randomized controlled study of women with pPROM during singleton live pregnancy-between 26 and 33+6weeks-whose amniotic fluid index (AFI) was less than the 5th percentile. The study group underwent transabdominal amnioinfusion at admission and then weekly if their AFI fell below the 5th percentile again. The control group received expectant management. The difference in the mean interval from pPROM to delivery between the groups was not statistically significant. Neonatal and maternal outcomes were significantly improved in the study group compared with the control group (fetal distress [10% vs 37%]; early neonatal sepsis [17% vs 63%]; neonatal mortality [17% vs 63%]; spontaneous delivery [83% vs 53%]; and postpartum sepsis [7% vs 33%]). Transabdominal amnioinfusion reduced fetal distress, early neonatal sepsis, and neonatal mortality. In the study group, more participants delivered spontaneously and there were fewer cases of postpartum sepsis, although the pPROM-delivery interval was not increased.

Complement activation fragment Bb in early pregnancy and spontaneous preterm birth.

PubMed

Lynch, Anne M; Gibbs, Ronald S; Murphy, James R; Byers, Tim; Neville, Margaret C; Giclas, Patricia C; Salmon, Jane E; Van Hecke, Trisha M; Holers, V Michael

2008-10-01

The objective of this study was to determine whether an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks' gestation or SPTB between 34 and 37 weeks' gestation (late SPTB). This was a prospective study of 784 women enrolled at less than 20 weeks' gestation. Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks' gestation and 25 (3.2%) a SPTB between 34 and 37 weeks' gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks' gestation as compared with women who had levels of Bb in the lower 3 quartiles (95% confidence interval [CI] 1.5-14, P = .003). There was no association between Bb and late SPTB (relative risk 0.8, 95% CI 0.3-2). A significant relationship was found between an elevated Bb in early pregnancy and SPTB less than 34 weeks' gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition.

COMPLEMENT ACTIVATION FRAGMENT Bb IN EARLY PREGNANCY AND SPONTANEOUS PRETERM BIRTH

PubMed Central

LYNCH, ANNE M.; GIBBS, RONALD S.; MURPHY, JAMES R.; BYERS, TIM; NEVILLE, MARGARET C.; GICLAS, PATRICIA C.; SALMON, JANE E.; VAN HECKE, TRISHA M; MICHAEL HOLERS, V.

2008-01-01

Objective To determine if an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks gestation or SPTB between 34 and 37 weeks gestation (late SPTB). Study Design Prospective study of 784 women enrolled at < 20 weeks gestation. Results Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks gestation and 25 (3.2%) a SPTB between 34 and 37 weeks gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks gestation as compared with women who had levels of Bb in the lower three quartiles (95% CI 1.5 to 14, P = 0.003). There was no association between Bb and late SPTB (RR= 0.8, 95% CI = 0.3 to 2). Conclusions A significant relationship was found between an elevated Bb in early pregnancy and SPTB < 34 weeks gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition. PMID:18928972

A translational approach to studying preterm labour

PubMed Central

Tribe, Rachel Marie

2007-01-01

Preterm labour continues to be a major contributor to neonatal and infant morbidity. Recent data from the USA indicate that the number of preterm deliveries (including those associated with preterm labour) has risen in the last 20 years by 30%. This increase is despite considerable efforts to introduce new therapies for the prevention and treatment of preterm labour and highlights the need to assess research in this area from a fresh perspective. In this paper we discuss i) the limitations of our knowledge concerning prediction, prevention and treatment of preterm labour and ii) future multidisciplinary strategies for improving our approach. PMID:17570168

Early communicative behaviors and their relationship to motor skills in extremely preterm infants.

PubMed

Benassi, Erika; Savini, Silvia; Iverson, Jana M; Guarini, Annalisa; Caselli, Maria Cristina; Alessandroni, Rosina; Faldella, Giacomo; Sansavini, Alessandra

2016-01-01

Despite the predictive value of early spontaneous communication for identifying risk for later language concerns, very little research has focused on these behaviors in extremely low-gestational-age infants (ELGA<28 weeks) or on their relationship with motor development. In this study, communicative behaviors (gestures, vocal utterances and their coordination) were evaluated during mother-infant play interactions in 20 ELGA infants and 20 full-term infants (FT) at 12 months (corrected age for ELGA infants). Relationships between gestures and motor skills, evaluated using the Bayley-III Scales were also examined. ELGA infants, compared with FT infants, showed less advanced communicative, motor, and cognitive skills. Giving and representational gestures were produced at a lower rate by ELGA infants. In addition, pointing gestures and words were produced by a lower percentage of ELGA infants. Significant positive correlations between gestures (pointing and representational gestures) and fine motor skills were found in the ELGA group. We discuss the relevance of examining spontaneous communicative behaviors and motor skills as potential indices of early development that may be useful for clinical assessment and intervention with ELGA infants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Parenting stress and development of late preterm infants at 4 months corrected age.

PubMed

Mughal, Muhammad K; Ginn, Carla S; Magill-Evans, Joyce; Benzies, Karen M

2017-10-01

Parenting stress has been linked to child development issues in early preterm infants, but less is known about its effects on development in infants born late preterm. We examined relationships between parenting stress of 108 mothers and 108 fathers and development of late preterm infants born at 34 0/7 to 36 6/7 weeks gestation. At 4 months corrected age, mothers and fathers completed the Parenting Stress Index (PSI-3); mothers were primary caregivers in almost all families and completed the Ages and Stages Questionnaire (ASQ-2) on child development. Mothers reported significantly more stress than fathers on the PSI-3 Parent Domain. PSI-3 subscale scores from the Child Domain were significant predictors of mother-reported infant development as measured by the ASQ-2 in regression models: Reinforces Parent predicted Gross Motor, Mood predicted Communication, and Acceptability predicted Communication, Fine Motor, Problem Solving, and Personal -Social development scale scores. Experiences of parenting stress differed for mothers and fathers. Further research is required on specific dimensions of parenting stress related to development of late preterm infants. © 2017 Wiley Periodicals, Inc.

Fetal DNA methylation of autism spectrum disorders candidate genes: association with spontaneous preterm birth.

PubMed

Behnia, Fara; Parets, Sasha E; Kechichian, Talar; Yin, Huaizhi; Dutta, Eryn H; Saade, George R; Smith, Alicia K; Menon, Ramkumar

2015-04-01

Autism spectrum disorder (ASD) is associated with preterm birth (PTB), although the reason underlying this relationship is still unclear. Our objective was to examine DNA methylation patterns of 4 ASD candidate genes in human fetal membranes from spontaneous PTB and uncomplicated term birth. A literature search for genes that have been implicated in ASD yielded 14 candidate genes (OXTR, SHANK3, BCL2, RORA, EN2, RELN, MECP2, AUTS2, NLGN3, NRXN1, SLC6A4, UBE3A, GABA, AFF2) that were epigenetically modified in relation to ASD. DNA methylation in fetal leukocyte DNA in 4 of these genes (OXTR, SHANK3, BCL2, and RORA) was associated with PTB in a previous study. This study evaluated DNA methylation, transcription (reverse transcription polymerase chain reaction), and translation patterns (immunostaining and Western blot) in fetal membrane from term labor (n = 14), term not in labor (TNIL; n = 29), and spontaneous preterm birth (PTB; n = 27). Statistical analysis was performed with analysis of variance; a probability value of < .05 was significant. Higher methylation of the OXTR promoter was seen in fetal membranes from PTB, compared with term labor or TNIL. No other gene showed any methylation differences among groups. Expression of OXTR was not different among groups, but the 70 kDa OXTR protein was seen only in PTB, and immunostaining was more intense in PTB amniocytes than term labor or TNIL. Among the 4 genes that were studied, fetal membranes from PTB demonstrate differences in OXTR methylation and regulation and expression, which suggest that epigenetic alteration of this gene in fetal membrane may likely be indicating an in utero programing of this gene and serve as a surrogate in a subset of PTB. The usefulness of OXTR hypermethylation as a surrogate for a link to ASD should be further evaluated in longitudinal and in vitro studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Oxidative stress damage as a detrimental factor in preterm birth pathology.

PubMed

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal-fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.

Oxidative Stress Damage as a Detrimental Factor in Preterm Birth Pathology

PubMed Central

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal–fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways. PMID:25429290

Maternal Characteristics for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes (GOS) Study.

PubMed

Boutin, Amélie; Gasse, Cédric; Demers, Suzanne; Giguère, Yves; Tétu, Amélie; Bujold, Emmanuel

2018-05-01

Low-dose aspirin started in early pregnancy significantly reduces the risk of preeclampsia (PE) in high-risk women, especially preterm PE. This study aimed to evaluate the influence of maternal characteristics on the risk of PE in nulliparous women. The Great Obstetrical Syndromes (GOS) study recruited nulliparous women with singleton pregnancies at 11 to 13 weeks. The following maternal characteristics were collected: age, BMI, ethnicity, chronic diseases, smoking, and assisted reproductive technologies. Relative weight analyses were conducted, and predictive multivariate proportional hazard models were constructed. Receiver operating characteristic curve analyses with their area under the curve (AUC) were used to evaluate the value of each factor for the prediction of PE and preterm PE. The study also evaluated the SOGC guidelines for identification of women at high risk of PE. Of 4739 participants, 232 (4.9%) developed PE, including 30 (0.6%) with preterm PE. In univariate analyses, only BMI was significantly associated with the risk of PE (AUC 0.60; 95% CI 0.55-0.65) and preterm PE (AUC 0.64; 95% CI 054-0.73). Adding other maternal characteristics to BMI had a non-significant and marginal impact on the discriminative ability to the models for PE (AUC 0.62; 95% CI 0.58-0.66) and preterm PE (AUC 0.65; 95% CI 0.56-0.74). At a false-positive rate of 10%, maternal characteristics could have predicted 23% of PE and 19% of preterm PE. The SOGC guidelines were not discriminant for PE (detecting 96% of PE and 93% of preterm PE with a 94% false-positive rate). In nulliparous women, BMI is the most discriminant maternal characteristic for the prediction of PE. Maternal characteristics should not be used alone to identify nulliparous women at high risk of PE. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

[Predictive factors of mortality in extremely preterm infants].

PubMed

Lin, L; Fang, M C; Jiang, H; Zhu, M L; Chen, S Q; Lin, Z L

2018-04-02

Objective: To investigate the predictive factors of mortality in extremely preterm infants. Methods: The retrospective case-control study was accomplished in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. A total of 268 extremely preterm infants seen from January 1, 1999 to December 31, 2015 were divided into survival group (192 cases) and death group (76 cases). The potential predictive factors of mortality were identified by univariate analysis, and then analyzed by multivariate unconditional Logistic regression analysis. The mortality and predictive factors were also compared between two time periods, which were January 1, 1999 to December 31, 2007 (65 cases) and January 1, 2008 to December 31, 2015 (203 cases). Results: The median gestational age (GA) of extremely preterm infants was 27 weeks (23 +3 -27 +6 weeks). The mortality was higher in infants with GA of 25-<26 weeks ( OR= 2.659, 95% CI: 1.211-5.840) and<25 weeks ( OR= 10.029, 95% CI: 3.266-30.792) compared to that in infants with GA> 26 weeks. From January 1, 2008 to December 31, 2015, the number of extremely preterm infants was increased significantly compared to the previous 9 years, while the mortality decreased significantly ( OR= 0.490, 95% CI: 0.272-0.884). Multivariate unconditional Logistic regression analysis showed that GA below 25 weeks ( OR= 6.033, 95% CI: 1.393-26.133), lower birth weight ( OR= 0.997, 95% CI: 0.995-1.000), stage Ⅲ necrotizing enterocolitis (NEC) ( OR= 15.907, 95% CI: 3.613-70.033), grade Ⅰ and Ⅱ intraventricular hemorrhage (IVH) ( OR= 0.260, 95% CI: 0.117-0.575) and dependence on invasive mechanical ventilation ( OR= 3.630, 95% CI: 1.111-11.867) were predictive factors of mortality in extremely preterm infants. Conclusions: GA below 25 weeks, lower birth weight, stage Ⅲ NEC and dependence on invasive mechanical ventilation are risk factors of mortality in extremely preterm infants. But grade ⅠandⅡ IVH is protective factor.

The effect of prepartum antibiotics on the type of neonatal bacteraemia: insights from the MRC ORACLE trials.

PubMed

Gilbert, R E; Pike, K; Kenyon, S L; Tarnow-Mordi, W; Taylor, D J

2005-06-01

We analysed the type of bacteraemia before discharge from Neonatal Intensive Care Units in babies born to women randomised to the MRC ORACLE Trials. There was no evidence for an effect of oral antibiotics given prior to delivery on bacteraemia due to gram negative or enterococci bacteria, but Group B streptococcal (GBS) bacteraemia was significantly reduced in women with preterm prelabour rupture of the membranes (1.58% to 0.55%, relative risk 0.34; 95% CI: 0.17-0.70). There was no detectable effect in women in spontaneous preterm labour with intact membranes as the risk of GBS bacteraemia in their babies was very small regardless of treatment.

Thyroid storm causing placental abruption: Cardiovascular and management complications for the Intensivist.

PubMed

Lane, Andrew S; Tarvade, Sanjay

2015-08-01

Thyroid storm is a rare and serious complication of pregnancy which can lead to spontaneous abortion, preterm delivery, preeclampsia and cardiac failure. It is also associated with high maternal and foetal mortality if not diagnosed and managed promptly. The diagnosis of thyroid storm in pregnancy can pose significant challenges due to its presentation being similar to other pregnancy-related complications. We present a patient who developed thyroid storm at 29 weeks of pregnancy, which resulted in pre-term delivery, cardiac failure and thyroidectomy. We discuss the treatment of thyroid storm in pregnancy, the decision making involved in proceeding to thyroidectomy or to use radio-iodine, and foetal thyroid status in thyrotoxicosis.

Born Too Soon: The global epidemiology of 15 million preterm births

PubMed Central

2013-01-01

This second paper in the Born Too Soon supplement presents a review of the epidemiology of preterm birth, and its burden globally, including priorities for action to improve the data. Worldwide an estimated 11.1% of all livebirths in 2010 were born preterm (14.9 million babies born before 37 weeks of gestation), with preterm birth rates increasing in most countries with reliable trend data. Direct complications of preterm birth account for one million deaths each year, and preterm birth is a risk factor in over 50% of all neonatal deaths. In addition, preterm birth can result in a range of long-term complications in survivors, with the frequency and severity of adverse outcomes rising with decreasing gestational age and decreasing quality of care. The economic costs of preterm birth are large in terms of immediate neonatal intensive care, ongoing long-term complex health needs, as well as lost economic productivity. Preterm birth is a syndrome with a variety of causes and underlying factors usually divided into spontaneous and provider-initiated preterm births. Consistent recording of all pregnancy outcomes, including stillbirths, and standard application of preterm definitions is important in all settings to advance both the understanding and the monitoring of trends. Context specific innovative solutions to prevent preterm birth and hence reduce preterm birth rates all around the world are urgently needed. Strengthened data systems are required to adequately track trends in preterm birth rates and program effectiveness. These efforts must be coupled with action now to implement improved antenatal, obstetric and newborn care to increase survival and reduce disability amongst those born too soon. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format. PMID:24625129

Maternal Responses and Development of Communication Skills in Extremely Preterm Infants

ERIC Educational Resources Information Center

Benassi, Erika; Guarini, Annalisa; Savini, Silvia; Iverson, Jana Marie; Caselli, Maria Cristina; Alessandroni, Rosina; Faldella, Giacomo; Sansavini, Alessandra

2018-01-01

The present study examined maternal responses to infants' spontaneous communicative behaviors in a sample of 20 extremely-low-gestational-age (ELGA) infants and 20 full-term (FT) infants during 30 minutes of play interaction when infants were 12 months of age. Relations between maternal responses and infants' communication skills at 12 and 24…

Early- or mid-trimester amniocentesis biomarkers for predicting preterm delivery: a meta-analysis.

PubMed

Liu, Yinglin; Liu, Yukun; Zhang, Rui; Zhu, Liqiong; Feng, Ziya

2017-02-01

To determine the value of early- or mid-trimester amniotic fluid levels of interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8), and glucose for predicting preterm delivery. Randomized controlled trials and two-arm prospective, retrospective, cohorts, and case-controlled studies in which patients received early- or mid-trimester amniocentesis for karyotyping, and biomarker testing of the amniotic fluid was performed and delivery data were available were included in the analysis. Outcome measures were the associations of amniotic fluid IL-6, MMP-8, and glucose levels with preterm delivery. Differences in means with 95% confidence intervals (CIs) were calculated. Of 288 articles identified, 14 were included in the meta-analysis with a total of 675 patients who had preterm birth and 2518 patients who had term births. The preterm-delivery group had significantly higher amniotic fluid IL-6 and MMP-8 levels, and a significantly lower glucose level than the term delivery group (IL-6: difference in means = 0.32, 95% CI: 0.22-0.43, p < 0.001; MMP-8: difference in means = 4.47, 95% CI: 0.83-8.11), p = 0.016; glucose: difference in means = -5.22, 95% CI: -8.19 to -2.26, p = 0.001) Conclusion: Early- or mid-trimester amniotic fluid IL-6, MMP-8, and glucose levels are useful for predicting the risk of preterm delivery. KEY MESSAGES Median amniotic fluid ferritin and IL-6 levels, and mean amniotic fluid ALP levels were higher in the preterm group. The preterm-delivery group had significantly higher amniotic fluid IL-6 and MMP-8 levels, and a significantly lower glucose level than the term-delivery group.

Physiological responses of preterm newborn infants submitted to classical music therapy.

PubMed

da Silva, Camila Mendes; Cação, Jessica Marcelle R; Silva, Karin Cristina dos S; Marques, Cassia Fernandes; Merey, Leila Simone F

2013-01-01

To evaluate the physiological effects of music therapy on hospitalized preterm newborns. A noncontrolled clinical trial including 12 newborn infants with gestational age <36 weeks, spontaneously breathing. The preterm infants were submitted to 15-minute sessions of classical music therapy twice a day (morning and afternoon) for three consecutive days. The variables: heart and respiratory rates, oxygen saturation, diastolic and systolic arterial pressures, and body temperature were analyzed before and immediately after each music therapy session. There was a decrease in the heart rate after the second session of music therapy (paired t-test; p=0.002), and an increase at the end of the third session (paired t-test; p=0.005). Respiratory rate decreased during the fourth and fifth sessions (paired t-test; p=0.01 and 0.03, respectively). Regarding oxygen saturation, there was an increase after the fifth session (p=0.008). Comparison of physiological parameters among sessions, for the six studied sessions, showed only that the gain in oxygen saturation during the fifth session was significantly higher than during the sixth one (Tukey's test after variance analysis; p=0.04). Music therapy may modify short-term physiological responses of hospitalized preterm newborn infants.

Preterm birth by vacuum extraction and neonatal outcome: a population-based cohort study.

PubMed

Åberg, Katarina; Norman, Mikael; Ekéus, Cecilia

2014-01-22

Very few studies have investigated the neonatal outcomes after vacuum extraction delivery (VE) in the preterm period and the results of these studies are inconclusive. The objective of this study was to describe the use of VE for preterm delivery in Sweden and to compare rates of neonatal complications after preterm delivery by VE to those found after cesarean section during labor (CS) or unassisted vaginal delivery (VD). Data was obtained from Swedish national registers. In a population-based cohort from 1999 to 2010, all live-born, singleton preterm infants in a non-breech presentation at birth, born after onset of labor (either spontaneously, by induction, or by rupture of membranes) by VD, CS, or VE were included, leaving a study population of 40,764 infants. Logistic regression analyses were used to calculate adjusted odds ratios (AOR), using unassisted vaginal delivery as reference group. VE was used in 5.7% of the preterm deliveries, with lower rates in earlier gestations. Overall, intracranial hemorrhage (ICH) occurred in 1.51%, extracranial hemorrhage (ECH) in 0.64%, and brachial plexus injury in 0.13% of infants. Infants delivered by VE had higher risks for ICH (AOR = 1.84 (95% CI: 1.09-3.12)), ECH (AOR = 4.48 (95% CI: 2.84-7.07)) and brachial plexus injury (AOR = 6.21 (95% CI: 2.22-17.4)), while infants delivered by CS during labor had no increased risk for these complications, as compared to VD. While rates of neonatal complications after VE are generally low, higher odds ratios for intra- and extracranial hemorrhages and brachial plexus injuries after VE, compared with other modes of delivery, support a continued cautious use of VE for preterm delivery.

The relative kicking frequency of infants born full-term and preterm during learning and short-term and long-term memory periods of the mobile paradigm.

PubMed

Heathcock, Jill C; Bhat, Anjana N; Lobo, Michele A; Galloway, James C

2005-01-01

Infants born preterm differ in their spontaneous kicking, as well as their learning and memory abilities in the mobile paradigm, compared with infants born full-term. In the mobile paradigm, a supine infant's ankle is tethered to a mobile so that leg kicks cause a proportional amount of mobile movement. The purpose of this study was to investigate the relative kicking frequency of the tethered (right) and nontethered (left) legs in these 2 groups of infants. Ten infants born full-term and 10 infants born preterm (<33 weeks gestational age, <2,500 g) and 10 comparison infants participated in the study. The relative kicking frequencies of the tethered and nontethered legs were analyzed during learning and short-term and long-term memory periods of the mobile paradigm. Infants born full-term showed an increase in the relative kicking frequency of the tethered leg during the learning period and the short-term memory period but not for the long-term memory period. Infants born preterm did not show a change in kicking pattern for learning or memory periods, and consistently kicked both legs in relatively equal amounts. Infants born full-term adapted their baseline kicking frequencies in a task-specific manner to move the mobile and then retained this adaptation for the short-term memory period. In contrast, infants born preterm showed no adaptation, suggesting a lack of purposeful leg control. This lack of control may reflect a general decrease in the ability of infants born preterm to use their limb movements to interact with their environment. As such, the mobile paradigm may be clinically useful in the early assessment and intervention of infants born preterm and at risk for future impairment.

Perinatal Risks in "Late Motherhood" Defined Based On Parity and Preterm Birth Rate - an Analysis of the German Perinatal Survey (20th Communication).

PubMed

Schure, V; Voigt, M; Schild, R L; Hesse, V; Carstensen, M; Schneider, K T M; Straube, S

2012-01-01

Aim: "Late motherhood" is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what "late motherhood" associated with "high risk" is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998-2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of "late" mothers (with high preterm birth rates) with "control" groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the "control" group included women aged 22-26 (27-31; 29-33) years. Women in the "late motherhood" group were aged > 33 (> 35; > 38) years. Results: The "late motherhood" groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the "control" group, but only in 84.5 % (90 %; 90.4 %) in the "late motherhood" group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the "control" group, but only in 51.4 % (72.2 %; 76.4 %) in the "late motherhood" group. Five-minute APGAR scores were likewise worse for neonates of "late" mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: "Late motherhood" that is associated with greater perinatal risks can be defined based on parity and preterm birth rate.

Critical evaluation of national vital statistics: the case of preterm birth trends in Portugal.

PubMed

Correia, Sofia; Rodrigues, Teresa; Montenegro, Nuno; Barros, Henrique

2015-11-01

Using vital statistics, the Portuguese National Health Plan predicts that 14% of live births will be preterm in 2016. The prediction was based on a preterm birth rise from 5.9% in 2000 to 8.8% in 2009. However, the same source showed an actual decline from 2010 onwards. To assess the plausibility of national preterm birth trends, we aimed to compare the evolution of preterm birth and low birthweight rates between vital statistics and a hospital database. A time-trend analysis (2004-2011) of preterm birth (<37 gestational weeks) and low birthweight (<2500 g) rates was conducted using data on singleton births from the national birth certificates (n = 801,783) and an electronic maternity unit database (n = 21,392). Annual prevalence estimates, ratios of preterm birth:low birthweight and adjusted prevalence ratios were estimated to compare data sources. Although the national prevalence of preterm birth increased from 2004 (5.4%), particularly between 2006 and 2009 (highest rate was 7.5% in 2007), and decreased after 2009 (5.7% in 2011), the prevalence at the maternity unit remained constant. Between 2006 and 2009, preterm birth was almost 1.4 times higher in the national statistics (using the national or the catchment region samples) than in the maternity unit, but no differences were found for low birthweight. Portuguese preterm birth prevalence seems biased between 2006 and 2009, suggesting that early term babies were misclassified as preterm. As civil registration systems are important to support public health decisions, monitoring strategies should be taken to assure good quality data. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Vaginal progesterone pessaries for pregnant women with a previous preterm birth to prevent neonatal respiratory distress syndrome (the PROGRESS Study): A multicentre, randomised, placebo-controlled trial.

PubMed

Crowther, Caroline A; Ashwood, Pat; McPhee, Andrew J; Flenady, Vicki; Tran, Thach; Dodd, Jodie M; Robinson, Jeffrey S

2017-09-01

Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity. The withdrawal of progesterone, either actual or functional, is thought to be an antecedent to the onset of labour. There remains limited information on clinically relevant health outcomes as to whether vaginal progesterone may be of benefit for pregnant women with a history of a previous preterm birth, who are at high risk of a recurrence. Our primary aim was to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth reduced the risk and severity of respiratory distress syndrome in their infants, with secondary aims of examining the effects on other neonatal morbidities and maternal health and assessing the adverse effects of treatment. Women with a live singleton or twin pregnancy between 18 to <24 weeks' gestation and a history of prior preterm birth at less than 37 weeks' gestation in the preceding pregnancy, where labour occurred spontaneously or in association with cervical incompetence or following preterm prelabour rupture of the membranes, were eligible. Women were recruited from 39 Australian, New Zealand, and Canadian maternity hospitals and assigned by randomisation to vaginal progesterone pessaries (equivalent to 100 mg vaginal progesterone) (n = 398) or placebo (n = 389). Participants and investigators were masked to the treatment allocation. The primary outcome was respiratory distress syndrome and severity. Secondary outcomes were other respiratory morbidities; other adverse neonatal outcomes; adverse outcomes for the woman, especially related to preterm birth; and side effects of progesterone treatment. Data were analysed for all the 787 women (100%) randomised and their 799 infants. Most women used their allocated study treatment (740 women, 94.0%), with median use similar for both study groups (51.0 days, interquartile range [IQR] 28.0-69.0, in the progesterone group versus 52.0 days, IQR 27.0-76.0, in the placebo group). The incidence of respiratory distress syndrome was similar in both study groups-10.5% (42/402) in the progesterone group and 10.6% (41/388) in the placebo group (adjusted relative risk [RR] 0.98, 95% confidence interval [CI] 0.64-1.49, p = 0.912)-as was the severity of any neonatal respiratory disease (adjusted treatment effect 1.02, 95% CI 0.69-1.53, p = 0.905). No differences were seen between study groups for other respiratory morbidities and adverse infant outcomes, including serious infant composite outcome (155/406 [38.2%] in the progesterone group and 152/393 [38.7%] in the placebo group, adjusted RR 0.98, 95% CI 0.82-1.17, p = 0.798). The proportion of infants born before 37 weeks' gestation was similar in both study groups (148/406 [36.5%] in the progesterone group and 146/393 [37.2%] in the placebo group, adjusted RR 0.97, 95% CI 0.81-1.17, p = 0.765). A similar proportion of women in both study groups had maternal morbidities, especially those related to preterm birth, or experienced side effects of treatment. In 9.9% (39/394) of the women in the progesterone group and 7.3% (28/382) of the women in the placebo group, treatment was stopped because of side effects (adjusted RR 1.35, 95% CI 0.85-2.15, p = 0.204). The main limitation of the study was that almost 9% of the women did not start the medication or forgot to use it 3 or more times a week. Our results do not support the use of vaginal progesterone pessaries in women with a history of a previous spontaneous preterm birth to reduce the risk of neonatal respiratory distress syndrome or other neonatal and maternal morbidities related to preterm birth. Individual participant data meta-analysis of the relevant trials may identify specific women for whom vaginal progesterone might be of benefit. Current Clinical Trials ISRCTN20269066.

Natural evolution of patent ductus arteriosus in the extremely preterm infant.

PubMed

Rolland, Audrey; Shankar-Aguilera, Shivani; Diomandé, Douty; Zupan-Simunek, Véronique; Boileau, Pascal

2015-01-01

The persistence of the patent ductus arteriosus (PDA) is frequently encountered in very preterm infants. Neither preventive nor curative treatments of PDA have been shown to improve the outcome of these infants. Since no consensus on optimal treatment of PDA is established, we evaluated the rate of spontaneous PDA closure in infants born before 28 weeks of gestation. We studied a retrospective cohort of 103 infants (gestational age 24-27 weeks) admitted to our neonatal intensive care unit from 1 June 2008 to 31 July 2010. Maternal and neonatal characteristics were collected. The PDA was defined by the persistence of ductal patency after 72 h and was followed up by regular echocardiography. Twelve infants died within the first 72 h and were excluded from the analysis. Among 91 infants analysed, 8 (9%) closed their ductus arteriosus before 72 h and the ductus could not be determined patent in 13. Of the 70 infants with a PDA still persistent, one underwent surgical ligation and echocardiography showed spontaneous closure in 51 (73%) of them. In the remaining 18 infants, the date of PDA closure could not be determined either because of their death (n=11) or due to discharge (n=7). Overall, a spontaneous closure of the ductus arteriosus was observed in 59 of the 91 infants. We have to question whether exposure to the risks of therapeutic interventions targeted for ductal closure is warranted since a PDA closes spontaneously in at least 73% of infants born before 28 weeks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Perinatal outcomes after natural conception versus in vitro fertilization (IVF) in gestational surrogates: a model to evaluate IVF treatment versus maternal effects.

PubMed

Woo, Irene; Hindoyan, Rita; Landay, Melanie; Ho, Jacqueline; Ingles, Sue Ann; McGinnis, Lynda K; Paulson, Richard J; Chung, Karine

2017-12-01

To study the perinatal outcomes between singleton live births achieved with the use of commissioned versus spontaneously conceived embryos carried by the same gestational surrogate. Retrospective cohort study. Academic in vitro fertilization center. Gestational surrogate. None. Pregnancy outcome, gestational age at birth, birth weight, perinatal complications. We identified 124 gestational surrogates who achieved a total of 494 pregnancies. Pregnancy outcomes for surrogate and spontaneous pregnancies were significantly different (P<.001), with surrogate pregnancies more likely to result in twin pregnancies: 33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies, there were 352 singleton live births: 103 achieved from commissioned embryos and 249 conceived spontaneously. Surrogate births had lower mean gestational age at delivery (38.8 ± 2.1 vs. 39.7 ± 1.4), higher rates of preterm birth (10.7% vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from surrogacy had birth weights that were, on average, 105 g lower. Surrogate births had significantly higher obstetrical complications, including gestational diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic requirement during labor, and cesarean section. Neonates born from commissioned embryos and carried by gestational surrogates have increased adverse perinatal outcomes, including preterm birth, low birth weight, hypertension, maternal gestational diabetes, and placenta previa, compared with singletons conceived spontaneously and carried by the same woman. Our data suggest that assisted reproductive procedures may potentially affect embryo quality and that its negative impact can not be overcome even with a proven healthy uterine environment. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Psychiatric Outcomes at Age Seven for Very Preterm Children: Rates and Predictors

ERIC Educational Resources Information Center

Treyvaud, Karli; Ure, Alexandra; Doyle, Lex W.; Lee, Katherine J.; Rogers, Cynthia E.; Kidokoro, Hiroyuki; Inder, Terrie E.; Anderson, Peter J.

2013-01-01

Background: Uncertainty remains about the rate of specific psychiatric disorders and associated predictive factors for very preterm (VPT) children. The aims of this study were to document rates of psychiatric disorders in VPT children aged 7 years compared with term born children, and to examine potential predictive factors for psychiatric…

Women's prepregnancy underweight as a risk factor for preterm birth: a retrospective study.

PubMed

Girsen, A I; Mayo, J A; Carmichael, S L; Phibbs, C S; Shachar, B Z; Stevenson, D K; Lyell, D J; Shaw, G M; Gould, J B

2016-11-01

To investigate the distribution of known factors for preterm birth (PTB) by severity of maternal underweight; to investigate the risk-adjusted relation between severity of underweight and PTB, and to assess whether the relation differed by gestational age. Retrospective cohort study. State of California, USA. Maternally linked hospital and birth certificate records of 950 356 California deliveries in 2007-2010 were analysed. Singleton live births of women whose prepregnancy body mass index (BMI) was underweight (<18.5 kg/m 2 ) or normal (18.50-24.99 kg/m 2 ) were analysed. Underweight BMI was further categorised as: severe (<16.00), moderate (16.00-16.99) or mild (17.00-18.49). PTB was grouped as 22-27, 28-31, 32-36 or <37 weeks (compared with 37-41 weeks). Adjusted multivariable Poisson regression modeling was used to estimate relative risk for PTB. Risk of PTB. About 72 686 (7.6%) women were underweight. Increasing severity of underweight was associated with increasing percent PTB: 7.8% (n = 4421) in mild, 9.0% (n = 1001) in moderate and 10.2% (475) in severe underweight. The adjusted relative risk of PTB also significantly increased: adjusted relative risk (aRR) = 1.22 (95% CI 1.19-1.26) in mild, aRR = 1.41 (95% CI 1.32-1.50) in moderate and aRR = 1.61 (95% CI 1.47-1.76) in severe underweight. These findings were similar in spontaneous PTB, medically indicated PTB, and the gestational age groupings. Increasing severity of maternal prepregnancy underweight BMI was associated with increasing risk-adjusted PTB at <37 weeks. This increasing risk was of similar magnitude in spontaneous and medically indicated births and in preterm delivery at 28-31 and at 32-36 weeks of gestation. Increasing severity of maternal underweight BMI was associated with increasing risk of preterm birth. © 2016 Royal College of Obstetricians and Gynaecologists.

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes.

PubMed

Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

2008-04-24

The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660.

MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes

PubMed Central

Kenyon, Sara; Brocklehurst, Peter; Jones, David; Marlow, Neil; Salt, Alison; Taylor, David

2008-01-01

Background The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. Methods The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. Discussion This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. Trial registration The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660 PMID:18435833

Risk of spontaneous preterm birth in relation to maternal experience of serious life events during pregnancy

PubMed Central

Barrios, Yasmin V; Sanchez, Sixto E; Qiu, Chunfang; Gelaye, Bizu; Williams, Michelle A

2014-01-01

Background The purpose of this study was to examine the risk of preterm birth (PTB) in relation to serious life events experienced during pregnancy in Peruvian women. Methods This case-control study included 479 PTB cases and 480 term controls. In-person interviews asked information regarding sociodemographics, medical and reproductive histories, and serious life events experienced during pregnancy. Multivariate logistic regression procedures were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results Compared with women who did not experience a serious life event during pregnancy, those who experienced the following life events had a more than two-fold increased odds of PTB: death of first-degree relative (adjusted OR 2.10; 95% CI 1.38–3.20), divorce or separation (adjusted OR 2.09; 95% CI 1.10–4.00), financial troubles (adjusted OR 2.70; 95% CI 1.85–3.94), or serious fight with partner (adjusted OR 2.40; 95% CI 1.78–3.17). Women who experienced any serious life events during pregnancy had higher odds (adjusted OR 2.29; 95% CI 1.65–3.18) of suffering spontaneous preterm labor and preterm premature rupture of membranes (adjusted OR 2.19; 95% CI 1.56–3.08), compared with women who did not experience any such events. Associations of similar directions and extent were observed for severity of PTB (ie, very, moderate, or late PTB). The magnitude of the associations increased as increased frequency of serious life events (Ptrend <0.001). Conclusion Experiencing serious life events during pregnancy was associated with increased odds of PTB among Peruvian women. Interventions aimed at assisting women experiencing serious life events may reduce the risk of PTB. Future studies should include objective measures of stress and stress response to understand better the biological underpinnings of these associations. PMID:24591850

Birth outcomes following immunization of pregnant women with pandemic H1N1 influenza vaccine 2009-2010.

PubMed

Eaton, Abigail; Lewis, Ned; Fireman, Bruce; Hansen, John; Baxter, Roger; Gee, Julianne; Klein, Nicola P

2018-05-03

Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.66vs 2.43/100 births). Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pathophysiology of preterm labor with intact membranes.

PubMed

Talati, Asha N; Hackney, David N; Mesiano, Sam

2017-11-01

Preterm labor with intact membranes is a major cause of spontaneous preterm birth (sPTB). To prevent sPTB a clear understanding is needed of the hormonal interactions that initiate labor. The steroid hormone progesterone acting via its nuclear progesterone receptors (PRs) in uterine cells is essential for the establishment and maintenance of pregnancy and disruption of PR signaling (i.e., functional progesterone/PR withdrawal) is key trigger for labor. The process of parturition is also associated with inflammation within the uterine tissues and it is now generally accepted that inflammatory stimuli from multiple extrinsic and intrinsic sources induce labor. Recent studies suggest inflammatory stimuli induce labor by affecting PR transcriptional activity in uterine cells to cause functional progesterone/PR withdrawal. Advances in understanding the functional interaction of inflammatory load on the pregnancy uterus and progesterone/PR signaling is opening novel areas of research and may lead to rational therapeutic strategies to effectively prevent sPTB. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of epoxy-eicosanoid degradation improves the tocolytic effects of indomethacin in the uterus from pregnant women.

PubMed

Corriveau, Stéphanie; Berthiaume, Maryse; Rousseau, Eric; Pasquier, Jean-Charles

2011-11-01

The incidence of preterm birth is an increasing problem. Indomethacin, a non-specific cyclooxygenase inhibitor, has been largely used as tocolytic in the treatment of preterm labor. The aim of the present study was to assess a putative synergistic tocolytic effect between the inhibition of the production of prostanoids and stabilization of epoxides fatty acids, particularly arachidonate on spontaneous uterine contractile activity. The experimental work was performed on uterine biopsies from consenting women undergoing elective cesarean delivery at term. Isometric tension measurements were performed on fresh human myometrial strips. Contractile activities have been monitored upon individual and combined treatments of indomethacin, DDMS, an inhibitor of hydroxy-eicosanoids production and AUDA, an inhibitor of epoxy-eicosanoids degradation. Interestingly, a significant and consistent synergic effect was observed when indomethacin and AUDA were simultaneously added, raising the possibility of a combined clinical use of cyclooxygenase and sEH inhibitors in attempt to treat preterm labor. Copyright © 2011 Elsevier Inc. All rights reserved.

Deficits in Top-Down Sensory Prediction in Infants At Risk due to Premature Birth.

