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.

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.

Preterm Labor

MedlinePlus

Preterm labor is labor that starts before 37 completed weeks of pregnancy. It can lead to premature birth. Premature babies may face serious health risks. Symptoms of preterm labor include Contractions every 10 minutes or more often ...

Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth.

PubMed

Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A; Romero, Roberto

2009-01-01

The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode.

Immune cells in term and preterm labor

PubMed Central

Gomez-Lopez, Nardhy; StLouis, Derek; Lehr, Marcus A; Sanchez-Rodriguez, Elly N; Arenas-Hernandez, Marcia

2014-01-01

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm. PMID:24954221

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.

Maternal asthma and idiopathic preterm labor.

PubMed

Kramer, M S; Coates, A L; Michoud, M C; Dagenais, S; Moshonas, D; Davis, G M; Hamilton, E F; Nuwayhid, B; Joshi, A K; Papageorgiou, A

1995-11-15

Previous studies suggest that women with asthma are at increased risk of preterm birth. Moreover, drugs (especially beta-agonists) used to treat asthma are also used to treat preterm labor. The authors carried out a case-control study of 555 women from three hospital centers with idiopathic preterm labor (< 37 weeks), including two overlapping (i.e., non-mutually exclusive) subsamples: cases with early idiopathic preterm labor (< 34 weeks) and cases with idiopathic recurrent preterm labor (< 37 weeks plus a previous history of preterm delivery or second-trimester miscarriage). Controls were matched to cases according to race and smoking history prior to and during pregnancy. All subjects responded in person to questions about atopic, respiratory, obstetric, and sociodemographic histories. Subjects in the early and recurrent preterm labor subsamples were also asked to undergo spirometric testing with methacholine challenge 6-12 weeks after delivery. Cases were significantly more likely to report histories of asthma symptoms and physician-diagnosed asthma (matched odds ratios of 2-3) than controls, particularly those cases with recurrent preterm labor. No significant associations were observed, however, with methacholine responsiveness. These results could not be explained by residual confounding by smoking or other variables, nor by selective recall of asthma symptoms and histories by cases. Women with asthma are at increased risk of idiopathic preterm labor. The fact that no such association was seen with methacholine responsiveness suggests that nonatopic, noncholinergic mechanisms may link bronchial and uterine smooth muscle lability.

Plasma C16-Cer levels are increased in patients with preterm labor.

PubMed

Laudanski, Piotr; Charkiewicz, Karol; Kisielewski, Rafal; Kuc, Pawel; Koc-Zorawska, Ewa; Raba, Grzegorz; Kraczkowski, Janusz; Dymicka-Piekarska, Violetta; Chabowski, Adrian; Kacerovsky, Marian; Jacobsson, Bo; Zabielski, Piotr; Blachnio-Zabielska, Agnieszka

2016-03-01

The pathogenesis of preterm labor is fragmentarily explained. The most widely accepted theory points out to infection and inflammation as possible causes, which can be mediated by potentially different factors, including sphingolipid mediators. Sphingolipids are a class of lipids that have been shown as important mediators in various cell processes such as: proliferation, growth, apoptosis, stress response, necrosis and inflammation. The aim of the study was to assess plasma concentrations of selected sphingolipids in patients with preterm labor. We used ultra-high performance liquid chromatography with triple mass spectrometry (UHPLC-ESI-MS/MS) to assess plasma concentrations of the 11 sphingolipids in patients presenting with symptoms of preterm labor (n=61) and threatened preterm labor (n=40). We observed a statistically significant increase (p-value<0.004) in plasma concentrations of C16-Cer in patients with preterm labor as compared to the control group. We also found C16-Cer to be the best predictor of preterm labor in the group of patients with symptoms occurring after 32 weeks of gestation. Our findings show a possible involvement of selected sphingolipids, especially C16-Cer, in the pathogenesis of preterm labor. Their role as predictors of preterm delivery needs to be validated in the future on larger group of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

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

TRPC3 Overexpression Promotes the Progression of Inflammation-Induced Preterm Labor and Inhibits T Cell Activation.

PubMed

Jing, Chen; Dongming, Zheng; Hong, Cui; Quan, Na; Sishi, Liu; Caixia, Liu

2018-01-01

To detect the expression of the TRPC3 channel protein in the tissues of women experiencing preterm labor and investigate its interaction with T lymphocytes, providing a theoretical basis for the clinical prevention of threatened preterm labor and the development of drug-targeted therapy. Forty-seven women experiencing preterm labor and 47 women experiencing normal full-term labor were included in this study. All included women underwent delivery via cesarean section; uterine samples were obtained at delivery. The expression of TRPC3 in uterine tissue was detected by immunohistochemistry, real-time quantitative reverse transcription-PCR, and western blot assay. Activation of T lymphocytes in peripheral blood and uterine tissue were detected by flow cytometry. A TRPC3-/- mouse model of inflammation-induced preterm labor was established; expression of TRPC3, Cav3.1, and Cav3.2 were analyzed in mouse uterine tissue. Activation of T lymphocytes in female mouse and human peripheral blood samples was determined using flow cytometry. In women experiencing preterm labor, expression of TRPC3 and the Cav3.1 and Cav3.2 proteins was significantly increased; in addition, the percentage of CD3+, CD4+, and CD8+ T cells in peripheral blood was significantly decreased. TRPC3 knockout significantly delayed the occurrence of preterm labor in mice. The muscle tension of ex vivo uterine strips was lower, Cav3.1 and Cav3.2 protein expression was lower, and the percentage of CD8+ T lymphocytes was significantly increased in wild-type mice subjected to an inflammation-induced preterm labor than in wild-type mice experiencing normal full-term labor. TRPC3 is closely related to the initiation of labor. TRPC3 relies on Cav3.1 and Cav3.2 proteins to inhibit inflammation-induced preterm labor by inhibiting the activation of T cells, in particular CD8+ T lymphocytes. © 2018 The Author(s). Published by S. Karger AG, Basel.

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

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.

Plasma inflammatory and immune proteins as predictors of intra-amniotic infection and spontaneous preterm delivery in women with preterm labor: a retrospective study.

PubMed

Park, Hyunsoo; Park, Kyo Hoon; Kim, Yu Mi; Kook, Song Yi; Jeon, Se Jeong; Yoo, Ha-Na

2018-05-09

We investigated whether various inflammatory and immune proteins in plasma predict intra-amniotic infection and imminent preterm delivery in women with preterm labor and compared their predictive ability with that of amniotic fluid (AF) interleukin (IL)-6 and serum C-reactive protein (CRP). This retrospective cohort study included 173 consecutive women with preterm labor who underwent amniocentesis for diagnosis of infection and/or inflammation in the AF. The AF was cultured, and assayed for IL-6. CRP levels and cervical length by transvaginal ultrasound were measured at the time of amniocentesis. The stored maternal plasma was assayed for IL-6, matrix metalloproteinase (MMP)-9, and complements C3a and C5a using ELISA kits. The primary and secondary outcome criteria were positive AF cultures and spontaneous preterm delivery (SPTD) within 48 h, respectively. Univariate, multivariate, and receiver operating characteristic analysis were used for the statistical analysis. In bivariate analyses, elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery, whereas elevated plasma levels of MMP-9, C3a, and C5a were not associated with these two outcomes. On multivariate analyses, an elevated plasma IL-6 level was significantly associated with intra-amniotic infection and imminent preterm delivery after adjusting for confounders, including high serum CRP levels and short cervical length. In predicting intra-amniotic infection, the area under the curve (AUC) was significantly lower for plasma IL-6 than for AF IL-6 but was similar to that for serum CRP. Differences in the AUCs between plasma IL-6, AF IL-6, and serum CRP were not statistically significant in predicting imminent preterm delivery. Maternal plasma IL-6 independently predicts intra-amniotic infection in women with preterm labor; however, it has worse diagnostic performance than that of AF IL-6 and similar performance to that of serum CRP. To predict imminent preterm delivery, plasma IL-6 had an overall diagnostic performance similar to that of AF IL-6 and serum CRP. Plasma MMP-9, C3a, and C5a levels could not predict intra-amniotic infection or imminent preterm delivery.

[Management of threatening preterm labor with intact membranes: indications for antibiotics].

PubMed

Winer, N

2002-11-01

To analyse the benefits and disadvantages of systematic antibiotic therapy in patient presenting a preterm labor with intact membranes. We reviewed French and English reports on Medline using to the following key words: "antibiotic therapy and preterm labor, preterm labor, streptococcus B, vaginose, mycoplasma, antenatal infection". The systematic prescription of antibiotics is not recommended for patients presenting preterm labor who have intact membranes and no symptoms of infection. The benefit of antibiotics is small and shows a tendency to prolong the pregnancy and the reduction of maternal infection. No benefit has been shown for neonatal results. When early-onset neonatal sepsis develops in a case in which antepartum chemoprophylaxis was used, the isolated bacteria will present an increasing risk of bacterial drug resistance. Local treatment (cream or pessary) do not belong in the treatment of threatening preterm labor and are not recommended for the prevention of prematurity or materno fetal infection. Risk groups of patients who present a positive vaginal colonization are subject to discussion. Studies do not allow us to ascertain that antibiotics have a beneficial effect on prematurity in these groups. Antibiotics are recommended for the treatment of asymptomatic bacteriuria. This treatment reduces prematurity and maternal infections. Despite poor consensus criteria, if threatening preterm labor is associated with a bacteriuria, experts usually recommend treatment.

The Effect of Treating Bacterial Vaginosis on Preterm Labor

PubMed Central

Tebes, Christine C.; Lynch, Catherine

2003-01-01

Objective: Multiple studies suggest that bacterial vaginosis (BV) causes preterm labor; yet its routine treatment remains controversial. In order to help to elucidate this controversy, we performed a thorough review of studies with levels of evidence ranging from I to II–II. Methods: We searched for all of the studies from the years 1994 to 2001 via Medline’s database, including MD Consult and Ovid Mednet. Results: Several trials discovered a decrease in the incidence of preterm labor when BV was treated, but most of those trials were performed on women with a history of preterm labor. However, the majority of trials reviewed advise against treatment of a general low-risk obstetric population, as there was no significant decrease in preterm labor. Conclusions: Therefore, based on the above studies and the current guidelines of the Centers for Disease Control and Prevention (CDC), treating pregnant women in high-risk populations who are diagnosed with BV provides the clinician with an opportunity to possibly prevent preterm labor in this population. In nulliparous women without a history of preterm birth, treatment is recommended if other risk factors are present (e.g. gonorrhea or chlamydia). However, in the general low-risk populations, routine screening is not indicated. PMID:14627219

The effect of treating bacterial vaginosis on preterm labor.

PubMed

Tebes, Christine C; Lynch, Catherine; Sinnott, John

2003-01-01

Multiple studies suggest that bacterial vaginosis (BV) causes preterm labor; yet its routine treatment remains controversial. In order to help to elucidate this controversy, we performed a thorough review of studies with levels of evidence ranging from I to II-II. We searched for all of the studies from the years 1994 to 2001 via Medline's database, including MD Consult and Ovid Mednet. Several trials discovered a decrease in the incidence of preterm labor when BV was treated, but most of those trials were performed on women with a history of preterm labor. However, the majority of trials reviewed advise against treatment of a general low-risk obstetric population, as there was no significant decrease in preterm labor. Therefore, based on the above studies and the current guidelines of the Centers for Disease Control and Prevention (CDC), treating pregnant women in high-risk populations who are diagnosed with BV provides the clinician with an opportunity to possibly prevent preterm labor in this population. In nulliparous women without a history of preterm birth, treatment is recommended if other risk factors are present (e.g. gonorrhea or chlamydia). However, in the general low-risk populations, routine screening is not indicated.

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.

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

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.

Imbalances between Matrix Metalloproteinases (MMPs) and Tissue Inhibitor of Metalloproteinases (TIMPs) in Maternal Serum during Preterm Labor

PubMed Central

Tency, Inge; Verstraelen, Hans; Kroes, Ivo; Holtappels, Gabriële; Verhasselt, Bruno; Vaneechoutte, Mario

2012-01-01

Background Matrix metalloproteinases (MMPs) are involved in remodeling of the extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM degradation by MMPs or an imbalance between MMPs and their tissue inhibitors (TIMPs) have been implicated in the pathogenesis of preterm labor, however few studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor. Methods A case control study with 166 singleton pregnancies, divided into four groups: (1) women with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA) matched controls, not in preterm labor; (3) women at term in labor and (4) at term not in labor. MMP and TIMP concentrations were measured using Luminex technology. Results MMP-9 and TIMP-4 concentrations were higher in women with PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP-9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with groups recoded as three key covariates showed significantly higher MMP-9 concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and -2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4 concentrations and MMP-9:TIMP-2 ratios were observed for labor. Conclusions Serum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised in labor. These observations suggest that aberrant serum expression of MMP:TIMP ratios and TIMPs reflect pregnancy and labor status, providing a far less invasive method to determine enzymes essential in ECM remodeling during pregnancy and parturition. PMID:23145060

A role of stretch-activated potassium currents in the regulation of uterine smooth muscle contraction

PubMed Central

Buxton, Iain L O; Heyman, Nathanael; Wu, Yi-ying; Barnett, Scott; Ulrich, Craig

2011-01-01

Rates of premature birth are alarming and threaten societies and healthcare systems worldwide. Premature labor results in premature birth in over 50% of cases. Preterm birth accounts for three-quarters of infant morbidity and mortality. Children that survive birth before 34 weeks gestation often face life-long disability. Current treatments for preterm labor are wanting. No treatment has been found to be generally effective and none are systematically evaluated beyond 48 h. New approaches to the treatment of preterm labor are desperately needed. Recent studies from our laboratory suggest that the uterine muscle is a unique compartment with regulation of uterine relaxation unlike that of other smooth muscles. Here we discuss recent evidence that the mechanically activated 2-pore potassium channel, TREK-1, may contribute to contraction-relaxation signaling in uterine smooth muscle and that TREK-1 gene variants associated with human labor and preterm labor may lead to a better understanding of preterm labor and its possible prevention. PMID:21642947

The diagnosis and natural history of false preterm labor.

PubMed

Chao, Tamara T; Bloom, Steven L; Mitchell, Judith S; McIntire, Donald D; Leveno, Kenneth J

2011-12-01

To estimate the natural history of pregnancies in women who present with preterm labor symptoms and who are sent home with a diagnosis of false labor. A prospective observational study of women with singletons and intact membranes who presented to triage between 24 0/7 and 33 6/7 weeks of gestation with preterm labor symptoms and cervical dilation less than 2 cm was conducted. Women sent home with a diagnosis of false preterm labor were analyzed against a comparable general obstetric population delivered during the same time period. The primary outcome was delivery before 37 weeks of gestation. Secondary outcomes included the interval between presentation and delivery, as well as maternal and neonatal outcomes. Of the 843 women who met inclusion criteria, 690 (82%) were sent home with a diagnosis of false preterm labor and 153 (18%) were admitted to labor and delivery. When analyzed compared with a comparable general obstetric population, women sent home had a similar rate of birth before 34 weeks of gestation (2% compared with 1%, P=.28) but a higher rate of birth between 34 and 36 weeks of gestation (5% compared with 2%, P<.001). There was no difference in neonatal mortality (0% compared with 0.3%, P=.18). Women with cervical dilation of 1 cm at discharge were more likely to deliver before 34 weeks of gestation compared with nondilated women (5% compared with 1%, P=.02); however, 89% of the 1-cm group delivered more than 21 days after presentation. Women sent home with a diagnosis of false preterm labor are not at increased risk for early preterm birth or neonatal mortality; however, they are at increased risk for late preterm birth. II.

Progesterone in women with arrested premature labor, a report of a randomised clinical trial and updated meta-analysis.

PubMed

Wood, Stephen; Rabi, Yacov; Tang, Selphee; Brant, Rollin; Ross, Susan

2017-08-02

Progesterone may be effective in prevention of premature birth in some high risk populations. Women with arrested premature labor are at risk of recurrent labor and maintenance therapy with standard tocolytics has not been successful. Randomized double blinded clinical trial of daily treatment with 200 mg vaginal progesterone in women with arrested premature labor and an updated meta-analysis. The clinical trial was terminated early after 41 women were enrolled. Vaginal progesterone treatment did not change the median gestational age at delivery: 36+2 weeks versus 36+4 weeks, p = .865 nor increase the mean latency to delivery: 44.5 days versus 46.6 days, p = .841. In the updated meta-analysis, progesterone treatment did reduce delivery <37 weeks gestation and increase latency to delivery, but this treatment effect was not evident in the high quality trials: (OR 1.23, 95% CI 0.91, 1.67) and (-0.95 days, 95% CI -5.54, 3.64) respectively. Progesterone is not effective for preventing preterm birth following arrested preterm labor.

Density of Stromal Cells and Macrophages Associated With Collagen Remodeling in the Human Cervix in Preterm and Term Birth

PubMed Central

Dubicke, Aurelija; Ekman-Ordeberg, Gunvor; Mazurek, Patricia; Miller, Lindsay; Yellon, Steven M.

2015-01-01

Remodeling of the cervix occurs in advance of labor both at term and at preterm birth. Morphological characteristics associated with remodeling in rodents were assessed in cervix biopsies from women at term (39 weeks’ gestation) and preterm (<33 weeks’ gestation). Collagen I and III messenger RNA and hydroxyproline concentrations declined in cervix biopsies from women in labor at term and preterm compared to that in the cervix from nonlaboring women. Extracellular collagen was more degraded in sections of cervix from women at term, based on optical density of picrosirius red stain, versus that in biopsies from nonpregnant women. However, collagen structure was unchanged in the cervix from women at preterm labor versus the nonpregnant group. As an indication of inflammation, cell nuclei density was decreased in cervix biopsies from pregnant women irrespective of labor compared to the nonpregnant group. Moreover, CD68-stained macrophages increased to an equivalent extent in cervix subepithelium and stroma from groups in labor, both at term and preterm, as well as in women not in labor at term. Evidence for a similar inflammatory process in the remodeled cervix of women at term and preterm birth parallels results in rodent models. Thus, a conserved final common mechanism involving macrophages and inflammation may characterize the transition to a ripe cervix before birth at term and in advance of premature birth. PMID:26608218

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

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

Intestinal microbiota is different in women with preterm birth: results from terminal restriction fragment length polymorphism analysis.

PubMed

Shiozaki, Arihiro; Yoneda, Satoshi; Yoneda, Noriko; Yonezawa, Rika; Matsubayashi, Takamichi; Seo, Genichiro; Saito, Shigeru

2014-01-01

Preterm birth is a leading cause of perinatal morbidity and mortality. Studies using a cultivation method or molecular identification have shown that bacterial vaginosis is one of the risk factors for preterm birth. However, an association between preterm birth and intestinal microbiota has not been reported using molecular techniques, although the vaginal microbiota changes during pregnancy. Our aim here was to clarify the difference in intestinal and vaginal microbiota between women with preterm birth and women without preterm labor. 16S ribosomal ribonucleic acid genes were amplified from fecal and vaginal DNA by polymerase chain reaction. Using terminal restriction fragment length polymorphism (T-RFLP), we compared the levels of operational taxonomic units of both intestinal and vaginal flora among three groups: pregnant women who delivered term babies without preterm labor (non-PTL group) (n = 20), those who had preterm labor but delivered term babies (PTL group) (n = 11), and those who had preterm birth (PTB group) (n = 10). Significantly low levels of Clostridium subcluster XVIII, Clostridium cluster IV, Clostridium subcluster XIVa, and Bacteroides, and a significantly high level of Lactobacillales were observed in the intestinal microbiota in the PTB group compared with those in the non-PTL group. The levels of Clostridium subcluster XVIII and Clostridium subcluster XIVa in the PTB group were significantly lower than those in the PTL group, and these levels in the PTL group were significantly lower than those in non-PTL group. However, there were no significant differences in vaginal microbiota among the three groups. Intestinal microbiota in the PTB group was found to differ from that in the non-PTL group using the T-RFLP method.

Association between ß2-adrenergic receptor gene polymorphisms and adverse events of ritodrine in the treatment of preterm labor: a prospective observational study.

PubMed

Chung, Jee Eun; Choi, Soo An; Hwang, Han Sung; Park, Jin Young; Lee, Kyung Eun; Yee, Jeong; Kim, Young Ju; Gwak, Hye Sun

2017-11-13

Ritodrine, a tocolytic β2-agonist, has been used extensively in Europe and Asia despite its safety concerns. This study was designed to identify associations between β2-adrenergic receptor (ADRB2) polymorphisms and adverse drug events (ADEs) in patients with preterm labor treated with ritodrine. This follow-up study was prospectively conducted at Ewha Womans University Mokdong Hospital in Korea. Five single nucleotide polymorphisms (SNPs) of the ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) were analyzed in 186 pregnant women with preterm labor. Patients with the AA genotype of rs1042717 had significantly lower incidence of ADEs compared to those with the G allele (p = 0.009). In multivariate analysis, one of the predictors of ADEs was the maximum infusion rate of ritodrine (AOR 4.47, 95% CI 1.31-15.25). Rs1042719 was also a significant factor for ritodrine-induced ADEs. The CC genotype carriers had 78% decreased risk of ADEs compared to those with other genotypes. This study demonstrates that ADEs induced by ritodrine are associated with ADRB2 gene polymorphisms, as well as the infusion rate of ritodrine in pregnant women with preterm labor.

Clinical factors associated with failed trials of labor in late preterm and term twin pregnancies.

PubMed

Ko, Hyun-Joo; Jun, Jong Kwan

2014-07-01

To evaluate the perinatal outcomes and clinical factors of unsuccessful trials of labor (TOLs) in late preterm and term twin pregnancies. We enrolled 896 consecutive twin pregnancies delivered between 1999 and 2012 in a single center, which met the following inclusion criteria: a vertex first twin, live twins, and attempted TOLs after 34 weeks. Obstetric characteristics and perinatal outcomes were compared between vaginal delivery and cesarean delivery groups. Successful TOLs were carried out in 81% (726/896). Failed TOLs occurred in 15% (37/247) of late preterm twins and 20% (133/649) of term twins. Comparisons of neonatal outcomes between the groups showed no significant differences in NICU admission, ventilator use, and composite morbidity. On univariable analysis, nulliparity, preeclampsia, induced labor, excessive weight gain, and intertwin weight discordance of >30% showed significant associations with failed TOLs. Multivariable analyses revealed nulliparity (adjusted odds ratio 9.89, 95% confidence interval 4.64-21.1) and preeclampsia (adjusted odds ratio 2.17, 95% confidence interval 1.30-3.63) as significantly associated with failed TOLs. In late preterm and term twins, trials of labor can be performed successfully without a significant increase in adverse neonatal outcomes. Nulliparity and preeclampsia are clinical factors associated with failed TOLs in twin pregnancies.

[Prevalence of urinary tract infection in hospitalized patients with preterm labor].

PubMed

Acosta-Terriquez, Jorge Emmanuel; Ramos-Martínez, Martín Alberto; Zamora-Aguilar, Liliana María; Murillo-Llanes, Joel

2014-11-01

To determine the prevalence of urinary tract infection (UTI) in patients with preterm labor. A prospective, observational, descriptive study, with a sample of 272 patients who were hospitalized in the Hospital de la Mujer at Culiacan, Sinaloa that presented symptoms of preterm labor. Age body mass index (BMI), parity, education, weeks of gestation, mode of delivery, history of preterm delivery and UTI were assessed. Of the 272 patients with threatened preterm delivery, 97 (35.6%) had positive urine culture and of these patients, 32 (32.9%) had preterm labor. Association between urinary tract infection and patients with a hemoglobin (Hb) less than 11 g/dL OR: 2.66 95% CI (1.55-4.55), p 0.0003. Was isolated E. coli in 72 (74.4%) patients, Proteus in 9 (9.2%) patients. It was found that 42% of E. coli strains were resistant to ampicillin and 38.4% to ciprofloxacin. The prevalence of UTI is higher than the national prevalence.

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 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.

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.

Effect of Maintenance Therapy with Isoxsuprine in the Prevention of Preterm Labor: Randomized controlled trial

PubMed Central

Alavi, Azin; Rajaee, Minoo; Amirian, Malihe; Mahboobi, Hamidreza; Jahanshahi, Keramat Allah; Faghihi, Armaghan

2015-01-01

Background: Isoxsuprine (Vasodilan) is a beta-adrenergic that directly affects the vascular smooth muscle and results in peripheral vascular dilation. Isoxsuprine relaxes the uterine smooth muscles and is used for treatment of pre-term labor and dysmenorrhea. Isoxsuprine is used extensively in hospitals and private clinics in Iran; however, few studies have reported its safety and efficacy in the prevention of pre-term labor. Objective: The aim of this study was to assess the effect of maintenance therapy with oral isoxsuprine for the prevention of pre-term labor. Methods: We undertook a blinded prospective randomized trial of 70 women with singleton pregnancies who presented in pre-term labor between 26 to 34 weeks of gestation. After arresting the contractions with intravenous magnesium sulfate, the patients were randomized into two groups, with the treatment group receiving oral isoxsuprine until 34 weeks of gestation. Response to treatment was assessed by the progression of the pregnancies in both groups. The data were analyzed using SPSS software. Results: Our results showed that 14 (40%) of the patients in the case group and 12 (34.29%) of patients in the control group had pre-term births, and there was no significant difference between the two groups (P=0.621). Also four women (11.43%) in the case group and five women (14.29%) in the control group delivered before 34 weeks (P=0.721). Conclusion: Oral isoxsuprine was not effective as a maintenance treatment in preventing pre-term births or in delaying delivery until after 34 weeks. Larger studies are needed to identify the best treatment for pre-term labor. PMID:26396726

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

Population differences and the effect of vaginal progesterone on preterm birth in women with threatened preterm labor (.).

PubMed

Hermans, Frederik Jan Robin; Karolinski, Ariel; Othenin-Girard, Véronique; Bertolino, María Victoria; Schuit, Ewoud; Salgado, Pablo; Hösli, Irene; Irion, Olivier; Laterra, Cristina; Mol, Ben Willem J; Martinez de Tejada, Begoña

2016-10-01

Threatened preterm labor (tPTL) is a complication of pregnancy. Identification of women and clinical definition differs between countries. This study investigated differences in tPTL and effectiveness of vaginal progesterone to prevent preterm birth (PTB) between two countries. Secondary analysis of a randomized controlled trial (RCT) from Argentina and Switzerland comparing vaginal progesterone to placebo in women with tPTL (n = 379). Cox proportional hazards analysis was performed to compare placebo groups of both countries and to compare progesterone to placebo within each country. We adjusted for baseline differences. Iatrogenic onset of labor or pregnancy beyond gestational age of interest was censored. Swiss and Argentinian women were different on baseline. Risks for delivery <14 days and PTB < 34 and < 37 weeks were increased in Argentina compared to Switzerland, HR 3.3 (95% CI 0.62-18), 54 (95% CI 5.1-569) and 3.1 (95% CI 1.1-8.4). In Switzerland, progesterone increased the risk for delivery <14 days [HR 4.4 (95% CI 1.3-15.7)] and PTB <37 weeks [HR 2.5 (95% CI 1.4-4.8)], in Argentina there was no such effect. In women with tPTL, the effect of progesterone may vary due to population differences. Differences in populations should be considered in multicenter RCTs.

Military duty: risk factor for preterm labor? A review.

PubMed

McNeary, A M; Lomenick, T S

2000-08-01

The female military population represents a high-risk group for preterm labor and other adverse pregnancy outcomes. As the number of women entering the armed forces continues to increase, concerns regarding the effects of military service on pregnancy must persist. Although active duty females have access to prenatal care and maintain consistent follow-up, previous research has noted a 5-fold increase in preterm labor compared with civilian working women. Hospitalization and loss of work attributable to pregnancy complications directly affect productivity and mission accomplishment; therefore, it is crucial to identify those at risk to institute measures that will prevent such occurrences and decrease time away from work. This article provides a review of the existing literature concerning preterm labor in military women, comparisons with the civilian population, and recommendations for future research.

The impact of changes in preterm birth among twins on stillbirth and infant mortality in the United States.

PubMed

Getahun, D; Demissie, K; Marcella, S W; Rhoads, G G

2014-11-01

To examine trends for preterm births, stillbirths, neonatal and infant deaths in twin births by gestational age and birth weight categories, as well as trends in induction of labor and cesarean delivery during 1995-2006. A trend analysis was performed on data derived from the National Centers for Health Statistics' Vital Statistics Data files (1995-2006). The primary outcomes examined were preterm birth, stillbirth, neonatal and infant mortality. During the study period, rates of labor induction among twins decreased by 8% and rates of cesarean delivery increased by 35%. Concurrently, the preterm birth rate increased by 13% from 54% in 1995-96 to 61% in 2005-06. The overall stillbirth rate, and neonatal and infant death rates decreased during the same period by 21% (95% confidence interval (CI): 18-25%), 13% (95% CI: 9-16%) and 12% (95% CI: 8-15%), respectively. There were significant reductions in neonatal death rates related to respiratory distress syndrome (RDS; 48%, 95% CI: 41-54%) and congenital anomalies (25%, 95% CI: 16-33%) during the study period. Reductions in post-neonatal infant mortality were mainly in RDS (88%) and sudden infant death syndrome (26%). Mortality rates among infants born by either induction of labor or cesarean delivery fell during the study period and remained much lower than the overall infant mortality rate. The findings of this study suggest that during 1995-2006 there was an increase in preterm birth rates and a decrease in labor inductions with a sharp decline in stillbirth, neonatal and infant mortality rates.

In vivo T-cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth

PubMed Central

Gomez-Lopez, Nardhy; Romero, Roberto; Arenas-Hernandez, Marcia; Ahn, Hyunyoung; Panaitescu, Bogdan; Vadillo-Ortega, Felipe; Sanchez-Torres, Carmen; Salisbury, Katherine S; Hassan, Sonia S.

2016-01-01

PROBLEM Activated/effector T cells seem to play a role in the pathological inflammation associated with preterm labor. The aim of this study was to determine whether in vivo T-cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth. METHOD OF STUDY Pregnant B6 mice were intraperitoneally injected with a monoclonal αCD3ε antibody or its isotype control. The gestational age and the rates of preterm birth and pup mortality at birth, as well as the fetal heart rate and umbilical artery pulsatility index, were determined. RESULTS Injection of a monoclonal αCD3ε antibody led to preterm labor/birth [αCD3ε 83 ± 16.97% (10/12) vs. isotype 0% (0/8)], and increased the rate of pup mortality at birth [αCD3ε 87.30 ± 8.95% (77/85) vs. isotype 4.91 ± 4.34% (3/59)]. In addition, injection of a monoclonal αCD3ε antibody decreased the fetal heart rate and increased the umbilical artery pulsatility index when compared to isotype controls. CONCLUSION In vivo T-cell activation by a monoclonal αCD3ε antibody in late gestation induces preterm labor and birth. PMID:27658719

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

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

Predictive performance of PAMG-1 vs fFN test for risk of spontaneous preterm birth in symptomatic women attending an emergency obstetric unit: retrospective cohort study.

PubMed

Melchor, J C; Navas, H; Marcos, M; Iza, A; De Diego, M; Rando, D; Melchor, I; Burgos, J

2018-05-01

To compare the performance of the placental alpha microglobulin-1 (PAMG-1) and fetal fibronectin (fFN) tests for the prediction of spontaneous preterm delivery in patients presenting to an emergency obstetric unit with threatened preterm labor, by conducting a retrospective audit of patient medical records from separate 1-year periods during which either fFN or PAMG-1 was used as the standard-of-care biochemical test. This was a retrospective cohort study based on chart review of electronic medical records of women with threatened preterm labor presenting at a level-III maternity hospital over two different periods: (1) the 'baseline' period (year 2012), during which the qualitative fFN test with a cut-off of 50 ng/mL was used as the standard-of-care biochemical test for the risk assessment of preterm delivery, and (2) the 'comparative' period (year 2016), during which the PAMG-1 test with a cut-off of 1 ng/mL was used as the standard-of-care biomarker test. Patients with a singleton pregnancy between 24 + 0 and 34 + 6 weeks' gestation with symptoms of early preterm labor, clinically intact membranes and cervical dilatation < 3 cm, who did not have a medically indicated preterm delivery within 14 days of testing, were selected for chart review and included in the analysis. Key parameters used for the analysis were biochemical test results, time of testing and time of delivery. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and positive and negative likelihood ratios (LR+ and LR-) for the prediction of spontaneous preterm delivery ≤ 7 and ≤ 14 days of presentation were calculated for the PAMG-1 and fFN tests. Four hundred and twenty patients were identified as having presented with threatened preterm labor during the baseline period, of whom 378 (90.0%) met the eligibility criteria. Of these, 38 (10.1%) were fFN positive and 10 (2.6%) had spontaneous preterm delivery ≤ 7 days of presentation. PPV, NPV, LR+ and LR- of fFN were 7.9%, 97.9%, 3.2 and 0.8, respectively, for spontaneous preterm delivery ≤ 7 days. Four hundred and ten patients were identified as having presented with threatened preterm labor during the comparative period and 367 (89.5%) subjects met the eligibility criteria. Of these, 17 (4.6%) were PAMG-1 positive and 12 (3.3%) had spontaneous preterm delivery ≤ 7 days of presentation. PAMG-1 PPV and NPV were 35.3% and 98.3%, respectively, and LR+ and LR- were 16.1 and 0.5, respectively, for spontaneous preterm delivery ≤ 7 days. Before switching to PAMG-1, fFN was the standard-of-care test for the risk assessment of spontaneous preterm delivery. This retrospective audit of each test's performance over separate 1-year periods shows that we were more than twice as likely to get a positive fFN test than a positive PAMG-1 test, while the rate of discharging women who ultimately delivered spontaneously within 14 days of testing was not affected. Furthermore, a positive PAMG-1 test was more than four times more reliable than a positive fFN test in predicting imminent spontaneous preterm delivery. The use of a more reliable biomarker that is associated with fewer false-positive results could lead to a reduction in unnecessary admissions, interventions and use of hospital resources. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Effect of urinary trypsin inhibitor on preterm labor with high granulocyte elastase concentration in cervical secretions.

PubMed

Hayashi, Masako; Oya, Atsuko; Miyake, Hidehiko; Nakai, Akihito; Takeshita, Toshiyuki

2010-04-01

To explore whether intravaginal treatment with urinary trypsin inhibitor (UTI) prevents preterm delivery in patients in preterm labor with increased levels of granulocyte elastase in cervical secretions. The subjects were patients in preterm labor with increased levels of granulocyte elastase in cervical secretions from 16 to 33 weeks gestation. Maternal and neonatal outcomes were compared between patients receiving UTI treatment (UTI group; n=33) and those not receiving UTI treatment (control group; n=40). In patients receiving UTI, the mean gestational age at delivery was greater than that in the control group (37.8 vs. 35.6 weeks, p=0.003), and the rates of premature delivery before 34 and 37 weeks gestation were lower (3% vs. 20%, p=0.028; and 18% vs. 47%, p=0.008, respectively). The percentage of neonates weighing more than 2,500 g was significantly higher in the UTI group, with no neonates weighing less than 1,500 g. The neonatal hospitalization rate was lower in the UTI group (9% vs. 42%, p=0.001). In patients in preterm labor with a high elastase concentration in cervical secretions, treatment with UTI reduced the risk of preterm delivery and improved neonatal outcomes.

Preterm labor in the quadriplegic parturient.

PubMed

Catanzarite, V A; Ferguson, J E; Weinstein, C; Belton, S R

1986-04-01

The occurrence of preterm labor is not uncommon in the pregnant quadriplegic. Early diagnosis is hampered by the inability of most quadriplegics to sense uterine contractions in the usual way. A patient we recently treated for preterm labor learned to recognize contractions by the associated symptoms of autonomic hyper-reflexia: flushing, headache, and piloerection. Tocolytic therapy was successful and a favorable neonatal outcome occurred. Increased awareness by the physician and the pregnant quadriplegic patient is encouraged so that symptoms of autonomic hyper-reflexia may be recognized as potentially indicative of uterine contractions.

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.

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.

The impact of changes in preterm birth among twins on stillbirth and infant mortality in the United States

PubMed Central

Getahun, D; Demissie, K; Marcella, SW; Rhoads, GG

2015-01-01

OBJECTIVE To examine trends for preterm births, stillbirths, neonatal and infant deaths in twin births by gestational age and birth weight categories, as well as trends in induction of labor and cesarean delivery during 1995–2006. STUDY DESIGN A trend analysis was performed on data derived from the National Centers for Health Statistics’ Vital Statistics Data files (1995–2006). The primary outcomes examined were preterm birth, stillbirth, neonatal and infant mortality. RESULT During the study period, rates of labor induction among twins decreased by 8% and rates of cesarean delivery increased by 35%. Concurrently, the preterm birth rate increased by 13% from 54% in 1995–96 to 61% in 2005–06. The overall stillbirth rate, and neonatal and infant death rates decreased during the same period by 21% (95% confidence interval (CI): 18–25%), 13% (95% CI: 9–16%) and 12% (95% CI: 8–15%), respectively. There were significant reductions in neonatal death rates related to respiratory distress syndrome (RDS; 48%, 95% CI: 41–54%) and congenital anomalies (25%, 95% CI: 16–33%) during the study period. Reductions in post-neonatal infant mortality were mainly in RDS (88%) and sudden infant death syndrome (26%). Mortality rates among infants born by either induction of labor or cesarean delivery fell during the study period and remained much lower than the overall infant mortality rate. CONCLUSION The findings of this study suggest that during 1995–2006 there was an increase in preterm birth rates and a decrease in labor inductions with a sharp decline in stillbirth, neonatal and infant mortality rates. PMID:24968177

Melatonin prevents experimental preterm labor and increases offspring survival.

PubMed

Domínguez Rubio, Ana P; Sordelli, Micaela S; Salazar, Ana I; Aisemberg, Julieta; Bariani, María V; Cella, Maximiliano; Rosenstein, Ruth E; Franchi, Ana M

2014-03-01

Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circulating erythroblasts in maternal blood are not elevated before onset of preterm labor.

PubMed

Hoesli, Irene; Danek, Milan; Lin, Dexin; Li, Ying; Hahn, Sinuhe; Holzgreve, Wolfgang

2002-11-01

Preterm labor has recently been reported to be associated with an increased release of cell free fetal deoxyribonucleic acid (DNA) into the maternal circulation. We have previously observed increases in both fetal cell traffic and cell free fetal DNA in preeclamptic pregnancies. In this study, we investigated whether fetal cell traffic is also disturbed in pregnancies with preterm labor. In a case-control study, we examined 47 pregnancies complicated by preterm contractions that occurred between 20 and 34 weeks' gestation and an equal number of matched controls. Erythroblasts were enriched for by magnetic cell sorting and enumerated. These values were then correlated with subsequent pregnancy outcome. In the study group 16 patients delivered prematurely (subgroup A). The other 31 (subgroup B) delivered at term, as did all those in the control group. No significant difference was noted in erythroblast numbers between either one of the subgroups and the controls. Contrary to the reported increased levels of free fetal DNA in maternal serum, erythroblasts in maternal blood are not elevated significantly in pregnancies with threatened premature labor or in those that deliver preterm.

[Contemporary methods for preterm labor diagnostics].

PubMed

Kolev, N; Kovachev, E; Ivanov, S; Kornovski, Y; Tsvetkov, K; Angelova, M; Tsonev, A; Ismail, E

2013-01-01

Authors track current trends in preterm labor diagnostics. The emphasis is laid on biochemical tests for examination of fibronectin (fFN) and insulin-like growth factor-binding protein (IGFBP-1) in cervical and vaginal secretions, as well as ultrasound assessment of cervical length.

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

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).

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

The effects of standing, lifting and noise exposure on preterm birth, growth restriction, and perinatal death in healthy low-risk working military women.

PubMed

Magann, Everett F; Evans, Sharon F; Chauhan, Suneet P; Nolan, Thomas E; Henderson, Jenni; Klausen, Jack H; Newnham, John P; Morrison, John C

2005-09-01

The effects of standing, lifting and noise in low-risk, healthy pregnant women are uncertain. In the past, the heterogeneity of the populations studied, the limitations of the designs of the retrospective and case control studies, and a failure of some of the larger investigations to evaluate all the potential confounding variables has hampered many studies. The purpose of this investigation was to evaluate, throughout pregnancy, the effects of standing, repetitive lifting, and noise in the workplace compared with no standing, lifting or noise exposure, on maternal and perinatal outcomes in a large prospective study of a low-risk healthy population of working women cared for by a single group of health providers. This prospective observational study used an extensive questionnaire to collect antepartum, intrapartum, and postpartum information. Information was collected on the initial visit, each subsequent visit, and immediately after delivery. The participating women were divided into groups based on the amount of time spent standing, the amount and extent of repetitive lifting, and noise exposure in the workplace. Eight hundred and fourteen low-risk active duty women participated in this investigation over a 4-year period. Multivariate analysis with non-exposure compared with exposure reinforced the effect of standing on preterm labor (OR 1.80, 95% CI 1.05, 3.16) and preterm birth (OR 1.69, 95% CI 1.03, 2.80) and showed a trend toward an effect of noise exposure on preterm labor (OR 1.76, 95% CI 0.78, 3.39) after controlling for other exposures. This investigation suggests an association of occupational standing with preterm labor and preterm birth.

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.

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.

Infection, antibiotics, and preterm delivery.

PubMed

Locksmith, G; Duff, P

2001-10-01

The relationship between genital tract infection and preterm delivery has been established on the basis of biochemical, microbiological, and clinical evidence. In theory, pathogenic bacteria may ascend from the lower reproductive tract into the uterus, and the resulting inflammation leads to preterm labor, rupture of the membranes, and birth. A growing body of evidence suggests that preterm labor and/rupture of the membranes are triggered by micro-organisms in the genital tract and by the host response to these organisms, ie, elaboration of cytokines and proteolytic enzymes. Epidemiologic and in vitro studies do not prove a cause-and-effect relationship between infection and preterm birth. However, the preponderance of evidence indicates that treatment of asymptomatic bacteriuria and symptomatic lower genital tract infections such as bacterial vaginosis (BV), trichomoniasis, gonorrhea, and chlamydia will lower the risk of preterm delivery. Based on current evidence, pregnant women who note an abnormal vaginal discharge should be tested for BV, trichomonas, gonorrhea, and chlamydia. Those who test positive should be treated appropriately. A 3- to 7-day course of antibiotic treatment for asymptomatic bacteriuria during pregnancy is clinically indicated to reduce the risk of pyelonephritis and preterm delivery. Routine screening for chlamydia and gonorrhea should be performed for women at high risk of acquiring sexually transmitted diseases. The practice of routine screening for BV in asymptomatic women who are at low risk for preterm delivery cannot be supported based on evidence from the literature. Routine screening for asymptomatic bacteriuria during pregnancy is cost-effective, particularly in high-prevalence populations. The results of antibiotic trials for the treatment of preterm labor have been inconsistent. In the absence of reasonable evidence that antimicrobial therapy leads to significant prolongation of pregnancy in the setting of preterm labor, antibiotics should be used only for protecting the neonate from group B streptococci sepsis. They should not be used for the purpose of prolonging pregnancy. Multiple investigations have shown that, in patients with preterm premature rupture of the membranes, prophylactic antibiotics are of value in prolonging the latent period between rupture of the membranes and onset of labor and in reducing the incidence of maternal and neonatal infection. The most extensively tested effective antibiotic regimen for prophylaxis involves erythromycin alone or in combination with ampicilln. Controversy still exists regarding the appropriate length and route of antibiotic prophylaxis.

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.

Allergy-induced preterm labor after the ingestion of shellfish

PubMed Central

ROMERO, ROBERTO; KUSANOVIC, JUAN PEDRO; MUÑOZ, HERNAN; GOMEZ, RICARDO; LAMONT, RONALD F.; YEO, LAMI

2012-01-01

Preterm parturition is a syndrome caused by several mechanisms of disease, including intrauterine infection/inflammation, uteroplacental ischemia, uterine overdistension, cervical disease, maternal/fetal stress, abnormal allogeneic responses, allergic reactions, and unknown insults. An allergic-like mechanism was proposed as a potential etiology for the preterm parturition syndrome, based on the observation that eosinophils were present in the amniotic fluid in a fraction of women with preterm labor and a history of allergy, coupled with the observation that conditioned media from degranulated mast cells (the effector cells of type 1 hypersensitivity) induced contractility of human myometrial strips. This communication describes a case of a pregnant woman who had an allergic reaction and regular uterine contractions after the ingestion of lobster meat, to which she was known to be allergic. Preterm labor subsided after the treatment of antihistamines and steroids. The patient subsequently delivered at term. At follow-up, the child was diagnosed with atopy and asthma, and required frequent use of inhaled corticosteroids and beta-2 adrenergic agents. PMID:19900031

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

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5′and 3′ UTR regions. Conclusions The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. PMID:28879060

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.

Magnesium Sulfate and Betamethasone Reduce NUR77 Expression in a Preterm Labor Mouse Model

DTIC Science & Technology

2016-06-29

Women in preterm labor are commonly treated with magnesium sulfate (MgSO4) and betamethasone (BMTZ) to reduce complications of prematurity including...neurologic injury. MgSO4, however, prevents cerebral palsy in only 1 in 40 women who receive it. Understanding the cellular responses to MgSO4/BMTZ

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.

Mechanisms leading to increased risk of preterm birth in growth-restricted guinea pig pregnancies.

PubMed

Palliser, Hannah K; Kelleher, Meredith A; Welsh, Toni N; Zakar, Tamas; Hirst, Jonathan J

2014-02-01

Intrauterine growth restriction (IUGR) is a risk factor for preterm labor; however, the mechanisms of the relationship remain unknown. Prostaglandin (PG), key stimulants of labor, availability is regulated by the synthetic enzymes, prostaglandin endoperoxidases 1 and 2 (PTGS1 and 2), and the metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (HPGD). We hypothesized that IUGR increases susceptibility to preterm labor due to the changing balance of synthetic and metabolizing enzymes and hence greater PG availability. We have tested this hypothesis using a surgically induced IUGR model in guinea pigs, which results in significantly shorter gestation. Myometrium, amnion, chorion, and placentas were collected from sham operated or IUGR pregnancies, and PTGS1 and HPGD protein expression were quantified throughout late gestation (>62 days) and labor. The PTGS1 expression was significantly upregulated in the myometrium of IUGR animals, and chorionic HPGD expression was markedly decreased (P < .01 and P < .001, respectively). These findings suggest a shift in the balance of PG production over metabolism in IUGR pregnancies leads to a greater susceptibility to preterm birth.

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.

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.

TRANSDERMAL NITROGLYCERIN FOR THE TREATMENT OF PRETERM LABOR: A SYSTEMATIC REVIEW AND META-ANALYSIS

PubMed Central

CONDE-AGUDELO, Agustín; ROMERO, Roberto

2014-01-01

OBJECTIVE To evaluate the efficacy and safety of transdermal nitroglycerin as tocolytic agent in women with preterm labor. STUDY DESIGN Systematic review and meta-analysis of randomized controlled trials. RESULTS Thirteen studies (1302 women) were included. Two studies evaluated transdermal nitroglycerin versus placebo (N=186), 9 evaluated transdermal nitroglycerin versus β2-adrenergic-receptor agonists (N=1024), and 1 each evaluated transdermal nitroglycerin versus nifedipine (N=50) and transdermal nitroglycerin versus magnesium sulfate (N=42). There were no significant differences between transdermal nitroglycerin and placebo for delivery within 48 hours of initiation of treatment or before 28, 34 or 37 weeks’ gestation, adverse neonatal outcomes, and neurodevelopmental status at 24 months of age. Nevertheless, one study found a marginally significant reduction in the risk of a composite outcome of significant neonatal morbidity and perinatal mortality (3/74 [4.1%] versus 11/79 [13.9%]; relative risk 0.29, 95% confidence interval 0.08–1.00). When compared with β2-adrenergic-receptor agonists, transdermal nitroglycerin was associated with a significant reduction in the risk of preterm birth <34 and <37 weeks’ gestation, admission to the neonatal intensive care unit, use of mechanical ventilation, and maternal side effects. There were no significant differences between transdermal nitroglycerin and nifedipine and magnesium sulfate in delivery within 48 hours of treatment and pregnancy prolongation, respectively. Overall, women receiving transdermal nitroglycerin had a higher risk of headache. CONCLUSION Although transdermal nitroglycerin appears to be more effective than β 2-adrenergic-receptor agonists, the current evidence does not support its routine use as tocolytic agent for the treatment of preterm labor. Further additional double-blind placebo-controlled trials are needed. PMID:23891631

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.

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.

Estimation of preterm labor immediacy by nonlinear methods

PubMed Central

Martinez, Luis; Matorras, Roberto; Bringas, Carlos; Aranburu, Larraitz; Fernández-Llebrez, Luis; Gonzalez, Leire; Arana, Itziar; Pérez, Martín-Blas; Martínez de la Fuente, Ildefonso

2017-01-01

Preterm delivery affects about one tenth of human births and is associated with an increased perinatal morbimortality as well as with remarkable costs. Even if there are a number of predictors and markers of preterm delivery, none of them has a high accuracy. In order to find quantitative indicators of the immediacy of labor, 142 cardiotocographies (CTG) recorded from women consulting because of suspected threatened premature delivery with gestational ages comprehended between 24 and 35 weeks were collected and analyzed. These 142 samples were divided into two groups: the delayed labor group (n = 75), formed by the women who delivered more than seven days after the tocography was performed, and the anticipated labor group (n = 67), which corresponded to the women whose labor took place during the seven days following the recording. As a means of finding significant differences between the two groups, some key informational properties were analyzed by applying nonlinear techniques on the tocography recordings. Both the regularity and the persistence levels of the delayed labor group, which were measured by Approximate Entropy (ApEn) and Generalized Hurst Exponent (GHE) respectively, were found to be significantly different from the anticipated labor group. As delivery approached, the values of ApEn tended to increase while the values of GHE tended to decrease, suggesting that these two methods are sensitive to labor immediacy. On this paper, for the first time, we have been able to estimate childbirth immediacy by applying nonlinear methods on tocographies. We propose the use of the techniques herein described as new quantitative diagnosis tools for premature birth that significantly improve the current protocols for preterm labor prediction worldwide. PMID:28570658

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

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

Bacterial vaginosis in pregnancy and the risk of prematurity: a meta-analysis.

PubMed

Flynn, C A; Helwig, A L; Meurer, L N

1999-11-01

We conducted this meta-analysis to determine the magnitude of risk conferred by bacterial vaginosis during pregnancy on preterm delivery. We selected articles from a combination of the results of a MEDLINE search (1966-1996), a manual search of bibliographies, and contact with leading researchers. We included case control and cohort studies evaluating the risk of preterm delivery, low birth weight, preterm premature rupture of membranes, or preterm labor for pregnant women who had bacterial vaginosis and those who did not. DATA COLLECTION AND ANALYSIS. Two investigators independently conducted literature searches, applied inclusion criteria, performed data extraction, and critically appraised included studies. Summary estimates of risk were calculated as odds ratios (ORs) using the fixed and random effects models. We included 19 studies in the final analysis. Bacterial vaginosis during pregnancy was associated with a statistically significant increased risk for all outcomes evaluated. In the subanalyses for preterm delivery, bacterial vaginosis remained a significant risk factor. Pooling adjusted ORs yielded a 60% increased risk of preterm delivery given the presence of bacterial vaginosis. Bacterial vaginosis is an important risk factor for prematurity and pregnancy morbidity. Further studies will help clarify the benefits of treating bacterial vaginosis and the potential role of screening during pregnancy.

The Impact of Magnesium Sulfate Therapy on Angiogenic Factors in Preeclampsia

PubMed Central

VADNAIS, Mary A.; RANA, Sarosh; QUANT, Hayley S.; SALAHUDDIN, Saira; DODGE, Laura E.; LIM, Kee-Hak; KARUMANCHI, S. Ananth; HACKER, Michele R.

2011-01-01

Objective The objective was to evaluate whether intravenous magnesium sulfate (magnesium) alters levels of angiogenic factors in women with preeclampsia. Study Design This was a prospective cohort study comparing women with preeclampsia treated with magnesium for seizure prophylaxis to those who were not. Serum levels of angiogenic factors, soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor, were measured at the time of diagnosis and approximately 24 hours later. Secondary analysis compared women receiving magnesium for preeclampsia to women receiving magnesium for preterm labor. Analysis of covariance was used to compare levels at 24 hours, adjusting for levels at enrollment and potential confounders. Results Angiogenic factor levels did not differ between preeclampsia groups with and without magnesium or between preeclampsia and preterm labor groups treated with magnesium (all P > 0.05). Conclusion Magnesium likely decreases seizure risk in preeclampsia by a mechanism other than altering angiogenic factor levels. PMID:22247820

The Impact of Magnesium Sulfate Therapy on Angiogenic Factors in Preeclampsia.