PubMed

Emberson, Lauren L; Boldin, Alex M; Riccio, Julie E; Guillet, Ronnie; Aslin, Richard N

2017-02-06

A prominent theoretical view is that the brain is inherently predictive [1, 2] and that prediction helps drive the engine of development [3, 4]. Although infants exhibit neural signatures of top-down sensory prediction [5, 6], in order to establish that prediction supports development, it must be established that deficits in early prediction abilities alter trajectories. We investigated prediction in infants born prematurely, a leading cause of neuro-cognitive impairment worldwide [7]. Prematurity, independent of medical complications, leads to developmental disturbances [8-12] and a broad range of developmental delays [13-17]. Is an alteration in early prediction abilities the common cause? Using functional near-infrared spectroscopy (fNIRS), we measured top-down sensory prediction in preterm infants (born <33 weeks gestation) before infants exhibited clinically identifiable developmental delays (6 months corrected age). Whereas preterm infants had typical neural responses to presented visual stimuli, they exhibited altered neural responses to predicted visual stimuli. Importantly, a separate behavioral control confirmed that preterm infants detect pattern violations at the same rate as full-terms, establishing selectivity of this response to top-down predictions (e.g., not in learning an audiovisual association). These findings suggest that top-down sensory prediction plays a crucial role in development and that deficits in this ability may be the reason why preterm infants experience altered developmental trajectories and are at risk for poor developmental outcomes. Moreover, this work presents an opportunity for establishing a neuro-biomarker for early identification of infants at risk and could guide early intervention regimens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bottle-feeding histories of preterm infants.

PubMed

Pickler, R H; Mauck, A G; Geldmaker, B

1997-01-01

To describe the bottle-feeding histories of preterm infants and determine physical indices related to and predictive of bottle-feeding initiation and progression. Ex post facto. Academic medical center. A convenience sample of 40 preterm infants without concomitant cardiac, gastrointestinal, or cognitive impairment. Postconceptional age at first bottle-feeding, full bottle-feeding, and discharge. The morbidity rating, using the Neonatal Medical Index (NMI), was most strongly correlated with postconceptional age at first bottle-feeding (r = .34, p < .05), full bottle-feeding (r = .65, p < .01), and discharge (r = .55, p < .05). The morbidity rating also accounted for 12%, 42%, and 30% of the variance in postconceptional age at first bottle-feeding, full bottle-feeding, and discharge, respectively. The NMI may be a useful tool for predicting the initiation and progression of bottle-feeding in preterm infants.

NODAL in the Uterus Is Necessary for Proper Placental Development and Maintenance of Pregnancy1

PubMed Central

Park, Craig B.; DeMayo, Francesco J.; Lydon, John P.; Dufort, Daniel

2012-01-01

Preterm birth is the single leading cause of perinatal mortality in developed countries, affecting approximately 12% of pregnancies and accounting for 75% of neonatal loss in the United States. Despite the prevalence and severity of premature delivery, the causes and mechanisms that underlie spontaneous and idiopathic preterm birth remain unknown. Our inability to elucidate these fundamental causes has been attributed to a poor understanding of the signaling pathways associated with the premature induction of parturition and a lack of suitable animal models available for preterm birth research. In this study, we describe the generation and analysis of a novel conditional knockout of the transforming growth factor beta (TGFB) superfamily member, Nodal, from the maternal reproductive tract of mice. Strikingly, uterine Nodal knockout females exhibited a severe malformation of the maternal decidua basalis during placentation, leading to significant intrauterine growth restriction, and ultimately preterm birth and fetal loss on Day 17.5 of gestation. Using several approaches, we characterized aberrant placental development and demonstrated that reduced proliferation combined with increased apoptosis resulted in a diminished decidua basalis and compromised maternal-fetal interface. Last, we evaluated various components of the established parturition cascade and determined that preterm birth derived from the maternal Nodal knockout occurs prior to PTGS2 (COX-2) upregulation at the placental interface. Taken together, the results presented in this study highlight an in vivo role for maternal NODAL during placentation, present an interesting link between disrupted decidua basalis formation and premature parturition, and describe a potentially valuable model toward elucidating the complex processes that underlie preterm birth. PMID:22378764

Cumulative Psychosocial and Medical Risk as Predictors of Early Infant Development and Parenting Stress in an African-American Preterm Sample

ERIC Educational Resources Information Center

Candelaria, Margo A.; O'Connell, Melissa A.; Teti, Douglas M.

2006-01-01

The present study examined predictive linkages between cumulative psychosocial and medical risk, assessed neonatally, and infant development and parenting stress at 4 months of infant corrected age. Predominantly low-income, African-American mothers and their preterm infants served as participants. Cumulative psychosocial risk predicted early…

Effects of psychosocial characteristics of work on pregnancy outcomes: a critical review.

PubMed

Mutambudzi, Miriam; Meyer, John D; Warren, Nicholas; Reisine, Susan

2011-05-01

Birth outcomes may influence subsequent susceptibility to chronic diseases. With the increased number of women who continue to work during pregnancy, occupational stress has been hypothesized to be a potential contributor to adverse reproductive health outcomes. The Job Demand and Control model has been primarily used in investigating associations between work-related stress and outcomes such as preterm delivery, low birth weight, and spontaneous abortion. A literature review of occupational factors that have been associated with adverse reproductive outcomes was conducted. In studies assessing preterm delivery and low birth weight, some evidence has suggested a modest association with work-related stress but has not been conclusive. In the literature on psychosocial characteristics of work and spontaneous abortion, job strain alone was often not associated with adverse outcomes. However the presence of other risk factors resulted in a synergistic effect which strengthened the odds of an adverse outcome. Future studies should use a prospective design with a large study sample, in which work-related stress exposure data are collected before or in the early stages of the pregnancy. In addition, future research should measure psychosocial characteristics of work both objectively and subjectively.

An fMRI compatible wrist robotic interface to study brain development in neonates.

PubMed

Allievi, A G; Melendez-Calderon, A; Arichi, T; Edwards, A D; Burdet, E

2013-06-01

A comprehensive understanding of the mechanisms that underlie brain development in premature infants and newborns is crucial for the identification of interventional therapies and rehabilitative strategies. fMRI has the potential to identify such mechanisms, but standard techniques used in adults cannot be implemented in infant studies in a straightforward manner. We have developed an MR safe wrist stimulating robot to systematically investigate the functional brain activity related to both spontaneous and induced wrist movements in premature babies using fMRI. We present the technical aspects of this development and the results of validation experiments. Using the device, the cortical activity associated with both active and passive finger movements were reliably identified in a healthy adult subject. In two preterm infants, passive wrist movements induced a well localized positive BOLD response in the contralateral somatosensory cortex. Furthermore, in a single preterm infant, spontaneous wrist movements were found to be associated with an adjacent cluster of activity, at the level of the infant's primary motor cortex. The described device will allow detailed and objective fMRI studies of somatosensory and motor system development during early human life and following neonatal brain injury.

Prenatal Therapy of Large Placental Chorioangiomas: Case Report and Review of the Literature

PubMed Central

Hosseinzadeh, Pardis; Shamshirsaz, Alireza A.; Javadian, Pouya; Espinoza, Jimmy; Gandhi, Manisha; Ruano, Rodrigo; Cass, Darrell L.; Olutoye, Oluyinka A.; Belfort, Michael A.

2015-01-01

Objective To review techniques and outcomes of different prenatal treatments for large placental chorioangiomas. Study Design Presentation of a case of laparoscopic-assisted laser coagulation and a systematic review of the literature for articles related to intervention for placental chorioangioma. Results A total of 37 cases of definitive (n = 23) and supportive therapy (n = 14) were evaluated, including one case treated in our center. Approximately 35% of the patients had a spontaneous preterm delivery in definitive treatment group versus 36% in the supportive group. The infant survival rates were 65 and 71% in the two groups, respectively. We further compared the two types of laser ablation (fetoscopic [n = 10] and interstitial [n = 4]). Approximately 30% of the patients in the fetoscopic and 25% in interstitial group, had a spontaneous preterm delivery. Survival rates were 60 and 100% in fetoscopic and interstitial groups, respectively. Conclusion Laser ablation and embolization of chorioangiomas via minimally invasive approach may prevent or reverse fetal hydrops due to high cardiac states. However, further studies are needed to refine the appropriate selection criteria that will justify the risk of this invasive in utero therapy for chorioangiomas. PMID:26495184

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

PubMed

Sengpiel, Verena; Bacelis, Jonas; Myhre, Ronny; Myking, Solveig; Devold Pay, Aase Serine; Haugen, Margaretha; Brantsæter, Anne-Lise; Meltzer, Helle Margrete; Nilsen, Roy Miodini; Magnus, Per; Vollset, Stein Emil; Nilsson, Staffan; Jacobsson, Bo

2014-11-02

Health authorities in numerous countries recommend periconceptional folic acid supplementation to prevent neural tube defects. The objective of this study was to examine the association of dietary folate intake and folic acid supplementation during different periods of pregnancy with the risk of spontaneous preterm delivery (PTD). The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 66,014 women with singleton pregnancies resulting in live births in 2002-2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until pregnancy week 24. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4-5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,755). The median total folate intake was 313 μg/d (interquartile range IQR 167-558) in the overall population and 530 μg/d (IQR 355-636) in the supplement users. Eighty-five percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while only 44% initiated folic acid supplementation before pregnancy. Cox regression analysis showed that the amount of dietary folate intake (hazard ratio HR 1.00; confidence interval 95% CI 0.61-1.65) and supplemental folate intake (HR 1.00; CI 1.00-1.00) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for spontaneous PTD (HR 1.18; CI 1.05-1.32) compared to no folic acid supplementation preconception. There was no significant association with PTD when supplementation was initiated within 8 weeks preconception (HR 0.99; CI 0.87-1.13). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Preconceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of spontaneous PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

A Norwegian prospective study of preterm mother–infant interactions at 6 and 18 months and the impact of maternal mental health problems, pregnancy and birth complications

PubMed Central

Misund, Aud R; Bråten, Stein; Nerdrum, Per; Pripp, Are Hugo; Diseth, Trond H

2016-01-01

Objective Pregnancy, birth and health complications, maternal mental health problems following preterm birth and their possible impact on early mother–infant interaction at 6 and 18 months corrected age (CA) were explored. Predictors of mother–infant interaction at 18 months CA were identified. Design and methods This prospective longitudinal and observational study included 33 preterm mother–infant (<33 gestational age (GA)) interactions at 6 and 18 months CA from a socioeconomic low-risk, middle-class sample. The Parent–Child Early Relational Assessment (PCERA) scale was used to assess the mother–infant interaction. Results ‘Bleeding in pregnancy’ predicted lower quality in preterm mother–infant interaction in 6 PCERA scales, while high ‘maternal trait anxiety’ predicted higher interactional quality in 2 PCERA scales and ‘family size’ predicted lower interactional quality in 1 PCERA scale at 18 months CA. Mothers with symptoms of post-traumatic stress reactions, general psychological distress and anxiety at 2 weeks postpartum (PP) showed significantly better outcome than mothers without symptoms in 6 PCERA subscales at 6 months CA and 2 PCERA subscales at 18 months CA. Conclusions Our study detected a correspondence between early pregnancy complications and lower quality of preterm mother–infant interaction, and an association between high levels of maternal mental health problems and better quality in preterm mother–infant interaction. PMID:27147380

Prediction of permanent hearing loss in high-risk preterm infants at term age.

PubMed

Valkama, A M; Laitakari, K T; Tolonen, E U; Väyrynen, M R; Vainionpää, L K; Koivisto, M E

2000-06-01

The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age < 34 weeks, birth weight < 1500 g) underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of 18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50% and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively. Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage. Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants.

Reproductive, Perinatal, and Environmental Factors as Predictors of the Cognitive and Language Development of Preterm and Full-Term Infants.

ERIC Educational Resources Information Center

Siegel, Linda S.

1982-01-01

The accuracy of a risk index based on reproductive and demographic factors for predicting subsequent development was tested with 51 full-term and 53 preterm infants. In addition, the possibility that scores on the Home Observation for Measurement of the Environment scale might contribute significantly to the prediction of subsequent development…

Patterns of Functioning and Predictive Factors in Children Born Moderately Preterm or at Term

ERIC Educational Resources Information Center

Cserjesi, Renata; van Braeckel, Koenraad N. J. A.; Timmerman, Marieke; Butcher, Phillipa R.; Kerstjens, Jorien M.; Reijneveld, Sijmen A.; Bouma, Anke; Bos, Arend F.; Geuze, Reint H.

2012-01-01

Aim: The aim of this study was to identify subgroups of children born moderately preterm (MPT) and term with distinctive levels and patterns of functioning, and the perinatal and demographic factors that predict subgroup membership. Method: A total of 378 children aged 7 years, 248 MPT (138 males, 110 females; gestational age 32-36 wks) and a…

ADIPONECTIN IN AMNIOTIC FLUID IN NORMAL PREGNANCY, SPONTANEOUS LABOR AT TERM, AND PRETERM LABOR: A NOVEL ASSOCIATION WITH SUBCLINICAL INTRAUTERINE INFECTION/INFLAMMATION

PubMed Central

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Kusanovic, Juan Pedro; Erez, Offer; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Than, Nandor Gabor; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Dong, Zhong; Hassan, Sonia S.

2012-01-01

Objective Adiponectin, an anti-inflammatory and anti-diabetogenic adipokine, has an important regulatory effect on both the innate and adaptive limbs of the immune response. The objective of this study was to determine whether adiponectin is present in amniotic fluid (AF) and if its concentration changes with gestational age, in the presence of labor and in the presence of intra-amniotic infection (IAI) in patients with spontaneous preterm labor (PTL) and intact membranes. Study design This cross-sectional study included 468 patients in the following groups: 1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=49) and without (n=41) spontaneous labor; 3) patients with an episode of PTL and intact membranes who were classified into: a) PTL who delivered at term (n=149); b) PTL who delivered preterm (<37 weeks gestation) without IAI (n=108); and c) PTL with IAI (n=69) Adiponectin concentration in AF was determined by ELISA. Results 1) The median AF adiponectin concentration at term was significantly higher than in the mid-trimester (35.6 ng/mL, interquartile range [IQR] 26.4–52.7 vs. 29.9 ng/mL, IQR 19.9–35.2; p=0.01); 2) among women with PTL and intact membranes, the median amniotic fluid adiponectin concentration was significantly higher in patients with IAI than in those without IAI who delivered either at term (54.3 ng/mL, 39.0–91.8 vs. 50.1 ng/mL, 33.2–72.8; p = 0.02) or preterm (47.6 ng/mL, 32.6–74.6; p = 0.01); and 3) among women at term, there was no significant difference in the median amniotic fluid adiponectin concentration between those with and without labor (33.7 ng/mL, IQR 21.7–53.9 vs. 35.6 ng/mL IQR 26.4–52.7; respectively p=0.5). Conclusions 1) Adiponectin is a physiologic constituent of AF; and 2) adiponectin concentrations in AF are increased significantly with advancing gestation and in the presence of IAI. Collectively, these findings suggest that adiponectin plays a dynamic role in normal gestation and in the presence of IAI. PMID:19591073

Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

PubMed Central

Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

2015-01-01

Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral, and language disabilities that limit academic achievement and well-being. Limited progress has been made to develop therapies that improve neurologic outcomes. The overall objective of this study is to understand the effect of early brain injury on activity-dependent brain development and cortical plasticity to develop new treatments that will optimize repair and recovery after brain injury. PMID:26311776

Automatic burst detection for the EEG of the preterm infant.

PubMed

Jennekens, Ward; Ruijs, Loes S; Lommen, Charlotte M L; Niemarkt, Hendrik J; Pasman, Jaco W; van Kranen-Mastenbroek, Vivianne H J M; Wijn, Pieter F F; van Pul, Carola; Andriessen, Peter

2011-10-01

To aid with prognosis and stratification of clinical treatment for preterm infants, a method for automated detection of bursts, interburst-intervals (IBIs) and continuous patterns in the electroencephalogram (EEG) is developed. Results are evaluated for preterm infants with normal neurological follow-up at 2 years. The detection algorithm (MATLAB®) for burst, IBI and continuous pattern is based on selection by amplitude, time span, number of channels and numbers of active electrodes. Annotations of two neurophysiologists were used to determine threshold values. The training set consisted of EEG recordings of four preterm infants with postmenstrual age (PMA, gestational age + postnatal age) of 29-34 weeks. Optimal threshold values were based on overall highest sensitivity. For evaluation, both observers verified detections in an independent dataset of four EEG recordings with comparable PMA. Algorithm performance was assessed by calculation of sensitivity and positive predictive value. The results of algorithm evaluation are as follows: sensitivity values of 90% ± 6%, 80% ± 9% and 97% ± 5% for burst, IBI and continuous patterns, respectively. Corresponding positive predictive values were 88% ± 8%, 96% ± 3% and 85% ± 15%, respectively. In conclusion, the algorithm showed high sensitivity and positive predictive values for bursts, IBIs and continuous patterns in preterm EEG. Computer-assisted analysis of EEG may allow objective and reproducible analysis for clinical treatment.

Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study.

PubMed

Myers, J E; Kenny, L C; McCowan, L M E; Chan, E H Y; Dekker, G A; Poston, L; Simpson, N A B; North, R A

2013-09-01

To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Predictive test accuracy study. Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation). Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial.

PubMed

Vento, Giovanni; Pastorino, Roberta; Boni, Luca; Cota, Francesco; Carnielli, Virgilio; Cools, Filip; Dani, Carlo; Mosca, Fabio; Pillow, Jane; Polglase, Graeme; Tagliabue, Paolo; van Kaam, Anton H; Ventura, Maria Luisa; Tana, Milena; Tirone, Chiara; Aurilia, Claudia; Lio, Alessandra; Ricci, Cinzia; Gambacorta, Alessandro; Consigli, Chiara; D'Onofrio, Danila; Gizzi, Camilla; Massenzi, Luca; Cardilli, Viviana; Casati, Alessandra; Bottino, Roberto; Pontiggia, Federica; Ciarmoli, Elena; Martinelli, Stefano; Ilardi, Laura; Colnaghi, Mariarosa; Matassa, Piero Giuseppe; Vendettuoli, Valentina; Villani, Paolo; Fusco, Francesca; Gazzolo, Diego; Ricotti, Alberto; Ferrero, Federica; Stasi, Ilaria; Magaldi, Rosario; Maffei, Gianfranco; Presta, Giuseppe; Perniola, Roberto; Messina, Francesco; Montesano, Giovanna; Poggi, Chiara; Giordano, Lucio; Roma, Enza; Grassia, Carolina; Ausanio, Gaetano; Sandri, Fabrizio; Mescoli, Giovanna; Giura, Francesco; Garani, Giampaolo; Solinas, Agostina; Lucente, Maria; Nigro, Gabriella; Del Vecchio, Antonello; Petrillo, Flavia; Orfeo, Luigi; Grappone, Lidia; Quartulli, Lorenzo; Scorrano, Antonio; Messner, Hubert; Staffler, Alex; Gargano, Giancarlo; Balestri, Eleonora; Nobile, Stefano; Cacace, Caterina; Meli, Valerio; Dallaglio, Sara; Pasqua, Betta; Mattia, Loretta; Gitto, Eloisa; Vitaliti, Marcello; Re, Maria Paola; Vedovato, Stefania; Grison, Alessandra; Berardi, Alberto; Torcetta, Francesco; Guidotti, Isotta; di Fabio, Sandra; Maranella, Eugenia; Mondello, Isabella; Visentin, Stefano; Tormena, Francesca

2016-08-18

Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. In this study, 206 spontaneously breathing infants born at 24(+0)-27(+6) weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.

Predicting Live Birth, Preterm Delivery, and Low Birth Weight in Infants Born from In Vitro Fertilisation: A Prospective Study of 144,018 Treatment Cycles

PubMed Central

Nelson, Scott M.; Lawlor, Debbie A.

2011-01-01

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF. Please see later in the article for the Editors' Summary PMID:21245905

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis

PubMed Central

Wotherspoon, Lisa M; Boyd, Kathleen A; Morris, Rachel K; Jackson, Lesley; Chandiramani, Manju; David, Anna L; Khalil, Asma; Shennan, Andrew; Hodgetts Morton, Victoria; Lavender, Tina; Khan, Khalid; Harper-Clarke, Susan; Mol, Ben W; Riley, Richard D; Norrie, John; Norman, Jane E

2018-01-01

Introduction The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors. Methods and analysis The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing). Ethics and dissemination The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). PROSPERO registration number CRD42015027590. Version Protocol version 2, date 1 November 2016. PMID:29627817

Motor development and sensory processing: A comparative study between preterm and term infants.

PubMed

Cabral, Thais Invenção; Pereira da Silva, Louise Gracelli; Tudella, Eloisa; Simões Martinez, Cláudia Maria

2014-10-16

Infants born preterm and/or with low birth weight may present a clinical condition of organic instability and usually face a long period of hospitalization in the Neonatal Intensive Care Units, being exposed to biopsychosocial risk factors to their development due to decreased spontaneous movement and excessive sensory stimuli. This study assumes that there are relationships between the integration of sensory information of preterm infants, motor development and their subsequent effects. To evaluate the sensory processing and motor development in preterm infants aged 4-6 months and compare performance data with their peers born at term. This was a cross-sectional and comparative study consisting of a group of preterm infants (n=15) and a group of term infants (n=15), assessed using the Test of Sensory Functions in Infants (TSFI) and the Alberta Infant Motor Scale (AIMS). The results showed no significant association between motor performance on the AIMS scale (total score) and sensory processing in the TSFI (total score). However, all infants who scored abnormal in the total TSFI score, subdomain 1, and subdomain 5 presented motor performance at or below the 5th percentile on the AIMS scale. Since all infants who presented definite alteration in tolerating tactile deep pressure and poor postural control are at risk of delayed gross motor development, there may be peculiarities not detected by the tests used that seem to establish some relationship between sensory processing and motor development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births.

PubMed

Kroese, S J; de Hair, M J H; Limper, M; Lely, A T; van Laar, J M; Derksen, R H W M; Fritsch-Stork, R D E

2017-01-01

To investigate the effect of hydroxychloroquine (HCQ) in pregnant women with systemic lupus erythematosus (SLE). In SLE pregnancies of a single Dutch center (2000-2015), lupus activity and flares before and during pregnancy and postpartum were assessed using the SLE Disease Activity Index (SLEDAI)/SLEPDAI (SLEDAI adjusted for pregnancy). The association between HCQ use and pregnancy outcomes (early spontaneous abortion, fetal death, and preterm and term live birth) was analyzed using generalized estimating equations (GEE) accounting for the occurrence of multiple pregnancies per patient. Analyses were adjusted for antiphospholipid antibody (aPL) status. 110 pregnancies (63 mostly Caucasian patients) were included, of which, in 30, HCQ was used; overall occurrence of flares was low (non-HCQ group: 5 mild (6.4%) and 2 severe (2.6%); HCQ group: 2 mild (6.7%) and no severe flares). The HCQ group showed a trend towards lower dosage of prednisone (OR 0.2 (95% CI 0.0-1.4); p = 0.10). Pregnancy outcomes were comparable between groups. Among preterm live births, pregnancy duration was significantly longer in HCQ users (2.4 weeks (95% CI 1.0-3.8; p ≤ 0.001)). HCQ use was associated with longer pregnancy duration in the vulnerable preterm birth population, underscoring the beneficial effect of HCQ use during pregnancy.

The impact of fetal gender and ethnicity on the risk of spontaneous preterm delivery in women with symptoms of preterm labor.

PubMed

Wilms, Femke F; Vis, Jolande Y; Oudijk, Martijn A; Kwee, Anneke; Porath, Martina M; Scheepers, Hubertina C J; Spaanderman, Marc E A; Bloemenkamp, Kitty W M; Bolte, Antoinette C; Bax, Caroline J; Cornette, Jérôme M J; Duvekot, Johannes J; Nij Bijvanck, Bas W A; Eijck, Jim van; Franssen, Maureen T M; Sollie, Krystyna M; Vandenbussche, Frank P H A; Woiski, Mallory D; van der Post, Joris A M; Bossuyt, Patrick M M; Opmeer, Brent C; Mol, Ben W J; van Baaren, Gert-Jan

2016-11-01

The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD). A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated. Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0)). The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity.

Bullying of preterm children and emotional problems at school age: cross-culturally invariant effects.

PubMed

Wolke, Dieter; Baumann, Nicole; Strauss, Victoria; Johnson, Samantha; Marlow, Neil

2015-06-01

To investigate whether adolescents who were born extremely preterm (<26 weeks gestation), very preterm (<32 weeks gestation), or with very low birth weight (<1500 g) are more often bullied, and whether this contributes to higher emotional problem scores. We used 2 whole population samples: the German Bavarian Longitudinal Study (BLS) (287 very preterm/very low birth weight and 293 term comparison children) and the UK EPICure Study (183 extremely preterm and 102 term comparison children). Peer bullying was assessed by parent report in both cohorts at school years 2 and 6/7. The primary outcome was emotional problems in year 6/7. The effects of prematurity and bullying on emotional problems were investigated with regression analysis and controlled for sex, socioeconomic status, disability, and preexisting emotional problems. Preterm-born children were more often bullied in both cohorts than term comparisons (BLS: relative risk, 1.27; 95% CI, 1.07-1.50; EPICure: relative risk, 1.69; 95% CI, 1.19-2.41). Both preterm birth and being bullied predicted emotional problems, but after controlling for confounders, only being bullied at both ages remained a significant predictor of emotional problem scores in both cohorts (BLS: B, 0.78; 95% CI, 0.28-1.27; P < .01; EPICure: B, 1.55; 95% CI, 0.79-2.30; P < .001). In the EPICure sample, being born preterm and being bullied at just a single time point also predicted emotional problems. Preterm-born children are more vulnerable to being bullied by peers. Those children who experience bullying over years are more likely to develop emotional problems. Health professionals should routinely ask about peer relationships. Copyright © 2015 Elsevier Inc. All rights reserved.

Bed rest in singleton pregnancies for preventing preterm birth.

PubMed

Sosa, C; Althabe, F; Belizán, J; Bergel, E

2004-01-01

Bed rest in hospital or at home is widely recommended for the prevention of preterm birth. This advice is based on the observation that hard work and hard physical activity during pregnancy could be associated with preterm birth and with the idea that bed rest could reduce uterine activity. However, bed rest may have some adverse effects on other outcomes. To evaluate the effect of prescription of bed rest in hospital or at home for preventing preterm birth in pregnant women at high risk of preterm birth. We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (July 2003), LILACS (July 2003), EMBASE (July 2003), POPLINE (July 2003) and bibliographies of relevant papers. Randomized and quasi-randomized controlled trials with reported data that assess clinical outcomes in women at high risk of spontaneous preterm birth who were prescribed bed rest in hospital or at home for preventing preterm birth, and their babies. Two reviewers independently assessed eligibility, trial quality and extracted data. One study met the inclusion criteria (1266 women). This trial has uncertain methodological quality due to lack of reporting. Four hundred and thirty-two women were prescribed bed rest at home and a total of 834 women received a placebo (412) or no intervention (422). Preterm birth before 37 weeks was similar in both groups (7.9% in the intervention group versus 8.5% in the control group), and the relative risk was 0.92 with a 95% confidence interval from 0.62 to 1.37. No other results were available. There is no evidence, either supporting or refuting the use of bed rest at home or in hospital, to prevent preterm birth. Although bed rest in hospital or at home is widely used as the first step of treatment, there is no evidence that this practice could be beneficial. Due to the potential adverse effects that bed rest could have on women and their families, and the increased costs for the healthcare system, clinicians should not routinely advise women to rest in bed to prevent preterm birth. Potential benefits and harms should be discussed with women facing an increased risk of preterm birth. Appropriate research is mandatory. Future trials should evaluate both the effectiveness of bed rest, and the effectiveness of the prescription of bed rest, to prevent preterm birth.

Role of Perceived Stress on the Occurrence of Preterm Labor and Preterm Birth among Urban Women

PubMed Central

Seravalli, Laura; Patterson, Freda; Nelson, Deborah B.

2013-01-01

Introduction This study examined whether prenatal perceived stress levels during pregnancy were associated with preterm labor (PTL) or preterm birth (PTB). Methods Perceived stress levels were measured at 16 weeks gestation or less and between 20 and 24 weeks gestation in a sample of 1,069 low-income pregnant women attending Temple University prenatal care clinics. Scores were averaged to create a single measure of prenatal stress. PTB was defined as the occurrence of a spontaneous birth prior to 37 weeks gestation. PTL was defined as the occurrence of regular contractions between 20 and 37 weeks of pregnancy that were associated with changes in the cervix. Results Independent of potential confounding factors, prenatal perceived stress was not associated with PTL (OR 1.10; 95% CI 0.69-1.78, P = .66); however, prenatal stress trended toward an association with PTB (OR 1.49; 95% CI: 1.00-2.23, P =.05). The strongest predictor of preterm labor was a history of preterm labor in a prior pregnancy. Women with a history of PTL were two times more likely to experience PTL in the current pregnancy than women who did not have a PTL history (OR 2.16; 95% CI 1.05-4.41, P =.04). Historical risk factors of PTB, such as African American race, a history of abortion or a history of PTB were not related to PTL. The strongest predictor of PTB was having a history of PTB in a prior pregnancy (OR 2.55; 95% CI 1.54-4.24, P <.001). Discussion Prenatal perceived stress levels may be a risk factor for PTB independent of PTL; however, prenatal stress was not associated with PTL. Risk factors for PTL may be different from those of PTB. PMID:24890400

Aeromedical transfer of women at risk of preterm delivery in remote and rural Western Australia: why are there no births in flight?

PubMed

Akl, Natalie; Coghlan, Edwina A; Nathan, Elizabeth A; Langford, Stephen A; Newnham, John P

2012-08-01

For more than three decades, women at imminent risk of preterm birth (PTB) in Western Australia have been transferred by small aircraft over long distances to the single tertiary level perinatal centre in Perth, with no known case of birth during the flight. We aimed to review recent experience to understand how aircraft travel may delay PTB. Retrospective observational study of 500 consecutive Royal Flying Doctor Service (RFDS) transfers of women at risk of preterm labour to the tertiary referral centre, from September 2007 to December 31, 2009. In-flight delivery, complications associated with transfer and factors associated with delay in preterm delivery. There were no in-flight deliveries or serious complications associated with the aeromedical transfer of these patients. In a multivariable Cox proportional hazards regression analysis, clinical factors in the presentation that were associated with a shorter time from landing to subsequent delivery included cervical dilatation ≥ 4 cm, ruptured membranes, gestational age > 32 weeks and nulliparity. The aircraft reaching an ambient altitude > 14,000 feet, or cabin altitude above zero (sea level), was associated with a delay in time from landing to delivery for women who were not in spontaneous preterm labour. Our findings add to a 30-year experience that women at risk of preterm labour do not deliver during aeromedical transfer. Ambient and cabin altitude of the aircraft were associated with an extension in the time to delivery after arrival. The mechanisms underpinning this effect warrant further investigation. © 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Inflammatory Markers Related to Microbial Translocation Among HIV-Infected Pregnant Women: A Risk Factor of Preterm Delivery.

PubMed

López, Marta; Figueras, Francesc; Coll, Oriol; Goncé, Anna; Hernández, Sandra; Loncá, Montse; Vila, Jordi; Gratacós, Eduard; Palacio, Montse

2016-02-01

This study was performed to assess the role of lipopolysaccharide modulators as a marker of microbial translocation among human immunodeficiency virus (HIV)-infected women during pregnancy and to evaluate their association with preterm delivery. The study had a prospective cohort design and was performed at the Hospital Clínic in Barcelona, Spain. Thirty-six pregnant women with and 36 without HIV infection, matched on the basis of age and parity, were included. Maternal blood samples were obtained during the first trimester, during the third trimester, and at delivery. Levels of soluble CD14 (sCD14), human lipopolysaccharide-binding protein (LBP), immunoglobulin M endotoxin core antibodies to lipopolysaccharide (EndoCAb), and interleukin 6 (IL-6) were determined. Fetal cord blood levels of sCD14, LBP, and IL-6 were determined. Results were compared between groups. First trimester sCD14 and LBP levels and third trimester sCD14 levels were significantly higher in the HIV-infected group. HIV-infected women with preterm births and spontaneous preterm births had significantly increased levels of sCD14 throughout pregnancy and significantly increased levels of LBP during the first trimester, compared with HIV-infected women with delivery at term or with HIV-negative women. On multivariate analysis, an independent association was observed between first trimester sCD14 levels and preterm delivery among HIV-infected women. This is the first study to assess inflammatory markers related to microbial translocation during pregnancy among HIV-infected women. Higher levels of sCD14 and LBP were observed in HIV-infected pregnant women and were associated with preterm delivery. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Computer-based analysis of general movements reveals stereotypies predicting cerebral palsy.

PubMed

Philippi, Heike; Karch, Dominik; Kang, Keun-Sun; Wochner, Katarzyna; Pietz, Joachim; Dickhaus, Hartmut; Hadders-Algra, Mijna

2014-10-01

To evaluate a kinematic paradigm of automatic general movements analysis in comparison to clinical assessment in 3-month-old infants and its prediction for neurodevelopmental outcome. Preterm infants at high risk (n=49; 26 males, 23 females) and term infants at low risk (n=18; eight males, 10 females) of developmental impairment were recruited from hospitals around Heidelberg, Germany. Kinematic analysis of general movements by magnet tracking and clinical video-based assessment of general movements were performed at 3 months of age. Neurodevelopmental outcome was evaluated at 2 years. By comparing the general movements of small samples of children with and without cerebral palsy (CP), we developed a kinematic paradigm typical for infants at risk of developing CP. We tested the validity of this paradigm as a tool to predict CP and neurodevelopmental impairment. Clinical assessment correctly identified almost all infants with neurodevelopmental impairment including CP, but did not predict if the infant would be affected by CP or not. The kinematic analysis, in particular the stereotypy score of arm movements, was an excellent predictor of CP, whereas stereotyped repetitive movements of the legs predicted any neurodevelopmental impairment. The automatic assessment of the stereotypy score by magnet tracking in 3-month-old spontaneously moving infants at high risk of developmental abnormalities allowed a valid detection of infants affected and unaffected by CP. © 2014 Mac Keith Press.

Hemidiaphragmatic paralysis in preterm neonates: a rare complication of peripherally inserted central catheter extravasation.

PubMed

Tosello, Barthelemy; Michel, Fabrice; Merrot, Thierry; Chaumoître, Kathia; Hassid, Sophie; Lagier, Pierre; Martin, Claude

2011-07-01

Unilateral diaphragmatic paralysis was diagnosed in 2 preterm neonates born at 29 and 25 weeks of gestation, respectively. In both instances, the pathophysiology was phrenic nerve injury after extravasation of parenteral nutrition fluid. Misplacement and infection were predisposing factors. Diaphragmatic movement analysis by time-motion-mode ultrasonography was helpful in achieving a diagnosis. The first neonate required a diaphragmatic placation, whereas the other infant was managed nonoperatively. These cases confirm a rare etiology of diaphragmatic paralysis and possible spontaneous recovery. In neonates with very low birth weight, general anesthesia and thoracic surgery may be associated with a high morbidity, suggesting that nonoperative medical treatment, when possible, is preferable if the neonate does not require supplemental oxygen. Copyright © 2011 Elsevier Inc. All rights reserved.

Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

PubMed Central

Sveinsdóttir, Kristbjörg; Länsberg, John-Kalle; Sveinsdóttir, Snjólaug; Garwicz, Martin; Ohlsson, Lennart; Hellström, Ann; Smith, Lois; Gram, Magnus; Ley, David

2018-01-01

Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p < 0.05) than in the T group. Postnatal weight development correlated with circulating IGF-1 (r2 = 0.89) independently of gestational age at birth and postnatal age. The proliferative (Ki-67-positive) portion of the external granular layer (EGL) was decreased in the PT group at postnatal day 2 (P2) compared to in the T group (p = 0.01). Purkinje cells exhibited decreased calbindin staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population. PMID:28972955

Differential effects of parenting in preterm and full-term children on developmental outcomes.

PubMed

Maupin, Angela N; Fine, Jodene Goldenring

2014-12-01

To examine the relations between preterm birth, parenting behavior during early childhood, cognitive development, and social-emotional outcomes at Kindergarten entry, and to determine whether parenting behavior differentially influences this developing system in children born preterm compared to children born full-term. The nationally representative sample comprised 3600 full-term and 1300 preterm children born in the US in the year 2001. All children who entered Kindergarten and who participated in data collection at 9 months, 24 months, and Kindergarten entry were included in the study. Measures of parenting behavior were collected at 9 and 24 months and cognitive development at 24 months via home visits. Social-emotional outcomes were assessed at Kindergarten entry via parent and teacher report. Multiple-sample Structural Equation Modeling was used to analyze group differences in a model whereby early childhood parenting behavior predicted cognitive outcomes, and social-emotional outcomes at Kindergarten entry, and indirectly predicted social-emotional outcomes via early cognitive processes. The full sample developmental model indicated excellent fit to the data. Preterm birth status indirectly influenced social-emotional outcomes at Kindergarten entry via its effect on early childhood parenting behavior and cognitive development. The multi-sample model revealed significant differences in the way in which early parenting behavior exerted its influence on outcomes at Kindergarten entry in preterm children compared to full-term children. For preterm children, parenting indirectly influenced social-emotional outcomes via early cognitive functioning. Findings highlight the importance of early identification and targeted parenting programs to support early cognitive development in preterm children. Copyright © 2014 Elsevier Ltd. All rights reserved.

Risk of Spontaneous Preterm Birth in Relation to Maternal Exposure to Intimate Partner Violence During Pregnancy in Peru

PubMed Central

Sanchez, Sixto E.; Alva, Andrea V.; Chang, Guillermo Diez; Qiu, Chungfang; Yanez, David; Gelaye, Bizu; Williams, Michelle A.

2012-01-01

Objective Intimate partner violence (IPV) is increasingly recognized as an important cause of maternal and perinatal morbidity. We assessed the relation between IPV and risk of spontaneous preterm birth (PTB) among Peruvian women. Methods The study was conducted among 479 pregnant women who delivered a preterm singleton infant (<37 weeks gestation) and 480 controls (≥37 weeks gestation). Participants’ exposure to physical and emotional violence during pregnancy was collected during in-person interviews conducted after delivery and while patients were in hospital. Odds ratios (aOR) and 95% confidence intervals (CI) were estimated from logistic regression models. Results The prevalence of any IPV during pregnancy was 52.2% among cases and 34.6% among controls. Compared with those reporting no exposure to IPV during pregnancy, women reporting any exposure had a 2.1-fold increased risk of PTB (95% CI 1.59–2.68). The association was attenuated slightly after adjusting for maternal age, pre-pregnancy weight, and other covariates (OR=1.99; 95% CI: 1.52–2.61). Emotional abuse in the absence of physical violence was associated with a 1.6-fold (95% CI 1.21–2.15) increased risk of PTB. Emotional and physical abuse during pregnancy was associated with a 4.7-fold increased risk of PTB (95% CI 2.74–7.92). Associations of similar directions and magnitudes were observed when PTB were sub-categorized according to clinical presentation or severity. Conclusion IPV among pregnant women is common and is associated with an increased risk of PTB. Our findings and those of others support recent calls for coordinated global health efforts to prevent violence against women. PMID:22527763

Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study

PubMed Central

Weber-Schoendorfer, Corinna; Oppermann, Marc; Wacker, Evelin; Bernard, Nathalie; Beghin, Delphine; Cuppers-Maarschalkerweerd, Benedikte; Richardson, Jonathan L; Rothuizen, Laura E; Pistelli, Alessandra; Malm, Heli; Eleftheriou, Georgios; Kennedy, Debra; Kadioglu Duman, Mine; Meister, Reinhard; Schaefer, Christof

2015-01-01

Aims TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors. Methods Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. Results In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. Conclusions TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs. PMID:25808588

Risk of spontaneous preterm delivery in a low-risk population: the impact of maternal febrile episodes, urinary tract infection, pneumonia and ear-nose-throat infections.

PubMed

Morken, Nils-Halvdan; Gunnes, Nina; Magnus, Per; Jacobsson, Bo

2011-12-01

To assess the associations between maternal infections during pregnancy (i.e. ear-nose-throat infection, pneumonia, urinary tract infection, febrile episodes and influenza-like infection) and spontaneous preterm delivery (SPTD). Prospective questionnaire data from the Norwegian Mother and Child Cohort (MoBa) study, including more than 100000 pregnancies and, collected during 1999-2008, were used. Linked data from the Medical Birth Registry of Norway were added. SPTD occurring between gestational weeks 22+0 days and 36+6 days was the main outcome. Data were analysed in two steps because questionnaires (including information about occurrence of the various infections so far) were completed at different stages of pregnancy. Hazard ratios (HR) were obtained using Cox regression. The SPTD proportion was low in this cohort: 2.9% and 2.7% at the two analysis steps, respectively. After exclusions, 67310 and 60689 pregnancies, respectively, remained for the analyses. Ear-nose-throat infections occurring before week 17 were associated with an increased risk of SPTD in the first (HR: 1.27, 95% CI: 1.08-1.50) and second (HR: 1.26, 95% CI: 1.04-1.52) step of the analysis, but not if occurring later in pregnancy. None of the other maternal infections were associated with an increased risk of SPTD. In this low-risk population, ear-nose-throat infection in early pregnancy was associated with an increased risk of SPTD. However, infectious morbidity in later pregnancy was not. Thus, the link between maternal infection and preterm delivery may vary in different populations and health care settings. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Auditory maturation in premature infants: a potential pitfall for early cochlear implantation.

PubMed

Hof, Janny R; Stokroos, Robert J; Wix, Eduard; Chenault, Mickey; Gelders, Els; Brokx, Jan

2013-08-01

To describe spontaneous hearing improvement in the first years of life of a number of preterm neonates relative to cochlear implant candidacy. Retrospective case study. Hearing levels of 14 preterm neonates (mean gestational age at birth = 29 weeks) referred after newborn hearing screening were evaluated. Initial hearing thresholds ranged from 40 to 105 dBHL (mean = 85 dBHL). Hearing level improved to normal levels for four neonates and to moderate levels for five, whereas for five neonates, no improvement in hearing thresholds was observed and cochlear implantation was recommended. Three of the four neonates in whom the hearing improved to normal levels were born prior to 28 weeks gestational age. Hearing improvement was mainly observed prior to a gestational age of 80 weeks. Delayed maturation of an immature auditory pathway might be an important reason for referral after newborn hearing screening in premature infants. Caution is advised regarding early cochlear implantation in preterm born infants. Audiological follow-ups until at least 80 weeks gestational age are therefore recommended. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Factors implicated in the initiation of human parturition in term and preterm labor: a review.

PubMed

Ravanos, Konstantinos; Dagklis, Themistoklis; Petousis, Stamatios; Margioula-Siarkou, Chrysoula; Prapas, Yannis; Prapas, Nikolaos

2015-01-01

After accommodating the pregnancy for an average of 40 weeks, the uterus expels the fetus, the placenta and the membranes through the birth canal in a process named parturition. The absolute sequence of events that trigger and sustain human parturition are not yet fully clarified. Evidence suggests that spontaneous preterm and term labor seem to share a common inflammatory pathway. However, there are several other factors being involved in the initiation of human parturition. Placental corticotropin releasing hormone production seems to serve as a placental clock that might be set to ring earlier or later determining the duration of pregnancy and timing of labor. Estrogens do not cause contractions but their properties seem to capacitate uterus to coordinate and enhance contractions. Cytokines, prostaglandins, nitric oxide and steroids seem also to induce ripening by mediating remodeling of the extracellular matrix and collagen. Infection and microbe invasion resulting in chorioamnionitis also represents a common cause of early preterm labour. This review provides an overview of all these factors considered to be implicated in the initiation of human parturition.

A Norwegian prospective study of preterm mother-infant interactions at 6 and 18 months and the impact of maternal mental health problems, pregnancy and birth complications.

PubMed

Misund, Aud R; Bråten, Stein; Nerdrum, Per; Pripp, Are Hugo; Diseth, Trond H

2016-05-04

Pregnancy, birth and health complications, maternal mental health problems following preterm birth and their possible impact on early mother-infant interaction at 6 and 18 months corrected age (CA) were explored. Predictors of mother-infant interaction at 18 months CA were identified. This prospective longitudinal and observational study included 33 preterm mother-infant (<33 gestational age (GA)) interactions at 6 and 18 months CA from a socioeconomic low-risk, middle-class sample. The Parent-Child Early Relational Assessment (PCERA) scale was used to assess the mother-infant interaction. 'Bleeding in pregnancy' predicted lower quality in preterm mother-infant interaction in 6 PCERA scales, while high 'maternal trait anxiety' predicted higher interactional quality in 2 PCERA scales and 'family size' predicted lower interactional quality in 1 PCERA scale at 18 months CA. Mothers with symptoms of post-traumatic stress reactions, general psychological distress and anxiety at 2 weeks postpartum (PP) showed significantly better outcome than mothers without symptoms in 6 PCERA subscales at 6 months CA and 2 PCERA subscales at 18 months CA. Our study detected a correspondence between early pregnancy complications and lower quality of preterm mother-infant interaction, and an association between high levels of maternal mental health problems and better quality in preterm mother-infant interaction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Birth-Weight, Pregnancy Term, Pre-Natal and Natal Complications Related to Child's Dental Anomalies.

PubMed

Prokocimer, T; Amir, E; Blumer, S; Peretz, B

2015-01-01

This cross-sectional study was aimed at determining whether certain pre-natal and natal conditions can predict specific dental anomalies. The conditions observed were: low birth-weight, preterm birth, pre-natal & natal complications. The dental anomalies observed were: enamel defects, total number of decayed, missing and filled teeth (total DMFT), disturbances in the tooth shape and disturbances in the number of teeth. Out of more than 2000 medical files of children aged 2-17 years old which were reviewed, 300 files met the selection criteria. Information recorded from the files included: age, gender, health status (the ASA physical status classification system by the American Society of Anesthesiologists), birth week, birth weight, total DMFT, hypomineralization, abnormal tooth shape, abnormal number of teeth and hypoplasia. Twenty one children out of 300 (7%) were born after a high-risk pregnancy, 25 children (8.3%) were born after high-risk birth, 20 children (6.7%) were born preterm - before week 37, and 29 children (9.7%) were born with a low birth weight (LBW) - 2500 grams or less. A relationship between a preterm birth and LBW to hypomineralization was found. And a relationship between a preterm birth and high-risk pregnancy to abnormal number of teeth was found. No relationship was found between birth (normal/high-risk) and the other parameters inspected. Preterm birth and LBW may predict hypomineralization in both primary and permanent dentitions. Furthermore, the study demonstrated that preterm birth and high-risk pregnancy may predict abnormal number of teeth in both dentitions.

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

PubMed

Norman, Jane E; Mackenzie, Fiona; Owen, Philip; Mactier, Helen; Hanretty, Kevin; Cooper, Sarah; Calder, Andrew; Mires, Gary; Danielian, Peter; Sturgiss, Stephen; MacLennan, Graeme; Tydeman, Graham; Thornton, Steven; Martin, Bill; Thornton, James G; Neilson, James P; Norrie, John

2009-06-13

Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51). Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. Chief Scientist Office of the Scottish Government Health Directorate.

Perinatal Risks in “Late Motherhood” Defined Based On Parity and Preterm Birth Rate – an Analysis of the German Perinatal Survey (20th Communication)

PubMed Central

Schure, V.; Voigt, M.; Schild, R. L.; Hesse, V.; Carstensen, M.; Schneider, K. T. M.; Straube, S.

2012-01-01

Aim: “Late motherhood” is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what “late motherhood” associated with “high risk” is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998–2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of “late” mothers (with high preterm birth rates) with “control” groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the “control” group included women aged 22–26 (27–31; 29–33) years. Women in the “late motherhood” group were aged > 33 (> 35; > 38) years. Results: The “late motherhood” groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the “control” group, but only in 84.5 % (90 %; 90.4 %) in the “late motherhood” group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the “control” group, but only in 51.4 % (72.2 %; 76.4 %) in the “late motherhood” group. Five-minute APGAR scores were likewise worse for neonates of “late” mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: “Late motherhood” that is associated with greater perinatal risks can be defined based on parity and preterm birth rate. PMID:25253904

Early urinary biomarkers of acute kidney injury in preterm infants.

PubMed

Hanna, Mina; Brophy, Patrick D; Giannone, Peter J; Joshi, Mandar S; Bauer, John A; RamachandraRao, Satish

2016-08-01

Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

Does the development of executive functioning in infants born preterm benefit from maternal directiveness?

PubMed

van de Weijer-Bergsma, Eva; Wijnroks, Lex; van Haastert, Ingrid C; Boom, Jan; Jongmans, Marian J

2016-12-01

Problems in early development of executive functioning may underlie the vulnerability and individual variability of infants born preterm for behavioral and learning problems. Parenting behaviors may aggravate or temper this increased risk for dysfunction. This study assessed how maternal parenting behaviors predict individual differences in early development of executive functioning in infants born preterm, and whether this varies with infant temperament, i.e., self-regulation. Participants were 76 infants born preterm (≤36weeks' gestation and <2500g birth weight) and their mothers. Maternal sensitive responsiveness and directiveness were observed during a mother-infant interaction situation at 7, 10 and 14months corrected age. At the same ages, executive functioning was measured using the A-not-B task. An infant self-regulation questionnaire (IBQ-R) was completed by mothers at 7months. After controlling for perinatal risk factors, Multivariate Latent Growth Modeling showed that consistently higher levels of maternal directiveness predicted a stronger increase in A-not-B performance, which did not vary with infant self-regulation. No relationship between maternal sensitive responsiveness and development in A-not-B performance in infants born preterm was found. These results suggest that preterm infants' early executive functioning development in the first year of life may benefit from a more and consistent directive approach by their mothers. These findings have important implications for early intervention programs aimed at facilitating preterm infants' development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antioxidative defence mechanisms against reactive oxygen species in bovine retained and not-retained placenta: activity of glutathione peroxidase, glutathione transferase, catalase and superoxide dismutase.

PubMed

Kankofer, M

2001-05-01

Glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), catalase (CAT) and superoxide dismutase (SOD)-the members of enzymatic antioxidative defence mechanisms against reactive oxygen species-may play an important role in proper or improper release of bovine fetal membranes. The aim of the following study was the determination of GSH-Px, GSH-Tr, CAT and SOD activity in order to define antioxidative status of bovine placenta during retention of fetal membranes (RFM) in cows. Placental samples were collected immediately after spontaneous parturition or during caesarean section before term and at term and divided into six groups as follows: A: caesarean section before term without RFM; B: caesarean section before term with RFM; C: caesarean section at term without RFM; D: caesarean section at term with RFM; E: spontaneous delivery at term without RFM; F: spontaneous delivery at term with RFM. The enzyme activities in placental homogenates were measured spectrophotometrically. GSH-Px activity was statistically significantly higher in fetal than in maternal placenta in all examined groups, increased towards parturition and was higher in caesarean section groups than spontaneous delivery groups. Statistically significantly higher activities were noticed in retained than not-retained placentae. GSH-Tr activity was significantly lower in fetal than in maternal placenta. In preterm groups, the activity was statistically significantly higher in retained than not retained placenta. In term groups, the opposite relationship was observed, higher values in caesarean section groups than spontaneous delivery were noticed. CAT activity was statistically significantly higher in fetal than in maternal part of placenta in all groups examined. The highest values in C and D groups and the differences between retained and not-retained placenta were observed. SOD exhibited the highest values in preterm placenta and alterations between retained and not-retained fetal membranes. In conclusion, the activities of GSH-Px, GSH-Tr, CAT and SOD are altered in cases of retained fetal membranes which may suggest the activation of antioxidative mechanisms caused by the imbalance between production and neutralization of reactive oxygen species. Copyright 2001 Harcourt Publishers Ltd.

Interaction between Maternal Passive Smoking during Pregnancy and CYP1A1 and GSTs Polymorphisms on Spontaneous Preterm Delivery

PubMed Central

Luo, Yi-Juan; Wen, Xiao-Zhong; Ding, Peng; He, Yan-Hui; Xie, Chuan-Bo; Liu, Tao; Lin, Jian-miao; Yuan, Shi-Xin; Guo, Xiao-Ling; Jia, De-Qin; Chen, Li-Hua; Huang, Bao-Zhen; Chen, Wei-Qing

2012-01-01

Objective The present study aimed to examine the association between maternal passive smoking during pregnancy and the risk of spontaneous PTD and to explore the potential interaction of the single or joint gene polymorphism of CYP1A1 and GSTs with maternal passive smoking on the risk of spontaneous PTD. Method We investigated whether the association between maternal passive smoking and PTD can be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic regression to test gene-passive smoking interaction, adjusting for maternal socio-demographics and prepregnancy body mass index. Results Overall, maternal passive smoking during pregnancy was associated with higher risk of PTD (adjusted odds ratio = 2.20 [95% confidence interval: 1.56–3.12]). This association was modified by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher risk of PTD among those women with CYP1A1 “TC/CC”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 2.66 [95% CI: 1.19–5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs, maternal passive smoking was associated with higher risk of PTD only among those women with CYP1A1“AG/GG”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 3.00 [95% CI: 1.17–7.74]; P-value: 0.023). Conclusions Our findings suggest that the combined genotypes of CYP1A1 and GSTs can help to identify vulnerable pregnant women who are subject to high risk of spontaneous PTD due to passive smoking. PMID:23152866

Lipoprotein particle concentration measured by nuclear magnetic resonance spectroscopy is associated with gestational age at delivery: a prospective cohort study.

PubMed

Grace, M R; Vladutiu, C J; Nethery, R C; Siega-Riz, A M; Manuck, T A; Herring, A H; Savitz, D; Thorp, J T

2018-06-01

To estimate the association between lipoprotein particle concentrations in pregnancy and gestational age at delivery. Prospective cohort study. The study was conducted in the USA at the University of North Carolina. We assessed 715 women enrolled in the Pregnancy, Infection, and Nutrition study from 2001 to 2005. Fasting blood was collected at two time points (<20 and 24-29 weeks of gestation). Nuclear magnetic resonance (NMR) quantified lipoprotein particle concentrations [low-density lipoprotein (LDL), high-density lipoprotein (HDL), very-low density lipoprotein (VLDL)] and 10 subclasses of lipoproteins. Concentrations were assessed as continuous measures, with the exception of medium HDL which was classified as any or no detectable level, given its distribution. Cox proportional hazards models estimated hazard ratios (HR) for gestational age at delivery adjusting for covariates. Gestational age at delivery, preterm birth (<37 weeks of gestation), and spontaneous preterm birth. At <20 weeks of gestation, three lipoproteins were associated with later gestational ages at delivery [large LDL NMR (HR 0.78, 95% CI 0.64-0.96), total VLDL NMR (HR 0.77, 95% CI 0.61-0.98), and small VLDL NMR (HR 0.78, 95% CI 0.62-0.98], whereas large VLDL NMR (HR 1.19, 95% CI 1.01-1.41) was associated with a greater hazard of earlier delivery. At 24-28 weeks of gestation, average VLDL NMR (HR 1.25, 95% CI 1.03-1.51) and a detectable level of medium HDL NMR (HR 1.90, 95% CI 1.19-3.02) were associated with earlier gestational ages at delivery. In this sample of pregnant women, particle concentrations of VLDL NMR , LDL NMR , IDL NMR , and HDL NMR were each independently associated with gestational age at delivery for all deliveries or spontaneous deliveries <37 weeks of gestation. These findings may help formulate hypotheses for future studies of the complex relationship between maternal lipoproteins and preterm birth. Nuclear magnetic resonance spectroscopy may identify lipoprotein particles associated with preterm delivery. © 2017 Royal College of Obstetricians and Gynaecologists.

The clinical content of preconception care: reproductive history.

PubMed

Stubblefield, Phillip G; Coonrod, Dean V; Reddy, Uma M; Sayegh, Raja; Nicholson, Wanda; Rychlik, Daniel F; Jack, Brian W

2008-12-01

A history of previous birth of a low birthweight infant, previous cesarean sections, multiple previous spontaneous abortions, prior stillbirth, or uterine anomaly identifies women at increased risk for recurrent abortion, preterm birth, or stillbirth. We review the evidence for the potential benefit of reproductive history in identifying strategies for evaluation and treatment to prevent recurrent adverse pregnancy outcome. We offer evidence-based recommendations for management of women with these histories.

Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

PubMed

Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

2016-01-01

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

The relationship between resolution of asymptomatic bacterial vaginosis and spontaneous preterm birth in fetal fibronectin-positive women.

PubMed

Hendler, Israel; Andrews, William W; Carey, Christopher J; Klebanoff, Mark A; Noble, William D; Sibai, Baha M; Hillier, Sharon L; Dudley, Donald; Ernest, Joseph M; Leveno, Kenneth J; Wapner, Ronald; Iams, Jay D; Varner, Michael; Moawad, Atef; Miodovnik, Menachem; O'Sullivan, Mary J; Van Dorsten, Peter J

2007-11-01

The purpose of this study was to determine the impact of persistent bacterial vaginosis (BV) on the occurrence of spontaneous preterm birth (SPB) in women who test positive for fetal fibronectin. This is a secondary analysis of a subset of pregnant women who tested positive for BV and fetal fibronectin between 16(0/7) and 25(6/7) weeks of gestation and who participated in randomized placebo controlled trials of antibiotic therapy. Nugent's criteria were used for the diagnosis of BV. Patients were reassessed for the presence of BV after treatment. The rate of SPB at <34 weeks of gestation was analyzed on the basis of treatment mode and BV status at the follow-up visit. The primary studies included a total of 3285 women. A subset of 215 women met the criteria for this analysis. Seventy-seven of 100 patients (77%) in the antibiotics group vs 33 of the 115 patients (28.7%) in the placebo group became BV negative (P < .0001). The rate of SPB at <34 weeks of gestation was lower for BV resolution compared with persistent BV (0 vs 5.7%, respectively; P = .01). In women who tested positive for fetal fibronectin and BV, resolution of BV is associated with less SPB before 34 weeks of gestation.

Changes in amniotic fluid concentration of thrombin-antithrombin III complexes in patients with preterm labor: evidence of an increased thrombin generation

PubMed Central

Erez, Offer; Romero, Roberto; Vaisbuch, Edi; Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Gotsch, Francesca; Gomez, Ricardo; Maymon, Eli; Pacora, Percy; Edwin, Samuel S.; Kim, Chong Jai; Than, Nandor Gabor; Mittal, Pooja; Yeo, Lami; Dong, Zhong; Yoon, Bo Hyun; Hassan, Sonia S; Mazor, Moshe

2012-01-01

Objective Preterm labor is associated with excessive maternal thrombin generation as evidenced by increased circulating thrombin–antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation. The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with increased amniotic fluid (AF) thrombin generation in women with preterm and term deliveries. Study design This cross-sectional study included the following groups: 1) mid-trimester (n=74); 2) term not in labor (n=39); 3) term in labor (n=25); 4) term in labor with IAI (n=22); 5) spontaneous preterm labor (PTL) who delivered at term (n=62); 6) PTL without IAI who delivered preterm (n=59); 7) PTL with IAI (n=71). The AF TAT III complexes concentration was measured by ELISA. Non-parametric statistics were used for analysis. Results 1) TAT III complexes were identified in all AF samples; 2) patients with PTL who delivered preterm, with and without IAI, had a significantly higher median AF TAT III complexes concentration than those with an episode of PTL who delivered at term (p<0.001, p=0.03, respectively); 3) among patients with preterm labor without IAI, elevated AF TAT III complexes concentration were independently associated with a shorter amniocentesis-to-delivery interval (hazard ratio- 1.5, 95%CI, 1.07–2.1); 4) among patients at term, those with IAI had a higher median AF TAT III complexes concentration than those without IAI, whether in labor or not in labor (p=0.02); 5) there was no significant difference between the median AF TAT III complexes concentration of patients at term with and without labor; and 6) patients who had a mid-trimester amniocentesis had a lower median AF TAT III complexes concentration than that of patients at term not in labor (p<0.001). Conclusions We present herein a distinct difference in the pattern of intra-amniotic thrombin generation between term and preterm parturition. Preterm labor leading to preterm delivery is associated with an increased intra-amniotic thrombin generation, regardless of the presence of IAI. In contrast, term delivery is associated with an increased intra-amniotic thrombin generation only in patients with IAI. PMID:19900035

Detection of bloodstream infections and prediction of bronchopulmonary dysplasia in preterm neonates with an electronic nose.

PubMed

Rogosch, Tobias; Herrmann, Nina; Maier, Rolf F; Domann, Eugen; Hattesohl, Akira; Koczulla, Andreas Rembert; Zemlin, Michael

2014-09-01

We show that smellprints of volatile organic components measured with an electronic nose (Cyranose 320; Smiths Detection Group Ltd, Watford, United Kingdom) differ between tracheal aspirates from preterm neonates with or without laboratory-confirmed bloodstream infections and with or without subsequent development of bronchopulmonary dysplasia. Tracheal aspirate smellprints could be useful noninvasive diagnostic markers for preterm neonates. Copyright © 2014 Elsevier Inc. All rights reserved.

Outcome of pregnancy complicated by threatened abortion.

PubMed

Dongol, A; Mool, S; Tiwari, P

2011-01-01

Threatened abortion is the most common complication in the first half of pregnancy. Most of these pregnancies continue to term with or without treatment. Spontaneous abortion occurs in less than 30% of these women. Threatened abortion had been shown to be associated with increased incidence of antepartum haemorrhage, preterm labour and intra uterine growth retardation. This study was to asses the outcome of threatened abortion following treatment. This prospective study was carried out in Dhulikhel Hospital - Kathmandu University Hospital from January 2009 till May 2010. Total 70 cases of threatened abortion were selected, managed with complete bed rest till 48 hrs of cessation of bleeding, folic acid supplementation, uterine sedative, and hormonal treatment till 28 weeks of gestation. Ultrasonogram was performed for diagnosis and to detect the presence of subchorionic hematoma. Patients were followed up until spontaneous abortion or up to delivery of the fetus. The measures used for the analysis were maternal age, parity, gestational age at the time of presentation, previous abortions, presence of subchorionic hematoma, complete abortion, continuation of pregnancy, antepartum hemorrhage, intrauterine growth retardation and intrauterine death of fetus. Out of 70 cases subchorionic haematoma was found in 30 (42.9%) cases. There were 12 (17.1%) patients who spontaneously aborted after diagnosis of threatened abortion during hospital stay, 5 (7.1%) aborted on subsequent visits while 53 (75.8%) continued pregnancy till term. Among those who continued pregnancy intrauterine growth retardation was seen in 7 (13.2%), antepartum hemorrhage in 4 (7.5%), preterm premature rupture of membrane in 3 (5.66%) and IUD in 3 (5.66%). Spontaneous abortion was found more in cases with subchorionic hematoma of size more than 20 cm2. In cases of threatened abortion with or without the presence of subchorionic hematoma, prognostic outcome is better following treatment with bed rest, uterine sedatives, folic acid supplementation and hormonal treatment.

Preterm birth and low birth weight among in vitro fertilization twins: a systematic review and meta-analyses.

PubMed

McDonald, Sarah D; Han, Zhen; Mulla, Sohail; Ohlsson, Arne; Beyene, Joseph; Murphy, Kellie E

2010-02-01

The objective of this systematic review and meta-analyses was to determine the risks of preterm birth (PTB) and low birth weight (LBW) in twins conceived through in vitro fertilization (IVF) or IVF/intracytoplasmic sperm injection (ICSI) compared to spontaneously-conceived twins after matching or controlling for at least maternal age. The MOOSE guidelines for meta-analysis of observational studies were followed. Medline and Embase were searched using comprehensive search strategies. Bibliographies of identified articles were reviewed. English language studies of twins conceived by IVF or IVF/ICSI, compared with spontaneously twins, that matched or controlled for at least maternal age. Two reviewers independently assessed titles, abstracts, articles and study quality and extracted data. Statistical analyses were performed using the Review Manager (RevMan 5.0) software using a random effects model. Dichotomous data were meta-analyzed using relative risks (RR) and continuous data with a weighted mean difference. Twelve studies were included which had a total of 4385 twins conceived after IVF or IVF/ICSI (one stillbirth was excluded) and 11,793 spontaneously-conceived twins. After matching or controlling for maternal age and often other factors, compared to spontaneously-conceived twins, IVF twins had increased risks of both our primary outcomes: PTB (RR 1.23, 95% CI 1.09, 1.41) and LBW (<2500 g, RR 1.14, 95% CI 1.06, 1.22). They were at increased risk for PTB <32-33 weeks (RR 1.63, 95% CI 1.17, 2.27) although the risks of late PTB (32-36 weeks, RR 1.12, 95% CI 0.85, 1.47), very LBW (<1500 g, RR 1.28, 95% CI 0.73, 2.24), extremely LBW (<1000 g, RR 0.88, 0.04, 19.40), intrauterine growth restriction (RR 1.06, 95% CI 0.72, 1.55) and the difference in the duration of gestation (-0.5 weeks, 95% CI -1.2 weeks, 0.2 weeks) were not statistically significantly increased compared to spontaneously-conceived twins. IVF twins had significantly lower mean birth weights (-105 g, 95% CI -204 g, -3 g). IVF twins have small but significantly increased risks of PTB, LBW, and lower mean birth weight compared to spontaneously-conceived twins after matching or controlling for at least maternal age. 2009 Elsevier Ireland Ltd. All rights reserved.

Meta-Analysis of Maternal and Fetal Transcriptomic Data Elucidates the Role of Adaptive and Innate Immunity in Preterm Birth

PubMed Central

Vora, Bianca; Wang, Aolin; Kosti, Idit; Huang, Hongtai; Paranjpe, Ishan; Woodruff, Tracey J.; MacKenzie, Tippi; Sirota, Marina

2018-01-01

Preterm birth (PTB) is the leading cause of newborn deaths around the world. Spontaneous preterm birth (sPTB) accounts for two-thirds of all PTBs; however, there remains an unmet need of detecting and preventing sPTB. Although the dysregulation of the immune system has been implicated in various studies, small sizes and irreproducibility of results have limited identification of its role. Here, we present a cross-study meta-analysis to evaluate genome-wide differential gene expression signals in sPTB. A comprehensive search of the NIH genomic database for studies related to sPTB with maternal whole blood samples resulted in data from three separate studies consisting of 339 samples. After aggregating and normalizing these transcriptomic datasets and performing a meta-analysis, we identified 210 genes that were differentially expressed in sPTB relative to term birth. These genes were enriched in immune-related pathways, showing upregulation of innate immunity and downregulation of adaptive immunity in women who delivered preterm. An additional analysis found several of these differentially expressed at mid-gestation, suggesting their potential to be clinically relevant biomarkers. Furthermore, a complementary analysis identified 473 genes differentially expressed in preterm cord blood samples. However, these genes demonstrated downregulation of the innate immune system, a stark contrast to findings using maternal blood samples. These immune-related findings were further confirmed by cell deconvolution as well as upstream transcription and cytokine regulation analyses. Overall, this study identified a strong immune signature related to sPTB as well as several potential biomarkers that could be translated to clinical use.

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis.

PubMed

Stock, Sarah J; Wotherspoon, Lisa M; Boyd, Kathleen A; Morris, Rachel K; Dorling, Jon; Jackson, Lesley; Chandiramani, Manju; David, Anna L; Khalil, Asma; Shennan, Andrew; Hodgetts Morton, Victoria; Lavender, Tina; Khan, Khalid; Harper-Clarke, Susan; Mol, Ben W; Riley, Richard D; Norrie, John; Norman, Jane E

2018-04-07

The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors. The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing). The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). CRD42015027590. Protocol version 2, date 1 November 2016. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

New developments in cerebral blood flow autoregulation analysis in preterm infants: a mechanistic approach.

PubMed

Riera, Joan; Cabañas, Fernando; Serrano, José Javier; Madero, Rosario; Pellicer, Adelina

2016-03-01

Impaired autoregulation capacity implies that changes in cerebral perfusion follow changes in blood pressure; however, no analytical method has explored such a signal causality relationship in infants. We sought to develop a method to assess cerebral autoregulation from a mechanistic point of view and explored the predictive capacity of the method to classify infants at risk for adverse outcomes. The partial directed coherence (PDC) method, which considers synchronicity and directionality of signal dependence across frequencies, was used to analyze the relationship between spontaneous changes in mean arterial pressure (MAP) and the cerebral tissue oxygenation index (TOI). PDCMAP>TOI indicated that changes in TOI were induced by MAP changes, and PDCTOI>MAP indicated the opposite. The PDCMAP>TOI and PDCTOI>MAP values differed. PDCMAP>TOI adjusted by gestational age predicted low superior vena cava flow (≤41 ml/kg per min), with an area under the receiver operating characteristic curve of 0.72 (95% CI: 0.63-0.81; P < 0.001), whereas PDCTOI>MAP did not. The adjusted pPDCMAP>TOI (the average value per patient) predicted severe intracranial hemorrhage and mortality. PDCMAP>TOI allows for a noninvasive physiological interpretation of the pressure autoregulation process in neonates. PDCMAP>TOI is a good classifier for infants at risk of brain hypoperfusion and adverse outcomes.

Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

PubMed

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

Towards BirthAlert—A Clinical Device Intended for Early Preterm Birth Detection

PubMed Central

Etemadi, Mozziyar; Chung, Philip; Heller, J. Alex; Liu, Jonathan A.; Rand, Larry; Roy, Shuvo

2015-01-01

Preterm birth causes 1 million infant deaths worldwide every year, making it the leading cause of infant mortality. Existing diagnostic tests such as transvaginal ultrasound or fetal fibronectin either cannot determine if preterm birth will occur in the future or can only predict the occurrence once cervical shortening has begun, at which point it is too late to reverse the accelerated parturition process. Using iterative and rapid prototyping techniques, we have developed an intravaginal proof-of-concept device that measures both cervical bioimpedance and cervical fluorescence to characterize microstructural changes in a pregnant woman's cervix in hopes of detecting preterm birth before macroscopic changes manifest in the tissue. If successful, such an early alert during this “silent phase” of the preterm birth syndrome may open a new window of opportunity for interventions that may reverse and avoid preterm birth altogether. PMID:23893706

Deep grey matter growth predicts neurodevelopmental outcomes in very preterm children.

PubMed

Young, Julia M; Powell, Tamara L; Morgan, Benjamin R; Card, Dallas; Lee, Wayne; Smith, Mary Lou; Sled, John G; Taylor, Margot J

2015-05-01

We evaluated whether the volume and growth rate of critical brain structures measured by MRI in the first weeks of life following very preterm (<32/40 weeks) birth could predict subsequent neurodevelopmental outcomes at 4 years of age. A significant proportion of children born very prematurely have cognitive deficits, but these problems are often only detected at early school age. Structural T2-weighted magnetic resonance images were acquired in 96 very preterm neonates scanned within 2 weeks of birth and 70 of these at term-equivalent age. An automated 3D image analysis procedure was used to measure the volume of selected brain structures across all scans and time points. At 4 years of age, 53 children returned for neuropsychological assessments evaluating IQ, language and visual motor integration. Associations with maternal education and perinatal measures were also explored. Multiple regression analyses revealed that growth of the caudate and globus pallidus between preterm birth and term-equivalent age predicted visual motor integration scores after controlling for sex and gestational age. Further associations were found between caudate and putamen growth with IQ and language scores. Analyses at either preterm or term-equivalent age only found associations between normalized deep grey matter growth and visual motor integration scores at term-equivalent age. Maternal education levels were associated with measures of IQ and language, but not visual motor integration. Thalamic growth was additionally linked with perinatal measures and presence of white matter lesions. These results highlight deep grey matter growth rates as promising biomarkers of long-term outcomes following very preterm birth, and contribute to our understanding of the brain-behaviour relations in these children. Copyright © 2015 Elsevier Inc. All rights reserved.

Preterm Infants Who Are Prone to Distress: Differential Effects of Parenting on 36-month Behavioral and Cognitive Outcomes

PubMed Central

Poehlmann, Julie; Hane, Amanda; Burnson, Cynthia; Maleck, Sarah; Hamburger, Elizabeth; Shah, Prachi E.

2012-01-01

Background The differential susceptibility (DS) model suggests that temperamentally prone-to-distress infants may exhibit adverse outcomes in negative environments but optimal outcomes in positive environments. This study explored temperament, parenting, and 36-month cognition and behavior in preterm infants using the DS model. We hypothesized that temperamentally prone to distress preterm infants would exhibit more optimal cognition and fewer behavior problems when early parenting was positive; and less optimal cognition and more behavior problems when early parenting was less positive. Methods Participants included 109 preterm infants (gestation < 37 weeks) and their mothers. We assessed neonatal risk and basal vagal tone in the neonatal intensive care unit (NICU); infant temperament and parenting interactions at 9 months postterm; and child behavior and cognitive skills at 36 months postterm. Hierarchical regression analyses tested study hypotheses. Results Temperamentally prone-to-distress infants exhibited more externalizing problems if they experienced more critical parenting at 9 months (β= -.20, p<0.05) but fewer externalizing problems with more positive parenting. Similarly, variations in maternal positive affect (β= .25, p< .01) and intrusive behaviors (β= .23, p< .05) at 9 months predicted 36-month cognition at high but not at low levels of infant temperamental distress. Higher basal vagal tone predicted fewer externalizing problems (β= -.19, p< .05). Conclusions Early parenting behaviors relate to later behavior and development in preterm infants who are temperamentally prone to distress, and neonatal basal vagal tone predicts subsequent externalizing behaviors. These findings suggest that both biological reactivity and quality of caregiving are important predictors for later outcomes in preterm infants and may be considered as foci for developmental surveillance and interventions. PMID:22582942

Treatment of vaginal candidiasis for the prevention of preterm birth: a systematic review and meta-analysis.

PubMed

Roberts, Christine L; Algert, Charles S; Rickard, Kristen L; Morris, Jonathan M

2015-03-21

Recognition that ascending infection leads to preterm birth has led to a number of studies that have evaluated the treatment of vaginal infections in pregnancy to reduce preterm birth rates. However, the role of candidiasis is relatively unexplored. Our aim was to undertake a systematic review and meta-analysis to assess whether treatment of pregnant women with vulvovaginal candidiasis reduces preterm birth rates and other adverse birth outcomes. We undertook a systematic review and meta-analysis of published randomised controlled trials (RCTs) in which pregnant women were treated for vulvovaginal candidiasis (compared to placebo or no treatment) and where preterm birth was reported as an outcome. Trials were identified by searching the Cochrane Central Register of Controlled Trials, Medline and Embase databases to January 2014. Trial eligibility and outcomes were pre-specified. Two reviewers independently assessed the studies against the agreed criteria and extracted relevant data using a standard data extraction form. Meta-analysis was used to calculate pooled rate ratios (RR) and 95% confidence intervals (CI) using a fixed-effects model. There were two eligible RCTs both among women with asymptomatic candidiasis, with a total of 685 women randomised. Both trials compared treatment with usual care (no screening for, or treatment of, asymptomatic candidiasis). Data from one trial involved a post-hoc subgroup analysis (n = 586) of a larger trial of treatment of 4,429 women with asymptomatic infections in pregnancy and the other was a pilot study (n = 99). There was a significant reduction in spontaneous preterm births in treated compared with untreated women (meta-analysis RR = 0.36, 95% CI = 0.17 to 0.75). Other outcomes were reported by one or neither trial. This systematic review found two trials comparing the treatment of asymptomatic vaginal candidiasis in pregnancy for the outcome of preterm birth. Although the effect estimate suggests that treatment of asymptomatic candidiasis may reduce the risk of preterm birth, the result needs to be interpreted with caution as the primary driver for the pooled estimate comes from a post-hoc (unplanned) subgroup analysis. A prospective trial with sufficient power to answer the clinical question 'does treatment of asymptomatic candidiasis in early pregnancy prevent preterm birth' is warranted. PROSPERO CRD42014009241.

Impact of neonatal risk and temperament on behavioral problems in toddlers born preterm.

PubMed

Guilherme Monte Cassiano, Rafaela; Gaspardo, Claudia Maria; Cordaro Bucker Furini, Guilherme; Martinez, Francisco Eulogio; Martins Linhares, Maria Beatriz

2016-12-01

Children born preterm are at risk for later developmental disorders. The present study examined the predictive effects of neonatal, sociodemographic, and temperament characteristics on behavioral outcomes at toddlerhood, in children born preterm. The sample included 100 toddlers born preterm and with very-low-birth-weight, and their mothers. Neonatal characteristics were evaluated using medical records. The mothers were interviewed using the Early Childhood Behavior Questionnaire for temperament assessment, and the Child Behavior Checklist for behavioral assessment. Multiple linear regression analyses were performed. Predictors of 39% of the variability of the total behavioral problems in toddlers born prematurely were: temperament with more Negative Affectivity and less Effortful Control, lower family socioeconomic status, and younger mothers at childbirth. Temperament with more Negative Affectivity and less Effortful Control and lower family socioeconomic status were predictors of 23% of the variability of internalizing behavioral problems. Additionally, 37% of the variability of externalizing behavioral problems was explained by temperament with more Negative Affectivity and less Effortful Control, and younger mothers at childbirth. The neonatal characteristics and stressful events in the neonatal intensive care unit did not predict behavioral problems at toddlerhood. However, temperament was a consistent predictor of behavioral problems in toddlers born preterm. Preventive follow-up programs could assess dispositional traits of temperament to provide early identification of preterm infants at high-risk for behavioral problems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of health compromising behaviors on preterm births.