PubMed

Vadnais, Mary A; Rana, Sarosh; Quant, Hayley S; Salahuddin, Saira; Dodge, Laura E; Lim, Kee-Hak; Karumanchi, S Ananth; Hacker, Michele R

2012-01-01

OBJECTIVE: The objective was to evaluate whether intravenous magnesium sulfate (magnesium) alters levels of angiogenic factors in women with preeclampsia. STUDY DESIGN: This was a prospective cohort study comparing women with preeclampsia treated with magnesium for seizure prophylaxis to those who were not. Serum levels of angiogenic factors, soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor, were measured at the time of diagnosis and approximately 24 hours later. Secondary analysis compared women receiving magnesium for preeclampsia to women receiving magnesium for preterm labor. Analysis of covariance was used to compare levels at 24 hours, adjusting for levels at enrollment and potential confounders. RESULTS: Angiogenic factor levels did not differ between preeclampsia groups with and without magnesium or between preeclampsia and preterm labor groups treated with magnesium (all P > 0.05). CONCLUSION: Magnesium likely decreases seizure risk in preeclampsia by a mechanism other than altering angiogenic factor levels.

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.

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.

Preterm labor--modeling the uterine electrical activity from cellular level to surface recording.

PubMed

Rihana, S; Marque, C

2008-01-01

Uterine electrical activity is correlated to the appearance of uterine contractions. forceful contractions appear at the end of term. Therefore, understanding the genesis and the propagation of uterine electrical activity may provide an efficient tool to diagnose preterm labor. Moreover, the control of uterine excitability seems to have important consequences in the control of preterm labor. Modeling the electrical activity in uterine tissue is thus an important step in understanding physiological uterine contractile mechanisms and to permit uterine EMG simulation. Our model presented in this paper, incorporates ion channel models at the cell level, the reaction diffusion equations at the tissue level and the spatiotemporal integration at the uterine EMG reconstructed level. This model validates some key physiological observation hypotheses concerning uterine excitability and propagation.

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.

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.

Ureaplasma and BPD

PubMed Central

Kallapur, Suhas G.; Kramer, Boris W.; Jobe, Alan H.

2013-01-01

Ureaplasma is an organism with low virulence and is a commensal of the lower genito-urinary tract in females. From here, it can gain entry in the amniotic fluid to cause inflammation in the amniotic compartment during pregnancy. Ureaplasma spp. are the most common organisms isolated from women with chorioamnionitis. Ureaplasma spp. are associated with increased risk for preterm labor and morbidity in the preterm neonate. However, there is some controversy regarding the importance of Ureaplasma in the pathogenesis of bronchopulmonary dysplasia (BPD). This article will review the microbiology of Ureaplasma, host innate immune responses, and the pathology of lung injury in animal models of Ureaplasma chorioamnionitis. We will review epidemiological studies of Ureaplasma and BPD in preterm infants and efficacy of antibiotics in preventing preterm labor and BPD. PMID:23582963

The Evidence Regarding Maintenance Tocolysis

PubMed Central

Elliott, John P.; Morrison, John C.

2013-01-01

Preterm delivery is a public health issue of major proportion. More than 12% of deliveries in the United States that occur at less than 37 weeks gestation preterm labor (PTL) represents the largest single reason for preterm birth (PTB). Attempts to prevent PTB have been unsuccessful. This paper of maintenance tocolytic therapy will examine the efficacy and safety of the drugs, both oral and subcutaneous, which have been utilized for prolongation of pregnancy following successful arrest of a documented episode of acute preterm labor. The evidence for oral tocolytics as maintenance therapy as well as parenteral medications for such patients is offered. Finally, the effects in the United States of the Food and Drug Administration (FDA) action on such medications are reported. PMID:23577034

Stress and preterm labor and birth in Black women.

PubMed

Gennaro, Susan; Shults, Justine; Garry, David J

2008-01-01

To examine (a) 3 commonly used measures of stress during pregnancy, (b) changes in stress over time to determine when stress is highest, and (c) whether any of the stress measures predict who will deliver preterm in pregnant Black women. Prospective descriptive study. Perinatal evaluation center and outpatient clinics of a teaching hospital in the northeast. Fifty-nine Black women: 39 were recruited in preterm labor from a Perinatal Evaluation Center, and 20 experiencing healthy pregnancies were recruited from the prenatal clinic. Stress was measured using 2 paper and pencil tests (the Prenatal Distress Questionnaire and the Perceived Stress Scale) and corticotropin-releasing hormone. There was not a high correlation between stress measures. Stress at 28 weeks as measured by Prenatal Distress Questionnaire and Perceived Stress Scale was at its highest, but corticotropin-releasing hormone increased to 32 weeks and then decreased. Perceived stress, prenatal distress, and corticotropin-releasing hormone do not all appear to be measuring the same phenomenon. Screening for stress in Black women at 28 weeks requires further research as perceived stress levels in Black women experiencing preterm labor around 28 weeks differentiated women who delivered preterm infants from Black women who delivered at term.

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

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.

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.

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

Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy.

PubMed

Sachs, Adam; Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

2017-05-01

Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9 points). Approximately 5% of women experience adverse obstetrical outcomes after appendectomy or cholecystectomy during pregnancy. The major risk factors for such outcomes are cervical incompetence, preterm labor during current pregnancy, vaginitis or vulvovaginitis, and sepsis.

Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy

PubMed Central

Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

2017-01-01

Importance Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. Objectives To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. Design, Setting, and Participants A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. Main Outcomes and Measures A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Results Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9 points). Conclusions and Relevance Approximately 5% of women experience adverse obstetrical outcomes after appendectomy or cholecystectomy during pregnancy. The major risk factors for such outcomes are cervical incompetence, preterm labor during current pregnancy, vaginitis or vulvovaginitis, and sepsis. PMID:28114513

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

Ureaplasma and BPD.

PubMed

Kallapur, Suhas G; Kramer, Boris W; Jobe, Alan H

2013-04-01

Ureaplasma is an organism with low virulence and is a commensal of the lower genito-urinary tract in females. From here, it can gain entry in the amniotic fluid to cause inflammation in the amniotic compartment during pregnancy. Ureaplasma spp. are the most common organisms isolated from women with chorioamnionitis. Ureaplasma spp. are associated with increased risk for preterm labor and morbidity in the preterm neonate. However, there is some controversy regarding the importance of Ureaplasma in the pathogenesis of bronchopulmonary dysplasia (BPD). This article will review the microbiology of Ureaplasma, host innate immune responses, and the pathology of lung injury in animal models of Ureaplasma chorioamnionitis. We will review epidemiological studies of Ureaplasma and BPD in preterm infants and efficacy of antibiotics in preventing preterm labor and BPD. Copyright © 2013 Elsevier Inc. All rights reserved.

Domestic Violence Prior to and During Pregnancy within a Selected Military Population and its Relationship to Depressive Symptomatology

DTIC Science & Technology

1996-01-01

weight infant, fetal injury, preeclampsia , preterm labor, preterm delivery, hemorrhage, impaired bonding, and delayed postpartum recovery (Bullock et...currently afforded to gestational diabetes and preeclampsia " (p. 156) . In a cohort study, Schei, Samuelsen, and Bakketeig (1991) compared the... preeclampsia , hemorrhage, premature labor, and hospital admission) were reported more frequently in the women exposed to an abusive relationship. In an

Use of microbial cultures and antibiotics in the prevention of infection-associated preterm birth.

PubMed

Klein, Laura L; Gibbs, Ronald S

2004-06-01

The purpose of this study was to summarize recent evidence regarding infection-associated preterm birth and to make appropriate recommendations. Antepartum treatment of lower genital tract infection or bacterial colonization has been found to reduce the incidence of preterm birth in the case of asymptomatic bacteriuria and bacterial vaginosis in selected patients but has been proved to be ineffective for vaginal colonization with organisms such as Ureaplasma urealyticum and group B streptococcus. This is a clinical opinion based on a review of recent data related to 1) the association between lower genital tract infection and preterm birth and 2) antibiotic trials to prevent preterm birth. Antepartum treatment of lower genital tract infection or bacterial colonization has been found to reduce the incidence of preterm birth in the case of asymptomatic bacteriuria and bacterial vaginosis in selected patients, but has been proven to be ineffective for vaginal colonization with organisms such as Ureaplasma urealyticum and group B streptococcus. Large well-designed trials have shown that the routine administration of antibiotics to women with preterm labor and intact membranes is not beneficial; however, antibiotic regimens including macrolides are recommended for preterm premature rupture of the membranes. Large well-designed trials have shown that the routine administration of antibiotics to women with preterm labor and intact membranes is not beneficial; however, antibiotic regimens that include macrolides are recommended for preterm premature rupture of the membranes.

Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid.

PubMed

Hitti, Jane; Lapidus, Jodi A; Lu, Xinfang; Reddy, Ashok P; Jacob, Thomas; Dasari, Surendra; Eschenbach, David A; Gravett, Michael G; Nagalla, Srinivasa R

2010-07-01

We analyzed the vaginal fluid proteome to identify biomarkers of intraamniotic infection among women in preterm labor. Proteome analysis was performed on vaginal fluid specimens from women with preterm labor, using multidimensional liquid chromatography, tandem mass spectrometry, and label-free quantification. Enzyme immunoassays were used to quantify candidate proteins. Classification accuracy for intraamniotic infection (positive amniotic fluid bacterial culture and/or interleukin-6 >2 ng/mL) was evaluated using receiver-operator characteristic curves obtained by logistic regression. Of 170 subjects, 30 (18%) had intraamniotic infection. Vaginal fluid proteome analysis revealed 338 unique proteins. Label-free quantification identified 15 proteins differentially expressed in intraamniotic infection, including acute-phase reactants, immune modulators, high-abundance amniotic fluid proteins and extracellular matrix-signaling factors; these findings were confirmed by enzyme immunoassay. A multi-analyte algorithm showed accurate classification of intraamniotic infection. Vaginal fluid proteome analyses identified proteins capable of discriminating between patients with and without intraamniotic infection. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics.

PubMed

Migale, Roberta; MacIntyre, David A; Cacciatore, Stefano; Lee, Yun S; Hagberg, Henrik; Herbert, Bronwen R; Johnson, Mark R; Peebles, Donald; Waddington, Simon N; Bennett, Phillip R

2016-06-13

Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for the development of PTL prevention strategies.

Decreasing prematurity in twin gestations: predicaments and possibilities.

PubMed

Zork, Noelia; Biggio, Joseph; Tita, Alan; Rouse, Dwight; Gyamfi-Bannerman, Cynthia

2013-08-01

The twin birth rate has been steadily increasing in the United States over the past 10 years attributable in large part to the increased use of reproductive technologies. Despite advancements in the prevention of preterm labor for singletons, the overall rate of preterm birth has decreased only minimally. Several interventions to prevent preterm birth in twins have been studied, but none has proven effective. Inpatient bedrest has not been shown to be effective and can cause significant maternal morbidity. Although intramuscular 17α-hydroxyprogesterone caproate is effective in decreasing the risk of recurrent preterm delivery in singletons, neither it nor cerclage is effective in twin gestations, even in those with a short cervix. However, small trials, subgroup analyses, and a meta-analysis suggest that vaginal progesterone and the Arabin cervical pessary may reduce rates of preterm birth in twins of mothers with a short cervix. Given the current lack of effective therapies to prevent preterm birth in twins, large multicenter trials are needed to assess the effectiveness of vaginal progesterone and pessary in twins of mothers with a short cervix.

Preterm (Premature) Labor and Birth

MedlinePlus

... with serious health problems. Some health problems, like cerebral palsy , can last a lifetime. Other problems, such as ... This medication may help reduce the risk of cerebral palsy that is associated with early preterm birth. What ...

Management of preterm labor: atosiban or nifedipine?

PubMed

de Heus, Roel; Mulder, Eduard J H; Visser, Gerard H A

2010-08-09

Preterm birth is strongly associated with neonatal death and long-term neurological morbidity. The purpose of tocolytic drug administration is to postpone threatening preterm delivery for 48 hours to allow maximal effect of antenatal corticosteroids and maternal transportation to a center with specialized neonatal care facilities. There is uncertainty about the value of atosiban (oxytocin receptor antagonist) and nifedipine (calcium channel blocker) as first-line tocolytic drugs in the management of preterm labor. For nifedipine, concerns have been raised about unproven safety, lack of placebo-controlled trials, and its off-label use. The tocolytic efficacy of atosiban has also been questioned because of a lack of reduction in neonatal morbidity. This review discusses the available evidence, the pros and cons of either drug and aims to provide information to support a balanced choice of first-line tocolytic drug: atosiban or nifedipine?

[Atosiban treatment for preterm labor--financial considerations and savings by implementing clinical guidelines].

PubMed

Hadar, Eran; Mansur, Nariman; Ambar, Irit; Hod, Moshe

2011-06-01

Preterm delivery is a significant cause of neonatal morbidity and mortality. Pregnant women, with symptoms and signs consistent with preterm labor, can be treated with various tocolytic drugs. Atosiban is one of many drugs indicated to arrest imminent preterm labor. Various studies show that the efficacy of atosiban is similar to other tocolytic drugs. The main advantage of atosiban is a relativeLy low incidence of adverse maternal reactions. Its considerable shortcoming is the financial cost, compared to other available drugs. In view of its cost, we have decided to implement a strict protocol to direct the use of atosiban, with the intent to reduce costs, without hampering quality of care. The protocol was implemented from July 2009, and it outlines the medical and procedural terms to use atosiban. We compared similar time periods before and after implementation of the protocol. The outcomes compared included: treatment success, rates of preterm deliveries and financial costs. Within the timeframe that the protocol was implemented, we have been able to demonstrate a 40% reduction in atosiban related costs, compared to a parallel period, when the clinical guidelines were not implemented. This translates into savings of about NIS 40,000 (New Israeli Shekel) (approximately $10,000). This was achieved without an increase in the rate of preterm deliveries. Implementing and enforcing a simple protocol of supervision on the use of atosiban enables a considerable reduction of financial costs related to atosiban, without hampering medical care.

Economic analysis comparing induction of labor and expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks (PPROMEXIL trial).

PubMed

Vijgen, Sylvia M C; van der Ham, David P; Bijlenga, Denise; van Beek, Johannes J; Bloemenkamp, Kitty W M; Kwee, Anneke; Groenewout, Mariët; Kars, Michael M; Kuppens, Simone; Mantel, Gerald; Molkenboer, Jan F M; Mulder, Antonius L M; Nijhuis, Jan G; Pernet, Paula J M; Porath, Martina; Woiski, Mallory D; Weinans, Martin J N; van Wijngaarden, Wim J; Wildschut, Hajo I J; Akerboom, Bertina; Sikkema, J Marko; Willekes, Christine; Mol, Ben W J; Opmeer, Brent C

2014-04-01

To compare the costs of induction of labor and expectant management in women with preterm prelabor rupture of membranes (PPROM). Economic analysis based on a randomized clinical trial. Obstetric departments of eight academic and 52 non-academic hospitals in the Netherlands. Women with PPROM near term who were not in labor 24 h after PPROM. A cost-minimization analysis was done from a health care provider perspective, using a bottom-up approach to estimate resource utilization, valued with unit-costs reflecting actual costs. Primary health outcome was the incidence of neonatal sepsis. Direct medical costs were estimated from start of randomization to hospital discharge of mother and child. Induction of labor did not significantly reduce the probability of neonatal sepsis [2.6% vs. 4.1%, relative risk 0.64 (95% confidence interval 0.25-1.6)]. Mean costs per woman were €8094 for induction and €7340 for expectant management (difference €754; 95% confidence interval -335 to 1802). This difference predominantly originated in the postpartum period, where the mean costs were €5669 for induction vs. €4801 for expectant management. Delivery costs were higher in women allocated to induction than in women allocated to expectant management (€1777 vs. €1153 per woman). Antepartum costs in the expectant management group were higher because of longer antepartum maternal stays in hospital. In women with pregnancies complicated by PPROM near term, induction of labor does not reduce neonatal sepsis, whereas costs associated with this strategy are probably higher. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Uterine electromyography and light-induced fluorescence in the management of term and preterm labor.

PubMed

Garfield, R E; Maul, H; Maner, W; Fittkow, C; Olson, G; Shi, L; Saade, G R

2002-01-01

Understanding the physiology of the uterus and cervix during term and preterm parturition is crucial for developing methods to control their function and is essential to solving clinical problems related to labor. To date, only crude, inaccurate, and subjective methods are used to assess changes in uterine and cervical function in pregnancy. In the past several years, we have developed noninvasive methods to quantitatively evaluate the uterus and cervix based on recording of uterine electrical signals from the abdominal surface (uterine electromyography) and measurement of light-induced fluorescence (LIF) of cervical collagen (Collascope), respectively. Both methods are rapid and allow immediate assessment of uterine contractility and cervical ripening. Studies in animals and humans indicated that uterine and cervical performance can be monitored successfully during pregnancy using those approaches and that these techniques can be used during labor to better define management in a variety of conditions associated with labor. The potential benefits of the proposed instrumentation and methods include reducing the rate of preterm delivery, improving maternal and perinatal outcome, monitoring treatment, decreasing cesarean rate and providing research methods to understand uterine and cervical function.

Use of uterine electromyography to diagnose term and preterm labor

PubMed Central

LUCOVNIK, MIHA; KUON, RUBEN J.; CHAMBLISS, LINDA R.; MANER, WILLIAM L.; SHI, SHAO-QING; SHI, LEILI; BALDUCCI, JAMES; GARFIELD, ROBERT E.

2011-01-01

Current methodologies to assess the process of labor, such as tocodynamometry or intrauterine pressure catheters, fetal fibronectin, cervical length measurement and digital cervical examination, have several major drawbacks. They only measure the onset of labor indirectly and do not detect cellular changes characteristic of true labor. Consequently, their predictive values for term or preterm delivery are poor. Uterine contractions are a result of the electrical activity within the myometrium. Measurement of uterine electromyography (EMG) has been shown to detect contractions as accurately as the currently used methods. In addition, changes in cell excitability and coupling required for effective contractions that lead to delivery are reflected in changes of several EMG parameters. Use of uterine EMG can help to identify patients in true labor better than any other method presently employed in the clinic. PMID:21241260

Antibiotic administration to patients with preterm labor and intact membranes: is there a beneficial effect in patients with endocervical inflammation?

PubMed

Ovalle, Alfredo; Romero, Roberto; Gómez, Ricardo; Martínez, M Angélica; Nien, Jyh Kae; Ferrand, Pedro; Aspillaga, Carlos; Figueroa, Jorge

2006-08-01

To determine whether broad-spectrum antibiotic administration to patients with preterm labor and intact membranes is associated with an improvement in neonatal and maternal outcomes, particularly in patients with microbial invasion of the amniotic cavity (MIAC) or endocervical inflammation (ECI). A prospective clinical trial was conducted in which women in premature labor were alternately allocated to receive either antibiotics or placebo, and information about MIAC and ECI collected. Eighty-four pregnant women between 24 and 34 weeks of gestation with spontaneous preterm labor were enrolled. Exclusion criteria were cervical dilatation greater than 3 cm, clinical chorioamnionitis, abruption, rupture of membranes, vaginal bleeding, and several additional fetal and maternal conditions that may influence perinatal outcome. Amniocentesis was offered to all patients and the cervix and vagina were sampled for microbiological and cytological studies. Eligible patients were allocated to receive either clindamycin-gentamycin or placebo for 7 days. Corticosteroids and tocolysis with beta-adrenergic agents were used according to the standard management of our institution. MIAC was defined as the presence of a positive amniotic fluid culture obtained by trans-abdominal amniocentesis. ECI was diagnosed when a significant increase in the white blood cell count of the endocervical secretions was found. A composite neonatal morbidity/mortality outcome was created, including severe neonatal morbidity (respiratory distress syndrome, asphyxia, sepsis, pneumonia, intraventricular hemorrhage) and mortality. Thirty-nine women received antibiotics and 40 received placebo. The prevalence of ECI and MIAC in both groups was comparable (antibiotic group ECI 61.5% (24/39) and MIAC 20.5% (8/39); placebo group ECI 62.5% (25/40) and MIAC 20% (8/40); p > 0.05). Overall, there were no significant differences in maternal infections and composite neonatal outcomes between antibiotic and placebo groups. Women who received antibiotics had a lower rate of subsequent rupture of membranes compared to patients who received placebo (2.6% (1/39) vs. 25% (10/40), respectively; p = 0.007). A sub-analysis showed that among patients with ECI, antibiotic administration was associated with a lower rate of composite neonatal morbidity/mortality outcome compared to those who received placebo (4.2% (1/24) vs. 28% (7/25), respectively; p < 0.05). This association was also present in patients with ECI without MIAC (0% (0/16) vs. 27.8% (5/18); p < 0.05), but not in patients with ECI and MIAC (antibiotic group 12.5% (1/8) vs. placebo group 28.6% (2/7); p > 0.05). The combination of antibiotics used in this study did not improve maternal or perinatal outcome in patients with preterm labor and intact membranes. Further studies are required to determine if women with endocervicitis presenting with preterm labor and intact membranes may benefit from antibiotic administration.

Reduced Expression of Hydrogen Sulfide-Generating Enzymes Down-Regulates 15-Hydroxyprostaglandin Dehydrogenase in Chorion during Term and Preterm Labor.

PubMed

Sun, Qianqian; Chen, Zixi; He, Ping; Li, Yuan; Ding, Xiaoying; Huang, Ying; Gu, Hang; Ni, Xin

2018-01-01

Chorionic NAD-dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) plays a pivotal role in controlling the amount of prostaglandins in the uterus and has been implicated in the process of labor. Prior studies identified hydrogen sulfide-generating enzymes cystathionine-β-synthetase (CBS) and cystathionine-γ-lyase (CSE) in fetal membranes. We investigated whether hydrogen sulfide is involved in the regulation of PGDH expression in the chorion during labor. The chorionic tissues were obtained from pregnant women at preterm in labor and at term in labor or not in labor at term. Levels of CSE and CBS and hydrogen sulfide production rate were down-regulated in term in labor and preterm in labor groups compared with not in labor at term group. The CBS level correlated to PGDH expression in the chorion. Hydrogen sulfide donor NaHS and precursor l-cysteine dose-dependently stimulated PGDH expression and activity in cultured chorionic trophoblasts. The effect of l-cysteine was blocked by CBS inhibitor and CBS siRNA but not by CSE inhibitor and CSE siRNA. Hydrogen sulfide treatment suppressed miR-26b and miR-199a expression in chorionic trophoblasts. miR-26b and miR-199a mimics blocked hydrogen sulfide upregulation of PGDH expression. Our results indicate that hydrogen sulfide plays pivotal roles in maintenance of PGDH expression in the chorion during human pregnancy. Reduced expression of hydrogen sulfide-generating enzymes contributes to an increased amount of prostaglandins in the uterus during labor. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Difficulties in establishing routine amniocentesis for preterm labor evaluation.

PubMed

McIntosh, Jennifer J; McHugh, Katherine; Haas, David M

2012-03-01

After a recent practice change implementing amniocentesis into the evaluation of preterm labor (PTL) or preterm premature rupture of membranes (PPROM), actual performance of the procedure was tracked. Fifty-nine patients were admitted with these diagnoses. Twenty-three patients (39%) were offered amniocentesis and 36 patients (61%) were not offered amniocentesis as part of the clinical protocol. Seven (30%) patients of those offered an amniocentesis underwent the procedure. The predominant reasons for not performing an amniocentesis were patient refusal and provider discomfort. In conclusion, implementation of amniocentesis to evaluate for subclinical infection/inflammation in the setting of PTL or PPROM proved difficult, as only 7 of 59 (11.9%) patients admitted with these diagnoses actually received an amniocentesis.

Effects of Progesterone Treatment on Expression of Genes Involved in Uterine Quiescence

PubMed Central

Jeng, Yow-Jiun; Izban, Michael G.; Sinha, Mala; Luxon, Bruce A.; Stamnes, Susan J.; England, Sarah K.

2011-01-01

An important action of progesterone during pregnancy is to maintain the uterus in a quiescent state and thereby prevent preterm labor. The causes of preterm labor are not well understood, so progesterone action on the myometrium can provide clues about the processes that keep the uterus from contracting prematurely. Accordingly, we have carried out Affymetrix GeneChip analysis of progesterone effects on gene expression in immortalized human myometrial cells cultured from a patient near the end of pregnancy. Progesterone appears to inhibit uterine excitability by a number of mechanisms, including increased expression of calcium and voltage-operated K+ channels, which dampens the electrical activity of the myometrial cell, downregulation of agents, and receptors involved in myometrial contraction, reduction in cell signal components that lead to increased intracellular Ca2+ concentrations in response to contractile stimuli, and downregulation of proteins involved in the cross-linking of actin and myosin filaments to produce uterine contractions. PMID:21795739

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.

Placental Alpha Microglobulin-1 Compared With Fetal Fibronectin to Predict Preterm Delivery in Symptomatic Women.

PubMed

Wing, Deborah A; Haeri, Sina; Silber, Angela C; Roth, Cheryl K; Weiner, Carl P; Echebiri, Nelson C; Franco, Albert; Pappas, Lanissa M; Yeast, John D; Brebnor, Angelle A; Quirk, J Gerald; Murphy, Aisling M; Laurent, Louise C; Field, Nancy T; Norton, Mary E

2017-12-01

To compare the rapid bedside test for placental α microglobulin-1 with the instrumented fetal fibronectin test for prediction of imminent spontaneous preterm delivery among women with symptoms of preterm labor. We conducted a prospective observational study on pregnant women with signs or symptoms suggestive of preterm labor between 24 and 35 weeks of gestation with intact membranes and cervical dilatation less than 3 cm. Participants were prospectively enrolled at 15 U.S. academic and community centers. Placental α microglobulin-1 samples did not require a speculum examination. Health care providers were blinded to placental α microglobulin-1 results. Fetal fibronectin samples were collected through speculum examination per manufacturer requirements and sent to a certified laboratory for testing using a cutoff of 50 ng/mL. The coprimary endpoints were positive predictive value (PPV) superiority and negative predictive value (NPV) noninferiority of placental α microglobulin-1 compared with fetal fibronectin for the prediction of spontaneous preterm birth within 7 days and within 14 days. Of 796 women included in the study cohort, 711 (89.3%) had both placental α microglobulin-1 and fetal fibronectin results and valid delivery outcomes available for analysis. The overall rate of preterm birth was 2.4% (17/711) within 7 days of testing and 4.2% (30/711) within 14 days of testing with respective rates of spontaneous preterm birth of 1.3% (9/703) and 2.9% (20/701). Fetal fibronectin was detected in 15.5% (110/711), and placental α microglobulin-1 was detected in 2.4% (17/711). The PPVs for spontaneous preterm delivery within 7 days or less among singleton gestations (n=13) for placental α microglobulin-1 and fetal fibronectin were 23.1% (3/13) and 4.3% (4/94), respectively (P<.025 for superiority). The NPVs were 99.5% (619/622) and 99.6% (539/541) for placental α microglobulin-1 and fetal fibronectin, respectively (P<.001 for noninferiority). Although placental α microglobulin-1 performed the same as fetal fibronectin in ruling out spontaneous preterm delivery among symptomatic women, it demonstrated statistical superiority in predicting it.

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.

Relationship between Revised Graduated Index (R-GINDEX) of prenatal care utilization & preterm labor and low birth weight.

PubMed

Tayebi, Tahereh; Hamzehgardeshi, Zeinab; Ahmad Shirvani, Marjan; Dayhimi, Marjaneh; Danesh, Mahmonir

2014-02-28

Prenatal care refers to accurate and consistent performance of the principles important to maintain healthy pregnancy outcomes and also for mother and child health. One of the new indices to assess the adequacy of care is Revised Graduated Index of Prenatal Care Utilization (R-GINDEX).The study aims to assess the relationship between quantitative prenatal care factors and preterm labor and low birth weight using R-GINDEX. This historical cohort study has been conducted on 420 mothers during the first two years after delivery in 2010. The adequacy of care was calculated by R-GINDEX. Based on this index, participants have been divided into three care groups including inadequate, adequate and intensive care groups. A significant relationship has been found between R-GINDEX and preterm birth and low birth weight (P<0.05). Thus the probability of premature labor in inadequate care group (RR=3.93) and low birth weight (RR= 2.53) was higher than that of the adequate and intensive care group. The results showed that the quantity of prenatal care is effective in reducing preterm birth and low birth weight.

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.

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.

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

Use of progesterone and progestin analogs for inhibition of preterm birth and other uterine contractility disorders

PubMed Central

Garfield, R.E.; Shi, L.; Shi, S-Q.

2012-01-01

In this paper we focus on preterm birth as a uterine contractility disorder caused by hypercontractility of the myometrium. We describe changes in uterine function during term and preterm labor and delivery. We also examine the usefulness of measurement of uterine electromyographic (EMG) activity, noninvasively monitored from the abdominal surface of pregnant patients. The use of progesterone treatment for preterm birth is discussed and we conclude that present therapies with progesterone could be improved by changing the route of administration. Finally we show the results of recent studies that show that progesterone injections completely inhibit uterine EMG activity when given several days to hours before normal delivery. These studies illustrate how progesterone suppresses labor at term or preterm, probably through repression of genes which control excitability and conduction of electrical activity. However, direct profusion of soluble progesterone into the uterine cavity has little immediate inhibitory action and this may demonstrate that progesterone has no direct, nongenomic effects, at least in the rat model used. Further studies are required to determine the effects of progesterone on human uterine EMG activity and whether progesterone treatments will prevent preterm birth. PMID:24753915

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.

Adjunctive clindamycin therapy for preterm labor: results of a double-blind, placebo-controlled trial.

PubMed

McGregor, J A; French, J I; Seo, K

1991-10-01

A double-blind, placebo-controlled, randomized trial was conducted to evaluate the efficacy, safety, and tolerance of a course of clindamycin (administered for 3 days intravenously and 4 days orally) among hospitalized women with preterm labor at less than or equal to 34 weeks' gestation who were treated with tocolytics. One hundred three woman-perinate pairs were analyzed. Univariate analysis demonstrated that pregnancies were continued longer in women treated with clindamycin than in women who received placebo (clindamycin-treated group, 35 days; placebo-treated group, 25 days; p = 0.02). Survival analysis showed that pregnancy continued at least 35.5 days in 50% of clindamycin-treated women versus 20 days for control women (p = 0.03). Obstetric and microbiologic parameters associated with treatment outcomes were also sought. Women with bacterial vaginosis more often delivered preterm (p = 0.03; relative risk, 1.4; 95% confidence interval, 1.04 to 2.0). Among women with bacterial vaginosis, trends for increased duration of pregnancy (clindamycin-treated group, 36 days; placebo-treated group, 19 days), increased birth weight (clindamycin-treated group, 2634 gm; placebo-treated group, 2256 gm), and increased mean gestational age at delivery (clindamycin-treated group, 35 weeks; placebo-treated group, 34 weeks) were associated with clindamycin treatment. Women with either group B streptococcus, Chlamydia trachomatis, Trichomonas vaginalis, or Staphylococcus aureus were more likely to have preterm premature rupture of membranes (p = 0.01). Clindamycin treatment of these women reduced the incidence of preterm premature rupture of membranes to that of uninfected subjects. Stratification by gestational age at enrollment showed clindamycin treatment to be associated with an increased interval to delivery only among mothers enrolled before 33 weeks' gestation (clindamycin-treated group, 40 days; placebo-treated group, 28 days; p less than 0.05). Treatment with clindamycin appeared safe and well tolerated, with benefits limited to women who were less than or equal to 32 weeks' gestation.

Race differences in infant mortality from endogenous causes: a population-based study in North Carolina.

PubMed

Michielutte, R; Moore, M L; Meis, P J; Ernest, J M; Wells, H B

1994-02-01

This study examines the associations between race, birth weight, and mortality from endogenous causes for all singleton births born in 1984-1987 in a 20-county region of North Carolina. A more detailed analysis of preterm low birth weight infants examines these associations according to the proximate medical causes (medical etiology) of the preterm birth. Overall, black infants were found to have approximately twice the mortality risk of white infants. Most of the excess black mortality risk is explained by the larger proportion of black infants born at lower birth weights. The pattern of race differences in infant mortality by birth weight generally replicates the results of earlier studies, but the relative risk ratios within specific birth weight categories are smaller than previously reported. Among preterm low birth weight infants, the association between race and endogenous mortality differs within categories of medical etiology. The mortality risk is the same for black and white infants born preterm due to premature rupture of the membranes (PROM), lower for black infants born preterm due to medical problems, and higher for black infants born preterm due to idiopathic premature labor (IPL).

[Management of preterm labor].

PubMed

Kayem, G; Lorthe, E; Doret, M

2016-12-01

To define the management of preterm labor (MAP). The literature search was conducted using computer databases Medline and the Cochrane Library for a period from 1969 to March 2016. Leukocytosis screening may be useful in case of hospitalization for Preterm labor (PTL). Its use is not routine (professional consensus). Screening for urinary tract infection by urine culture should be systematic and antibiotic treatment should be performed in cases of bacterial colonization or urinary tract infection for a period of 7 days (grade A). The vaginal swab is useful to detect a strep B and was prescribed antibiotics during labor if positive (grade A). Routine antibiotic therapy is not recommended in case of PTL (grade A). Prolonged hospitalization does not reduce the risk of preterm delivery (NP3) and is not recommended (grade B). Bed rest does not reduce the risk of PTL (NP3), increases the risk of thromboembolism (NP3), and is not recommended (grade C). After hospitalization for PTL, a regular visit by a caregiver at home may be helpful when patients belong to a precarious environment or are psychologically vulnerable (Professional consensus). The benefit of monitoring home uterine activity repeated in the aftermath of hospitalization for PTL is not shown (NP3). It is not recommended to follow-up uterine activity systematically after hospitalization for PTL (grade C). The management of PTL should be individualized, include searching and treatment of infection and avoid prolonged hospitalization or bed rest. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Blood SC5b-9 complement levels increase at parturition during term and preterm labor.

PubMed

Segura-Cervantes, Enrique; Mancilla-Ramirez, Javier; Zurita, Luis; Paredes, Yuriria; Arredondo, José Luis; Galindo-Sevilla, Norma

2015-06-01

We explored the hypothesis that complement, an innate and adaptive immune effector, is active in the plasma of parturient women and is deposited on fetal membranes collected after delivery. A cross-sectional study was designed to evaluate complement activity at parturition. Pregnant women (n = 97) between 15 and 41 years of age were enrolled in a hospital protocol during the perinatal period to assess both SC5b-9 complement activity in blood and complement deposition on fetal membranes during parturition. Soluble SC5b-9 complement activity in plasma fractions was measured using a standard enzyme-linked immunosorbent assay (ELISA) that included specific anti-complement antibodies. Complement deposition on membranes was analyzed using immuno-dot blots and immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL), preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P < 0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen in C5b-9 complexes, was deposited on fetal membranes, with no difference between term and preterm delivery. The deposition of active complement on fetal membranes was confirmed by immunohistochemistry. Women who underwent non-labor-indicated Cesarean sections did not exhibit complement deposition. Soluble SC5b-9 complement complex levels increased in the plasma of women during parturition, and complement C5b-9 complexes were deposited on fetal membranes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Risk factors associated with preterm birth in a second level hospital].

PubMed

Escobar-Padilla, Beatriz; Gordillo-Lara, Limberg Darinel; Martínez-Puon, Horacio

2017-01-01

Preterm birth is one of the biggest problems in obstetrics and gynecology, given that it has an incidence of 10-11%. The objective was to identify the risk factors associated with a preterm birth. A retrospective, observational, transversal and analytic case-control study was made. All premature birth incidences were determined as study objects and controls were integrated with term deliveries. A sample size of 344 patients with a control per case was calculated. A total of 688 patients were studied. Statistical analysis was descriptive, univariate and bivariate and we used the Pearson chi square test, with a p < 0.05, odds ratios (OR) and 95% confidence intervals (95% CI). The risk factors associated with a preterm labor were placenta praevia: OR = 10.2 (p = 0.005); previous preterm delivery: OR = 10.2 (p = 0.005); preeclampsia: OR = 6.38 (p = 0.00); twin pregnancy: OR = 5.8 (p = 0.000); oligohydramnios: OR = 5.8 (p = 0.000); tobacco use: OR = 4.6 (p = 0.002); premature rupture of membranes (PROM): OR = 4.1 (p = 0.000); cervicovaginitis: OR = 3 (p = 0.000); urinary tract infections (UTI): OR = 1.5 (p = 0.010). Maternal history of prenatal care, preclampsia, PROM, twin pregnancy, placenta praevia, cervicovaginitis, previous preterm delivery and UTI are risk factors with statistical significance associated with preterm delivery.

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

Temporal Trends in Late Preterm and Early Term Birth Rates in 6 High-Income Countries in North America and Europe and Association With Clinician-Initiated Obstetric Interventions.

PubMed

Richards, Jennifer L; Kramer, Michael S; Deb-Rinker, Paromita; Rouleau, Jocelyn; Mortensen, Laust; Gissler, Mika; Morken, Nils-Halvdan; Skjærven, Rolv; Cnattingius, Sven; Johansson, Stefan; Delnord, Marie; Dolan, Siobhan M; Morisaki, Naho; Tough, Suzanne; Zeitlin, Jennifer; Kramer, Michael R

2016-07-26

Clinicians have been urged to delay the use of obstetric interventions (eg, labor induction, cesarean delivery) until 39 weeks or later in the absence of maternal or fetal indications for intervention. To describe recent trends in late preterm and early term birth rates in 6 high-income countries and assess association with use of clinician-initiated obstetric interventions. Retrospective analysis of singleton live births from 2006 to the latest available year (ranging from 2010 to 2015) in Canada, Denmark, Finland, Norway, Sweden, and the United States. Use of clinician-initiated obstetric intervention (either labor induction or prelabor cesarean delivery) during delivery. Annual country-specific late preterm (34-36 weeks) and early term (37-38 weeks) birth rates. The study population included 2,415,432 Canadian births in 2006-2014 (4.8% late preterm; 25.3% early term); 305,947 Danish births in 2006-2010 (3.6% late preterm; 18.8% early term); 571,937 Finnish births in 2006-2015 (3.3% late preterm; 16.8% early term); 468,954 Norwegian births in 2006-2013 (3.8% late preterm; 17.2% early term); 737,754 Swedish births in 2006-2012 (3.6% late preterm; 18.7% early term); and 25,788,558 US births in 2006-2014 (6.0% late preterm; 26.9% early term). Late preterm birth rates decreased in Norway (3.9% to 3.5%) and the United States (6.8% to 5.7%). Early term birth rates decreased in Norway (17.6% to 16.8%), Sweden (19.4% to 18.5%), and the United States (30.2% to 24.4%). In the United States, early term birth rates decreased from 33.0% in 2006 to 21.1% in 2014 among births with clinician-initiated obstetric intervention, and from 29.7% in 2006 to 27.1% in 2014 among births without clinician-initiated obstetric intervention. Rates of clinician-initiated obstetric intervention increased among late preterm births in Canada (28.0% to 37.9%), Denmark (22.2% to 25.0%), and Finland (25.1% to 38.5%), and among early term births in Denmark (38.4% to 43.8%) and Finland (29.8% to 40.1%). Between 2006 and 2014, late preterm and early term birth rates decreased in the United States, and an association was observed between early term birth rates and decreasing clinician-initiated obstetric interventions. Late preterm births also decreased in Norway, and early term births decreased in Norway and Sweden. Clinician-initiated obstetric interventions increased in some countries but no association was found with rates of late preterm or early term birth.

Impact of cesarean section on intermediate and late preterm births: United States, 2000-2003.

PubMed

Malloy, Michael H

2009-03-01

Cesarean section appears to be associated with increased risk of neonatal mortality among infants of low-risk term pregnancies, but it may offer some survival advantage among the most extremely preterm infants. The impact on intermediate (32-33 wk) and late preterm (34-36 wk) deliveries remains uncertain. The objective of this analysis was to compare the neonatal mortality rate (death at 0-27 days), the mechanical ventilation usage rate, and the incidence of hyaline membrane disease among intermediate and late preterm infants delivered by primary cesarean section compared with those delivered vaginally. United States Linked Birth and Infant Death Certificate files from the years 2000 to 2003 were used. Maternal demographic characteristics, medical complications, and labor and delivery complications were abstracted from the files along with infant information. Because of concern for misclassification of gestational age, a procedure was used to trim away births in which the birthweight of an infant for a specific gestational age was inconsistent. Adjusted odds ratios were calculated using logistic regression for the risk of the three outcomes of interest relative to the mode of delivery. A total of 422,001 live births were available with complete data from the trimmed data set (60% of untrimmed data). After adjustment by logistic regression for infant size at birth, birthweight, sex, Apgar score at 5 minutes less than 4, multiple births, breech presentation, presence of an anomaly, the presence of any maternal medical condition or complication of labor and delivery, labor induction, maternal race, age, education, and gravidity, the adjusted odds ratios (95% CI for neonatal mortality at gestational ages of 32, 33, 34, 35, and 36 wk) were, respectively, 1.69 (1.31-2.20), 1.79 (1.40-2.29), 1.08 (0.83-1.40), 2.31 (1.78-3.00), and 1.98 (1.50-2.62). These data suggest that for low-risk preterm infants at 32 to 36 weeks' gestation, independent of any reported risk factors, primary cesarean section may pose an increased risk of neonatal mortality and morbidity.

Low birth weight in the United States.

PubMed

Goldenberg, Robert L; Culhane, Jennifer F

2007-02-01

Pregnancy outcomes in the United States and other developed countries are considerably better than those in many developing countries. However, adverse pregnancy outcomes are generally more common in the United States than in other developed countries. Low-birth-weight infants, born after a preterm birth or secondary to intrauterine growth restriction, account for much of the increased morbidity, mortality, and cost. Wide disparities exist in both preterm birth and growth restriction among different population groups. Poor and black women, for example, have twice the preterm birth rate and higher rates of growth restriction than do most other women. Low birth weight in general is thought to place the infant at greater risk of later adult chronic medical conditions, such as diabetes, hypertension, and heart disease. Of interest, maternal thinness is a strong predictor of both preterm birth and fetal growth restriction. However, in the United States, several nutritional interventions, including high-protein diets, caloric supplementation, calcium and iron supplementation, and various other vitamin and mineral supplementations, have not generally reduced preterm birth or growth restriction. Bacterial intrauterine infections play an important role in the etiology of the earliest preterm births, but, at least to date, antibiotic treatment either before labor for risk factors such as bacterial vaginosis or during preterm labor have not consistently reduced the preterm birth rate. Most interventions have failed to reduce preterm birth or growth restriction. The substantial improvement in newborn survival in the United States over the past several decades is mostly due to better access to improved neonatal care for low-birth-weight infants.

What Is Labor?

MedlinePlus

... know about postpartum depression? Related A-Z Topics Breastfeeding and Breast Milk Preconception Care and Prenatal Care Preterm Labor and Birth NICHD News and Features Release: Women with pregnancy-related diabetes may be at risk for chronic kidney disease ...

When Parents Ask ... about Preterm Birth, Breastfeeding Success, Breast Cancer, or Waterbirth.

PubMed

Moore, Mary Lou

2003-01-01

IN THIS COLUMN, THE AUTHOR REVIEWS RESEARCH ON FOUR SEPARATE TOPICS: the prevention of preterm birth, the effect of epidurals on breastfeeding success, the possible protective effect of lactation on breast cancer, and laboring in water. In two separate studies-a multisite study in the United States and a second study from Brazil-natural progesterone was shown to significantly reduce the incidence of preterm birth in women at high risk. A third study conducted in the United Kingdom examined the effect of clindamycin on preventing infection that can lead to preterm birth. A group of studies related to lactation found that early breastfeeding was more successful in women who did not have epidural anesthesia. In a Korean study, the lifetime duration of breastfeeding was associated with a significant reduction in breast cancer. Concerning waterbirth, Swiss researchers found that, when a woman labored in water, she regulated both water temperature and bathing duration to ensure that her body temperature and that of the fetus remained within a normal physiological range.

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

Cervical Length in Patients at Risk for Placenta Accreta.

PubMed

Rac, Martha W F; McIntire, Donald D; Wells, C Edward; Moschos, Elysia; Twickler, Diane D

2017-07-01

To evaluate cervical length measurements in women with placenta accreta compared to women with a nonadherent low-lying placenta or placenta previa and evaluate this relationship in terms of vaginal bleeding, preterm labor, and preterm birth. We conducted a retrospective cohort study between 1997 and 2011 of gravidas with more than 1 prior cesarean delivery who had a transvaginal ultrasound examination between 24 and 34 weeks for a low-lying placenta or placenta previa. Cervical length was measured from archived images in accordance with national guidelines by a single investigator, who was blinded to outcomes and ultrasound reports. The diagnosis of placental accreta was based on histologic confirmation. For study purposes, preterm birth was defined as less than 36 weeks, and cervical lengths of 3 cm or less were considered short. Standard statistical analyses were used. A total of 125 patients met inclusion criteria. The cohort was divided into patients with (n = 43 [34%]) and without (n = 82 [66%]) placenta accreta and stratified by gestational age at the ultrasound examinations. Women with placenta accreta had shorter cervical length measurements during their 32- to 34-week ultrasound examinations (mean ± SD, 3.23 ± 0.98 versus 3.95 ± 1.0 cm; P < .01) and were more likely to have a short cervix of 3 cm or less (P = .001). However, these findings did not correlate with the degree of invasion (P = .3), or higher rates of vaginal bleeding and preterm labor (P = .19) resulting in preterm birth before 36 weeks (P = .64). Women with placenta accreta had shorter cervical lengths at 32 to 34 weeks than women with a nonadherent low-lying placenta or placenta previa, but this finding did not correlate with a higher risk of vaginal bleeding or preterm labor resulting in preterm birth before 36 weeks. © 2017 by the American Institute of Ultrasound in Medicine.

Born a bit too early: recent trends in late preterm births.

PubMed

Martin, Joyce A; Kirmeyer, Sharon; Osterman, Michelle; Shepherd, Ruth A

2009-11-01

The U.S. late preterm birth rate rose 20% from 1990 to 2006. If the late preterm rate had not risen from the 1990 level, more than 50,000 fewer infants would have been delivered late preterm in 2006. On average, more than 900 late preterm babies are born every day in the United States, or a total of one-third of 1 million infants (333,461). Increases in late preterm births are seen for mothers of all ages, and for non-Hispanic white and Hispanic mothers. The rate for black mothers declined during the 1990s, but has been on the rise since 2000. Late preterm birth rates rose for all U.S. states, but declined in the District of Columbia. The percentage of late preterm births for which labor was induced more than doubled from 1990 to 2006; the percentage of late preterm births delivered by cesarean also rose markedly.

Recent Declines in Induction of Labor by Gestational Age

MedlinePlus

... Individual live birth in a singleton (one fetus) pregnancy. Singleton induction rate : Number of labor inductions for singleton births per 100 singleton births. Gestational age categories : Early preterm: Births prior to 34 completed weeks of ...

[Diagnosis and prognosis of preterm labor: physical examination and ultrasonography].

PubMed

Goffinet, F; Kayem, G

2002-11-01

Diagnosis. Preterm labor is defined by cervical changes associated with regular painful uterine contractions (UC) between 22 and 36 weeks + 6 days. Tocometry does not improve diagnosis or prognosis, despite the identification of more UC (NP 4). Electromyography and cervical distensibility (cervicotonometer) are promising techniques but are still in the research field. Clinical markers for prognosis. Clinical markers associated with clinical cervical examination tested in scoring systems are not validated and can't be recommended in clinical practise (NP 4). Ultrasonographic examination of the cervix. Technical evaluation of ultrasonographic examination of the cervix is satisfactory (NP 3); the transvaginal technical have to be used (NP 3). This method has a better accuracy and reproducibility than clinical examination provided a good apprenticeship (NP 3). Three ultrasound abnormal criteria are defined: a short length, a large internal cervical os and the presence of a funnel in the cervical canal. The best cut-off of cervical length to predict preterm delivery lies between 18 and 30 mm (NP 3). The choice of the cutt-off level depends on the prectitioner: high sensitivity but with many false-positives (cut-off close to 30 mm) or lower sensitivity with few false-positives (close to 20 mm). Cervical length seems to be more accurate that internal os or presence of a funnel which should be used with caution in clinical decisions (NP 3). There is no comparative study about the use of ultrasonographic examination of the cervix in women with preterm labor to evaluate benefits and adverse effects in clinical practice. However, ultrasonographic examination of the cervix supply a progress identifying women at risk of preterm delivery and this technique has a better predictive value than clinical cervical examination (NP 3). It seems reasonable to recommend utilisation of ultrasonographic examination of the cervic in preterm labor. It would not seem reasonable to replace the vaginal examination by ultrasonography. Ultrasonography could be used in association with clinical examination or in a second time if clinical examination is doubtful (NP 3). For these women, ultrasonography could reduce the number of hospitalizations, limiting treatment for some and, for others, increasing intensive interventions such as tocolysis, in utero transfer or corticsteroid treatment.

Beta-2 adrenoceptor genotype and progress in term and late preterm active labor

PubMed Central

MILLER, Russell S.; SMILEY, Richard M.; DANIEL, Danette; WENG, Chunhua; EMALA, Charles W.; BLOUIN, Jean-Louis; FLOOD, Pamela D.

2011-01-01

OBJECTIVE To evaluate whether beta-2 adrenoceptor genotype at a functional polymorphic site encoding for amino acid residue 16 influences rate of cervical dilatation in term and late preterm active labor. STUDY DESIGN Subjects that underwent vaginal delivery at 34 or greater weeks gestational age between May, 2006, and August, 2007, were identified. Each subject had provided venous blood from which DNA was extracted for beta-2 adrenoceptor genotyping. Digital cervical examinations with paired examination times were collected from intrapartum records. Rate of cervical dilatation in active labor was determined using linear regression and rates were compared between genotype groups. RESULTS Among 401 subjects with satisfactory genotype and intrapartum data, overall rate of active labor was 0.76+/−0.01 cm/hr. When labor was compared by genotype, homozygous Arg/Arg16 subjects progressed at a slower rate (0.64+/−0.03 cm/hr) than all other pooled genotypes (0.8+/−0.02 cm/hr). CONCLUSION Homozygous beta-2 adrenoceptor genotype encoding for Arg/Arg16 was associated with slower progress in active labor. PMID:21600547

Trends in twin neonatal mortality rates in the United States, 1989 through 1999: influence of birth registration and obstetric intervention.

PubMed

Ananth, Cande V; Joseph Ks, K s; Smulian, John C

2004-05-01

We sought to evaluate the contributions of changes in birth registration, labor induction, and cesarean delivery on trends in twin neonatal mortality rates. We conducted a population-based, retrospective cohort study of twin live births, using linked birth-infant death data in the United States (1989-1999). Relative risks and 95% confidence intervals that quantified changes in neonatal (0-27 days) mortality rates were derived from ecologic logistic regression models that were fit after aggregation of the data by each state in the United States. The frequency of live born twins who weighed <500 g increased 72%, from 0.7% in 1989 to 1.2% in 1999, of live born twins who weighed 500 to 749 g and 750 to 999 g increased by 55% and 28%, respectively, between 1989 and 1999. Preterm birth rates increased by 19%, from 46.2% in 1989 to 57.2% in 1999. The rate of labor induction increased from 5.8% to 13.9%, and the cesarean delivery rate increased from 49.8% to 56.3%. Between 1989 to 1991 and 1997 to 1999, the crude neonatal mortality rates among twins who weighed >or=500 g declined by 37% (95% CI, 35%-40%) from 21.5 to 13.6 per 1000 twin live births. Adjustments for preterm labor induction, preterm cesarean delivery, term labor induction, term cesarean delivery, and sociodemographic factors had little influence on neonatal mortality rate trends. Increases in preterm birth because of obstetric intervention among twins have not led to increases in twin neonatal mortality rates in the United States.

Lipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B4

PubMed Central

Maddipati, Krishna Rao; Romero, Roberto; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Zhou, Sen-Lin; Xu, Zhonghui; Tarca, Adi L.; Kusanovic, Juan Pedro; Gomez, Ricardo; Chaiyasit, Noppadol; Honn, Kenneth V.

2016-01-01

Bioactive lipids derived from the metabolism of polyunsaturated fatty acids are important mediators of the inflammatory response. Labor per se is considered a sterile inflammatory process. Intra-amniotic inflammation (IAI) due to microorganisms (i.e., intra-amniotic infection) or danger signals (i.e., sterile IAI) has been implicated in the pathogenesis of preterm labor and clinical chorioamnionitis at term. Early and accurate diagnosis of microbial invasion of the amniotic cavity (MIAC) requires analysis of amniotic fluid (AF). It is possible that IAI caused by microorganisms is associated with a stereotypic lipidomic profile, and that analysis of AF may help in the identification of patients with this condition. To test this hypothesis, we analyzed the fatty acyl lipidome of AF by liquid chromatography—mass spectrometry from patients in spontaneous labor at term and preterm gestations. We report that the AF concentrations of proinflammatory lipid mediators of the 5-lipoxygenase pathway are significantly higher in MIAC than in cases of sterile IAI. These results suggest that the concentrations of 5-lipoxygenase metabolites of arachidonic acid, 5-hydroxyeicosatetraenoic acid, and leukotriene B4 in particular could serve as potential biomarkers of MIAC. This finding could have important implications for the rapid identification of patients who may benefit from anti-microbial treatment.—Maddipati, K. R., Romero, R., Chaiworapongsa ,T., Chaemsaithong, P., Zhou, S.-L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Gomez, R., Chaiyasit, N., Honn, K. V. Lipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B4. PMID:27312808

[Pilot tests using molecular diagnostic assay cervicovaginal infection during pregnancy].

PubMed

Beltrán-Montoya, J; Escudero-Gontes, S; Martínez-Huerta, N E; Ávila-Vergara, M A; Morales-Hernández, V; Canchola-Sotelo, C; Palacios-González, B; Vadillo-Ortega, F

2016-08-01

The prevalence of cervicovaginal infections during pregnancy has been associated with adverse perinatal outcomes however, the actual approach used for diagnosis is not effective. The aim of this study was to compare the diagnosis of vaginal infections in pregnant women using clinical, molecular diagnostic and traditional microbiological culture in a pilot study, to determine the prevalence and association with the development of preterm labor. We performed a nested cross-sectional study composed by 54 women in a cohort of pregnant women in Mexico City. Cervicovaginal infections were evaluated by clinical methods, microbiology culture and a commercially available molecular biology test. Prevalence of cervicovaginal infections during pregnancy was estimated between 28% and 50% according to methodologies. Considering the clinical diagnosis of preterm labor as the gold standard, all diagnostic tests were poor as predictors of preterm labor. Traditional approaches to establish the significance of cervicovaginal infection in pregnancy are exhausted, so be sought new ways to understand this complex relationship. Meanwhile it is recommended to continue to use traditional methods to identify infections during pregnancy in both knowledge of new methods aimed at understanding these relationships are sophisticated.

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.

Resveratrol protects from lipopolysaccharide-induced inflammation in the uterus and prevents experimental preterm birth.

PubMed

Bariani, María Victoria; Correa, Fernando; Leishman, Emma; Domínguez Rubio, Ana Paula; Arias, Andreína; Stern, Aníbal; Bradshaw, Heather B; Franchi, Ana María

2017-08-01

Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice? Resveratrol prevented the LPS-induced onset of preterm labor in 64% of the cases and showed anti-inflammatory and tocolytic effects by downregulating COX-2 and iNOS expression and NOS activity, and by changing the uterine prostaglandin and endocannabinoid profiling. Genital tract infections by Gram-negative bacteria are a common complication in human pregnancy and have been shown to increase risk of preterm delivery. Bacterial LPS elicits a strong maternal inflammatory response that results in preterm delivery and fetal death in a murine model endotoxin-induced preterm labor. An in vivo animal study was conducted. On Day 15 of pregnancy, mice received at 8:00 h a dose of vehicle (40% ethanol in saline solution) or resveratrol (3 mg/kg in vehicle) via oral gavage followed by two doses of LPS or vehicle administered intraperitoneally (i.p.), the first one at 10:00 h (0.17 mg/kg in 0.1 ml of sterile saline solution) and the second at 13:00 h (0.5 mg/kg in 0.1 ml of sterile saline solution). The mice were closely observed for any signs of morbidity (piloerection, decreased movement, and diarrhea), vaginal bleeding or preterm delivery. The beginning of preterm delivery was defined by early delivery of the first pup. Normal term labor occurs on Day 19 of gestation. Time of labor, pregnancy outcome and morphological features were evaluated after LPS and/or resveratrol administration. Uterine stripes were collected 5 h after the last LPS injection and prostaglandin and endocannabinoid profiling was analyzed by mass spectrometry. Nitric oxide synthase (NOS) activity was measured by radioconversion assay. Cyclooxygenase-2 (Cox-2) and 15-hydroxyprostaglandin dehydrogenase (15-Pgdh) mRNA levels were analyzed by RT-PCR whilst the protein expression of inducible nitric oxide synthase (iNOS), COX-1 and COX-2 were studied by western blot. In vivo treatment of 15-day pregnant BALB/c mice with resveratrol prevented the LPS-induced preterm birth in 64% of the cases, whereas only 15% of mice with LPS alone escaped preterm birth. Treatment with resveratrol resulted in a reduced NOS activity (P < 0.05) in the uterus of LPS-treated mice. Similarly, resveratrol reduced the expression of LPS-induced pro-inflammatory agents such as iNOS (P < 0.05), COX-2 (P < 0.05), prostaglandin E2 (PGE2) (P < 0.05) and anandamide (AEA) (P < 0.05). Moreover, resveratrol administration resulted in changes in the uterine endocannabinoid profiling altered by LPS. N/A. Since our experimental design involves the use of mice, the extrapolation of the results presented here to humans is limited. Our findings provide evidence for the tocolytic effects of resveratrol. Dr Ana María Franchi was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013/0097) and by Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Heather B. Bradshaw was funded by NIH (DA006668). The authors have no competing interests. © The Author 2017. 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

[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.

[Labor monitoring in high-risk situations].

PubMed

Houfflin-Debarge, V; Closset, E; Deruelle, P

2008-02-01

Intrapartum asphyxia is increased in several situations such as intrauterine growth retardation, preterm labor, postdate pregnancy or maternal diabetes. In all these cases, fetal heart rate monitoring should be preferred to intermittent auscultation. Fetal scalp blood pH or lactates can be used to identify fetuses at risk of intrapartum asphyxia. However, fetal scalp blood sampling should not delay delivery in case of severe abnormal fetal heart rate as fetal asphyxia could occur rapidly in theses high-risk pregnancies. Data is insufficient to recommend fetal pulse oximetry or ECG analysis. Research should be undertaken to evaluate their performance in these situations.

Cervical collagen imaging for determining preterm labor risks using a colposcope with full Mueller matrix capability

NASA Astrophysics Data System (ADS)

Stoff, Susan; Chue-Sang, Joseph; Holness, Nola A.; Gandjbakhche, Amir; Chernomordik, Viktor; Ramella-Roman, Jessica

2016-02-01

Preterm birth is a worldwide health issue, as the number one cause of infant mortality and neurological disorders. Although affecting nearly 10% of all births, an accurate, reliable diagnostic method for preterm birth has, yet, to be developed. The primary constituent of the cervix, collagen, provides the structural support and mechanical strength to maintain cervical closure, through specific organization, during fetal gestation. As pregnancy progresses, the disorganization of the cervical collagen occurs to allow eventual cervical pliability so the baby can be birthed through the cervical opening. This disorganization of collagen affects the mechanical properties of the cervix and, if the changes occur prematurely, may be a significant factor leading to preterm birth. The organization of collagen can be analyzed through the use of Mueller Matrix Polarimetric imaging of the characteristic birefringence of collagen. In this research, we have built a full Mueller Matrix Polarimetry attachment to a standard colposcope to enable imaging of human cervixes during standard prenatal exams at various stages of fetal gestation. Analysis of the polarimetric images provides information of quantity and organization of cervical collagen at specific gestational stages of pregnancy. This quantitative information may provide an indication of risk of preterm birth.

Discontinuation of Tocolytics for Preterm Labor in an Academic Safety Net Hospital: Impact on the Duration of Betamethasone Exposure.

PubMed

Alston, Meredith J; Alexandrovic, Kara; Stiglich, Norma; Metz, Torri D

2016-01-01

To evaluate the impact of discontinuation of tocolytics on the completion of the corticosteroid course among preterm neonates in an academic safety net hospital. Retrospective cohort study of all singleton pregnancies with preterm labor resulting in delivery between 24 and 34 weeks' gestation at Denver Health Medical Center (DHMC) between 1/1/2004 and 5/31/2009. In January 2007 DHMC discontinued the use of tocolytic therapy for preterm labor. Study subjects were grouped based on whether their delivery occurred before or after the change in policy. Multivariable logistic regression was used to determine whether the use of tocolysis increased the odds of completion of the betamethasone while adjusting for cervical examination at admission. Of 169 infant/mother pairs who met inclusion criteria, 102 delivered prior to the discontinuation of tocolytics and 67 delivered after the discontinuation of tocolytics. Treatment with tocolysis increased the odds of completing the 48-hour betamethasone window (OR 2.59, 95% CI 1.16-5.79). Each centimeter increase in cervical dilation at the time of admission decreased the odds of completing the betamethasone window (OR 0.50, 95% CI 0.39-0.62). The use of tocolytics increased the odds of completion of the betamethasone window in an academic safety net hospital among neonates born between 24 and 34 weeks' gestation.

Alcohol, indomethacin, and salbutamol. A comparative trial of their use in preterm labor.

PubMed

Spearing, G

1979-02-01

In a comparative trial, ethanol effectively arrested preterm labor for 48 hours for more in 32% of cases, a beta-adrenergic agent (salbutamol) in 60% of cases (not statistically significant), and a combination of ethanol and indomethacin in 70% of cases (statistically significant, P less than 0.5). Labor was delayed for 14 days or more in 36, 60, and 50%, respectively (not statistically significant). The numbers studied were small, and tests of statistical significance were of doubtful value. Salbutamol was more acceptable to patients and the staff than ethanol. The trial was suspended and eventually abandoned due to reports of prostaglandin synthetase inhibitors causing premature closure of the ductus arteriosus. In this series no problems were encountered with the use of indomethacin.

Temporal Trends in Late Preterm and Early Term Birth Rates in 6 High-Income Countries in North America and Europe and Association With Clinician-Initiated Obstetric Interventions

PubMed Central

Richards, Jennifer L.; Kramer, Michael S.; Deb-Rinker, Paromita; Rouleau, Jocelyn; Mortensen, Laust; Gissler, Mika; Morken, Nils-Halvdan; Skjærven, Rolv; Cnattingius, Sven; Johansson, Stefan; Delnord, Marie; Dolan, Siobhan M.; Morisaki, Naho; Tough, Suzanne; Zeitlin, Jennifer; Kramer, Michael R.

2017-01-01

IMPORTANCE Clinicians have been urged to delay the use of obstetric interventions (eg, labor induction, cesarean delivery) until 39 weeks or later in the absence of maternal or fetal indications for intervention. OBJECTIVE To describe recent trends in late preterm and early term birth rates in 6 high-income countries and assess association with use of clinician-initiated obstetric interventions. DESIGN Retrospective analysis of singleton live births from 2006 to the latest available year (ranging from 2010 to 2015) in Canada, Denmark, Finland, Norway, Sweden, and the United States. EXPOSURES Use of clinician-initiated obstetric intervention (either labor induction or prelabor cesarean delivery) during delivery. MAIN OUTCOMES AND MEASURES Annual country-specific late preterm (34–36 weeks) and early term (37–38 weeks) birth rates. RESULTS The study population included 2 415 432 Canadian births in 2006–2014 (4.8% late preterm; 25.3% early term); 305 947 Danish births in 2006–2010 (3.6% late preterm; 18.8% early term); 571 937 Finnish births in 2006–2015 (3.3% late preterm; 16.8% early term); 468 954 Norwegian births in 2006–2013 (3.8% late preterm; 17.2% early term); 737 754 Swedish births in 2006–2012 (3.6% late preterm; 18.7% early term); and 25 788 558 US births in 2006–2014 (6.0% late preterm; 26.9% early term). Late preterm birth rates decreased in Norway (3.9% to 3.5%) and the United States (6.8% to 5.7%). Early term birth rates decreased in Norway (17.6% to 16.8%), Sweden (19.4% to 18.5%), and the United States (30.2% to 24.4%). In the United States, early term birth rates decreased from 33.0% in 2006 to 21.1% in 2014 among births with clinician-initiated obstetric intervention, and from 29.7% in 2006 to 27.1% in 2014 among births without clinician-initiated obstetric intervention. Rates of clinician-initiated obstetric intervention increased among late preterm births in Canada (28.0% to 37.9%), Denmark (22.2% to 25.0%), and Finland (25.1% to 38.5%), and among early term births in Denmark (38.4% to 43.8%) and Finland (29.8% to 40.1%). CONCLUSIONS AND RELEVANCE Between 2006 and 2014, late preterm and early term birth rates decreased in the United States, and an association was observed between early term birth rates and decreasing clinician-initiated obstetric interventions. Late preterm births also decreased in Norway, and early term births decreased in Norway and Sweden. Clinician-initiated obstetric interventions increased in some countries but no association was found with rates of late preterm or early term birth. PMID:27458946

Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1

PubMed Central

Romero, Roberto; Chaiworapongsa, Tinnakorn; Savasan, Zeynep Alpay; Xu, Yi; Hussein, Youssef; Dong, Zhong; Kusanovic, Juan Pedro; Kim, Chong Jai; Hassan, Sonia S

2012-01-01

Objective Preterm parturition is a syndrome caused by multiple etiologies. Although intra-amniotic infection is causally linked with intrauterine inflammation and the onset of preterm labor, other patients have preterm labor in the absence of demonstrable infection. It is now clear that inflammation may be elicited by activation of the Damage-Associated Molecular Patterns (DAMPs), which include pathogen-associated molecular patterns (PAMPs) as well as “alarmins” (endogenous molecules that signal tissue and cellular damage). A prototypic alarmin is high-mobility group box-1 (HMGB1) protein, capable of inducing inflammation and tissue repair when it reaches the extracellular environment. HMGB1 is a late-mediator of sepsis, and blockade of HMGB1 activity reduces mortality in an animal model of endotoxemia, even if administered late during the course of the disorder. The objectives of this study were to: 1) determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in amniotic fluid concentrations of HMGB1; and 2) localize immunoreactivity of HMGB1 in the fetal membranes and umbilical cord of patients with chorioamnionitis. Methods Amniotic fluid samples were collected from the following groups: 1) preterm labor with intact membranes (PTL) with (n=42) and without IAI (n=84); and 2) preterm prelabor rupture of membranes (PROM) with (n=38) and without IAI (n=35). IAI was defined as either a positive amniotic fluid culture or amniotic fluid concentration of interleukin-6 (IL-6) ≥2.6 ng/mL. HMGB1 concentrations in amniotic fluid were determined by ELISA. Immunofluorescence staining for HMGB1 was performed in the fetal membranes and umbilical cord of pregnancies with acute chorioamnionitis. Results Amniotic fluid HMGB1 concentrations were higher in patients with IAI than in those without IAI in both the PTL and preterm PROM groups (PTL IAI: median 3.1 ng/mL vs. without IAI; median 0.98 ng/mL; p<0.001; and preterm PROM with IAI median 7.3 ng/mL vs. without IAI median 2.6 ng/mL; p=0.002); patients with preterm PROM without IAI had a higher median amniotic fluid HMGB1 concentration than those with PTL and intact membranes without IAI (p<0.001); and HMGB1 was immunolocalized to amnion epithelial cells and stromal cells in the Wharton’s jelly (prominent in the nuclei and cytoplasm). Myofibroblasts and macrophages of the chorioamniotic connective tissue layer and infiltrating neutrophils showed diffuse cytoplasmic HMGB1 immunoreactivity. Conclusions Intra-amniotic infection/inflammation is associated with elevated amniotic fluid HMGB1 concentrations regardless of membrane status; preterm PROM was associated with a higher amniotic fluid HMGB1 concentration than PTL with intact membranes, suggesting that rupture of membranes is associated with an elevation of alarmins; immunoreactive HMGB1 was localized to amnion epithelial cells, Wharton’s jelly and cells involved in the innate immune response; and we propose that HMGB1 released from stress or injured cells into amniotic fluid may be responsible, in part, for intra-amniotic inflammation due to non-microbial insults. PMID:21958433

Utilization of fetal fibronectin testing and pregnancy outcomes among women with symptoms of preterm labor.

PubMed

Blackwell, Sean C; Sullivan, Erin M; Petrilla, Allison A; Shen, Xian; Troeger, Kathleen A; Byrne, James D

2017-01-01

To identify pregnant health plan members triaged through the emergency department (ED), including labor and delivery (ELD) units, with symptoms of preterm labor (PTL), and evaluate the use of fetal fibronectin (fFN) testing; and to calculate the rate of hospitalization and timing of delivery in relation to the ED visit. Retrospective cohort study using Medical Outcomes Research for Effectiveness and Economics Registry ® , a national multipayer claims database. A cohort of pregnant women evaluated in an ELD with a diagnosis of PTL from June 2012 through November 2015 was identified. The proportion of women with PTL who received fFN testing was calculated. A total of 23,062 patients met the criteria for inclusion in the study. The rate of fFN testing prior to delivery was 12.0%. Of the 23,062 patients included in the analysis, 75.9% were discharged home. Of those who were discharged from the emergency room, one in five went on to deliver within 3 days and almost 96% of this group was not screened for the presence of fFN. Of the remaining 24.1% of patients admitted to the hospital, 91.3% delivered during their stay. In a sensitivity analysis, the percentage of women who delivered within 3 days of the ELD encounter was lower for women who received fFN testing only (6.6%) versus those who had a history of transvaginal ultrasound (TVUS) only (21.6%). Furthermore, the rate of delivery within 3 days was lowest among patients who had both fFN testing and TVUS (4.7%). The utilization of fFN testing is 12%. The majority of pregnant patients triaged through the ELD with symptomatic PTL do not receive an fFN test. As part of PTL evaluation, fFN testing may identify women at increased risk for preterm delivery and help determine appropriate patient management.

Utilization of fetal fibronectin testing and pregnancy outcomes among women with symptoms of preterm labor

PubMed Central

Blackwell, Sean C; Sullivan, Erin M; Petrilla, Allison A; Shen, Xian; Troeger, Kathleen A; Byrne, James D

2017-01-01

Objectives To identify pregnant health plan members triaged through the emergency department (ED), including labor and delivery (ELD) units, with symptoms of preterm labor (PTL), and evaluate the use of fetal fibronectin (fFN) testing; and to calculate the rate of hospitalization and timing of delivery in relation to the ED visit. Methods Retrospective cohort study using Medical Outcomes Research for Effectiveness and Economics Registry®, a national multipayer claims database. A cohort of pregnant women evaluated in an ELD with a diagnosis of PTL from June 2012 through November 2015 was identified. The proportion of women with PTL who received fFN testing was calculated. Results A total of 23,062 patients met the criteria for inclusion in the study. The rate of fFN testing prior to delivery was 12.0%. Of the 23,062 patients included in the analysis, 75.9% were discharged home. Of those who were discharged from the emergency room, one in five went on to deliver within 3 days and almost 96% of this group was not screened for the presence of fFN. Of the remaining 24.1% of patients admitted to the hospital, 91.3% delivered during their stay. In a sensitivity analysis, the percentage of women who delivered within 3 days of the ELD encounter was lower for women who received fFN testing only (6.6%) versus those who had a history of transvaginal ultrasound (TVUS) only (21.6%). Furthermore, the rate of delivery within 3 days was lowest among patients who had both fFN testing and TVUS (4.7%). Conclusion The utilization of fFN testing is 12%. The majority of pregnant patients triaged through the ELD with symptomatic PTL do not receive an fFN test. As part of PTL evaluation, fFN testing may identify women at increased risk for preterm delivery and help determine appropriate patient management. PMID:29042802

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.

A hemolytic pigment of Group B Streptococcus allows bacterial penetration of human placenta

PubMed Central

Whidbey, Christopher; Harrell, Maria Isabel; Burnside, Kellie; Ngo, Lisa; Becraft, Alexis K.; Iyer, Lakshminarayan M.; Aravind, L.; Hitti, Jane

2013-01-01

Microbial infection of the amniotic fluid is a significant cause of fetal injury, preterm birth, and newborn infections. Group B Streptococcus (GBS) is an important human bacterial pathogen associated with preterm birth, fetal injury, and neonatal mortality. Although GBS has been isolated from amniotic fluid of women in preterm labor, mechanisms of in utero infection remain unknown. Previous studies indicated that GBS are unable to invade human amniotic epithelial cells (hAECs), which represent the last barrier to the amniotic cavity and fetus. We show that GBS invades hAECs and strains lacking the hemolysin repressor CovR/S accelerate amniotic barrier failure and penetrate chorioamniotic membranes in a hemolysin-dependent manner. Clinical GBS isolates obtained from women in preterm labor are hyperhemolytic and some are associated with covR/S mutations. We demonstrate for the first time that hemolytic and cytolytic activity of GBS is due to the ornithine rhamnolipid pigment and not due to a pore-forming protein toxin. Our studies emphasize the importance of the hemolytic GBS pigment in ascending infection and fetal injury. PMID:23712433

H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition

PubMed Central

Nancy, Patrice; Siewiera, Johan; Tagliani, Elisa; Osokine, Ivan; Manandhar, Priyanka; Clementi, Caterina

2017-01-01

Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a noncontractile state until term and then surmounts this state to enter labor. Here, we show that dynamic generation and erasure of the repressive histone modification tri-methyl histone H3 lysine 27 (H3K27me3) in decidual stromal cells dictate both elements of pregnancy success in mice. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets ensured uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and most unexpectedly, generating myofibroblasts and associated wound-healing responses. In late gestation, genome-wide H3K27 demethylation allowed for target gene upregulation, decidual activation, and labor entry. Pharmacological inhibition of H3K27 demethylation in late gestation not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a noninflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders. PMID:29202469

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.

Patient satisfaction and psychological well-being after internet-based cognitive behavioral stress management (IB-CBSM) for women with preterm labor: A randomized controlled trial.

PubMed

Scherer, S; Alder, J; Gaab, J; Berger, T; Ihde, K; Urech, C

2016-01-01

Despite its value for the management of psychological burden, little is known about the efficacy of and patient satisfaction with internet-based cognitive behavioral stress management (IB-CBSM) for women with preterm labor. The present study sets out to analyze stress/anxiety reduction, patient satisfaction and patient's working alliance in a group of 58 women with preterm labor participating in an online psychological stress management project. As part of the project, women were randomly assigned to online stress management or a control condition. Levels of stress and anxiety decreased significantly in both conditions from pre- to post-treatment measure. Participants in IB-CBSM reported significant higher working alliance inventory (WAI) scores in the task and goal subscale (p<.001; p<.05) than women in the control condition. In Addition the IB-CBSM group showed significant correlations of the WAI subscale task and goal and the stress/anxiety outcome. Regarding patient satisfaction, women in the IB-CBSM reported significantly higher satisfaction scores (p<.001) than women in the control condition. WAI explained nearly 40% of the variance in patient satisfaction. Furthermore, WAI mediates, at least in part, the relationship between group condition and patient satisfaction. The current analysis indicated that participants in IB-CBSM had higher WAI scores and were more satisfied with the program. In addition only the IB-CBSM group showed significant correlations of the WAI with the stress/anxiety reduction outcome. Based on these findings, it can be presumed that measures of agreement with working alliance parameters, especially task and goal components, are substantially important for more effective and satisfactory therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Determination of nifedipine in serum of women in preterm labor by high-performance liquid chromatography with diode array detection.

PubMed

Kowalczuk, Dorota; Wawrzycka, Maria Bozena; Haratym Maj, Agnieszka

2006-01-01

Nifedipine (Nif) is widely used in treating cardiovascular disorders (especially hypertension) and for inhibiting preterm labor. A fully validated selective high-performance liquid chromatographic method with diode array detection, using solid-phase extraction, was developed for the determination of Nif in human serum. To assess specificity, Nif and its degradation products were separated on a Purospher RP-18 (5 microm, 125 x 4 mm) column plus a LiChrospher 100 RP-18 (5 microm, 4 x 4 mm) precolumn with a mobile phase of methanol-10 mM aqueous trifluoroacetic acid, pH 7.3 (57 + 43, v/v); chromatographic separation was followed by UV detection at 238 nm. For toxicological analysis, Nif in the presence of other calcium-channel antagonist drugs was identified under optimum chromatographic conditions. The calibration graph was constructed over the concentration range of 12.5-400 ng/mL in serum with good correlation (r = 0.9956). This method was not subject to interference by other plasma components and was successfully applied to the assay of Nif in spiked human serum and in serum of women in preterm labor after sublingual administration of 30 mg Nif per day divided into 3 equal doses. The mean recovery based on the ratio of the slopes of serum and mobile phase standard curves was 96.5%. The detection and quantification limits of the drug in spiked human serum were found to be 6 and 17.5 ng/mL, respectively. Validation of the method demonstrated good intraday and interday precision, which ranged from 2.18 to 6.67% and from 6.52 to 11.93%, respectively.

CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor.

PubMed

Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Docheva, Nikolina; Dong, Zhong; Kim, Chong Jai; Kim, Yeon Mee; Kim, Jung-Sun; Qureshi, Faisal; Jacques, Suzanne M; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S; Erez, Offer; Korzeniewski, Steven J

2017-07-01

To determine whether amniotic fluid (AF) CXCL10 concentration is associated with histologic chronic chorioamnionitis in patients with preterm labor (PTL) and preterm prelabor rupture of the membranes (PROM). This study included 168 women who had an episode of PTL or preterm PROM. AF interleukin (IL)-6 and CXCL10 concentrations were determined by immunoassay. (i) Increased AF CXCL10 concentration was associated with chronic (OR: 4.8; 95% CI: 1.7-14), but not acute chorioamnionitis; (ii) increased AF IL-6 concentration was associated with acute (OR: 4.2; 95% CI: 1.3-13.7) but not chronic chorioamnionitis; and (iii) an increase in AF CXCL10 concentration was associated with placental lesions consistent with maternal anti-fetal rejection (OR: 3.7; 95% CI: 1.3-10.4). (iv) All patients with elevated AF CXCL10 and IL-6 delivered preterm. Increased AF CXCL10 concentration is associated with chronic chorioamnionitis or maternal anti-fetal rejection, whereas increased AF IL-6 concentration is associated with acute histologic chorioamnionitis. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.

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.

Racial Differences in DNA-Methylation of CpG Sites Within Preterm-Promoting Genes and Gene Variants.

PubMed

Salihu, H M; Das, R; Morton, L; Huang, H; Paothong, A; Wilson, R E; Aliyu, M H; Salemi, J L; Marty, P J

2016-08-01

Objective To evaluate the role DNA methylation may play in genes associated with preterm birth for higher rates of preterm births in African-American women. Methods Fetal cord blood samples from births collected at delivery and maternal demographic and medical information were used in a cross-sectional study to examine fetal DNA methylation of genes implicated in preterm birth among black and non-black infants. Allele-specific DNA methylation analysis was performed using a methylation bead array. Targeted maximum likelihood estimation was applied to examine the relationship between race and fetal DNA methylation of candidate preterm birth genes. Receiver-operating characteristic analyses were then conducted to validate the CpG site methylation marker within the two racial groups. Bootstrapping, a method of validation and replication, was employed. Results 42 CpG sites were screened within 20 candidate gene variants reported consistently in the literature as being associated with preterm birth. Of these, three CpG sites on TNFAIP8 and PON1 genes (corresponding to: cg23917399; cg07086380; and cg07404485, respectively) were significantly differentially methylated between black and non-black individuals. The three CpG sites showed lower methylation status among infants of black women. Bootstrapping validated and replicated results. Conclusion for Practice Our study identified significant differences in levels of methylation on specific genes between black and non-black individuals. Understanding the genetic/epigenetic mechanisms that lead to preterm birth may lead to enhanced prevention strategies to reduce morbidity and mortality by eventually providing a means to identify individuals with a genetic predisposition to preterm labor.

Successful external cephalic version after amnioinfusion in a patient with preterm premature rupture of membranes.

PubMed

Buek, John D; McVearry, Ingrid; Lim, Elaine; Landy, Helain; Afriyie-Gray, Akua

2005-06-01

After hospitalization subsequent to preterm premature rupture of membranes at 29 weeks, our patient was scheduled for induction of labor at 34 weeks. When the fetus was found to be breech with oligohydramnios, amnioinfusion was performed to facilitate external cephalic version, and this successful procedure enabled the patient to deliver vaginally.

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).

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.

Comparison of the effectiveness of a PAMG-1 test and standard clinical assessment in the prediction of preterm birth and reduction of unnecessary hospital admissions.

PubMed

Lotfi, Ghassan; Faraz, Saima; Nasir, Razan; Somini, Sreenisha; Abdeldayem, Rasha M; Koratkar, Raghunandini; Alsawalhi, Nadia; Ammar, Abeer

2017-10-26

The purpose of this study is to first compare the performance of the PAMG-1 biomarker test to that of standard clinical assessment (SCA) for the risk assessment of spontaneous preterm delivery (sPTD) among women with symptoms of preterm labor (PTL) and then calculate the potential impact on unnecessary admission reduction. Patients of gestational age 24 0/7 -36 6/7 with PTL symptoms, cervical dilatation ≤3 cm, no intercourse within 24 h, and clinically intact membranes were recruited consecutively into this prospective observational study. Specificity (SP), sensitivity (SN), positive-predictive value (PPV), and negative-predictive value (NPV) for the PAMG-1 test and SCA, for which a positive result was defined as patient admission, for predicting spontaneous delivery ≤7 and ≤14 d of presentation were calculated. One hundred and forty-eight patients were included in the analysis, 132 of which had both SCA and PAMG-1 results available. For the prediction of sPTD ≤7 d for SCA and PAMG-1, the PPV and NPV were 10% and 100%, and 71% and 98%, respectively. For prediction of sPTD ≤14 d for SCA and PAMG-1, the PPV and NPV were 14% and 100%, and 86% and 96%, respectively. Sixty-one per cent (81/132) of patients were admitted for treatment and/or observation. Our study reinforces the critical role of the PAMG-1 biomarker test to aid in risk assessment of imminent spontaneous preterm delivery in patients with symptoms of PTL. The PAMG-1 test was found to be statistically superior to standard clinical assessment alone, with respect to specificity. Based on our data, the introduction of a PAMG-1 test result into clinical decision making could reduce up to 91% of unnecessary admissions for women presenting with threatened preterm labor.

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.

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

Paternal and maternal birthweights and the risk of infant preterm birth.

PubMed

Klebanoff, Mark A

2008-01-01

Increasing paternal birthweight has been associated with increased risk of fathering a preterm infant, causing speculation that a fetus programmed to grow rapidly can trigger preterm labor. Pregnancies occurring from 1974-1989 among women themselves born in the Danish Perinatal Study (1959-1961) were identified through the Population Register; obstetric records were abstracted. Paternal birthweight was obtained by linking Personal Identification Numbers of the fathers to archived midwifery records. Paternal birthweight was not associated with preterm infants overall. However, there was a significant interaction between paternal and maternal birthweights (P = .003). When the mother weighed less than 3 kg at birth, increasing paternal birthweight was associated with increased occurrence of preterm birth (P for trend = .02); paternal birthweight was unassociated with preterm birth for mothers weighing 3 kg or more at birth (P = .34). When the mother was born small, increasing paternal birthweight was associated with increased risk of preterm birth, suggesting that a fetus growing faster than its mother can accommodate might trigger preterm birth.

Mitochondrial MnSOD mRNA expression in human chorioamniotic membranes and its association with labor, inflammation and infection

PubMed Central

Than, Nandor Gabor; Romero, Roberto; Tarca, Adi L.; Draghici, Sorin; Erez, Offer; Chaiworapongsa, Tinnakorn; Kim, Yeon Mee; Kim, Sun Kwon; Vaisbuch, Edi; Tromp, Gerard

2010-01-01

Objective Human parturition is characterized by the activation of genes involved in acute inflammatory in the fetal membranes. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that scavenges reactive oxygen species (ROS). MnSOD is up-regulated in sites of inflammation and has an important role in the down-regulation of acute inflammatory processes. Therefore, the aim of this study was to determine the differences in MnSOD mRNA expression in the fetal membranes in patients with term and preterm labor as well as in acute chorioamnionitis. Study design Fetal membranes were obtained from patients in the following groups: 1) term not in labor (n=29); 2) term in labor (n=29); 3) spontaneous preterm labor with intact mebranes (n=16); 4) PTL with histological chorioamnionitis (n=12); 5) preterm prelabor rupture of membranes (PPROM; n=17); and 6) PPROM with histological chorioamnionitis (n=21). MnSOD mRNA expression in the membranes was determined by quantitative real-time RT-PCR. Results 1) MnSOD mRNA expression was higher in the fetal membranes of patients at term in labor than those not in labor (2.4-fold; p=0.02); 2) the amount of MnSOD mRNA in the fetal membranes was higher in PTL than in term labor or in PPROM (7.2-fold, p=0.03; 3.2-fold, p=0.03, respectively); 3) MnSOD mRNA expression was higher when histological chorioamnionitis was present both among patients with PPROM (3.8-fold, p=0.02) and with PTL (5.4-fold, p=0.02) than in patients with these conditions without histological chorioamnionitis; 4) expression of MnSOD mRNA was higher in PTL with chorioamnionitis than in PPROM with chorioamnionitis (4.3-fold, p=0.03); Conclusion The increase in MnSOD mRNA expression by fetal membranes in term labor and in histological chorioamnionitis in PTL and PPROM suggests that the fetus deploys anti-oxidant mechanisms to constrain the inflammatory processes in the chorioamniotic membranes. PMID:19900038

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

Molecular Regulation of Parturition: The Role of the Decidual Clock.

PubMed

Norwitz, Errol R; Bonney, Elizabeth A; Snegovskikh, Victoria V; Williams, Michelle A; Phillippe, Mark; Park, Joong Shin; Abrahams, Vikki M

2015-04-27

The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a "parturition cascade" exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a "placental clock." We suggest that it is not a placental clock that regulates the timing of birth, but rather a "decidual clock." Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Molecular Regulation of Parturition: The Role of the Decidual Clock

PubMed Central

Norwitz, Errol R.; Bonney, Elizabeth A.; Snegovskikh, Victoria V.; Williams, Michelle A.; Phillippe, Mark; Park, Joong Shin; Abrahams, Vikki M.

2015-01-01

The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a “parturition cascade” exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a “placental clock.” We suggest that it is not a placental clock that regulates the timing of birth, but rather a “decidual clock.” Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. PMID:25918180

Prevention of preterm birth: harnessing science to address the global epidemic.

PubMed

Rubens, Craig E; Sadovsky, Yoel; Muglia, Louis; Gravett, Michael G; Lackritz, Eve; Gravett, Courtney

2014-11-12

Preterm birth is a leading cause of infant morbidity and mortality worldwide, but current interventions to prevent prematurity are largely ineffective. Preterm birth is increasingly recognized as an outcome that can result from a variety of pathological processes. Despite current research efforts, the mechanisms underlying these processes remain poorly understood and are influenced by a range of biological and environmental factors. Research with modern techniques is needed to understand the mechanisms responsible for preterm labor and birth and identify targets for diagnostic and therapeutic solutions. This review evaluates the state of reproductive science relevant to understanding the causes of preterm birth, identifies potential targets for prevention, and outlines challenges and opportunities for translating research findings into effective interventions. Copyright © 2014, American Association for the Advancement of Science.

Successful magnesium sulfate tocolysis: is "weaning" the drug necessary?

PubMed

Lewis, D F; Bergstedt, S; Edwards, M S; Burlison, S; Gallaspy, J W; Brooks, G G; Adair, C D

1997-10-01

Magnesium sulfate is the most commonly used tocolytic agent for preterm labor. A common clinical practice is to slowly discontinue the drug (wean) after successful tocolysis. Our objective was to determine the necessity of this practice. A prospective, randomized clinical trial was performed from June 1993 to July 1996. After successful magnesium sulfate tocolysis, patients with preterm labor were randomized to two groups: stopping the drug abruptly (no weaning) or gradually weaning the drug (approximately 1 gm every 4 hours). Preterm labor was defined as documented cervical change with regular uterine contractions or regular uterine contractions with a cervix of 2 cm and 75% effacement. The primary outcome variable was the necessity to reinstitute magnesium sulfate therapy within 24 hours of discontinuation of successful tocolysis. One hundred forty-one patients completed the study. No patient in the no-wean group required retocolysis within 24 hours of magnesium discontinuation. However, eight patients in the wean group required retocolysis within 24 hours of magnesium discontinuation (p = 0.01). Significantly more patients in the wean group had retocolysis during pregnancy (3 vs 12, p = 0.03). Patients in the wean group were also in the labor and delivery unit longer and, as would be anticipated, received magnesium sulfate significantly longer. No differences in the neonatal outcomes were noted between the two groups. Seventy-seven percent of the patients in the study were delivered prematurely. This study demonstrated an increased need for retocolysis in the group weaned from magnesium sulfate. We also found that patients in the wean group had an increased labor and delivery time and a longer administration time of magnesium sulfate. Thus weaning magnesium sulfate increases health care cost. The practice of weaning magnesium sulfate does not appear beneficial.

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.

Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth

PubMed Central

Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica; Merillat, Sean; Whidbey, Christopher; Ngo, Lisa Y.; Adams Waldorf, K. M.

2016-01-01

ABSTRACT Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae. However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. PMID:27353757

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.

Prevalence and Clinical Significance of Sterile Intra-amniotic Inflammation in Patients with Preterm Labor and Intact Membranes

PubMed Central

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Yoon, Bo Hyun; Hassan, Sonia S.; Kim, Chong J.; Yeo, Lami

2014-01-01

Problem Inflammation and infection play a major role in preterm birth. The purpose of this study was to: 1) determine the prevalence and clinical significance of sterile intra-amniotic inflammation; and 2) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis-to-delivery in patients with sterile intra-amniotic inflammation. Method of Study AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). Results 1) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) vs. 11% (15/135); (p=0.005)]; 2) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages, had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation; and 3) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥ 8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (p=0.02). Conclusions 1) sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation; and 2) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor. PMID:25078709

Successful tocolysis: does cervical change affect time to delivery?

PubMed

Lewis, D F; Gallaspy, J W; Fontenot, M T; Burlison, R D; Imseis, J M; Edwards, M S

1997-11-01

Generally, it is preferable to tocolyze patients with idiopathic preterm labor (PTL). Little information is available about ultimate outcomes after successful tocolysis. Our objective is to evaluate the relationship between cervical change after the initiation of tocolysis and the delay in time to delivery in patients with preterm labor. A historical analysis of all patients with successful tocolysis after PTL between January 1992 and December 1993 was undertaken. The patients were then placed in one of three categories (regression, unchanged, or progression) based on cervical change after the initiation of tocolysis. Various demographic pregnancy characteristics and pregnancy outcome data were analyzed. One hundred and twenty-six patients had successful tocolysis and met the admission criteria. Patients who had cervical progression had shorter delay to delivery, delivered at an earlier gestational age (31.7 weeks compared to 34.0 and 34.1 weeks, respectively, p < 0.05), and were more likely to deliver before 35 weeks (88% compared to 50.0 and 55.0%, respectively, p < 0.05). Also, neonates remained in the hospital longer and were more likely to have respiratory distress syndrome when compared to the other two groups. Patients who had cervical progression after the initiation of tocolysis are more likely to deliver prematurely, had a shorter delay to delivery, and delivered lower birth weight infants than did patients whose cervix regressed or remained unchanged. In our population, patients who had successful tocolysis had a preterm delivery rate of 59.5% before the 35th week of gestation.

Impact of Intended Mode of Delivery on Outcomes in Preterm Growth-Restricted Fetuses.

PubMed

Baalbaki, Sima H; Kuper, Spencer G; Wang, Michelle J; Steele, Robin A; Biggio, Joseph R; Harper, Lorie M

2018-06-01

 Scheduled cesarean is frequently performed for fetal growth restriction due to concerns for fetal intolerance of labor.  We compared neonatal outcomes in preterm growth-restricted fetuses by intended mode of delivery.  We performed a retrospective cohort study of indicated preterm births with prenatally diagnosed growth restriction from 2011 to 2014 at a single institution. Patients were classified by intended mode of delivery. The primary outcome was a composite of adverse neonatal outcomes, including perinatal death, cord blood acidemia, chest compressions during neonatal resuscitation, seizures, culture-proven sepsis, necrotizing enterocolitis, and grade III-IV intraventricular hemorrhage. Secondary analysis was performed examining the impact of umbilical artery Dopplers.  Of 101 fetuses with growth restriction, 75 underwent planned cesarean deliveries. Of those induced, 46.2% delivered vaginally. Delivery by scheduled cesarean was not associated with a decreased risk of the composite outcome (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 0.45-5.78), even when only those with abnormal umbilical artery Dopplers were considered (aOR, 2.8; 95% CI, 0.40-20.2).  In this cohort, planned cesarean was not associated with a reduction in neonatal morbidity, even when considering only those with abnormal umbilical artery Dopplers. In otherwise appropriate candidates for vaginal delivery, fetal growth restriction should not be considered a contraindication to trial of labor. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of Pregnancy on the Army Physical Fitness Test

DTIC Science & Technology

2003-05-01

preeclampsia , and premature labor (Lombardi, Wilson, Peniston, 1999). The most relevant finding was that women who exercised during pregnancy retained...preterm labor, pregnancy induced hypertension, preeclampsia , deep vein thrombosis, premature contractions, or intrauterine growth retardation. (Table...fetal distress, low forceps delivery, pregnancy induced hypertension, preeclampsia , nuchal cord, oligohydramnios, hyperemesis, anemia, and

[Management of pre-term labor: use of nifedipine in Conakry, Guinea].

PubMed

Sy, T; Diallo, F B; Diallo, Y; Camara, M K; Diallo, A; Cissoko, M; Lontsi, G R; Diallo, M S

2010-04-01

This purpose of this prospective and descriptive study was to evaluate the utility of a calcium-channel inhibitor, i.e. nifedipine, for management of preterm labor in our work setting in terms of safety and cost-effectiveness in comparison with betamimetics classically used for this indication. Study was carried out over a six-month period in the department of Gynecology-Obstetrics Department of Ignace Deen National Hospital in Conakry, Guinea. Pregnant women meeting the following criteria were included: 28 to 33 weeks of amenorrhea, six days of hospitalization either for preterm labor or for another diagnosis that was associated with the occurrence of preterm labor during hospitalization, and absence of contraindications for tocolysis using nifedipine. A total of 42 women were included. Pregnancy was extended for more than 48 hours after the first dose of nifedipine in 86.8% of cases. Administration of nifedipine failed in 5 cases including one case in which it was necessary to change the tocolytic and 4 cases in which delivery occurred less than 48 hours after the first dose of nifedipine. In 68% of cases, 90 mg of nifedipine were sufficient to stop uterine contractions within 48 hours. In 39.5% of cases, no side effects were observed. Adverse effects in the other cases were dizziness (39.5%) and headache (18.4%). The mean term of delivery was 36 weeks +/- 5 days of amenorrhea with a mean extension of 6.2 weeks. Apgar score was low in 30.5% of the newborns and normal in 69.5%. One newborn (2.8%) died. The results of this study indicate that nifedipine is an effective, economical and safe drug for tocolysis and that it can be used as an alternative to betamimetis in countries with limited resources. An information campaign is needed to promote use of nifedipine as a tocolytic in obstetrical facilities of our country.

Residential proximity to major roads and obstetrical complications.

PubMed

Yorifuji, Takashi; Naruse, Hiroo; Kashima, Saori; Murakoshi, Takeshi; Doi, Hiroyuki

2015-03-01

Exposure to air pollution is linked with an increased risk of preterm births. To provide further evidence on this relationship, we evaluated the association between proximity to major roads--as an index for air pollution exposure--and various obstetrical complications. Data were extracted from a database maintained by the perinatal hospital in Shizuoka, Japan. We restricted the analysis to mothers with singleton pregnancies of more than 22 weeks of gestation from 1997 to 2012 (n=19,077). Using the geocoded residential information, each mother was assigned proximity to major roads. We then estimated multivariate adjusted odds ratios and their 95% confidence intervals (CIs) for the effects of proximity to major roads on various obstetrical complications (preeclampsia, gestational diabetes mellitus, placenta abruption, placenta previa, preterm premature rupture of membrane (pPROM), preterm labor, and preterm births). We found positive associations of proximity to major roads with preeclampsia and pPROM. Living within 200 m increased the odds of preeclampsia by 1.3 times (95% CI, 1.0-1.8) and pPROM by 1.6 times (95% CI, 1.1-2.2). Furthermore, living within 200 m increased the odds of preterm births by 1.4 fold (95% CI, 1.2-1.7). Exposure to traffic-related air pollution increased the risk of preeclampsia and pPROM in this study. We propose a mechanism responsible for the association between air pollution and preterm births. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes.

PubMed

Combs, C Andrew; Garite, Thomas J; Lapidus, Jodi A; Lapointe, Jerome P; Gravett, Michael; Rael, Julie; Amon, Erol; Baxter, Jason K; Brady, Kim; Clewell, William; Eddleman, Keith A; Fortunato, Stephen; Franco, Albert; Haas, David M; Heyborne, Kent; Hickok, Durlin E; How, Helen Y; Luthy, David; Miller, Hugh; Nageotte, Michael; Pereira, Leonardo; Porreco, Richard; Robilio, Peter A; Simhan, Hyagriv; Sullivan, Scott A; Trofatter, Kenneth; Westover, Thomas

2015-04-01

Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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.

The Interaction Between Chronic Stress and Pregnancy: Preterm Birth from A Biobehavioral Perspective

PubMed Central

Latendresse, Gwen

2009-01-01

Women's health care providers are increasingly aware that chronic stressors—such as poverty, ongoing perceived stress and anxiety, intimate partner violence, and experiences of racism—are associated with an increased incidence of preterm birth in the United States. It is important to increase our understanding of the explanatory pathways involved in these associations. This article discusses the concepts of stress, chronic stress response, allostatic load, the physiology of labor initiation, and the pathophysiologic interactions that may contribute to the occurrence of chronic stress-related preterm birth. Implications for future research and interventions are explored. PMID:19114234

Is Sonographic Assessment of the Cervix Necessary and Helpful?

PubMed Central

Larma, Joel D.; Iams, Jay D.

2012-01-01

Transvaginal sonography of the cervix has emerged as a useful window onto preterm parturition. Cervical sonography allows measurements of cervical length which can aid clinicians in identifying women at risk for preterm birth. The use of transvaginal assessments of cervical length can assist in the triage of patients with possible preterm labor. Recent studies also support the use of cervical length measurements as a means of determining appropriate candidates for cerclage placement and progesterone supplementation to reduce the risk of premature birth, further highlighting the importance of this modality in modern obstetric management. PMID:22343248

Prostaglandin dehydrogenase is a target for successful induction of cervical ripening

PubMed Central

Kishore, Annavarapu Hari; Liang, Hanquan; Xing, Chao; Ganesh, Thota; Akgul, Yucel; Posner, Bruce; Ready, Joseph M.; Markowitz, Sanford D.; Word, Ruth Ann

2017-01-01

The cervix represents a formidable structural barrier for successful induction of labor. Approximately 10% of pregnancies undergo induction of cervical ripening and labor with prostaglandin (PG) E2 or PGE analogs, often requiring many hours of hospitalization and monitoring. On the other hand, preterm cervical ripening in the second trimester predicts preterm birth. The regulatory mechanisms of this paradoxical function of the cervix are unknown. Here, we show that PGE2 uses cell-specific EP2 receptor-mediated increases in Ca2+ to dephosphorylate and translocate histone deacetylase 4 (HDAC4) to the nucleus for repression of 15-hydroxy prostaglandin dehydrogenase (15-PGDH). The crucial role of 15-PGDH in cervical ripening was confirmed in vivo. Although PGE2 or 15-PGDH inhibitor alone did not alter gestational length, treatment with 15-PGDH inhibitor + PGE2 or metabolism-resistant dimethyl-PGE2 resulted in preterm cervical ripening and delivery in mice. The ability of PGE2 to selectively autoamplify its own synthesis in stromal cells by signaling transcriptional repression of 15-PGDH elucidates long sought-after molecular mechanisms that govern PG action in the cervix. This report details unique mechanisms of action in the cervix and serves as a catalyst for (i) the use of 15-PGDH inhibitors to initiate or amplify low-dose PGE2-mediated cervical ripening or (ii) EP2 receptor antagonists, HDAC4 inhibitors, and 15-PGDH activators to prevent preterm cervical ripening and preterm birth. PMID:28716915

The genomics of preterm birth: from animal models to human studies

PubMed Central

2013-01-01

Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of infant mortality worldwide. So far, the application of animal models to understand human birth timing has not substantially revealed mechanisms that could be used to prevent prematurity. However, with amassing data implicating an important role for genetics in the timing of the onset of human labor, the use of modern genomic approaches, such as genome-wide association studies, rare variant analyses using whole-exome or genome sequencing, and family-based designs, holds enormous potential. Although some progress has been made in the search for causative genes and variants associated with preterm birth, the major genetic determinants remain to be identified. Here, we review insights from and limitations of animal models for understanding the physiology of parturition, recent human genetic and genomic studies to identify genes involved in preterm birth, and emerging areas that are likely to be informative in future investigations. Further advances in understanding fundamental mechanisms, and the development of preventative measures, will depend upon the acquisition of greater numbers of carefully phenotyped pregnancies, large-scale informatics approaches combining genomic information with information on environmental exposures, and new conceptual models for studying the interaction between the maternal and fetal genomes to personalize therapies for mothers and infants. Information emerging from these advances will help us to identify new biomarkers for earlier detection of preterm labor, develop more effective therapeutic agents, and/or promote prophylactic measures even before conception. PMID:23673148

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.

Impact of microbial invasion of amniotic cavity and the type of microorganisms on short-term neonatal outcome in women with preterm labor and intact membranes.

PubMed

Cobo, Teresa; Vives, Irene; Rodríguez-Trujillo, Adriano; Murillo, Clara; Ángeles, Martina A; Bosch, Jordi; Vergara, Andrea; Gratacós, Eduard; Palacio, Montse

2017-05-01

The objective of this study was to evaluate the impact of microbial invasion of the amniotic cavity and the type of microorganisms on pregnancy and short-term neonatal outcomes in women with preterm labor. Prospective observational cohort study including women with preterm labor from 22.0 to 36.0 weeks. Microbial invasion of the amniotic cavity was defined based on amniotic fluid aerobic/anaerobic/mycoplasma cultures, and intra-amniotic inflammation on amniotic fluid interleukin-6 levels. Demographic data and pregnancy outcomes were compared among women exposed to microbial invasion of the amniotic cavity by Ureaplasma spp., women with microbial invasion of the amniotic cavity by other microorganisms, and a No-microbial invasion of the amniotic cavity/No-intra-amniotic inflammation group. The short-term neonatal outcome was evaluated in women delivering after 24.0 weeks. We included 228 women with preterm labor. Microbial invasion of the amniotic cavity occurred in 35% (80/228), 28% (22/80) being caused by Ureaplasma spp. Gestational age at admission and at delivery were significantly earlier and the rate of delivery at <24.0 weeks' gestation and of women who further developed clinical chorioamnionitis were significantly higher in women with microbial invasion of the amniotic cavity by microorganisms other than Ureaplasma spp. However, after 24 weeks, regardless of the microorganisms isolated, the short-term neonatal outcome was similar between women exposed to microbial invasion of the amniotic cavity and the No-microbial invasion of the amniotic cavity/No-intra-amniotic inflammation group when gestational age was considered. Microbial invasion of the amniotic cavity by microorganisms other than Ureaplasma spp. was associated with earlier gestational age at admission and at delivery, and a higher rate of preterm delivery <24.0 weeks and of women who developed clinical chorioamnionitis. However, we did not find differences in the short-term neonatal outcome between women exposed to microbial invasion of the amniotic cavity and the no-microbial invasion of the amniotic cavity/no-intra-amniotic inflammation group delivering after 24.0 weeks' gestation when adjusted by gestational age at delivery. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1).

PubMed

Madaan, Ankush; Nadeau-Vallée, Mathieu; Rivera, Jose Carlos; Obari, Dima; Hou, Xin; Sierra, Estefania Marin; Girard, Sylvie; Olson, David M; Chemtob, Sylvain

2017-01-01

Uterine inflammatory processes trigger prolabor pathways and orchestrate on-time labor onset. Although essential for successful labor, inflammation needs to be regulated to avoid uncontrolled amplification and resolve postpartum. During labor, myometrial smooth muscle cells generate ATP mainly via anaerobic glycolysis, resulting in accumulation of lactate. Aside from its metabolic function, lactate has been shown to activate a G protein-coupled receptor, GPR81, reported to regulate inflammation. We therefore hypothesize that lactate produced during labor may act via GPR81 in the uterus to exert in a feedback manner antiinflammatory effects, to resolve or mitigate inflammation. We sought to investigate the role of lactate produced during labor and its receptor, GPR81, in regulating inflammation in the uterus. We investigated the expression of GPR81 in the uterus and the pharmacological role of lactate acting via GPR81 during labor, using shRNA-GPR81 and GPR81 -/- mice. (1) Uterine lactate levels increased substantially from 2 to 9 mmol/L during labor. (2) Immunohistological analysis revealed expression of GPR81 in the uterus with high expression in myometrium. (3) GPR81 expression increased during gestation, and peaked near labor. (4) In primary myometrial smooth muscle cell and ex vivo uteri from wild-type mice, lactate decreased interleukin-1β-induced transcription of key proinflammatory Il1b, Il6, Ccl2, and Pghs2; suppressive effects of lactate were not observed in cells and tissues from GPR81 -/- mice. (5) Conversely, proinflammatory gene expression was augmented in the uterus at term in GPR81 -/- mice and wild-type mice treated intrauterine with lentiviral-encoded shRNA-GPR81; GPR81 silencing also induced proinflammatory gene transcription in the uterus when labor was induced by endotoxin (lipopolysaccharide). (6) Importantly, administration to pregnant mice of a metabolically stable specific GPR81 agonist, 3,5-dihydroxybenzoic acid, decreased endotoxin-induced uterine inflammation, preterm birth, and associated neonatal mortality. Collectively, our data uncover a novel link between the anaerobic glycolysis and the control of uterine inflammation wherein the high levels of lactate produced during labor act on uterine GPR81 to down-regulate key proinflammatory genes. This discovery may represent a novel feedback mechanism to regulate inflammation during labor, and conveys a potential rationale for the use of GPR81 agonists to attenuate inflammation and resulting preterm birth. Copyright © 2016 Elsevier Inc. All rights reserved.