PubMed

Dew, Paul C; Guillory, V James; Okah, Felix A; Cai, Jinwen; Hoff, Gerald L

2007-05-01

The objective of our study was to determine whether there were combined effects of smoking, alcohol, and illicit drug use during pregnancy on the frequency of preterm births, and if so, the magnitude of the association after adjusting for confounding factors. We conducted a retrospective cohort study of singleton live births in Kansas City, Missouri from 1990-2002. We defined health compromising behaviors as the use of cigarettes, alcohol, and illicit drugs. The effect of these behaviors on preterm births was considered for each substance individually, and in combination. The rates of preterm births for these groups were calculated. Using logistic regression, adjusted odds ratios were used to estimate the relative risk of preterm births among these groups. Over 13% of infants born to women who smoked were preterm, compared to 9.6% for non-smokers. Of infants born to women who reported alcohol use, 17.3% were preterm compared to 10.1% for non-drinkers. Smoking and alcohol use in combination was associated with 18.0% preterm births, while alcohol and drug use in combination was associated with 20.8% preterm births. The use of all three substances was associated with 31.4% preterm births. Women who engaged in health compromising behaviors during pregnancy showed an increased proportion of preterm births compared to those who did not. There is significant interaction between these behaviors leading to higher rates of preterm births than predicted by their additive effects. To decrease preterm births, we must deal with the effects of smoking, drinking, and drug use simultaneously.

Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial.

PubMed

Tita, Alan T; Doherty, Lindsay; Roberts, Jim M; Myatt, Leslie; Leveno, Kenneth J; Varner, Michael W; Wapner, Ronald J; Thorp, John M; Mercer, Brian M; Peaceman, Alan; Ramin, Susan M; Carpenter, Marshall W; Iams, Jay; Sciscione, Anthony; Harper, Margaret; Tolosa, Jorge E; Saade, George R; Sorokin, Yoram

2018-06-01

 To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB).  A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity.  Of 9,867 women, 10.4% ( N  = 1,038) were PTBs; 32.7% ( n  = 340) IPTBs and 67.3% ( n  = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI, 1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8 times).  Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Severe Diabetic Nephropathy in Type 1 Diabetes and Pregnancy - A Case Series

PubMed Central

Piccoli, Giorgina B.; Tavassoli, Elisabetta; Melluzza, Carmela; Grassi, Giorgio; Monzeglio, Clara; Donvito, Valentina; Leone, Filomena; Attini, Rossella; Ghiotto, Sara; Clari, Roberta; Moro, Irene; Fassio, Federica; Parisi, Silvia; Pilloni, Eleonora; Vigotti, Federica N.; Giuffrida, Domenica; Rolfo, Alessandro; Todros, Tullia

2013-01-01

BACKGROUND: Diabetes and nephropathy are important challenges during pregnancy, increasingly encountered because of the advances in maternal-fetal care. AIM: To evaluate the maternal and fetal outcomes recorded in "severe" diabetic nephropathy in type 1 diabetic patients referred to nephrological healtcare. METHODS: The study was performed in an outpatient unit dedicated to kidney diseases in pregnancy (with joint nephrological and obstetric follow-up and strict cooperation with the diabetes unit). 383 pregnancies were referred to the outpatient unit in 2000-2012, 14 of which were complicated by type 1 diabetes. The report includes 12 deliveries, including 2 pregnancies in 1 patient; one twin pregnancy; 2 spontaneous abortions were not included. All cases had long-standing type 1 diabetes (median of 21 (15-31) years), relatively high median age (35 (29-40) years) and end-organ damage (all patients presented laser-treated retinopathy and half of them clinical neuropathy). Median glomerular filtration rate (GFR) at referral was 67 ml/min (48-122.6), proteinuria was 1.6 g/day (0.1-6.3 g/day). RESULTS: Proteinuria steeply increased in 11/12 patients, reaching the nephrotic range in nine (6 above 5 g/day). One patient increased by 2 chronic kidney disease (CKD) stages. Support therapy included blood pressure and diabetes control, bed rest, and moderate protein restriction. All children were preterm (7 early preterm); early spontaneous labor occurred in 4/12 patients. All singletons were appropriate for gestational age and developed normally after birth. The male twin child died 6 days after birth (after surgery for great vessel transposition). CONCLUSIONS: Diabetic patients with severe diabetic nephropathy are still present a considerable challenge. Therefore, further investigations are required, particularly on proteinuria management and the occurrence of spontaneous labor. PMID:24172700

Amniotic Fluid Metabolomic Analysis in Spontaneous Preterm Birth

PubMed Central

Jones, Janice; Gunst, Phillip R.; Kacerovsky, Marian; Fortunato, Stephen J.; Saade, George R.; Basraon, Sanmaan

2014-01-01

Objective: To identify metabolic changes associated with early spontaneous preterm birth (PTB; <34 weeks) and term births, using high-throughput metabolomics of amniotic fluid (AF) in African American population. Method: In this study, AF samples retrieved from spontaneous PTB (<34 weeks [n = 25]) and normal term birth (n = 25) by transvaginal amniocentesis at the time of labor prior to delivery were subjected to metabolomics analysis. Equal volumes of samples were subjected to a standard solvent extraction method and analyzed using gas chromatography/mass spectrometry (MS) and liquid chromatography/MS/MS. Biochemicals were identified through matching of ion features to a library of biochemical standards. After log transformation and imputation of minimum observed values for each compound, t test, correlation tests, and false discovery rate corrections were used to identify differentially regulated metabolites. Data were controlled for clinical/demographic variables and medication during pregnancy. Results: Of 348 metabolites measured in AF samples, 121 metabolites had a gestational age effect and 116 differed significantly between PTB and term births. A majority of significantly altered metabolites could be classified into 3 categories, namely, (1) liver function, (2) fatty acid and coenzyme A (CoA) metabolism, and (3) histidine metabolism. The signature of altered liver function was apparent in many cytochrome P450-related pathways including bile acids, steroids, xanthines, heme, and phase II detoxification of xenobiotics with the largest fold change seen with pantothenol, a CoA synthesis inhibitor that was 8-fold more abundant in PTB. Conclusion: Global metabolic profiling of AF revealed alteration in hepatic metabolites involving xenobiotic detoxification and CoA metabolism in PTB. Maternal and/or fetal hepatic function differences may be developmentally related and its contribution PTB as a cause or effect of PTB is still unclear. PMID:24440995

Evaluation of potential factors predicting attainment of full gavage feedings in preterm infants

USDA-ARS?s Scientific Manuscript database

The clinical measures of gastric residuals and abdominal distention are often used to guide feeding in preterm infants, but there are few data demonstrating their usefulness. Similarly, techniques are now available to investigate gastrointestinal (GI) function noninvasively and safely, but their abi...

Prematurity and parental self-efficacy: the Preterm Parenting & Self-Efficacy Checklist.

PubMed

Pennell, Claire; Whittingham, Koa; Boyd, Roslyn; Sanders, Matthew; Colditz, Paul

2012-12-01

There is a lack of research investigating parental self-efficacy in parents of infants born preterm as well as a paucity of parental self-efficacy measures that are domain-specific and theoretically grounded. This study aimed to compare parental self-efficacy in parents of infants born term, preterm and very preterm as well as to test whether parental self-efficacy mediates the relationship between psychological symptoms and parental competence. In order to achieve this, a new measure of parental self-efficacy and parental competence relevant for the preterm population and consistent with Bandura's (1977, 1986, 1989) conceptualisation of self-efficacy was developed. Participants included 155 parents, 83 of whom were parents of very preterm (GA<32 weeks), 40 parents of preterm (GA<37 weeks) and 32 parents of term born infants. Parents completed the Preterm Parenting & Self-Efficacy Checklist (the new measure), Family Demographic Questionnaire, Depression Anxiety Stress Scale and Self-Efficacy Questionnaire. This initial study indicates that the Preterm Parenting & Self-Efficacy Checklist has adequate content validity, construct validity, internal consistency and split half reliability. Contrary to expectations, parents of very preterm infants did not report significantly lower overall levels of parental self-efficacy or significantly higher levels of psychological symptoms compared to parents of preterm and term infants. Parental self-efficacy about parenting tasks mediated the relationship between psychological symptoms and self perceived parental competence as predicted. Clinical implications of the results and suggestions for future research are discussed. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Epigenetic Biomarkers of Preterm Birth and Its Risk Factors

PubMed Central

Knight, Anna K.; Smith, Alicia K.

2016-01-01

A biomarker is a biological measure predictive of a normal or pathogenic process or response. Biomarkers are often useful for making clinical decisions and determining treatment course. One area where such biomarkers would be particularly useful is in identifying women at risk for preterm delivery and related pregnancy complications. Neonates born preterm have significant morbidity and mortality, both in the perinatal period and throughout the life course, and identifying women at risk of delivering preterm may allow for targeted interventions to prevent or delay preterm birth (PTB). In addition to identifying those at increased risk for preterm birth, biomarkers may be able to distinguish neonates at particular risk for future complications due to modifiable environmental factors, such as maternal smoking or alcohol use during pregnancy. Currently, there are no such biomarkers available, though candidate gene and epigenome-wide association studies have identified DNA methylation differences associated with PTB, its risk factors and its long-term outcomes. Further biomarker development is crucial to reducing the health burden associated with adverse intrauterine conditions and preterm birth, and the results of recent DNA methylation studies may advance that goal. PMID:27089367

Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues.

PubMed

van den Berg, C B; Chaves, I; Herzog, E M; Willemsen, S P; van der Horst, G T J; Steegers-Theunissen, R P M

2017-01-01

The placenta is important in providing a healthy environment for the fetus and plays a central role in the pathophysiology of preeclampsia (PE). Fetal and placental developments are influenced by epigenetic programming. There is some evidence that PE is controlled to an altered circadian homeostasis. In a nested case-control study embedded in the Rotterdam Periconceptional Cohort, we obtained placental tissue, umbilical cord leukocytes (UCL), and human umbilical venous endothelial cells of 13 early-onset PE, 16 late-onset PE and 83 controls comprising 36 uncomplicated and 47 complicated pregnancies, i.e. 27 fetal growth restricted and 20 spontaneous preterm birth. To investigate the associations between PE and the epigenetics of circadian clock and clock-controlled genes in placental and newborn tissues, genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation450K BeadChip and a candidate-gene approach using ANCOVA was applied on 939 CpGs of 39 circadian clock and clock-controlled genes. DNA methylation significantly differed in early-onset PE compared with spontaneous preterm birth at 6 CpGs in placental tissue (3.73 E-5 ≤ p ≤ 0.016) and at 21 CpGs in UCL (1.09 E-5 ≤ p ≤ 0.024). In early-onset PE compared with fetal growth restriction 2 CpGs in placental tissue (p < 0.05) and 8 CpGs in uncomplicated controls (4.78 E-5 ≤ p ≤ 0.049) were significantly different. Moreover, significantly different DNA methylation in early-onset PE compared with uncomplicated controls was shown at 6 CpGs in placental tissue (1.36 E-4 ≤ p ≤ 0.045) and 11 CpGs in uncomplicated controls (2.52 E-6 ≤ p ≤ 0.009). No significant associations were shown with late-onset PE between study groups or tissues. The most differentially methylated CpGs showed hypomethylation in placental tissue and hypermethylation in uncomplicated controls. In conclusion, DNA methylation of circadian clock and clock-controlled genes demonstrated most differences in UCL of early-onset PE compared with spontaneous preterm birth. Implications of the tissue-specific variations in epigenetic programming for circadian performance and long-term health need further investigation.

Cervical pessary to prevent preterm birth in women with twin gestation and sonographic short cervix: a multicenter randomized controlled trial (PECEP-Twins).

PubMed

Goya, Maria; de la Calle, Maria; Pratcorona, Laia; Merced, Carme; Rodó, Carlota; Muñoz, Begoña; Juan, Miquel; Serrano, Ariana; Llurba, Elisa; Higueras, Teresa; Carreras, Elena; Cabero, Luis

2016-02-01

Spontaneous preterm birth (SPB) is the leading cause of perinatal morbidity and mortality. In twins, the rate of preterm birth is higher than in singletons; interventions to prevent preterm birth are needed in this high-risk population. We sought to test whether a cervical pessary reduces the preterm birth rate in twin pregnancies with sonographic short cervix. A prospective, open-label, multicenter, randomized clinical trial was conducted in 5 hospitals in Spain. The ethics committees of all participating hospitals approved the protocol. The trial was registered as ClinicalTrials.gov, number NCT01242410. Eligible women were scanned in Spain. The primary outcome was SPB <34 weeks of gestation. Neonatal morbidity and mortality were also evaluated. Cervical length was measured in 2287 women; 137 pregnant women with a sonographic cervical length ≤25 mm (of 154 detected with a short cervix) were randomly assigned to receive a cervical pessary or expectant management (1:1 ratio). SPB <34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (11/68 [16.2%] vs 26/66 [39.4%]; relative risk, 0.41; 95% confidence interval, 0.22-0.76). Pessary use was associated with a significant reduction in the rate of birthweight <2500 g (P = .01). No significant differences were observed in composite neonatal morbidity outcome (8/136 [5.9%] vs 12/130 [9.1%]; relative risk, 0.64; 95% confidence interval, 0.27-1.50) or neonatal mortality (none) between the groups. No serious adverse effects associated with the use of a cervical pessary were observed. The insertion of a cervical pessary was associated with a significant reduction in the SPB rate. We propose the use of a cervical pessary for preventing preterm birth in twin pregnancies of mothers with a short cervix. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of maternal age on the risk of preterm birth: A large cohort study

PubMed Central

Monet, Barbara; Ducruet, Thierry; Chaillet, Nils; Audibert, Francois

2018-01-01

Background Maternal age at pregnancy is increasing worldwide as well as preterm birth. However, the association between prematurity and advanced maternal age remains controversial. Objective To evaluate the impact of maternal age on the occurrence of preterm birth after controlling for multiple known confounders in a large birth cohort. Study design Retrospective cohort study using data from the QUARISMA study, a large Canadian randomized controlled trial, which collected data from 184,000 births in 32 hospitals. Inclusion criteria were maternal age over 20 years. Exclusion criteria were multiple pregnancy, fetal malformation and intra-uterine fetal death. Five maternal age categories were defined and compared for maternal characteristics, gestational and obstetric complications, and risk factors for prematurity. Risk factors for preterm birth <37 weeks, either spontaneous or iatrogenic, were evaluated for different age groups using multivariate logistic regression. Results 165,282 births were included in the study. Chronic hypertension, assisted reproduction techniques, pre-gestational diabetes, invasive procedure in pregnancy, gestational diabetes and placenta praevia were linearly associated with increasing maternal age whereas hypertensive disorders of pregnancy followed a “U” shaped distribution according to maternal age. Crude rates of preterm birth before 37 weeks followed a “U” shaped curve with a nadir at 5.7% for the group of 30–34 years. In multivariate analysis, the adjusted odds ratio (aOR) of prematurity stratified by age group followed a “U” shaped distribution with an aOR of 1.08 (95%CI; 1.01–1.15) for 20–24 years, and 1.20 (95% CI; 1.06–1.36) for 40 years and older. Confounders found to have the greatest impact were placenta praevia, hypertensive complications, and maternal medical history. Conclusion Even after adjustment for confounders, advanced maternal age (40 years and over) was associated with preterm birth. A maternal age of 30–34 years was associated with the lowest risk of prematurity. PMID:29385154

Effect of maternal age on the risk of preterm birth: A large cohort study.

PubMed

Fuchs, Florent; Monet, Barbara; Ducruet, Thierry; Chaillet, Nils; Audibert, Francois

2018-01-01

Maternal age at pregnancy is increasing worldwide as well as preterm birth. However, the association between prematurity and advanced maternal age remains controversial. To evaluate the impact of maternal age on the occurrence of preterm birth after controlling for multiple known confounders in a large birth cohort. Retrospective cohort study using data from the QUARISMA study, a large Canadian randomized controlled trial, which collected data from 184,000 births in 32 hospitals. Inclusion criteria were maternal age over 20 years. Exclusion criteria were multiple pregnancy, fetal malformation and intra-uterine fetal death. Five maternal age categories were defined and compared for maternal characteristics, gestational and obstetric complications, and risk factors for prematurity. Risk factors for preterm birth <37 weeks, either spontaneous or iatrogenic, were evaluated for different age groups using multivariate logistic regression. 165,282 births were included in the study. Chronic hypertension, assisted reproduction techniques, pre-gestational diabetes, invasive procedure in pregnancy, gestational diabetes and placenta praevia were linearly associated with increasing maternal age whereas hypertensive disorders of pregnancy followed a "U" shaped distribution according to maternal age. Crude rates of preterm birth before 37 weeks followed a "U" shaped curve with a nadir at 5.7% for the group of 30-34 years. In multivariate analysis, the adjusted odds ratio (aOR) of prematurity stratified by age group followed a "U" shaped distribution with an aOR of 1.08 (95%CI; 1.01-1.15) for 20-24 years, and 1.20 (95% CI; 1.06-1.36) for 40 years and older. Confounders found to have the greatest impact were placenta praevia, hypertensive complications, and maternal medical history. Even after adjustment for confounders, advanced maternal age (40 years and over) was associated with preterm birth. A maternal age of 30-34 years was associated with the lowest risk of prematurity.

Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?

PubMed

Papiernik, E; Grangé, G; Zeitlin, J

1998-01-01

This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.

Chest physiotherapy in preterm infants with lung diseases

PubMed Central

2010-01-01

Background In neonatology the role of chest physiotherapy is still uncertain because of the controversial outcomes. Methods The aim of this study was to test the applicability in preterm infants of 'reflex rolling', from the Vojta method, in preterm neonates with lung pathology, with particular attention to the effects on blood gases and oxygen saturation, on the spontaneous breathing, on the onset of stress or pain. The study included 34 preterm newborns with mean gestational age of 30.5 (1.6) weeks - mean (DS) - and birth weight of 1430 (423) g - mean (DS) -, who suffered from hyaline membrane disease, under treatment with nasal CPAP (continuous positive airways pressure), or from pneumonia, under treatment with oxygen-therapy. The neonates underwent phase 1 of 'reflex rolling' according to Vojta method three times daily. Respiratory rate, SatO2, transcutaneous PtcCO2 e PtcO2 were monitored; in order to evaluate the onset of stress or pain following the stimulations, the NIPS score and the PIPP score were recorded; cerebral ultrasound scans were performed on postnatal days 1-3-5-7, and then weekly. Results In this population the first phase of Vojta's 'reflex rolling' caused an increase of PtcO2 and SatO2 values. No negative effects on PtcCO2 and respiratory rate were observed, NIPS and PIPP stress scores remained unmodified during the treatment; in no patient the intraventricular haemorrhage worsened in time and none of the infants developed periventricular leucomalacia. Conclusions Our experience, using the Vojta method, allows to affirm that this method is safe for preterm neonates, but further investigations are necessary to confirm its positive effects and to evaluate long-term respiratory outcomes. PMID:20868518

[Prolonged hospitalization versus home management for women with arrested preterm labour: a before-after study].

PubMed

Salzmann, M; Gaucherand, P; Doret, M

2013-04-01

To compare gestational age at birth and incidence of preterm birth inferior to 37 weeks of gestation (WG) in single pregnancies with either prolonged hospitalization, or early home discharge after arrested preterm labour. Management of preterm labour was changed in our public academic hospital because no evidence of benefits for prolonged hospitalization was found and because adverse effects related to long-term hospitalization were described. In this retrospective before-after study, we compare the attitude A (December 2006 to April 2008), a prolonged hospitalization until 32 or 34WG, with new attitude B (May 2008 to February 2010), an early discharge home if the cervical exam was unchanged since admission. A total of 140 patients were included: 70 in each group. Initial hospitalization stay was significantly shorter in Group B (respectively, 5.4±5.4 days and 11.4±12.1 days; P<0.05). Preterm spontaneous delivery is 14 (20%) in group A and 21 (28.6%) in Group B (P>0.05). Gestational ages at birth were 33(5/7) and 33(0/7) WG in groups A and B, respectively (P>0.05). If we focus on patients who were discharged home in the two groups (women who did not deliver no matter the hospitalization length), the gestational age at birth (38(4/7) and 38WG; ns) and the prematurity rate inferior to 37WG (17.2% and 22.4%; ns) were statistically similar. This study suggests that shorter hospitalization does not decrease the delivery term, nor does it increase the premature delivery incidence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators.

PubMed

Lim, R; Barker, G; Lappas, M

2015-04-01

In non-gestational tissues, the activation of adenosine monophosphate (AMP)-activated kinase (AMPK) is associated with potent anti-inflammatory actions. Infection and/or inflammation, by stimulating pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9, play a central role in the rupture of fetal membranes. However, no studies have examined the role of AMPK in human labour. Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and after preterm pre-labour rupture of membranes (PPROM). AMPK activity was assessed by Western blotting of phosphorylated AMPK expression. To determine the effect of AMPK activators on pro-inflammatory cytokines, fetal membranes were pre-treated with AMPK activators then stimulated with bacterial products LPS and flagellin or viral dsDNA analogue poly(I:C). Primary amnion cells were used to determine the effect of AMPK activators on IL-1β-stimulated MMP-9 expression. AMPK activity was decreased with term labour. There was no effect of preterm labour. AMPK activity was also decreased in preterm fetal membranes, in the absence of labour, with PROM compared to intact membranes. AMPK activators AICAR, phenformin and A769662 significantly decreased IL-6 and IL-8 stimulated by LPS, flagellin and poly(I:C). Primary amnion cells treated with AMPK activators significantly decreased IL-1β-induced MMP-9 expression. The decrease in AMPK activity in fetal membranes after spontaneous term labour and PPROM indicates an anti-inflammatory role for AMPK in human labour and delivery. The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preterm EEG: a multimodal neurophysiological protocol.

PubMed

Stjerna, Susanna; Voipio, Juha; Metsäranta, Marjo; Kaila, Kai; Vanhatalo, Sampsa

2012-02-18

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked. In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

A cohort study found that white blood cell count and endocrine markers predicted preterm birth in symptomatic women.

PubMed

Campbell, M Karen; Challis, John R G; DaSilva, Orlando; Bocking, Alan D

2005-03-01

This cohort study investigated potential clinical and biochemical predictors of subsequent preterm birth in women presenting with threatened preterm labor. Subjects were 218 pregnant women admitted to hospital with a diagnosis of threatened preterm labor at 22-36 weeks gestation. Exclusion criteria were multiple pregnancy, fetal anomalies, diabetes mellitus, abruptio placenta, preeclampsia, intrauterine growth restriction, cervical dilatation > 4 cm, and clinical signs of infection. Analyses used logistic regression. The presence of ruptured membranes was the best predictor of birth within 48 hours. Other important predictors were maternal white blood cell count at 22-27 weeks gestation and maternal adrenocorticotropin and corticotropin-releasing hormone concentrations at 28-36 weeks gestation. Subclinical infection may be an important etiologic factor in preterm births of gestational age < 28 weeks. For those at > or = 28 weeks gestation, the findings support the etiologic role of activation of the fetal and/or maternal hypothalamic pituitary adrenal axis leading to preterm birth.

Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

PubMed Central

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

Mediation of the Relationship between Maternal Phthalate Exposure and Preterm Birth by Oxidative Stress with Repeated Measurements across Pregnancy.

PubMed

Ferguson, Kelly K; Chen, Yin-Hsiu; VanderWeele, Tyler J; McElrath, Thomas F; Meeker, John D; Mukherjee, Bhramar

2017-03-01

Mediation analysis is useful for understanding mechanisms and has been used minimally in the study of the environment and disease. We examined mediation of the association between phthalate exposure during pregnancy and preterm birth by oxidative stress. This nested case-control study of preterm birth ( n = 130 cases, 352 controls) included women who delivered in Boston, Massachusestts, from 2006 through 2008. Phthalate metabolites and 8-isoprostane, an oxidative stress biomarker, were measured in urine from three visits in pregnancy. We applied four counterfactual mediation methods: method 1, utilizing exposure and mediator averages; method 2, using averages but allowing for an exposure-mediator interaction; method 3, incorporating longitudinal measurements of the exposure and mediator; and method 4, using longitudinal measurements and allowing for an exposure-mediator interaction. We observed mediation of the associations between phthalate metabolites and all preterm birth by 8-isoprostane, with the greatest estimated proportion mediated observed for spontaneous preterm births specifically. Fully utilizing repeated measures of the exposure and mediator improved precision of indirect (i.e., mediated) effect estimates, and including an exposure-mediator interaction increased the estimated proportion mediated. For example, for mono(2-ethyl-carboxy-propyl) phthalate (MECPP), a metabolite of di(2-ethylhexyl) phthalate (DEHP), the percent of the total effect mediated by 8-isoprostane increased from 47% to 60% with inclusion of an exposure-mediator interaction term, in reference to a total adjusted odds ratio of 1.67 or 1.48, respectively. This demonstrates mediation of the phthalate-preterm birth relationship by oxidative stress, and the utility of complex regression models in capturing mediated associations when repeated measures of exposure and mediator are available and an exposure-mediator interaction may exist. Citation: Ferguson KK, Chen YH, VanderWeele TJ, McElrath TF, Meeker JD, Mukherjee B. 2017. Mediation of the relationship between maternal phthalate exposure and preterm birth by oxidative stress with repeated measurements across pregnancy. Environ Health Perspect 125:488-494; http://dx.doi.org/10.1289/EHP282.

Evaluation of the WinROP system for identifying retinopathy of prematurity in Czech preterm infants.

PubMed

Timkovic, Juraj; Pokryvkova, Martina; Janurova, Katerina; Barinova, Denisa; Polackova, Renata; Masek, Petr

2017-03-01

Retinopathy of Prematurity (ROP) is a potentially serious condition that can afflict preterm infants. Timely and correct identification of individuals at risk of developing a serious form of ROP is therefore of paramount importance. WinROP is an online system for predicting ROP based on birth weight and weight increments. However, the results vary significantly for various populations. It has not been evaluated in the Czech population. This study evaluates the test characteristics (specificity, sensitivity, positive and negative predictive values) of the WinROP system in Czech preterm infants. Data on 445 prematurely born infants included in the ROP screening program at the University Hospital Ostrava, Czech Republic, were retrospectively entered into the WinROP system and the outcomes of the WinROP and regular screening were compared. All 24 infants who developed high-risk (Type 1 or Type 2) ROP were correctly identified by the system. The sensitivity and negative predictive values for this group were 100%. However, the specificity and positive predictive values were substantially lower, resulting in a large number of false positives. Extending the analysis to low risk ROP, the system did not provide such reliable results. The system is a valuable tool for identifying infants who are not likely to develop high-risk ROP and this could help to substantially reduce the number of preterm infants in need of regular ROP screening. It is not suitable for predicting the development of less serious forms of ROP which is however in accordance with the declared aims of the WinROP system.

Preventing newborn deaths due to prematurity.

PubMed

Azad, Kishwar; Mathews, Jiji

2016-10-01

Preterm births (PTBs), defined as births before 37 weeks of gestation account for the majority of deaths in the newborn period. Prediction and prevention of PTB is challenging. A history of preterm labour or second trimester losses and accurate measurement of cervical length help to identify women who would benefit from progesterone and cerclage. Fibronectin estimation in the cervicovaginal secretions of a symptomatic woman with an undilated cervix can predict PTB within 10 days of testing. Antibiotics should be given to women with preterm prelabour rupture of membranes but tocolysis has a limited role in the management of preterm labour. Antenatal corticosteroids to prevent complications in the neonate should be given only when gestational age assessment is accurate PTB is considered imminent, maternal infection and the preterm newborn can receive adequate care. Magnesium sulphate for fetal neuroprotection should be given when delivery is imminent. After birth, most babies respond to simple interventions essential newborn care, basic care for feeding support, infections and breathing difficulties. Newborns weighing 2000 g or less, benefit from KMC. Babies, who are clinically unstable or cannot be given KMC may be nursed in an incubator or under a radiant warmer. Treatment modalities include oxygen therapy, CPAP, surfactant and assisted ventilation. Copyright © 2016. Published by Elsevier Ltd.

DNA Methylation: An Epigenetic Risk Factor in Preterm Birth

PubMed Central

Menon, Ramkumar; Conneely, Karen N.; Smith, Alicia K.

2012-01-01

Spontaneous preterm birth (PTB; birth prior to 37 weeks of gestation) is a complex phenotype with multiple risk factors that complicate our understanding of its etiology. A number of recent studies have supported the hypothesis that epigenetic modifications such as DNA methylation induced by pregnancy-related risk factors may influence the risk of PTB or result in changes that predispose a neonate to adult-onset diseases. The critical role of timing of gene expression in the etiology of PTB makes it a highly relevant disorder in which to examine the potential role of epigenetic changes. Because changes in DNA methylation patterns can result in long-term consequences, it is of critical interest to identify the epigenetic patterns associated with adverse pregnancy outcomes. This review examines the potential role of DNA methylation as a risk factor for PTB and discusses several issues and limitations that should be considered when planning DNA methylation studies. PMID:22228737

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angell, N.F.; Lavery, J.P.

Lead represents a significant environmental hazard to pregnant women and their offspring. Exposure to high environmental levels of lead has been associated with spontaneous abortion, premature rupture of fetal membranes (PROM), and preterm delivery. The relationship between lower exposures and obstetric complications is unknown. The concentration of lead in the blood was measured in 635 specimens of umbilical cord blood collected at delivery. No relationship was found between concentrations of lead in cord blood and the incidence of PROM, preterm delivery, preeclampsia, or meconium staining. Maternal and infant capillary blood was collected 24 hours post partum from 154 of thesemore » deliveries. The concentrations of lead in the blood did not vary significantly among cord, infant, and maternal samples, and the three measurements were highly correlated. Levels of zinc protoporphyrin (ZnP) were increased in cord blood as compared with mothers' blood, but no concentration-response relationships between the ratio of cord ZnP to maternal ZnP and lead were found.« less

Predictors of preterm births and low birthweight in an inner-city hospital in sub-Saharan Africa.

PubMed

Olusanya, Bolajoko O; Ofovwe, Gabriel E

2010-11-01

Adverse birth outcomes remain significant contributors to perinatal mortality as well as developmental disabilities worldwide but limited evidence exists in sub-Saharan Africa based on a conceptual framework incorporating neighborhood context. This study therefore set out to determine the prevalence and risk factors for preterm births and low birthweight in an urban setting from this region. A cross-sectional study of all live births from May 2005 to December 2007 in an inner-city maternity hospital in Lagos, Nigeria. Factors predictive of preterm births and low birthweight were determined by unconditional multivariable logistic regression within a conceptual framework for adverse birth outcomes. Population attributable risk (PAR%) for each factor was also determined. Of the 4,314 newborns enrolled, 859 (19.9%) were preterm and 440 (10.2%) were low birthweight. One-third of mothers received no antenatal care while about 6% had HIV and another 6% had a history of hypertensive disorders. About 43% of the low birthweight infants were born full term. Maternal predictors of preterm delivery and/or low birthweight were marital status, occupation, residential accommodation with shared sanitation facilities, lack of antenatal care, absence of previous cesarean section, hypertensive disorders and antepartum hemorrhage. Gender and intrauterine growth restriction (IUGR) were also predictive of low birthweight. Premature rupture of membranes (PAR = 33.91%) and antepartum hemorrhage (PAR = 33.54%) were the leading contributors to preterm birth in contrast to IUGR (PAR = 82.28%) and premature rupture of membranes (PAR = 32.31%) for low birthweight. [corrected] The burden of preterm and low birthweight deliveries in this setting is associated with modifiable individual and neighborhood-level risk factors that warrant community-oriented public health interventions.

Application of a global reference for fetal-weight and birthweight percentiles in predicting infant mortality.

PubMed

Ding, G; Tian, Y; Zhang, Y; Pang, Y; Zhang, J S; Zhang, J

2013-12-01

To determine whether the recently published A global reference for fetal-weight and birthweight percentiles (Global Reference) improves small- (SGA), appropriate- (AGA), and large-for-gestational-age (LGA) definitions in predicting infant mortality. Population-based cohort study. The US Linked Livebirth and Infant Death records between 1995 and 2004. Singleton births with birthweight >500 g born at 24-41 weeks of gestation. We compared infant mortality rates of SGA, AGA, and LGA infants classified by three different references: the Global Reference; a commonly used birthweight reference; and Hadlock's ultrasound reference. Infant mortality rates. Among 33 997 719 eligible liveborn singleton births, 25% of preterm and 9% of term infants were classified differently for SGA, AGA, and LGA by the Global Reference and the birthweight reference. The Global Reference indicated higher mortality rates in preterm SGA and preterm LGA infants than the birthweight reference. The mortality rate was considerably higher in infants classified as preterm SGA by the Global Reference but not by the birthweight reference, compared with the corresponding infants classified by the birthweight reference but not by the Global Reference (105.7 versus 12.9 per 1000, RR 8.17, 95% CI 7.38-9.06). Yet, the differences in mortality rates were much smaller in term infants than in preterm infants. Black infants had a particularly higher mortality rate than other races in AGA and LGA preterm and term infants. In respect to the commonly used birthweight reference, the Global Reference increases the identification of infant deaths by improved classification of abnormal newborn size at birth, and these advantages were more obvious in preterm than in term infants. © 2013 RCOG.

Bacterial vaginosis in association with spontaneous abortion and recurrent pregnancy losses.

PubMed

Işik, Gözde; Demirezen, Şayeste; Dönmez, Hanife Güler; Beksaç, Mehmet Sinan

2016-01-01

Bacterial vaginosis (BV) is related to the increased risk of miscarriage, preterm labor, and postpartum endometritis. The aim of this study was to evaluate the association between BV and the history of spontaneous abortion and recurrent pregnancy losses. We also examined periods of gestation, including the first and second trimester miscarriages. The study population consisted of 200 fertile women. Sixty one (30.5%) of 200 women had the history of a spontaneous abortion in the last six months ( N = 30) and at least three recurrent pregnancy losses ( N = 31). BV was diagnosed either by using Papanicolaou staining, Gram staining, or by culturing with BV-associated bacteria, Gardnerella vaginalis . The presence of BV was statistically associated with the history of a spontaneous abortion in the last 6 months ( P < 0.05), whereas there was no significant relationship between BV and recurrent pregnancy losses ( P > 0.05). These women were also evaluated in view of periods of gestation. Forty-seven (77%) of 61 women had first trimester miscarriage (≤12 weeks) and 14 (23%) of 61 women had second trimester miscarriage (>12 weeks). There was a statistically significant relationship between BV and second trimester miscarriage ( P < 0.05). Positive BV findings were not associated with discharge, itching, and pain ( P > 0.05). BV may contribute to spontaneous abortion and second trimester miscarriage.

First-trimester antihistamine exposure and risk of spontaneous abortion or preterm birth.

PubMed

Aldridge, Tiara D; Hartmann, Katherine E; Michels, Kara A; Velez Edwards, Digna R

2014-10-01

We tested whether antihistamine exposure during early pregnancy is associated with spontaneous abortion (SAB) or preterm birth (PTB). Women were enrolled in Right from the Start (2004-2010), a prospective pregnancy cohort. Data about first-trimester antihistamine use were obtained from screening and first-trimester interviews. Self-reported outcomes included SAB and PTB and were verified by medical records. Cox proportional hazards models were used to test for an association between antihistamine use and each outcome, both performed adjusting for confounders. Among the 2685 pregnancies analyzed, 14% (n = 377) reported use of antihistamines. Among antihistamine users, 12% (n = 44) experienced SABs, and 6% (n = 21) had PTBs. Antihistamine exposure was not associated with SAB (adjusted hazard ratio [aHR] = 0.88, 95% confidence interval [CI] 0.64, 1.21) or PTB, which was modified by maternal race (aHR = 1.03, 95%CI 0.61, 1.72 among White women and aHR = 0.43, 95%CI 0.14, 1.34 among Black women). Despite the biologic plausibility that antihistamine use may influence pregnancy outcomes, we did not detect evidence of an association with SAB or PTB. These data demonstrate the utility of large prospective cohorts for evaluating drug safety in pregnancy when concerns are raised from animal models. Copyright © 2014 John Wiley & Sons, Ltd.

Delayed Luminance and Chromatic Contrast Sensitivity in Infants with Spontaneously Regressed Retinopathy of Prematurity

PubMed Central

Bosworth, Rain; Robbins, Shira L.; Granet, David B.; Dobkins, Karen

2013-01-01

Background The current study assessed whether contrast sensitivity is affected in preterm infants with a history of spontaneously regressed retinopathy of prematurity (ROP, Stages 1–3). Specifically, we employed luminance (light/dark) and chromatic (red/green) stimuli, which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. Methods Contrast sensitivity (CS) was measured using forced choice preferential looking testing in 21 infants with a history of ROP and 41 control preterm infants who were born prematurely but did not develop ROP, tested between 8 and 47 weeks (2–11 months) postterm age. Infants were presented with chromatic and luminance drifting sinusoidal gratings, which appeared randomly on the left or right side of the monitor on each trial. The contrast of the stimuli varied across trials and was defined in terms of root mean squared cone contrast for long- and medium-wavelength cones. Results Between 8 and 25 weeks postterm, ROP infants had significantly worse CS, and there was a trend for greater impairment for Luminance than Chromatic CS. This delay was not seen at older ages between 26 and 47 weeks postterm. Conclusions These findings are consistent with the concept that early maturation of the M pathway is vulnerable to biological insult, as in the case of ROP, to a greater extent than is the P pathway. PMID:23744448

Relaxant effect of proton pump inhibitors on in vitro myometrium from pregnant women.

PubMed

Terranova, C; Petrella, C; Improta, G; Severini, C; Signore, F; Damiani, P; Plotti, F; Scarpignato, C; Angioli, R

2014-02-14

In this study we investigate in in vitro myometrial tissue samples of pregnant women: (a) the effects of proton pomp inhibitors (PPIs) (omeprazole, esomeprazole, pantoprazole, lansoprazole and rabeprazole) on spontaneous contractions; (b) the muscle-relaxant efficacy of the most active PPI considered (pantoprazole) in comparison with that of other known tocolytics (nifedipine, atosiban, MgSO4, isoxsuprine); (c) the effect of pantoprazole on contractions induced by calcium (Ca(++)), KCl, oxytocin and prostaglandin (PGE2); (d) the possible mediators of pantoprazole relaxant effect. Organ bath studies were performed on myometrial tissue samples (40×10×10 mm) from pregnant women (38-42 weeks of gestational age) undergoing elective caesarian section. All the PPIs studied reduce the spontaneous contraction of the myometrial smooth muscle. Pantoprazole is the most effective and most potent inhibitor among those analyzed. Pantoprazole also reduces the contractions induced by Ca(++), KCl, oxytocin and PGE2. Neither NO, nor PGs, or the activation of Ca(++)-dependent K(+) currents mediate the muscle-relaxant effect of this PPI. These data, together with the fact that PPIs almost do not present side effects, suggest that these drugs can offer new therapeutic strategies for preterm delivery. Undoubtedly, further investigations and clinical studies are necessary before adding PPIs to the list of drugs available for the treatment of preterm delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

Contingent use of fetal fibronectin testing and cervical length measurement in women with preterm labour.