Ethanol for preventing preterm birth in threatened preterm labor.

PubMed

Haas, David M; Morgan, Amanda M; Deans, Samantha J; Schubert, Frank P

2015-11-05

Preterm birth is the leading cause of death and disability in newborns worldwide. A wide variety of tocolytic agents have been utilized to delay birth for women in preterm labor. One of the earliest tocolytics utilized for this purpose was ethanol infusion, although this is not generally used in current practice due to safety concerns for both the mother and her baby. To determine the efficacy of ethanol in stopping preterm labor, preventing preterm birth, and the impact of ethanol on neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved studies. We included randomized and quasi-randomized studies. Cluster-randomized trials and cross-over design trials were not eligible for inclusion. We only included studies published in abstract form if there was enough information on methods and relevant outcomes. Trials were included if they compared ethanol infusion to stop preterm labor versus placebo/control or versus other tocolytic drugs. At least two review authors independently assessed studies for inclusion and risk of bias. At least two review authors independently extracted data. Data were checked for accuracy. Twelve trials involving 1586 women met inclusion criteria for this review. One trial did not report on the outcomes of interest in this review.Risk of bias of included studies: The included studies generally were of low quality based on inadequate reporting of methodology. Only three trials had low risk of bias for random sequence generation and one had low risk of bias for allocation concealment and participant blinding. Most studies were either high risk of bias or uncertain in these key areas. Comparison 1: Ethanol versus placebo/control (two trials, 77 women) Compared to controls receiving pain medications and dextrose solution, ethanol did not improve any of the primary outcomes: birth < 48 hours after trial entry (one trial, 35 women; risk ratio (RR) 0.93, 95% confidence interval (CI) 0.43 to 2.00), or neonatal mortality (one trial, 35 women; RR 1.06, 95% CI 0.31 to 3.58). Serious maternal adverse events and perinatal mortality were not reported by either of the two trials in this comparison. Maternal adverse events (overall) were not reported but one trial (42 women) reported that there were no maternal adverse events that required stopping or changing drug) in either group. One trial did report delay until delivery but this outcome was reported as a median with no mention of the standard deviation (median 19 days in ethanol group versus "less than 1" day in the glucose/water group). There were no differences in any secondary outcomes reported: preterm birth < 34 weeks or < 37 weeks; serious infant outcome; fetal alcohol syndrome/fetal alcohol spectrum disorder; or small-for-gestational age. Comparison 2: Ethanol versus other tocolytic (betamimetics) (nine trials, 1438 women) Compared to betamimetics (the only tocolytic used as a comparator in these studies), ethanol was associated with no clear difference in the rate of birth < 48 hours after trial entry (two trials, 130 women; average RR 1.12, 95% CI 0.53 to 2.37, Tau² = 0.19, I² = 59%), similar rates of perinatal mortality (six trials, 698 women; RR1.20, 95% CI 0.78 to 1.84), higher rates of neonatal mortality (eight trials, 1238 women; RR 1.43, 95% CI 1.02 to 2.02), higher rates of preterm birth < 34 weeks (two trials, 599 women; RR 1.56, 95% CI 1.11 to 2.19), higher rates of neonatal respiratory distress syndrome (three trials, 823 women; RR 1.76, 95% CI 1.33 to 2.33), and higher rates of low birthweight babies < 2500 g (five trials, 834 women; RR 1.30, 95% CI 1.09 to 1.54). These outcomes are likely all related to the lower incidence of preterm birth seen with other tocolytics, which for all these comparisons were betamimetics. Serious maternal adverse events were not reported in any of the nine trial reports. However, ethanol had a trend towards a lower rate of maternal adverse events requiring stopping or changing the drug (three trials, 214 women; RR 0.25, 95% CI 0.06 to 0.97). There were no differences in other secondary outcomes of preterm birth < 37 weeks, number of days delivery was delayed, or overall maternal adverse events.Planned sensitivity analysis, excluding quasi-randomized trials did not substantially change the results of the primary outcome analyses with the exception of neonatal mortality which no longer showed a clear difference between the ethanol and other tocolytic groups (3 trials, 330 women; RR 1.49, 95% CI 0.82 to 2.72). This review is based on evidence from twelve studies which were mostly low quality. There is no evidence that to suggest that ethanol is an effective tocolytic compared to placebo. There is some evidence that ethanol may be better tolerated than other tocolytics (in this case betamimetics), but this result is based on few studies and small sample size and therefore should be interpreted with caution. Ethanol appears to be inferior to betamimetics for preventing preterm birth in threatened preterm labor.Ethanol is generally no longer used in current practice due to safety concerns for the mother and her baby. There is no need for new studies to evaluate the use of ethanol for preventing preterm birth in threatened preterm labour. However, it would be useful for long-term follow-up studies on the babies born to mothers from the existing studies in order to assess the risk of long-term neurodevelopmental status.

Prevalence and clinical significance of sterile intra-amniotic inflammation in patients with preterm labor and intact membranes.

PubMed

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I; Yoon, Bo Hyun; Hassan, Sonia S; Kim, Chong Jai; Yeo, Lami

2014-11-01

Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra-amniotic inflammation and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box-1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra-amniotic inflammation. AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad-range PCR and mass spectrometry (PCR/ESI-MS). Sterile intra-amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra-amniotic inflammation (AF interleukin-6 ≥ 2.6 ng/mL). (i) The frequency of sterile intra-amniotic inflammation was significantly greater than that of microbial-associated intra-amniotic inflammation [26% (35/135) versus 11% (15/135); (P = 0.005)], (ii) patients with sterile intra-amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial-associated intra-amniotic inflammation, and (iii) patients with sterile intra-amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02). (i) Sterile intra-amniotic inflammation is more frequent than microbial-associated intra-amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra-amniotic inflammation in the setting of preterm labor. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Transdermal nitroglycerin for the treatment of preterm labor: a systematic review and metaanalysis.

PubMed

Conde-Agudelo, Agustín; Romero, Roberto

2013-12-01

The purpose of this study was to evaluate the efficacy and safety of transdermal nitroglycerin as a tocolytic agent in women with preterm labor. We conducted a systematic review and metaanalysis of randomized controlled trials. Thirteen studies were included (1302 women) comparing transdermal nitroglycerin vs placebo (2 studies; n = 186); β2-adrenergic receptor agonists (9 studies; n = 1024); nifedipine (1 study; n = 50); and magnesium sulfate (1 study; n = 42). There were no significant differences between transdermal nitroglycerin and placebo for delivery within 48 hours of the initiation of treatment or at <28, <34, or <37 weeks of gestation, adverse neonatal outcomes, and neurodevelopmental status at 24 months of life. Nevertheless, 1 study found a marginally significant reduction in the risk of a composite outcome of major neonatal morbidity and perinatal death (3/74 [4.1%] vs 11/79 [13.9%]; relative risk, 0.29; 95% confidence interval, 0.08-1.00). When compared with β2-adrenergic receptor agonists, transdermal nitroglycerin was associated with a significant reduction in the risk of preterm birth at <34 and <37 weeks of gestation, admission to the neonatal intensive care unit, use of mechanical ventilation, and maternal side effects. There were no significant differences between transdermal nitroglycerin and nifedipine and magnesium sulfate in delivery within 48 hours of treatment and pregnancy prolongation, respectively. Overall, women who received transdermal nitroglycerin had a higher risk of headache. Although transdermal nitroglycerin appears to be more effective than β2-adrenergic receptor agonists, the current evidence does not support its routine use as a tocolytic agent for the treatment of preterm labor. Further double-blind placebo-controlled trials are needed. Copyright © 2013 Mosby, Inc. All rights reserved.

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

Tocolysis in women with advanced preterm labor: a secondary analysis of a randomized clinical trial.

PubMed

Klauser, Chad K; Briery, Christian M; Tucker, Ann R; Martin, Rick W; Magann, Everett F; Chauhan, Suneet P; Morrison, John C

2016-03-01

To compare the efficacy of tocolytic treatment with indomethacin (I), magnesium sulfate (M) and nifedipine (N) for acute tocolysis in women with advanced cervical dilation (4-6 cm). A single center, randomized trial was carried out involving patients in preterm labor (cervix 1-6 cm). Secondary analysis of women with advanced cervical dilation (cervix 4-6 cm) at 24-32 weeks' gestation who received intravenous M, oral N or I suppositories comprised this study population. Over 38 months, 92 women with advanced cervical dilation were randomized to one tocoloytic type. Days gained in utero (11.7) and percent remaining undelivered at 48 h (60.8%), 72 h (53.1%) and >7 days (38.3%) were similar regardless of tocolytic employed (p = 0.923, 0.968, 0.791, 0.802, respectively). Likewise, gestational age at delivery (30.7 ± 3.2) was similar between groups (p = 0.771). Finally, neonatal statistics were not different when stratified by tocolytic treatment. There were no statistical differences between tocolytics in treating women with advanced cervical dilation. All offered significant days gained in utero after therapy, a high percentage remaining undelivered after 48 or 72 h and after 7 days. It would appear from data that there may be advantages to tocolytic treatment even in women with advanced cervical dilation.

The role of progesterone in prevention of preterm birth

PubMed Central

Dodd, Jodie M; Crowther, Caroline A

2010-01-01

Preterm birth continues to provide an enormous challenge in the delivery of perinatal health care, and is associated with considerable short and long-term health consequences for surviving infants. Progesterone has a role in maintaining pregnancy, by suppression of the calcium–calmodulin–myosin light chain kinase system. Additionally, progesterone has recognized anti-inflammatory properties, raising a possible link between inflammatory processes, alterations in progesterone receptor expression and the onset of preterm labor. Systematic reviews of randomized controlled trials evaluating the use of intramuscular and vaginal progesterone in women considered to be at increased risk of preterm birth have been published, with primary outcomes of perinatal death, preterm birth <34 weeks, and neurodevelopmental handicap in childhood. Eleven randomized controlled trials were included in the systematic review, involving 2714 women and 3452 infants, with results presented according to the reason women were considered to be at increased risk of preterm birth. While there is a potential beneficial effect in the use of progesterone for some women considered to be at increased risk of preterm birth, primarily in the reduction in the risk of preterm birth before 34 weeks gestation, it remains unclear if the observed prolongation of pregnancy translates into improved health outcomes for the infant. PMID:21072277

Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

PubMed Central

2010-01-01

Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor. PMID:21184677

An examination of the clinical benefits and cost-effectiveness of tocolytic replacement following recurrent preterm labor.

PubMed

Flick, Amy A; de la Torre, Lesley; Roca, Luis E; Istwan, Niki; Rhea, Debbie; Desch, Cheryl; González-Quintero, Victor Hugo

2010-01-01

We examined pregnancy outcomes in women receiving nifedipine tocolysis having recurrent preterm labor (RPTL). Singleton gestations enrolled for outpatient nursing surveillance and prescribed nifedipine tocolysis were identified (N = 4748). Women hospitalized for RPTL at <35 weeks then resuming outpatient surveillance were included (N = 1366). Pregnancy outcomes of women resuming nifedipine (N = 830) were compared with those having an alteration in treatment to continuous subcutaneous terbutaline (N = 536). Overall, 56.7% (2692/4748) experienced RPTL. Half (50.7%) were stabilized and resumed outpatient surveillance with nifedipine or continuous subcutaneous terbutaline. Infants from women resuming nifedipine versus those with alteration of treatment to terbutaline were more likely to deliver at <35 weeks (28.0% versus 13.8%), weigh <2500 g (32.9% versus 20.3%), and require a stay in the neonatal intensive care unit (34.0% versus 23.1%), all P < 0.001. Alteration of tocolytic treatment following RPTL resulted in a decreased incidence of preterm birth and low birth weight, resulting in less admission to the neonatal intensive care unit and fewer nursery days. Thieme Medical Publishers.

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

The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth.

PubMed

Goldenberg, Robert L; Mwatha, Anthony; Read, Jennifer S; Adeniyi-Jones, Samuel; Sinkala, Moses; Msmanga, Gernard; Martinson, Francis; Hoffman, Irving; Fawzi, Wafaie; Valentine, Megan; Emel, Lynda; Brown, Elizabeth; Mudenda, Victor; Taha, Taha E

2006-03-01

The use of antibiotics to prevent preterm birth has achieved mixed results. Our goal in this study was to determine if antibiotics given prenatally and during labor reduce the incidence of preterm birth and histologic chorioamnionitis. A double-blind randomized placebo-controlled trial of antibiotics to reduce preterm birth was conducted in 4 African sites. Both HIV-infected and uninfected pregnant women were given 2 courses of antibiotics, prenatally at 24 weeks (metronidazole 250 mg and erythromycin 250 mg tid orally for 7 days), and during labor (metronidazole 250 mg and ampicillin 500 mg q 4 hours) or identically appearing placebos. Two thousand ninety-eight HIV-infected and 335 HIV-uninfected women had evaluable end points, including gestational age determined by both obstetric and pediatric criteria and birth weight (BWT). Pre- and post-treatment rates of various sexually transmitted infections (STI) were determined and placentas were evaluated for histologic chorioamnionitis. Comparing antibiotic versus placebo treated HIV-infected and uninfected women, there were few differences in mean gestational age at delivery, the percent of preterm births, the time between randomization and delivery, or BWT. Four weeks after the 24-week antibiotic/placebo course, bacterial vaginosis, and trichomoniasis were reduced by 49% to 61% in the antibiotic groups compared with the placebo groups. However, in both the HIV-infected and uninfected groups, the placentas showed no difference in the rate of histologic chorioamnionitis. There were significant differences between HIV-infected and uninfected women, with the former having less education, a history of more stillbirths, more STIs, and in this pregnancy, a lower BWT (2949 vs 3100 g, P < .0001). Despite reducing the rate of vaginal infections, the antibiotic regimen used in this study did not reduce the rate of preterm birth, increase the time to delivery, or increase BWT. Failure of this regimen to reduce the rate of histologic chorioamnionitis may explain the reason the antibiotics failed to reduce preterm birth.

Assessment of Parturition with Cervical Light-Induced Fluorescence and Uterine Electromyography

PubMed Central

Lucovnik, Miha; Kuon, Ruben J.; Garfield, Robert E.

2013-01-01

Parturition involves increasing compliance (ripening) of the uterine cervix and activation of the myometrium. These processes take place in a different time frame. Softening and shortening of the cervix starts in midpregnancy, while myometrial activation occurs relatively close to delivery. Methods currently available to clinicians to assess cervical and myometrial changes are subjective and inaccurate, which often causes misjudgments with potentially adverse consequences. The inability to reliably diagnose true preterm labor leads to unnecessary treatments, missed opportunities to improve neonatal outcome, and inherently biased research of treatments. At term, the likelihood of cesarean delivery depends on labor management, which in turn depends on accurate assessments of cervical change and myometrial contractility. Studies from our group and others show that noninvasive measurements of light-induced fluorescence (LIF) of cervical collagen and uterine electromyography (EMG) objectively detect changes in the composition of the cervix and myometrial preparedness to labor and are more reliable than clinical observations alone. We present a conceptual model of parturition constructed on cervical LIF and uterine EMG studies. We also explore how these methodologies could be helpful with managing patients experiencing preterm contractions and with optimizing labor management protocols aimed to reduce cesarean section. PMID:24187578

[Right ventricular hypertrophic cardiomyopathy in the fetus --may it be caused by chronic oral tocolysis with fenoterol?].

PubMed

Hamela-Olkowska, Anita; Szymkiewicz-Dangel, Joanna; Własienko, Paweł; Majewska, Urszula; Bokiniec, Renata

2012-02-01

The use of fenoterol in the treatment of preterm labor is associated with the risk of many complications in the mother and the fetus. We present a case of a multipara treated with oral fenoterol due to threatening preterm labor 14 weeks. At 35 weeks of gestation the fetus was diagnosed with hypertrophic cardiomyopathy with severe impairment of the right ventricle. The only factor that might have caused such a state of the fetal circulatory system was fenoterol, used from 21 weeks of gestation. After the withdrawal of the fenoterol the fetal right ventricular function improved gradually. However fetal cardiac hypertrophy persisted until the birth at 39 weeks of gestation. Concentric hypertrophy of the right ventricular wall and interventricular septum were confirmed in the newborn.

Immunology of term and preterm labor

PubMed Central

Peltier, Morgan R

2003-01-01

During pregnancy there is an alteration in maternal immunity within the uterus where innate, proinflammatory immune responses are tightly regulated to prevent immunological rejection of the fetal allograft. Disruption of the delicate balance of cytokines by bacteria or other factors increases the production of proinflammatory cytokines at the maternal-fetal interface and activates the parturition mechanism prematurely. Despite years of searching, there is still no broadly effective strategy for preventing preterm labor and most therapies are directed at inhibiting myometrial contractions and improving neonatal outcome. Recent studies with progestins and interleukin-10 (IL-10), however, are showing promise in randomized clinical trials and animal studies. Furthermore, the identification of the Toll-like receptors as upstream mediators of inflammation may offer alternative therapeutic targets for preventing this common pregnancy complication. PMID:14651749

[Clinical or subclinical hypothyroidism and thyroid autoantibody before 20 weeks pregnancy and risk of preterm birth: a systematic review].

PubMed

Wang, Shaowei; Li, Min; Chu, Defa; Liang, Lin; Zhao, Xiaodong; Zhang, Junrong

2014-11-01

To evaluate the relationship between clinical or subclinical hypothyroidism and positive thyroid autoantibody before 20 weeks pregnancy and risk of preterm birth. Literature search was done in PubMed, EMBASE, Wanfang Medical Database, China Academic Journal Network Publishing Database and China Biology Medicine disc databases from January 1st, 1980 to December 31th, 2013. The following search terms were used:hypothyroidism, subclinical hypothyroidism, hypothyroxinnism, thyroid antibody, preterm labor, preterm birth, etc. (1) Criteria for inclusion:cohort studies and clinical studies were included; only articles that described at least 10 patients were eligible;the exposure was clinical or subclinical hypothyroidism and positive thyroid autoantihody, and outcome was preterm birth. (2) The excluded subjects were articles that described less than 10 patients; controls were pregnant women without eurothyrodisim. Meta-analysis was performed by RevMan 5. The relationship between clinical or subclinical hypothyroidism and positive thyroid autoantibody and risk of preterm birth was evaluated by OR or RR. (1) Twenty cohort studies were enrolled. A total of 39 596 cases of preterm birth occurred among 498 418 pregnant women. The controls in these studies were pregnant women with eurothyrodisim. (2) Clinical hypothyroidism in pregnancy: eight studies were included, reported data on 478 418 pregnant women (5 473 women with clinical hypothyroidism and 472 945 euthyroid pregnant women). The risk of preterm birth in pregnant women with clinical hypothyroidism was higher than those eurothyroid pregnant women in control group (OR = 1.25, 95% CI:1.15-1.36, P < 0.01). (3) Subclinical hypothyroidism in pregnancy: ten studies were included, reported data on 277 531 pregnant women (5 257 women with subclinical hypothyroidism and 272 274 euthyroid pregnant women). The risk of preterm birth in pregnant women with subclinical hypothyroidism was higher than those in control group by random effects analysis (OR = 1.25, 95% CI:1.14-1.36, P < 0.01). (4) Thyroid autoantibodys positive in pregnancy:eleven studies were included, reported data on 28 781 pregnant women (3 036 women with thyroid autoanti body positive and 25 745 euthyroid pregnant women). The risk of preterm birth in pregnant women with positive thyroid autoantibody was higher than those negative thyroid autoantibody in control group (OR = 1.47, 95% CI: 1.27- 1.70, P < 0.01). The funnel plots presented symmetrical graphics, indicating that there was no publication bias. Clinical or subclinical hypothyroidism and positive thyroid autoantibody in pregnant women is risk factors of preterm birth.

A Novel Molecular Microbiologic Technique for the Rapid Diagnosis of Microbial Invasion of the Amniotic Cavity and Intra-Amniotic Infection in Preterm Labor with Intact Membranes

PubMed Central

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Yoon, Bo Hyun; Hassan, Sonia; Kim, Chong J.; Korzeniewski, Steven J.; Yeo, Lami

2014-01-01

Objective The major challenges in using amniotic fluid (AF) cultivation techniques to diagnose microbial invasion of the amniotic cavity (MIAC) are: 1) several days are typically required to obtain results, and 2) many organisms implicated in the pathogenesis of human disease are difficult to culture. Here, we compare the performance of AF culture with a novel technique for the diagnosis of MIAC that can provide results within eight hours by combining broad-range real-time polymerase chain reaction with electrospray ionization mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses in AF. Methods AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor (PTL) and intact membranes were analyzed using cultivation techniques (aerobic, anaerobic and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF Interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined according to the results of these two tests. Results 1) The prevalence of MIAC in patients with preterm labor and intact membranes was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; 2) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)] 3) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and histologic acute chorioamnionitis, shorter intervals to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) vs. 32% (39/122); (p<0.001); 70% (7/10) vs. 35% (39/112); (p=0.04); 1 (IQR: <1 – 2) days vs. 25 (IQR: 5 – 51) days; (p=0.002); OR: 5.6; 95% CI: 1.4 – 22, respectively]; 5) there were no significant differences in these factors between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures compared to those with positive AF cultures; and 6) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%). Conclusion 1) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS, which can provide results within 8 hours; 2) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the rapid identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and 3) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth. PMID:24417618

Beta-2- Adrenergic Receptor Genotype and Other Variables that Contribute to Labor Pain and Progress

PubMed Central

Reitman, Elena; Conell-Price, Jessamyn; Evansmilth, Jennifer; Olson, Luke; Drosinos, Sofia; Jasper, Nancy; Randolph, Paula; Smiley, Richard; Shafer, Steven; Flood, Pamela

2011-01-01

Background Beta-2-adrenergic receptor (β2AR) activity influences labor and its genotype affects the incidence of preterm delivery. We determined the effect of β2AR genotype on term labor progress and pain. Methods We prospectively enrolled 150 nulliparous parturients in the third trimester and obtained sensory thresholds, demographic information and DNA. Cervical dilation, pain scores and labor management data were extracted with associated times. The association of genetic and demographic factors with labor was tested with mixed effects models. Results Parturients who express Gln at the 27 position of the β2AR had slower labor (P<0.03). They progressedfrom 1–10cm dilation in approximately 21 hours compared to 14 hours in otherpatients. Asian ethnicity, previously associated with slower labor, is highly associated with this polymorphism (P<0.0001). Heavier and Black patients had slower latent labor (P<0.01, 0.01) and neuraxial analgesia was associated with slower labor progress (P<0.0001). It could take up to 36 hours for the heaviest and the Black parturients to transition from 1cm cervical dilation to active labor; however once the active phase began, labor rate was the same as other patients’. Conclusion We detected a strong association between β2AR genotype and slower labor. Asian ethnicity may be a proxy for β2AR genotype. Black and heavy women have slower latent labor. These results confirm many of the associations found when this mathematical model was applied to a large retrospectivecohort, further validating this approach to description and analysis of labor progress. PMID:21394004

The Frequency and Clinical Significance of Intra-amniotic Inflammation in Women With Preterm Uterine Contractility but Without Cervical Change: Do the Diagnostic Criteria for Preterm Labor Need to be Changed?

PubMed Central

KIM, Sun Min; ROMERO, Roberto; LEE, JoonHo; LEE, Seung Mi; PARK, Chan-Wook; PARK, Joong Shin; YOON, Bo Hyun

2011-01-01

OBJECTIVE The objective of this study was to determine the frequency and clinical significance of intra-amniotic inflammation in patients with preterm increased uterine contractility with intact membranes but without cervical change. METHODS Amniocentesis was performed in 132 patients with regular uterine contractions and intact membranes without cervical change. Amniotic fluid was cultured for bacteria and mycoplasmas and assayed for matrix metalloproteinase-8 (MMP-8). Intra-amniotic inflammation was defined as an elevated amniotic fluid MMP-8 concentration (>23 ng/mL). RESULTS 1) Intra-amniotic inflammation was present in 12.1% (16/132); 2) Culture-proven intra-amniotic infection was diagnosed in 3% (4/132) of patients without demonstrable cervical change on admission or during the period of observation; and 3) Patients with intra-amniotic inflammation had significantly higher rates of preterm delivery and adverse outcomes, and shorter amniocentesis-to-delivery intervals than those without intra-amniotic inflammation (P < .05 for each). Adverse outcomes included chorioamnionitis, funisitis, and neonatal death. CONCLUSION Intra-amniotic inflammation was present in 12% of patients with regular uterine contractions without cervical change, while culture-proven intra-amniotic infection was present in 3%. The presence of intra-amniotic inflammation was a significant risk factor for adverse neonatal outcomes. These observations question whether cervical changes should be required for the diagnosis of preterm labor, because patients without modifications in cervical status on admission or during a period of observation are at risk for adverse pregnancy outcomes. PMID:21999173

Small fetal thymus and adverse obstetrical outcome: a systematic review and a meta-analysis.

PubMed

Caissutti, Claudia; Familiari, Alessandra; Khalil, Asma; Flacco, Maria E; Manzoli, Lamberto; Scambia, Giovanni; Cagnacci, Angelo; D'antonio, Francesco

2018-02-01

The aim of this study was to explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome. Medline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks of gestation in fetuses with, compared to those without, a small thymus on ultrasound. occurrence of chorioamnionitis, intrauterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and preeclampsia. Twelve studies including 1744 fetuses who had ultrasound assessment of thymus during pregnancy were included. Women with preterm premature rupture of the membranes or with preterm labor were at higher risk of preterm birth before 37 weeks (p = 0.01), or before 34 weeks (p < 0.001) for fetuses with a small fetal thymus compared to those without a small thymus, and the risk of chorioamnionitis was higher when the thymus was small (p < 0.001). Fetuses with small thymus were not at higher risk of intrauterine growth restriction (p = 0.3). A small thymus increased the risk of neonatal sepsis (p = 0.007) and morbidity (p = 0.003), but not the risk of preeclampsia (p = 0.9). A small fetal thymus is associated with a higher risk of preterm birth, chorioamnionitis, neonatal sepsis and morbidity, but not with intrauterine growth restriction and preeclampsia. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Preterm Labor and Birth

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Preterm labor

MedlinePlus

... SG, Niebyl JR, Simpson JL, et al, eds. Obstetrics: Normal and Problem Pregnancies . 7th ed. Philadelphia, PA: ... Burd, MD, PhD, Associate Professor of Gynecology and Obstetrics at Johns Hopkins University School of Medicine, Baltimore, ...

Dynamic Changes in the Myometrium during the Third Stage of Labor, Evaluated Using Two-Dimensional Ultrasound, in Women with Normal and Abnormal Third Stage of Labor and in Women with Obstetric Complications.

PubMed

Patwardhan, Manasi; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Korzeniewski, Steven J; Schwartz, Alyse; Hassan, Sonia S; Romero, Roberto

2015-01-01

To investigate dynamic changes in myometrial thickness during the third stage of labor. Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the mid-region of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n = 30), postpartum hemorrhage (n = 4), preterm delivery (n = 7) and clinical chorioamnionitis (n = 4). Differences between myometrial thickness of the uterine segments and as a function of time were evaluated. There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p < 0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p < 0.0001). In women with postpartum hemorrhage, preterm delivery, and clinical chorioamnionitis, an uncoordinated pattern among the uterine segments was observed. A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk of postpartum hemorrhage. © 2015 S. Karger AG, Basel.

Dynamic changes in the myometrium during the third stage of labor, evaluated using two-dimensional ultrasound, in women with normal and abnormal third stage of labor and in women with obstetric complications

PubMed Central

Patwardhan, Manasi; Hernandez-Andrade, Edgar; Ahn, Hyunyoung; Korzeniewski, Steven J; Schwartz, Alyse; Hassan, Sonia S; Romero, Roberto

2015-01-01

Objective To investigate dynamic changes in myometrial thickness during the third stage of labor. Methods Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the mid-region of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n=30), post-partum hemorrhage (n=4), preterm delivery (n=7) or clinical chorioamnionitis (n=4). Differences between uterine segments and as a function of time were evaluated. Results There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p<0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p<0.0001). In women with postpartum hemorrhage, preterm delivery and clinical chorioamnionitis, an uncoordinated pattern between the uterine segments was observed. Conclusion A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk for post-partum hemorrhage. PMID:25634647

Extraction, quantification and characterization of uterine magnetomyographic activity--a proof of concept case study.

PubMed

Eswaran, Hari; Govindan, Rathinaswamy B; Furdea, Adrian; Murphy, Pam; Lowery, Curtis L; Preissl, Hubert T

2009-05-01

The objective was to extract, quantify and characterize the uterine magnetomyographic (MMG) signals that correspond to the electrophysiological activity of the uterus. Transabdominal MMG recordings with high spatial-temporal resolution were performed with the use of the 151 non-invasive magnetic sensor system. The extraction, quantification and characterization procedures were developed and applied to representative MMG signals that were recorded from a pregnant woman at regular intervals starting at 37 weeks of gestation until the subject reached active labor. Multiple MMG recordings were successfully performed on the subject before she went into active labor. The extracted MMG burst activity showed a statistically significant correlation (r=0.2; p<0.001) with the contractile events perceived by mothers. The time-frequency analysis of the burst activity showed a power shift towards higher-frequency at 48 h before the subject went into active labor as compared to earlier recordings. Further there was a gradual increase in the synchrony in the higher-frequency band as the subject reached close to active labor. The non-invasive recording of the magnetic signals of pregnant uterus with high spatial-temporal resolution can provide an insight into the preparatory phase of labor and has the potential of predicting term and preterm labor.

Prediction of preterm birth in twin gestations using biophysical and biochemical tests

PubMed Central

Conde-Agudelo, Agustin; Romero, Roberto

2018-01-01

The objective of this study was to determine the performance of biophysical and biochemical tests for the prediction of preterm birth in both asymptomatic and symptomatic women with twin gestations. We identified a total of 19 tests proposed to predict preterm birth, mainly in asymptomatic women. In these women, a single measurement of cervical length with transvaginal ultrasound before 25 weeks of gestation appears to be a good test to predict preterm birth. Its clinical potential is enhanced by the evidence that vaginal progesterone administration in asymptomatic women with twin gestations and a short cervix reduces neonatal morbidity and mortality associated with spontaneous preterm delivery. Other tests proposed for the early identification of asymptomatic women at increased risk of preterm birth showed minimal to moderate predictive accuracy. None of the tests evaluated in this review meet the criteria to be considered clinically useful to predict preterm birth among patients with an episode of preterm labor. However, a negative cervicovaginal fetal fibronectin test could be useful in identifying women who are not at risk for delivering within the next week, which could avoid unnecessary hospitalization and treatment. This review underscores the need to develop accurate tests for predicting preterm birth in twin gestations. Moreover, the use of interventions in these patients based on test results should be associated with the improvement of perinatal outcomes. PMID:25072736

Prediction of preterm birth in twin gestations using biophysical and biochemical tests.

PubMed

Conde-Agudelo, Agustin; Romero, Roberto

2014-12-01

The objective of this study was to determine the performance of biophysical and biochemical tests for the prediction of preterm birth in both asymptomatic and symptomatic women with twin gestations. We identified a total of 19 tests proposed to predict preterm birth, mainly in asymptomatic women. In these women, a single measurement of cervical length with transvaginal ultrasound before 25 weeks of gestation appears to be a good test to predict preterm birth. Its clinical potential is enhanced by the evidence that vaginal progesterone administration in asymptomatic women with twin gestations and a short cervix reduces neonatal morbidity and mortality associated with spontaneous preterm delivery. Other tests proposed for the early identification of asymptomatic women at increased risk of preterm birth showed minimal to moderate predictive accuracy. None of the tests evaluated in this review meet the criteria to be considered clinically useful to predict preterm birth among patients with an episode of preterm labor. However, a negative cervicovaginal fetal fibronectin test could be useful in identifying women who are not at risk for delivering within the next week, which could avoid unnecessary hospitalization and treatment. This review underscores the need to develop accurate tests for predicting preterm birth in twin gestations. Moreover, the use of interventions in these patients based on test results should be associated with the improvement of perinatal outcomes. Copyright © 2014. Published by Elsevier Inc.

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.

Preterm labor and premature birth: Are you at risk?

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What Is Preterm Labor and Birth?

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Treatments for Preterm Labor

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... brain. NEC is a condition that affects a baby's intestines. Antibiotics . These kill infections caused by bacteria. You may need antibiotics to help prevent infections in you and your baby if you have Group B strep infection or ...

Outdoor Air Pollution, Preterm Birth, and Low Birth Weight: Analysis of the World Health Organization Global Survey on Maternal and Perinatal Health

PubMed Central

Merialdi, Mario; van Donkelaar, Aaron; Vadillo-Ortega, Felipe; Martin, Randall V.; Betran, Ana Pilar; Souza, João Paulo

2014-01-01

Background: Inhaling fine particles (particulate matter with diameter ≤ 2.5 μm; PM2.5) can induce oxidative stress and inflammation, and may contribute to onset of preterm labor and other adverse perinatal outcomes. Objectives: We examined whether outdoor PM2.5 was associated with adverse birth outcomes among 22 countries in the World Health Organization Global Survey on Maternal and Perinatal Health from 2004 through 2008. Methods: Long-term average (2001–2006) estimates of outdoor PM2.5 were assigned to 50-km–radius circular buffers around each health clinic where births occurred. We used generalized estimating equations to determine associations between clinic-level PM2.5 levels and preterm birth and low birth weight at the individual level, adjusting for seasonality and potential confounders at individual, clinic, and country levels. Country-specific associations were also investigated. Results: Across all countries, adjusting for seasonality, PM2.5 was not associated with preterm birth, but was associated with low birth weight [odds ratio (OR) = 1.22; 95% CI: 1.07, 1.39 for fourth quartile of PM2.5 (> 20.2 μg/m3) compared with the first quartile (< 6.3 μg/m3)]. In China, the country with the largest PM2.5 range, preterm birth and low birth weight both were associated with the highest quartile of PM2.5 only, which suggests a possible threshold effect (OR = 2.54; CI: 1.42, 4.55 and OR = 1.99; CI: 1.06, 3.72 for preterm birth and low birth weight, respectively, for PM2.5 ≥ 36.5 μg/m3 compared with PM2.5 < 12.5 μg/m3). Conclusions: Outdoor PM2.5 concentrations were associated with low birth weight but not preterm birth. In rapidly developing countries, such as China, the highest levels of air pollution may be of concern for both outcomes. Citation: Fleischer NL, Merialdi M, van Donkelaar A, Vadillo-Ortega F, Martin RV, Betran AP, Souza JP, O´Neill MS. 2014. Outdoor air pollution, preterm birth, and low birth weight: analysis of the World Health Organization Global Survey on Maternal and Perinatal Health. Environ Health Perspect 122:425–430; http://dx.doi.org/10.1289/ehp.1306837 PMID:24508912

Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

PubMed

Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

2018-04-01

Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P<.05). A total of 609 probe sets were expressed differentially (>1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis, angiogenesis, and tissue remodeling (eg, angiotensin I converting enzyme 2, STEAP family member 4, natriuretic peptide A, and secreted frizzled-related protein 4; all P<.05). Multiple gene sets and pathways that are involved in cardiac morphogenesis and vasculogenesis were downregulated significantly by gene set and Ingenuity Pathway Analysis (hallmark transforming growth factor beta signaling, cellular morphogenesis during differentiation, morphology of cardiovascular system; all P<.05). Disruption of gene networks for cardiac morphogenesis and vasculogenesis occurred in the preterm fetal heart of nonhuman primates with preterm labor, intraamniotic infection, and severe fetal inflammation. Inflammatory injury to the fetal heart in utero may contribute to the development of heart disease later in life. Development of preterm labor therapeutics must also target fetal inflammation to lessen organ injury and potential long-term effects on cardiac function. Copyright © 2018 Elsevier Inc. All rights reserved.

17-alpha-hydroxyprogesterone caproate versus vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix: A randomized controlled trial.

PubMed

Pirjani, Reihaneh; Heidari, Reza; Rahimi-Foroushani, Abbas; Bayesh, Seyedehsara; Esmailzadeh, Arezoo

2017-01-01

The aim of this study was to compare 17-alpha-hydroxyprogesterone caproate (17OHP-C) with vaginal progesterone suppository for the prevention of preterm birth in women with a sonographically short cervix and to evaluate the changes of the cervical length (CL) over time. In this prospective randomized controlled trial, eligible patients were asymptomatic pregnant women with a sonographically short cervix. The participants in group 1 (n = 147) received vaginal progesterone suppositories at a dose of 400 mg daily and the women in group 2 (n = 150) received an i.m. dose of 250 mg 17OHP-C once a week. Transvaginal sonography was repeated every 3 weeks until 36 gestational weeks or the occurrence of preterm labor. A total of 304 singleton pregnant women between 16 and 24 gestational weeks with CL < 25 mm were enrolled in our study. The rates of preterm birth were 10.4% in the progesterone group and 14% in the 17OHP-C group: a difference that was not statistically significant (P = 0.416). Moreover, 264 participants underwent ultrasound examination five times and CL changes were studied for 15 weeks. The results showed that the CL changes over 15 weeks were statistically significant (P < 0.001), but the method of intervention (progesterone/17OHP-C) had no significant effect on CL change (P = 0.64). Our findings showed that vaginal progesterone and 17OHP-C had the same effect on the risk of preterm labor in asymptomatic women with a sonographically short cervix. We detected no significant difference between the effect of 17OHP-C and vaginal progesterone on CL changes over time. © 2016 Japan Society of Obstetrics and Gynecology.

Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1

PubMed Central

Furcron, Amy-Eunice; Romero, Roberto; Mial, Tara N.; Balancio, Amapola; Panaitescu, Bogdan; Hassan, Sonia S.; Sahi, Aashna; Nord, Claire; Gomez-Lopez, Nardhy

2016-01-01

Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution. PMID:27146032

The Icelandic 16-electrode electrohysterogram database

PubMed Central

Alexandersson, Asgeir; Steingrimsdottir, Thora; Terrien, Jeremy; Marque, Catherine; Karlsson, Brynjar

2015-01-01

External recordings of the electrohysterogram (EHG) can provide new knowledge on uterine electrical activity associated with contractions. Better understanding of the mechanisms underlying labor can contribute to preventing preterm birth which is the main cause of mortality and morbidity in newborns. Promising results using the EHG for labor prediction and other uses in obstetric care are the drivers of this work. This paper presents a database of 122 4-by-4 electrode EHG recordings performed on 45 pregnant women using a standardized recording protocol and a placement guide system. The recordings were performed in Iceland between 2008 and 2010. Of the 45 participants, 32 were measured repeatedly during the same pregnancy and participated in two to seven recordings. Recordings were performed in the third trimester (112 recordings) and during labor (10 recordings). The database includes simultaneously recorded tocographs, annotations of events and obstetric information on participants. The publication of this database enables independent and novel analysis of multi-electrode EHG by the researchers in the field and hopefully development towards new life-saving technology. PMID:25984349

The Icelandic 16-electrode electrohysterogram database

NASA Astrophysics Data System (ADS)

Alexandersson, Asgeir; Steingrimsdottir, Thora; Terrien, Jeremy; Marque, Catherine; Karlsson, Brynjar

2015-04-01

External recordings of the electrohysterogram (EHG) can provide new knowledge on uterine electrical activity associated with contractions. Better understanding of the mechanisms underlying labor can contribute to preventing preterm birth which is the main cause of mortality and morbidity in newborns. Promising results using the EHG for labor prediction and other uses in obstetric care are the drivers of this work. This paper presents a database of 122 4-by-4 electrode EHG recordings performed on 45 pregnant women using a standardized recording protocol and a placement guide system. The recordings were performed in Iceland between 2008 and 2010. Of the 45 participants, 32 were measured repeatedly during the same pregnancy and participated in two to seven recordings. Recordings were performed in the third trimester (112 recordings) and during labor (10 recordings). The database includes simultaneously recorded tocographs, annotations of events and obstetric information on participants. The publication of this database enables independent and novel analysis of multi-electrode EHG by the researchers in the field and hopefully development towards new life-saving technology.

Outdoor air pollution, preterm birth, and low birth weight: analysis of the world health organization global survey on maternal and perinatal health.

PubMed

Fleischer, Nancy L; Merialdi, Mario; van Donkelaar, Aaron; Vadillo-Ortega, Felipe; Martin, Randall V; Betran, Ana Pilar; Souza, João Paulo

2014-04-01

Inhaling fine particles (particulate matter with diameter ≤ 2.5 μm; PM2.5) can induce oxidative stress and inflammation, and may contribute to onset of preterm labor and other adverse perinatal outcomes. We examined whether outdoor PM2.5 was associated with adverse birth outcomes among 22 countries in the World Health Organization Global Survey on Maternal and Perinatal Health from 2004 through 2008. Long-term average (2001-2006) estimates of outdoor PM2.5 were assigned to 50-km-radius circular buffers around each health clinic where births occurred. We used generalized estimating equations to determine associations between clinic-level PM2.5 levels and preterm birth and low birth weight at the individual level, adjusting for seasonality and potential confounders at individual, clinic, and country levels. Country-specific associations were also investigated. Across all countries, adjusting for seasonality, PM2.5 was not associated with preterm birth, but was associated with low birth weight [odds ratio (OR) = 1.22; 95% CI: 1.07, 1.39 for fourth quartile of PM2.5 (> 20.2 μg/m3) compared with the first quartile (< 6.3 μg/m3)]. In China, the country with the largest PM2.5 range, preterm birth and low birth weight both were associated with the highest quartile of PM2.5 only, which suggests a possible threshold effect (OR = 2.54; CI: 1.42, 4.55 and OR = 1.99; CI: 1.06, 3.72 for preterm birth and low birth weight, respectively, for PM2.5 ≥ 36.5 μg/m3 compared with PM2.5 < 12.5 μg/m3). Outdoor PM2.5 concentrations were associated with low birth weight but not preterm birth. In rapidly developing countries, such as China, the highest levels of air pollution may be of concern for both outcomes.

What Is a Cesarean Delivery?

MedlinePlus

... know about postpartum depression? Related A-Z Topics Breastfeeding and Breast Milk Preconception Care and Prenatal Care Preterm Labor and Birth NICHD News and Features Release: Women with pregnancy-related diabetes may be at risk for chronic kidney disease ...

What Are the Risks Factors for Preterm Labor and Birth?

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... of the Scientific Director (OSD) Affinity Groups & Labs (AG&L) Scientists Emeriti National Center for Medical Rehabilitation ... for Disease Control and Prevention. (2018). Births: Final Data for 2016. Retrieved May 16, 2018, from https:// ...

VIRAL INFECTIONS DURING PREGNANCY

PubMed Central

Silasi, Michelle; Cardenas, Ingrid; Racicot, Karen; Kwon, Ja-Young; Aldo, Paula; Mor, Gil

2015-01-01

Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be “immunosuppressed”, the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy, and offer potential mechanisms for the associated adverse pregnancy outcomes. PMID:25582523

What Treatments Can Reduce the Chances of Preterm Labor and Birth?

MedlinePlus

... NICHD Research Information Find a Study More Information Cerebral Palsy Condition Information NICHD Research Information Find a Study ... magnesium sulfate may also reduce the risk of cerebral palsy if the child is born early. 2 American ...

Bleeding during Pregnancy

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... in pregnancy? • What problems with the placenta can cause bleeding during pregnancy? • Can bleeding be a sign of preterm labor? • ... the hospital. What problems with the placenta can cause bleeding during pregnancy? Several problems with the placenta later in pregnancy ...

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

Fetal Fibronectin Signaling Induces Matrix Metalloproteases and Cyclooxygenase-2 (COX-2) in Amnion Cells and Preterm Birth in Mice*

PubMed Central

Mogami, Haruta; Kishore, Annavarapu Hari; Shi, Haolin; Keller, Patrick W.; Akgul, Yucel; Word, R. Ann

2013-01-01

Fetal fibronectin (fFN) in cervical and vaginal secretions has been used as a predictor of preterm delivery. Here, we clarified the pathological function of fFN on cell type-specific matrix metalloproteinases (MMPs) and prostaglandin synthesis in fetal membranes. Treatment of amnion mesenchymal cells with fFN resulted in dramatic increases in MMP-1 and MMP-9 mRNA and enzymatic activity as well as COX-2 mRNA and prostaglandin E2 synthesis, activating both NFκB and ERK1/2 signaling. Fetal FN-induced increases in MMPs and COX-2 were mediated through its extra domain A and Toll-like receptor 4 expressed in mesenchymal cells. Lipopolysaccharide and TNF-α increased the release of free FN in medium of amnion epithelial cells in culture. Finally, injection of fFN in pregnant mice resulted in preterm birth. Collectively, these results indicate that fFN is not only a marker of preterm delivery but also plays a significant role in the pathogenesis of preterm labor and premature rupture of fetal membranes. PMID:23184961

Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial.

PubMed

El-Sayed, Y Y; Holbrook, R H; Gibson, R; Chitkara, U; Druzin, M L; Baba, D

1998-01-01

The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

Personality, preterm labor contractions, and psychological consequences.

PubMed

Handelzalts, Jonathan E; Krissi, Haim; Levy, Sigal; Freund, Yael; Carmiel, Naama; Ashwal, Eran; Peled, Yoav

2016-03-01

Research of psychological factors associated with imminent preterm labor (PTL) is sparse, compared with considerable research of preterm birth. We explored state and trait psychological variables associated with PTL, both pre- and postpartum. During 2012-2014, 56 women hospitalized due to PTL, and 33 pregnant women without PTL, responded during gestational week 20-33, to a demographic questionnaire, the Big-Five Inventory (BFI), the Brief Symptom Inventory (BSI), the Fear of Childbirth Questionnaire, and the Maternal-Fetal Attachment Inventory (MFAS). At 4-6 weeks postpartum, 35 and 23 of the women in the respective groups responded online to the Edinburgh Postnatal Depression Scale (EPDS) and the Mother to Infant Bonding Scale (MIBS). Compared to women without PTL, women with PTL scored higher on neuroticism, openness to experience, and MFAS (p < 0.01 each), scored lower on consciousness and agreeableness (p < 0.01 each), and showed greater fear of childbirth (p < 0.05). Significant differences were not found in the postpartum variables of EPDS and MIBS. In the PTL group, MFAS (β = 0.36, p < 0.01), but not fear of childbirth (β = 0.08, p = NS), remained higher, after controlling for demographic variables and neuroticism. PTL was associated with personality variables, but not with psychological consequences, other than elevated prepartum attachment to the fetus.

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

Progestin Treatment for the Prevention of Preterm Birth

PubMed Central

Lucovnik, Miha; Kuon, Ruben J.; Chambliss, Linda R.; Maner, William L.; Shi, Shao-Qing; Shi, Leili; Balducci, James; Garfield, Robert E.

2011-01-01

Progestin supplementation appears to be a promising approach to both preventing initiation of preterm labor and treating it once it is already established, given progesterone’s role in maintaining pregnancy as well as support from basic and clinical research. Progesterone and 17- alpha-hydroxyprogesterone-acetate (17-OH P) slow the process of cervical ripening and this is the rationale for prophylactic long-term progestin supplementation mostly studied so far. However, progesterone (but not 17-OH P) also inhibits myometrial activity even after the cervix is already ripened. Moreover, these effects depend greatly on the vehicle used and the route of administration. Understanding different mechanisms of action, as well as the importance of progestin formulation, vehicle, and route of administration is the key to finding the optimal progestin treatment for prevention of preterm birth. PMID:21564026

Bacterial Hyaluronidase Promotes Ascending GBS Infection and Preterm Birth.

PubMed

Vornhagen, Jay; Quach, Phoenicia; Boldenow, Erica; Merillat, Sean; Whidbey, Christopher; Ngo, Lisa Y; Adams Waldorf, K M; Rajagopal, Lakshmi

2016-06-28

Preterm birth increases the risk of adverse birth outcomes and is the leading cause of neonatal mortality. A significant cause of preterm birth is in utero infection with vaginal microorganisms. These vaginal microorganisms are often recovered from the amniotic fluid of preterm birth cases. A vaginal microorganism frequently associated with preterm birth is group B streptococcus (GBS), or Streptococcus agalactiae However, the molecular mechanisms underlying GBS ascension are poorly understood. Here, we describe the role of the GBS hyaluronidase in ascending infection and preterm birth. We show that clinical GBS strains associated with preterm labor or neonatal infections have increased hyaluronidase activity compared to commensal strains obtained from rectovaginal swabs of healthy women. Using a murine model of ascending infection, we show that hyaluronidase activity was associated with increased ascending GBS infection, preterm birth, and fetal demise. Interestingly, hyaluronidase activity reduced uterine inflammation but did not impact placental or fetal inflammation. Our study shows that hyaluronidase activity enables GBS to subvert uterine immune responses, leading to increased rates of ascending infection and preterm birth. These findings have important implications for the development of therapies to prevent in utero infection and preterm birth. GBS are a family of bacteria that frequently colonize the vagina of pregnant women. In some cases, GBS ascend from the vagina into the uterine space, leading to fetal injury and preterm birth. Unfortunately, little is known about the mechanisms underlying ascending GBS infection. In this study, we show that a GBS virulence factor, HylB, shows higher activity in strains isolated from cases of preterm birth than those isolates from rectovaginal swabs of healthy women. We discovered that GBS rely on HylB to avoid immune detection in uterine tissue, but not placental tissue, which leads to increased rates of fetal injury and preterm birth. These studies provide novel insight into the underlying mechanisms of ascending infection. Copyright © 2016 Vornhagen et al.

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.

Timing of induction of labor.

PubMed

Bacak, Stephen J; Olson-Chen, Courtney; Pressman, Eva

2015-10-01

Determining the optimal timing for induction of labor is critical in minimizing the risks to maternal and fetal health. While data are available to guide us in some clinical situations, such as hypertension and diabetes, many gaps in knowledge still exist in others, including cholestasis of pregnancy, fetal anomalies, and placental abruption. This review of the currently available literature assesses the risks and benefits of preterm and early term induction in a wide variety of maternal and fetal conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Altered activity of lysophospholipase D, which produces bioactive lysophosphatidic acid and choline, in serum from women with pathological pregnancy.

PubMed

Tokumura, A; Kume, T; Taira, S; Yasuda, K; Kanzaki, H

2009-05-01

Altered lipid metabolism is associated with human abnormal pregnancy, such as pre-eclampsia and preterm labor, and potentially leads to fetus loss. A causative factor for the onset and progress of the systemic multifactorial syndromes associated with the pathological pregnancy is oxidized low-density lipoprotein, an active identity of which was postulated to be lysophosphatidic acid (LPA). We previously found that LPA is produced extracellularly by plasma lysophospholipase D (lysoPLD) activity of autotaxin, a tumor cell motility-stimulating protein. In this study, a convenient assay based on the choline released from endogenous substrate or exogenous lysophosphatidylcholine (LPC) was used for comparison of serum lysoPLD activity among patients with normal and abnormal pregnancy. The serum choline-producing activity was found to be mainly due to autotaxin, and dependent on its dilution rate. There was some association between low dilution dependency of serum lysoPLD activity toward an exogenous LPC and high lysoPLD activity toward endogenous substrates in cases of patients with preterm labor and pre-eclampsia. However, there was no difference in the serum level of LPC between women with normal pregnancy and those with pathological pregnancy. These results indicate that production of bioactive LPA by lysoPLD activity is elevated by an unknown mechanism that may be related to increased availability of endogenous substrates LPC, but not its concentration in human serum. If the level of LPA in blood circulation is elevated in the pathological pregnancies in vivo, it may play a role in induction and/or progression of systemic vascular dysfunction seen patients with preterm labor or pre-eclampsia.

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

Polymicrobial Amniotic Fluid Infection with Mycoplasma/Ureaplasma and Other Bacteria Induces Severe Intra-Amniotic Inflammation Associated with Poor Perinatal Prognosis in Preterm Labor.

PubMed

Yoneda, Noriko; Yoneda, Satoshi; Niimi, Hideki; Ueno, Tomohiro; Hayashi, Shirou; Ito, Mika; Shiozaki, Arihiro; Urushiyama, Daichi; Hata, Kenichiro; Suda, Wataru; Hattori, Masahira; Kigawa, Mika; Kitajima, Isao; Saito, Shigeru

2016-02-01

To study the relationship between perinatal prognosis in cases of preterm labor (PTL) and polymicrobial infection in amniotic fluid (AF) and intra-amniotic (IA) inflammation using a highly sensitive and reliable PCR-based method. To detect prokaryotes using a nested PCR-based method, eukaryote-made thermostable DNA polymerase without bacterial DNA contamination was used in combination with bacterial universal primers. We collected AF aseptically from 118 PTL cases and 50 term subjects. The prevalence of microorganisms was 33% (39/118) by PCR and only 7.6% (9/118) by culture. PTL caused by a combination of positive Mycoplasma/Ureaplasma and other bacteria had significantly higher AF IL-8 levels and a significantly shorter amniocentesis-to-delivery interval. Our newly established PCR method is useful for detecting IA microorganisms. Polymicrobial infection with Mycoplasma/Ureaplasma and other bacteria induces severe IA inflammation associated with poor perinatal prognosis in PTL. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor.

PubMed

Gawriluk, Thomas R; Ko, CheMyong; Hong, Xiaoman; Christenson, Lane K; Rucker, Edmund B

2014-10-07

Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclin1 (Becn1) is a putative tumor suppressor gene that has been shown to undergo a loss of heterozygosity in 40-75% of human breast, ovarian, and prostate cancers. Because Becn1 is a key regulator of autophagy, we sought to investigate its role in female reproduction by using a conditional knockout approach in mice. We find that pregnant females lacking Becn1 in the ovarian granulosa cell population have a defect in progesterone production and a subsequent preterm labor phenotype. Luteal cells in this model exhibit defective autophagy and a failure to accumulate lipid droplets needed for steroidogenesis. Collectively, we show that Becn1 provides essential functions in the ovary that are essential for mammalian reproduction.

The Effect of Activity Restriction on Infant's Birth Weight and Gestational Age at Birth: PRAMS Data Analysis.

PubMed

Omar, Abeer

2018-01-01

Activity restriction is extensively prescribed for pregnant women with major comorbidities despite the lack of evidence to support its effectiveness in preventing preterm birth or low birth weight. To determine the moderation effect of home activity restriction for more than a week on infant's birth weight and gestational age at birth for high-risk women with obstetrical and medical comorbidities. A secondary analysis of 2004-2008 New York Pregnancy Risk Assessment Monitoring System was conducted with 1426 high-risk women. High-risk group included 41% of women treated with activity restriction and 59% of those not treated with activity restriction. Women with preterm premature rupture of membrane (PPROM) who were treated with activity restriction had a lower infant birth weight ( b = -202.85, p = ≤.001) and gestational age at birth ( b = -.91, p = ≤.001) than those without activity restriction. However, women with preterm labor and hypertensive disorders of pregnancy who were not treated with activity restriction had lower infant gestational age at birth ( b = -96, p = ≤.01) and ( b = -92, p = ≤.001), respectively, compared to those who were treated with activity restriction. Findings suggest a contrary effect of activity restriction on infants born to women with PPROM, which is a major reason for prescribing activity restriction. The current study results may trigger the need to conduct randomized control trials to determine the effect of severity of activity restriction on maternal and infant outcomes.

Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder.

PubMed

Silva, Desiree; Colvin, Lyn; Hagemann, Erika; Bower, Carol

2014-01-01

Early environmental risk factors associated with attention-deficit/hyperactivity disorder (ADHD) have been increasingly suggested. Our study investigates the maternal, pregnancy, and newborn risk factors by gender for children prescribed stimulant medication for treatment of ADHD in Western Australia. This is a population-based, record linkage case-control study. The records of all non-Aboriginal children and adolescents born in Western Australia and aged <25 years who were diagnosed with ADHD and prescribed stimulant medication (cases = 12,991) were linked to the Midwives Notification System (MNS) to obtain maternal, pregnancy, and birth information. The control population of 30,071 children was randomly selected from the MNS. Mothers of children with ADHD were significantly more likely to be younger, be single, have smoked in pregnancy, have labor induced, and experience threatened preterm labor, preeclampsia, urinary tract infection in pregnancy, or early term delivery irrespective of the gender of the child, compared with the control group. In the fully adjusted model, a novel finding was of a possible protective effect of oxytocin augmentation in girls. Low birth weight, postterm pregnancy, small for gestational age infant, fetal distress, and low Apgar scores were not identified as risk factors. Smoking in pregnancy, maternal urinary tract infection, being induced, and experiencing threatened preterm labor increase the risk of ADHD, with little gender difference, although oxytocin augmentation of labor appears protective for girls. Early term deliveries marginally increased the risk of ADHD. Studies designed to disentangle possible mechanisms, confounders, or moderators of these risk factors are warranted.

Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by Ureaplasma urealyticum during pregnancy - Results of a pilot study.

PubMed

Koucký, Michal; Malíčková, Karin; Cindrová-Davies, Tereza; Smíšek, Jan; Vráblíková, Hana; Černý, Andrej; Šimják, Patrik; Slováčková, Miroslava; Pařízek, Antonín; Zima, Tomáš

2016-08-01

Preterm birth is a leading cause of perinatal mortality and morbidity. Heavy cervicovaginal Ureaplasma colonization is thought to play a role in the pathogenesis of preterm birth. The administration of vaginal progesterone has been shown to reduce the incidence of preterm birth in women with short cervical length. Steroid hormones seem to modulate the presence of microorganisms in the vagina. The aim of this study was to assess whether the treatment with vaginal progesterone could reduce the incidence of preterm birth and cervicovaginal colonization by Ureaplasma urealyticum in a cohort of pregnant women with threatened preterm labor. A cohort of 63 females who presented with regular contractions and/or short cervical length between 24-32 weeks of gestation were recruited into a prospective study. 70% of patients had been treated with vaginal progesterone prior to recruitment and these patients continued with the treatment until birth. All patients were tested for the presence of cervicovaginal Ureaplasma urealyticum colonization at admission. The primary endpoint was preterm birth before 37 weeks. The incidence of preterm delivery was significantly increased in patients who tested positive for Ureaplasma urealyticum. Prolonged vaginal progesterone administration was associated with less frequent cervicovaginal colonization by U. urealyticum. Cervicovaginal colonization by U. urealyticum and absence of progesterone treatment were identified as two independent risk factors for preterm delivery. Our results demonstrate the beneficial effects of progesterone administration in reducing the incidence of cervicovaginal colonization by Ureaplasma urealyticum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Maternal age and risk of labor and delivery complications.

PubMed

Cavazos-Rehg, Patricia A; Krauss, Melissa J; Spitznagel, Edward L; Bommarito, Kerry; Madden, Tessa; Olsen, Margaret A; Subramaniam, Harini; Peipert, Jeffrey F; Bierut, Laura Jean

2015-06-01

We utilized an updated nationally representative database to examine associations between maternal age and prevalence of maternal morbidity during complications of labor and delivery. We used hospital inpatient billing data from the 2009 United States Nationwide Inpatient Sample, part of the Healthcare Cost and Utilization Project. To determine whether the likelihood that maternal morbidity during complications of labor and delivery differed among age groups, separate logistic regression models were run for each complication. Age was the main independent variable of interest. In analyses that controlled for demographics and clinical confounders, we found that complications with the highest odds among women, 11-18 years of age, compared to 25-29 year old women, included preterm delivery, chorioamnionitis, endometritis, and mild preeclampsia. Pregnant women who were 15-19 years old had greater odds for severe preeclampsia, eclampsia, postpartum hemorrhage, poor fetal growth, and fetal distress. Pregnant women who were ≥35 years old had greater odds for preterm delivery, hypertension, superimposed preeclampsia, severe preeclampsia, and decreased risk for chorioamnionitis. Older women (≥40 years old) had increased odds for mild preeclampsia, fetal distress, and poor fetal growth. Our findings underscore the need for pregnant women to be aware of the risks associated with extremes of age so that they can watch for signs and symptoms of such complications.

Interleukin-33 in the Human Placenta

PubMed Central

Topping, Vanessa; Romero, Roberto; Than, Nandor Gabor; Tarca, Adi L.; Xu, Zhonghui; Kim, Sun Young; Wang, Bing; Yeo, Lami; Kim, Chong Jai; Hassan, Sonia S.; Kim, Jung-Sun

2012-01-01

Objective Interleukin-33 (IL-33) is the newest member of the IL-1 cytokine family, a group of key regulators of inflammation. The purpose of this study was to determine whether IL-33 is expressed in the human placenta and to investigate its expression in the context of acute and chronic chorioamnionitis. Methods Placental tissues were obtained from five groups of patients: (1) normal pregnancy at term without labor (n=10); (2) normal pregnancy at term in labor (n=10); (3) preterm labor without inflammation (n=10); (4) preterm labor with acute chorioamnionitis (n=10); and (5) preterm labor with chronic chorioamnionitis (n=10). Immunostaining was performed to determine IL-33 protein expression patterns in the placental disk, chorioamniotic membranes, and umbilical cord. mRNA expression of IL-33 and its receptor IL1RL1 (ST2) was measured in primary amnion epithelial and mesenchymal cells (AECs and AMCs, n=4) and human umbilical vein endothelial cells (HUVECs, n=4) treated with IL-1β (1ng/ml and 10ng/ml) and CXCL10 (0.5ng/ml and 1ng/ml or 5ng/ml). Results 1) Nuclear IL-33 expression was found in endothelial and smooth muscle cells in the placenta, chorioamniotic membranes, and umbilical cord; 2) IL-33 was detected in the nucleus of CD14+ macrophages in the chorioamniotic membranes, chorionic plate, and umbilical cord, and in the cytoplasm of myofibroblasts in the Wharton’s jelly; 3) acute (but not chronic) chorioamnionitis was associated with the presence of IL-33+ macrophages in the chorioamniotic membranes and umbilical cord; 4) expression of IL-33 or IL1RL1 (ST2) mRNA in AECs was undetectable; 5) IL-33 mRNA expression increased in AMCs and HUVECs after IL-1β treatment but did not change with CXCL10 treatment; and 6) IL1RL1 (ST2) expression decreased in AMCs and increased in HUVECs after IL-1β but not CXCL10 treatment. Conclusions IL-33 is expressed in the nucleus of placental endothelial cells, CD14+ macrophages, and myofibroblasts in the Wharton’s jelly. IL-1β can induce the expression of IL-33 and its receptor. Protein expression of IL-33 is detectable in macrophages of the chorioamniotic membranes in acute (but not chronic) chorioamnionitis. PMID:23039129

Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort1234

PubMed Central

Bodnar, Lisa M; Olsen, Jorn; Olsen, Sjurdur; Nohr, Ellen A

2011-01-01

Background: The intake of periconceptional multivitamins may decrease the risk of preterm births (PTBs) or small-for-gestational-age (SGA) births. Objective: We related the timing and frequency of periconceptional multivitamin use to SGA births and PTBs and its clinical presentations (ie, preterm labor, premature rupture of membranes, and medical induction). Design: Women in the Danish National Birth Cohort (n = 35,897) reported the number of weeks of multivitamin use during a 12-wk periconceptional period. Cox regression was used to estimate the relation between any multivitamin use and PTBs (<37 wk) or SGA births (birth weight adjusted for gestational age >2 SDs below the mean on the basis of fetal growth curves). The timing (preconception and postconception) and frequency of use were also analyzed. Regular users (4–6 wk) and partial users (1–3 wk) in each period were compared with nonusers. Results: The association between periconceptional multivitamin use and PTBs varied according to prepregnancy overweight status (P-interaction = 0.07). Regular preconception and postconception multivitamin use in women with a prepregnancy BMI (in kg/m2) <25 was associated with reduced risks of a PTB (HR: 0.84; 95% CI: 0.73, 0.95) and preterm labor (HR: 0.80; 95% CI: 0.69, 0.94). No similar associations were shown for overweight women. The adjusted risk of an SGA birth was reduced in multivitamin users regardless of their prepregnancy BMI (HR: 0.83; 95% CI: 0.73, 0.95), with the strongest association in regular users in the postconception period. Conclusion: Regular periconceptional multivitamin use was associated with reduced risk of SGA births and PTBs in nonoverweight women. PMID:21795441

Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort.

PubMed

Catov, Janet M; Bodnar, Lisa M; Olsen, Jorn; Olsen, Sjurdur; Nohr, Ellen A

2011-09-01

The intake of periconceptional multivitamins may decrease the risk of preterm births (PTBs) or small-for-gestational-age (SGA) births. We related the timing and frequency of periconceptional multivitamin use to SGA births and PTBs and its clinical presentations (ie, preterm labor, premature rupture of membranes, and medical induction). Women in the Danish National Birth Cohort (n = 35,897) reported the number of weeks of multivitamin use during a 12-wk periconceptional period. Cox regression was used to estimate the relation between any multivitamin use and PTBs (<37 wk) or SGA births (birth weight adjusted for gestational age >2 SDs below the mean on the basis of fetal growth curves). The timing (preconception and postconception) and frequency of use were also analyzed. Regular users (4-6 wk) and partial users (1-3 wk) in each period were compared with nonusers. The association between periconceptional multivitamin use and PTBs varied according to prepregnancy overweight status (P-interaction = 0.07). Regular preconception and postconception multivitamin use in women with a prepregnancy BMI (in kg/m(2)) <25 was associated with reduced risks of a PTB (HR: 0.84; 95% CI: 0.73, 0.95) and preterm labor (HR: 0.80; 95% CI: 0.69, 0.94). No similar associations were shown for overweight women. The adjusted risk of an SGA birth was reduced in multivitamin users regardless of their prepregnancy BMI (HR: 0.83; 95% CI: 0.73, 0.95), with the strongest association in regular users in the postconception period. Regular periconceptional multivitamin use was associated with reduced risk of SGA births and PTBs in nonoverweight women.

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

Nifedipine versus fenoterol in the management of preterm labor: a randomized, multicenter clinical study.

PubMed

Valdés, E; Salinas, H; Toledo, V; Lattes, K; Cuellar, E; Perucca, E; Diaz, R; Montecinos, F; Reyes, A

2012-01-01

To compare the efficacy of nifedipine and fenoterol in the management of threatened preterm labor (TPL). A randomized and multicenter study assessing the tocolytic effect of nifedipine versus fenoterol in patients admitted to the participating maternity units with a diagnosis of TPL and a cost-savings study for economic assessment. For a power of 80% and an α error equal to 0.05, 132 consecutive patients were recruited during the study period; 66 patients were assigned to each group. A χ(2) analysis and a mean differences test were performed according to variable types and survival curves per intention-to-treat. Demographics were similar in both groups. The latency period was similar in both groups (26.7 vs. 25.6; p = 0.3). There were no differences in the results obtained. Nifedipine failed more frequently to obtain tocolysis when used as a first-line agent (80 vs. 90%, p = 0.0001). The group treated with fenoterol showed more drug adverse events (57.8 vs. 19.0%, p = 0.0001). The economic assessment did not evidence a significant difference in terms of cost savings between groups treated with either drug. The present study failed to demonstrate either clinical or economic superiority of any of the two drugs used in TPL management. The highest failure percentage of nifedipine when used as a first-line agent should encourage further research. Copyright © 2012 S. Karger AG, Basel.

Estimation of the Incidence of Bacterial Vaginosis and other Vaginal Infections and its Consequences on Maternal/Fetal Outcome in Pregnant Women Attending an Antenatal Clinic in a Tertiary Care Hospital in North India

PubMed Central

Lata, Indu; Pradeep, Yashodhara; Sujata; Jain, Amita

2010-01-01

Aims: This study was undertaken to estimate the incidence of bacterial vaginosis (BV) and other vaginal infections during pregnancy and its association with urinary tract infections (UTI) and its consequences on pregnancy outcome, maternal and fetal morbidity and mortality. Settings and Design: Prospective cohort study. Materials and Methods: The present prospective cohort study was conducted on 200 women attending the antenatal clinic (ANC) of a tertiary hospital. All pertinent obstetric and neonatal data covering antenatal events during the course of pregnancy, delivery, puerperium and condition of each newborn at the time of birth were collected. BV was detected by both Gram stain and gold standard clinical criteria (Amsel’s composite criteria). Statistical analysis used: Data were analyzed using SPSS version 9. Fischer’s exact test, chi square tests and Student’s’ test has been used for analysis. The probability of 5% was considered as significant for continuous variables such as age, period of gestation and birth weight. Odds ratio (OR) and confidence interval (CI) with 95% probability were determined. Results: The incidence of bacterial vaginosis was 41 in 200 patients. Adverse outcomes such as preterm labor, PROM and fetal complications were found more in pregnant women who had bacterial vaginosis (N=41), bacterial vaginosis with UTI (N=14) as compared to those without bacterial vaginosis (N=118). Conclusions: The incidence of poor pregnancy outcome was higher in bacterial vaginosis with UTI. Prevention of BV and UTI is cost effective to minimize the pregnancy-related complications and preterm labor to decrease in perinatal and maternal mortality and morbidity. We recommend all antenatal patients should be screened for the presence of bacterial vaginosis, other infections and UTI. PMID:20922108

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.

Perinatal sepsis caused by Williamsia serinedens infection in a 31-year-old pregnant woman.

PubMed

Yassin, Atteyet F; Lombardi, Salvatore J; Fortunato, Stephen J; McNabb, Paul C; Carr, Mark B; Trabue, Christopher H

2010-07-01

Williamsia serinedens has been isolated from soil but has not yet been implicated in human disease. We report the first case of perinatal sepsis caused by a dual-morphotype form of Williamsia serinedens in a 31-year-old pregnant woman hospitalized with preterm labor.

Cost-effectiveness of ritodrine and fenoterol for treatment of preterm labor in a low-middle-income country: a case study.

PubMed

Jakovljevic, Mihajlo; Varjacic, Mirjana; Jankovic, Slobodan M

2008-01-01

In countries with high income, tocolytic therapy with beta-mimetic agents is a cost-effective strategy compared to placebo. In our study, the cost-effectiveness of two beta-mimetic agents, ritodrine and fenoterol, used in the management of preterm labor was compared in the setting of a low-middle-income transitional country, Serbia & Montenegro. This case study was conducted at the Gynecology-Obstetrics Clinic, Clinical Center "Kragujevac," in Kragujevac, Serbia & Montenegro, between October 2004 and January 2006. In total, 235 pregnant patients with threatened preterm labor were enrolled, but 35 were lost to follow-up. Of the remaining 200 patients, 85 were given ritodrine, and 115 fenoterol. The perspective of Republic Institute for Health Insurance in Serbia was taken into account. Only direct costs were calculated; primary outcomes of the study were length of pregnancy (in weeks), time passed from the onset of uterine contractions to delivery (in weeks), and score on modified Flanagan's quality-of-life scale for chronic diseases, measured after discharge from hospital. Prolongation of pregnancy was significantly longer in the fenoterol group (12.7 +/- 8.4 weeks) than in the ritodrine group (11.6 +/- 7.1 weeks). The mean duration of hospitalization was shorter in the fenoterol group (11.9 +/- 8.8 days) than in the ritodrine group (14.9 +/- 11.3 days). The treatment with fenoterol was less costly and more cost-effective than the treatment with ritodrine, but the difference in cost-effectiveness was not statistically significant. The cost of treatment per gained week of pregnancy prolongation was 3345.51 +/- 7668.04 CSD in the fenoterol group, and 4181.96 +/- 12,069.83 CSD in the ritodrine group. The observed differences in treatment costs and duration of hospitalization per patient did not translate into significant differences in cost-effectiveness ratios, because of low costs of hospitalization and human labor in Serbian health system. Nevertheless, fenoterol treatment still has a tendency to be more cost-effective, and its lower acquisition cost is an advantage to this treatment option.

Characteristics and risk factors of preterm births in a tertiary center in Lagos, Nigeria.

PubMed

Butali, Azeez; Ezeaka, Chinyere; Ekhaguere, Osayame; Weathers, Nancy; Ladd, Jenna; Fajolu, Iretiola; Esezobor, Christopher; Makwe, Christian; Odusanya, Bukola; Anorlu, Rose; Adeyemo, Wasiu; Iroha, Edna; Egri-Okwaji, Mathias; Adejumo, Prisca; Oyeneyin, Lawal; Abiodun, Moses; Badejoko, Bolaji; Ryckman, Kelli

2016-01-01

Preterm birth is a dire complication of pregnancy that poses huge long-term medical and financial burdens for affected children, their families, and the health care system. The aim of the present study was to identify characteristics associated with preterm births at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria from 2011 to 2013. We obtained Information from 5,561 maternal, fetal/neonatal and obstetric records from the labor ward. We excluded delivery at less than 22 weeks (0.25%), post-term birth at ≥42 weeks gestation (1.3%), and unknown gestation (1.4%). Additionally, we excluded records of multiple births (5.4%) and stillbirths (8.3%) leaving 4,691 records of singleton live-births for analysis. Logistic regression analysis was performed comparing preterm birth (22-36 weeks gestation) to term birth (37-41 weeks gestation). Multiple variable models adjusting for maternal age, parity, fetal position, delivery method and booking status were also evaluated. Multinomial regression was used to identify characteristics associated with preterm birth (PTB) defined as early PTB (22-31 weeks gestation), moderate PTB (32-34 weeks gestation), late PTB (35-36 weeks gestation), compared to term birth (37-41 completed weeks gestation). From our data, 16.8% of the singleton live-birth deliveries were preterm (<37 weeks gestation). Of these, 4.7% were early (22-31 weeks), 4.5% were moderate (32-34 weeks) and 7.7% were late (35-36) PTBs. Older maternal age (≥35 years) [odds ratio (OR) = 1.41], hypertension (OR = 3.44) and rupture of membranes (OR = 4.03) were significantly associated with increased odds of PTB. Women being treated for the prevention of mother-to-child transmission of HIV were at a significantly decreased risk for PTB (OR = 0.70). Sixteen percent of women in this cohort were not registered for antenatal care in LUTH. These non-registered subjects had significantly greater odds of all categories of PTB, including early (odds ratio (OR) = 20.8), moderate (OR = 8.68), and late (OR = 2.15). PTB and risks for PTB remain high in Nigeria. We recommend that any high risk pregnancy should be referred to a tertiary center for prenatal care in order to significantly reduce adverse birth outcomes such as PTBs.

Characteristics and risk factors of preterm births in a tertiary center in Lagos, Nigeria

PubMed Central

Butali, Azeez; Ezeaka, Chinyere; Ekhaguere, Osayame; Weathers, Nancy; Ladd, Jenna; Fajolu, Iretiola; Esezobor, Christopher; Makwe, Christian; Odusanya, Bukola; Anorlu, Rose; Adeyemo, Wasiu; Iroha, Edna; Egri-Okwaji, Mathias; Adejumo, Prisca; Oyeneyin, Lawal; Abiodun, Moses; Badejoko, Bolaji; Ryckman, Kelli

2016-01-01

Introduction Preterm birth is a dire complication of pregnancy that poses huge long-term medical and financial burdens for affected children, their families, and the health care system. The aim of the present study was to identify characteristics associated with preterm births at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria from 2011 to 2013. Methods We obtained Information from 5,561 maternal, fetal/neonatal and obstetric records from the labor ward. We excluded delivery at less than 22 weeks (0.25%), post-term birth at ≥42 weeks gestation (1.3%), and unknown gestation (1.4%). Additionally, we excluded records of multiple births (5.4%) and stillbirths (8.3%) leaving 4,691 records of singleton live-births for analysis. Logistic regression analysis was performed comparing preterm birth (22-36 weeks gestation) to term birth (37-41 weeks gestation). Multiple variable models adjusting for maternal age, parity, fetal position, delivery method and booking status were also evaluated. Multinomial regression was used to identify characteristics associated with preterm birth (PTB) defined as early PTB (22-31 weeks gestation), moderate PTB (32-34 weeks gestation), late PTB (35-36 weeks gestation), compared to term birth (37-41 completed weeks gestation). Results From our data, 16.8% of the singleton live-birth deliveries were preterm (<37 weeks gestation). Of these, 4.7% were early (22-31 weeks), 4.5% were moderate (32-34 weeks) and 7.7% were late (35-36) PTBs. Older maternal age (≥35 years) [odds ratio (OR) = 1.41], hypertension (OR = 3.44) and rupture of membranes (OR = 4.03) were significantly associated with increased odds of PTB. Women being treated for the prevention of mother-to-child transmission of HIV were at a significantly decreased risk for PTB (OR = 0.70). Sixteen percent of women in this cohort were not registered for antenatal care in LUTH. These non-registered subjects had significantly greater odds of all categories of PTB, including early (odds ratio (OR) = 20.8), moderate (OR = 8.68), and late (OR = 2.15). Conclusion PTB and risks for PTB remain high in Nigeria. We recommend that any high risk pregnancy should be referred to a tertiary center for prenatal care in order to significantly reduce adverse birth outcomes such as PTBs. PMID:27583065

Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study.

PubMed

Ramos, Bruna Ribeiro de Andrade; Mendes, Niele Dias; Tanikawa, Aline Aki; Amador, Marcos Antônio Trindade; dos Santos, Ney Pereira Carneiro; dos Santos, Sidney Emanuel Batista; Castelli, Erick C; Witkin, Steven S; da Silva, Márcia Guimarães

2016-02-05

A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; however the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. The aim of this study was to evaluate the contribution of maternal and fetal SNPs in the IL1B, IL6, IL6R, TNFA, TNFR, IL10, TLR2, TLR4, MMP9, TIMP1 and TIMP2 genes and the influence of ancestry background in the susceptibility to PTL or PPROM in Brazilian women. Case-control study conducted at a tertiary hospital in São Paulo State, Brazil. We included women with PTL or PPROM and their babies (PTL: 136 women and 88 babies; PPROM: 65 women and 44 babies). Control group included 402 mother-babies pairs of term deliveries. Oral swabs were collected for identification of AIMs by fragment analysis and SNPs by Taqman® SNP Genotyping Assays and PCR. Linkage Disequilibrium and Hardy-Weinberg proportions were evaluated using Genepop 3.4. Haplotypes were inferred using the PHASE algorithm. Allele, genotype and haplotype frequencies were compared by Fisher's exact test or χ (2) and Odds Ratio. Logistic regression was performed. Clinical and sociodemographic data were analyzed by Fisher's exact test and Mann-Whitney. PTL was associated with European ancestry and smoking while African ancestry was protective. The fetal alleles IL10-592C (rs800872) and IL10-819C (rs1800871) were also associated with PTL and the maternal haplotype TNFA-308G-238A was protective. Maternal presence of IL10-1082G (rs1800896) and TLR2A (rs4696480) alleles increased the risk for PPROM while TNFA-238A (rs361525) was protective. Family history of PTL/PPROM was higher in cases, and time to delivery was influenced by IL1B-31T (rs1143627) and TLR4-299G (rs4986790). There is an association between European ancestry and smoking and PTL in our Brazilian population sample. The presence of maternal or fetal alleles that modify the inflammatory response increase the susceptibility to PTL and PPROM. The family history of PTL/PPROM reinforces a role for genetic polymorphisms in susceptibility to these outcomes.

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.

Congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.

PubMed

Samedi, Veronica; Field, Stephen K; Al Awad, Essa; Ratcliffe, Gregory; Yusuf, Kamran

2017-02-20

Congenital tuberculosis is a rare manifestation of tuberculosis. The diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy. We report a case of congenital tuberculosis in an infant born at 24 weeks of gestation to a mother who presented with uncontrolled seizures during preterm labor. Maternal diagnosis was initially made by placental pathology, and later confirmed by isolation of Mycobacterium tuberculosis in urine, gastric aspirates and sputum. Full screening was performed on the newborn infant, and both mother and infant were successfully treated for tuberculosis with a four drug regimen. Pregnancy can exacerbate latent tuberculosis and women originating from endemic areas are especially susceptible. The best way to prevent congenital tuberculosis is to have a high index of suspicion and identify and treat tuberculosis in pregnant women.

Reciprocal Feedback Between miR-181a and E2/ERα in Myometrium Enhances Inflammation Leading to Labor

PubMed Central

Wang, Gang; Liu, Wei-Na; Kinser, Holly; Franco, Hector L.

2016-01-01

Context: The initiation of term and preterm labor is associated with an up-regulated inflammatory response in myometrium; however, the underlying signaling pathways remain incompletely defined. Objective: To define the regulatory mechanisms that mediate the increased myometrial inflammatory response leading to labor, we investigated the roles of microRNAs (miRNA/miR). Design and Setting: Human myometrial tissues, isolated smooth muscle cells, and animal models were used to study miR-181a regulation of uterine inflammatory pathways and contractility. Patients: Myometrial tissues from 15 term pregnant women undergoing elective cesarean section (not in labor) and 10 term pregnant women undergoing emergency cesarean section (in labor) were used. Results: Expression of the highly conserved microRNA, miR-181a, was significantly decreased in mouse and human myometrium during late gestation. By contrast, the putative miR-181a targets, TNF-α, and estrogen receptor (ER)-α, and the validated target, c-Fos, key factors in the inflammatory response leading to parturition, were coordinately up-regulated. In studies using human myometrial cells, overexpression of miR-181a mimics repressed basal as well as IL-1β-induced TNF-α, C-C motif chemokine ligand 2 and 8 expression, whereas the expression of the antiinflammatory cytokine, IL-10, was increased. Overexpression of miR-181a dramatically inhibited both spontaneous and IL-1β-induced contraction of human myometrial cells. Notably, miR-181a directly targeted ERα and decreased its expression, whereas estradiol-17β reciprocally inhibited expression of mature miR-181a in myometrial cells. Conclusions: Thus, increased estradiol-17β/ERα signaling in myometrium near term inhibits miR-181a, resulting in a further increase in ERα and proinflammatory signaling. This escalating feedback loop provides novel targets and therapeutic strategies for the prevention of preterm labor and its consequences. PMID:27459534

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.

Delayed Parturition and Altered Myometrial Progesterone Receptor Isoform A Expression in Mice Null for Kruppel-like Factor 9

USDA-ARS?s Scientific Manuscript database

Pre-term and delayed labor conditions are devastating health problems, with currently unknown etiologies. We previously showed that the transcription factor Krüppel-like factor 9 (KLF9) influences the expression and/or transcriptional activity of receptors for estrogen and progesterone in endometria...

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

PubMed Central

Gawriluk, Thomas R.; Ko, CheMyong; Hong, Xiaoman; Christenson, Lane K.; Rucker, Edmund B.

2014-01-01

Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclin1 (Becn1) is a putative tumor suppressor gene that has been shown to undergo a loss of heterozygosity in 40–75% of human breast, ovarian, and prostate cancers. Because Becn1 is a key regulator of autophagy, we sought to investigate its role in female reproduction by using a conditional knockout approach in mice. We find that pregnant females lacking Becn1 in the ovarian granulosa cell population have a defect in progesterone production and a subsequent preterm labor phenotype. Luteal cells in this model exhibit defective autophagy and a failure to accumulate lipid droplets needed for steroidogenesis. Collectively, we show that Becn1 provides essential functions in the ovary that are essential for mammalian reproduction. PMID:25246579

A Randomized Trial of Vitamin D Supplementation in Two Community Health Center Networks in South Carolina

PubMed Central

WAGNER, Carol L.; MCNEIL, Rebecca; HAMILTON, Stuart A.; WINKLER, Joyce; COOK, Carolina Rodriguez; WARNER, Gloria; BIVENS, Betty; DAVIS, Deborah J.; SMITH, Pamela G.; MURPHY, Martha; SHARY, Judy; HOLLIS, Bruce W.

2015-01-01

Objective To determine whether 4000 IU vitamin D3/day (vs. 2000 IU/day) during pregnancy is safe and improves maternal/neonatal 25(OH)D in a dose-dependent manner. Study Design 257 pregnant women 12–16 weeks’ gestation were enrolled. Randomization to 2000- vs. 4000 IU/day followed one-month run-in at 2000 IU/day. Participants were monitored for hypercalciuria, hypercalcemia and 25(OH)D status. Results Maternal 25(OH)D (n=161) increased from 22.7(SD 9.7) at baseline to 36.2(SD 15) and 37.9(SD 13.5) in the 2000- and 4000 IU groups, respectively. While maternal 25(OH)D change from baseline did not differ between groups, 25(OH)D monthly increase differed between groups (p<0.01). No supplementation-related adverse events occurred. Mean cord blood 25(OH)D (ng/mL) was 22.1±10.3 in 2000- and 27.0±13.3 in 4000 IU group (p=0.024). After controlling for race and study site, preterm birth and labor were inversely associated with pre-delivery- and mean 25(OH)D, but not baseline 25(OH)D,. Conclusions Maternal supplementation with 2000 and 4000 IU vitamin D/day during pregnancy improved maternal/neonatal vitamin D status. Evidence of risk reduction in infection, preterm labor and preterm birth was suggestive, requiring additional studies powered for these endpoints. PMID:23131462

Remote midwifery in Nunavik, Québec, Canada: outcomes of perinatal care for the Inuulitsivik health centre, 2000-2007.

PubMed

Van Wagner, Vicki; Osepchook, Claire; Harney, Evelyn; Crosbie, Colleen; Tulugak, Mina

2012-09-01

The Inuulitsivik midwifery service is a community-based, Inuit-led initiative serving the Hudson coast of the Nunavik region of northern Québec. This study of outcomes for the Inuulitsivik birth centers, aims to improve understanding of maternity services in remote communities. We used a retrospective review of perinatal outcome data collected at each birth at the Inuulitsivik birth centers to examine outcomes for 1,372 labors and 1,382 babies from 2000 to 2007. Data were incomplete for some indicators, particularly for transfers to Montreal. Findings revealed low rates of intervention with safe outcomes in this young, largely multiparous "all risk" Inuit population. Ninety-seven percent of births were documented as spontaneous vaginal deliveries, and 85 percent of births were attended by midwives. Eighty-six percent of the labors occurred in Nunavik, whereas 13.7 percent occurred outside Nunavik. The preterm birth rate was found to be 10.6 percent. Postpartum hemorrhage was documented in 15.4 percent of women; of these cases, 6.9 percent had blood loss greater than 1,000 mL. Four fetal deaths (2.9 per 1,000) and five neonatal deaths (< 3.6 per 1,000) were documented. Nine percent (9%) of births involved urgent transfers of mother or baby. The most common reasons for medical evacuation were preterm labor and preeclampsia, and preterm birth was the most common reason for urgent neonatal transfer. The success of the Innulitsivik midwifery service rests on the knowledge and skills of the Inuit midwives, and support of an interprofessional health team. Our study points to the potential for safe, culturally competent local care in remote communities without cesarean section capacity. Our findings support recommendations for integration of midwifery services and Aboriginal midwifery education programs in remote communities. © 2012, Copyright the Authors, Journal compilation © 2012, Wiley Periodicals, Inc.

Antibiotics for bacterial vaginosis or Trichomonas vaginalis in pregnancy: a systematic review.

PubMed

Okun, Nan; Gronau, Karen A; Hannah, Mary E

2005-04-01

To determine whether antibiotic treatment for bacterial vaginosis or Trichomonas vaginalis during pregnancy decreases the risk of preterm birth and associated adverse outcomes. Pre-MEDLINE and MEDLINE (1966-2003), EMBASE (1980-2003), and the Cochrane Library were searched using the keywords "bacterial vaginosis", "Trichomonas", "Trichomonas vaginalis", "Trichomonas vaginitis", "Trichomonas infections", "pregnancy", "pregnant", "antibiotics", and "antibiotic prophylaxis". The search produced 1,888 titles, of which 1,256 abstracts were reviewed further. Of these, 1,217 were ineligible. Inclusion criteria were the following: randomized controlled trials in which antibiotics were compared with no antibiotic or placebo, for women in the second or third trimester of pregnancy with symptomatic or asymptomatic bacterial vaginosis or Trichomonas vaginalis, intact membranes, and not in labor. Exclusion criteria were as follows: published in a language other than English, dropout rate of more than 20% of women in either group, and lack of usable outcomes. Of the 39 papers reviewed in detail, 14 studies were included in the meta-analysis. One of the authors reviewed titles obtained from the searches, and 2 reviewers independently reviewed the abstracts, excluded those that were ineligible, identified eligible papers, and abstracted the data. For women with bacterial vaginosis, antibiotics reduced the risk of persistent infection but did not reduce the risk of preterm birth or the incidence of associated adverse outcomes for the general population or for any subgroup analyzed. For women with Trichomonas vaginalis, metronidazole reduced the risk of persistent infection but increased the incidence of preterm birth. Contrary to the conclusions of 3 recent systematic reviews, we found no evidence to support the use of antibiotic treatment for bacterial vaginosis or Trichomonas vaginalis in pregnancy to reduce the risk of preterm birth or its associated morbidities in low- or high-risk women.

Association of maternal fever during labor with neonatal and infant morbidity and mortality.

PubMed

Petrova, A; Demissie, K; Rhoads, G G; Smulian, J C; Marcella, S; Ananth, C V

2001-07-01

To examine the association of intrapartum fever with infant morbidity and early neonatal (0-6 days) and infant (0-364 days) death. We carried out a retrospective cohort analysis among singleton live births in the United States for the period 1995-1997 using the National Center for Health Statistics linked birth-infant death cohort data. Among the 11,246,042 singleton live births during the study period, intrapartum fever (at least 38C) was recorded in 1.6%. Intrapartum fever was associated with early neonatal (adjusted odds ratio [OR], 95% confidence interval [CI] for preterm and term infants respectively: 1.32; 1.11, 1.56 and 1.67; 1.14, 2.46) and infant (OR, 95% CI for preterm and term, respectively: 1.31; 1.14, 1.51 and 1.27; 1.01, 1.59) death among nulliparous mothers. Among preterm infants of parous mothers, intrapartum fever was associated with early neonatal (OR 1.29, 95% CI 1.01, 1.64) death. In the combined analyses (infants of nulliparous and parous mothers), intrapartum fever was a strong predictor of infection-related death. These associations were stronger among term (OR 3.16, 95% CI 1.56, 6.40 for early neonatal; OR 1.75, 95% CI 1.20, 2.57 for infant death) than preterm infants (OR 1.52, 95% CI 1.15, 2.00 for early neonatal; OR 1.29, 95% CI 1.05, 1.57 for infant death). Intrapartum fever was also a risk factor for meconium aspiration syndrome, hyaline membrane disease, neonatal seizures, and assisted ventilation. Intrapartum fever is an important predictor of neonatal morbidity and infection-related mortality.

Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study

PubMed Central

Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu

2017-01-01

Objectives To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. Methods We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. Results The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23–1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. Conclusions We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age. PMID:28850585

Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study.

PubMed

Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu; Kim, Eun-A

2017-01-01

To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23-1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age.

A novel molecular microbiologic technique for the rapid diagnosis of microbial invasion of the amniotic cavity and intra-amniotic infection in preterm labor with intact membranes.

PubMed

Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I; Yoon, Bo Hyun; Hassan, Sonia S; Kim, Chong Jai; Korzeniewski, Steven J; Yeo, Lami

2014-04-01

The diagnosis of microbial invasion of the amniotic cavity (MIAC) has been traditionally performed using traditional cultivation techniques, which require growth of microorganisms in the laboratory. Shortcomings of culture methods include the time required (days) for identification of microorganisms, and that many microbes involved in the genesis of human diseases are difficult to culture. A novel technique combines broad-range real-time polymerase chain reaction with electrospray ionization time-of-flight mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses. AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor and intact membranes (PTL) were analyzed using cultivation techniques (aerobic, anaerobic, and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined. (i) The prevalence of MIAC in patients with PTL was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; (ii) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)]; (iii) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and acute histologic chorioamnionitis, a shorter interval to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) versus 32% (39/122) OR: 5.6; 95% CI: 1.4-22; (P < 0.001); 70% (7/10) versus 35% (39/112); (P = 0.04); 1 (IQR: <1-2) days versus 25 (IQR: 5-51) days; (P = 0.002), respectively]; (iv) there were no significant differences in these outcomes between patients with positive PCR/ESI-MS (≥17 GE/well) who had negative AF cultures and those with positive AF cultures; and (v) PCR/ESI-MS detected genomic material from viruses in two patients (1.4%). (i) Rapid diagnosis of intra-amniotic infection is possible using PCR/ESI-MS; (ii) the combined use of biomarkers of inflammation and PCR/ESI-MS allows for the identification of specific bacteria and viruses in women with preterm labor and intra-amniotic infection; and (iii) this approach may allow for administration of timely and specific interventions to reduce morbidity attributed to infection-induced preterm birth. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Maternal and neonatal outcomes in labor and at delivery when long QT syndrome is present.

PubMed

Tanaka, Hiroaki; Katsuragi, Shinji; Tanaka, Kayo; Sawada, Masami; Iwanaga, Naoko; Yoshimatsu, Jun; Ikeda, Tomoaki

2016-01-01

Women during labor may be susceptible to torsades de pointes (TdP), which may cause the fetal condition to deteriorate. The aim of the present investigation was to analyze maternal and fetal outcomes during labor when long QT syndrome (LQTS) was present. We examined the maternal and neonatal outcomes of 25 pregnancies (18 women) with LQT between 1995 and 2012 at the Department of Perinatology, National Cardiovascular Center, Japan. Maternal and neonatal outcomes including cardiovascular events, cardiovascular events within a week after delivery, caesarean delivery rate, still births, preterm births, and non-reassuring fetal heart rate pattern (NRFHR) during labor were investigated. All the mothers survived, and no cardiovascular events occurred in labor or postpartum due to LQTS in either vaginal delivery or caesarean delivery. A total of 23 women (92%) had used beta blockers in this study. Caesarean delivery was performed due to NRFHR during labor in 5 pregnancies (20%). Delivery when LQTS is present has a low likelihood of cardiovascular events, but pregnancy with LQTS had a higher caesarean delivery rate due to NRFHR in labor. Most women used beta blockers in this study, and it is possible that beta blocker use prevents cardiovascular events during labor. NRFHR during labor may be related with inherited LQT through the mother.

ROLE OF THE MATERNAL ACUTE PHASE RESPONSE AND TUMOR NECROSIS FACTOR ALPHA IN THE DEVELOPMENTAL TOXICITY OF LIPOPOLYSACCHARIDE IN THE CD-1 MOUSE

EPA Science Inventory

ABSTRACT
The acute phase response (APR) functions to reset metabolic homeostasis following infectious, toxic or traumatic insult. TNF- , a putative mediator of the APR, has been associated with fetal death in rodents and preterm labor and delivery in humans. We hypothesized...

Vaginal microbial flora and outcome of pregnancy.

PubMed

Donati, Laura; Di Vico, Augusto; Nucci, Marta; Quagliozzi, Lorena; Spagnuolo, Terryann; Labianca, Antonietta; Bracaglia, Marina; Ianniello, Francesca; Caruso, Alessandro; Paradisi, Giancarlo

2010-04-01

The vaginal microflora of a healthy asymptomatic woman consists of a wide variety of anaerobic and aerobic bacterial genera and species dominated by the facultative, microaerophilic, anaerobic genus Lactobacillus. The activity of Lactobacillus is essential to protect women from genital infections and to maintain the natural healthy balance of the vaginal flora. Increasing evidence associates abnormalities in vaginal flora during pregnancy with preterm labor and delivery with potential neonatal sequelae due to prematurity and poor perinatal outcome. Although this phenomenon is relatively common, even in populations of women at low risk for adverse events, the pathogenetic mechanism that leads to complications in pregnancy is still poorly understood. This review summarizes the current knowledge and uncertainties in defining alterations of vaginal flora in non-pregnant adult women and during pregnancy, and, in particular, investigates the issue of bacterial vaginosis and aerobic vaginitis. This could help specialists to identify women amenable to treatment during pregnancy leading to the possibility to reduce the preterm birth rate, preterm premature rupture of membranes, chorioamnionitis, neonatal, puerperal and maternal-fetal infectious diseases. Vaginal ecosystem study with the detection of pathogens is a key instrument in the prevention of preterm delivery, pPROM, chorioamnionitis, neonatal, puerperal and maternal-fetal infections.

Racial/ethnic disparities in maternal morbidities: a statewide study of labor and delivery hospitalizations in Wisconsin.

PubMed

Cabacungan, Erwin T; Ngui, Emmanuel M; McGinley, Emily L

2012-10-01

We examined racial/ethnic disparities in maternal morbidities (MM) and the number of MM during labor and delivery among hospital discharges in Wisconsin. We conducted a retrospective cohort study of hospital discharge data for 206,428 pregnant women aged 13-53 years using 2005-2007 Healthcare Cost and Utilization Project State Inpatient Dataset (HCUP-SID) for Wisconsin. After adjustments for covariates, MM (preterm labor, antepartum and postpartum hemorrhage, hypertension in pregnancy, gestational diabetes, membrane-related disorders, infections and 3rd and 4th perineal lacerations) were examined using logistic regression models, and number of MM (0, 1, 2, >2 MM) were examined using multivariable ordered logistic regressions with partial proportional odds models. African-Americans had significantly higher likelihood of infections (OR = 1.74; 95% CI 1.60-1.89), preterm labor (OR = 1.42; 1.33-1.50), antepartum hemorrhage (OR = 1.63; 1.44-1.83), and hypertension complicating pregnancy (OR = 1.39; 1.31-1.48) compared to Whites. Hispanics, Asian/Pacific Islanders, and Native Americans had significantly higher likelihood of infections, postpartum hemorrhage, and gestational diabetes than Whites. Major perineal lacerations were significantly higher among Asian/Pacific Islanders (OR = 1.53; 1.34-1.75). All minority racial/ethnic groups, except Asians, had significantly higher likelihood of having 0 versus 1, 2 or >2 MM, 0 or 1 versus 2 or >2 MM, and 0, 1 or 2 versus >2 MM than white women. Findings show significant racial/ethnic disparities in MM, and suggest the need for better screening, management, and timely referral of these conditions, particularly among racial/ethnic women. Disparities in MM may be contributing to the high infant mortality and adverse birth outcomes among different racial/ethnic groups in Wisconsin.

Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice.

PubMed

Wahid, Hanan H; Dorian, Camilla L; Chin, Peck Yin; Hutchinson, Mark R; Rice, Kenner C; Olson, David M; Moldenhauer, Lachlan M; Robertson, Sarah A

2015-10-01

An inflammatory response is instrumental in the physiological process of parturition but the upstream signals initiating inflammation are undefined. Because endogenous ligands for Toll-like receptor 4 (TLR4) are released in late gestation, we hypothesized that on-time labor requires TLR4 signaling, to trigger a cytokine and leukocyte response and accelerate the parturition cascade. In pregnant TLR4-deficient (Tlr4-/-) mice, average gestation length was extended by 13 hours and increased perinatal mortality was seen compared with wild-type controls. Quantification of cytokine and uterine activation gene expression showed that late gestation induction of Il1b, Il6, Il12b, and Tnf expression seen in control placenta and fetal membranes was disrupted in Tlr4-/- mice, and accompanied by a transient delay in expression of uterine activation genes, including prostaglandin F receptor, oxytocin receptor, and connexin-43. Leukocyte populations were altered before birth in TLR4-deficient females, with fewer neutrophils and macrophages in the placenta, and fewer dendritic cells and more regulatory T cells in the myometrium. Administration of TLR4 ligand lipopolysaccharide to pregnant wild-type mice induced cytokine expression and fetal loss, whereas Tlr4-/- pregnancies were protected. The small molecule TLR4 antagonist (+)-naloxone increased mean duration of gestation by 16 hours in wild-type mice. Collectively, these data demonstrate that TLR4 is a key upstream regulator of the inflammatory response acting to drive uterine activation and control the timing of labor. Because causal pathways for term and preterm labor converge with TLR4, interventions to manipulate TLR4 signaling may have therapeutic utility for women at risk of preterm labor, or in postterm pregnancy.

Toll-Like Receptor 4 Is an Essential Upstream Regulator of On-Time Parturition and Perinatal Viability in Mice

PubMed Central

Wahid, Hanan H.; Dorian, Camilla L.; Chin, Peck Yin; Hutchinson, Mark R.; Rice, Kenner C.; Olson, David M.; Moldenhauer, Lachlan M.

2015-01-01

An inflammatory response is instrumental in the physiological process of parturition but the upstream signals initiating inflammation are undefined. Because endogenous ligands for Toll-like receptor 4 (TLR4) are released in late gestation, we hypothesized that on-time labor requires TLR4 signaling, to trigger a cytokine and leukocyte response and accelerate the parturition cascade. In pregnant TLR4-deficient (Tlr4−/−) mice, average gestation length was extended by 13 hours and increased perinatal mortality was seen compared with wild-type controls. Quantification of cytokine and uterine activation gene expression showed that late gestation induction of Il1b, Il6, Il12b, and Tnf expression seen in control placenta and fetal membranes was disrupted in Tlr4−/− mice, and accompanied by a transient delay in expression of uterine activation genes, including prostaglandin F receptor, oxytocin receptor, and connexin-43. Leukocyte populations were altered before birth in TLR4-deficient females, with fewer neutrophils and macrophages in the placenta, and fewer dendritic cells and more regulatory T cells in the myometrium. Administration of TLR4 ligand lipopolysaccharide to pregnant wild-type mice induced cytokine expression and fetal loss, whereas Tlr4−/− pregnancies were protected. The small molecule TLR4 antagonist (+)-naloxone increased mean duration of gestation by 16 hours in wild-type mice. Collectively, these data demonstrate that TLR4 is a key upstream regulator of the inflammatory response acting to drive uterine activation and control the timing of labor. Because causal pathways for term and preterm labor converge with TLR4, interventions to manipulate TLR4 signaling may have therapeutic utility for women at risk of preterm labor, or in postterm pregnancy. PMID:26151355

Thyroid Diseases and Adverse Pregnancy Outcomes in a Contemporary US Cohort

PubMed Central

Männistö, Tuija; Grewal, Jagteshwar; Xie, Yunlong; Chen, Zhen; Laughon, S. Katherine

2013-01-01

Context: Thyroid diseases are inconsistently reported to increase risk for pregnancy complications. Objective: The objective of this study was to study pregnancy complications associated with common and uncommon thyroid diseases. Design, Setting, and Participants: We analyzed singleton pregnancies (N = 223 512) from a retrospective US cohort, the Consortium on Safe Labor (2002–2008). Thyroid diseases and outcomes were derived from electronic medical records. Multivariable logistic regression with generalized estimating equations estimated adjusted odds ratios (ORs) with 99% confidence intervals (99% CI). Main Outcome Measures: Hypertensive diseases, diabetes, preterm birth, cesarean sections, inductions, and intensive care unit (ICU) admissions were analyzed. Results: Primary hypothyroidism was associated with increased odds of preeclampsia (OR = 1.47, 99% CI = 1.20–1.81), superimposed preeclampsia (OR = 2.25, 99% CI = 1.53–3.29), gestational diabetes (OR = 1.57, 99% CI = 1.33–1.86), preterm birth (OR = 1.34, 99% CI = 1.17–1.53), induction (OR = 1.15, 99% CI = 1.04–1.28), cesarean section (prelabor, OR = 1.31, 99% CI = 1.11–1.54; after spontaneous labor OR = 1.38, 99% CI = 1.14–1.66), and ICU admission (OR = 2.08, 99% CI = 1.04–4.15). Iatrogenic hypothyroidism was associated with increased odds of placental abruption (OR = 2.89, 99% CI = 1.14–7.36), breech presentation (OR = 2.09, 99% CI = 1.07–4.07), and cesarean section after spontaneous labor (OR = 2.05, 99% CI = 1.01–4.16). Hyperthyroidism was associated with increased odds of preeclampsia (OR = 1.78, 99% CI = 1.08–2.94), superimposed preeclampsia (OR = 3.64, 99% CI = 1.82–7.29), preterm birth (OR = 1.81, 99% CI = 1.32–2.49), induction (OR = 1.40, 99% CI = 1.06–1.86), and ICU admission (OR = 3.70, 99% CI = 1.16–11.80). Conclusions: Thyroid diseases were associated with obstetrical, labor, and delivery complications. Although we lacked information on treatment during pregnancy, these nationwide data suggest either that there is a need for better thyroid disease management during pregnancy or that there may be an intrinsic aspect of thyroid disease that causes poor pregnancy outcomes. PMID:23744409

Impact of Azithromycin on Pregnancy Prolongation in Women at Risk of Preterm Labor: A Time-to-Event Analysis.

PubMed

Goyer, Isabelle; Ferland, Gabrielle; Ruo, Ni; Morin, Caroline; Brochet, Marie-Sophie; Morin, Lucie; Ferreira, Ema

2016-09-13

Since 2006, the empiric use of azithromycin in women at risk of premature birth has become prevalent in our institution without any evidence of its efficacy. Although antibiotics can prolong pregnancy in preterm prolonged rupture of membranes, no published data are available for women with intact membranes. To describe the purpose of adding azithromycin to the usual treatments (cerclage, tocolysis, rest, etc.) to prolong pregnancy in women with intact membranes who are at risk of or already in preterm labour. A retrospective observational cohort study was done at a Mother-Child University Hospital Centre. Patients admitted to obstetric ward who received azithromycin between January 1 st , 2006 and August 1 st , 2010 were included. A total of 127 exposed women were matched to 127 controls through medical records and pharmacy software. A time-to-event analysis was done to compare gestational age at the time of the recorded composite event (delivery, or rupture of membranes, or second intervention to prolong pregnancy). To compare proportions of composite event at different time points, χ 2 tests were used. Patients who received azithromycin had a more severe condition at presentation. Once adjusted for confounding factors, prolongation of pregnancy (HR =1.049; CI 95%: 0.774-1.421 [p=0.758]) and gestational age at the event (HR=1.200; CI 95%: 0.894-1.609 [p=0.225]) did not differ between the groups. The proportions of women with an event ≥7 days post-diagnosis or ≥37 gestational weeks were similar. Azithromycin was added to medical therapy in a more at-risk population and no clear benefit was measured.

Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth.