PubMed

Audibert, François; Fortin, Suzanne; Delvin, Edgard; Djemli, Anissa; Brunet, Suzanne; Dubé, Johanne; Fraser, William D

2010-04-01

To evaluate the contingent use of fetal fibronectin (fFN) testing and cervical length (CL) measurement to predict preterm delivery, and to validate the use of phosphorylated IGFBP-1 as a predictor of preterm delivery. We recruited 71 women with a clinical diagnosis of preterm labour between 24 and 34 weeks, and tested for the presence of fFN and IGFBP-1 in the cervicovaginal secretions of all women immediately before CL measurement. Among the 66 women with complete outcome, four were excluded from the final analysis as two had assessment for fFN but no CL measurement, and another two had CL measured but no screening for fFN. Among 62 women with complete results, the mean gestational age at recruitment was 29.4 +/- 2.5 weeks. Six women (9.6%) delivered within two weeks of assessment, and 14 (22.5%) delivered before 34 weeks. A positive fFN test resulted in a sensitivity of 83%, a specificity of 84%, a positive predictive value of 36%, and a negative predictive value of 98% for delivery within two weeks; for CL < 25 mm, these figures were 50%, 52%, 10%, and 91%, respectively, and for a positive IGFBP-1, they were 17%, 93%, 20%, and 91%, respectively. A policy of contingent use of fFN (in which the test was assumed to be positive if CL < or = 15 mm, and fFN was only measured if the CL was between 16 and 30 mm) gave sensitivity, specificity, positive and negative predictive values of 80%, 61%, 17%, and 97%, respectively for delivery within two weeks. Using this contingent use protocol, only one third of women needed fFN screening after CL measurement. In this study, IGFBP-1 screening did not predict preterm delivery and fFN screening provided the best predictive capacity. A policy of contingent use of testing for fFN after CL measurement, or contingent use of CL measurement after fFN screening (depending on available resources) is a promising approach to limit use of resources.

Risk of preterm birth by subtype among Medi-Cal participants with mental illness.

PubMed

Baer, Rebecca J; Chambers, Christina D; Bandoli, Gretchen; Jelliffe-Pawlowski, Laura L

2016-10-01

Previous studies have demonstrated an association between mental illness and preterm birth (before 37 weeks). However, these investigations have not simultaneously considered gestation of preterm birth, the indication (eg, spontaneous or medically indicated), and specific mental illness classifications. The objective of the study was to examine the likelihood of preterm birth across gestational lengths and indications among Medi-Cal (California's Medicaid program) participants with a diagnostic code for mental illness. Mental illnesses were studied by specific illness classification. The study population was drawn from singleton live births in California from 2007 through 2011 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes birth certificate and hospital discharge records. The sample was restricted to women with Medi-Cal coverage for prenatal care. Women with mental illness were identified using International Classification of Diseases, ninth revision, codes from their hospital discharge record. Women without a mental illness International Classification of Diseases, ninth revision, code were randomly selected at a 4:1 ratio. Adjusting for maternal characteristics and obstetric complications, relative risks and 95% confidence intervals were calculated for preterm birth comparing women with a mental illness diagnostic code with women without such a code. We identified 6198 women with a mental illness diagnostic code and selected 24,792 women with no such code. The risk of preterm birth in women with a mental illness were 1.2 times higher than women without a mental illness (adjusted relative risk, 1.2, 95% confidence interval, 1.1-1.3). Among the specific mental illnesses, schizophrenia, major depression, and personality disorders had the strongest associations with preterm birth (adjusted relative risks, 2.0, 2.0 and 3.3, respectively). Women receiving prenatal care through California's low-income health insurance who had at least 1 mental illness diagnostic code were 1.2-3.3-times more likely to have a preterm birth than women without a mental illness, and these risks persisted across most illness classifications. Although it cannot be determined from these data whether specific treatments for mental illness contribute to the observed associations, elevated risk across different diagnoses suggests that some aspects of mental illness itself may confer risk. Copyright © 2016 Elsevier Inc. All rights reserved.

An elevated amniotic fluid prostaglandin F2α concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes.

PubMed

Park, Jee Yoon; Romero, Roberto; Lee, JoonHo; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun

2016-01-01

To determine whether an elevated amniotic fluid concentration of prostaglandin F2α (PGF2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes. The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (≥170 pg/mL). (1) The prevalence of an elevated amniotic fluid PGF2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2α (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]. The concentration of PGF2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.

Changes in Association between Previous Therapeutic Abortion and Preterm Birth in Scotland, 1980 to 2008: A Historical Cohort Study

PubMed Central

Oliver-Williams, Clare; Fleming, Michael; Monteath, Kirsten; Wood, Angela M.; Smith, Gordon C. S.

2013-01-01

Background Numerous studies have demonstrated that therapeutic termination of pregnancy (abortion) is associated with an increased risk of subsequent preterm birth. However, the literature is inconsistent, and methods of abortion have changed dramatically over the last 30 years. We hypothesized that the association between previous abortion and the risk of preterm first birth changed in Scotland between 1 January 1980 and 31 December 2008. Methods and Findings We studied linked Scottish national databases of births and perinatal deaths. We analysed the risk of preterm birth in relation to the number of previous abortions in 732,719 first births (≥24 wk), adjusting for maternal characteristics. The risk (adjusted odds ratio [95% CI]) of preterm birth was modelled using logistic regression, and associations were expressed for a one-unit increase in the number of previous abortions. Previous abortion was associated with an increased risk of preterm birth (1.12 [1.09–1.16]). When analysed by year of delivery, the association was strongest in 1980–1983 (1.32 [1.21–1.43]), progressively declined between 1984 and 1999, and was no longer apparent in 2000–2003 (0.98 [0.91–1.05]) or 2004–2008 (1.02 [0.95–1.09]). A statistical test for interaction between previous abortion and year was highly statistically significant (p<0.001). Analysis of data for abortions among nulliparous women in Scotland 1992–2008 demonstrated that the proportion that were surgical without use of cervical pre-treatment decreased from 31% to 0.4%, and that the proportion of medical abortions increased from 18% to 68%. Conclusions Previous abortion was a risk factor for spontaneous preterm birth in Scotland in the 1980s and 1990s, but the association progressively weakened and disappeared altogether by 2000. These changes were paralleled by increasing use of medical abortion and cervical pre-treatment prior to surgical abortion. Although it is plausible that the two trends were related, we could not test this directly as the data on the method of prior abortions were not linked to individuals in the cohort. However, we speculate that modernising abortion methods may be an effective long-term strategy to reduce global rates of preterm birth. Please see later in the article for the Editors' Summary PMID:23874161

Changes in association between previous therapeutic abortion and preterm birth in Scotland, 1980 to 2008: a historical cohort study.

PubMed

Oliver-Williams, Clare; Fleming, Michael; Monteath, Kirsten; Wood, Angela M; Smith, Gordon C S

2013-01-01

Numerous studies have demonstrated that therapeutic termination of pregnancy (abortion) is associated with an increased risk of subsequent preterm birth. However, the literature is inconsistent, and methods of abortion have changed dramatically over the last 30 years. We hypothesized that the association between previous abortion and the risk of preterm first birth changed in Scotland between 1 January 1980 and 31 December 2008. We studied linked Scottish national databases of births and perinatal deaths. We analysed the risk of preterm birth in relation to the number of previous abortions in 732,719 first births (≥24 wk), adjusting for maternal characteristics. The risk (adjusted odds ratio [95% CI]) of preterm birth was modelled using logistic regression, and associations were expressed for a one-unit increase in the number of previous abortions. Previous abortion was associated with an increased risk of preterm birth (1.12 [1.09-1.16]). When analysed by year of delivery, the association was strongest in 1980-1983 (1.32 [1.21-1.43]), progressively declined between 1984 and 1999, and was no longer apparent in 2000-2003 (0.98 [0.91-1.05]) or 2004-2008 (1.02 [0.95-1.09]). A statistical test for interaction between previous abortion and year was highly statistically significant (p<0.001). Analysis of data for abortions among nulliparous women in Scotland 1992-2008 demonstrated that the proportion that were surgical without use of cervical pre-treatment decreased from 31% to 0.4%, and that the proportion of medical abortions increased from 18% to 68%. Previous abortion was a risk factor for spontaneous preterm birth in Scotland in the 1980s and 1990s, but the association progressively weakened and disappeared altogether by 2000. These changes were paralleled by increasing use of medical abortion and cervical pre-treatment prior to surgical abortion. Although it is plausible that the two trends were related, we could not test this directly as the data on the method of prior abortions were not linked to individuals in the cohort. However, we speculate that modernising abortion methods may be an effective long-term strategy to reduce global rates of preterm birth.

The Clinical Significance of Eosinophils in the Amniotic Fluid in Preterm Labor

PubMed Central

ROMERO, ROBERTO; KUSANOVIC, JUAN PEDRO; GOMEZ, RICARDO; LAMONT, RONALD; BYTAUTIENE, EGLE; GARFIELD, ROBERT E.; MITTAL, POOJA; HASSAN, SONIA S.; YEO, LAMI

2012-01-01

Objective White blood cells are not traditionally considered to be normally present in amniotic fluid. This study was conducted after the observation that a patient with preterm labor and intact membranes had eosinophils as a predominant cell in the amniotic fluid, and had an episode of asthma during the index pregnancy. The goal of this study was to determine whether women presenting with preterm labor with eosinophils in the amniotic fluid had a different outcome than those without eosinophils as the predominant white blood cell in the amniotic cavity. Methods This retrospective case-control study included women who presented with preterm labor and intact membranes between 24 and 34 weeks of gestation. Patients underwent an amniocentesis shortly after admission for the assessment of the microbiologic status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Cytologic studies included amniotic fluid white blood cell count and differential, which was performed on cytocentrifuged specimens. Patients with microbial invasion of the amniotic cavity and/or a white blood cell count >20 cells/mm3 were excluded from the study. Cases were defined as women in whom the differential contained >20% of eosinophils. Controls were selected among women with an amniotic fluid eosinophil count ≤20% and matched for gestational age at amniocentesis. The analysis was conducted with non-parametric statistics. Results The study population consisted of 10 cases and 50 controls. Gestational age and cervical dilatation at admission were similar in both groups. Cases had a lower gestational age at delivery than controls [34.6 weeks, inter-quartile range (IQR) 32–37.3 weeks vs. 38.0 weeks, IQR 35–40 weeks, respectively; p=0.018]. The prevalence of preterm delivery ≤35 weeks was higher among patients who had >20% eosinophils than in the control group [50% (5/10) vs. 18% (9/50), respectively; p=0.029]. Similar results were observed for delivery at <37 weeks [Cases: 70% (7/10) vs. Controls: 36% (18/50); p=0.046]. Conclusions Women with preterm labor and intact membranes who have a large proportion of eosinophils in the amniotic fluid are at an increased risk for spontaneous preterm delivery. These patients may have had an episode of preterm labor related to a type I hypersensitivity reaction. PMID:19900034

Maternal underweight and perinatal outcomes: a restrospective cohort study

PubMed

Vilar Sánchez, Ángel; Fernández Alba, Juan Jesús; González Macías, María Del Carmen; Paublete Herrera, María Del Carmen; Carnicer Fuentes, Concepción; Carral San Laureano, Florentino; Torrejón Cardoso, Rafael; Moreno Corral, Luis Javier

2017-06-05

Introduction: Some studies have linked maternal underweight with adverse perinatal outcomes such as spontaneous abortion, abruptio placentae, small for gestational age newborn, intrauterine growth retardation and preterm birth. Objective: To determine the influence of maternal underweight in the onset of labor, route of delivery, birth weight, Apgar score and preterm birth. Methods: Retrospective cohort study. We included pregnant women from the Hospital Universitario de Puerto Real. Period of study: 2002-2011. Study group: underweight at the beginning of gestation (BMI < 18.5 kg/m2). Control group: pregnant women with normal body mass index (BMI) at the beginning of gestation (18.5-24.9 kg/m2). The risk (OR) of induction of labor, cesarean section, small for gestational age newborn, macrosomia, 5’ Apgar score < 7, and preterm birth was calculated. Results: The prevalence of underweight was 2.5% versus 58.9% of pregnant women who had a normal BMI. We found no significant differences in the rate of induction of labor, fetal macrosomia, Apgar at 5’ < 7 or preterm delivery. Maternal underweight was associated with a decreased risk of caesarean section (adjusted OR 0.45, 95% CI 0.22 to 0.89) and an increased risk of small for gestational age newborn (adjusted OR 1.74; 95% CI 1.05 to 2.90). Conclusions: Maternal underweight at the start of pregnancy is associated with a lower risk of caesarean section and a greater risk of small for gestational age newborns (birth weight < P10).

[Biopsychosocial predictors of preterm labor and preterm delivery? Results of a prospective study].

PubMed

Rauchfuss, M; Gauger, U

2003-05-01

In addition to medical, job related, sociodemographic risk factors, and health related behavior, topics that traditionally have been less in the focus of attention in this context, such as biographic data, coping with stress, personality variables, pregnancy related attitudes, fears, and the social network were examined. 589 women between 16(th) and 22(nd) week of pregnancy were examined using a questionnaire that was designed for the study. This resulted in 508 women pregnant with a single child, whose pregnancy and delivery were examined based on their medical records. Factor analysis and main component analysis with subsequent varimax rotation resulted in factors that were subject to a proof of reliability. Statistical analysis was based on logistic regression. 129 (27.7%) of women displayed signs/indices of an imminent preterm delivery, 29% (5.8%) of whom later actually had a preterm delivery before the end of the 37(th) week of pregnancy. Pregnant women who were in treatment for an imminent preterm delivery appear to have been subject to higher social stress as compared to those, who later later actually gave birth before completing the 37(th) week of pregnancy. Lack of a female network and lack of emotional understanding from the partner are correlated to both of these complications. Specifically, actual preterm delivery appears to be significantly influenced by partner relationship. Another significant predicting variable for imminent and actual preterm delivery appears to be a history of gynecological problems. A distinct risk factor for delivery before completion of the 37(th) week of pregnancy was a history of colpitis. In addition, pronounced anxieties in respect to the pregnancy, and low general anxiety were significant predicting variables for delivery before completion of the 37(th) week of pregnancy. Partner relationship, female networks, psychosomatic reactivity in terms of diseases/disorders of the reproductive organs, and anxieties appear to be worthwhile targets in the prevention of preterm delivery.

Bed rest in singleton pregnancies for preventing preterm birth.

PubMed

Sosa, Claudio G; Althabe, Fernando; Belizán, José M; Bergel, Eduardo

2015-03-30

Bed rest in hospital or at home is widely recommended for the prevention of preterm birth. This advice is based on the observation that hard work and hard physical activity during pregnancy could be associated with preterm birth and with the idea that bed rest could reduce uterine activity. However, bed rest may have some adverse effects on other outcomes. To evaluate the effect of prescription of bed rest in hospital or at home for preventing preterm birth in pregnant women at high risk of preterm birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (18 December 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 12), MEDLINE (December 2014), EMBASE (December 2014), LILACS (December 2014), and bibliographies of relevant papers. Randomized, cluster-randomized and quasi-randomized controlled trials with reported data that assess clinical outcomes in women at high risk of spontaneous preterm birth who were prescribed bed rest in hospital or at home for preventing preterm birth, and their babies. Two review authors independently assessed eligibility, trial quality and extracted data. Two studies met the inclusion criteria. One study was not considered for the meta-analysis, since data combined singleton and multiple pregnancies. No differences in any maternal and perinatal outcomes were reported by the authors. This study was at low risk of selection, performance, detection and attrition bias. Only data from one study were included in the meta-analysis (1266 women). This study was at unclear risk of bias for most domains due to lack of reporting. Four hundred and thirty-two women were prescribed bed rest at home and a total of 834 women received a placebo (412) or no intervention (422). Preterm birth before 37 weeks was similar in both groups (7.9% in the intervention group versus 8.5% in the control group; risk ratio (RR) 0.92, 95% confidence interval (CI) 0.62 to 1.37). No other results were reported for any of the other primary or secondary outcomes. There is no evidence, either supporting or refuting the use of bed rest at home or in hospital, to prevent preterm birth. Although bed rest in hospital or at home is widely used as the first step of treatment, there is no evidence that this practice could be beneficial. Due to the potential adverse effects that bed rest could have on women and their families, and the increased costs for the healthcare system, clinicians should discuss the pros and cons of bed rest to prevent preterm birth. Potential benefits and harms should be discussed with women facing an increased risk of preterm birth. Appropriate research is mandatory. Future trials should evaluate both the effectiveness of bed rest, and the effectiveness of the prescription of bed rest, to prevent preterm birth.

Predictive value of early amplitude-integrated electroencephalography for later diagnosed cerebral white matter damage in preterm infants.

PubMed

Song, Juan; Zhu, Changlian; Xu, Falin; Guo, Jiajia; Zhang, Yanhua

2014-10-01

 The aim of the article is to assess the predictive value of amplitude-integrated electroencephalogram (aEEG) for cerebral white matter damage (WMD) in preterm infants. Patients and  Preterms ≤ 32 weeks' gestational age (GA) born between March 2012 and December 2012 were enrolled. The aEEG patterns within 72 hours were classified and recorded to predict their neurodevelopmental prognosis and the predictive results were used to compare with the results by cerebral ultrasound examination. Neurobehavioral disorder (neonatal behavioral neurological assessment score < 35, dyskinesia or dysgnosia) or death was thought as poor neurodevelopmental prognosis. Psychomotor development index (PDI) or mental development index (MDI) ≤ 79 was regarded as dyskinesia or dysgnosia, respectively.  Of the 63 preterms, 3.2% were born < 27 weeks' gestation and 96.8% at 27 to 32 weeks' gestation. The median GA was 29.3 weeks and the median birth weight was 1,030 g. On the basis of the aEEG results, normal, mildly abnormal, and severely abnormal cases were 10, 24, and 29; whereas determined by cerebral ultrasound, normal, mild, and severe cases were 17, 20, and 26, respectively. The aEEG degree showed significantly positive correlations with both WMD and poor neurodevelopmental prognosis (p < 0.01).  Abnormal aEEG of preterm infants within 72 hours after birth may imply WMD occurrence and poor neurodevelopmental prognosis. Georg Thieme Verlag KG Stuttgart · New York.

Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: a multicenter study.

PubMed

Yu, Zhangbin; Han, Shuping; Wu, Jinxia; Li, Mingxia; Wang, Huaiyan; Wang, Jimei; Liu, Jiebo; Pan, Xinnian; Yang, Jie; Chen, Chao

2014-01-01

to prospectively validate a previously constructed transcutaneous bilirubin (TcB) nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants. this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subsequent significant hyperbilirubinemia. in the present study, 972 neonates (10.6%) developed significant hyperbilirubinemia. The 40(th) percentile of the nomogram could identify all neonates who were at risk of significant hyperbilirubinemia, but with a low positive predictive value (PPV) (18.9%). Of the 453 neonates above the 95(th) percentile, 275 subsequently developed significant hyperbilirubinemia, with a high PPV (60.7%), but with low sensitivity (28.3%). The 75(th) percentile was highly specific (81.9%) and moderately sensitive (79.8%). The area under the curve (AUC) for the TcB nomogram was 0.875. this study validated the previously developed TcB nomogram, which could be used to predict subsequent significant hyperbilirubinemia in healthy Chinese term and late-preterm infants. However, combining TcB nomogram and clinical risk factors could improve the predictive accuracy for severe hyperbilirubinemia, which was not assessed in the study. Further studies are necessary to confirm this combination. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Preterm delivery at low gestational age: risk factors for short latency. A multivariated analysis

PubMed Central

Marzano, Sara; Padula, Francesco; Meloni, Paolo; Anceschi, Maurizio Marco

2008-01-01

Objective The aim of this study is to identify the risk factors for a short latency in preterm delivery at low gestational ages (GA). Study design A retrospective analysis involving, between January 2004 and May 2006, 204 singleton pregnancies with admission diagnosis of preterm labor and, in particular, 91 pregnant women admitted between 24+0 and 31+6 weeks’ gestation. Results In pregnant women with a diagnosis of preterm labor at 24-31+6 weeks’ gestation, at ROC curve, a value of considering WBC and cervical dilatation, combined in the following formula (75.237 - (2.290 * “WBC”) - (10.787 * “cervical dilatation”)) <=33.101 has a 74.2% Sensitivity and a 78.3% Specificity in predicting a latency =< 4 days (+LR 3.42 and -LR 0.33) and a 70% Sensitivity and a 84.3% Specificity in predicting GA at delivery at 24-31 weeks’ gestation (+LR 4.46 and -LR 0.36). Conclusion We suggest a more strictly monitoring and a more aggressive therapy in presence of prognostic parameters of shorter latency. PMID:22439021

Detecting changes during pregnancy with Raman spectroscopy

NASA Astrophysics Data System (ADS)

Vargis, Elizabeth; Robertson, Kesha; Al-Hendy, Ayman; Reese, Jeff; Mahadevan-Jansen, Anita

2010-02-01

Preterm labor is the second leading cause of neonatal mortality and leads to a myriad of complications like delayed development and cerebral palsy. Currently, there is no way to accurately predict preterm labor, making its prevention and treatment virtually impossible. While there are some at-risk patients, over half of all preterm births do not fall into any high-risk category. This study seeks to predict and prevent preterm labor by using Raman spectroscopy to detect changes in the cervix during pregnancy. Since Raman spectroscopy has been used to detect cancers in vivo in organs like the cervix and skin, it follows that spectra will change over the course of pregnancy. Previous studies have shown that fluorescence decreased during pregnancy and increased during post-partum exams to pre-pregnancy levels. We believe significant changes will occur in the Raman spectra obtained during the course of pregnancy. In this study, Raman spectra from the cervix of pregnant mice and women will be acquired. Specific changes that occur due to cervical softening or changes in hormonal levels will be observed to understand the likelihood that a female mouse or a woman will enter labor.

The association of children's mathematic abilities with both adults' cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals.

PubMed

Bäuml, J G; Meng, C; Daamen, M; Baumann, N; Busch, B; Bartmann, P; Wolke, D; Boecker, H; Wohlschläger, A; Sorg, C; Jaekel, Julia

2017-03-01

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8 years and resting-state fMRI and full-scale IQ testing at 26 years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults' IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children's mathematic abilities and adults' fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults' IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children's mathematic abilities may represent potential neurocognitive targets for early intervention.

Physiology and Electrical Activity of Uterine Contractions

PubMed Central

Garfield, Robert E.; Maner, William L.

2007-01-01

Presently, there is no effective treatment for preterm labor. The most obvious reason for this anomaly is that there is no objective manner to evaluate the progression of pregnancy through steps leading to labor, either at term or preterm. Several techniques have been adopted to monitor labor, and/or to diagnose labor, but they are either subjective or indirect, and they do not provide an accurate prediction of when labor will occur. With no method to determine preterm labor, treatment might never improve. Uterine EMG (electromyography) methods may provide such needed diagnostics. PMID:17659954

A comparison of methods for estimating the weight of preterm infants.

PubMed

Elser, A S; Vessey, J A

1995-09-01

Four methods of predicting a preterm infant's weight (upper mid-arm circumference, gestational age, tape measure nomogram, and guessing) were investigated to see which was the most accurate. The weights of 37 preterm neonates were initially guessed by an experienced clinician, then estimated by the other three approaches applied in a random order, and then confirmed through actual weighing. The correlations between the four estimated weights and the actual weights were .96, .84, .97, and .98, respectively. The tape measure nomogram method was the best overall approach for clinical use.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

PubMed

Sengpiel, Verena; Bacelis, Jonas; Myhre, Ronny; Myking, Solveig; Pay, Aase Devold; Haugen, Margaretha; Brantsæter, Anne-Lise; Meltzer, Helle Margrete; Nilsen, Roy M; Magnus, Per; Vollset, Stein Emil; Nilsson, Staffan; Jacobsson, Bo

2013-08-12

Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999-2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4-5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). The median total folate intake was 266 μg/d (interquartile range IQR 154-543) in the overall population and 540 μg/d (IQR 369-651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

Preterm infants who are prone to distress: differential effects of parenting on 36-month behavioral and cognitive outcomes.

PubMed

Poehlmann, Julie; Hane, Amanda; Burnson, Cynthia; Maleck, Sarah; Hamburger, Elizabeth; Shah, Prachi E

2012-10-01

The differential susceptibility (DS) model suggests that temperamentally prone-to-distress infants may exhibit adverse outcomes in negative environments but optimal outcomes in positive environments. This study explored temperament, parenting, and 36-month cognition and behavior in preterm infants using the DS model. We hypothesized that temperamentally prone to distress preterm infants would exhibit more optimal cognition and fewer behavior problems when early parenting was positive; and less optimal cognition and more behavior problems when early parenting was less positive. Participants included 109 preterm infants (gestation <37 weeks) and their mothers. We assessed neonatal risk and basal vagal tone in the neonatal intensive care unit; infant temperament and parenting interactions at 9 months post-term; and child behavior and cognitive skills at 36 months post-term. Hierarchical regression analyses tested study hypotheses. Temperamentally prone-to-distress infants exhibited more externalizing problems if they experienced more critical parenting at 9 months (β = -.20, p < 0.05) but fewer externalizing problems with more positive parenting. Similarly, variations in maternal positive affect (β = .25, p < .01) and intrusive behaviors (β = .23, p < .05) at 9 months predicted 36-month cognition at high but not at low levels of infant temperamental distress. Higher basal vagal tone predicted fewer externalizing problems (β = -.19, p < .05). Early parenting behaviors relate to later behavior and development in preterm infants who are temperamentally prone to distress, and neonatal basal vagal tone predicts subsequent externalizing behaviors. These findings suggest that both biological reactivity and quality of caregiving are important predictors for later outcomes in preterm infants and may be considered as foci for developmental surveillance and interventions. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial.

PubMed

Goya, Maria; Pratcorona, Laia; Merced, Carme; Rodó, Carlota; Valle, Leonor; Romero, Azahar; Juan, Miquel; Rodríguez, Alberto; Muñoz, Begoña; Santacruz, Belén; Bello-Muñoz, Juan Carlos; Llurba, Elisa; Higueras, Teresa; Cabero, Luis; Carreras, Elena

2012-05-12

Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery. The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264. 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0·18, 95% CI 0·08-0·37; p<0·0001). No serious adverse effects associated with the use of a cervical pessary were reported. Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan. Instituto Carlos III. Copyright © 2012 Elsevier Ltd. All rights reserved.

CXCL6 (Granulocyte Chemotactic Protein-2): a novel chemokine involved in the innate immune response of the amniotic cavity

PubMed Central

Mittal, Pooja; Romero, Roberto; Kusanovic, Juan Pedro; Edwin, Samuel S.; Gotsch, Francesca; Mazaki-Tovi, Shali; Espinoza, Jimmy; Erez, Offer; Nhan-Chang, Chia-Ling; Than, Nandor G; Vaisbuch, Edi; Hassan, Sonia S

2008-01-01

PROBLEM CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (preterm and term) or intra-amniotic infection/inflammation (IAI). METHOD OF STUDY A cross-sectional study was conducted with the following groups: 1) mid-trimester (n=65); 2) term no labor (n=20); 3) term labor (n=44); 4) patients with PTL with subsequent term delivery (n=57); 5) preterm labor (PTL) without IAI who delivered preterm (n=47); and 6) PTL with IAI (n=62). AF CXCL6 concentrations were determined by ELISA. RESULTS CXCL6 was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median CXCL6 AF concentration than those with PTL without IAI [228.9 pg/ml (0.0–8344.8) vs. 55.7 pg/ml (0–454.4); p<0.05] and those with PTL and term delivery [41.5 pg/ml (0–279.0); p<0.05]. Median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/ml (8.5–201.7) vs. term labor: 75.2 pg/ml (6.7–378.7): p=0.74]. CONCLUSIONS 1) CXCL6 is detectable in AF and its concentration increases with gestational age; 2) IAI results in increased CXCL6 AF concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; 3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity. PMID:18782286

Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: a meta-analysis of randomized controlled trials.

PubMed

Lu, Chang; Liu, Yong; Jiang, Hai-Li

2018-01-10

This study was designed to evaluate the efficacy of aspirin or heparin or both in the treatment for recurrent spontaneous abortion (RSA) in women with antiphospholipid antibody syndrome (APS). Systematic searches for randomized clinical trials (RCTs) evaluating on live birth and preterm delivery, preeclampsia, intrauterine growth restriction, gestational diabetes, bleeding of RSA with APS patients receiving aspirin, and heparin therapy were carried out, from PubMed, EMBASE, ScienceDirect, and CNKI. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Relative risk (RR) and its 95% confidence interval were calculated. Nineteen publications with randomized controlled trials were selected for this study, which included a total of 1251 pregnant patients with diagnosis of RSA with APS. With respect to live birth, it was remarkably improved in aspirin plus heparin or heparin alone group [RR =1.23, 95% CI (1.12-1.36), p < .0001; RR = 1.18, 95% CI (1.03-1.35), p = .02]; aspirin alone group, however, there was no statistically significant difference compare to placebo [RR = 0.97, 95% CI (0.80-1.16), p = .71]. Meanwhile, aspirin plus heparin therapy did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications including preterm birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor bleeding. A beneficial therapeutic effect of heparin alone therapy was found on preventing preterm birth and low-dose aspirin plus heparin therapy was significant reduce the risk of preeclampsia. An improvement of pregnancy outcomes in women with RSA and APS can be achieved by treatment strategies combining low-dose aspirin plus heparin or heparin alone. Aspirin alone, by contrast, seemed inferior to other treatments in achieving more live birth.

Validation of CRIB II for prediction of mortality in premature babies.

PubMed

Rastogi, Pallav Kumar; Sreenivas, V; Kumar, Nirmal

2010-02-01

Validation of Clinical Risk Index for Babies (CRIB II) score in predicting the neonatal mortality in preterm neonates < or = 32 weeks gestational age. Prospective cohort study. Tertiary care neonatal unit. 86 consecutively born preterm neonates with gestational age < or = 32 weeks. The five variables related to CRIB II were recorded within the first hour of admission for data analysis. The receiver operating characteristics (ROC) curve was used to check the accuracy of the mortality prediction. HL Goodness of fit test was used to see the discrepancy between observed and expected outcomes. A total of 86 neonates (males 59.6% mean birthweight: 1228 +/- 398 grams; mean gestational age: 28.3 +/- 2.4 weeks) were enrolled in the study, of which 17 (19.8%) left hospital against medical advice (LAMA) before reaching the study end point. Among 69 neonates completing the study, 24 (34.8%) had adverse outcome during hospital stay and 45 (65.2%) had favorable outcome. CRIB II correctly predicted adverse outcome in 90.3% (Hosmer Lemeshow goodness of fit test P=0.6). Area under curve (AUC) for CRIB II was 0.9032. In intention to treat analysis with LAMA cases included as survivors, the mortality prediction was 87%. If these were included as having died then mortality prediction was 83.1%. The CRIB II score was found to be a good predictive instrument for mortality in preterm infants < or = 32 weeks gestation.

Validation of spontaneous assessment of baroreceptor reflex sensitivity and its relation to heart rate variability in the ovine fetus pre- and near-term.

PubMed

Frasch, Martin G; Müller, Thomas; Szynkaruk, Mark; Schwab, Matthias

2009-09-01

Assessment of baroreceptor reflex sensitivity (BRS) in the ovine fetus provides insight into autonomic cardiovascular regulation. Currently, assessment of BRS relies on vasoactive drugs, but this approach is limited by feasibility issues and by the nonphysiologic nature of the stimulus. Thus we aimed to validate the method of spontaneous BRS assessment against the reference method of using vasoactive drugs in preterm (0.76 gestation, n = 16) and near-term (0.86 gestation, n = 16) chronically instrumented ovine fetuses. The BRS measures derived from the spontaneous and reference methods correlated at both gestational ages (R = 0.67 +/- 0.03). The sequence method of spontaneous BRS measures also correlated both to the root mean square of standard deviations (RMSSD), which is a measure of fetal heart rate variability reflecting vagal modulation (R = 0.69 +/- 0.03), and to fetal body weight (R = 0.65 +/- 0.03), which is a surrogate for growth trajectory of each fetus. The methodology presented may aid in developing new models to study BRS and cardiovascular control in ovine fetus in the last trimester of pregnancy.

Arsenic exposure in pregnant mice disrupts placental vasculogenesis and causes spontaneous abortion.

PubMed

He, Wenjie; Greenwell, Robert J; Brooks, Diane M; Calderón-Garcidueñas, Lilian; Beall, Howard D; Coffin, J Douglas

2007-09-01

Arsenic is an abundant toxicant in ground water and soil around areas with extractive industries. Human epidemiological studies have shown that arsenic exposure is linked to developmental defects and miscarriage. The placenta is known to utilize vasculogenesis to develop its circulation. The hypothesis tested here states the following: arsenic exposure causes placental dysmorphogenesis and defective placental vasculogenesis resulting in placental insufficiency and subsequent spontaneous abortion. To test this hypothesis, pregnant mice were exposed to sodium arsenite (AsIII) through drinking water from conception through weanling stages. Neonatal assessment of birth rates, pup weights, and litter sizes in arsenic exposed and control mothers revealed that AsIII-exposed mothers had only 40% the fecundity of controls. Preterm analysis at E12.5 revealed a loss of fecundity at E12.5 from either 20 ppm or greater exposures to AsIII. There was no loss of fecundity at E7.5 suggesting that spontaneous abortion occurs during placentation. Histomorphometry on E12.5 placentae from arsenic-exposed mice revealed placental dysplasia especially in the vasculature. These results suggest that arsenic toxicity is causative for mammalian spontaneous abortion by virtue of aberrant placental vasculogenesis and placental insufficiency.

Quantification of fetal magnetoencephalographic activity in low-risk fetuses using burst duration and interburst interval.

PubMed

Vairavan, Srinivasan; Govindan, Rathinaswamy B; Haddad, Naim; Preissl, Hubert; Lowery, Curtis L; Siegel, Eric; Eswaran, Hari

2014-07-01

To identify quantitative MEG indices of spontaneous brain activity for fetal neurological maturation in normal pregnancies and examine the effect of fetal state on these indices. Spontaneous MEG brain activity was examined in 22 low-risk fetal recordings with gestational age (GA) ranging from 30 to 37 weeks. As major quantitative characteristics of spontaneous activity, burst duration (BD) and interburst interval (IBI) were studied in correlation with GA and fetal state. IBI showed a decrease with gestational age (-0.21 s/week, P=0.0031). This trend was only maintained in the quiet-sleep state. With respect to BD, no significant trends were detected with GA and state. IBI can be quantified as a fetal brain maturational parameter. The decrease in IBI over gestation was similar to the trend reported in the preterm neonatal EEG studies. Quiet sleep could be the optimal state to study such MEG maturational indices. With further investigation, indices extracted from spontaneous fetal brain activity may serve as an early warning for fetal neurological distress. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Predictors of preterm birth in patients with mild systemic lupus erythematosus.

PubMed

Clowse, Megan E B; Wallace, Daniel J; Weisman, Michael; James, Andra; Criscione-Schreiber, Lisa G; Pisetsky, David S

2013-09-01

While increased disease activity is the best predictor of preterm birth in women with systemic lupus erythematosus (SLE), even women with low disease activity are at increased risk of this complication. Biomarkers that would identify at-risk pregnancies could allow interventions to prevent preterm birth. Measures of SLE activity, inflammation, placental health and renal function between 20 and 28 weeks gestation (mid-gestation) were correlated to preterm birth and gestational age at delivery in a prospective cohort of pregnant women with SLE. Of the 40 pregnancies in 39 women, all with mild-moderate SLE disease, 9 (23.7%) of the 38 live births were delivered preterm. Low C4 was the only marker of SLE activity associated with younger gestational age at delivery. Elevated ferritin and lower oestradiol correlated with younger gestational age at delivery. Renal function remained normal during all pregnancies at mid-gestation and did not correlate with preterm birth. Higher serum uric acid, however, correlated with younger gestational age at delivery. In women with SLE with mild-moderate disease activity, ferritin, oestradiol and uric acid levels at mid-gestation may predict preterm birth. These markers may prove to be clinically useful in identifying pregnancies at particularly high risk for adverse outcomes.

Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

PubMed

Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

2017-10-01

We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

Predicting motor development in very preterm infants at 12 months' corrected age: the role of qualitative magnetic resonance imaging and general movements assessments.

PubMed

Spittle, Alicia J; Boyd, Roslyn N; Inder, Terrie E; Doyle, Lex W

2009-02-01

The objective of this study was to compare the predictive value of qualitative MRI of brain structure at term and general movements assessments at 1 and 3 months' corrected age for motor outcome at 1 year's corrected age in very preterm infants. Eighty-six very preterm infants (<30 weeks' gestation) underwent MRI at term-equivalent age, were evaluated for white matter abnormality, and had general movements assessed at 1 and 3 months' corrected age. Motor outcome at 1 year's corrected age was evaluated with the Alberta Infant Motor Scale, the Neuro-Sensory Motor Development Assessment, and the diagnosis of cerebral palsy by the child's pediatrician. At 1 year of age, the Alberta Infant Motor Scale categorized 30 (35%) infants as suspicious/abnormal; the Neuro-Sensory Motor Development Assessment categorized 16 (18%) infants with mild-to-severe motor dysfunction, and 5 (6%) infants were classified with cerebral palsy. White matter abnormality at term and general movements at 1 and 3 months significantly correlated with Alberta Infant Motor Scale and Neuro-Sensory Motor Development Assessment scores at 1 year. White matter abnormality and general movements at 3 months were the only assessments that correlated with cerebral palsy. All assessments had 100% sensitivity in predicting cerebral palsy. White matter abnormality demonstrated the greatest accuracy in predicting combined motor outcomes, with excellent levels of specificity (>90%); however, the sensitivity was low. On the other hand, general movements assessments at 1 month had the highest sensitivity (>80%); however, the overall accuracy was relatively low. Neuroimaging (MRI) and functional (general movements) examinations have important complementary roles in predicting motor development of very preterm infants.

One-year neurodevelopmental outcome of very and late preterm infants: Risk factors and correlation with maternal stress.