PubMed

Willcockson, Alexandra R; Nandu, Tulip; Liu, Cheuk-Lun; Nallasamy, Shanmugasundaram; Kraus, W Lee; Mahendroo, Mala

2018-03-01

With half a million babies born preterm each year in the USA and about 15 million worldwide, preterm birth (PTB) remains a global health issue. Preterm birth is a primary cause of infant morbidity and mortality and can impact lives long past infancy. The fact that there are numerous, and many currently unidentified, etiologies of PTB has hindered development of tools for risk evaluation and preventative therapies. Infection is estimated to be involved in nearly 40% of PTBs of known etiology; therefore, understanding how infection-mediated inflammation alters the cervical milieu and leads to preterm tissue biomechanical changes are questions of interest. Using RNA-seq, we identified enrichment of components involved in inflammasome activation and unique proteases in the mouse cervix during lipopolysaccharide (LPS)-mediated PTB and not physiologically at term before labor. Despite transcriptional induction of inflammasome components, there was no evidence of functional activation based on assessment of mature IL1B and IL18 proteins. The increased transcription of proteases that target both elastic fibers and collagen and concentration of myeloid-derived cells capable of protease synthesis in the cervical stroma support the structural disruption of elastic fibers as a functional output of protease activity. The recent demonstration that elastic fibers contribute to the biomechanical function of the pregnant cervix suggests their protease-induced disruption in the infection model of LPS-mediated PTB and may contribute to premature loss of mechanical competency and preterm delivery. Collectively, the transcriptomics and ultrastructural data provide new insights into the distinct mechanisms of premature cervical remodeling in response to infection.

Neonatal outcome of very preterm twins: policy of planned vaginal or cesarean delivery.

PubMed

Sentilhes, Loïc; Oppenheimer, Anne; Bouhours, Anne-Charlotte; Normand, Estelle; Haddad, Bassam; Descamps, Philippe; Marpeau, Loïc; Goffinet, François; Kayem, Gilles

2015-07-01

The objective of the study was to compare neonatal mortality and morbidity in very preterm twins with the first twin in cephalic presentation in hospitals with a policy of planned vaginal delivery (PVD) and those with a policy of planned cesarean delivery (PCD). Women with preterm cephalic first twins delivered after preterm labor and/or premature preterm rupture of membranes from 26(0/7) to 31(6/7) weeks of gestation were identified from the databases of 6 perinatal centers and classified as PVD or PCD according to the center's management policy from 1999 to 2010. Severe neonatal morbidity was defined as any of the following: intraventricular hemorrhage grades 3-4, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, and hospital death. The independent effect of the planned mode of delivery, defined by the center's management policy, was tested and quantified with a 2-level multivariable logistic regression. The PVD group included 248 women, and the PCD group 63. Maternal characteristics did not differ between the 2 groups. The rate of vaginal delivery was 85.9% (213 of 248) vs 20.6% (13 of 63) (P < .001), and the rate of cesarean delivery for the second twin was 1.6% (4 of 248) vs 4.8% (3 of 63) (P = .13) for PVD and PCD. PVD had no independent effect on either newborn hospital mortality or severe neonatal composite morbidity. A policy of planned vaginal delivery of very preterm twins with the first twin in cephalic presentation does not increase either severe neonatal morbidity or mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

Strengthening intrapartum and immediate newborn care to reduce morbidity and mortality of preterm infants born in health facilities in Migori County, Kenya and Busoga Region, Uganda: a study protocol for a randomized controlled trial.

PubMed

Otieno, Phelgona; Waiswa, Peter; Butrick, Elizabeth; Namazzi, Gertrude; Achola, Kevin; Santos, Nicole; Keating, Ryan; Lester, Felicia; Walker, Dilys

2018-06-05

Preterm birth (birth before 37 weeks of gestation) and its complications are the leading contributors to neonatal and under-5 mortality. The majority of neonatal deaths in Kenya and Uganda occur during the intrapartum and immediate postnatal period. This paper describes our study protocol for implementing and evaluating a package of facility-based interventions to improve care during this critical window. This is a pair-matched, cluster randomized controlled trial across 20 facilities in Eastern Uganda and Western Kenya. The intervention facilities receive four components: (1) strengthening of routine data collection and data use activities; (2) implementation of the WHO Safe Childbirth Checklist modified for preterm birth; (3) PRONTO simulation training and mentoring to strengthen intrapartum and immediate newborn care; and (4) support of quality improvement teams. The control facilities receive both data strengthening and introduction of the modified checklist. The primary outcome for this study is 28-day mortality rate among preterm infants. The denominator will include all live births and fresh stillbirths weighing greater than 1000 g and less than 2500 g; all live births and fresh stillbirths weighing between 2501 and 3000 g with a documented gestational age less than 37 weeks. The results of this study will inform interventions to improve personnel and facility capacity to respond to preterm labor and delivery, as well as care for the preterm infant. ClinicalTrials.gov, ID: NCT03112018 . Registered on 13 April 2017.

The common vaginal commensal bacterium Ureaplasma parvum is associated with chorioamnionitis in extreme preterm labor.

PubMed

Cox, Ciara; Saxena, Nita; Watt, Alison P; Gannon, Caroline; McKenna, James P; Fairley, Derek J; Sweet, David; Shields, Michael D; L Cosby, Sara; Coyle, Peter V

2016-11-01

To assess the association of vaginal commensal and low-grade pathogenic bacteria including Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Group B streptococcus (GBS), and Gardnerella vaginalis, in women who delivered preterm at less than 37-week gestation in the presence or absence of inflammation of the chorioamnionitic membranes. A case control study involving women who delivered before 37-week gestation with and without inflammation of chorioamnionitic membranes. A total of 57 placental samples were histologically examined for polymorphonuclear leukocyte infiltration of placental tissue for evidence of chorioamnionitis, and by type-specific nucleic acid amplification for evidence of infection with one or more of the target bacteria. Demographic data were collected for each mother. Among the 57 placental samples, 42.1% had chorioamnionitis and 24.6% delivered in the second trimester of pregnancy; U. parvum, U. urealyticum, G. vaginalis, and GBS were all detected in the study with respective prevalence of 19.3%, 3.5%, 17.5%, and 15.8%; M. genitalium and M. hominis were not detected. U. parvum was significantly associated with chorioamnionitis (p = 0.02; OR 5.0; (95% CI 1.2-21.5) and was more common in women who delivered in the second (35.7%) compared to the third trimester of pregnancy (13.9%). None of the other bacteria were associated with chorioamnionitis or earlier delivery, and all G. vaginalis-positive women delivered in the third trimester of pregnancy (p = 0.04). The detection of U. parvum in placental tissue was significantly associated with acute chorioamnionitis in women presenting in extreme preterm labor.

[Application of Monural to treat pregnant women with asymptomatic bacteriuria and acute cystitis].

PubMed

Michova, M; Ivanov, St; Batashki, I

2009-01-01

Asymptomatic bacteriuria (AB) and cystitis affect 4-9% of pregnancies and are associated with pyelonephritis and preterm labor. Screening for AB and adequate antimicrobal therapy prevent most of these serious complications. Twenty- nine pregnant patients, suffering from AB and 9 cases with cystitis were treated with single dose Monura (Fosfomycin trometamol) in a prospective study.

Deficiency in memory B cell compartment in a patient with infertility and recurrent pregnancy losses.

PubMed

Sung, N; Byeon, H J; Garcia, M D Salazar; Skariah, A; Wu, L; Dambaeva, S; Beaman, K; Gilman-Sachs, A; Kwak-Kim, J

2016-11-01

Alterations in normal balance of B cell subsets have been reported in various rheumatic diseases. In this study, we report a woman with a history of recurrent pregnancy losses (RPL) and infertility who had low levels of memory B cells. A 35-year-old woman with a history of RPL and infertility was demonstrated to have increased peripheral blood CD19+ B cells with persistently low levels of memory B cell subsets. Prior to the frozen donor egg transfer cycle, prednisone and intravenous immunoglobulin G (IVIg) treatment was initiated and patient achieved dichorionic diamniotic twin pregnancies. During pregnancy, proportion (%) of switched memory B cells CD27+IgD- increased, while percent of total CD19+ B cells and CD27-IgD+ naive B cells were gradually decreased with a high dose IVIg treatment. She developed cervical incompetence at 20 weeks of gestation, received a Cesarean section at 32 weeks of gestation due to preterm labor, and delivered twin babies. B cell subset abnormalities may be associated with infertility, RPL and preterm labor, and further investigation is needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A role for CXCL13 (BCA-1) in pregnancy and intra-amniotic infection/inflammation

PubMed Central

Nhan-Chang, Chia-Ling; Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel S.; Erez, Offer; Mittal, Pooja; Kim, Chong Jai; Kim, Mi Jeong; Espinoza, Jimmy; Friel, Lara A.; Vaisbuch, Edi; Than, Nandor Gabor; Mazaki-Tovi, Shali; Hassan, Sonia S.

2011-01-01

Objective CXCL13 is a potent chemokine, produced by mature and recently recruited macrophages to sites of inflammation, which has anti-microbial and anti-angiogenic properties. The purpose of this study was to determine whether CXCL13 is present in maternal serum, umbilical cord blood and amniotic fluid (AF); if AF concentration changes with intra-amniotic infection/inflammation (IAI); and localize the production of CXCL13 in chorio-amniotic membranes and umbilical cord. Study design A cross-sectional study on maternal serum was performed including patients in the following groups: 1) non-pregnant women (n=20); 2) normal pregnant women (n=49); 3) patients at term not in labor (n=30); and 4) patients in spontaneous labor at term (n=29). Umbilical cord blood was collected from term neonates with (n=30) and without labor (n=28). Amniotic fluid was attained from patients in the following groups: 1) midtrimester (n=65); 2) term not in labor (n=22); 3) term in labor (n=47); 4) preterm labor (PTL) with intact membranes leading to term delivery (n=70); and 5) PTL leading to preterm delivery with IAI (n=79) and without IAI (n=60). CXCL13 concentrations were determined by ELISA. Chorio-amniotic membranes and umbilical cords were examined with immunohistochemistry. Non-parametric statistics were used for analysis. Results 1) CXCL13 was present in 100% of serum and cord blood samples, and 99% of AF samples (339/343); 2) Serum CXCL13 concentration was significantly higher in pregnant women when compared to non-pregnant women [median 313.3 pg/mL (IQR: 197.2–646.9) vs. 40.5 pg/mL (IQR: 29.5–93.5), respectively; p<0.001]; 3) Serum CXCL13 concentration decreases with advancing gestational age (Spearman’s rho = −0.424; p<0.001); 4) There were no significant differences in the median serum CXCL13 concentration between women at term with and without labor [371.6 pg/mL (IQR: 194.3–614.3) vs. 235.1 pg/mL (IQR: 182.8–354.7), respectively; p=0.6]; 5) The concentration of CXCL13 in AF did not change with gestational age (p=0.11); 6) Patients with PTL and delivery with IAI had a significantly higher median concentration of CXCL13 than those without IAI [median 513.2 pg/mL (199.7–2505.5) vs 137.3 pg/mL (96.7–209.6), respectively; p<0.001] and those who delivered at term [133.7 pg/mL (97.8–174.8); p<0.001]; 7) Spontaneous labor did not result in a change in the median AF concentration of CXCL13 [labor: 86.9 pg/mL (55.6–152) vs no labor: 77.8 pg/mL (68–98); p=0.75]; 8) CXCL13 was immunolocalized to macrophages in fetal membranes and umbilical vein. Conclusions 1) We report for the first time the presence of CXCL13 in AF; 2) AF CXCL13 concentrations are dramatically increased in intra-amniotic infection/inflammation; 3) Unlike other chemokines, AF and serum CXCL13 concentrations did not change with spontaneous parturition. PMID:19031272

Estimation of the Incidence of Bacterial Vaginosis and other Vaginal Infections and its Consequences on Maternal/Fetal Outcome in Pregnant Women Attending an Antenatal Clinic in a Tertiary Care Hospital in North India.

PubMed

Lata, Indu; Pradeep, Yashodhara; Sujata; Jain, Amita

2010-04-01

This study was undertaken to estimate the incidence of bacterial vaginosis (BV) and other vaginal infections during pregnancy and its association with urinary tract infections (UTI) and its consequences on pregnancy outcome, maternal and fetal morbidity and mortality. Prospective cohort study. The present prospective cohort study was conducted on 200 women attending the antenatal clinic (ANC) of a tertiary hospital. All pertinent obstetric and neonatal data covering antenatal events during the course of pregnancy, delivery, puerperium and condition of each newborn at the time of birth were collected. BV was detected by both Gram stain and gold standard clinical criteria (Amsel's composite criteria). Data were analyzed using SPSS version 9. Fischer's exact test, chi square tests and Student's' test has been used for analysis. The probability of 5% was considered as significant for continuous variables such as age, period of gestation and birth weight. Odds ratio (OR) and confidence interval (CI) with 95% probability were determined. The incidence of bacterial vaginosis was 41 in 200 patients. Adverse outcomes such as preterm labor, PROM and fetal complications were found more in pregnant women who had bacterial vaginosis (N=41), bacterial vaginosis with UTI (N=14) as compared to those without bacterial vaginosis (N=118). The incidence of poor pregnancy outcome was higher in bacterial vaginosis with UTI. Prevention of BV and UTI is cost effective to minimize the pregnancy-related complications and preterm labor to decrease in perinatal and maternal mortality and morbidity. We recommend all antenatal patients should be screened for the presence of bacterial vaginosis, other infections and UTI.

The effect of marital status on pregnancy outcome in Israel: a retrospective case-control study.

PubMed

Lurie, Samuel; Zalmanovitch, Anath; Golan, Abraham; Sadan, Oscar

2010-12-01

Previous studies have observed an association between unmarried status of the mother and adverse perinatal outcome such as increased rate of preterm deliveries, low birthweight and small-for-gestational-age infants. In Israel, attendance of prenatal care is imposed by the state and is not related to socioeconomic status; therefore, unmarried women are expected to have a similar prenatal care as married women. The objective of this study is to test the hypothesis that unmarried and married pregnant women have a similar perinatal outcome. In a retrospective case-control study, analysis of the records of women who gave birth at the delivery ward of Edith Wolfson Medical Center (a tertiary health care center) over a one-year period (2005) with respect to marital status was performed. The cases group included 304 unmarried women who were matched with 1:1 ratio for maternal age, parity, and number of fetuses in the current pregnancy. Unmarried women (n = 304) were more likely to smoke during pregnancy (35.2% vs 15.2%, P < 0.001), had a longer second stage (44.4 ± 9.8 min vs 54.4 ± 4.4 min, P < 0.05) and a shorter first stage (484.0 ± 34.8 min vs 421.0 ± 25.3 min P < 0.05) of labor. The unmarried women had similar length of gestation, preterm delivery rate, mode of delivery, low birthweight rates, low Apgar scores or meconium passage during labor as married women. In Israel, unmarried and married pregnant women may have almost similar pregnancy outcomes on length of gestation, mode of delivery and Apgar score. © 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions.

PubMed

Barros, Fernando C; Bhutta, Zulfiqar Ahmed; Batra, Maneesh; Hansen, Thomas N; Victora, Cesar G; Rubens, Craig E

2010-02-23

Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: Two interventions prevent preterm births--smoking cessation and progesterone. Eight interventions prevent stillbirths--balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery. Eleven interventions improve survival of preterm newborns--prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions.

Fetal gender and pregnancy outcomes in Libya: a retrospective study.

PubMed

Khalil, Mounir M; Alzahra, Esgair

2013-01-01

The relationship between pregnancy outcomes and fetal gender is well reported from different areas in the world, but not from Africa. In this study, we try to understand whether the recorded phenomenon of association of adverse pregnancy outcomes with a male fetus applies to our population. A total of 29,140 patient records from 2009 and 2010 were retrieved from Aljalaa Maternity Hospital, Tripoli, Libya. Analysis was carried out to find the correlation between fetal gender and different pregnancy outcomes. A male fetus was associated with an increased incidence of gestational diabetes mellitus (odds risk 1.4), preterm delivery (6.7% for males, 5.5% for females, odds risk 1.24), cesarean section (23.9% for males, 20% for females, odds risk 1.25), and instrumental vaginal delivery (4.4% for males, 3.1% for females, odds risk 1.48), p<0.005. Preeclampsia was more frequent among preterm females and postterm males, p<0.005. It was also more frequent in male-bearing primigravids, p<0.01. We confirm the existence of an adverse effect of a male fetus on pregnancy and labor in our population. We recommend further research to understand the mechanisms and clinical implications of this phenomenon.

Premature labor and neonatal sepsis caused by Actinomyces neuii.

PubMed

Alsohime, Fahad; Assiri, Rasha A; Al-Shahrani, Fatimah; Bakeet, Hind; Elhazmi, Malak; Somily, Ali M

2018-04-26

Actinomycosis is a rare infection in patients younger than 10years of age. It mainly affects the cervicofacial region, but many other sites of infection have been recognized. About 70% of infections are due to either Actinomyces israelii or Actinomyces gerencseriae. Actinomyces neuii was first described in 1985 in two patients with post cataract endophthalmitis, A. neuii represents 17% of clinical Actinomyces isolates. Several reports indicated a well-known association between Actinomyces infections and Intrauterine devices (IUD). We are reporting a case of neonatal sepsis due to A. neuii as a first case reported from Saudi Arabia. It was thought to be the cause of the premature labor and neonatal sepsis. The prevalence of Actinomyces infection is likely underestimated and additional premature labors and abortions could have been caused by Actinomyces infections that were never detected. More studies are needed to confirm the association of maternal Actinomyces infections with preterm labor. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Toll receptor 4 Asp299Gly polymorphism and its association with preterm birth and premature rupture of membranes in a South American population

PubMed Central

Rey, G.; Skowronek, F.; Alciaturi, J.; Alonso, J.; Bertoni, B.; Sapiro, R.

2008-01-01

Preterm birth (PTB) is a worldwide health problem and remains the leading cause of perinatal morbidity and mortality. Systemic and local intrauterine infections have been implicated in the pathogenesis of preterm labor and delivery. Common pathways between PTB, premature rupture of ovular membranes (PROM) and altered molecular routes of inflammation have been proposed. There is evidence to support a genetic component in these conditions. Lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria, is thought to play a key role in eliciting an inflammatory response. LPS is recognized by proteins of the innate immune system, including Toll-like receptor 4 (TLR4). Individuals from some European countries carrying the variant alleles resulting in an amino acid substitution (Asp299Gly) are at increased risk of Gram-negative infections and premature birth. The objective of this study was to determine if preterm newborns have different allele frequency of the Asp299Gly TLR4 variant from healthy term neonates in Uruguay. The impact of PROM was also examined. There was an increase in the risk for fetuses carrying the Asp299Gly substitution in TLR4 of being severely premature (<33 weeks) and to present PROM at the same time. PMID:18723631

The incidence of low birth weight and intrauterine growth restriction in relationship to maternal ethnicity and gestational age at birth – A PEARL study analysis from the State of Qatar

PubMed Central

Abdulkader, Zeyad Mohannad; ur Rahman, Sajjad; Nimeri, Nuha

2012-01-01

Objective: To analyze the association between maternal ethnicity and gestational age with the incidence of low birth weight and intrauterine growth restriction. Study Design: Prospective, analytic study Methods: The study was conducted between March 14th and April 4th 2011 in Women's Hospital HMC. The data was ascertained from the delivery register of labor ward on daily basis using predesigned, structured questionnaire. Data was stratified according to the maternal ethnicity groups and gestational age at birth (term and preterm). Results: The total deliveries during the study period were 890; 35.5% Qatari (n 316) and 64.5% non-Qatari (n 574). The incidence of LBW was 12.36% (n 110). The difference of LBW incidence between Qatari (13.6% n 43) and non-Qatari (11.67% n 67) groups was non significant (RR 1.17, 95% CI 0.82-1.67, p = 0.401). The same was between non-Qatari sub groups (p < 0.05). The incidence of IUGR was 6% (n 54; 49.09% of LBW). The incidence of IUGR between Qatari (5.7% n 18) and non-Qatari (6.27% n 36) groups was significant (RR 0.45, 95% CI 0.3-0.6 p>0.05). The incidence of LBW was 7.85% (n 60) in term babies and 39.68% (n 50) in preterm babies. The incidence if IUGR was 3.79% (n 29) in term babies and 19.84% (n 25) in preterm babies. Preterm babies had a five times higher risk of both being LBW (RR 5.05; 95%CI 3.65-6.99; p < 0.001) and IUGR (RR 5.23; 95% CI 3.17-8.62; p < 0.001). Conclusion: The incidence of low birth weight is independent of maternal ethnicity in Qatar. However, the incidence of IUGR is significantly higher among the non-Qatari population. The relative risk of being LBW or IUGR is five times higher in preterm babies. Further in depth studies are indicated. PMID:25003038

Center for Integration of Medicine and Innovative Technology

DTIC Science & Technology

2008-11-01

can lead to complications such as dissection of the gestational membranes, infection, and preterm labor. Originally, we proposed to initiate the...precise optical properties of the amniotic fluid at different gestational ages and thus be able to determine the optimal light wavelength for...Approach The focus of the project is to consolidate the bedside assistive and adaptive equipment into a comprehensive unit that promotes patient

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.

Vaginal douching by women with vulvovaginitis and relation to reproductive health hazards.

PubMed

Shaaban, Omar M; Youssef, Alaa Eldin A; Khodry, Mostafa M; Mostafa, Sayed A

2013-05-14

Vaginal douching (VD) is a common practice among married women all over the world specially those in the Middle East. It is used for personal hygiene or for other aesthetic reasons in many countries. The current study investigates the prevalence of VD among patients with vulvovaginitis in Egypt. It also compares the reproductive health hazards among women performing routine VD with those using external hygiene. It also investigates why, and how women practice this douching. A cross sectional observational study was conducted in a tertiary university affiliated hospital in Assiut, Egypt. An interview administered questionnaire was administered to 620 women by two trained clinic nurses. Women presented to the outpatient clinic and diagnosed to have any type of vaginal infections were approached for participation. The principle outcome was the history of preterm labor in women who routinely performed VD versus those who did not (upon which sample size was estimated). Other outcome measures were the types of vaginal infections, and reproductive implications comprising, ectopic pregnancy, abortion and pelvic inflammatory disease (PID). The participants were predominantly multiparas from semi-urban background and middle socioeconomic level. Considering VD as a religious duty and a kind of personal cleanliness were the most common reasons for performing VD in 88.9% and 80.6% of the studied population, respectively. History of preterm labor was reported in 19.2% versus 11.9% (p=0.048), while history of PID in 13.2% versus 6.0% (p=0.008) in women performing VD compared to those not performing this habit, respectively. There were no significant differences between the two groups as regard the history of ectopic pregnancy or the number of previous abortions. Vaginal douching is a prevalent practice in Egypt and has traditional and religious roots within the community. There are many misbeliefs around this habit in Egypt. Vaginal douching increases certain reproductive health hazards especially preterm labor and PID. Much effort and awareness campaigns are needed to increase women awareness about health hazards of this incorrect practice and to limit its use.

Vaginal douching by women with vulvovaginitis and relation to reproductive health hazards

PubMed Central

2013-01-01

Background Vaginal douching (VD) is a common practice among married women all over the world specially those in the Middle East. It is used for personal hygiene or for other aesthetic reasons in many countries. The current study investigates the prevalence of VD among patients with vulvovaginitis in Egypt. It also compares the reproductive health hazards among women performing routine VD with those using external hygiene. It also investigates why, and how women practice this douching. Methods A cross sectional observational study was conducted in a tertiary university affiliated hospital in Assiut, Egypt. An interview administered questionnaire was administered to 620 women by two trained clinic nurses. Women presented to the outpatient clinic and diagnosed to have any type of vaginal infections were approached for participation. The principle outcome was the history of preterm labor in women who routinely performed VD versus those who did not (upon which sample size was estimated). Other outcome measures were the types of vaginal infections, and reproductive implications comprising, ectopic pregnancy, abortion and pelvic inflammatory disease (PID). Results The participants were predominantly multiparas from semi-urban background and middle socioeconomic level. Considering VD as a religious duty and a kind of personal cleanliness were the most common reasons for performing VD in 88.9% and 80.6% of the studied population, respectively. History of preterm labor was reported in 19.2% versus 11.9% (p=0.048), while history of PID in 13.2% versus 6.0% (p=0.008) in women performing VD compared to those not performing this habit, respectively. There were no significant differences between the two groups as regard the history of ectopic pregnancy or the number of previous abortions. Conclusion Vaginal douching is a prevalent practice in Egypt and has traditional and religious roots within the community. There are many misbeliefs around this habit in Egypt. Vaginal douching increases certain reproductive health hazards especially preterm labor and PID. Much effort and awareness campaigns are needed to increase women awareness about health hazards of this incorrect practice and to limit its use. PMID:23672530

Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance

PubMed Central

Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

2015-01-01

Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic vasculitis, and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intra-amniotic infection has been generally considered to be the cause of acute histologic chorioamnionitis and funisitis; however, recent evidence indicates that “sterile” intra-amniotic inflammation, which occurs in the absence of demonstrable microorganisms but can be induced by “danger signals”, is frequently associated with these lesions. In the context of intra-amniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient favoring the migration of neutrophils from maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and is present in 3-5% of placentas delivered at term, but in 94% of placentas delivered between 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks for the fetal inflammatory response syndrome, a condition characterized by an elevation in fetal plasma concentrations of interleukin-6, associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multi-organ fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

Effect of tocolytic drugs on fetal heart rate variability: a systematic review.

PubMed

Verdurmen, Kim M J; Hulsenboom, Alexandra D J; van Laar, Judith O E H; Oei, S Guid

2017-10-01

Tocolytics may cause changes in fetal heart rate (HR) pattern, while fetal heart rate variability (HRV) is an important marker of fetal well-being. We aim to systematically review the literature on how tocolytic drugs affect fetal HRV. We searched CENTRAL, PubMed and EMBASE up to June 2016. Studies published in English, using computerized or visual analysis to describe the effect of tocolytics on HRV in human fetuses were included. Studies describing tocolytics during labor, external cephalic version, pre-eclampsia and infection were excluded. Eventually, we included six studies, describing 169 pregnant women. Nifedipine, atosiban and indomethacin administration show no clinically important effect on fetal HRV. Following administration of magnesium sulfate decreased variability and cases of bradycardia are described. Fenoterol administration results in a slight increase in fetal HR with no changes in variability. After ritodrine administration increased fetal HR and decreased variability is seen. The effect of co-administration of corticosteroids should be taken into account. In order to prevent iatrogenic preterm labor, the effects of tocolytic drugs on fetal HRV should be taken into account when monitoring these fetuses.

Bitter taste receptors as targets for tocolytics in preterm labor therapy.

PubMed

Zheng, Kaizhi; Lu, Ping; Delpapa, Ellen; Bellve, Karl; Deng, Ruitang; Condon, Jennifer C; Fogarty, Kevin; Lifshitz, Lawrence M; Simas, Tiffany A Moore; Shi, Fangxiong; ZhuGe, Ronghua

2017-09-01

Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity, with few prevention and treatment options. Uterine contraction is a central feature of PTB, so gaining new insights into the mechanisms of this contraction and consequently identifying novel targets for tocolytics are essential for more successful management of PTB. Here we report that myometrial cells from human and mouse express bitter taste receptors (TAS2Rs) and their canonical signaling components ( i.e., G-protein gustducin and phospholipase C β2). Bitter tastants can completely relax myometrium precontracted by different uterotonics. In isolated single mouse myometrial cells, a phenotypical bitter tastant (chloroquine, ChQ) reverses the rise in intracellular Ca 2+ concentration ([Ca 2+ ] i ) and cell shortening induced by uterotonics, and this reversal effect is inhibited by pertussis toxin and by genetic deletion of α-gustducin. In human myometrial cells, knockdown of TAS2R14 but not TAS2R10 inhibits ChQ's reversal effect on an oxytocin-induced rise in [Ca 2+ ] i Finally, ChQ prevents mouse PTBs induced by bacterial endotoxin LPS or progesterone receptor antagonist mifepristone more often than current commonly used tocolytics, and this prevention is largely lost in α-gustducin-knockout mice. Collectively, our results reveal that activation of the canonical TAS2R signaling system in myometrial cells produces profound relaxation of myometrium precontracted by a broad spectrum of contractile agonists, and that targeting TAS2Rs is an attractive approach to developing effective tocolytics for PTB management.-Zheng, K., Lu, P., Delpapa, E., Bellve, K., Deng, R., Condon, J. C., Fogarty, K., Lifshitz, L. M., Simas, T. A. M., Shi, F., ZhuGe, R. Bitter taste receptors as targets for tocolytics in preterm labor therapy. © FASEB.

Comparison of obstetric outcome in pregnant women with and without microalbuminuria

PubMed Central

Singh, Harneet; Samal, Sunita; Mahapatro, Akshaya; Ghose, Seetesh

2015-01-01

Background: Maternal and neonatal outcome is an index of quality of health and life in human society. To predict serious outcomes in pregnancy various parameters are being researched so that pregnant women who are at risk are identified early and measures taken to ensure a good outcome of pregnancy. Studies have shown an association between microalbuminuria and adverse pregnancy outcome. This study was undertaken to compare obstetric outcome in pregnant women with and without microalbuminuria. Materials and Methods: A prospective cohort study was performed on 69 pregnant women between 20 and 28 weeks of gestation. Urine tests for albuminuria and creatinine measurements were performed in all women and the albumin to creatinine ratio was calculated. The women with microalbuminuria and those without microalbuminuria were monitored until the end of their pregnancy and compared for pregnancy outcome. Results: The age distribution in the two groups was found to be similar and comparable. Preterm labor was strongly associated with microalbuminuria group (P = 0.001**)strongly significant. Incidence of maternal complications were more with microalbuminuria group (P < 0.001**). Fetal complications were significantly more in terms of intrauterine growth restriction, prematurity, low birth weight, low Apgar score and more incidence of neonatal intensive care unit admission with microalbuminuria group (P = 0.010*)moderately significant. Conclusion: It was found that fetal complications were more associated with babies of pregnant women with microalbuminuria. Though maternal complications were more associated with microalbuminuria group, individual events like premature rupture of membrane, preterm premature rupture of membrane had no statistically significant association with microalbuminuria except preterm labor. However, occurrence of pre-eclampsia was more with microalbuminuria, though it didn’t carry any statistical significance. PMID:25810648

Progesterone and gravidity differentially regulate expression of extracellular matrix components in the pregnant rat myometrium.

PubMed

Shynlova, Oksana; Mitchell, Jennifer A; Tsampalieros, Anne; Langille, B Lowell; Lye, Stephen J

2004-04-01

Myometrial growth and remodeling during pregnancy depends on increased synthesis of interstitial matrix proteins. We hypothesize that the presence of mechanical tension in a specific hormonal environment regulates the expression of extracellular matrix (ECM) components in the uterus. Myometrial tissue was collected from pregnant rats on Gestational Days 0, 12, 15, 17, 19, 21, 22, 23 (labor), and 1 day postpartum and ECM expression was analyzed by Northern blotting. Expression of fibronectin, laminin beta2, and collagen IV mRNA was low during early gestation but increased dramatically on Day 23 during labor. Expression of fibrillar collagens (type I and III) peaked Day 19 and decreased near term. In contrast, elastin mRNA remained elevated from midgestation onward. Injection of progesterone (P4) on Days 20-23 (to maintain elevated plasma P4 levels) delayed the onset of labor, caused dramatic reductions in the levels of fibronectin and laminin mRNA, and prevented the fall of collagen III mRNA levels on Day 23. Treatment of pregnant rats with the progesterone receptor antagonist RU486 on Day 19 induced preterm labor on Day 20 and a premature increase in mRNA levels of collagen IV, fibronectin, and laminin. Analysis of the uterine tissue from unilaterally pregnant rats revealed that most of the changes in ECM gene expression occurred specifically in the gravid horn. Our results show a decrease in expression of fibrillar collagens and a coordinated temporal increase in expression of components of the basement membrane near term associated with decreased P4 and increased mechanical tension. These ECM changes contribute to myometrial growth and remodeling during late pregnancy and the preparation for the synchronized contractions of labor.

The effects of oxytocin and atosiban on the modulation of heart rate in pregnant women.

PubMed

Weissman, Amir; Tobia, Rana Swed; Burke, Yechiel Z; Maxymovski, Olga; Drugan, Arie

2017-02-01

To evaluate autonomic modulation of heart rate in pregnant women treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist) to arrest preterm labor. A prospective study with two cohorts: 14 pregnant women treated with atosiban for premature uterine contractions, and 28 women undergoing induction of labor with oxytocin. Computerized analyses of the electrocardiogram were performed with spectral and nonlinear dynamic analyses. Atosiban did not alter any of the variables associated with heart rate variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p < 0.05) and a significant increase in all spectral variables studied (p < 0.01). Atosiban has no adverse effects on the cardiovascular system or the modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent bradycardic effect and an increase in the spectral power, thus should be used with caution in certain pregnant women.

Comparison of Different EHG Feature Selection Methods for the Detection of Preterm Labor

PubMed Central

Alamedine, D.; Khalil, M.; Marque, C.

2013-01-01

Numerous types of linear and nonlinear features have been extracted from the electrohysterogram (EHG) in order to classify labor and pregnancy contractions. As a result, the number of available features is now very large. The goal of this study is to reduce the number of features by selecting only the relevant ones which are useful for solving the classification problem. This paper presents three methods for feature subset selection that can be applied to choose the best subsets for classifying labor and pregnancy contractions: an algorithm using the Jeffrey divergence (JD) distance, a sequential forward selection (SFS) algorithm, and a binary particle swarm optimization (BPSO) algorithm. The two last methods are based on a classifier and were tested with three types of classifiers. These methods have allowed us to identify common features which are relevant for contraction classification. PMID:24454536

Oxytocin Receptor Antagonist (Atosiban) in the Threat of Preterm Birth: Does It Have Any Effect on Breastfeeding in the Term Newborn?

PubMed

López Gómez, Lucía; Marín Gabriel, Miguel A; Encinas, Begoña; de la Cruz Troca, Juan J; Rodríguez Marrodán, Belén

2018-03-01

Oxytocin is a hormone involved in the mechanism of breastfeeding, uterine contractions, and social relationships. Atosiban (competitive oxytocin antagonist) is one of the most commonly used tocolytics for the threat of preterm labor in Europe. The aim of this study is to determinate if the administration of atosiban has any influence in the type of feeding in the term newborn at discharge. The secondary objective is to verify its effectiveness for the prevention of preterm delivery and in the possibility of applying treatment to complete lung maturation. Retrospective cohort study carried out in a tertiary University Hospital distinguished by WHO-UNICEF as a Baby-Friendly Hospital Initiative. The analysis included 264 women exposed to atosiban during a period of 4 years. One hundred met inclusion criteria. Unexposed infants born right after and before the exposed ones were selected as the not exposed subgroup (n = 200). Among women treated with atosiban, 82% maintained exclusively breastfed (EBF), 8% had mixed breastfeeding, and 10% had formula feeding at discharge. In the nonexposed group, 82% maintained EBF, 9.5% had mixed breastfeeding, and 8.5% had formula feeding at discharge (p = 0.84). 97.5% of pregnant women treated with atosiban received corticosteroid for lung maturation, and 49.5% completed gestation with term newborns. There were no significant differences in the type of feeding at discharge between the atosiban group and the nonexposed group. In most cases, the administration of tocolytic therapy allowed to complete lung maturation.

BLOOD pH AND GASES IN FETUSES IN PRETERM LABOR WITH AND WITHOUT SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

PubMed Central

Romero, Roberto; Soto, Eleazar; Berry, Stanley M.; Hassan, Sonia S.; Kusanovic, Juan Pedro; Yoon, Bo Hyun; Edwin, Samuel; Mazor, Moshe; Chaiworapongsa, Tinnakorn

2012-01-01

OBJECTIVE Fetal hypoxemia has been proposed to be one of the mechanisms of preterm labor (PTL) and delivery. This may have clinical implications since it may alter: 1) the method/frequency of fetal surveillance; and 2) the indications and duration of tocolysis to an already compromised fetus. The aim of this study was to examine whether there is a difference in the fetal blood gas analysis [pH, PaO2 and base excess (BE)] and in the prevalence of fetal acidemia and hypoxia between: 1) patients in PTL who delivered within 72 hours vs. those who delivered more than 72 hours after cordocentesis; and 2) patients with Fetal Inflammatory Response Syndrome (FIRS) vs. those without this condition. STUDY DESIGN Patients admitted with PTL underwent amniocentesis and cordocentesis. Ninety women with singleton pregnancies and PTL were classified according to 1) those who delivered within 72 hours (n = 30) and after 72 hours of the cordocentesis (n = 60); and 2) with and without FIRS. FIRS was defined as a fetal plasma concentration of IL-6 >11 pg/mL. Fetal blood gases were determined. Acidemia and hypoxemia were defined as fetal pH and PaO2 below the 5th percentile for gestational age, respectively. For comparisons between the two study groups, ΔpH and ΔPaO2 were calculated by adjusting for gestational age (Δ = observed value-mean for gestational age). Non-parametric statistics were employed. RESULTS No differences in the median Δ pH (−0.026 vs. −0.016), ΔPaO2 (0.25 mmHg vs. 5.9 mmHg) or BE (−2.4 mEq/L vs. −2.6 mEq/L) were found between patients with PTL who delivered within 72 hours and those who delivered 72 hours after the cordocentesis (p>0.05 for all comparisons). Fetal plasma IL-6 concentration was determined in 63% (57/90) of fetuses and the prevalence of FIRS was 28% (16/57). There was no difference in fetal pH, PaO2 and BE between fetuses with and without FIRS (p>0.05 for all comparisons). Moreover, there was no difference in the rate of fetal acidemia between fetuses with and without FIRS (6.3% vs. 9.8%; p>0.05) and fetal hypoxia between fetuses with or without FIRS (12.5% vs. 19.5%; p>0.05). CONCLUSIONS Our data do not support a role for acute fetal hypoxemia and metabolic acidemia in the etiology of preterm labor and delivery. PMID:21988103

Maternal Factors Influencing Perinatal Transmission of HIV Infection

DTIC Science & Technology

1990-01-01

PET Chronic hypertension Eclampsia 17. IUGR 17. 18. Preterm Labor 18. 19. 3rd Trimester Bleeding 19. a) Placenta Previa b) Abruptio Placenta 20...Obstetrics/Gynecology, and laboratory procedures including those for maternal/neonatal drug screening and for handling and processing tissue ( placenta ...amniocentesis Is n done as a part of this study. After delivery, the placenta (afterbirth) will be examined for evidence of HIV infection (AIDS virus). Blood

Pregnancy outcome in hyperthyroidism: a case control study.

PubMed

Aggarawal, Neelam; Suri, Vanita; Singla, Rimpi; Chopra, Seema; Sikka, Pooja; Shah, Viral N; Bhansali, Anil

2014-01-01

Data comparing pregnancy outcome in hyperthyroid women with euthyroid women are scarce. Hence, this study was carried out to assess the maternal and fetal outcome in pregnant women with hyperthyroidism to ascertain the effect of disease on pregnancy. This retrospective study was conducted over a period of 28 years. We compared the maternal and fetal outcomes of 208 hyperthyroid women with 403 healthy controls, between women with well-controlled and uncontrolled disease and amongst women diagnosed with hyperthyroidism before and during pregnancy. Maternal outcome: women with hyperthyroidism were at increased risk for preeclampsia (OR = 3.94), intrauterine growth restriction (OR = 2.16), spontaneous preterm labor (OR = 1.73), preterm birth (OR = 1.7), gestational diabetes mellitus (OR = 1.8), and cesarean delivery (OR = 1.47). Hyperthyroid women required induction of labor more frequently (OR = 3.61). Fetal outcome: newborns of hyperthyroid mothers had lower birth weight than normal ones (p = 0.0001). Women with uncontrolled disease had higher odds for still birth (OR = 8.42; 95% CI: 2.01-35.2) and lower birth weight (p = 0.0001). Obstetrical complications were higher in women with hyperthyroidism than normal women. Outcome was worsened by uncontrolled disease. Women with pregestational hyperthyroidism had better outcomes than those diagnosed with it during pregnancy. © 2014 S. Karger AG, Basel.

Cerebral white matter maturation patterns in preterm infants: an MRI T2 relaxation anisotropy and diffusion tensor imaging study

PubMed Central

Knight, Michael J.; Smith-Collins, Adam; Newell, Sarah; Denbow, Mark; Kauppinen, Risto A.

2017-01-01

Background and Purpose Preterm birth is associated with worse neurodevelopmental outcome, but brain maturation in preterm infants is poorly characterised with standard methods. We evaluated white matter (WM) of infant brains at term-equivalent age, as a function of gestational age at birth, using multi-modal MRI. Methods Infants born very pre-term (< 32 weeks gestation) and late pre-term (33-36 weeks gestation) were scanned at 3T at term-equivalent age using diffusion tensor imaging (DTI) and T2 relaxometry. MRI data were analysed using tract-based spatial statistics, and anisotropy of T2 relaxation was also determined. Principal component analysis and linear discriminant analysis were applied to seek the variables best distinguishing very pre-term and late pre-term groups. Results Across widespread regions of WM, T2 is longer in very pre-term infants than in late pre-term ones. These effects are more prevalent in regions of WM which myelinate earlier and faster. Similar effects are obtained from DTI, showing that fractional anisotropy (FA) is lower and radial diffusivity higher in the very pre-term group, with a bias towards earlier myelinating regions. Discriminant analysis shows high sensitivity and specificity of combined T2 relaxometry and DTI for the detection of a distinct WM development pathway in very preterm infants. T2 relaxation is anisotropic, depending on the angle between WM fibre and magnetic field, and this effect is modulated by FA. Conclusions Combined T2 relaxometry and DTI characterises specific patterns of retarded WM maturation, at term equivalent age, in infants born very pre-term relative to late pre-term. PMID:29205635

Dynamic Changes in Cervical Glycosaminoglycan Composition during Normal Pregnancy and Preterm Birth

PubMed Central

Akgul, Yucel; Holt, Roxane; Mummert, Mark; Word, Ann

2012-01-01

Glycosaminoglycans (GAG) have diverse functions that regulate macromolecular assembly in the extracellular matrix. During pregnancy, the rigid cervix transforms to a pliable structure to allow birth. Quantitative assessment of cervical GAG is a prerequisite to identify GAG functions in term and preterm birth. In the current study, total GAG levels increased at term, yet the abundance, chain length, and sulfation levels of sulfated GAG remained constant. The increase in total GAG resulted exclusively from an increase in hyaluronan (HA). HA can form large structures that promote increased viscosity, hydration, and matrix disorganization as well as small structures that have roles in inflammation. HA levels increased from 19% of total GAG in early pregnancy to 71% at term. Activity of the HA-metabolizing enzyme, hyaluronidase, increased in labor, resulting in metabolism of large to small HA. Similar to mice, HA transitions from high to low molecular weight in term human cervix. Mouse preterm models were also characterized by an increase in HA resulting from differential expression of the HA synthase (Has) genes, with increased Has1 in preterm in contrast to Has2 induction at term. The Has2 gene but not Has1 is regulated in part by estrogen. These studies identify a shift in sulfated GAG dominance in the early pregnant cervix to HA dominance in term and preterm ripening. Increased HA synthesis along with hyaluronidase-induced changes in HA size in mice and women suggest diverse contributions of HA to macromolecular changes in the extracellular matrix, resulting in loss of tensile strength during parturition. PMID:22529214

Intra- versus retroplacental hematomas: a retrospective case-control study on pregnancy outcomes.

PubMed

Ott, Johannes; Pecnik, Philipp; Promberger, Regina; Pils, Sophie; Binder, Julia; Chalubinski, Kinga M

2017-10-26

Intrauterine hematomas are a common pregnancy complication. The literature lacks studies about outcomes based on hematoma localization. Thus, we aimed to compare pregnancies complicated by an intraplacental hematoma to cases with a retroplacental hematoma and to a control group. In a retrospective case-control study, 32 women with an intraplacental hematoma, 199 women with a retroplacental hematoma, and a control group consisting of 113 age-matched women with no signs of placental abnormalities were included. Main outcome measures were pregnancy complications. Second-trimester miscarriage was most common in the intraplacental hematoma group (9.4%), followed by women with a retroplacental hematoma (4.2%), and controls (0%; p = 0.007). The intraplacental hematoma group revealed the highest rates for placental insufficiency, intrauterine growth retardation, premature preterm rupture of membranes, preterm labor, preterm delivery <37 weeks, and early preterm delivery <34 weeks (p < 0.05), followed by the retroplacental hematoma group. When tested in multivariate models, intraplacental hematomas were independent predictors for placental insufficiency (ß = 4.19, p < 0.001) and intrauterine growth restriction (ß = 1.44, p = 0.035). Intrauterine fetal deaths occurred only in women with a retroplacental hematoma (p = 0.042). Intra- and retroplacental hematomas have different risk profiles for the affected pregnancy and act as independent risk factors.

Outcome of singleton preterm small for gestational age infants born to mothers with pregnancy-induced hypertension. A population-based study.

PubMed

Regev, Rivka H; Arnon, Shmuel; Litmanovitz, Ita; Bauer-Rusek, Sofia; Boyko, Valentina; Lerner-Geva, Liat; Reichman, Brian

2015-04-01

Pregnancy-induced hypertension (PIH) has been associated with a decreased risk of infant mortality in small for gestational age (SGA) preterm infants. To evaluate the influence of PIH on mortality and major neonatal morbidities in singleton preterm SGA infants, in the presence and absence of acute pregnancy complications. Population-based observational study of singleton SGA infants, born at 24 to 32 weeks gestation in the period 1995-2010 (n = 2139). Multivariable logistic regression analyses were used to assess the independent effect of PIH on mortality and neonatal morbidities. Acute pregnancy complications comprised premature labor, premature rupture of membranes >6 h, antepartum hemorrhage and clinical chorioamnionitis. In the absence of pregnancy complications, the odds ratio (95% confidence interval) for mortality (0.77; 0.50-1.16), survival without severe neurological morbidity (1.14; 0.79-1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85; 0.59-1.21) were similar in the PIH versus no-PIH groups. In the presence of pregnancy complications, mortality (0.76; 0.40-1.44), survival without severe neurological morbidity (1.16; 0.64-2.12) and survival without BPD (1.04; 0.58-1.86) were also similar in the PIH versus no-PIH groups. PIH was not associated with improved outcome in preterm SGA infants, both in the presence and absence of acute pregnancy complications.

Relation between amniotic fluid infection or cytokine levels and hearing screen failure in infants at 32 wk gestation or less.

PubMed

Jung, Eun Young; Choi, Byung Yoon; Rhee, Jihye; Park, Jaehong; Cho, Soo-Hyun; Park, Kyo Hoon

2017-02-01

To determine whether the presence of intra-amniotic infection and elevated proinflammatory cytokine levels in amniotic fluid (AF) are associated with failure in the newborn hearing screen (NHS) test in very preterm neonates. This is a retrospective cohort study of 112 premature singleton neonates born to women with preterm labor or preterm premature rupture of membranes at ≤32 wk. AF obtained through amniocentesis was cultured, and interleukin-6 (IL-6) and IL-8 levels were determined. Fourteen (12.5%) neonates failed the NHS test. The prevalence of a positive AF culture was 40% (45/112). Multiple logistic regression analyses indicated that intra-amniotic infection was significantly associated with failure in the NHS test after adjusting for baseline covariates such as maternal white blood cell count (WBC) and periventricular leukomalacia. However, the IL-6 and IL-8 levels in AF were not significantly associated with hearing screen failure. Moreover, neither gestational age at birth nor birth weight was associated with NHS failure. The presence of intra-amniotic infection, but not elevated levels of AF IL-6 and IL-8, may contribute to the risk for failure in the NHS test in very preterm neonates. This finding suggests that intra-amniotic infection in utero might contribute to the development of congenital sensorineural hearing loss.

Global report on preterm birth and stillbirth (3 of 7): evidence for effectiveness of interventions

PubMed Central

2010-01-01

Introduction Interventions directed toward mothers before and during pregnancy and childbirth may help reduce preterm births and stillbirths. Survival of preterm newborns may also be improved with interventions given during these times or soon after birth. This comprehensive review assesses existing interventions for low- and middle-income countries (LMICs). Methods Approximately 2,000 intervention studies were systematically evaluated through December 31, 2008. They addressed preterm birth or low birth weight; stillbirth or perinatal mortality; and management of preterm newborns. Out of 82 identified interventions, 49 were relevant to LMICs and had reasonable amounts of evidence, and therefore selected for in-depth reviews. Each was classified and assessed by the quality of available evidence and its potential to treat or prevent preterm birth and stillbirth. Impacts on other maternal, fetal, newborn or child health outcomes were also considered. Assessments were based on an adaptation of the Grades of Recommendation Assessment, Development and Evaluation criteria. Results Most interventions require additional research to improve the quality of evidence. Others had little evidence of benefit and should be discontinued. The following are supported by moderate- to high-quality evidence and strongly recommended for LMICs: • Two interventions prevent preterm births—smoking cessation and progesterone • Eight interventions prevent stillbirths—balanced protein energy supplementation, screening and treatment of syphilis, intermittant presumptive treatment for malaria during pregnancy, insecticide-treated mosquito nets, birth preparedness, emergency obstetric care, cesarean section for breech presentation, and elective induction for post-term delivery • Eleven interventions improve survival of preterm newborns—prophylactic steroids in preterm labor, antibiotics for PROM, vitamin K supplementation at delivery, case management of neonatal sepsis and pneumonia, delayed cord clamping, room air (vs. 100% oxygen) for resuscitation, hospital-based kangaroo mother care, early breastfeeding, thermal care, and surfactant therapy and application of continued distending pressure to the lungs for respiratory distress syndrome Conclusion The research paradigm for discovery science and intervention development must be balanced to address prevention as well as improve morbidity and mortality in all settings. This review also reveals significant gaps in current knowledge of interventions spanning the continuum of maternal and fetal outcomes, and the critical need to generate further high-quality evidence for promising interventions. PMID:20233384

Global report on preterm birth and stillbirth (2 of 7): discovery science

PubMed Central

2010-01-01

Background Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions. Pregnancy and parturition continuum The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy. Etiologies The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries. Recommendations Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs. Conclusion Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes. PMID:20233383

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus.

PubMed

Morsi, Amr; DeFranco, Donald; Witchel, Selma

2018-06-06

Glucocorticoids (GCs), cortisol in humans, influence multiple essential maturational events during gestation. In the human fetus, fetal hypothalamic-pituitary-adrenal (HPA) axis function, fetal adrenal steroidogenesis, placental 11β- hydroxysteroid dehydrogenase type 2 activity, maternal cortisol concentrations, and environmental factors impact fetal cortisol exposure. The beneficial effects of synthetic glucocorticoids (sGCs), such as dexamethasone and betamethasone, on fetal lung maturation have significantly shifted the management of preterm labor and threatened preterm birth. Accumulating evidence suggests that exposure to sGCs in utero at critical developmental stages can alter the function of organ systems and that these effects may have sequelae that extend into adult life. Maternal stress and environmental influences may also impact fetal GC exposure. This article explores the vulnerability of the fetal HPA axis to endogenous GCs and exogenous sGCs. © 2018 S. Karger AG, Basel.

A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery.

PubMed

Lim, Ratana; Barker, Gillian; Menon, Ramkumar; Lappas, Martha

2016-11-01

Preterm birth remains the major cause of neonatal mortality and morbidity, mediated largely by an inflammatory process. The sirtuin (SIRT) family of cellular regulators has been implicated as key inhibitors of inflammation. We have previously reported a role for SIRT1, SIRT2, and SIRT6 in regulating inflammation-induced prolabor mediators. In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5, and SIRT7 expression in human myometrium. Functional studies were also used to investigate the effect of small interfering RNA (siRNA) knockdown of SIRTs in regulating inflammation-induced prolabor mediators. Western blot analysis and qRT-PCR were used to determine SIRT3, SIRT4, SIRT5, and SIRT7 mRNA and protein expression in human myometrium. Small interfering RNA knockdown of SIRT3 in myometrial primary cells determined its role in response to inflammatory stimuli IL1B and TNF. SIRT3 mRNA and protein expression levels were significantly lower in term laboring myometrium compared with term nonlaboring myometrium. There was no effect of labor on SIRT4, SIRT5 or SIRT7 protein expression. The pro-inflammatory cytokines IL1B and TNF significantly decreased levels of SIRT3 mRNA and protein expression. SIRT3 knockdown by siRNA significantly augmented IL1B- and TNF-stimulated IL6, CXCL8, and CCL2 mRNA expression and release; PTGS2 mRNA expression and subsequent PGF 2alpha release; the mRNA expression and secretion of the adhesion molecule ICAM1 and the extracellular matrix remodeling enzyme MMP9; and nuclear factor kappa B1 (NFkappaB1) transcriptional activity. In human myometrium, SIRT3 expression decreases with term labor and regulates the mediators involved in the terminal effector pathways of human labor and delivery through the NFkappaB1 pathway. © 2016 by the Society for the Study of Reproduction, Inc.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

PubMed

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Recording of electrohysterogram laplacian potential.

PubMed

Alberola-Rubio, J; Garcia-Casado, J; Ye-Lin, Y; Prats-Boluda, G; Perales, A

2011-01-01

Preterm birth is the main cause of the neonatal morbidity. Noninvasive recording of uterine myoelectrical activity (electrohysterogram, EHG) could be an alternative to the monitoring of uterine dynamics which are currently based on tocodynamometers (TOCO). The analysis of uterine electromyogram characteristics could help the early diagnosis of preterm birth. Laplacian recordings of other bioelectrical signals have proved to enhance spatial selectivity and to reduce interferences in comparison to monopolar and bipolar surface recordings. The main objective of this paper is to check the feasibility of the noninvasive recording of uterine myoelectrical activity by means of laplacian techniques. Four bipolar EHG signals, discrete laplacian obtained from five monopolar electrodes and the signals picked up by two active concentric-ringed-electrodes were recorded on 5 women with spontaneous or induced labor. Intrauterine pressure (IUP) and TOCO were also simultaneously recorded. To evaluate the uterine contraction detectability of the different noninvasive methods in comparison to IUP the contractions consistency index (CCI) was calculated. Results show that TOCO is less consistent (83%) than most EHG bipolar recording channels (91%, 83%, 87%, and 76%) to detect the uterine contractions identified in IUP. Moreover laplacian EHG signals picked up by ringed-electrodes proved to be as consistent (91%) as the best bipolar recordings in addition to significantly reduce ECG interference.

Fetal gender and pregnancy outcomes in Libya: a retrospective study

PubMed Central

Khalil, Mounir M.; Alzahra, Esgair

2013-01-01

Objective The relationship between pregnancy outcomes and fetal gender is well reported from different areas in the world, but not from Africa. In this study, we try to understand whether the recorded phenomenon of association of adverse pregnancy outcomes with a male fetus applies to our population. Materials and methods A total of 29,140 patient records from 2009 and 2010 were retrieved from Aljalaa Maternity Hospital, Tripoli, Libya. Analysis was carried out to find the correlation between fetal gender and different pregnancy outcomes. Results A male fetus was associated with an increased incidence of gestational diabetes mellitus (odds risk 1.4), preterm delivery (6.7% for males, 5.5% for females, odds risk 1.24), cesarean section (23.9% for males, 20% for females, odds risk 1.25), and instrumental vaginal delivery (4.4% for males, 3.1% for females, odds risk 1.48), p<0.005. Preeclampsia was more frequent among preterm females and postterm males, p<0.005. It was also more frequent in male-bearing primigravids, p<0.01. Conclusion We confirm the existence of an adverse effect of a male fetus on pregnancy and labor in our population. We recommend further research to understand the mechanisms and clinical implications of this phenomenon. PMID:23308081

Intrauterine diagnosis and management of fetal goiter: a case report.

PubMed

Koyuncu, Faik Mumtaz; Tamay, Aslı Goker; Bugday, Sultan

2010-01-01

Fetal goiter can be the result of maternal hyperthyroidism treated with antithyroid drugs. Polyhydramnios may be the presenting symptom and can be diagnosed prenatally by sonography. We report a case of fetal goiter diagnosed at 30 weeks of gestation and fetal hypothyroidism confirmed by cordocentesis. Intra-amniotic levothyroxine was administered. Onset of preterm labor could not be prevented. The risks and benefits of intrauterine treatment of fetal goitrous hypothyroidism are discussed.

Retosiban Prevents Stretch-Induced Human Myometrial Contractility and Delays Labor in Cynomolgus Monkeys.

PubMed

Aye, Irving L M H; Moraitis, Alexandros A; Stanislaus, Dinesh; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-03-01

Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies. To determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates. Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys. Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015). The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.

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.

Work-related psychosocial stress and risk of preterm, low birthweight delivery.

PubMed Central

Homer, C J; James, S A; Siegel, E

1990-01-01

We investigated whether work-related psychologic stress--defined as work characterized by both high psychologic demands and limited control over the response to these demands--increases a woman's risk of delivering a preterm, low birthweight infant. We studied 786 employed pregnant women included in the National Longitudinal Survey of Labor Market Experience, Youth Cohort (NLSY), a nationally representative sample of 12,686 young adults. Data concerning work status, job title, and other factors affecting pregnancy outcome were obtained from the NLSY. Assessment of job experience was based on job title, using an established catalogue of occupation characteristics. After accounting for the physical exertion entailed in a job, occupational psychologic stress as measured by job title was not associated with preterm, low birthweight delivery for the sample as a whole (Relative risk = 1.16, 95% confidence interval .45, 2.95). For those women who did not want to remain in the work force, work-related stress increased their risk of experiencing this outcome (RR = 8.1, 95% CI 1.5, 50.2). Personal motivation toward work, as well as the physical effort of work, should be considered in evaluating the impact of a job's psychologic characteristics on pregnancy outcome. PMID:2297061

Work-related psychosocial stress and risk of preterm, low birthweight delivery.

PubMed

Homer, C J; James, S A; Siegel, E

1990-02-01

We investigated whether work-related psychologic stress--defined as work characterized by both high psychologic demands and limited control over the response to these demands--increases a woman's risk of delivering a preterm, low birthweight infant. We studied 786 employed pregnant women included in the National Longitudinal Survey of Labor Market Experience, Youth Cohort (NLSY), a nationally representative sample of 12,686 young adults. Data concerning work status, job title, and other factors affecting pregnancy outcome were obtained from the NLSY. Assessment of job experience was based on job title, using an established catalogue of occupation characteristics. After accounting for the physical exertion entailed in a job, occupational psychologic stress as measured by job title was not associated with preterm, low birthweight delivery for the sample as a whole (Relative risk = 1.16, 95% confidence interval .45, 2.95). For those women who did not want to remain in the work force, work-related stress increased their risk of experiencing this outcome (RR = 8.1, 95% CI 1.5, 50.2). Personal motivation toward work, as well as the physical effort of work, should be considered in evaluating the impact of a job's psychologic characteristics on pregnancy outcome.

Successful treatment with granulocyte-colony stimulating factor for ritodrine-induced neutropenia in a twin pregnancy.

PubMed

Wang, Chen-Yu; Lai, Yu-Ju; Hwang, Kwei-Shuai; Chen, Chi-Huang; Yu, Mu-Hsien; Chen, Huei-Tsung; Su, Her-Young

2016-10-01

Neutropenia developed after continuous intravenous infusion of ritodrine hydrochloride (Yutopar) for preterm uterine contractions in a twin pregnancy. We successfully returned the low neutrophil count to the normal range after discontinuation of infusion of ritodrine and treatment with granulocyte colony stimulating factor (G-CSF). A 34-year-old woman with twin pregnancy was treated with ritodrine for preterm uterine contractions at 27 weeks and 6 days gestation. Neutropenia developed after continuous intravenous infusion of ritodrine for about 4 weeks. We ceased the ritodrine infusion immediately and treated the neutropenia with G-CSF. A cesarean delivery was performed the day after cessation of the ritodrine infusion because of uncontrolled preterm labor. There were no adverse side effects or infectious complications in the mother or the newborns. The maternal neutrophil count recovered to the normal range 4 days after administration of G-CSF. Based on prior case reports and the clinical presentation of our case, G-CSF may be a useful treatment for pregnant women with ritodrine-induced neutropenia. However, more clinical studies are required to confirm the safety and efficacy of this treatment. Copyright © 2016. Published by Elsevier B.V.

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

The Relationship between Maternal Employment Status and Pregnancy Outcomes.

PubMed

Khojasteh, Farnoush; Arbabisarjou, Azizollah; Boryri, Tahere; Safarzadeh, Amneh; Pourkahkhaei, Mohammad

2016-09-01

Women comprise a large percentage of the workforce in industrial countries. In Europe and many other places in the world, women of reproductive age comprise a significant proportion of the workforce at the workplaces, and the rules and regulations require employers to evaluate and minimize health risks to pregnant women. In U.K, 70%, and in the United States 59% of women are employed. In Iran, 13% of women are employed, which comes down to less than 5% at Sistan& Baluchestan Province. Various studies have reported contradictory results about the effects of maternal employment tasks such as standing, repetitive bending, climbing stairs, and lifting heavy objects during pregnancy on fetal growth, preterm birth and other obstetric complications. Given the growing number of working women, and potential complications for mothers, the present study has conducted to investigate the relationship between maternal employment status and pregnancy outcomes in Zahedan city, Iran. This cross-sectional study was based on survey conducted on 227 women (121 housewives, and 106 employed women) attending health centers in 2014. Using purposive convenient sampling method, eligible pregnant mothers (with no chronic diseases, singleton pregnancy, gravida 1-3, and no addiction) were selected as study subjects. Data were collected and recorded through a researcher-made questionnaire and also from mothers' medical records, including personal details, prenatal and labor complications, and infant's details. Collected data were fed into the SPSS version 21(IBM Corp, USA). Frequency of placental abruption was greater among housewives (P=0.02), and a significant relationship was found between employment status and lifting heavy objects, which was more frequent among housewives (P=0.01). Lifting heavy objects during pregnancy was only significantly related to reduced amniotic fluid (P=0.001) and low birth weight (P=0.01). Frequency of preterm labor was higher among housewives compared to employed women, but not significantly. Type of delivery was significantly related to employment, and employed mothers had more cesarean deliveries (P=0.0001). The results suggest more frequent lifting of heavy objects by housewives than by employed mothers, leading to increased complications such as reduced amniotic fluid, placental abruption, and low birth weight. Perhaps due to higher education levels, frequency of cesarean section and preterm labor was higher among employed mothers. However, employment alone does not predict pregnancy outcomes.

The Sirenomelia Sequence: A Case History

PubMed Central

Fadhlaoui, Anis; Khrouf, Mohamed; Gaigi, Soumaya; Zhioua, Fethi; Chaker, Anis

2010-01-01

We report a case of sirenomelia sequence observed in an incident of preterm labor during the 29th gestational week. According to some authors, this syndrome should be classified separately from caudal regression syndrome and is likely to be the result of an abnormality taking place during the fourth gestational week, causing developmental abnormalities in the lower extremities, pelvis, genitalia, urinary tract and digestive organs. Despite recent progress in pathology, the etiopathogenesis of sirenomelia is still debated. PMID:21769253

CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY: INTERACTION WITH GLUCOCORTICOIDS IN PC12 CELLS

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

2012-01-01

Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on concentrations relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuri to genesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent. PMID:22796634

Rethinking Stress in Parents of Preterm Infants: A Meta-Analysis

PubMed Central

Schappin, Renske; Wijnroks, Lex; Uniken Venema, Monica M. A. T.; Jongmans, Marian J.

2013-01-01

Background With improved medical outcome in preterm infants, the psychosocial situation of their families is receiving increasing attention. For parents, the birth of a preterm infant is generally regarded as a stressful experience, and therefore many interventions are based on reducing parental stress. Nevertheless, it remains unclear whether parents of children born preterm experience more stress than parents of term-born children, which would justify these interventions. This meta-analysis provides a comprehensive account of parental stress in parents of preterm infants, from birth of the infant through to their adolescence. Mean levels of stress in specific domains of family functioning were investigated, and stress levels in parents of preterm and term infants, and fathers and mothers of preterm infants, were compared. Furthermore, we investigated moderators of parental stress. Methods and Findings A random-effects meta-analysis was conducted including 38 studies describing 3025 parents of preterm (<37 wk) and low birth weight (<2500 g) infants. Parental stress was measured with two parent-reported questionnaires, the Parenting Stress Index and the Parental Stressor Scale: Neonatal Intensive Care Unit. The results indicate that parents of preterm-born children experience only slightly more stress than parents of term-born children, with small effect sizes. Furthermore, mothers have slightly more stress than fathers, but these effect sizes are also small. Parents report more stress for infants with lower gestational ages and lower birth weights. There is a strong effect for infant birth year, with decreasing parental stress from the 1980s onward, probably due to increased quality of care for preterm infants. Conclusions Based on our findings we argue that prematurity can best be regarded as one of the possible complications of birth, and not as a source of stress in itself. PMID:23405105

Visual Perception and Visual-Motor Integration in Very Preterm and/or Very Low Birth Weight Children: A Meta-Analysis

ERIC Educational Resources Information Center

Geldof, C. J. A.; van Wassenaer, A. G.; de Kieviet, J. F.; Kok, J. H.; Oosterlaan, J.

2012-01-01

A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual…

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.

[Risk factors for elevated serum total bile acid in preterm infants].

PubMed

Song, Yan-Ting; Wang, Yong-Qin; Zhao, Yue-Hua; Zhu, Hai-Ling; Liu, Qian; Zhang, Xiao; Gao, Yi-Wen; Zhang, Wei-Ye; Sang, Yu-Tong

2018-03-01

To study the risk factors for elevated serum total bile acid (TBA) in preterm infants. A retrospective analysis was performed for the clinical data of 216 preterm infants who were admitted to the neonatal intensive care unit. According to the presence or absence of elevated TBA (TBA >24.8 μmol/L), the preterm infants were divided into elevated TBA group with 53 infants and non-elevated TBA group with 163 infants. A univariate analysis and an unconditional multivariate logistic regression analysis were used to investigate the risk factors for elevated TBA. The univariate analysis showed that there were significant differences between the elevated TBA group and the non-elevated TBA group in gestational age at birth, birth weight, proportion of small-for-gestational-age infants, proportion of infants undergoing ventilator-assisted ventilation, fasting time, parenteral nutrition time, and incidence of neonatal respiratory failure and sepsis (P<0.05). The unconditional multivariate logistic regression analysis showed that low birth weight (OR=3.84, 95%CI: 1.53-9.64) and neonatal sepsis (OR=2.56, 95%CI: 1.01-6.47) were independent risk factors for elevated TBA in preterm infants. Low birth weight and neonatal sepsis may lead to elevated TBA in preterm infants.

Perinatal implications of sickle cell disease.

PubMed

MacMullen, Nancy J; Dulski, Laura A

2011-01-01

Sickle cell disease (SCD) affects millions of people across the globe. In the United States, approximately 70,000 to 100,000 people have the disease, and 2 million have the sickle cell trait. SCD occurs once in every 500 African American births, and once in 36,000 Hispanic American births. Women with SCD can have more adverse maternal outcomes such as preeclampsia, eclampsia, preterm labor, placental abruption, intrauterine growth restriction, and low birthweight. Providing comprehensive nursing care to women with SCD is a challenge, particularly during labor and birth, with nursing management aimed at attaining healthy birth outcomes while preventing or treating manifestations of the disease. Labor and delivery nurses are responsible for specific knowledge and care practices for these women, including differentiating the pain of sickle cell crisis from contraction pain and monitoring maternal and fetal oxygenation, as oxygenation is jeopardized in laboring sickle cell patients. Intrapartum nursing care also requires vigilance in the need for emergency cesarean birth. Nursing interventions include symptom management, pain management, ensuring patient safety, and educating patients. Coordination of care and clear communication between the members of the healthcare team, patient, and family are essential elements to ensure a positive outcome for perinatal patients with SCD.

The economic burden of prematurity in Canada.

PubMed

Johnston, Karissa M; Gooch, Katherine; Korol, Ellen; Vo, Pamela; Eyawo, Oghenowede; Bradt, Pamela; Levy, Adrian

2014-04-05

Preterm birth is a major risk factor for morbidity and mortality among infants worldwide, and imposes considerable burden on health, education and social services, as well as on families and caregivers. Morbidity and mortality resulting from preterm birth is highest among early (< 28 weeks gestational age) and moderate (28-32 weeks) preterm infants, relative to late preterm infants (33-36 weeks). However, substantial societal burden is associated with late prematurity due to the larger number of late preterm infants relative to early and moderate preterm infants. The aim in this study was to characterize the burden of premature birth in Canada for early, moderate, and late premature infants, including resource utilization, direct medical costs, parental out-of-pocket costs, education costs, and mortality, using a validated and published decision model from the UK, and adapting it to a Canadian setting based on analysis of administrative, population-based data from Québec. Two-year survival was estimated at 56.0% for early preterm infants, 92.8% for moderate preterm infants, and 98.4% for late preterm infants. Per infant resource utilization consistently decreased with age. For moderately preterm infants, hospital days ranged from 1.6 at age two to 0.09 at age ten. Cost per infant over the first ten years of life was estimated to be $67,467 for early preterm infants, $52,796 for moderate preterm infants, and $10,010 for late preterm infants. Based on population sizes this corresponds to total national costs of $123.3 million for early preterm infants, $255.6 million for moderate preterm infants, $208.2 million for late preterm infants, and $587.1 million for all infants. Premature birth results in significant infant morbidity, mortality, healthcare utilization and costs in Canada. A comprehensive decision-model based on analysis of a Canadian population-based administrative data source suggested that the greatest national-level burden is associated with moderate preterm infants due to both a large cost per infant and population size while the highest individual-level burden is in early preterm infants and the largest total population size is in late preterm infants. Although the highest medical costs are incurred during the neonatal period, greater resource utilization and costs extend into childhood.

Preterm Versus Term Children: Analysis of Sedation/Anesthesia Adverse Events and Longitudinal Risk.

PubMed

Havidich, Jeana E; Beach, Michael; Dierdorf, Stephen F; Onega, Tracy; Suresh, Gautham; Cravero, Joseph P

2016-03-01

Preterm and former preterm children frequently require sedation/anesthesia for diagnostic and therapeutic procedures. Our objective was to determine the age at which children who are born <37 weeks gestational age are no longer at increased risk for sedation/anesthesia adverse events. Our secondary objective was to describe the nature and incidence of adverse events. This is a prospective observational study of children receiving sedation/anesthesia for diagnostic and/or therapeutic procedures outside of the operating room by the Pediatric Sedation Research Consortium. A total of 57,227 patients 0 to 22 years of age were eligible for this study. All adverse events and descriptive terms were predefined. Logistic regression and locally weighted scatterplot regression were used for analysis. Preterm and former preterm children had higher adverse event rates (14.7% vs 8.5%) compared with children born at term. Our analysis revealed a biphasic pattern for the development of adverse sedation/anesthesia events. Airway and respiratory adverse events were most commonly reported. MRI scans were the most commonly performed procedures in both categories of patients. Patients born preterm are nearly twice as likely to develop sedation/anesthesia adverse events, and this risk continues up to 23 years of age. We recommend obtaining birth history during the formulation of an anesthetic/sedation plan, with heightened awareness that preterm and former preterm children may be at increased risk. Further prospective studies focusing on the etiology and prevention of adverse events in former preterm patients are warranted. Copyright © 2016 by the American Academy of Pediatrics.

Reproductive immunology: current status and future directions (part I).

PubMed

Peeva, Elena

2010-12-01

Extensive research work over the past couple of decades has indicated a series of intricate relations between immune and reproductive systems. A range of reproductive immunology topics including the roles of adoptive and innate immunity in infertility and pregnancy, the immune system's role in induction of labor and preterm delivery, and immuno-modulatory effects of the female sex hormones will be discussed in this and the next issue of the Journal. The implications of this research on the development of novel therapeutic approaches are also addressed.

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

PubMed Central

Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

2011-01-01

Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently without symptoms and before the onset of the fetal systemic inflammatory response syndrome. PMID:22216148

Preterm birth disrupts cerebellar development by affecting granule cell proliferation program and Bergmann glia.

PubMed

Iskusnykh, Igor Y; Buddington, Randal K; Chizhikov, Victor V

2018-08-01

Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants. In this study, we analyzed the cerebellum of preterm pigs delivered via c-section at 91% term and raised for 10 days, until term-equivalent age. The pigs did not receive any treatments known or suspected to affect cerebellar development and had no evidence of brain damage. Term pigs sacrificed at birth were used as controls. Immunohistochemical analysis revealed that preterm birth did not affect either size or numbers of Purkinje cells or molecular layer interneurons at term-equivalent age. The number of granule cell precursors and Bergmann glial fibers, however, were reduced in preterm pigs. Preterm pigs had reduced proliferation but not differentiation of granule cells. qRT-PCR analysis of laser capture microdissected external granule cell layer showed that preterm pigs had a reduced expression of Ccnd1 (Cyclin D1), Ccnb1 (Cyclin B1), granule cell master regulatory transcription factor Atoh1, and signaling molecule Jag1. In vitro rescue experiments identified Jag1 as a central granule cell gene affected by preterm birth. Thus, preterm birth and precocious exposure to the ex-utero environment disrupt cerebellum by modulating expression of key cerebellar developmental genes, predominantly affecting development of granule precursors and Bergmann glia. Copyright © 2018 Elsevier Inc. All rights reserved.

Reading abilities in school-aged preterm children: a review and meta-analysis

PubMed Central

Kovachy, Vanessa N; Adams, Jenna N; Tamaresis, John S; Feldman, Heidi M

2014-01-01

AIM Children born preterm (at ≤32wk) are at risk of developing deficits in reading ability. This meta-analysis aims to determine whether or not school-aged preterm children perform worse than those born at term in single-word reading (decoding) and reading comprehension. METHOD Electronic databases were searched for studies published between 2000 and 2013, which assessed decoding or reading comprehension performance in English-speaking preterm and term-born children aged between 6 years and 13 years, and born after 1990. Standardized mean differences in decoding and reading comprehension scores were calculated. RESULTS Nine studies were suitable for analysis of decoding, and five for analysis of reading comprehension. Random-effects meta-analyses showed that children born preterm had significantly lower scores (reported as Cohen’s d values [d] with 95% confidence intervals [CIs]) than those born at term for decoding (d=−0.42, 95% CI −0.57 to −0.27, p<0.001) and reading comprehension (d=−0.57, 95% CI −0.68 to −0.46, p<0.001). Meta-regressions showed that lower gestational age was associated with larger differences in decoding (Q[1]=5.92, p=0.02) and reading comprehension (Q[1]=4.69, p=0.03) between preterm and term groups. Differences between groups increased with age for reading comprehension (Q[1]=5.10, p=0.02) and, although not significant, there was also a trend for increased group differences for decoding (Q[1]=3.44, p=0.06). INTERPRETATION Preterm children perform worse than peers born at term on decoding and reading comprehension. These findings suggest that preterm children should receive more ongoing monitoring for reading difficulties throughout their education. PMID:25516105

Impact of stillbirths on international comparisons of preterm birth rates: a secondary analysis of the WHO multi-country survey of Maternal and Newborn Health.

PubMed

Morisaki, N; Ganchimeg, T; Vogel, J P; Zeitlin, J; Cecatti, J G; Souza, J P; Pileggi Castro, C; Torloni, M R; Ota, E; Mori, R; Dolan, S M; Tough, S; Mittal, S; Bataglia, V; Yadamsuren, B; Kramer, M S

2017-08-01

To evaluate the extent to which stillbirths affect international comparisons of preterm birth rates in low- and middle-income countries. Secondary analysis of a multi-country cross-sectional study. 29 countries participating in the World Health Organization Multicountry Survey on Maternal and Newborn Health. 258 215 singleton deliveries in 286 hospitals. We describe how inclusion or exclusion of stillbirth affect rates of preterm births in 29 countries. Preterm delivery. In all countries, preterm birth rates were substantially lower when based on live births only, than when based on total births. However, the increase in preterm birth rates with inclusion of stillbirths was substantially higher in low Human Development Index (HDI) countries [median 18.2%, interquartile range (17.2-34.6%)] compared with medium (4.3%, 3.0-6.7%), and high-HDI countries (4.8%, 4.4-5.5%). Inclusion of stillbirths leads to higher estimates of preterm birth rate in all countries, with a disproportionately large effect in low-HDI countries. Preterm birth rates based on live births alone do not accurately reflect international disparities in perinatal health; thus improved registration and reporting of stillbirths are necessary. Inclusion of stillbirths increases preterm birth rates estimates, especially in low-HDI countries. © 2017 World Health Organization, licensed by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Molecular microbiological characterization of preterm neonates at risk of bronchopulmonary dysplasia.

PubMed

Payne, Matthew S; Goss, Kevin C W; Connett, Gary J; Kollamparambil, Tanoj; Legg, Julian P; Thwaites, Richard; Ashton, Mark; Puddy, Victoria; Peacock, Janet L; Bruce, Kenneth D

2010-04-01

The role of infection in bronchopulmonary dysplasia (BPD) is unknown. We present an observational study of 55 premature infants born weighing less than 1.3 kg within two level III neonatal intensive care units. Endotracheal aspirates (ETA) and nasogastric aspirates (NGA) were studied with denaturing gradient gel electrophoresis (DGGE) profiling to elucidate the total bacterial community, and species-specific PCR was used to detect the presence of Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum. DGGE identified bacterial species in 59% of NGA and ETA samples combined. A diverse range of species were identified including several implicated in preterm labor. Species-specific PCR identified M. hominis in 25% of NGA and 11% of ETA samples. Among the 48 infants surviving up to 36 wk-postconceptual age, ordinal logistic regression showed the odds ratio for BPD or death where Ureaplasma was present/absent as 4.80 (95% CI 1.15-20.13). After adjusting for number of days ventilated, this was reduced to 2.04 (0.41-10.25). These data demonstrate how the combined use of DGGE and species-specific PCR identifies a high exposure in utero and around the time of birth to bacteria that might be causally related to preterm delivery and subsequent lung injury.

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.

Integrated microRNA and mRNA network analysis of the human myometrial transcriptome in the transition from quiescence to labor.

PubMed

Ackerman, William E; Buhimschi, Irina A; Brubaker, Douglas; Maxwell, Sean; Rood, Kara M; Chance, Mark R; Jing, Hongwu; Mesiano, Sam; Buhimschi, Catalin S

2018-02-13

We conducted integrated transcriptomics network analyses of miRNA and mRNA interactions in human myometrium to identify novel molecular candidates potentially involved in human parturition. Myometrial biopsies were collected from women undergoing primary Cesarean deliveries in well-characterized clinical scenarios: 1) spontaneous term labor (TL, n = 5); 2) term non-labor (TNL, n = 5); 3) spontaneous preterm birth (PTB) with histologic chorioamnionitis (PTB-HCA, n = 5); and 4) indicated PTB non-labor (PTB-NL, n = 5). MicroRNAs and long RNAs were profiled using RNA sequencing, and miRNA-target interaction networks were mined for key discriminatory subnetworks. Forty miRNAs differed between TL and TNL myometrium while seven miRNAs differed between PTB-HCA vs. PTB-NL specimens; six of these miRNAs were cross-validated using quantitative PCR. Based on the combined sequencing data, unsupervised clustering revealed two non-overlapping cohorts that differed primarily by absence or presence of uterine quiescence, rather than gestational age or original clinical cohort. The intersection of differentially expressed miRNAs and their mRNA targets predicted 22 subnetworks with enriched representation of miR-146b-5p, miR-223-3p, and miR-150-5p among miRNAs, and of myocyte enhancer factor-2C (MEF2C) among mRNAs. Of four known MEF2 transcription factors, decreased MEF2A and MEF2C expression in women with uterine non-quiescence was observed in the transcriptome profiling data, and validated in a second cohort by quantitative PCR. Immunohistochemistry localized MEF2A and MEF2C to myometrial smooth muscle cells and confirmed decreased abundance with labor. Collectively, these results suggest that repression of MEF2 expression may represent a previously unrecognized process through which miRNAs contribute to the phenotypic switch from quiescence to labor in human myometrium. © The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Probiotics Prevent Late-Onset Sepsis in Human Milk-Fed, Very Low Birth Weight Preterm Infants: Systematic Review and Meta-Analysis.

PubMed

Aceti, Arianna; Maggio, Luca; Beghetti, Isadora; Gori, Davide; Barone, Giovanni; Callegari, Maria Luisa; Fantini, Maria Pia; Indrio, Flavia; Meneghin, Fabio; Morelli, Lorenzo; Zuccotti, Gianvincenzo; Corvaglia, Luigi

2017-08-22

Growing evidence supports the role of probiotics in reducing the risk of necrotizing enterocolitis, time to achieve full enteral feeding, and late-onset sepsis (LOS) in preterm infants. As reported for several neonatal clinical outcomes, recent data have suggested that nutrition might affect probiotics' efficacy. Nevertheless, the currently available literature does not explore the relationship between LOS prevention and type of feeding in preterm infants receiving probiotics. Thus, the aim of this systematic review and meta-analysis was to evaluate the effect of probiotics for LOS prevention in preterm infants according to type of feeding (exclusive human milk (HM) vs. exclusive formula or mixed feeding). Randomized-controlled trials involving preterm infants receiving probiotics and reporting on LOS were included in the systematic review. Only trials reporting on outcome according to feeding type were included in the meta-analysis. Fixed-effects models were used and random-effects models were used when significant heterogeneity was found. The results were expressed as risk ratio (RR) with 95% confidence interval (CI). Twenty-five studies were included in the meta-analysis. Overall, probiotic supplementation resulted in a significantly lower incidence of LOS (RR 0.79 (95% CI 0.71-0.88), p < 0.0001). According to feeding type, the beneficial effect of probiotics was confirmed only in exclusively HM-fed preterm infants (RR 0.75 (95% CI 0.65-0.86), p < 0.0001). Among HM-fed infants, only probiotic mixtures, and not single-strain products, were effective in reducing LOS incidence (RR 0.68 (95% CI 0.57-0.80) p < 0.00001). The results of the present meta-analysis show that probiotics reduce LOS incidence in exclusively HM-fed preterm infants. Further efforts are required to clarify the relationship between probiotics supplementation, HM, and feeding practices in preterm infants.

Probiotics Prevent Late-Onset Sepsis in Human Milk-Fed, Very Low Birth Weight Preterm Infants: Systematic Review and Meta-Analysis

PubMed Central

Aceti, Arianna; Maggio, Luca; Beghetti, Isadora; Barone, Giovanni; Callegari, Maria Luisa; Fantini, Maria Pia; Indrio, Flavia; Meneghin, Fabio; Morelli, Lorenzo; Corvaglia, Luigi

2017-01-01

Growing evidence supports the role of probiotics in reducing the risk of necrotizing enterocolitis, time to achieve full enteral feeding, and late-onset sepsis (LOS) in preterm infants. As reported for several neonatal clinical outcomes, recent data have suggested that nutrition might affect probiotics’ efficacy. Nevertheless, the currently available literature does not explore the relationship between LOS prevention and type of feeding in preterm infants receiving probiotics. Thus, the aim of this systematic review and meta-analysis was to evaluate the effect of probiotics for LOS prevention in preterm infants according to type of feeding (exclusive human milk (HM) vs. exclusive formula or mixed feeding). Randomized-controlled trials involving preterm infants receiving probiotics and reporting on LOS were included in the systematic review. Only trials reporting on outcome according to feeding type were included in the meta-analysis. Fixed-effects models were used and random-effects models were used when significant heterogeneity was found. The results were expressed as risk ratio (RR) with 95% confidence interval (CI). Twenty-five studies were included in the meta-analysis. Overall, probiotic supplementation resulted in a significantly lower incidence of LOS (RR 0.79 (95% CI 0.71–0.88), p < 0.0001). According to feeding type, the beneficial effect of probiotics was confirmed only in exclusively HM-fed preterm infants (RR 0.75 (95% CI 0.65–0.86), p < 0.0001). Among HM-fed infants, only probiotic mixtures, and not single-strain products, were effective in reducing LOS incidence (RR 0.68 (95% CI 0.57–0.80) p < 0.00001). The results of the present meta-analysis show that probiotics reduce LOS incidence in exclusively HM-fed preterm infants. Further efforts are required to clarify the relationship between probiotics supplementation, HM, and feeding practices in preterm infants. PMID:28829405

Antepartum Fetal Monitoring and Spectral Analysis of Preterm Birth Risk

NASA Astrophysics Data System (ADS)

Păsăricără, Alexandru; Nemescu, Dragoş; Arotăriţei, Dragoş; Rotariu, Cristian

2017-11-01

The monitoring and analysis of antepartum fetal and maternal recordings is a research area of notable interest due to the relatively high value of preterm birth. The interest stems from the improvement of devices used for monitoring. The current paper presents the spectral analysis of antepartum heart rate recordings conducted during a study in Romania at the Cuza Voda Obstetrics and Gynecology Clinical Hospital from Iasi between 2010 and 2014. The study focuses on normal and preterm birth risk subjects in order to determine differences between these two types or recordings in terms of spectral analysis.

Economic consequences of over-diagnosis of threatened preterm labor.

PubMed

Coloma, Marta; Kang, Fatima; Vallejo-Torres, Laura; Díaz, Paloma; Méndez, Yurena; Álvarez de la Rosa, Margarita

2018-05-01

To investigate whether adherence to a cervical length-based protocol can reduce both unnecessary admissions and the socioeconomic costs associated with inappropriately admitted patients. The present retrospective observational study included women admitted for threatened preterm labor (TPL) at 24-34 weeks of pregnancy to a tertiary hospital in the Canary Islands, 2009-2014. Data were reviewed from all patients admitted for TPL. Those with a long cervix (>25 mm) were classified as "inappropriate admissions", and both the economic burden based on diagnosis-related group (DRG) and the social costs associated with sick leave for these women were calculated. During the 6-year study period, 430 women were admitted for TPL. The rate of inappropriate hospital admissions was 45% in the first year, but was reduced to 23% in the final year (P<0.001); the premature delivery rates in these years did not differ (P=0.224). The mean DRG-based cost of the admission per patient with a long cervix was EU euros €2099. The total annual costs from inappropriate admission (both social security sick leave costs and hospital costs) were estimated to be up to €571 047.37 during the 6-year study period, and reduced from €60 420.76 in 2009 to €29 998.04 in 2014. Reductions in inappropriate admissions from applying cervical length-based management protocol could reduce healthcare costs without increasing the incidence of premature delivery. © 2018 International Federation of Gynecology and Obstetrics.

The Impact of Maternal Body Mass Index and Gestational Age on the Detection of Uterine Contractions by Tocodynamometry

PubMed Central

Aina-Mumuney, A.; Hwang, K.; Sunwoo, N.; Burd, I.; Blakemore, K.

2015-01-01

Objective: To examine the impact of maternal body mass index (BMI) and gestational age (GA) on uterine contraction detection by tocodynamometry. Methods: Gravidas with preterm labor (PTL) complaints who were evaluated by tocodynamometry, discharged from Labor and Delivery triage, and subsequently readmitted for preterm delivery were studied. Forty-six patients in whom contractions were detected (group 1) were compared to 49 women in whom contractions were not detected (group 2) with respect to BMI and GA at both evaluation and delivery. Multivariable logistic regression was used to adjust for confounders. Results: Group 2 had a higher mean BMI (31.7 vs 26.1, P < .001), were more likely to be obese (57.1% vs 19.6%, P < .001), and were more likely to have been evaluated in the mid-trimester (36.7% vs 17.4%, P = .04) compared to group 1. Independent risk factors for the inability of the tocodynamometer to detect contractions were obesity (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.07-0.46) and evaluation in the mid-trimester (OR 0.33, 95% CI 0.13-0.84). Conclusion: Our study provides evidence that the effectiveness of tocodynamometry diminishes with increasing maternal BMI. Efficacy of tocodynamometry is also decreased at earlier GA, most pronounced below 25 weeks. To evaluate women with PTL symptoms in the mid-trimester or symptomatic obese women at any GA, a modality other than tocodynamometry could be valuable to more accurately assess uterine activity. PMID:26499394

A TIME SERIES ANALYSIS OF AIR POLLUTION AND PRE-TERM BIRTH IN PENNSYLVANIA, 1997-2001

EPA Science Inventory

Background: Preterm delivery can lead to serious infant health outcomes including death and life-long disability. Small increases in preterm delivery risk in relation to air pollution have been reported, but prior investigations may have inadequately controlled for individual fac...

The choice of amniotic fluid in metabolomics for the monitoring of fetus health.

PubMed

Palmas, Francesco; Fattuoni, Claudia; Noto, Antonio; Barberini, Luigi; Dessì, Angelica; Fanos, Vassilios

2016-01-01

Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus's urine. Since AF reflects the mother's and the fetus's health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.

Prostaglandin E2 Regulates Its Own Inactivating Enzyme, 15-PGDH, by EP2 Receptor-Mediated Cervical Cell-Specific Mechanisms

PubMed Central

Kishore, A. Hari; Owens, David

2014-01-01

Context: Prostaglandins play important roles in parturition and have been used to induce cervical ripening and labor. Prior to cervical ripening at term, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is highly expressed in the cervix and metabolizes cyclooxygenase-2-mediated increases in active prostaglandin E2 (PGE2) to inactive 15-keto PGE2. At term, 15-PGDH gene expression decreases and PGE2 accumulates, leading to cervical ripening and labor. Previously, we found that the cervical isoform of microphthalmia-associated transcription factor (MiTF-CX) serves as a progestational transcription factor that represses IL-8 and hypoxia-mediated increases in cyclooxygenase-2. Objective: We tested the hypothesis that PGE2 regulates its own inactivation through MiTF-CX. Design: We used human cervical stromal cells to investigate the regulation of 15-PGDH. Setting: This was a laboratory-based study using cells from clinical tissue samples. Main Outcome Measures: We evaluated the mechanisms by which PGE2 regulates 15-PGDH in human cervical stromal cells. Results: PGE2 repressed MiTF-CX and 15-PGDH, whereas ectopic overexpression of MiTF-CX induced 15-PGDH expression levels. Stabilization of HIF-1α by deferoxamine resulted in concomitant down-regulation of MiTF-CX and 15-PGDH. Ectopic overexpression of MiTF-CX abrogated PGE2- and deferoxamine-mediated loss of MiTF-CX and 15-PGDH. PGE2-induced loss of MiTF-CX and 15-PGDH was mediated through prostaglandin E2 receptor (EP2) receptors (PTGER2), but not cAMP. Conclusions: The 15-PGDH gene is a MiTF-CX target gene in cervical stromal cells and is down-regulated by PGE2 through EP2 receptors. The findings suggest that EP2 receptor-specific antagonists may be used as an adjunct to present clinical management for the prevention of preterm cervical ripening and preterm labor. PMID:24471568

Cell-free DNA, inflammation, and the initiation of spontaneous term labor.

PubMed

Herrera, Christina A; Stoerker, Jay; Carlquist, John; Stoddard, Gregory J; Jackson, Marc; Esplin, Sean; Rose, Nancy C

2017-11-01

Hypomethylated cell-free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. To determine the changes in cell-free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor. In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cell-free DNA concentration, methylation ratio, and interleukin-6 were analyzed. The primary outcome was the difference in methylation ratio in women with labor vs without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status. A total of 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly greater methylation ratio (P = .001) and interleukin-6 (P < .001) on admission for delivery than women without labor. After we controlled for body mass index and maternal age, methylation ratio (adjusted relative risk, 1.38; 95% confidence interval, 1.13 to 1.68) and interleukin-6 (adjusted relative risk, 1.12, 95% confidence interval, 1.07 to 1.17) remained greater in women presenting in labor. Total cell-free DNA was not significantly different in women with labor compared with women without. Longitudinally, total cell-free DNA (P < .001 in labor, P = .002 without labor) and interleukin-6 (P < .001 in labor, P = .01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (P = .02). Spontaneous labor at term is associated with a greater cell-free DNA methylation ratio and interleukin-6 compared with nonlabored controls. As gestation advances, total cell-free DNA concentrations and interleukin-6 levels increase. A greater methylation ratio reflects a greater maternal contribution (vs placental) in women with labor, likely resulting from greater levels of neutrophils, lymphocytes, and uterine activation proteins at the time of labor. Although not significant, women in labor had a greater total cell-free DNA concentration and thus could theoretically have more hypomethylated DNA available for interaction with the inflammatory cascade. Larger studies are needed to investigate this theory. Published by Elsevier Inc.

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.

Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies.

PubMed

Vornhagen, Jay; Adams Waldorf, Kristina M; Rajagopal, Lakshmi

2017-11-01

Group B streptococcus (GBS) or Streptococcus agalactiae is a β-hemolytic, Gram-positive bacterium that is a leading cause of neonatal infections. GBS commonly colonizes the lower gastrointestinal and genital tracts and, during pregnancy, neonates are at risk of infection. Although intrapartum antibiotic prophylaxis during labor and delivery has decreased the incidence of early-onset neonatal infection, these measures do not prevent ascending infection that can occur earlier in pregnancy leading to preterm births, stillbirths, or late-onset neonatal infections. Prevention of GBS infection in pregnancy is complex and is likely influenced by multiple factors, including pathogenicity, host factors, vaginal microbiome, false-negative screening, and/or changes in antibiotic resistance. A deeper understanding of the mechanisms of GBS infections during pregnancy will facilitate the development of novel therapeutics and vaccines. Here, we summarize and discuss important advancements in our understanding of GBS vaginal colonization, ascending infection, and preterm birth. Copyright © 2017 Elsevier Ltd. All rights reserved.

High-order multiple gestations.

PubMed

Elliott, John P

2005-10-01

Infertility treatments have produced an increase in multiple gestations with twins accounting for 3.3% of births in the United States in 2002. Over that same time period, premature deliveries increased from 10.7% in 1992 to 12.1% in 2002. High-order multiple gestations have also increased, and virtually all of those deliver prematurely. Clinicians are facing the challenge of managing these complicated pregnancies. Neonatal outcome will primarily depend on the gestational age at delivery and the birth weight of the babies. Care is directed at aggressively and proactively preventing preterm delivery. Ultrasound assessments are made frequently to assess fetal anatomical abnormalities, nuchal translucency, fetal growth, cervical length, amniotic fluid, and biophysical profile. Stress reduction and activity reduction will decrease uterine activity, and tocolytic drugs are employed to decrease background contractions to reduce preterm labor (PTL). Fetal fibronectin testing helps predict risk of PTL, and magnesium sulfate tocolysis is used in aggressive dosing to arrest PTL if it occurs. Outcomes are presented and discussed. Successful outcomes are not only possible, but probable.

[Comparative analysis of risk factors for preterm and small-for-gestational-age births].

PubMed

Zhong, Xin-Qi; Cui, Qi-Liang

2014-12-01

To compare the risk factors between preterm and small-for-gestational-age (SGA) births. A total of 1 270 newborns who had no obstetric risk factors or maternal diseases were enrolled in this study. Their mothers' stature, body weight, passive smoking, and history of abnormal pregnancy were investigated using the self-designed questionnaire. The infants were divided into four groups: preterm, appropriate-for-gestational-age (AGA), SGA, and term infants. Multivariate logistic regression analysis was performed to compare the risk factors between preterm and SGA births. A weight gain less than 9 kg during pregnancy increased the risks of preterm (OR=1.63, 95% CI: 1.12-2.07) and SGA (OR=1.92, 95% CI: 1.56-2.58). The histories of abortion (OR=1.46, 95% CI: 1.09-1.93) and preterm birth (OR=2.63, 95% CI: 1.81-3.92) were independent risk factors for preterm births, while low pre-pregnancy body mass index (<18.5) (OR=2.16, 95% CI: 1.53-3.16), short stature (<1.55 m) (OR=2.46, 95% CI: 1.78-3.48), and passive smoking (OR=2.24, 95% CI: 1.65-2.98) were independent risk factors for SGA births. Due to different risk factors between preterm and SGA births, specific preventive measures should be taken pertinently to reduce the incidence of the two bad pregnancy outcomes.

Maternal Dietary Nutrient Intake and Its Association  with Preterm Birth: A Case-control Study in Beijing,  China.

PubMed

Zhang, Yan; Zhou, Hong; Perkins, Anthony; Wang, Yan; Sun, Jing

2017-03-01

This study aimed to evaluate dietary nutrient intake among Chinese pregnant women by comparison with Chinese Dietary Reference Intakes (DRIs) and to explore the association between dietary nutrients and preterm birth. A case-control design was conducted in Beijing with 130 preterm delivery mothers in case group and 381 term delivery mothers in control group. Information on mothers' diet was collected using a food frequency questionnaire, and nutrients and energy intakes were subsequently calculated based on DRIs. Multivariate analysis of variance was used to compare the differences between term and preterm groups in relation to dietary nutrients. Dietary nutrient intakes were imbalanced in both groups compared with Chinese DRIs. Preterm delivery mothers had a lower level of fat and vitamin E intake than term delivery mothers (p < 0.05). Multivariate analysis showed lower vitamin E intake in preterm delivery mothers with a prepregnancy BMI < 18.5 kg/m2 (p < 0.05) and higher carbohydrate intake in preterm delivery mothers with prepregnancy BMI ≥ 24 kg/m2 (p < 0.05). An imbalanced diet in both groups and low level of dietary intakes of fat and vitamin E in preterm group suggest health education measures should be taken to improve the dietary quality of pregnant women, especially for those with an abnormal prepregnancy BMI.

Determinants of preterm birth rates in Canada from 1981 through 1983 and from 1992 through 1994.

PubMed

Joseph, K S; Kramer, M S; Marcoux, S; Ohlsson, A; Wen, S W; Allen, A; Platt, R

1998-11-12

The rates of preterm birth have increased in many countries, including Canada, over the past 20 years. However, the factors underlying the increase are poorly understood. We used data from the Statistics Canada live-birth and stillbirth data bases to determine the effects of changes in the frequency of multiple births, registration of births occurring very early in gestation, patterns of obstetrical intervention, and use of ultrasonographic dating of gestational age on the rates of preterm birth in Canada from 1981 through 1983 and from 1992 through 1994. All births in 9 of the 12 provinces and territories of Canada were included. Logistic-regression analysis and Poisson regression analysis were used to estimate changes between the two three-year periods, after adjustment for the above-mentioned determinants of the likelihood of preterm births. Preterm births increased from 6.3 percent of live births in 1981 through 1983 to 6.8 percent in 1992 through 1994, a relative increase of 9 percent (95 percent confidence interval, 7 to 10 percent). Among singleton births, preterm births increased by 5 percent (95 percent confidence interval, 3 to 6 percent). Multiple births increased from 1.9 percent to 2.1 percent of all live births; the rates of preterm birth among live births resulting from multiple gestations increased by 25 percent (95 percent confidence interval, 21 to 28 percent). Adjustment for the determinants of the likelihood of preterm birth reduced the increase in the rate of preterm birth to 3 percent among all live births and 1 percent among singleton births. The recent increase in preterm births in Canada is largely attributable to changes in the frequency of multiple births, obstetrical intervention, and the use of ultrasound-based estimates of gestational age.

Hematopoietic Stem Cells in Neonates: Any Differences between Very Preterm and Term Neonates?

PubMed Central

Wisgrill, Lukas; Schüller, Simone; Bammer, Markus; Berger, Angelika; Pollak, Arnold; Radke, Teja Falk; Kögler, Gesine; Spittler, Andreas; Helmer, Hanns; Husslein, Peter; Gortner, Ludwig

2014-01-01

Background In the last decades, human full-term cord blood was extensively investigated as a potential source of hematopoietic stem and progenitor cells (HSPCs). Despite the growing interest of regenerative therapies in preterm neonates, only little is known about the biological function of HSPCs from early preterm neonates under different perinatal conditions. Therefore, we investigated the concentration, the clonogenic capacity and the influence of obstetric/perinatal complications and maternal history on HSPC subsets in preterm and term cord blood. Methods CD34+ HSPC subsets in UCB of 30 preterm and 30 term infants were evaluated by flow cytometry. Clonogenic assays suitable for detection of the proliferative potential of HSPCs were conducted. Furthermore, we analyzed the clonogenic potential of isolated HSPCs according to the stem cell marker CD133 and aldehyde dehydrogenase (ALDH) activity. Results Preterm cord blood contained a significantly higher concentration of circulating CD34+ HSPCs, especially primitive progenitors, than term cord blood. The clonogenic capacity of HSPCs was enhanced in preterm cord blood. Using univariate analysis, the number and clonogenic potential of circulating UCB HSPCs was influenced by gestational age, birth weight and maternal age. Multivariate analysis showed that main factors that significantly influenced the HSPC count were maternal age, gestational age and white blood cell count. Further, only gestational age significantly influenced the clonogenic potential of UCB HSPCs. Finally, isolated CD34+/CD133+, CD34+/CD133– and ALDHhigh HSPC obtained from preterm cord blood showed a significantly higher clonogenic potential compared to term cord blood. Conclusion We demonstrate that preterm cord blood exhibits a higher HSPC concentration and increased clonogenic capacity compared to term neonates. These data may imply an emerging use of HSPCs in autologous stem cell therapy in preterm neonates. PMID:25181353

A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants.

PubMed

Fenton, Tanis R; Kim, Jae H

2013-04-20

The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts.

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.

What is the impact of interventions that prevent fetal mortality on the increase of preterm live births in the State of Sao Paulo, Brazil?

PubMed

Alencar, Gizelton Pereira; da Silva, Zilda Pereira; Santos, Patrícia Carla; Raspantini, Priscila Ribeiro; Moura, Barbara Laisa Alves; de Almeida, Marcia Furquim; do Nascimento, Felipe Parra; Rodrigues, Laura C

2015-07-23

There is a global growing trend of preterm births and a decline trend of fetal deaths. Is there an impact of the decline of fetal mortality on the increase of preterm live births in State of Sao Paulo, Brazil? The time trends were evaluated by gestational age through exponential regression analysis. Data analyzed included the fetal mortality ratio, proportion of preterm live births, fertility rate of women 35 years and over, prenatal care, mother's education, multiple births and cesarean section deliveries. A survival analysis was carried out for 2000 and 2010. Preterm births showed the highest annual increase (3.2%) in the less than 28 weeks of gestation group and fetal mortality ratio decreased (7.4%) in the same gestational age group. There was an increase of cesarean section births and it was higher in the < 28 weeks group (6.1%). There was a decreased annual trend of mothers with inadequate prenatal care (6.1%) and low education (8.8%) and an increased trend in multiple births and fertility rates of women of 35 years and over. The variables were highly correlated to which other over time. In 2000, 8.2% of all pregnancies resulted in preterm births (0.9% in fetal deaths and 7.3% in live births). In 2010, the preterm birth increased to 9.4% (0.8% were preterm fetal deaths and 8.6% preterm live births). The results suggest that 45.2% could be the maximum contribution of successful interventions to prevent a fetal death on the increase in preterm live births. This increasing trend is also related to changes of the women reproductive profile with the change of the women reproductive profile and access to prenatal care.

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.

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.

Long-Term Impact of Intrauterine Neuroinflammation and Treatment with Magnesium Sulphate and Betamethasone: Sex-Specific Differences in a Preterm Labor Murine Model

DTIC Science & Technology

2017-12-20

offspring per litter assessed on post -natal day S with the exception of PBS vs. PBS+ MgS04/betamethasone control groups (student’s t- test P<O.OS... Design Timed pregnant CD1 mice - surgeries on E17.5 I I -----------------------------------1 1 Intrauterine injection 1 t t PBS LPS .- -----J...experimental adult animals and if there is a sex-specific difference in their response has not been tested . Based on the above, we hypothesize that

Listeriosis and Toxoplasmosis in Pregnancy: Essentials for Healthcare Providers.

PubMed

Pfaff, Nicole Franzen; Tillett, Jackie

2016-01-01

Listeriosis and toxoplasmosis are foodborne illnesses that can have long-term consequences when contracted during pregnancy. Listeriosis is implicated in stillbirth, preterm labor, newborn sepsis, and meningitis, among other complications. Toxoplasmosis is associated with blindness, cognitive delays, seizures, and hearing loss, among other significant disabilities. Healthcare providers who understand the fundamentals of Listeria and Toxoplasma infection will have the tools to identify symptoms and high-risk behaviors, educate women to make safer decisions, and provide anticipatory guidance if a pregnant woman would become infected with either of these foodborne illnesses.

Amniocentesis for Fetal Lung Maturity: Will It Become Obsolete?

PubMed Central

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

Amniocentesis for fetal lung maturity has historically been performed for many reasons: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate. PMID:24826202

Amniocentesis for fetal lung maturity: will it become obsolete?

PubMed

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

Preeclampsia and retinopathy of prematurity in preterm births.

PubMed

Yu, Xiao Dan; Branch, D Ware; Karumanchi, S Ananth; Zhang, Jun

2012-07-01

The relationship between gestational hypertension, preeclampsia, and the risk of retinopathy of prematurity (ROP) remains unclear. Thus, we used a large cohort database to study the influence of maternal gestational hypertension and preeclampsia on the occurrence of ROP in preterm infants. We used data from a previous retrospective cohort study that includes 25,473 eligible preterm neonates. We examined the association between gestational hypertension, preeclampsia, and ROP while controlling for potential confounders by multiple logistic regression analysis. Of the 8758 early preterm infants (gestational age <34 weeks), 1024 (11.69%) had ROP, while of the 16,715 late preterm infants, only 29 (0.17%) had ROP. After adjusting for confounders, preeclampsia was associated with a significantly reduced risk of ROP (adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI], 0.49-0.86 for early preterm birth; aOR, 0.10; 95% CI, 0.01-0.93 for late preterm birth; aOR, 0.66; 95% CI, 0.50-0.87 for all preterm births). Gestational hypertension was not significantly associated with ROP at early or late preterm births. Preeclampsia, but not gestational hypertension, was associated with a reduced risk of ROP in preterm births.

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.

Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel regulator of human parturition.