PubMed

Coletti, Maria Franca; Caravale, Barbara; Gasparini, Corinna; Franco, Francesco; Campi, Francesca; Dotta, Andrea

2015-05-01

Although "late preterm" (LP) newborns (33-36 weeks of gestational age) represent more than 70% of all preterm labors, little is known about the relation between certain risk factors and developmental outcomes in LP compared to "very preterm" (≤32 weeks) children (VP). This study investigates: (1) LP and VP infants' development at 12 months of corrected age (CA) using the Bayley Scales of Infant Development - 3rd Edition (BSID-III); (2) correlation between BSID-III performances and maternal stress (using Parenting Stress Index-Short Form, PSI-SF) among LP and VP at 12 months CA; and (3) the link between known neonatal and demographic risk factors and developmental outcomes of LP and VP infants. For both LP and VP infants the Mean Cognitive (LP: 102.69±7.68; VP: 103.63±10.68), Language (LP: 96.23±10.08; VP: 99.10±10.37) and Motor (LP: 91.11±10.33; VP: 93.85±10.17) composite scores were in the normal range, without significant differences between the groups. Correlations between PSI-SF and BSID-III showed that in the VP group (but not LP), Language score was negatively related to the PSI-SF 'Difficult Child' scale (r=-.34, p<.05). Regression models revealed that cognitive performance was significantly predicted by physical therapy in LP and by cesarean section in VP infants. For VP only maternal education and length of stay predicted Language score, whereas physical therapy predicted Motor score. Results of the study underline the importance of considering cognitive, language and motor developments separately when assessing a preterm child's development. Prediction models of developmental performance confirm the influence of some known neonatal risk factors and indicate the need for further research on the role of sociodemographic risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

Copper metabolism domain-containing 1 represses the mediators involved in the terminal effector pathways of human labour and delivery.

PubMed

Lappas, Martha

2016-04-01

Does Copper Metabolism MURR1 Domain 1 (COMMD1) play a role in regulating the mediators involved in the terminal processes of human labour and delivery? COMMD1 plays a critical role in the termination of nuclear factor-κB (NF-κB) activity and the control of pro-inflammatory and pro-labour mediators. Inflammation and infection are the biggest aetiological factors associated with preterm birth. NF-κB drives the transcription of pro-inflammatory mediators involved in the terminal effector pathways of human labour and delivery. In non-gestational tissues, COMMD1 is a negative regulator of NF-κB-induced inflammation. The mRNA and/or protein level of COMMD1 was assessed in myometrium (n = 8 per group) and fetal membranes (n = 8 per group) obtained from term non-labouring and labouring women at term, and fetal membranes (n = 8 per group) at preterm with and without histological chorioamnionitis. Primary human myometrial cells were used to determine the effect of pro-inflammatory mediators on COMMD1 level, and the effect of COMMD1 small interfering RNA (siRNA) on pro-labour mediators. Statistical significance was ascribed to a P < 0.05. COMMD1 expression was significantly decreased with spontaneous term labour in myometrium; in fetal membranes with histologically confirmed chorioamnionitis and in myometrial cells treated with pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α, the bacterial product fibroblast-stimulating lipopeptide and the viral double stranded RNA analogue polyinosinic polycytidilic acid. Loss-of-function studies revealed an increase in inflammation- and infection-induced TNF-α, IL-1α, IL-1β, IL-6, IL-8 and/or monocyte chemoattractant protein-1 mRNA abundance and/or release; and cyclo-oxygenase-2 mRNA level, release of prostaglandin (PG) F2α and mRNA level of the PGF2α receptor FP. In addition, siRNA knockdown of COMMD1 was associated with significantly increased NF-κB activation as evidenced by increased IL-1β-induced IκB-α protein degradation and NF-κB DNA binding activity. The conclusions are based on in vitro experiments with cells isolated from myometrium. Animal models, however, will be required to establish whether COMMD1 activators can prevent spontaneous preterm birth in vivo. The control of COMMD1 activation may provide an alternative therapeutic strategy for reducing the release of pro-labour mediators in spontaneous preterm labour. Not applicable. Associate Professor Martha Lappas is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025). Additional funding was provided by the Medical Research Foundation for Women and Babies and the Mercy Research Foundation. The author has no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Limitations of ultrasonography for diagnosing white matter damage in preterm infants.

PubMed

Debillon, T; N'Guyen, S; Muet, A; Quere, M P; Moussaly, F; Roze, J C

2003-07-01

To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. Prospective cohort study. A neonatal intensive care unit in France. All preterm infants (

Limitations of ultrasonography for diagnosing white matter damage in preterm infants

PubMed Central

Debillon, T; N'Guyen, S; Muet, A; Quere, M; Moussaly, F; Roze, J

2003-01-01

Objectives: To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. Design: Prospective cohort study. Setting: A neonatal intensive care unit in France. Patients: All preterm infants (≤ 33 weeks gestation) without severe respiratory distress syndrome precluding MRI. Main outcome measures: US and MRI performed contemporaneously during the third postnatal week were analysed by an independent observer. The findings were compared with those of a term MRI scan, the results of which were taken as the final diagnosis. Statistical analysis was performed to determine which early imaging study best predicted the term MRI findings. Results: The early US and MRI findings (79 infants) correlated closely for severe lesions (cystic periventricular leucomalacia and parenchymal infarction; κ coefficient = 0.86) but not for moderate lesions (non-cystic leucomalacia and parenchymal punctate haemorrhages; κ = 0.62). Overall, early MRI findings predicted late MRI findings in 98% of patients (95% confidence interval (CI) 89.5 to 99.9) compared with only 68% for early US (95% CI 52.1 to 79.2). Conclusions: US is highly effective in detecting severe lesions of the white matter in preterm infants, but MRI seems to be necessary for the diagnosis of less severe damage. MRI performed at about the third week of life is highly predictive of the final diagnosis at term. PMID:12819157

Late-Preterm Birth, Maternal Symptomatology, and Infant Negativity

PubMed Central

Voegtline, Kristin M.; Stifter, Cynthia A.

2010-01-01

The present study examined infant negativity and maternal symptomatology by term status in a predominately low-income, rural sample of 132 infants (66 late-preterm) and their mothers. Late-preterm and term infants were group-matched by race, income, and maternal age. Maternal depression and anxiety symptoms were measured with the Brief Symptom Inventory 18 (BSI-18) when infants were 2 and 6 months of age. Also at 6 months, infant negativity was assessed by global observer ratings, maternal ratings, and microanalytic behavioral coding of fear and frustration. Results indicate that after controlling for infant age, late-preterm status predicted higher ratings of infant negativity by mothers, but not by global observers or microanalytic coding, despite a positive association in negativity across the three measures. Further, mothers of late-preterm infants reported more elevated and chronic co-morbid symptoms of depression and anxiety, which in turn, was related to concurrent maternal ratings of their infant’s negativity. Mothers response to late-preterm birth and partiality in the assessment of their infant’s temperament is discussed. PMID:20732715

Assessment of maternal serum sialic acid levels in preterm versus term labor: a prospective-controlled clinical study.

PubMed

Ugur, Mete Gurol; Kurtul, Naciye; Balat, Ozcan; Ekici, Melek; Kul, Seval

2012-11-01

To compare total serum sialic acid (SA) levels between singleton pregnant women diagnosed with preterm labor between 24th and 36th weeks of pregnancy, singleton pregnant women at term, and their gestational age-matched controls. Thirty pregnants diagnosed with preterm labor (group I), 30 gestational age-matched control pregnants (group II), 30 pregnants with labor at term (group III), and 30 gestational age-matched control pregnants (group IV) were enrolled. Detailed history, demographic data (age, gravidity, parity, abortion), ultrasound parameters, cervical dilatation and effacement, fetal tococardiography, routine laboratory tests, and total SA levels were assessed. There was no statistically significant difference between the parameters other than SA. SA levels of the preterm labor group (group I) were significantly higher than the other three groups. We may suggest that pathways including SA or molecules containing SA in subclinical infection without the clinical manifestations of apparent infection may be involved in the pathogenesis of preterm birth. Future longitudinal studies are needed to investigate prediction performance and to better understand the role of SA in molecular mechanisms leading to preterm labor.

Maternal speech to preterm infants during the first 2 years of life: stability and change.

PubMed

Suttora, Chiara; Salerni, Nicoletta

2011-01-01

Studies on typical language development documented that mothers fine-tune their verbal input to children's advancing skills and development. Although premature birth has often been associated with delays in communicative and language development, studies investigating maternal language addressed to these children are still rare. The principal aim of this longitudinal study was to investigate the maternal speech directed at very preterm children by examining its changes across time and the stability of maternal individual styles. A sample of 16 mother-preterm infant dyads participated in semi-structured play sessions when children were 6, 12, 18 and 24 months of corrected age. Maternal speech directed at the children was analysed in terms of lexical and syntactical complexity as well as verbal productivity. Also children's motor, cognitive and communicative skills were assessed. Results highlight an overall increase in the lexical and syntactical complexity and in the amount of maternal speech across the first years of life. At the same time, individual maternal communicative styles seem stable as infants grow older, even if between 12 and 18 months all the indices' predictive values decrease, indicating a noteworthy modification in individual maternal styles. Furthermore, between 12 and 18 months predictive relationships between children's motor and vocal skills and maternal changes in input were found. Verbal input addressed to children born preterm during the first 2 years of life does not seem to differ considerably from the language usually used with full-term infants. Nevertheless, maternal verbal adjustments seem to be predicted by earlier infant achievements in vocal and motor development. This suggests that infants' motor skill maturation may function as a major signal for mothers of preterm babies to adjust aspects of their linguistic interactive style. © 2011 Royal College of Speech & Language Therapists.

Poor Sleep Quality and Associated Inflammation Predict Preterm Birth: Heightened Risk among African Americans.

PubMed

Blair, Lisa M; Porter, Kyle; Leblebicioglu, Binnaz; Christian, Lisa M

2015-08-01

Poor sleep promotes inflammation. In turn, inflammation is a causal mechanism in term as well as preterm parturition. In the United States, a persistent racial disparity in preterm birth exists, with African Americans showing ∼1.5 times greater risk. This study examined associations among sleep quality, serum proinflammatory cytokines, and length of gestation in a racially diverse sample of 138 pregnant women. Observational. Women completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α were determined by high-sensitivity assays. Birth outcomes were determined via medical record review. Among African American women (n = 79), shorter gestation was predicted by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs = -0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth compared to those with good sleep quality. In contrast, among European American women (n = 53), gestational length was not significantly predicted by sleep quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans, IL-8 significantly mediated the association between sleep quality and length of gestation (indirect effect estimate -0.029; 95% confidence interval -0.06, -0.002). The data provide novel evidence that African American women exhibit greater inflammation in response to sleep disturbance than European American women and these effects correspond with length of gestation. Racial differences in susceptibility to sleep induced immune dysregulation may contribute to marked racial disparities in preterm birth. © 2015 Associated Professional Sleep Societies, LLC.

Refining the Use of Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants.

PubMed

Manley, Brett J; Roberts, Calum T; Frøisland, Dag H; Doyle, Lex W; Davis, Peter G; Owen, Louise S

2018-05-01

To identify clinical and demographic variables that predict nasal high-flow (nHF) treatment failure when used as a primary respiratory support for preterm infants. This secondary analysis used data from a multicenter, randomized, controlled trial comparing nHF with continuous positive airway pressure as primary respiratory support in preterm infants 28-36 completed weeks of gestation. Treatment success or failure with nHF was determined using treatment failure criteria within the first 72 hours after randomization. Infants in whom nHF treatment failed received continuous positive airway pressure, and were then intubated if failure criteria were again met. There were 278 preterm infants included, with a mean gestational age (GA) of 32.0 ± 2.1 weeks and a birth weight of 1737 ± 580 g; of these, nHF treatment failed in 71 infants (25.5%). Treatment failure was moderately predicted by a lower GA and higher prerandomization fraction of inspired oxygen (FiO 2 ): area under a receiver operating characteristic curve of 0.76 (95% CI, 0.70-0.83). Nasal HF treatment success was more likely in infants born at ≥30 weeks GA and with prerandomization FiO 2 <0.30. In preterm infants ≥28 weeks' GA enrolled in a randomized, controlled trial, lower GA and higher FiO 2 before randomization predicted early nHF treatment failure. Infants were more likely to be successfully treated with nHF from soon after birth if they were born at ≥30 weeks GA and had a prerandomization FiO 2 <0.30. However, even in this select population, continuous positive airway pressure remains superior to nHF as early respiratory support in preventing treatment failure. Australian New Zealand Clinical Trials Registry: ACTRN12613000303741. Copyright © 2018 Elsevier Inc. All rights reserved.

The Aristotle score predicts mortality after surgery of patent ductus arteriosus in preterm infants.

PubMed

Chang, Yun Hee; Lee, Jae Young; Kim, Jeong Eun; Kim, Ji-yong; Youn, YoungAh; Lee, Eun-Jung; Moon, Sena; Lee, Ju Young; Sung, In Kyung

2013-09-01

Outcomes after surgical ligation of patent ductus arteriosus (PDA) in preterm infants are often complicated by prematurity associated comorbidities. The Aristotle comprehensive complexity score (ACCS) has been proposed as a useful tool for complexity adjustment in the analysis of outcome after congenital heart surgery. The aims of this study were to define preoperative risk factors for mortality and to demonstrate the usefulness of ACCS to predict mortality after surgical ligation of PDA in the preterm. Included were 49 preterm babies (≤35 weeks of gestation) who had surgical ligation of PDA between May 2009 and July 2012. Median gestational age was 27.6 weeks (range, 23 to 35 weeks) and median birth weight was 1,040 g (range, 520 to 2,280 g). Median age at operation was 15 days (range, 4 to 44 days) and median weight was 1,120 g (range, 400 to 2,880 g). Initial oral ibuprofen was ineffective in 24 patients and contraindicated in 25. All surgical ligations were done at bedside in the neonatal intensive care unit. Preoperative clinical and laboratory profiles were reviewed and ACCS was derived. Eight of 49 patients (16.3%) died at a median of 14 days (range, 2 to 73 days) after PDA ligation. Patients who had contraindications for oral ibuprofen (odds ratio [OR] 8.94; p=0.049), coagulopathy (OR 12.13; p=0.025), renal dysfunction (OR 28.88; p=0.003), intraventricular hemorrhage greater than grade II or seizure (OR 34.00; p=0.002), and ACCS points (OR 29.594; p<0.05) were significantly associated with an increased risk for mortality. Among the risk factors, ACCS showed the largest area under curve (0.991) by receiver-operating characteristic curve analysis. Optimal cutoff value of ACCS for mortality were 15 or greater, with sensitivity of 87.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 97.6%. The ACCS, especially for procedure-independent complexity factors, is a useful tool to predict mortality after ligation of PDA in preterm infants. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Feed-related Splanchnic Oxygenation in Preterm Infants With Abnormal Antenatal Doppler Developing Gut Complications.

PubMed

Martini, Silvia; Aceti, Arianna; Beghetti, Isadora; Faldella, Giacomo; Corvaglia, Luigi

2018-05-01

Preterm infants with antenatal absent or reversed end diastolic flow (AREDF) in umbilical arteries are at major risk for gastrointestinal (GI) complications, such as necrotizing enterocolitis, intestinal perforation and feeding intolerance. Near-infrared spectroscopy provides continuous monitoring of splanchnic oxygenation (SrSO2) and may represent a useful tool to predict GI outcomes in this high-risk population. This observational, pilot study assessed feed-related SrSO2 patterns at enteral feeding introduction and full enteral feeding (FEF) achievement in twenty AREDF infants with gestational age ≤34 weeks. Enrolled infants were divided into 2 groups according to the development versus lack of GI complications. Infants developing GI complications showed significantly lower SrSO2 and increased splanchnic oxygen extraction in response to enteral feeds at both enteral feeding introduction and FEF. The potential role of these findings in predicting GI complications in AREDF preterm infants seems promising and deserves further evaluation.

Placental Leucine Aminopeptidase- and Aminopeptidase A- Deficient Mice Offer Insight concerning the Mechanisms Underlying Preterm Labor and Preeclampsia

PubMed Central

Mizutani, Shigehiko; Wright, John W.; Kobayashi, Hiroshi

2011-01-01

Preeclampsia and preterm delivery are important potential complications in pregnancy and represent the leading causes for maternal and perinatal morbidity and mortality. The mechanisms underlying both diseases remain unknown, thus available treatments (beta2-stimulants and magnesium sulfate) are essentially symptomatic. Both molecules have molecular weights less than 5–8 kDa, cross the placental barrier, and thus exert their effects on the fetus. The fetus produces peptides that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP) and aminopeptidase A (APA) are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. P-LAP also acts as an antiuterotonic agent by degrading uterotonic peptides and thus prolongs gestation in the pregnant mouse. Given the ever increasing worldwide incidences of preeclampsia and preterm labor, it is imperative that new agents be developed to safely prolong gestation. We believe that the use of aminopeptidases hold promise in this regard. PMID:21188170

Deployment and Preterm Birth Among US Army Soldiers.

PubMed

Shaw, Jonathan G; Nelson, D Alan; Shaw, Kate A; Woolaway-Bickel, Kelly; Phibbs, Ciaran S; Kurina, Lianne M

2018-04-01

With increasing integration of women into combat roles in the US military, it is critical to determine whether deployment, which entails unique stressors and exposures, is associated with adverse reproductive outcomes. Few studies have examined whether deployment increases the risk of preterm birth; no studies (to our knowledge) have examined a recent cohort of servicewomen. We therefore used linked medical and administrative data from the Stanford Military Data Repository for all US Army soldiers with deliveries between 2011 and 2014 to estimate the associations of prior deployment, recency of deployment, and posttraumatic stress disorder with spontaneous preterm birth (SPB), adjusting for sociodemographic, military-service, and health-related factors. Of 12,877 deliveries, 6.1% were SPBs. The prevalence was doubled (11.7%) among soldiers who delivered within 6 months of their return from deployment. Multivariable discrete-time logistic regression models indicated that delivering within 6 months of return from deployment was strongly associated with SPB (adjusted odds ratio = 2.1, 95% confidence interval: 1.5, 2.9). Neither multiple past deployments nor posttraumatic stress disorder was significantly associated with SPB. Within this cohort, timing of pregnancy in relation to deployment was identified as a novel risk factor for SPB. Increased focus on servicewomen's pregnancy timing and predeployment access to reproductive counseling and effective contraception is warranted.

Obstetric outcomes of patients with abortus imminens in the first trimester.

PubMed

Evrenos, Ayşe Nur; Cakir Gungor, Ayse Nur; Gulerman, Cavidan; Cosar, Emine

2014-03-01

We aimed to find out the effect of abortus imminens (AI) on obstetric outcomes of pregnancies which continued beyond the 24th week of gestation. In this prospective study, 309 patients with AI were divided into high-risk group (with a risk factor for spontaneous abortus) (n = 92) and low-risk group (without a risk factor) (n = 217). The control group (n = 308) was chosen randomly. In AI group, preterm delivery, preterm premature rupture of membranes (PPROM), cesarean section (C/S) delivery, postpartum uterine atony and need of a neonatal intensive care unit (NICU) rates were significantly higher than control group. Gestational diabetes mellitus, PPROM, still birth, low APGAR scores were seen more frequently in the high-risk patients than in the control group. Furthermore in the high-risk group, preterm delivery, malpresentation, C/S delivery and need of NICU were increased much more than in the low-risk group. Gestational hypertension/preeclampsia, oligo/polyhydramniosis, intrauterine growth retardation, placenta previa, abruption of placenta, chorioamnionitis, congenital abnormalities, delivery induction, cephalopelvic disproportion, fetal distress and manual removal of placenta were not different among the groups. Patients with AI history, especially with high-risk factors can have adverse obstetric and neonatal results. So their antenatal follow-up has to be done cautiously for the early signs and symptoms of these complications.

In which preterm labor-patients is intravenous maintenance tocolysis effective?

PubMed

Yoneda, Satoshi; Yoneda, Noriko; Fukuta, Kaori; Shima, Tomoko; Nakashima, Akitoshi; Shiozaki, Arihiro; Yoshino, Osamu; Kigawa, Mika; Yoshida, Taketoshi; Saito, Shigeru

2018-03-01

We evaluated whether maintenance tocolysis (intravenous ritodrine hydrochloride and/or magnesium sulfate) was effective in cases of spontaneous preterm labor with intact membranes. One hundred and thirty preterm labor patients who reached 36 weeks of gestation by maintenance tocolysis were selected. Immediate delivery (ID) after ceasing maintenance tocolysis was defined as an 'effective case'. The correlated factors between ID and no immediate delivery (NID) were statistically analyzed. Thirty-six patients delivered < two days after ceasing maintenance tocolysis (27.7%) and were defined as effective cases. Multiple logistic regression analysis revealed that amniotic fluid interleukin-8 at admission (≥ 2.3 ng/mL; odds ratio [OR] 5.6, 95% confidence interval [CI] 2.1-17.6; P < 0.001), pre-pregnancy body mass index (≤ 21.4; OR 5.3, 95% CI 2.0-16.2; P < 0.001) and cerclage (OR 3.6, 95% CI 1.1-11.8; P = 0.028) were independent factors correlated with ID (< 2 days). Maintenance tocolysis may be effective in limited cases with mild intra-amniotic inflammation, in lean women and in cerclage cases. Maintenance tocolysis should be ceased in cases without these clinical factors when clinical symptoms disappear. © 2017 Japan Society of Obstetrics and Gynecology.

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

PubMed

Bruijn, Merel M C; Hermans, Frederik J R; Vis, Jolande Y; Wilms, Femke F; Oudijk, Martijn A; Kwee, Anneke; Porath, Martina M; Oei, Guid; Scheepers, Hubertina C J; Spaanderman, Marc E A; Bloemenkamp, Kitty W M; Haak, Monique C; Bolte, Antoinette C; Vandenbussche, Frank P H A; Woiski, Mallory D; Bax, Caroline J; Cornette, Jérôme M J; Duvekot, Johannes J; Bijvank, Bas W A N I J; van Eyck, Jim; Franssen, Maureen T M; Sollie, Krystyna M; van der Post, Joris A M; Bossuyt, Patrick M M; Kok, Marjolein; Mol, Ben W J; van Baaren, Gert-Jan

2017-02-01

Objective  We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods  We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results  Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion  The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults.

PubMed

Bäuml, Josef G; Daamen, Marcel; Meng, Chun; Neitzel, Julia; Scheef, Lukas; Jaekel, Julia; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Boecker, Henning; Wohlschläger, Afra M; Sorg, Christian

2015-11-01

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Parenting Behavior at 2 Years Predicts School-age Performance at 7 Years in Very Preterm Children

ERIC Educational Resources Information Center

Treyvaud, Karli; Doyle, Lex W.; Lee, Katherine J.; Ure, Alexandra; Inder, Terrie E.; Hunt, Rod W.; Anderson, Peter J.

2016-01-01

Parenting influences child development, but it is unclear whether early parenting behavior can influence school-age outcomes in very preterm (VPT) children, and/or if certain groups of VPT children may be more affected by early parenting behavior. These research questions were examined. Participants were 147 children born <30 weeks' gestation…

Do Healthy Preterm Children Need Neuropsychological Follow-Up? Preschool Outcomes Compared with Term Peers

ERIC Educational Resources Information Center

Dall'Oglio, Anna M.; Rossiello, Barbara; Coletti, Maria F.; Bultrini, Massimiliano; De Marchis, Chiara; Rava, Lucilla; Caselli, Cristina; Paris, Silvana; Cuttini, Marina

2010-01-01

Aim: The aim of this study was to determine neuropsychological performance (possibly predictive of academic difficulties) and its relationship with cognitive development and maternal education in healthy preterm children of preschool age and age-matched comparison children born at term. Method : A total of 35 infants who were born at less than 33…

Longitudinal Trajectories of Gestural and Linguistic Abilities in Very Preterm Infants in the Second Year of Life

ERIC Educational Resources Information Center

Sansavini, Alessandra; Guarini, Annalisa; Savini, Silvia; Broccoli, Serena; Justice, Laura; Alessandroni, Rosina; Faldella, Giacomo

2011-01-01

The present study involved a systematic longitudinal analysis, with three points of assessment in the second year of life, of gestures/actions, word comprehension, and word production in a sample of very preterm infants compared to a sample of full-term infants. The relationships among these competencies as well as their predictive value on…

Bacterial vaginosis in association with spontaneous abortion and recurrent pregnancy losses

PubMed Central

Işik, Gözde; Demirezen, Şayeste; Dönmez, Hanife Güler; Beksaç, Mehmet Sinan

2016-01-01

Context: Bacterial vaginosis (BV) is related to the increased risk of miscarriage, preterm labor, and postpartum endometritis. Aims: The aim of this study was to evaluate the association between BV and the history of spontaneous abortion and recurrent pregnancy losses. We also examined periods of gestation, including the first and second trimester miscarriages. Materials and Methods: The study population consisted of 200 fertile women. Sixty one (30.5%) of 200 women had the history of a spontaneous abortion in the last six months (N = 30) and at least three recurrent pregnancy losses (N = 31). BV was diagnosed either by using Papanicolaou staining, Gram staining, or by culturing with BV-associated bacteria, Gardnerella vaginalis. Results: The presence of BV was statistically associated with the history of a spontaneous abortion in the last 6 months (P < 0.05), whereas there was no significant relationship between BV and recurrent pregnancy losses (P > 0.05). These women were also evaluated in view of periods of gestation. Forty-seven (77%) of 61 women had first trimester miscarriage (≤12 weeks) and 14 (23%) of 61 women had second trimester miscarriage (>12 weeks). There was a statistically significant relationship between BV and second trimester miscarriage (P < 0.05). Positive BV findings were not associated with discharge, itching, and pain (P > 0.05). Conclusion: BV may contribute to spontaneous abortion and second trimester miscarriage. PMID:27756985

Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth

NASA Astrophysics Data System (ADS)

Akins, Meredith L.; Luby-Phelps, Katherine; Mahendroo, Mala

2010-03-01

We use second harmonic generation (SHG) microscopy to assess changes in collagen structure of murine cervix during cervical remodeling of normal pregnancy and in a preterm birth model. Visual inspection of SHG images revealed substantial changes in collagen morphology throughout normal gestation. SHG images collected in both the forward and backward directions were analyzed quantitatively for changes in overall mean intensity, forward to backward intensity ratio, collagen fiber size, and porosity. Changes in mean SHG intensity and intensity ratio take place in early pregnancy, suggesting that submicroscopic changes in collagen fibril size and arrangement occur before macroscopic changes become evident. Fiber size progressively increased from early to late pregnancy, while pores between collagen fibers became larger and farther apart. Analysis of collagen features in premature cervical remodeling show that changes in collagen structure are dissimilar from normal remodeling. The ability to quantify multiple morphological features of collagen that characterize normal cervical remodeling and distinguish abnormal remodeling in preterm birth models supports future studies aimed at development of SHG endoscopic devices for clinical assessment of collagen changes during pregnancy in women and for predicting risk of preterm labor which occurs in 12.5% of all pregnancies.

Using Raman spectroscopy to study the onset of labor: a pilot study

NASA Astrophysics Data System (ADS)

Vargis, Elizabeth; Webb, C. Nathan; Paria, B. C.; Bennett, Kelly; Reese, Jeff; Al-Hendy, Ayman; Mahadevan-Jansen, Anita

2011-03-01

Preterm birth is the second leading cause of neonatal mortality and leads to a myriad of complications like delayed development and cerebral palsy. Currently, there is no way to accurately predict preterm labor, making its prevention and treatment virtually impossible. While there are some at-risk patients, over half of all preterm births do not fall into any high-risk category. This study seeks to predict and prevent preterm labor by using Raman spectroscopy to detect changes in the cervix during pregnancy indicative of labor. Since Raman spectroscopy has been used to detect cancers in vivo in organs like the cervix and skin, it follows that spectra will change over the course of pregnancy. Previous studies have shown that fluorescence decreased during pregnancy and increased during post-partum exams to pre-pregnancy levels. We believe significant changes will occur in the Raman spectra obtained during the course of pregnancy. In this study, Raman spectra from the cervix of pregnant mice and women will be acquired. Specific changes that occur due to cervical softening or changes in hormonal levels will be observed to understand the likelihood that a female mouse or a woman will enter labor.

Assessment of general movements and heart rate variability in prediction of neurodevelopmental outcome in preterm infants.

PubMed

Dimitrijević, Lidija; Bjelaković, Bojko; Čolović, Hristina; Mikov, Aleksandra; Živković, Vesna; Kocić, Mirjana; Lukić, Stevo

2016-08-01

Adverse neurologic outcome in preterm infants could be associated with abnormal heart rate (HR) characteristics as well as with abnormal general movements (GMs) in the 1st month of life. To demonstrate to what extent GMs assessment can predict neurological outcome in preterm infants in our clinical setting; and to assess the clinical usefulness of time-domain indices of heart rate variability (HRV) in improving predictive value of poor repertoire (PR) GMs in writhing period. Qualitative assessment of GMs at 1 and 3 months corrected age; 24h electrocardiography (ECG) recordings and analyzing HRV at 1 month corrected age. Seventy nine premature infants at risk of neurodevelopmental impairments were included prospectively. Neurodevelopmental outcome was assessed at the age of 2 years corrected. Children were classified as having normal neurodevelopmental status, minor neurologic dysfunction (MND), or cerebral palsy (CP). We found that GMs in writhing period (1 month corrected age) predicted CP at 2 years with sensitivity of 100%, and specificity of 72.1%. Our results demonstrated the excellent predictive value of cramped synchronized (CS) GMs, but not of PR pattern. Analyzing separately a group of infants with PR GMs we found significantly lower values of HRV parameters in infants who later developed CP or MND vs. infants with PR GMs who had normal outcome. The quality of GMs was predictive for neurodevelopmental outcome at 2 years. Prediction of PR GMs was significantly enhanced with analyzing HRV parameters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Associations between maternal serum free beta human chorionic gonadotropin (β-hCG) levels and adverse pregnancy outcomes.

PubMed

Sirikunalai, P; Wanapirak, C; Sirichotiyakul, S; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K; Tongsong, T

2016-01-01

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (β-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free β-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free β-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low β-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high β-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high β-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free β-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free β-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

Brucellosis in pregnancy: clinical aspects and obstetric outcomes.

PubMed

Vilchez, Gustavo; Espinoza, Miguel; D'Onadio, Guery; Saona, Pedro; Gotuzzo, Eduardo

2015-09-01

Brucellosis is a zoonosis with high morbidity in humans. This disease has gained interest recently due to its re-emergence and potential for weaponization. Pregnant women with this disease can develop severe complications. Its association with adverse obstetric outcomes is not clearly understood. The objective of this study was to describe the obstetric outcomes of brucellosis in pregnancy. Cases of pregnant women with active brucellosis seen at the Hospital Nacional Cayetano Heredia from 1970 to 2012 were reviewed. Diagnostic criteria were a positive agglutination test and/or positive blood/bone marrow culture. Presentation and outcomes data were collected. The Chi-square test was used for nominal variables. A p-value of <0.05 indicated significance. One hundred and one cases were included; 27.7% had a threatened abortion/preterm labor, 12.8% experienced spontaneous abortion, 13.9% preterm delivery, 8.1% fetal death, and 1.1% congenital malformations. There was one maternal death secondary to severe sepsis. After delivery, neonatal death occurred in 8.1%, low birth weight in 14.5%, and congenital brucellosis in 6.4%. The most common treatment was aminoglycosides plus rifampicin (42.2% of cases). Complication rates decreased if treatment was started within 2 weeks of presentation (p < 0.001). This is the largest series of brucellosis in pregnancy reported in the literature. Brucella presents adverse obstetric outcomes including fetal and maternal/neonatal death. Cases with unexplained spontaneous abortion should be investigated for brucellosis. Prompt treatment is paramount to decrease the devastating outcomes. Copyright © 2015. Published by Elsevier Ltd.

Magnitude of income-related disparities in adverse perinatal outcomes.

PubMed

Shankardass, Ketan; O'Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, Ks; Morinis, Julia; Allen, Victoria M

2014-03-04

To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases.

Magnitude of income-related disparities in adverse perinatal outcomes

PubMed Central

2014-01-01

Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212

Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review.

PubMed

Lu, Ellen; Wang, Bing Wei; Guimond, Colleen; Synnes, Anne; Sadovnick, Dessa; Tremlett, Helen

2012-09-11

To systematically review the literature regarding safety of disease-modifying drug (DMD) use during pregnancy on perinatal and developmental outcomes in offspring of patients with multiple sclerosis (MS). A PubMed and EMBASE search up to February 2012 was conducted with a manual search of references from relevant articles. Selected studies were evaluated using internationally accepted criteria. Fifteen studies identified 761 interferon β-, 97 glatiramer acetate-, and 35 natalizumab-exposed pregnancies. Study quality ranged from poor to good; no study was rated excellent. Small sample sizes limited most studies. Compared with data for unexposed pregnancies, fair- to good-quality prospective cohort studies reported that interferon β exposure was associated with lower mean birth weight, shorter mean birth length, and preterm birth (<37 weeks), but not low birth weight (<2,500 g), cesarean delivery, congenital anomaly (including malformation), or spontaneous abortion. Fewer studies of fair quality were available for glatiramer acetate and natalizumab. Glatiramer acetate exposure was not associated with lower mean birth weight, congenital anomaly, preterm birth, or spontaneous abortion. Natalizumab exposure did not appear to be associated with shorter mean birth length, lower mean birth weight, or lower mean gestational age. No studies examined mitoxantrone or fingolimod exposure. One study of paternal DMD use during conception found no effect on gestational age or birth weight. Few studies examined longer-term developmental outcomes. Further studies are needed to determine the potential risks associated with preconceptional and in utero DMD exposure in patients with MS. Discontinuation of DMDs before conception is still recommended.

The motor repertoire in 3- to 5-month old infants with Down syndrome.

PubMed

Herrero, Dafne; Einspieler, Christa; Panvequio Aizawa, Carolina Y; Mutlu, Akmer; Yang, Hong; Nogolová, Alice; Pansy, Jasmin; Nielsen-Saines, Karin; Marschik, Peter B

2017-08-01

Even though Down syndrome is the most common chromosomal cause of intellectual disability, studies on early development are scarce. To describe movements and postures in 3- to 5-month-old infants with Down syndrome and assess the relation between pre- and perinatal risk factors and the eventual motor performance. Exploratory study; 47 infants with Down syndrome (26 males, 27 infants born preterm, 22 infants with congenital heart disease) were videoed at 10-19 weeks post-term (median=14 weeks). We assessed their Motor Optimality Score (MOS) based on postures and movements (including fidgety movements) and compared it to that of 47 infants later diagnosed with cerebral palsy and 47 infants with a normal neurological outcome, matched for gestational and recording ages. The MOS (median=13, range 10-28) was significantly lower than in infants with a normal neurological outcome (median=26), but higher than in infants later diagnosed with cerebral palsy (median=6). Fourteen infants with Down syndrome showed normal fidgety movements, 13 no fidgety movements, and 20 exaggerated, too fast or too slow fidgety movements. A lack of movements to the midline and several atypical postures were observed. Neither preterm birth nor congenital heart disease was related to aberrant fidgety movements or reduced MOS. The heterogeneity in fidgety movements and MOS add to an understanding of the large variability of the early phenotype of Down syndrome. Studies on the predictive values of the early spontaneous motor repertoire, especially for the cognitive outcome, are warranted. The significance of this exploratory study lies in its minute description of the motor repertoire of infants with Down syndrome aged 3-5 months. Thirty percent of infants with Down syndrome showed age-specific normal fidgety movements. The rate of abnormal fidgety movements (large amplitude, high/slow speed) or a lack of fidgety movements was exceedingly high. The motor optimality score of infants with Down syndrome was lower than in infants with normal neurological outcome but higher than in infants who were later diagnosed with cerebral palsy. Neither preterm birth nor congenital heart disease were related to the motor performance at 3-5 months. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk.

PubMed

Kindinger, Lindsay M; Bennett, Phillip R; Lee, Yun S; Marchesi, Julian R; Smith, Ann; Cacciatore, Stefano; Holmes, Elaine; Nicholson, Jeremy K; Teoh, T G; MacIntyre, David A

2017-01-19

Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth (n = 161) to assess (1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and (2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix. Lactobacillus iners dominance at 16 weeks of gestation was significantly associated with both a short cervix <25 mm (n = 15, P < 0.05) and preterm birth <34 +0  weeks (n = 18; P < 0.01; 69% PPV). In contrast, Lactobacillus crispatus dominance was highly predictive of term birth (n = 127, 98% PPV). Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28, and 34 weeks) was then undertaken in women receiving vaginal progesterone (400 mg/OD, n = 25) versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks). L. iners dominance of the vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about "infection risk" associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.

Academic performance of children born preterm: a meta-analysis and meta-regression.

PubMed

Twilhaar, E Sabrina; de Kieviet, Jorrit F; Aarnoudse-Moens, Cornelieke Sh; van Elburg, Ruurd M; Oosterlaan, Jaap

2017-08-28

Advances in neonatal healthcare have resulted in decreased mortality after preterm birth but have not led to parallel decreases in morbidity. Academic performance provides insight in the outcomes and specific difficulties and needs of preterm children. To study academic performance in preterm children born in the antenatal steroids and surfactant era and possible moderating effects of perinatal and demographic factors. PubMed, Web of Science and PsycINFO were searched for peer-reviewed articles. Cohort studies with a full-term control group reporting standardised academic performance scores of preterm children (<37 weeks of gestation) at age 5 years or older and born in the antenatal steroids and surfactant era were included. Academic test scores and special educational needs of preterm and full-term children were analysed using random effects meta-analysis. Random effects meta-regressions were performed to explore the predictive role of perinatal and demographic factors for between-study variance in effect sizes. The 17 eligible studies included 2390 preterm children and 1549 controls. Preterm children scored 0.71 SD below full-term peers on arithmetic (p<0.001), 0.44 and 0.52 SD lower on reading and spelling (p<0.001) and were 2.85 times more likely to receive special educational assistance (95% CI 2.12 to 3.84, p<0.001). Bronchopulmonarydysplasia explained 44% of the variance in academic performance (p=0.006). Preterm children born in the antenatal steroids and surfactant era show considerable academic difficulties. Preterm children with bronchopulmonarydysplasia are at particular risk for poor academic outcome. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial.

PubMed

Kenyon, S; Pike, K; Jones, D R; Brocklehurst, P; Marlow, N; Salt, A; Taylor, D J

2008-10-11

The ORACLE II trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women in spontaneous preterm labour and intact membranes, without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study II--was to determine the long-term effects on children after exposure to antibiotics in this clinical situation. We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. Outcome was determined for 3196 (71%) eligible children. Overall, a greater proportion of children whose mothers had been prescribed erythromycin, with or without co-amoxiclav, had any functional impairment than did those whose mothers had received no erythromycin (658 [42.3%] of 1554 children vs 574 [38.3%] of 1498; odds ratio 1.18, 95% CI 1.02-1.37). Co-amoxiclav (with or without erythromycin) had no effect on the proportion of children with any functional impairment, compared with receipt of no co-amoxiclav (624 [40.7%] of 1523 vs 608 [40.0%] of 1520; 1.03, 0.89-1.19). No effects were seen with either antibiotic on the number of deaths, other medical conditions, behavioural patterns, or educational attainment. However, more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav, respectively (erythromycin: 53 [3.3%] of 1611 vs 27 [1.7%] of 1562, 1.93, 1.21-3.09; co-amoxiclav: 50 [3.2%] of 1587 vs 30 [1.9%] of 1586, 1.69, 1.07-2.67). The number needed to harm with erythromycin was 64 (95% CI 37-209) and with co-amoxiclav 79 (42-591). The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age. The risk of cerebral palsy was increased by either antibiotic, although the overall risk of this condition was low. UK Medical Research Council.

Costs of unnecessary admissions and treatments for "threatened preterm labor".

PubMed

Lucovnik, Miha; Chambliss, Linda R; Garfield, Robert E

2013-09-01

Cervical length (CL) of 3 cm or greater has been shown to have a 97-99% negative predictive value for preterm delivery in women with threatened preterm labor. Consequently, hospitalization and treatment are not indicated in these patients. We analyzed how often patients with a CL of 3 cm or greater are still being admitted and treated for preterm labor and how much this contributes to the economic burden of preterm labor hospitalizations. Twelve month hospitalizations for preterm labor at less than 34 weeks at a single institution were reviewed and patients with a CL of 3 cm or greater were identified. We chose to use patients' hospital charges as a surrogate for health care costs, recognizing that charges are not synonymous with the final patient bill and also do not reflect additional costs such as the cost of treatment at the referring facility, transportation, physician fees, and other such costs as lost wages, need for additional child care, etc. Between July 2009 and June 2010, 139 patients were admitted and treated for preterm labor at our level III center. Fifty of these patients (36%) had a CL of 3 cm or greater. None of them delivered preterm. Total hospital charges for the management of these patients were $1,018 589 (mean, $20,372; median, $14,444). Unnecessary admissions and treatments for threatened preterm labor are part of clinical practice and contribute to exploding health care costs. Using currently available diagnostics, these costs could be lowered significantly without jeopardizing outcome. Copyright © 2013 Mosby, Inc. All rights reserved.

Intrauterine midgut volvulus without malrotation: Diagnosis from the ‘coffee bean sign’

PubMed Central

Park, Jun Seok; Cha, Seong Jae; Kim, Beom Gyu; Kim, Yong Seok; Choi, Yoo Shin; Chang, In Taik; Kim, Gwang Jun; Lee, Woo Seok; Kim, Gi Hyeon

2008-01-01

Fetal midgut volvulus is quite rare, and most cases are associated with abnormalities of intestinal rotation or fixation. We report a case of midgut volvulus without malrotation, associated with a meconium pellet, during the gestation period. This 2.79 kg, 33-wk infant was born via a spontaneous vaginal delivery caused by preterm labor. Prenatal ultrasound showed dilated bowel loops with the appearance of a ‘coffee bean sign’. This patient had an unusual presentation with a distended abdomen showing skin discoloration. An emergency laparotomy revealed a midgut volvulus and a twisted small bowel, caused by complicated meconium ileus. Such nonspecific prenatal radiological signs and a low index of suspicion of a volvulus during gestation might delay appropriate surgical management and result in ischemic necrosis of the bowel. Preterm labor, specific prenatal sonographic findings (for example, the coffee bean sign) and bluish discoloration of the abdominal wall could suggest intrauterine midgut volvulus requiring prompt surgical intervention. PMID:18322966

Continuous amnioinfusion via an epidural catheter following spontaneous membrane rupture: A case report.

PubMed

Turgut, Abdulkadir; Katar, Selahattin; Sak, Muhammet Erdal; Turgut, Fethiye Gülden; Sahin, Alparslan; Başaranoğlu, Serdar; Yalınkaya, Ahmet

2013-01-01

Preterm premature rupture of membranes (PPROM) is seen in 3% of all pregnancies, and is a frequent cause of preterm birth, neonatal mortality and morbidity. The most important complications are maternal and foetal infection, prematurity, umbilical cord compression, hypoxia or asphyxia due to cord prolapse, pulmonary hypoplasia and extremity deformities. The basic approach to PPROM therapy aims to prevent premature birth and the development of foetal distress, and decrease the risk of maternal and foetal infection, and amniotic fluid loss. In compliance with these objectives, alternatives of PPROM therapy demonstrate a wide spectrum, including watchful waiting, amniopatch application, recurrent amnioinfusions and emergency birth. However, repeated amnioinfusions in cases of fluid loss, especially within 6 hours of therapy, provides only minimal benefit. In this case presentation, we attempted to describe a different and cost-effective continuous amnioinfusion technique performed to confer survival benefit for an immature anhydramniotic foetus affected by PPROM at the border of viability.

Continuous amnioinfusion via an epidural catheter following spontaneous membrane rupture: A case report

PubMed Central

Turgut, Abdulkadir; Katar, Selahattin; Sak, Muhammet Erdal; Turgut, Fethiye Gülden; Şahin, Alparslan; Başaranoğlu, Serdar; Yalınkaya, Ahmet

2013-01-01

Preterm premature rupture of membranes (PPROM) is seen in 3% of all pregnancies, and is a frequent cause of preterm birth, neonatal mortality and morbidity. The most important complications are maternal and foetal infection, prematurity, umbilical cord compression, hypoxia or asphyxia due to cord prolapse, pulmonary hypoplasia and extremity deformities. The basic approach to PPROM therapy aims to prevent premature birth and the development of foetal distress, and decrease the risk of maternal and foetal infection, and amniotic fluid loss. In compliance with these objectives, alternatives of PPROM therapy demonstrate a wide spectrum, including watchful waiting, amniopatch application, recurrent amnioinfusions and emergency birth. However, repeated amnioinfusions in cases of fluid loss, especially within 6 hours of therapy, provides only minimal benefit. In this case presentation, we attempted to describe a different and cost-effective continuous amnioinfusion technique performed to confer survival benefit for an immature anhydramniotic foetus affected by PPROM at the border of viability. PMID:24592114

Endocrinology of parturition

PubMed Central

Kota, Sunil K.; Gayatri, Kotni; Jammula, Sruti; Kota, Siva K.; Krishna, S. V. S.; Meher, Lalit K.; Modi, Kirtikumar D.

2013-01-01

The myometrium must remain relatively quiescent during pregnancy to accommodate growth and development of the feto-placental unit, and then must transform into a highly coordinated, strongly contracting organ at the time of labour for successful expulsion of the new born. The control of timing of labour is complex involving interactions between mother, fetus and the placenta. The timely onset of labour and delivery is an important determinant of perinatal outcome. Both preterm birth (delivery before 37 week of gestation) and post term pregnancy (pregnancy continuing beyond 42 weeks) are both associated with a significant increase in perinatal morbidity and mortality. There are multiple paracrine/autocrine events, fetal hormonal changes and overlapping maternal/fetal control mechanisms for the triggering of parturition in women. Our current article reviews the mechanisms for uterine distension and reduced contractions during pregnancy and the parturition cascade responsible for the timely and spontaneous onset of labour at term. It also discusses the mechanisms of preterm labour and post term pregnancy and the clinical implications thereof. PMID:23776853

Relationship of blood lead levels to obstetric outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angell, N.F.; Lavery, J.P.

1982-01-01

Lead represents a significant environmental hazard to pregnant women and their offspring. Exposure to high environmental levels of lead has been associated with spontaneous abortion, premature rupture of fetal membranes (PROM), and preterm delivery. The relationship between lower exposures and obstetric complications is unknown. The concentration of lead in the blood was measured in 635 specimens of umbilical cord blood collected at delivery. No relationship was found between concentrations of lead in cord blood and the incidence of PROM, preterm delivery, preeclampsia, or meconium staining. Maternal and infant capillary blood was collected 24 hours post partum from 154 of thesemore » deliveries. The concentrations of lead in the blood did not vary significantly among cord, infant, and maternal samples, and the three measurements were highly correlated. Levels of zinc protoporphyrin (ZnP) were increased in cord blood as compared with mothers' blood, but no concentration-response relationships between the ratio of cord ZnP to maternal ZnP and lead were found.« less

A novel role for GSK3 in the regulation of the processes of human labour.

PubMed

Lim, Ratana; Lappas, Martha

2015-02-01

Preterm birth remains the largest single cause of neonatal death and morbidity. Infection and/or inflammation are strongly associated with preterm delivery. Glycogen synthase kinase 3 (GSK3) is known to be a crucial mediator of inflammation homeostasis. The aims of this study were to determine the effect of spontaneous human labour in foetal membranes and myometrium on GSK3α/β expression, and the effect of inhibition of GSK3α/β on pro-labour mediators in foetal membranes and myometrium stimulated with Toll-like receptor (TLR) ligands and pro-inflammatory cytokines. Term and preterm labour in foetal membranes was associated with significantly decreased serine phosphorylated GSK3α and β expression, and thus increased GSK3 activity. There was no effect of term labour on serine phosphorylated GSK3β expression in myometrium. The specific GSK3α/β inhibitor CHIR99021 significantly decreased lipopolysaccharide (ligand to TLR4)-stimulated pro-inflammatory cytokine gene expression and release; COX2 gene expression and prostaglandin release; and MMP9 gene expression and pro MMP9 release in foetal membranes and/or myometrium. CHIR99021 also decreased FSL1 (TLR2 ligand) and flagellin (TLR5 ligand)-induced pro-inflammatory cytokine gene expression and release and COX2 mRNA expression and prostaglandin release. GSK3β siRNA knockdown in primary myometrial cells was associated with a significant decrease in IL1β and TNFα-induced pro-inflammatory cytokine and prostaglandin release. In conclusion, GSK3α/β activity is increased in foetal membranes after term and preterm labour. Pharmacological blockade of the kinase GSK3 markedly reduced pro-inflammatory and pro-labour mediators in human foetal membranes and myometrium, providing a possible therapeutics for the management of preterm labour. © 2015 Society for Reproduction and Fertility.

Periodontal treatment during pregnancy and birth outcomes: a meta-analysis of randomised trials.

PubMed

George, Ajesh; Shamim, Simin; Johnson, Maree; Ajwani, Shilpi; Bhole, Sameer; Blinkhorn, Anthony; Ellis, Sharon; Andrews, Karen

2011-06-01

The objective of this review was to conduct a meta-analysis of all up-to-date randomised control trials to determine whether periodontal treatment during pregnancy has the potential of reducing preterm birth and low birth weight incidence. Bibliographic databases MEDLINE (1966-present), EMBASE (1980-present), CINAHL (1982-present) and the Cochrane library up to and including 2010 Issue 10 were searched. The reference list of included studies and reviews were also searched for additional literature. Eligible studies were, published and ongoing randomised control trials that compared pregnancy outcomes for pregnant women who received periodontal treatment during the prenatal period. Two of the investigators independently assessed the studies and then extracted and summarised data from eligible trials. Extracted data were entered into Review Manager software and analysed. A total of 5645 pregnant women participated in the 10 eligible trials. Meta-analysis found that periodontal treatment significantly lowered preterm birth (odd ratio 0.65; 95% confidence interval, 0.45-0.93; P = 0.02) and low birth weight (odd ratio 0.53; 95% confidence interval, 0.31-0.92; P = 0.02) rates while no significant difference was found for spontaneous abortion/stillbirth (odd ratio 0.71; 95% confidence interval, 0.43-1.16; P = 0.17). Moderate heterogeneity was observed among the studies for preterm birth and low birth weight. Subgroup analysis showed significant effect of periodontal treatment in pregnant women with low rate of previous preterm birth/low birth weight (odd ratio 0.35; 95% confidence interval, 017-0.70; P = 0.003) and less severe periodontal disease (odd ratio 0.49; confidence interval, 028-0.87; P = 0.01) as defined by probing depth. The cumulative evidence suggests that periodontal treatment during pregnancy may reduce preterm birth and low birth weight incidence. However, these findings need to be further validated through larger more targeted randomised control trials. © 2011 The Authors. International Journal of Evidence-Based Healthcare © 2011 The Joanna Briggs Institute.

Spontaneous abortion and the prophylactic effect of folic acid supplementation in epileptic women undergoing antiepileptic therapy.

PubMed

Pittschieler, Sabine; Brezinka, Christoph; Jahn, Beate; Trinka, Eugen; Unterberger, Iris; Dobesberger, Judith; Walser, Gerald; Auckenthaler, Andrea; Embacher, Norbert; Bauer, Gerhard; Luef, Gerhard

2008-12-01

Antiepileptic drugs (AEDs) like phenytoin (PHE), carbamazepine (CBZ), barbiturates and valproic acid (VPA) interfere with folic acid absorption and metabolism, which in turn can be the cause of adverse pregnancy outcome. To study the prophylactic effect of folic acid supplementation with regard to spontaneous abortion and preterm delivery (fetal demise after week 20 of gestational age) in pregnant women receiving AED therapy, as well as benefits of most common dosage and preconceptional commencement. Prospective examination of 104 patients, registered in EURAP from 1999-2004 at a single center and a retrospective analysis of data from our epilepsy databank completed with medical records and patients interviews of the Department of Neurology of Innsbruck University Hospital from 1971 to 1999. 388 pregnancies in 244 patients were analyzed. Pregnancies with folic acid supplementation showed significant reduction of spontaneous abortion. With regard to monotherapies, in the group of women taking VPA, supplementation of folic acid had significant benefit. Other examined monotherapies (CBZ, PHE, and PB) known to interfere with folic acid showed no significant results. This study confirms the prophylactic effect of folic acid supplementation on spontaneous abortion. For AED therapy, folic acid supplementation should be part of the therapy of every pregnant epileptic woman, especially for those treated with VPA.

Acid oro-pharyngeal secretions can predict gastro-oesophageal reflux in preterm infants.

PubMed

James, M E; Ewer, A K

1999-05-01

Acid gastro-oesophageal reflux (GOR) is common in preterm infants but there is a lack of a non-invasive technique to establish the diagnosis. The aim of this study was to identify whether the presence of acid in oro-pharyngeal secretions (OPS) was a valid indicator of clinically significant acid GOR in preterm infants. A total of 23 infants with suspected GOR were studied with 24 h lower-oesophageal pH monitoring and during this period the OPS were tested for acid with litmus paper at 6 hourly intervals. Median (range) gestation was 28 weeks (24-31), birth weight 1023 g (480-1750) and age at study 34 days (11-76). Significant GOR was defined as a reflux index >5%. Of the investigated infants, 18 subjects (78%) had significant GOR. Of this group, 16 infants had acid in the OPS on at least one occasion. Five infants did not demonstrate significant GOR and in four of these acid was not detected in the OPS. Our data indicate that as a predictor for significant GOR, litmus-testing OPS for acid has a sensitivity of 89%, specificity of 80%, positive predictive value of 94% and a negative predictive value of 67%. The difference in the incidence of acid OPS between the GOR and the No GOR group was significant (P<0.03). The presence of acid in the oropharyngeal secretions may help in the prediction of acid gastro-oesophageal reflux in preterm infants. The method is simple, inexpensive cheap and involves minimal disturbance. We suggest that it could aid clinical diagnosis and indicate a need for further investigation of gastro-oesophageal reflux.

Prediction of brain maturity in infants using machine-learning algorithms.

PubMed

Smyser, Christopher D; Dosenbach, Nico U F; Smyser, Tara A; Snyder, Abraham Z; Rogers, Cynthia E; Inder, Terrie E; Schlaggar, Bradley L; Neil, Jeffrey J

2016-08-01

Recent resting-state functional MRI investigations have demonstrated that much of the large-scale functional network architecture supporting motor, sensory and cognitive functions in older pediatric and adult populations is present in term- and prematurely-born infants. Application of new analytical approaches can help translate the improved understanding of early functional connectivity provided through these studies into predictive models of neurodevelopmental outcome. One approach to achieving this goal is multivariate pattern analysis, a machine-learning, pattern classification approach well-suited for high-dimensional neuroimaging data. It has previously been adapted to predict brain maturity in children and adolescents using structural and resting state-functional MRI data. In this study, we evaluated resting state-functional MRI data from 50 preterm-born infants (born at 23-29weeks of gestation and without moderate-severe brain injury) scanned at term equivalent postmenstrual age compared with data from 50 term-born control infants studied within the first week of life. Using 214 regions of interest, binary support vector machines distinguished term from preterm infants with 84% accuracy (p<0.0001). Inter- and intra-hemispheric connections throughout the brain were important for group categorization, indicating that widespread changes in the brain's functional network architecture associated with preterm birth are detectable by term equivalent age. Support vector regression enabled quantitative estimation of birth gestational age in single subjects using only term equivalent resting state-functional MRI data, indicating that the present approach is sensitive to the degree of disruption of brain development associated with preterm birth (using gestational age as a surrogate for the extent of disruption). This suggests that support vector regression may provide a means for predicting neurodevelopmental outcome in individual infants. Copyright © 2016 Elsevier Inc. All rights reserved.

Prediction of brain maturity in infants using machine-learning algorithms

PubMed Central

Smyser, Christopher D.; Dosenbach, Nico U.F.; Smyser, Tara A.; Snyder, Abraham Z.; Rogers, Cynthia E.; Inder, Terrie E.; Schlaggar, Bradley L.; Neil, Jeffrey J.

2016-01-01

Recent resting-state functional MRI investigations have demonstrated that much of the large-scale functional network architecture supporting motor, sensory and cognitive functions in older pediatric and adult populations is present in term- and prematurely-born infants. Application of new analytical approaches can help translate the improved understanding of early functional connectivity provided through these studies into predictive models of neurodevelopmental outcome. One approach to achieving this goal is multivariate pattern analysis, a machine-learning, pattern classification approach well-suited for high-dimensional neuroimaging data. It has previously been adapted to predict brain maturity in children and adolescents using structural and resting state-functional MRI data. In this study, we evaluated resting state-functional MRI data from 50 preterm-born infants (born at 23–29 weeks of gestation and without moderate–severe brain injury) scanned at term equivalent postmenstrual age compared with data from 50 term-born control infants studied within the first week of life. Using 214 regions of interest, binary support vector machines distinguished term from preterm infants with 84% accuracy (p < 0.0001). Inter- and intra-hemispheric connections throughout the brain were important for group categorization, indicating that widespread changes in the brain's functional network architecture associated with preterm birth are detectable by term equivalent age. Support vector regression enabled quantitative estimation of birth gestational age in single subjects using only term equivalent resting state-functional MRI data, indicating that the present approach is sensitive to the degree of disruption of brain development associated with preterm birth (using gestational age as a surrogate for the extent of disruption). This suggests that support vector regression may provide a means for predicting neurodevelopmental outcome in individual infants. PMID:27179605

Increased risk of pregnancy-induced hypertension and operative delivery after conception induced by in vitro fertilization/intracytoplasmic sperm injection in women aged 40 years and older.

PubMed

Toshimitsu, Masatake; Nagamatsu, Takeshi; Nagasaka, Takaaki; Iwasawa-Kawai, Yuki; Komatsu, Atsushi; Yamashita, Takahiro; Osuga, Yutaka; Fujii, Tomoyuki

2014-10-01

To clarify the association between preconception fertility status and obstetric outcomes in women aged 40 years and older. Retrospective study by reviewing medical records. Tertiary perinatal center in a university hospital. 330 women aged 40 years and older who delivered a singleton from 2006 to 2010, and 450 women aged 30 to 34 years who delivered at the same facility as controls. None. Incidence of pregnancy-induced hypertension, gestational diabetes mellitus, preterm birth, low birth weight, and mode of delivery assessed based on the mode of conception; spontaneous conception (SC) and in vitro fertilization/intracytoplasmic sperm injection conception (IVF-ICSI). The incidence of pregnancy-induced hypertension was statistically significantly higher in IVF-ICSI group than the SC group. This gap was commonly observed in both the women aged 40 years and older and those in the 30 to 34 age group. No statistically significant difference was observed in the frequency of gestational diabetes mellitus, preterm birth, or low birth weight. As a characteristic of nulliparous women of advanced age, the rate of operative delivery, which includes emergency cesarean section and instrumental delivery, was statistically significantly higher in IVF-ICSI group than in the SC group. Detailed investigation into the medical indications for operative delivery revealed that the difference was attributable to the elevated incidence of labor protraction and arrest. Preconception fertility status can be a predicting factor of the incidence of pregnancy-induced hypertension and labor outcome, especially for women aged 40 years and older. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study

PubMed Central

2013-01-01

Background Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). Methods The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). Results The median total folate intake was 266 μg/d (interquartile range IQR 154–543) in the overall population and 540 μg/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. Conclusions Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines. PMID:23937678

Early developmental trajectories of preterm infants.

PubMed

Yaari, Maya; Mankuta, David; Harel-Gadassi, Ayelet; Friedlander, Edwa; Bar-Oz, Benjamin; Eventov-Friedman, Smadar; Maniv, Nimrod; Zucker, David; Yirmiya, Nurit

2017-11-04

Preterm infants are at risk for neuro-developmental impairments and atypical developmental trajectories. The aims of this study were to delineate early developmental trajectories of preterm and full-term infants. The cognitive, language, and motor development of 149 infants - 19 extremely preterm (EPT), 34 very preterm (VPT), 57 moderately preterm (MPT), and 39 full-term (FT) - was evaluated using Mullen Scales at 1, 4, 8, 12, and 18 months. Mixed models were applied to examine group differences. Gender, maternal education, and neurobehavior were included as predictors of developmental trajectories. The EPT and VPT infants achieved significantly lower scores than the FT infants in all domains, with a significantly increasing gap over time. The MPT infants' trajectories were more favorable than those of the EPT and VPT infants yet lower than the FT infants on the Visual Reception, Gross, and Fine Motor subscales. Male gender and lower maternal education were associated with lower scores that declined over time. Abnormal neonatal neurobehavior was associated lower Mullen scores and with less stability in scores over time. The EPT and VPT infants were found to have disadvantages across all domains. The MPT infants revealed more favorable developmental trajectories yet displayed vulnerability compared to the FT infants. Gender, maternal education, and neonatal neurobehavior are important in predicting the developmental outcomes of preterm infants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Individual differences in physiological flexibility predict spontaneous avoidance.

PubMed

Aldao, Amelia; Dixon-Gordon, Katherine L; De Los Reyes, Andres

2016-08-01

People often regulate their emotions by resorting to avoidance, a putatively maladaptive strategy. Prior work suggests that increased psychopathology symptoms predict greater spontaneous utilisation of this strategy. Extending this work, we examined whether heightened resting cardiac vagal tone (which reflects a general ability to regulate emotions in line with contextual demands) predicts decreased spontaneous avoidance. In Study 1, greater resting vagal tone was associated with reduced spontaneous avoidance in response to disgust-eliciting pictures, beyond anxiety and depression symptoms and emotional reactivity. In Study 2, resting vagal tone interacted with anxiety and depression symptoms to predict spontaneous avoidance in response to disgust-eliciting film clips. The positive association between symptoms and spontaneous avoidance was more pronounced among participants with reduced resting vagal tone. Thus, increased resting vagal tone might protect against the use of avoidance. Our findings highlight the importance of assessing both subjective and biological processes when studying individual differences in emotion regulation.

Alberta infant motor scale: reliability and validity when used on preterm infants in Taiwan.

PubMed

Jeng, S F; Yau, K I; Chen, L C; Hsiao, S F

2000-02-01

The goal of this study was to examine the reliability and validity of measurements obtained with the Alberta Infant Motor Scale (AIMS) for evaluation of preterm infants in Taiwan. Two independent groups of preterm infants were used to investigate the reliability (n=45) and validity (n=41) for the AIMS. In the reliability study, the AIMS was administered to the infants by a physical therapist, and infant performance was videotaped. The performance was then rescored by the same therapist and by 2 other therapists to examine the intrarater and interrater reliability. In the validity study, the AIMS and the Bayley Motor Scale were administered to the infants at 6 and 12 months of age to examine criterion-related validity. Intraclass correlation coefficients (ICCs) for intrarater and interrater reliability of measurements obtained with the AIMS were high (ICC=.97-.99). The AIMS scores correlated with the Bayley Motor Scale scores at 6 and 12 months (r=.78 and.90), although the AIMS scores at 6 months were only moderately predictive of the motor function at 12 months (r=.56). The results suggest that measurements obtained with the AIMS have acceptable reliability and concurrent validity but limited predictive value for evaluating preterm Taiwanese infants.

Lung ultrasonography of pulmonary complications in preterm infants with respiratory distress syndrome.

PubMed

Lovrenski, Jovan

2012-03-01

To evaluate the diagnostic possibilities of lung ultrasonography (LUS) in detecting pulmonary complications in preterm infants with respiratory distress syndrome (RDS). A prospective study included 120 preterm infants with clinical and radiographic signs of RDS. LUS was performed using both a transthoracic and a transabdominal approach within the first 24 h of life, and, after that, follow-up LUS examinations were performed. In 47 detected pulmonary complications of RDS (hemorrhage, pneumothorax, pneumonia, atelectasis, bronchopulmonary dysplasia), comparisons between LUS and chest X-ray (CXR) were made. Also, 90 subpleural consolidations registered during LUS examinations were analysed. Statistical analysis included MANOVA and discriminant analysis, t-test, confidence interval, and positive predictive value. In 45 of 47 instances the same diagnosis of complication was detected with LUS as with CXR, indicating a high reliability of the method in premature infants with RDS. The only two false negative findings concerned partial pneumothorax. The positive predictive value of LUS was 100%. A statistically significant difference of LUS findings between the anterior and posterior lung areas was observed in both right and left hemithoraces. LUS enables the detection of pulmonary complications in preterm infants with RDS and has the potential to reduce the number of CXRs. The specific guidelines for its use should be provided in a more extensive study.

First-trimester mean arterial blood pressure and the risk of preeclampsia: The Great Obstetrical Syndromes (GOS) study.

PubMed

Gasse, Cédric; Boutin, Amélie; Coté, Maxime; Chaillet, Nils; Bujold, Emmanuel; Demers, Suzanne

2018-04-01

To estimate the predictive value of first-trimester mean arterial pressure (MAP) for the hypertensive disorders of pregnancy (HDP). We performed a prospective cohort study of nulliparous women recruited at 11 0/7 -13 6/7  weeks. MAP was calculated from blood pressure measured on both arms simultaneously using an automated device taking a series of recordings until blood pressure stability was reached. MAP was reported as multiples of the median adjusted for gestational age. Participants were followed for development of gestational hypertension (GH), preeclampsia (PE), preterm PE (<37 weeks) and early-onset (EO) PE (<34 weeks). Receiver operating characteristic curves and the area under the curve (AUC) were used to estimate the predictive values of MAP. Multivariate logistic regressions were used to develop predictive models combining MAP and maternal characteristics. We obtained complete follow-up in 4700 (99%) out of 4749 eligible participants. GH without PE was observed in 250 (5.3%) participants, and PE in 241 (5.1%), including 33 (0.7%) preterm PE and 10 (0.2%) EO-PE. First-trimester MAP was associated with GH (AUC: 0.77; 95%CI: 0.74-0.80); term PE (0.73; 95%CI: 0.70-0.76), preterm PE (0.80; 95%CI: 0.73-0.87) and EO-PE (0.79; 95%CI: 0.62-0.96). At a 10% false-positive rate, first-trimester MAP could have predicted 39% of GH, 34% of term PE, 48% of preterm PE and 60% of EO-PE. The addition of maternal characteristics improved the predictive values (to 40%, 37%, 55% and 70%, respectively). First-trimester MAP is a strong predictor of GH and PE in nulliparous women. Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Magnetic resonance imaging of the preterm infant brain.

PubMed

Doria, Valentina; Arichi, Tomoki; Edwards, David A

2014-01-01

Despite improvements in neonatal care, survivors of preterm birth are still at a significantly increased risk of developing life-long neurological difficulties including cerebral palsy and cognitive difficulties. Cranial ultrasound is routinely used in neonatal practice, but has a low sensitivity for identifying later neurodevelopmental difficulties. Magnetic Resonance Imaging (MRI) can be used to identify intracranial abnormalities with greater diagnostic accuracy in preterm infants, and theoretically might improve the planning and targeting of long-term neurodevelopmental care; reducing parental stress and unplanned healthcare utilisation; and ultimately may improve healthcare cost effectiveness. Furthermore, MR imaging offers the advantage of allowing the quantitative assessment of the integrity, growth and function of intracranial structures, thereby providing the means to develop sensitive biomarkers which may be predictive of later neurological impairment. However further work is needed to define the accuracy and value of diagnosis by MR and the techniques's precise role in care pathways for preterm infants.

First-trimester serum folate levels and subsequent risk of abortion and preterm birth among Japanese women with singleton pregnancies.

PubMed

Yamada, Takashi; Morikawa, Mamoru; Yamada, Takahiro; Kishi, Reiko; Sengoku, Kazuo; Endo, Toshiaki; Saito, Tsuyoshi; Cho, Kazutoshi; Minakami, Hisanori

2013-01-01

To determine whether a low serum folate level during the first trimester predicts subsequent late abortion, preterm birth, or fetal growth restriction (FGR). A prospective cohort study involving 5,075 women whose serum folate levels were measured during the first trimester. The participants were informed of their serum folate levels. The pregnancy duration, birthweight, rate of late abortion/preterm birth, and the rate of FGR did not differ significantly among the four groups classified according to folate status. The mean serum folate levels did not differ among quartiles classified according to the gestational week at the time of delivery. Nineteen of the 20 women with folate deficiency gave birth at term to infants with a birthweight of 3.132 ± 321 g; only one infant had FGR. Low serum folate levels during the first trimester were not associated with the risk of late abortion, preterm birth, or FGR.

Detection and risk stratification of women at high risk of preterm birth in rural communities near Nagpur, India.

PubMed

Patel, Archana; Prakash, Amber Abhijeet; Pusdekar, Yamini V; Kulkarni, Hemant; Hibberd, Patricia

2017-09-19

Presently, preterm birth is globally the leading cause of neonatal mortality. Prompt community based identification of women at high risk for preterm births (HRPB) can either help to avert preterm births or avail effective interventions to reduce neonatal mortality due to preterm births. We evaluated the performance of a package to train community workers to detect the presence of signs or symptoms of HRPB. Pregnant women enrolled in the intervention arm of a cluster randomized trial of Antenatal Corticosteroids (ACT Trial) conducted at Nagpur, India were informed about 4 directly observable signs and symptoms of preterm labor. Community health workers actively monitored these women from 24 to 36 weeks of gestation for these signs or symptoms. If they were present (HRPB positive) the identified women were brought to government health facilities for assessment and management. HRPB positive could also be determined by the provider if the woman presented directly to the facility. Risk stratification was based on the number of signs or symptoms present. The outcome of preterm birth was based on the clinical assessment of gestational age < 37 weeks at delivery or a birth weight of <2000 g. Between July 1, 2012 and 30 November, 2013, 686 of 7050 (9.7%) pregnant women studied, delivered preterm. 732 (10.4%) women were HRPB positive, of whom 333 (45.5%) delivered preterm. Of the remaining 6318(89.6%) HRPB negative women 353 (5.6%) delivered preterm. The likelihood ratio (LR) of a preterm birth in the HRPB positives was 8.14 (95% confidence interval 7.16-9.26). The LR of a preterm birth increased in women who had more signs or symptoms of HRBP (p < 0.00001). More signs or symptoms of HRPB were also associated with a shorter time to delivery, lower birth weight and higher rates of stillbirths, neonatal deaths and postnatal complications. Addition of risk stratification improved the prediction of preterm delivery (Integrated Discrimination Improvement 17% (95% CI 15-19%)). The package for detection of signs and symptoms of HRPB is feasible, promising and likely to improve management of preterm labor. NCT01073475 on February 21, 2010 and NCT01084096 on March 9, 2010.

Cannabis use during pregnancy in France in 2010.

PubMed

Saurel-Cubizolles, M-J; Prunet, C; Blondel, B

2014-07-01

The aim was to estimate the proportion of women who reported cannabis use during pregnancy, to analyse the demographic and social characteristics of users, and the link between cannabis use and either preterm or small-for-gestational-age birth. Data were obtained from interviews of a representative sample of women giving birth in France in 2010 in the days after delivery, and from their medical records. All maternity units in France. The analysis includes women with live singleton births in metropolitan France who responded to the question about cannabis use during pregnancy: in total, 13 545 women. The percentage of cannabis users during pregnancy was estimated, and variations according to social characteristics were described. Logistic regression analyses were used to investigate any associations between cannabis use and preterm birth or small-for-gestational-age status. Percentage of cannabis use, preterm birth rate, and small-for-gestational-age rate. In all, 1.2% of women reported having used cannabis during pregnancy. This percentage was higher among younger women, women living alone, or women who had a low level of education or low income. It was also associated with tobacco use and drinking alcohol. Cannabis users had higher rates of spontaneous preterm births: 6.4 versus 2.8%, for an adjusted odds ratio (aOR) of 2.15 (95% CI 1.10-4.18). The corresponding aOR was 2.64 (95% CI 1.12-6.22) among tobacco smokers and 1.22 (95% CI 0.29-5.06) among non-tobacco smokers. Although the reported rate of cannabis use during pregnancy in France is low, efforts should be continued to inform women and healthcare providers about the potential consequences of its use. © 2014 Royal College of Obstetricians and Gynaecologists.

Breath detection by transcutaneous electromyography of the diaphragm and the Graseby capsule in preterm infants.

PubMed

de Waal, Cornelia G; Kraaijenga, Juliette V; Hutten, Gerard J; de Jongh, Frans H; van Kaam, Anton H

2017-12-01

To compare triggering, breath detection and delay time of the Graseby capsule (GC) and transcutaneous electromyography of the diaphragm (dEMG) in spontaneous breathing preterm infants. In this observational study, a 30 minutes respiration measurement was conducted by respiratory inductance plethysmography (RIP), the GC, and dEMG in stable preterm infants. Triggering was investigated with an in vitro set-up using the Infant Flow ® SiPAP TM system. The possibility to optimize breath detection was tested by developing new algorithms with the abdominal RIP band (RIP AB ) as gold standard. In a subset of breaths, the delay time was calculated between the inspiratory onset in the RIP AB signal and in the GC and dEMG signal. Fifteen preterm infants with a mean gestational age of 28 ± 2 weeks and a mean birth weight of 1086 ± 317 g were included. In total, 14 773 breaths were analyzed. Based on the GC and dEMG signal, the Infant Flow ® SiPAP™ system, respectively, triggered 67.8% and 62.6% of the breaths. Breath detection was improved to 99.9% for the GC and 113.4% for dEMG in new algorithms. In 1492 stable breaths, the median delay time of inspiratory onset detection was +154 ms (IQR +118 to +164) in the GC and -50 ms (IQR -90 to -22) in the dEMG signal. Breath detection using the GC can be improved by optimizing the algorithm. Transcutaneous dEMG provides similar breath detection but with the advantage of detecting the onset of inspiration earlier than the GC. © 2017 Wiley Periodicals, Inc.

Impact of Scotland's Smoke-Free Legislation on Pregnancy Complications: Retrospective Cohort Study

PubMed Central

Mackay, Daniel F.; Nelson, Scott M.; Haw, Sally J.; Pell, Jill P.

2012-01-01

Background Both active smoking and environmental tobacco smoke exposure are associated with pregnancy complications. In March 2006, Scotland implemented legislation prohibiting smoking in all wholly or partially enclosed public spaces. The aim of this study was to determine the impact of this legislation on preterm delivery and small for gestational age. Methods and Findings We conducted logistic regression analyses using national administrative pregnancy data covering the whole of Scotland. Of the two breakpoints tested, 1 January 2006 produced a better fit than the date when the legislation came into force (26 March 2006), suggesting an anticipatory effect. Among the 716,941 eligible women who conceived between August 1995 and February 2009 and subsequently delivered a live-born, singleton infant between 24 and 44 wk gestation, the prevalence of current smoking fell from 25.4% before legislation to 18.8% after legislation (p<0.001). Three months prior to the legislation, there were significant decreases in small for gestational age (−4.52%, 95% CI −8.28, −0.60, p = 0.024), overall preterm delivery (−11.72%, 95% CI −15.87, −7.35, p<0.001), and spontaneous preterm labour (−11.35%, 95% CI −17.20, −5.09, p = 0.001). In sub-group analyses, significant reductions were observed among both current and never smokers. Conclusions Reductions were observed in the risk of preterm delivery and small for gestational age 3 mo prior to the introduction of legislation, although the former reversed partially following the legislation. There is growing evidence of the potential for tobacco control legislation to have a positive impact on health. Please see later in the article for the Editors' Summary PMID:22412353

Progesterone for Prevention of Preterm Birth: Shortcomings and Unintended Consequences of the Orphan Drug Act.

PubMed

Gee, Rebekah E; Kuy, SreyRam; Karas, Laura O

2017-12-01

Preterm birth is a problem of major public health significance that continues to plague our country despite the existence of a therapy, 17α-hydroxyprogesterone caproate, with known efficacy in reducing the risk of spontaneous preterm birth among high-risk women. Over the past several years, the Louisiana Department of Health has undertaken a robust, multifaceted initiative to improve access to 17α-hydroxyprogesterone caproate, which resulted in a 3.5-fold increase in the percentage of eligible high-risk pregnant women in the Medicaid program who received the therapy between 2013 and 2016. Yet despite Louisiana's progress, the vast majority of the eligible population still fails to receive 17α-hydroxyprogesterone caproate. In this Current Commentary, we argue that the high price of progesterone since U.S. Food and Drug Administration approval has unnecessarily complicated access, and our nation has potentially suffered nearly 60,000 avoidable premature births as a consequence. We present the history of the orphan drug approval and manufacturer-imposed price increase for injectable progesterone, the interplay between the drug's high price and the persistence of racial and ethnic disparities in preterm birth, which are particularly germane in Louisiana, and Louisiana's broad-reaching efforts to improve progesterone coverage. The story of 17α-hydroxyprogesterone caproate highlights the durable barriers that high prices place in the way of access and helps illuminate the shortcomings and unintended consequences of the Orphan Drug Act. This case, however, is not an outlier; it is the far-too-common product of monopoly pricing in the U.S. pharmaceutical market, inadvertently bolstered by existing law, at the expense of affordability and patient access.

An open-loop controlled active lung simulator for preterm infants.

PubMed

Cecchini, Stefano; Schena, Emiliano; Silvestri, Sergio

2011-01-01

We describe the underlying theory, design and experimental evaluation of an electromechanical analogue infant lung to simulate spontaneous breathing patterns of preterm infants. The aim of this work is to test the possibility to obtain breathing patterns of preterm infants by taking into consideration the air compressibility. Respiratory volume function represents the actuation pattern, and pulmonary pressure and flow-rate waveforms are mathematically obtained through the application of the perfect gas and adiabatic laws. The mathematical model reduces the simulation interval into a step shorter than 1 ms, allowing to consider an entire respiratory act as composed of a large number of almost instantaneous adiabatic transformations. The device consists of a spherical chamber where the air is compressed by four cylinder-pistons, moved by stepper motors, and flows through a fluid-dynamic resistance, which also works as flow-rate sensor. Specifically designed software generates the actuators motion, based on the desired ventilation parameters, without controlling the gas pneumatic parameters with a closed-loop. The system is able to simulate tidal volumes from 3 to 8 ml, breathing frequencies from 60 to 120 bpm and functional residual capacities from 25 to 80 ml. The simulated waveforms appear very close to the measured ones. Percentage differences on the tidal volume waveform vary from 7% for the tidal volume of 3 ml, down to 2.2-3.5% for tidal volumes in the range of 4-7 ml, and 1.3% for the tidal volume equal to 8 ml in the whole breathing frequency and functional residual capacity ranges. The open-loop electromechanical simulator shows that gas compressibility can be theoretically assessed in the typical pneumatic variable range of preterm infant respiratory mechanics. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

A new infant hybrid respiratory simulator: preliminary evaluation based on clinical data.

PubMed

Stankiewicz, Barbara; Pałko, Krzysztof J; Darowski, Marek; Zieliński, Krzysztof; Kozarski, Maciej

2017-11-01

A new hybrid (numerical-physical) simulator of the respiratory system, designed to simulate spontaneous and artificial/assisted ventilation of preterm and full-term infants underwent preliminary evaluation. A numerical, seven-compartmental model of the respiratory system mechanics allows the operator to simulate global and peripheral obstruction and restriction of the lungs. The physical part of the simulator is a piston-based construction of impedance transformer. LabVIEW real-time software coordinates the work of both parts of the simulator and its interaction with a ventilator. Using clinical data, five groups of "artificial infants" were examined: healthy full-term infants, very low-birth-weight preterm infants successfully (VLBW) and unsuccessfully extubated (VLBWun) and extremely low-birth-weight preterm infants without (ELBW) and with bronchopulmonary dysplasia (ELBW_BPD). Pressure-controlled ventilation was simulated to measure peak inspiratory pressure, mean airway pressure, total (patient + endotracheal tube) airway resistance (R), total dynamic compliance of the respiratory system (C), and total work of breathing by the ventilator (WOB). The differences between simulation and clinical parameters were not significant. High correlation coefficients between both types of data were obtained for R, C, and WOB (γ R  = 0.99, P < 0.0005; γ C  = 0.85, P < 0.005; γ WOB  = 0.96, P < 0.05, respectively). Thus, the simulator accurately reproduces infant respiratory system mechanics.

Surgical management of a patent ductus arteriosus: Is this still an option?

PubMed

Weisz, Dany E; Giesinger, Regan E

2018-03-07

The evolution of neonatal intensive care over the past decade has seen the role of surgical patent ductus arteriosus (PDA) ligation in preterm infants both decrease in scope and become laden with uncertainty. Associations of ligation with adverse neonatal and neurodevelopmental outcomes have rendered the ligation decision more challenging for clinicians and have been associated with a decline in surgical treatment, but these findings may be due to bias from confounding by indication in observational studies rather than a causal detrimental effect of ligation. Accordingly, ligation may still be indicated for infants with large ductal shunts and moderate-severe respiratory insufficiency in whom the prospect of timely spontaneous closure appears low. Ultimately a randomized trial of surgical ligation versus conservative management is necessary to assess the efficacy of this invasive intervention in a population of extremely preterm infants with large ductal shunts. Simultaneously, the transcatheter approach to ductal closure in the very immature infant represents an exciting therapeutic alternative but which is still in its infancy. Insights into the pathophysiology of postoperative cardiorespiratory deterioration, including the importance of left ventricular afterload, may help clinicians avoid instability and mitigate a potentially injurious aspect of surgical treatment. This review examines the evidence regarding the benefits and risks of PDA surgery in preterm neonates and provides a pathophysiology-based management paradigm to guide perioperative care in high-risk infants. © 2018 Published by Elsevier Ltd.

Precision of coherence analysis to detect cerebral autoregulation by near-infrared spectroscopy in preterm infants

NASA Astrophysics Data System (ADS)

Hahn, Gitte Holst; Christensen, Karl Bang; Leung, Terence S.; Greisen, Gorm

2010-05-01

Coherence between spontaneous fluctuations in arterial blood pressure (ABP) and the cerebral near-infrared spectroscopy signal can detect cerebral autoregulation. Because reliable measurement depends on signals with high signal-to-noise ratio, we hypothesized that coherence is more precisely determined when fluctuations in ABP are large rather than small. Therefore, we investigated whether adjusting for variability in ABP (variabilityABP) improves precision. We examined the impact of variabilityABP within the power spectrum in each measurement and between repeated measurements in preterm infants. We also examined total monitoring time required to discriminate among infants with a simulation study. We studied 22 preterm infants (GA<30) yielding 215 10-min measurements. Surprisingly, adjusting for variabilityABP within the power spectrum did not improve the precision. However, adjusting for the variabilityABP among repeated measurements (i.e., weighting measurements with high variabilityABP in favor of those with low) improved the precision. The evidence of drift in individual infants was weak. Minimum monitoring time needed to discriminate among infants was 1.3-3.7 h. Coherence analysis in low frequencies (0.04-0.1 Hz) had higher precision and statistically more power than in very low frequencies (0.003-0.04 Hz). In conclusion, a reliable detection of cerebral autoregulation takes hours and the precision is improved by adjusting for variabilityABP between repeated measurements.

Rate of Second and Third Trimester Weight Gain and Preterm Delivery Among Underweight and Normal Weight Women.

PubMed

Sharma, Andrea J; Vesco, Kimberly K; Bulkley, Joanna; Callaghan, William M; Bruce, F Carol; Staab, Jenny; Hornbrook, Mark C; Berg, Cynthia J

2016-10-01

Objectives Low gestational weight gain (GWG) in the second and third trimesters has been associated with increased risk of preterm delivery (PTD) among women with a body mass index (BMI) < 25 mg/m(2). However, few studies have examined whether this association differs by the assumptions made for first trimester gain or by the reason for PTD. Methods We examined singleton pregnancies during 2000-2008 among women with a BMI < 25 kg/m(2) who delivered a live-birth ≥28 weeks gestation (n = 12,526). Women received care within one integrated health care delivery system and began prenatal care ≤13 weeks. Using antenatal weights measured during clinic visits, we interpolated GWG at 13 weeks gestation then estimated rate of GWG (GWGrate) during the second and third trimesters of pregnancy. We also estimated GWGrate using the common assumption of a 2-kg gain for all women by 13 weeks. We examined the covariate-adjusted association between quartiles of GWGrate and PTD (28-36 weeks gestation) using logistic regression. We also examined associations by reason for PTD [premature rupture of membranes (PROM), spontaneous labor, or medically indicated]. Results Mean GWGrate did not differ among term and preterm pregnancies regardless of interpolated or assumed GWG at 13 weeks. However, only with GWGrate estimated from interpolated GWG at 13 weeks, we observed a U-shaped relationship where odds of PTD increased with GWGrate in the lowest (OR 1.36, 95 % CI 1.10, 1.69) or highest quartile (OR 1.49, 95 % CI 1.20, 1.85) compared to GWGrate within the second quartile. Further stratifying by reason, GWGrate in the lowest quartile was positively associated with spontaneous PTD while GWGrate in the highest quartile was positively associated with PROM and medically indicated PTD. Conclusions Accurate estimates of first trimester GWG are needed. Common assumptions applied to all pregnancies may obscure the association between GWGrate and PTD. Further research is needed to fully understand whether these associations are causal or related to common antecedents.

Focused Attention, Heart Rate Deceleration, and Cognitive Development in Preterm and Full-Term Infants

PubMed Central

Petrie Thomas, Julianne H.; Whitfield, Michael F.; Oberlander, Tim F.; Synnes, Anne R.; Grunau, Ruth E.

2012-01-01

The majority of children who are born very preterm escape major impairment, yet more subtle cognitive and attention problems are very common in this population. Previous research has linked infant focused attention during exploratory play to later cognition in children born full-term and preterm. Infant focused attention can be indexed by sustained decreases in heart rate (HR). However there are no preterm studies that have jointly examined infant behavioral attention and concurrent HR response during exploratory play in relation to developing cognition. We recruited preterm infants free from neonatal conditions associated with major adverse outcomes, and further excluded infants with developmental delay (Bayley Mental Development Index [MDI < 70]) at 8 months corrected age (CA). During infant exploratory play at 8 months CA, focused attention and concurrent HR response were compared in 83 preterm infants (born 23–32 weeks gestational age [GA]) who escaped major impairment to 46 full-term infants. Focused attention and HR response were then examined in relation to Bayley MDI, after adjusting for neonatal risk. MDI did not differ by group, yet full-term infants displayed higher global focused attention ratings. Among the extremely preterm infants born <29 weeks, fewer days on mechanical ventilation, mean longest focus, and greater HR deceleration during focused attention episodes, accounted for 49% of adjusted variance in predicting concurrent MDI. There were no significant associations for later-born gestational age (29–32 weeks) or full-term infants. Among extremely preterm infants who escape major impairment, our findings suggest unique relationships between focused attention, HR deceleration, and developing cognition. PMID:22487941

Predicting school readiness from neurodevelopmental assessments at age 2 years after respiratory distress syndrome in infants born preterm.

PubMed

Patrianakos-Hoobler, Athena I; Msall, Michael E; Huo, Dezheng; Marks, Jeremy D; Plesha-Troyke, Susan; Schreiber, Michael D

2010-04-01

To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric oxide for respiratory distress syndrome. Abnormal outcomes at the age of 2 years were defined as neurosensory disability (cerebral palsy, blindness, or bilateral hearing loss) or delay (no neurosensory disability but Bayley Scales of Infant Development mental or performance developmental index scores <70). School readiness (assessed at a mean age of 5y 6mo, SD 1y) was determined using neurodevelopmental assessments of motor, sensory, receptive vocabulary, perceptual, conceptual, and adaptive skills. The mean birthweight of the cohort (57 males, 64 females) was 987g (SD 374), and the mean gestational age was 27.3 weeks (SD 2.6). At the age of 2 years, the neurodevelopmental classification was 'disabled' in 11% and 'delayed' in 23%. At the age of 5 years 6 months, intensive special education was required for 11% and some special education for 21%. Disability and delay at the age of 2 years were 92% and 50% predictive of lack of school readiness respectively, whereas only 15% of children who were normal at the age of 2 years were not school ready at the later assessment. Children with delay at 2 years were more likely to need special education if they were socially disadvantaged. Without preschool developmental supports, preterm survivors living in poverty will require more special education services.

MOMS: Obstetrical Outcomes and Risk Factors for Obstetrical Complications Following Prenatal Surgery

PubMed Central

JOHNSON, Mark P.; BENNETT, Kelly A.; RAND, Larry; BURROWS, Pamela K.; THOM, Elizabeth A.; HOWELL, Lori J.; FARRELL, Jody A.; DABROWIAK, Mary E.; BROCK, John W.; FARMER, Diana L.; ADZICK, N. Scott

2016-01-01

Background The Management of Myelomeningocele Study (MOMS) was a multi-center randomized trial to compare prenatal and standard postnatal closure of myelomeningocele. The trial was stopped early at recommendation of the Data and Safety Monitoring Committee and outcome data for 158 of the 183 randomized women published. Objective In this report, pregnancy outcomes for the complete trial cohort are presented. We also sought to analyze risk factors for adverse pregnancy outcome among those women who underwent prenatal myelomeningocele repair. Study Design Pregnancy outcomes were compared between the two surgery groups. For women who underwent prenatal surgery antecedent demographic, surgical and pregnancy complication risk factors were evaluated for the following outcomes: premature spontaneous membrane rupture on or before 34 weeks 0 days (PPROM), spontaneous membrane rupture at any gestational age (SROM), preterm delivery at 34 weeks 0 days or earlier (PTD) and non-intact hysterotomy (minimal uterine wall tissue between fetal membranes and uterine serosa, or partial or complete dehiscence at delivery) and chorioamniotic membrane separation. Risk factors were evaluated using chi-square and Wilcoxon tests and multivariable logistic regression. Results A total of 183 women were randomized: 91 to prenatal surgery and 92 to postnatal surgery groups. Analysis of the complete cohort confirmed initial findings: that prenatal surgery was associated with an increased risk for membrane separation, oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor and earlier gestational age at birth. In multivariable logistic regression of the prenatal surgery group adjusting for clinical center, earlier gestational age at surgery and chorioamniotic membrane separation were associated with increased risk of SROM (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.01-2.22; OR 2.96, 95% CI 1.05-8.35, respectively). Oligohydramnios was associated with an increased risk of subsequent PTD (OR 9.21, 95% CI 2.19 - 38.78). Nulliparity was a risk factor for non-intact hysterotomy (OR 3.68, 95% CI 1.35 – 10.05). Conclusions Despite the confirmed benefits of prenatal surgery, considerable maternal and fetal risk exists compared with postnatal repair. Early gestational age at surgery and development of chorioamniotic membrane separation are risk factors for ruptured membranes. Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk factor for non-intact hysterotomy at delivery. PMID:27496687

Association Between Endometriosis and Preterm Birth in Women With Spontaneous Conception or Using Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of Cohort Studies.

PubMed

Pérez-López, Faustino R; Villagrasa-Boli, Pablo; Muñoz-Olarte, María; Morera-Grau, Álex; Cruz-Andrés, Pablo; Hernandez, Adrian V

2018-03-01

To perform a systematic review and meta-analysis to estimate the effect of endometriosis on preterm birth (PB) risk. Searches were conducted in PubMed-MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, Google Scholar, and SciELO for studies published in all languages from inception through April 2017. We included cohort studies evaluating pregnant women with and without endometriosis and conception either by spontaneous conception (SC) or with assisted reproductive technology (ART). Primary outcome was PB (<37 weeks), and secondary outcomes were intrauterine growth restriction (IUGR), low birthweight, small for gestational age (SGA), and birthweight. Pooled odds ratios (ORs) and its 95% confidence interval (CI) were calculated as effects, and random-effects models were used for meta-analyses. Risk of bias was assessed with the Newcastle-Ottawa Scale, and heterogeneity of effects among studies was described with the I 2 statistic. We identified 9 cohort studies including a total of 1 496 715 pregnancies (13 798 with endometriosis diagnosis). In women with endometriosis, the PB risk was significantly increased in both SC (OR: 1.59; 95% CI: 1.32-1.90) and ART (OR: 1.43; 95% CI: 1.14-1.79). The SGA risk was increased in women with endometriosis (OR: 1.16; 95% CI: 1.05-1.28), while the IUGR and low birthweight risks and birthweight were not affected by endometriosis. Endometriosis is associated with increased PB risk in both SC and women who obtained pregnancy using ART. Prospective studies evaluating relevant outcomes are needed to confirm these results.

Predicting Bradycardia in Preterm Infants Using Point Process Analysis of Heart Rate.

PubMed

Gee, Alan H; Barbieri, Riccardo; Paydarfar, David; Indic, Premananda

2017-09-01

Episodes of bradycardia are common and recur sporadically in preterm infants, posing a threat to the developing brain and other vital organs. We hypothesize that bradycardias are a result of transient temporal destabilization of the cardiac autonomic control system and that fluctuations in the heart rate signal might contain information that precedes bradycardia. We investigate infant heart rate fluctuations with a novel application of point process theory. In ten preterm infants, we estimate instantaneous linear measures of the heart rate signal, use these measures to extract statistical features of bradycardia, and propose a simplistic framework for prediction of bradycardia. We present the performance of a prediction algorithm using instantaneous linear measures (mean area under the curve = 0.79 ± 0.018) for over 440 bradycardia events. The algorithm achieves an average forecast time of 116 s prior to bradycardia onset (FPR = 0.15). Our analysis reveals that increased variance in the heart rate signal is a precursor of severe bradycardia. This increase in variance is associated with an increase in power from low content dynamics in the LF band (0.04-0.2 Hz) and lower multiscale entropy values prior to bradycardia. Point process analysis of the heartbeat time series reveals instantaneous measures that can be used to predict infant bradycardia prior to onset. Our findings are relevant to risk stratification, predictive monitoring, and implementation of preventative strategies for reducing morbidity and mortality associated with bradycardia in neonatal intensive care units.

Interrelationship of Cytokines, Hypothalamic-Pituitary-Adrenal Axis Hormones, and Psychosocial Variables in the Prediction of Preterm Birth

PubMed Central

Pearce, B.D.; Grove, J.; Bonney, E.A.; Bliwise, N.; Dudley, D.J.; Schendel, D.E.; Thorsen, P.

2010-01-01

Background/Aims To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. Methods In this prospective case-control study, maternal serum biomarkers were quantified at 9–23 weeks’ gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. Results Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-α were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743–0.874). Conclusion Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator. PMID:20160447

Interrelationship of cytokines, hypothalamic-pituitary-adrenal axis hormones, and psychosocial variables in the prediction of preterm birth.

PubMed

Pearce, B D; Grove, J; Bonney, E A; Bliwise, N; Dudley, D J; Schendel, D E; Thorsen, P

2010-01-01

To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. In this prospective case-control study, maternal serum biomarkers were quantified at 9-23 weeks' gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-alpha were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743-0.874). Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator. Copyright (c) 2010 S. Karger AG, Basel.

Racial and ethnic disparities in use of 17-alpha hydroxyprogesterone caproate for prevention of preterm birth.

PubMed

Yee, Lynn M; Liu, Lilly Y; Sakowicz, Allie; Bolden, Janelle R; Miller, Emily S

2016-03-01

Racial/ethnic disparities in preterm birth remain a major public health challenge in the United States. While 17-alpha hydroxyprogesterone caproate (17OHP-C) is recommended for preterm birth prevention in women with a prior preterm birth, non-Hispanic black women continue to experience higher rates of recurrent preterm birth than white women receiving the same treatment. Further investigation of disparities in 17OHP-C use and adherence is warranted. We sought to evaluate whether racial and ethnic disparities exist in the use of and adherence to 17OHP-C within a population of eligible women. This was a retrospective cohort study of women with a prior spontaneous, singleton preterm birth who were eligible for 17OHP-C for preterm birth prevention and received care at a single institution from 2010 through 2014. Associations between self-identified race/ethnicity (non-Hispanic black vs women in all other racial/ethnic groups) and documented counseling about 17OHP-C, receipt of any 17OHP-C, and adherence to 17OHP-C administration were each estimated by bivariable analysis and multivariable logistic regression. Adherence to 17OHP-C was defined as not >1 missed dose, initiation <20 weeks' gestational age, and continuation until 37 weeks or delivery. Of 472 women who were clinically eligible for 17OHP-C, 72% (N = 296) had documented 17OHP-C counseling and 48.9% (N = 229) received 17OHP-C. There were no differences in likelihood of 17OHP-C counseling or receipt of 17OHP-C based on race/ethnicity. While overall 83% (N = 176) of women were adherent to 17OHP-C, only 70% (N = 58) of non-Hispanic black women were adherent, compared to 91% (N = 118) of all other women (P < .001). Non-Hispanic black women had more missed doses (2.4 vs 0.4 doses, P < .001) and later initiation of care (12.0 vs 10.2 weeks, P < .001) than women in other racial/ethnic groups. After adjustment for potential confounders, non-Hispanic black women were significantly less likely to be adherent to 17OHP-C (adjusted odds ratio, 0.16; 95% confidence interval, 0.04-0.65). A significant interaction between non-Hispanic black race/ethnicity and public insurance was identified (adjusted odds ratio, 0.16; 95% confidence interval, 0.05-0.52). In a diverse cohort of women eligible for preterm birth prevention, non-Hispanic black women are at an increased risk of nonadherence to 17OHP-C. Non-Hispanic black women with public insurance are at a particularly increased risk of nonadherence. Copyright © 2016 Elsevier Inc. All rights reserved.

Racial residential segregation impacts on low birth weight using improved neighborhood boundary definitions.

PubMed

Grady, Sue C

2010-12-01

Research on local racial residential segregation and health generally utilize census tract boundaries as a proxy from within which to estimate individual exposures. Census tracts however, may not accurately reflect the neighborhood environments in which people live and interact. Census tract geography may also capture non-exchangeable populations in socially stratified cities, impacting statistical assumptions of independence. To address these concerns, this study assessed the impact of racial residential segregation (i.e., racial isolation and racial clusters) on low birth weight (i.e., intrauterine growth retardation (IUGR) and preterm birth) in the Detroit Metropolitan Area using optimized neighborhood boundary definitions. Automated zone-matching (AZM) methodology was applied to redefine neighborhood (zones). Maternal and infant health information was obtained from Michigan's vital statistics birth registry (n=137,965) for the years 2004-2006. Multilevel models were estimated to assess the effect of high racial isolation and high racial clusters on IUGR and preterm birth, controlling for maternal race, single marital status, smoking and area-level poverty. The results from this study showed that high racial isolation had a significant effect on IUGR, while the odds of preterm birth were higher in racially clustered zones. African American mothers were at increased odds of having IUGR or preterm infants than other mothers; however, these disparities reduced in highly segregated zones. The predicted incidence of IUGR across racially isolated zones and census tracts differed indicating a modifiable area unit problem (MAUP). MAUP effects were not observed in models predicting preterm incidence in high racial clusters or IUGR or preterm incidence in high poverty areas, demonstrating the stability-reliability of these estimates. Future research should continue to optimize neighborhood boundary definitions, while assessing the sensitivity of segregation measures to changes in scale, to improve our understanding of segregation impacts on racial disparities in low birth weight. Copyright © 2010 Elsevier Inc. All rights reserved.

Structural Connectivity Relates to Perinatal Factors and Functional Impairment at 7 Years in Children Born Very Preterm

PubMed Central

Thompson, Deanne K.; Chen, Jian; Beare, Richard; Adamson, Christopher L.; Ellis, Rachel; Ahmadzai, Zohra M.; Kelly, Claire E.; Lee, Katherine J.; Zalesky, Andrew; Yang, Joseph Y.M.; Hunt, Rodney W.; Cheong, Jeanie L.Y.; Inder, Terrie E.; Doyle, Lex W.; Seal, Marc L.; Anderson, Peter J.

2016-01-01

Objective To use structural connectivity to (1) compare brain networks between typically and atypically developing (very preterm) children, (2) explore associations between potential perinatal developmental disturbances and brain networks, and (3) describe associations between brain networks and functional impairments in very preterm children. Methods 26 full-term and 107 very preterm 7-year-old children (born <30 weeks’ gestational age and/or <1250 g) underwent T1- and diffusion-weighted imaging. Global white matter fiber networks were produced using 80 cortical and subcortical nodes, and edges created using constrained spherical deconvolution-based tractography. Global graph theory metrics were analysed, and regional networks were identified using network-based statistics. Cognitive and motor function were assessed at 7 years of age. Results Compared with full-term children, very preterm children had reduced density, lower global efficiency and higher local efficiency. Those with lower gestational age at birth, infection or higher neonatal brain abnormality score had reduced connectivity. Reduced connectivity within a widespread network was predictive of impaired IQ, while reduced connectivity within the right parietal and temporal lobes was associated with motor impairment in very preterm children. Conclusions This study utilized an innovative structural connectivity pipeline to reveal that children born very preterm have less connected and less complex brain networks compared with typically developing term-born children. Adverse perinatal factors led to disturbances in white matter connectivity, which in turn are associated with impaired functional outcomes, highlighting novel structure-function relationships. PMID:27046108

Probability distributions of the electroencephalogram envelope of preterm infants.

PubMed

Saji, Ryoya; Hirasawa, Kyoko; Ito, Masako; Kusuda, Satoshi; Konishi, Yukuo; Taga, Gentaro

2015-06-01

To determine the stationary characteristics of electroencephalogram (EEG) envelopes for prematurely born (preterm) infants and investigate the intrinsic characteristics of early brain development in preterm infants. Twenty neurologically normal sets of EEGs recorded in infants with a post-conceptional age (PCA) range of 26-44 weeks (mean 37.5 ± 5.0 weeks) were analyzed. Hilbert transform was applied to extract the envelope. We determined the suitable probability distribution of the envelope and performed a statistical analysis. It was found that (i) the probability distributions for preterm EEG envelopes were best fitted by lognormal distributions at 38 weeks PCA or less, and by gamma distributions at 44 weeks PCA; (ii) the scale parameter of the lognormal distribution had positive correlations with PCA as well as a strong negative correlation with the percentage of low-voltage activity; (iii) the shape parameter of the lognormal distribution had significant positive correlations with PCA; (iv) the statistics of mode showed significant linear relationships with PCA, and, therefore, it was considered a useful index in PCA prediction. These statistics, including the scale parameter of the lognormal distribution and the skewness and mode derived from a suitable probability distribution, may be good indexes for estimating stationary nature in developing brain activity in preterm infants. The stationary characteristics, such as discontinuity, asymmetry, and unimodality, of preterm EEGs are well indicated by the statistics estimated from the probability distribution of the preterm EEG envelopes. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation.

PubMed

Cook, Sarah F; Roberts, Jessica K; Samiee-Zafarghandy, Samira; Stockmann, Chris; King, Amber D; Deutsch, Nina; Williams, Elaine F; Allegaert, Karel; Wilkins, Diana G; Sherwin, Catherine M T; van den Anker, John N

2016-01-01

The aims of this study were to develop a population pharmacokinetic model for intravenous paracetamol in preterm and term neonates and to assess the generalizability of the model by testing its predictive performance in an external dataset. Nonlinear mixed-effects models were constructed from paracetamol concentration-time data in NONMEM 7.2. Potential covariates included body weight, gestational age, postnatal age, postmenstrual age, sex, race, total bilirubin, and estimated glomerular filtration rate. An external dataset was used to test the predictive performance of the model through calculation of bias, precision, and normalized prediction distribution errors. The model-building dataset included 260 observations from 35 neonates with a mean gestational age of 33.6 weeks [standard deviation (SD) 6.6]. Data were well-described by a one-compartment model with first-order elimination. Weight predicted paracetamol clearance and volume of distribution, which were estimated as 0.348 L/h (5.5 % relative standard error; 30.8 % coefficient of variation) and 2.46 L (3.5 % relative standard error; 14.3 % coefficient of variation), respectively, at the mean subject weight of 2.30 kg. An external evaluation was performed on an independent dataset that included 436 observations from 60 neonates with a mean gestational age of 35.6 weeks (SD 4.3). The median prediction error was 10.1 % [95 % confidence interval (CI) 6.1-14.3] and the median absolute prediction error was 25.3 % (95 % CI 23.1-28.1). Weight predicted intravenous paracetamol pharmacokinetics in neonates ranging from extreme preterm to full-term gestational status. External evaluation suggested that these findings should be generalizable to other similar patient populations.

Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation

PubMed Central

Cook, Sarah F.; Roberts, Jessica K.; Samiee-Zafarghandy, Samira; Stockmann, Chris; King, Amber D.; Deutsch, Nina; Williams, Elaine F.; Allegaert, Karel; Sherwin, Catherine M. T.; van den Anker, John N.

2017-01-01

Objectives The aims of this study were to develop a population pharmacokinetic model for intravenous paracetamol in preterm and term neonates and to assess the generalizability of the model by testing its predictive performance in an external dataset. Methods Nonlinear mixed-effects models were constructed from paracetamol concentration–time data in NONMEM 7.2. Potential covariates included body weight, gestational age, postnatal age, postmenstrual age, sex, race, total bilirubin, and estimated glomerular filtration rate. An external dataset was used to test the predictive performance of the model through calculation of bias, precision, and normalized prediction distribution errors. Results The model-building dataset included 260 observations from 35 neonates with a mean gestational age of 33.6 weeks [standard deviation (SD) 6.6]. Data were well-described by a one-compartment model with first-order elimination. Weight predicted paracetamol clearance and volume of distribution, which were estimated as 0.348 L/h (5.5 % relative standard error; 30.8 % coefficient of variation) and 2.46 L (3.5 % relative standard error; 14.3 % coefficient of variation), respectively, at the mean subject weight of 2.30 kg. An external evaluation was performed on an independent dataset that included 436 observations from 60 neonates with a mean gestational age of 35.6 weeks (SD 4.3). The median prediction error was 10.1 % [95 % confidence interval (CI) 6.1–14.3] and the median absolute prediction error was 25.3 % (95 % CI 23.1–28.1). Conclusions Weight predicted intravenous paracetamol pharmacokinetics in neonates ranging from extreme preterm to full-term gestational status. External evaluation suggested that these findings should be generalizable to other similar patient populations. PMID:26201306

The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations.

PubMed

Shah, Jaimin S; Roman, Tania; Viteri, Oscar A; Haidar, Ziad A; Ontiveros, Alejandra; Sibai, Baha M

2018-06-08

 To assess whether assisted reproductive technology (ART) is associated with increased risk of adverse perinatal outcomes in triplet gestations compared with spontaneous conception.  Secondary analysis of a multicenter randomized trial for the prevention of preterm birth in multiple gestations. Triplets delivered at ≥ 24 weeks were studied. The primary outcome was the rate of composite neonatal morbidity (CNM) that included one or more of the following: bronchopulmonary dysplasia, respiratory distress syndrome, necrotizing enterocolitis, culture proven sepsis, pneumonia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, or perinatal death.  There were 381 triplets (127 women) of which 89 patients conceived via ART and 38 patients spontaneously. Women with ART were more likely to be older, Caucasian, married, nulliparous, have higher level of education, and develop pre-eclampsia. Spontaneously conceived triplets were more likely to delivery at an earlier gestation (31.2 ± 3.5 vs 32.8 ± 2.7 weeks) ( p  = 0.009) with a lower birth weight ( p  < 0.001). After adjusting for confounders, no differences were noted in culture proven sepsis, perinatal death, CNM, respiratory distress syndrome, or Apgar score < 7 at 5 minutes. All remaining perinatal outcomes were similar.  Triplets conceived by ART had similar perinatal outcomes compared with spontaneously conceived triplets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Pregnancy outcome in women over the age of 35].

PubMed

Dakov, T; Dimitrova, V; Todorov, T

2014-01-01

To assess pregnancy outcome in women aged > or =35, followed prospectively, and the relation between maternal age and the incidence of abortions after 12 gw (spontaneous and medical), preterm delivery, mode of delivery and congenital anomalies. 495 women from the Fetal Medicine Clinic of the State University Hospital "Maichin Dom" in Sofia were enrolled in the study between 02/2012 and 02/2014 with gestational age > or =12 completed weeks. The patients were devided in 3 groups according to age-- < or =34, between 35 and 39 and > or = 40 years of age. Pregnancy outcome was veirified from hospital records and phone intenrviews with the patients themselves. Data were processed with SPSS 13.0 statistical package. Descriptive and comparative analysis was performed after grouping according to one or more characteristics; p values <0.05 were considered as evidence of statistical significance for tested effects. 131/495 (26.5%) of the patients were < or =34 years of age, 254/495 (51.3%) were between 35 and 39 and 110/495 (22.2%) were > or =40 years of age. Maternal age > or =35 was associated with statistically significant increase of the total late abortion rate (spontaneous and medical abortions)--from 6.9% for those < or =34 yars of age to 11.3%--for the ones between 35-39 and 11.4%--for the ones > or =40 years. There was also statistically significant increase in the incidence of late medical abortions in the group > or =40 years of age (p=0.011). It was 2/124 (1.6%) for the group aged < or =34, 7/230 (3%)--in the group aged 35-39 and 9/100 (9.0%)--in the group > or =40 years of age. The difference in late spontaneous abortions rate was not statistically significant among the groups. There was statistically significant increase in the incidence of preterm deliveries (spontaneous and induced)--14/131 (10.7%) in the group aged < or =34, 52/208 (25.0%)--in the group between 35-39 and 20/93 (21.5%)--in the group > or =40 years of age (p=0.013). There was also a significant increase in Cesarean section rate with age--from 44/131 (33.6%) in the group < or =34, to 139/254 (54.7%)--in the group between 35-39, and 69/110 (62.7%)--in the group > or =40 years (p=0.0001). There is a tendency for increased operative vaginal delivery rate with age; however the difference is not statistically significant, probably due to the small number of cases (p=O. 113). There was also statistically significant increase in the proportion of newborns with congenital anomalies in women > or =40 years of age (p=0.005)--from 1/131 (0.8%) in patients < or =34, to 2/254 (1.0%) for those between 35 and 39, and 6/110 (5.5%)--for those > or =40 years. Part of the congenital anomalies was prenatally diagnosed chromosomal defects without termination of pregnancy Maternal age > or =35 years is associated with statistically significant increase in late medical abortions, preterm delivery and Cesarean section rate and congenital fetal anomalies.

Maternal weight status and responsiveness to preterm infant behavioral cues during feeding.

PubMed

Arianas, Evanthia A; Rankin, Kristin M; Norr, Kathleen F; White-Traut, Rosemary C

2017-04-11

Parental obesity is highly predictive of child obesity, and preterm infants are at greater risk of obesity, but little is known about obese and non-obese mothers' responsiveness to preterm infant cues during feeding. The relationship between maternal weight status and response to preterm infant behavioral cues during feeding at 6-weeks corrected age was examined. This secondary analysis used data from a randomized clinical trial. Maternal weight was coded during a play session. Mother-infant interaction during feeding was coded using the Nursing Child Assessment Satellite Training Feeding Scale (NCAST). We used multivariate linear regressions to examine NCAST scores and multivariate logistic regressions for the two individual items, satiation cues and termination of feeding. Of the 139 mothers, 56 (40.3%) were obese, two underweight women were excluded. Obese mothers did not differ from overweight/normal weight mothers for overall NCAST scores, but they had higher scores on response to infant's distress subscale (mean = 10.2 vs. 9.6, p = 0.01). The proportion of infants who exhibited satiation cues did not differ by maternal weight. Obese mothers were more likely than overweight/normal weight mothers to terminate the feeding when the infant showed satiation cues (82.1% vs. 66.3%, p = 0.04, adjusted OR = 2.31, 95% CI = 0.97, 5.48). Limitations include lack of BMI measures and small sample size. Additional research is needed about maternal weight status and whether it influences responsiveness to preterm infant satiation cues. Results highlight the need for educating all mothers of preterm infants regarding preterm infant cues. NCT02041923 . Feeding and Transition to Home for Preterms at Social Risk (H-HOPE). Registered 15 January 2014.

Likelihood ratios for the prediction of preterm delivery with biomarkers.

PubMed

Hee, Lene

2011-11-01

To conduct a literature search for selected biomarkers on preterm delivery and estimate their likelihood ratios (LR). Structured review. Low and high-risk populations and women with symptoms of preterm delivery. METHODS. Publications were identified in PubMed. LR on selected biomarkers for preterm delivery. In asymptomatic women with low risk of preterm delivery, the following biomarkers gave major shifts in probability (LR above 5): twins (LR+ 10), Ureaplasma urealyticum in amniotic fluid (LR+ of 10), cervical length <25mm (LR+ 6), salival estriol (LR+ 5) and various combined tests. In asymptomatic women with high risk of preterm delivery, short cervical length (LR+ 11, LR- 0.7), high serum tumor necrosis factor-alpha (LR+ 10, LR- 0.6) gave major shifts in probability. In women with symptoms of preterm delivery, major shifts in probability can be obtained from the following amniotic fluid biomarkers: high matrix metalloproteinase-8 (LR+ 23, LR- 0.6), Ureaplasma urealyticum (LR+ 19, LR- 0.8), high interleukin (IL)-6 (LR+ 9, LR- 0.2), IL-8 (LR+10, LR- 0.2) and tumor necrosis factor-alpha (LR+ 8, LR- 0.4). In serum IL-6 (LR+ 12, LR- 0.2), Cluster of Differentiation 163 (LR+9, LR-0.8) and various combined tests. Vaginal fetal fibronectin (LR+ 3 and LR- 0.5) and short cervical length (LR+ 2, LR- 0.3) gave LRs of some importance (LR below 5). Several biomarkers have been identified for assessment of risk of preterm delivery. Their clinical relevance depends on the efficacy of the interventions which can be offered to these patients. © 2011 The Author Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Feasibility of event-related potential (ERP) biomarker use to study effects of mother's voice exposure on speech sound differentiation of preterm infants.

PubMed

D Chorna, Olena; L Hamm, Ellyn; Shrivastava, Hemang; Maitre, Nathalie L

2018-01-01

Atypical maturation of auditory neural processing contributes to preterm-born infants' language delays. Event-related potential (ERP) measurement of speech-sound differentiation might fill a gap in treatment-response biomarkers to auditory interventions. We evaluated whether these markers could measure treatment effects in a quasi-randomized prospective study. Hospitalized preterm infants in passive or active, suck-contingent mother's voice exposure groups were not different at baseline. Post-intervention, the active group had greater increases in/du/-/gu/differentiation in left frontal and temporal regions. Infants with brain injury had lower baseline/ba/-/ga/and/du/-/gu/differentiation than those without. ERP provides valid discriminative, responsive, and predictive biomarkers of infant speech-sound differentiation.

Strip test for bedside detection of interleukin-6 in cervical secretions is predictive for impending preterm delivery.

PubMed

Trébéden, H; Goffinet, F; Kayem, G; Maillard, F; Lemoine, E; Cabrol, D; Weill, B; Batteux, F

2001-01-01

Inflammatory cytokines in amniotic fluid are markers of prematurity which could characterize preterm labour of infectious origin. To avoid amniocentesis, we analyzed IL-6, IL-8, IL-10, and IL-13 by RT-PCR in cervical secretions (CS) of 307 women with preterm labour. IL-6 was detected in 26.3% patients who delivered at less than 34 weeks (specificity: 95.8%). In addition, IL-6 was associated with delivery within 7 days (specificity: 91.6%). To render the detection more rapid and cheaper, a strip test was designed and evaluated comparatively with RT-PCR in 76 women. This bedside strip test was twice more sensitive than RT-PCR, with little decrease in specificity.

The role of Mycoplasma and Ureaplasma in adverse pregnancy outcomes.

PubMed

Murtha, Amy P; Edwards, James M

2014-12-01

Genital mycoplasmas are frequently found in the vaginal flora across socioeconomic and ethnic groups and have been demonstrated to be involved in adverse perinatal outcomes. Both Mycoplasma and Ureaplasma spp cause inflammation potentially leading to spontaneous preterm birth and PPROM as well as postdelivery infectious complications and neonatal infections. Herein we have provided an overview of the existing literature and supportive evidence for genital mycoplasma's role in perinatal complications. Future research will need to focus on clearly delineating the species, allowing for discrimination of their effects. Copyright © 2014 Elsevier Inc. All rights reserved.