PubMed

Dunand, C; Hoffmann, P; Sapin, V; Blanchon, L; Salomon, A; Sergent, F; Benharouga, M; Sabra, S; Guibourdenche, J; Lye, S J; Feige, J J; Alfaidy, N

2014-09-01

EG-VEGF is an angiogenic factor that we identified as a new placental growth factor during human pregnancy. EG-VEGF is also expressed in the mouse fetal membrane (FM) by the end of gestation, suggesting a local role for this protein in the mechanism of parturition. However, injection of EG-VEGF to gravid mice did not induce labor, suggesting a different role for EG-VEGF in parturition. Here, we searched for its role in the FM in relation to human parturition. Human pregnant sera and total FM, chorion, and amnion were collected during the second and third trimesters from preterm no labor, term no labor, and term labor patients. Primary human chorion trophoblast and FM explants cultures were also used. We demonstrate that circulating EG-VEGF increased toward term and significantly decreased at the time of labor. EG-VEGF production was higher in the FM compared to placentas matched for gestational age. Within the FM, the chorion was the main source of EG-VEGF. EG-VEGF receptors, PROKR1 and PROKR2, were differentially expressed within the FM with increased expression toward term and an abrupt decrease with the onset of labor. In chorion trophoblast and FM explants collected from nonlaboring patients, EG-VEGF decreased metalloproteinase-2 and -9 activities and increased PGDH (prostaglandin-metabolizing enzyme) expression. Altogether these data demonstrate that EG-VEGF is a new cytokine that acts locally to ensure FM protection in late pregnancy. Its fine contribution to the initiation of human labor is exhibited by the abrupt decrease in its levels as well as a reduction in its receptors. © 2014 by the Society for the Study of Reproduction, Inc.

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.

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.

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

Age correction in cognitive, linguistic, and motor domains for infants born preterm: an analysis of the Bayley Scales of Infant and Toddler Development, Third Edition developmental patterns.

PubMed

Morsan, Valentina; Fantoni, Carlo; Tallandini, Maria Anna

2018-03-15

To verify whether it is appropriate to use age correction for infants born preterm in all the developmental domains (cognitive, linguistic, and motor) considered by the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Seventy-three infants born preterm (26-35wks) without major neurological sequelae and 67 infants born at term were assessed at 12 months (corrected age for infants born preterm). The performance of the infants born preterm was assessed with two different evaluations: scores based on uncorrected age and scores based on corrected age. The developmental trends of infants born at term and infants born preterm differ across domains. Statistical analysis shows that age correction produces an overrated estimate of motor performance (12.5 points [95% confidence interval 9.05-16.01]) but not of cognitive performance. Given the broad use of the Bayley-III by psychologists and paediatricians, these results are important in the early diagnosis of developmental difficulties for children born preterm. Correction for gestational age should be applied for the cognitive domain only; whereas for the motor domain, chronological age should be used. No clear data emerged for language. Age correction with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) for infants born preterm should be applied differently in cognitive, language, and motor domains. Using corrected age with Bayley-III, the motor skills are overrated. Correction for preterm births adequately measures cognitive skills. No clear indication emerged about language skills. © 2018 Mac Keith Press.

Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes.

PubMed

Luo, Xiucui; Pan, Jing; Wang, Leilei; Wang, Peirong; Zhang, Meijiao; Liu, Meilin; Dong, Ziqing; Meng, Qian; Tao, Xuguang; Zhao, Xinliang; Zhong, Julia; Ju, Weina; Gu, Yang; Jenkins, Edmund C; Brown, W Ted; Shi, Qingxi; Zhong, Nanbert

2015-02-15

Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. Here, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR. A total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB + PPROM), as compared to those from full-term labor (FTB + PROM) and from premature rupture of membranes (PPROM + PROM), as compared to those from non-rupture of membranes (sPTB + FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM. Differentially expressed lncRNAs that were identified from the human placentas of sPTB and PPROM may regulate their associated mRNAs through differential mechanisms and connect the ubiquitin-proteasome system with infection-inflammation pathways. Although the detailed mechanisms by which lncRNAs regulate their associated mRNAs in sPTB and PPROM are yet to be clarified, our findings open a new approach to explore the pathogenesis of sPTB and PPROM.

Drug delivery to the human and mouse uterus using immunoliposomes targeted to the oxytocin receptor.

PubMed

Paul, Jonathan W; Hua, Susan; Ilicic, Marina; Tolosa, Jorge M; Butler, Trent; Robertson, Sarah; Smith, Roger

2017-03-01

The ability to provide safe and effective pharmacotherapy during obstetric complications, such as preterm labor or postpartum hemorrhage, is hampered by the systemic toxicity of therapeutic agents leading to adverse side effects in the mother and fetus. Development of novel strategies to target tocolytic and uterotonic agents specifically to uterine myocytes would improve therapeutic efficacy while minimizing the risk of side effects. Ligand-targeted liposomes have emerged as a reliable and versatile platform for targeted drug delivery to specific cell types, tissues or organs. Our objective was to develop a targeted drug delivery system for the uterus utilizing an immunoliposome platform targeting the oxytocin receptor. We conjugated liposomes to an antibody that recognizes an extracellular domain of the oxytocin receptor. We then examined the ability of oxytocin receptor-targeted liposomes to deliver contraction-blocking (nifedipine, salbutamol and rolipram) or contraction-enhancing (dofetilide) agents to strips of spontaneously contracting myometrial tissue in vitro (human and mouse). We evaluated the ability of oxytocin receptor-targeted liposomes to localize to uterine tissue in vivo, and assessed if targeted liposomes loaded with indomethacin were capable of preventing lipopolysaccharide-induced preterm birth in mice. Oxytocin receptor-targeted liposomes loaded with nifedipine, salbutamol or rolipram consistently abolished human myometrial contractions in vitro, while oxytocin receptor-targeted liposomes loaded with dofetilide increased contraction duration. Nontargeted control liposomes loaded with these agents had no effect. Similar results were observed in mouse uterine strips. Following in vivo administration to pregnant mice, oxytocin receptor-targeted liposomes localized specifically to the uterine horns and mammary tissue. Targeting increased localization to the uterus 7-fold. Localization was not detected in the maternal brain or fetus. Targeted and nontargeted liposomes also localized to the liver. Oxytocin receptor-targeted liposomes loaded with indomethacin were effective in reducing rates of preterm birth in mice, whereas nontargeted liposomes loaded with indomethacin had no effect. Our results demonstrate that oxytocin receptor-targeted liposomes can be used to either inhibit or enhance human uterine contractions in vitro. In vivo, the liposomes localized to the uterine tissue of pregnant mice and were effective in delivering agents for the prevention of inflammation-induced preterm labor. The potential clinical advantage of targeted liposomal drug delivery to the myometrium is reduced dose and reduced toxicity to both mother and fetus. Copyright © 2016. Published by Elsevier Inc.

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

Actinomyces in Pregnancy: A Review of the Literature.

PubMed

Estrada, Sarah M; Magann, Everett F; Napolitano, Peter G

2017-04-01

Actinomyces is commonly found in many areas of the body where it derives a benefit without harming the host. When it does infect the host during pregnancy, is that infection a threat to the obstetric patient and does that infection cause adverse pregnancy outcomes? The aim of this study was to review what is known about Actinomyces infections and the impact of an Actinomyces infection on pregnancy outcomes. A PubMed search was undertaken with the search years unlimited to April 1, 2016, and restricted to articles in English. The search terms included "actinomyces," "pregnancy," "prenatal," "maternal," "actinomyces infection," "pregnancy," "chorioamnionitis," "preterm labor," "premature birth," or "postpartum actinomyces." Eighteen of the 154 identified articles are the basis of this review. Actinomyces is a rod-like positive bacterium. The diagnosis of an Actinomyces infection can be by culture or Gram stain. Actinomyces is commensal and typically only infects after a mucosal break or lesion. Seventeen cases were identified in pregnancy. Ten cases were complicated by chorioamnionitis and a preterm delivery. A nidus leading to infection was identified in 12 of the cases including women with a cervical cerclage, dental abscesses, appendicitis, renal actinomycosis, and ovarian abscesses. Adverse pregnancy outcomes have been linked with periodontal disease, but treatment did not prevent preterm delivery in a randomized, blinded, controlled trial. Actinomyces infections in pregnancy are rare but, if they occur, have been linked primarily with preterm deliveries. Obstetricians and gynecologists, family physicians. After completing this activity, the learner should be better able to identify the areas of the body where Actinomyces infections occur and how the infections typically occur, identify the pathophysiologic changes that occur during pregnancy that might lead to an Actinomyces infection and how that infection may affect pregnancy outcomes, and describe the treatment for mild and severe Actinomyces infections.

Prenatal betamethasone does not affect glutamatergic or GABAergic neurogenesis in preterm newborns

PubMed Central

Vose, Linnea R.; Vinukonda, Govindaiah; Diamond, Daniel; Korumilli, Ritesh; Hu, Furong; Zia, Muhammad TK; Hevner, Robert; Ballabh, Praveen

2014-01-01

Prenatal glucocorticoids (GCs) are routinely used for pregnant women in preterm labor to prevent respiratory distress syndrome and intraventricular hemorrhage in premature infants. However, the effect of antenatal GCs on neurogenesis in preterm neonates remains elusive. Herein, we hypothesized that prenatal GCs might suppress both glutamatergic and GABAergic neurogenesis in preterm rabbits and that this treatment would induce distinct changes in the expression of transcription factors regulating these developmental events. To test our hypotheses, we treated pregnant rabbits with betamethasone at E27 and E28, delivered the pups at E29 (term=32d), and assessed neurogenesis at birth and postnatal day 3. We quantified radial glia (Sox2+) and intermediate progenitor cells (Tbr2+) in the dorsal cortical subventricular zone to assess glutamatergic neuronal progenitors, and counted Nkx2.1+ and Dlx2+ cells in the ganglionic eminence to evaluate GABAergic neurogenesis. In addition, we assayed transcription factors regulating neurogenesis. We found that prenatal GCs did not affect the densities of radial glia and intermediate progenitors of glutamatergic or GABAergic neurons. The number of GABA+ interneurons in the ganglionic eminence was similar between the prenatal GC treated pups compared to untreated controls. Moreover, the mRNA expression of transcription factors, including Pax6, Ngn1/2, Emx1/2, Insm1, Dlx1, Nkx2.1, and Gsh2, were comparable between the two groups. However, there was a transient elevation in Mash1 protein in betamethasone treated pups relative to controls at birth. This data suggests that prenatal GC treatment does not significantly impact the balance of glutamatergic and GABAergic neurogenesis in premature infants. PMID:24735821

Expressive Language in Preschoolers Born Preterm: Results of Language Sample Analysis and Standardized Assessment

ERIC Educational Resources Information Center

Imgrund, Caitlin

2017-01-01

Children born preterm constitute one of the largest populations of children at risk for the development of language impairments. A little over one in ten pregnancies result in a preterm birth and approximately 25% of these children go on to experience subsequent difficulties with language (CDC, 2015; Foster-Cohen, Friesen, Champion, &…

Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor.

PubMed

Melamed, N; Hiersch, L; Gabbay-Benziv, R; Bardin, R; Meizner, I; Wiznitzer, A; Yogev, Y

2015-07-01

To assess the accuracy and determine the optimal threshold of sonographic cervical length (CL) for the prediction of preterm delivery (PTD) in women with twin pregnancies presenting with threatened preterm labor (PTL). This was a retrospective study of women with twin pregnancies who presented with threatened PTL and underwent sonographic measurement of CL in a tertiary center. The accuracy of CL in predicting PTD in women with twin pregnancies was compared with that in a control group of women with singleton pregnancies. Overall, 218 women with a twin pregnancy and 1077 women with a singleton pregnancy, who presented with PTL, were included in the study. The performance of CL as a predictive test for PTD was similar in twins and singletons, as reflected by the similar correlation between CL and the examination-to-delivery interval (r, 0.30 vs 0.29; P = 0.9), the similar association of CL with risk of PTD, and the similar areas under the receiver-operating characteristics curves for differing delivery outcomes (range, 0.653-0.724 vs 0.620-0.682, respectively; P = 0.3). The optimal threshold of CL for any given target sensitivity or specificity was lower in twin than in singleton pregnancies. However, in order to achieve a negative predictive value of 95%, a higher threshold (28-30 mm) should be used in twin pregnancies. Using this twin-specific CL threshold, women with twins who present with PTL are more likely to have a positive CL test, and therefore to require subsequent interventions, than are women with singleton pregnancies with PTL (55% vs 4.2%, respectively). In women with PTL, the performance of CL as a test for the prediction of PTD is similar in twin and singleton pregnancies. However, the optimal threshold of CL for the prediction of PTD appears to be higher in twin pregnancies, mainly owing to the higher baseline risk for PTD in these pregnancies. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

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.

Genomic sequence analysis and characterization of Sneathia amnii sp. nov

PubMed Central

2012-01-01

Background Bacteria of the genus Sneathia are emerging as potential pathogens of the female reproductive tract. Species of Sneathia, which were formerly grouped with Leptotrichia, can be part of the normal microbiota of the genitourinary tracts of men and women, but they are also associated with a variety of clinical conditions including bacterial vaginosis, preeclampsia, preterm labor, spontaneous abortion, post-partum bacteremia and other invasive infections. Sneathia species also exhibit a significant correlation with sexually transmitted diseases and cervical cancer. Because Sneathia species are fastidious and rarely cultured successfully in vitro; and the genomes of members of the genus had until now not been characterized, very little is known about the physiology or the virulence of these organisms. Results Here, we describe a novel species, Sneathia amnii sp. nov, which closely resembles bacteria previously designated "Leptotrichia amnionii". As part of the Vaginal Human Microbiome Project at VCU, a vaginal isolate of S. amnii sp. nov. was identified, successfully cultured and bacteriologically cloned. The biochemical characteristics and virulence properties of the organism were examined in vitro, and the genome of the organism was sequenced, annotated and analyzed. The analysis revealed a reduced circular genome of ~1.34 Mbp, containing ~1,282 protein-coding genes. Metabolic reconstruction of the bacterium reflected its biochemical phenotype, and several genes potentially associated with pathogenicity were identified. Conclusions Bacteria with complex growth requirements frequently remain poorly characterized and, as a consequence, their roles in health and disease are unclear. Elucidation of the physiology and identification of genes putatively involved in the metabolism and virulence of S. amnii may lead to a better understanding of the role of this potential pathogen in bacterial vaginosis, preterm birth, and other issues associated with vaginal and reproductive health. PMID:23281612

Delivery mode and intraventricular hemorrhage risk in very-low-birth-weight infants: Observational data of the German Neonatal Network.

PubMed

Humberg, Alexander; Härtel, Christoph; Paul, Pia; Hanke, Kathrin; Bossung, Verena; Hartz, Annika; Fasel, Laura; Rausch, Tanja K; Rody, Achim; Herting, Egbert; Göpel, Wolfgang

2017-05-01

Very-low-birth-weight infants (VLBWI) are frequently delivered by cesarean section (CS). However, it is unclear at what gestational age the benefits of spontaneous delivery outweigh the perinatal risks, i.e. intraventricular hemorrhage (IVH) or death. To assess the short-term outcome of VLBWI on IVH according to mode of delivery in a population-based cohort of the German Neonatal Network (GNN). A total cohort of 2203 singleton VLBWI with a birth weight <1500g and gestational age between 22 0/7 and 36 6/7 weeks born and discharged between 1st of January 2009 and 31st of December 2015 was available for analysis. VLBWI were stratified into three categories according to mode of delivery: (1) planned cesarean section (n=1381), (2) vaginal delivery (n=632) and (3) emergency cesarean section (n=190). Outcome was assessed in univariate and logistic regression analyses. Prevalence of IVH was significantly higher in the vaginal delivery (VD) (26.6%) and emergency CS group (31.1%) as compared to planned CS (17.2%), respectively. In a logistic regression analysis including known risk factors for IVH, vaginal delivery (OR 1.725 [1.325-2.202], p≤0.001) and emergency cesarean section (OR 1.916 [1.338-2.746], p≤0.001) were independently associated with IVH risk. In the subgroup of infants >30 weeks of gestation prevalence for IVH was not significantly different in VD and planned CS (5.3% vs. 4.4%). Our observational data demonstrate that elective cesarean section is associated with a reduced risk of IVH in preterm infants <30 weeks gestational age when presenting with preterm labor. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Comparative Analysis of 2-D Versus 3-D Ultrasound Estimation of the Fetal Adrenal Gland Volume and Prediction of Preterm Birth

PubMed Central

Turan, Ozhan M.; Turan, Sifa; Buhimschi, Irina A.; Funai, Edmund F.; Campbell, Katherine H.; Bahtiyar, Ozan M.; Harman, Chris R.; Copel, Joshua A.; Baschat, Ahmet A; Buhimschi, Catalin S.

2013-01-01

Objective We aim to test the hypothesis that 2D fetal AGV measurements offer similar volume estimates as volume calculations based on 3D technique Methods Fetal AGV was estimated by 3D ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2D measurements of the same blocks (0.523× length × width × depth). Comparisons were performed by intra-class correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The cAGV (AGV/fetal weight) was calculated for both methods and compared for prediction of PTB within 7 days. Results Among 168 volumes, there was a significant correlation between 3D and 2D methods (ICC=0.979[95%CI: 0.971-0.984]). The coefficient of repeatability for the 3D was superior to the 2D method (Intra-observer 3D: 30.8, 2D:57.6; inter-observer 3D: 12.2, 2D: 15.6). Based on 2D calculations, a cAGV≥433mm3/kg, was best for prediction of PTB (sensitivity: 75%(95%CI=59-87); specificity: 89%(95%CI=82-94). Sensitivity and specificity for the 3D cAGV (cut-off ≥420mm3/kg) was 85%(95%CI=70-94) and 95%(95%CI=90-98), respectively. In receiver-operating-curve curve analysis, 3D cAGV was superior to 2D cAGV for prediction of PTB (z=1.99, p=0.047). Conclusion 2D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3D AGV calculations for prediction of PTB. PMID:22644825

Alberta Infant Motor Scale (AIMS) Performance of Greek Preterm Infants: Comparisons With Full-Term Infants of the Same Nationality and Impact of Prematurity-Related Morbidity Factors.

PubMed

Syrengelas, Dimitrios; Kalampoki, Vassiliki; Kleisiouni, Paraskevi; Manta, Vassiliki; Mellos, Stavros; Pons, Roser; Chrousos, George P; Siahanidou, Tania

2016-07-01

Only a few studies have been conducted with the objective of creating norms of the Alberta Infant Motor Scale (AIMS) for the assessment of gross motor development of preterm infants. The AIMS performance of preterm infants has been compared with that of the Canadian norms of full-term infants, but not with that of full-term infants of the same nationality. Moreover, the possible impact of prematurity-related morbidity factors on AIMS performance is unknown. The aims of this study were: (1) to evaluate AIMS trajectory in a large population of Greek preterm infants and create norms, (2) to compare it with the AIMS trajectory of Greek full-term infants, and (3) to examine the possible influence of neonatal morbidity on AIMS scores in the preterm sample. This was a cross-sectional study. Mean AIMS scores were compared, per month (1-19), between 403 preterm infants (≤32 weeks of age, corrected for prematurity) and 1,038 full-term infants. In preterm infants, the association of AIMS scores with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) of grade ≤III, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and sepsis was assessed by hierarchical regression analysis. Alberta Infant Motor Scale scores were significantly lower in preterm infants than in full-term infants. Mean AIMS scores in preterm infants were significantly associated with RDS (b=-1.93; 95% CI=-2.70, -1.16), IVH (b=-0.97; 95% CI=-1.69, -0.25), and ROP (b=-1.12; 95% CI=-1.99, -0.24) but not with BPD or sepsis in hierarchical regression analysis. Alberta Infant Motor Scale norms were created for Greek preterm infants. This study confirms that AIMS trajectories of preterm infants are below those of full-term infants of the same nationality. The influence of morbidity factors, including RDS, IVH, and ROP, should be taken into account when administering the AIMS in preterm infants. © 2016 American Physical Therapy Association.

Cost of Racial Disparity in Preterm Birth: Evidence from Michigan

PubMed Central

Xu, Xiao; Grigorescu, Violanda; Siefert, Kristine A.; Lori, Jody R.; Ransom, Scott B.

2009-01-01

This study examined the economic costs associated with racial disparity in preterm birth and preterm fetal death in Michigan. Linked 2003 Michigan vital statistics and hospital discharge data were used for data analysis. Thirteen percent of the singleton births among non-Hispanic Blacks were before 37 completed weeks of gestation, compared to only 7.7% among non-Hispanic Whites (risk ratio = 1.66, 95% confidence interval: 1.59-1.72; p<0.0001). One thousand one hundred and eighty four non-Hispanic Black, singleton preterm births and preterm fetal deaths would have been avoided in 2003 had their preterm birth rate been the same as Michigan non-Hispanic Whites. Economic costs associated with these excess Black preterm births and preterm fetal deaths amounted to $329 million (range: $148 million - $598 million) across their lifespan over and above the costs if they were born at term, including costs associated with the initial hospitalization, productivity loss due to perinatal death, and major developmental disabilities. Hence, racial disparity in preterm birth and preterm fetal death has substantial cost implications for society. Improving pregnancy outcomes for African American women and reducing the disparity between Blacks and Whites should continue to be a focus of future research and interventions. PMID:19648701

Visuospatial perception in children born preterm with no major neurological disorders.

PubMed

Butcher, Phillipa R; Bouma, Anke; Stremmelaar, Elisabeth F; Bos, Arend F; Smithson, Michael; Van Braeckel, Koenraad N J A

2012-11-01

Many investigations have found deficits in visuospatial perception in children born preterm, however, it is not clear whether the deficits are specific to visuospatial perception or the consequences of deficits in other functional areas, which often accompany preterm birth. This study investigated whether children born preterm show a specific deficit in visuospatial perception. Fifty-six 7- to 11-year-old preterm born children (gestational age <34 weeks) without cerebral palsy and 51 age-matched, full-term children completed four computerized tasks tapping different levels and types of visuospatial perception. Accuracy and speed of responses were recorded. Task formats were designed to reduce demands on attentional deployment. Measures of intelligence and parental education were included in the analysis. Children born preterm performed less accurately and/or less rapidly on all tasks. Their poorer performance did not reflect differences in speed-accuracy trade-off. Parental education and IQ, both significantly lower in the preterm children, contributed positively to performance on all tasks. IQ mediated the association between preterm birth and visuospatial performance on the most cognitively demanding task. Children born preterm performed more poorly than full-term controls on four visuospatial perceptual tasks. Although intelligence and parental education were also associated with performance, preterm birth contributed independently of these factors on three of four tasks. Many children born preterm are thus multiply disadvantaged on visuospatial tasks: the lower IQ scores and parental educational levels frequently found in this group increase the deficit associated with preterm birth. (c) 2012 APA, all rights reserved.

The Association Between Socio-demographic Factors, Dental Problems, and Preterm Labor for Pregnant Women Residing in Hawai‘i

PubMed Central

Shannon, Maureen; Lim, Eunjung; Gandhi, Krupa

2016-01-01

Periodontal disease during pregnancy has the potential to increase the risk of adverse perinatal outcomes including preterm labor (PTL), prematurity, and low birth weight (LBW). Despite professional recommendations on the importance and safety of dental assessments and treatments, the rate of dental care utilization during pregnancy remains low. The purpose of this study was to document the utilization of dental services and explore the relationships among socio-demographic factors, dental problems, and PTL in pregnant women residing in Hawai‘i. Hawai‘i Pregnancy Risk Assessment Monitoring System (PRAMS) survey results were analyzed from 4,309 women who experienced live births between the years 2009–2011. Results revealed that 2 in 5 women in Hawai‘i had their teeth cleaned during pregnancy, while 1 in 5 reported seeing a dentist for a dental problem. Women who reported having a dental problem during pregnancy were more likely to experience PTL (OR=1.46, 95% CI=1.10–1.94, P=.008) compared to women without a dental problem. In addition, Native Hawaiian and Part-Hawaiian women were more likely to experience PTL (OR=1.73, 95% CI=1.22–2.46, P=.002) compared to Caucasian women. These findings document the underutilization of dental services in pregnant women in Hawai‘i and reveal an association between poor dental care and PTL. Identification of groups at risk for maternal complications may assist in the development of programs that are sensitive to the diverse cultures and variability of community resources that exist throughout Hawai‘i. PMID:27563498

Should asymptomatic bacteriuria be screened in pregnancy?

PubMed

Uncu, Y; Uncu, G; Esmer, A; Bilgel, N

2002-01-01

The incidence of asymptomatic bacteriuria is reported as 2-14% during pregnancy. Fetal and maternal complications like acute pyelonephritis, hypertension, anemia, preterm labor, low-birth-weight infants and intrauterine growth retardation can be expected. The purpose of this study was to determine the incidence of asymptomatic bacteriuria during pregnancy and its relation to pregnancy complications. The study involved 270 pregnant women up to 32 gestational weeks during a 9-month period. At the initial visit, they were screened with urine culture in order to detect asymptomatic bacteriuria. A control group was formed in a retrospective manner from the first day of the study with 186 pregnant women who delivered in our clinic and who were not screened for asymptomatic bacteriuria. The incidence of asymptomatic bacteriuria was 9.31%. Escherichia coli accounted for 79%, which was the most frequent of the isolates. We observed recurrence and had to apply treatment again to 21.7% of the women. The sensitivity, specificity, positive predictive and negative predictive values of leucocyturia as a screening test for asymptomatic bacteriuria were 91.3%, 83.6%, 45.6% and 98.5%, respectively. We diagnosed preterm labor in six of 23 (26%) with asymptomatic bacteriuria and 16 in 163 (9.3%) women in the urine culture negative group. The ratio acute pyelonephritis in the group which was routinely screened and treated for asymtomatic bacteriuria was 0.5% while the prevalence was 2.1% in the nonscreened group. Considering the relatively high incidence of asymptomatic bacteriuria during pregnancy and the relevant complications, we propose to screen and treat asymptomatic bacteriuria routinely in all pregnant women.

Associations of the pre-pregnancy body mass index and gestational weight gain with pregnancy outcomes in Taiwanese women.

PubMed

Tsai, I-Hsien; Chen, Chih-Ping; Sun, Fang-Ju; Wu, Chia-Hsun; Yeh, Sung-Ling

2012-01-01

Pre-pregnancy weight and gestational weight gain (GWG) are important factors in both maternal and infant outcomes. Little information is available in relation to different levels of pre-pregnancy body mass index (BMI) and body weight gain on obstetric outcomes in Taiwan. This study investigated the associations between pregnancy complications with pre-pregnant BMI and GWG, in Taiwanese women. Data were extracted from a delivery room information bank on all women delivering singleton babies in a medical center. Eight hundred and sixty pregnant women were included. The collected variables included basic information, GWG, and pregnancy and neonatal outcomes. Pregnant women were categorized according to their pre-pregnant BMI and GWG to evaluate the impacts of pre-pregnant BMI and maternal weight gain on the risk of pregnancy complications. Univariate and multivariable logistic regression analyses were performed, and odds ratios were calculated. Pre-pregnancy BMI>=24 kg/m2 increased the risks of gestational diabetes mellitus, preeclampsia, and preterm labor. Preeclampsia and Cesarean delivery were positively associated with high weight gains (>18 kg), whereas a low birth weight and preterm labor were strongly associated with low weight gains (<10 kg). A higher birth weight was found with a GWG of >14 kg in women who were underweight and normal weight before pregnancy. An appropriate maternal BMI (18.5-24 kg/m2) at conception followed by a suitable gestational weight gain (10-14 kg) has substantial impact on the overall health of pregnant women and would lead to better obstetric management for Taiwanese women.

Prenatal Dexamethasone Augments the Sex-Selective Developmental Neurotoxicity of Chlorpyrifos: Implications for Vulnerability after Pharmacotherapy for Preterm Labor

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J.

2013-01-01

Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. We evaluated indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, in brain regions possessing the majority of ACh projections and cell bodies; we measured nicotinic ACh receptor binding, hemicholinium-3 binding to the presynaptic choline transporter and choline acetyltransferase activity, all known targets for the adverse developmental effects of dexamethasone and chlorpyrifos given individually. Dexamethasone did not enhance the systemic toxicity of chlorpyrifos, as evidenced by weight gain and measurements of cholinesterase inhibition during chlorpyrifos treatment. Nevertheless, it enhanced the loss of presynaptic ACh function selectively in females, who ordinarily show sparing of organophosphate developmental neurotoxicity relative to males. Females receiving the combined treatment showed decrements in choline transporter binding and choline acetyltransferase activity that were unique (not found with either treatment alone), as well as additive decrements in nicotinic receptor binding. On the other hand, males given dexamethasone showed no augmentation of the effects of chlorpyrifos. Our findings indicate that prior dexamethasone exposure could create a subpopulation that is especially vulnerable to the adverse effects of organophosphates or other developmental neurotoxicants. PMID:23416428

Prenatal Dexamethasone Augments the Neurobehavioral Teratology of Chlorpyrifos: Significance for Maternal Stress and Preterm Labor

PubMed Central

Levin, Edward D.; Cauley, Marty; Johnson, Joshua E.; Cooper, Ellen M.; Stapleton, Heather M.; Ferguson, P. Lee; Seidler, Frederic J.; Slotkin, Theodore A.

2014-01-01

Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. We administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure-8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos’ effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants. PMID:24177596

Obstetric complications among US women with asthma

PubMed Central

MENDOLA, Pauline; LAUGHON, S. Katherine; MÄNNISTÖ, Tuija I.; LEISHEAR, Kira; REDDY, Uma M.; CHEN, Zhen; ZHANG, Jun

2012-01-01

Objective To characterize complications of pregnancy, labor and delivery associated with maternal asthma in a contemporary US cohort. Study Design A retrospective cohort based on electronic medical record data from 223,512 singleton deliveries from 12 clinical centers across the United States between 2002–2008. Results Women with asthma had higher odds of preeclampsia (adjusted odds ratio (aOR)=1.14; 95% confidence interval (95%CI)=1.06–1.22), superimposed preeclampsia (aOR=1.34; 95%CI=1.15–1.56), gestational diabetes (aOR=1.11; 95%CI=1.03–1.19), placental abruption (aOR=1.22; 95%CI=1.09–1.36), and placenta previa (aOR=1.30; 95%CI=1.08–1.56). Asthmatic women had a higher odds of preterm birth overall (aOR=1.17; 95%CI=1.12–1.23) and of medically-indicated preterm delivery (aOR=1.14; 95%CI=1.01–1.29). Asthmatics were less likely to have spontaneous labor (aOR=0.87; 95%CI=0.84–0.90) and vaginal delivery (aOR=0.84; 95%CI=0.80–0.87). Risks were higher for breech presentation (aOR=1.13; 95%CI=1.05–1.22), hemorrhage (aOR=1.09; 95%CI=1.03–1.16), pulmonary embolism (aOR=1.71; 95%CI=1.05–2.79), and maternal ICU admission (aOR=1.34; 95%CI=1.04–1.72). Conclusion Maternal asthma increased risk for nearly all outcomes studied in a general obstetric population. PMID:23159695

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.

A dynamical systems model of progesterone receptor interactions with inflammation in human parturition.

PubMed

Brubaker, Douglas; Barbaro, Alethea; R Chance, Mark; Mesiano, Sam

2016-08-19

Progesterone promotes uterine relaxation and is essential for the maintenance of pregnancy. Withdrawal of progesterone activity and increased inflammation within the uterine tissues are key triggers for parturition. Progesterone actions in myometrial cells are mediated by two progesterone receptor (PR) isoforms, PR-A and PR-B, that function as ligand-activated transcription factors. PR-B mediates relaxatory actions of progesterone, in part, by decreasing myometrial cell responsiveness to pro-inflammatory stimuli. These same pro-inflammatory stimuli promote the expression of PR-A which inhibits the anti-inflammatory activity of PR-B. Competitive interaction between the progesterone receptors then augments myometrial responsiveness to pro-inflammatory stimuli. The interaction between PR-B transcriptional activity and inflammation in the pregnancy myometrium is examined using a dynamical systems model in which quiescence and labor are represented as phase-space equilibrium points. Our model shows that PR-B transcriptional activity and the inflammatory load determine the stability of the quiescent and laboring phenotypes. The model is tested using published transcriptome datasets describing the mRNA abundances in the myometrium before and after the onset of labor at term. Surrogate transcripts were selected to reflect PR-B transcriptional activity and inflammation status. The model coupling PR-B activity and inflammation predicts contractile status (i.e., laboring or quiescent) with high precision and recall and outperforms uncoupled single and two-gene classifiers. Linear stability analysis shows that phase space bifurcations exist in our model that may reflect the phenotypic states of the pregnancy uterus. The model describes a possible tipping point for the transition of the quiescent to the contractile laboring phenotype. Our model describes the functional interaction between the PR-A:PR-B hypothesis and tissue level inflammation in the pregnancy uterus and is a first step in more sophisticated dynamical systems modeling of human partition. The model explains observed biochemical dynamics and as such will be useful for the development of a range of systems-based models using emerging data to predict preterm birth and identify strategies for its prevention.

Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index.

PubMed

Chang, Hannah H; Larson, Jim; Blencowe, Hannah; Spong, Catherine Y; Howson, Christopher P; Cairns-Smith, Sarah; Lackritz, Eve M; Lee, Shoo K; Mason, Elizabeth; Serazin, Andrew C; Walani, Salimah; Simpson, Joe Leigh; Lawn, Joy E

2013-01-19

Every year, 1·1 million babies die from prematurity, and many survivors are disabled. Worldwide, 15 million babies are born preterm (<37 weeks' gestation), with two decades of increasing rates in almost all countries with reliable data. The understanding of drivers and potential benefit of preventive interventions for preterm births is poor. We examined trends and estimate the potential reduction in preterm births for countries with very high human development index (VHHDI) if present evidence-based interventions were widely implemented. This analysis is to inform a rate reduction target for Born Too Soon. Countries were assessed for inclusion based on availability and quality of preterm prevalence data (2000-10), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1989-2004. For 39 countries with VHHDI with more than 10,000 births, we did country-by-country analyses based on target population, incremental coverage increase, and intervention efficacy. We estimated cost savings on the basis of reported costs for preterm care in the USA adjusted using World Bank purchasing power parity. From 2010, even if all countries with VHHDI achieved annual preterm birth rate reductions of the best performers for 1990-2010 (Estonia and Croatia), 2000-10 (Sweden and Netherlands), or 2005-10 (Lithuania, Estonia), rates would experience a relative reduction of less than 5% by 2015 on average across the 39 countries. Our analysis of preterm birth rise 1989-2004 in USA suggests half the change is unexplained, but important drivers include non-medically indicated labour induction and caesarean delivery and assisted reproductive technologies. For all 39 countries with VHHDI, five interventions modelling at high coverage predicted a 5% relative reduction of preterm birth rate from 9·59% to 9·07% of livebirths: smoking cessation (0·01 rate reduction), decreasing multiple embryo transfers during assisted reproductive technologies (0·06), cervical cerclage (0·15), progesterone supplementation (0·01), and reduction of non-medically indicated labour induction or caesarean delivery (0·29). These findings translate to roughly 58,000 preterm births averted and total annual economic cost savings of about US$3 billion. We recommend a conservative target of a relative reduction in preterm birth rates of 5% by 2015. Our findings highlight the urgent need for research into underlying mechanisms of preterm births, and development of innovative interventions. Furthermore, the highest preterm birth rates occur in low-income settings where the causes of prematurity might differ and have simpler solutions such as birth spacing and treatment of infections in pregnancy than in high-income countries. Urgent focus on these settings is also crucial to reduce preterm births worldwide. March of Dimes, USA, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institutes of Health, USA. Copyright © 2013 Elsevier Ltd. All rights reserved.

A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants

PubMed Central

2013-01-01

Background The aim of this study was to revise the 2003 Fenton Preterm Growth Chart, specifically to: a) harmonize the preterm growth chart with the new World Health Organization (WHO) Growth Standard, b) smooth the data between the preterm and WHO estimates, informed by the Preterm Multicentre Growth (PreM Growth) study while maintaining data integrity from 22 to 36 and at 50 weeks, and to c) re-scale the chart x-axis to actual age (rather than completed weeks) to support growth monitoring. Methods Systematic review, meta-analysis, and growth chart development. We systematically searched published and unpublished literature to find population-based preterm size at birth measurement (weight, length, and/or head circumference) references, from developed countries with: Corrected gestational ages through infant assessment and/or statistical correction; Data percentiles as low as 24 weeks gestational age or lower; Sample with greater than 500 infants less than 30 weeks. Growth curves for males and females were produced using cubic splines to 50 weeks post menstrual age. LMS parameters (skew, median, and standard deviation) were calculated. Results Six large population-based surveys of size at preterm birth representing 3,986,456 births (34,639 births < 30 weeks) from countries Germany, United States, Italy, Australia, Scotland, and Canada were combined in meta-analyses. Smooth growth chart curves were developed, while ensuring close agreement with the data between 24 and 36 weeks and at 50 weeks. Conclusions The revised sex-specific actual-age growth charts are based on the recommended growth goal for preterm infants, the fetus, followed by the term infant. These preterm growth charts, with the disjunction between these datasets smoothing informed by the international PreM Growth study, may support an improved transition of preterm infant growth monitoring to the WHO growth charts. PMID:23601190

Molecular Regulation of Parturition: A Myometrial Perspective

PubMed Central

Renthal, Nora E.; Williams, Koriand’r C.; Montalbano, Alina P.; Chen, Chien-Cheng; Gao, Lu; Mendelson, Carole R.

2015-01-01

The molecular mechanisms that maintain quiescence of the myometrium throughout most of pregnancy and promote its transformation to a highly coordinated contractile unit culminating in labor are complex and intertwined. During pregnancy, progesterone (P4) produced by the placenta and/or ovary serves a dominant role in maintaining myometrial quiescence by blocking proinflammatory response pathways and expression of so-called “contractile” genes. In the majority of placental mammals, increased uterine contractility near term is heralded by an increase in circulating estradiol-17β (E2) and/or increased estrogen receptor α (ERα) activity and a sharp decline in circulating P4 levels. However, in women, circulating levels of P4 and progesterone receptors (PR) in myometrium remain elevated throughout pregnancy and into labor. This has led to the concept that increased uterine contractility leading to term and preterm labor is mediated, in part, by a decline in PR function. The biochemical mechanisms for this decrease in PR function are also multifaceted and interwoven. In this paper, we focus on the molecular mechanisms that mediate myometrial quiescence and contractility and their regulation by the two central hormones of pregnancy, P4 and estradiol-17β. The integrative roles of microRNAs also are considered. PMID:26337112

Negative Effects of SRD5A1 on Nuclear Activity of Progesterone Receptor Isoform B in JEG3 Cells.

PubMed

Miao, Zhuo; Sun, Min; Jiang, Feng; Yao, Yuanqing; Li, Yi

2016-02-01

Progesterone withdrawal signals labor in mammals. Elevated intracellular metabolism contributes to progesterone functional withdrawal through unknown mechanism, which is thought to act via progesterone receptor (PR). This study aims to investigate molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. We investigated the role of 5α-reductase type I (SRD5A1) in enzymatic catalysis of progesterone and loss of PR function in a human trophoblast choriocarcinoma cell line JEG3. The PR isoform B (PR-B) was robustly expressed in JEG3 cells. The SRD5A1 small-interfering RNA knockdown led to significant increase in PR-B nuclear import, ectopic, whereas SRD5A1 overexpression resulted in remarkable inhibition of nuclear PR-B in P4-treated cells. Repression of SRD5A1 activated PR-B responsive gene, whereas overexpression of SRD5A1 possessed an inhibitory effect. JEG3 cell line is a valuable tool to study mechanisms responsible for loss of PR function and screening of drugs for preterm birth treatment. Our study aims to investigate the molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. © The Author(s) 2015.

Complementary and alternative medicine in pregnancy: a survey of North Carolina certified nurse-midwives.

PubMed

Allaire, A D; Moos, M K; Wells, S R

2000-01-01

To determine the prevalence and types of complementary and alternative medicine therapies used by certified nurse-midwives in North Carolina. Surveys were sent to all 120 licensed certified nurse-midwives in North Carolina requesting information concerning their recommendations for use of complementary and alternative medicine for their pregnant or postpartum patients. Eighty-two responses were received (68.3%). Seventy-seven (93.9%) reported recommending complementary and alternative medicine to their pregnant patients in the past year. Forty-seven (57.3%) reported recommending complementary and alternative medicine to more than 10% of patients. The percentage of nurse-midwives who recommended each type of complementary and alternative medicine was as follows: herbal therapy (73.2%), massage therapy (67.1%), chiropractic (57.3%), acupressure (52.4%), mind-body interventions (48.8%), aromatherapy (32.9%), homeopathy (30.5%), spiritual healing (23.2%), acupuncture (19.5%), and bioelectric or magnetic applications (14.6%). The 60 respondents who reported prescribing herbal therapies gave them for the following indications: nausea and vomiting, labor stimulation, perineal discomfort, lactation disorders, postpartum depression, preterm labor, postpartum hemorrhage, labor analgesia, and malpresentation. Complementary and alternative medicine, especially herbal therapy, is commonly prescribed to pregnant women by nurse-midwives in North Carolina.

Perceptions and experiences of community members on caring for preterm newborns in rural Mangochi, Malawi: a qualitative study.

PubMed

Gondwe, Austrida; Munthali, Alister C; Ashorn, Per; Ashorn, Ulla

2014-12-02

The number of preterm birth is increasing worldwide, especially in low income countries. Malawi has the highest incidence of preterm birth in the world, currently estimated at 18.1 percent. The aim of this study was to explore the perceived causes of preterm birth, care practices for preterm newborn babies and challenges associated with preterm birth among community members in Mangochi District, southern Malawi. We conducted 14 focus group discussions with the following groups of participants: mothers (n = 4), fathers (n = 6) and grandmothers (n = 4) for 110 participants. We conducted 20 IDIs with mothers to preterm newborns (n = 10), TBAs (n = 6) and traditional healers (n = 4). A discussion guide was used to facilitate the focus group and in-depth interview sessions. Data collection took place between October 2012 and January 2013. We used content analysis to analyze data. Participants mentioned a number of perceptions of preterm birth and these included young and old maternal age, heredity, sexual impurity and maternal illness during pregnancy. Provision of warmth was the most commonly reported component of care for preterm newborns. Participants reported several challenges to caring for preterm newborns such as lack of knowledge on how to provide care, poverty, and the high time burden of care leading to neglect of household, farming and business duties. Women had the main responsibility for caring for preterm newborns. In this community, the reported poor care practices for preterm newborns were associated with poverty and lack of knowledge of how to properly care for these babies at home. Action is needed to address the current care practices for preterm babies among the community members.

Parenting stress in mothers of very preterm infants -- influence of development, temperament and maternal depression.

PubMed

Gray, Peter H; Edwards, Dawn M; O'Callaghan, Michael J; Cuskelly, Monica; Gibbons, Kristen

2013-09-01

To measure levels of parenting stress and postnatal depression in mothers of very preterm infants in comparison with mothers of infants born at term is the objective of this study. The study also aimed to explore factors associated with parenting stress in the mothers of the preterm infants. One hundred and five mothers who delivered 124 babies at ≤30 weeks gestation were enrolled together with 105 term mothers who delivered 120 babies. At one year of age (corrected for prematurity for the preterm cohort), the mothers completed the Parenting Stress Index Short Form (PSI), the Edinburgh Postnatal Depression Scale (EPDS) and the Short Temperament Scale for Toddlers. The infants had neurodevelopmental assessment. The preterm and term groups were compared. Questionnaires were completed by 101 of the preterm mothers and 98 of the term mothers. The mean PSI Total Stress score was significantly higher for the preterm mothers (70.28 vs 64.52, p = 0.022), with 19% of the preterm group and 9% of the term group having high scores (p = 0.038).There was no group difference on the EPDS or measures of temperament, with disability being greater in the preterm infants. For the preterm group, maternal depression and infant temperament were independent predictors of Total Stress scores on multivariate analysis. Parenting stress in mothers of preterm infants at one year of age is significantly greater than that found in mothers of term infants. For preterm mothers, symptoms of depression and infant temperament are independent risk factors for higher levels of parenting stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Explaining the low risk of preterm birth among arab americans in the United States: an analysis of 617451 births.

PubMed

El-Sayed, Abdulrahman M; Galea, Sandro

2009-03-01

Arab Americans have a lower risk for preterm birth than white Americans. We assessed factors that may contribute to the association between ethnicity and preterm birth risk in Michigan, the state with the largest concentration of Arab Americans in the United States. Factors assessed as potential contributors to the ethnicity/preterm birth risk association were maternal age, parity, education, marital status, tobacco use, and maternal birthplace. Data were collected about all births in Michigan between 2000 and 2005. Stratified analyses, trivariate analyses, and manual stepwise logistic regression model building were used to assess potential contributors to the ethnicity/preterm birth risk association. Arab ethnicity was associated with lower preterm birth risk compared with non-Arab white subjects in the unadjusted model. Maternal birthplace inside or outside the United States explained 0.17 of the difference in preterm birth risk between Arab ethnicity and non-Arab white mothers; ethnic differences in marital status and tobacco use explained less of the observed ethnic difference in preterm birth risk. In the final model adjusted for all explanatory variables, Arab ethnicity was no longer associated with preterm birth risk. Maternal birthplace, marital status, and tobacco use may contribute to the preterm birth risk difference between Arab ethnicity and non-Arab white mothers. Additional work is needed to consider the mechanisms relating factors such as maternal birthplace and marital status to ethnic differences in preterm birth risk.

Predictors of unknown HIV serostatus at the time of labor and delivery in Kampala, Uganda.

PubMed

Ononge, Sam; Karamagi, Charles; Nakabiito, Clemensia; Wandabwa, Julius; Mirembe, Florence; Rukundo, Godfrey Z; Jennings, Larissa

2014-03-01

To determine factors associated with an unknown HIV serostatus among pregnant women admitted in labor to Mulago Hospital, Kampala, Uganda. In total, 665 pregnant women admitted to Mulago Hospital were interviewed about their sociodemographic characteristics, obstetric history, access to prenatal care, fears regarding HIV testing, and knowledge about modes of mother-to-child-transmission (MTCT). Knowledge of the HIV serostatus was assessed by self-report and verified by prenatal card review. The prevalence of unknown HIV serostatus at the time of labor was 27.1%. Factors associated with an unknown HIV serostatus included high parity (odds ratio [OR] 1.9; 95% confidence interval [CI], 1.16-3.14), preterm delivery (OR 2.60; 95% CI, 1.06-6.34), prenatal care at a private clinic (OR 12.87; 95% CI, 5.68-29.14), residence more than 5 km from the nearest prenatal clinic (OR 2.86; 95% CI, 1.18-17.9), high knowledge about MTCT (OR 0.25; 95% CI, 0.07-0.86), and fears related to disclosing the test result to the partner (OR 3.60; 95% CI, 1.84-7.06). The high prevalence of unknown HIV serostatus among women in labor highlights the need to improve accessibility to HIV testing services early during pregnancy to be able to take advantage of antiretroviral therapy. Copyright © 2013 International Federation of Gynecology and Obstetrics. All rights reserved.

Predictors of unknown HIV serostatus at the time of labor and delivery in Kampala, Uganda

PubMed Central

Ononge, Sam; Karamagi, Charles; Nakabiito, Clemensia; Wandabwa, Julius; Mirembe, Florence; Rukundo, Godfrey Z.; Jennings, Larissa

2014-01-01

Objective To determine factors associated with an unknown HIV serostatus among pregnant women admitted in labor to Mulago Hospital, Kampala, Uganda. Methods In total, 665 pregnant women admitted to Mulago Hospital were interviewed about their sociodemographic characteristics, obstetric history, access to prenatal care, fears regarding HIV testing, and knowledge about modes of mother-to-child-transmission (MTCT). Knowledge of the HIV serostatus was assessed by self-report and verified by prenatal card review. Results The prevalence of unknown HIV serostatus at the time of labor was 27.1%. Factors associated with an unknown HIV serostatus included high parity (odds ratio [OR] 1.9; 95% confidence interval [CI], 1.16–3.14), preterm delivery (OR 2.60; 95% CI, 1.06–6.34), prenatal care at a private clinic (OR 12.87; 95% CI, 5.68–29.14), residence more than 5 km from the nearest prenatal clinic (OR 2.86; 95% CI, 1.18–17.9), high knowledge about MTCT (OR 0.25; 95% CI, 0.07–0.86), and fears related to disclosing the test result to the partner (OR 3.60; 95% CI, 1.84–7.06). Conclusion The high prevalence of unknown HIV serostatus among women in labor highlights the need to improve accessibility to HIV testing services early during pregnancy to be able to take advantage of antiretroviral therapy. PMID:24290059

Prostacyclin primes pregnant human myometrium for an enhanced contractile response in parturition

PubMed Central

Fetalvero, Kristina M.; Zhang, Peisheng; Shyu, Maureen; Young, Benjamin T.; Hwa, John; Young, Roger C.; Martin, Kathleen A.

2008-01-01

An incomplete understanding of the molecular events that regulate the myometrial transition from the quiescent pregnant state to the active contractile state during labor has hindered the development of improved therapies for preterm labor. During myometrial activation, proteins that prime the smooth muscle for contraction are upregulated, allowing maximal responsiveness to contractile agonists and thereby producing strong phasic contractions. Upregulation of one such protein, COX-2, generates PGs that induce contractions. Intriguingly, the predominant myometrial PG produced just prior to labor is prostacyclin (PGI2), a smooth muscle relaxant. However, here we have shown that activation of PGI2 receptor (IP) upregulated the expression of several contractile proteins and the gap junction protein connexin 43 through cAMP/PKA signaling in human myometrial tissue in organ and cell culture. Functionally, these IP-dependent changes in gene expression promoted an enhanced contractile response to oxytocin in pregnant human myometrial tissue strips, which was inhibited by the IP antagonist RO3244794. Furthermore, contractile protein induction was dependent on the concentration and time of exposure to the PGI2 analog iloprost and was blocked by both RO3244794 and PKA knockdown. We therefore propose that PGI2-mediated upregulation of contractile proteins and connexin 43 is a critical step in myometrial activation, allowing for a maximal contractile response. Our observations have important implications regarding activation of the myometrium prior to the onset of labor. PMID:19033666

Labor management and mode of delivery among migrant and Spanish women: does the variability reflect differences in obstetric decisions according to ethnic origin?

PubMed

Bernis, Cristina; Varea, Carlos; Bogin, Barry; González-González, Antonio

2013-07-01

Based on previous findings showing both better birth outcomes in migrant than in Spanish women and different rates of medical intervention according to mother's origin, we hypothesize that mode of delivery decisions to solve similar problems differ according to ethnic origin. Ethnic differences for maternal characteristics, medical intervention, and mode of delivery were evaluated in 16,589 births from a Maternity Hospital in Madrid (Spain). Multinomial logistic regression analysis was used to evaluate the effect of mother's ethnic origin on the mode of delivery, adjusting for mother's age, parity, gestational age, birth weight, and epidural anesthesia. Compared with the Spanish mothers, the risk of having a Caesarean section is significantly higher in Latin Americans and significantly lower for the Chinese. Both low birth weight and macrosomic deliveries are at higher risk for Caesarean section. The interventionist system characterizing Spain is being extended to all ethnic groups and, at the same time, different medical interventions are applied to similar problems depending on women's ethnic origin. Obstetric interventions might be contributing to the increasing trend of low birth weight and late preterm/early full term deliveries (37-38 weeks) observed in Spain. Behavioral and cultural values of the women and of the health care providers may contribute to systematic differences in labor management and mode of delivery.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia.

PubMed

Figueira, R L; Gonçalves, F L; Simões, A L; Bernardino, C A; Lopes, L S; Castro E Silva, O; Sbragia, L

2016-06-23

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

PubMed Central

Figueira, R.L.; Gonçalves, F.L.; Simões, A.L.; Bernardino, C.A.; Lopes, L.S.; Castro e Silva, O.; Sbragia, L.

2016-01-01

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers. PMID:27356106

Protective Effect of Dual-Strain Probiotics in Preterm Infants: A Multi-Center Time Series Analysis

PubMed Central

Schwab, Frank; Garten, Lars; Geffers, Christine; Gastmeier, Petra; Piening, Brar

2016-01-01

Objective To determine the effect of dual-strain probiotics on the development of necrotizing enterocolitis (NEC), mortality and nosocomial bloodstream infections (BSI) in preterm infants in German neonatal intensive care units (NICUs). Design A multi-center interrupted time series analysis. Setting 44 German NICUs with routine use of dual-strain probiotics on neonatal ward level. Patients Preterm infants documented by NEO-KISS, the German surveillance system for nosocomial infections in preterm infants with birth weights below 1,500 g, between 2004 and 2014. Intervention Routine use of dual-strain probiotics containing Lactobacillus acidophilus and Bifidobacterium spp. (Infloran) on the neonatal ward level. Main outcome measures Incidences of NEC, overall mortality, mortality following NEC and nosocomial BSI. Results Data from 10,890 preterm infants in 44 neonatal wards was included in this study. Incidences of NEC and BSI were 2.5% (n = 274) and 15.0%, (n = 1631), respectively. Mortality rate was 6.1% (n = 665). The use of dual-strain probiotics significantly reduced the risk of NEC (HR = 0.48; 95% CI = 0.38–0.62), overall mortality (HR = 0.60, 95% CI = 0.44–0.83), mortality after NEC (HR = 0.51, 95% CI = 0.26–0.999) and nosocomial BSI (HR = 0.89, 95% CI = 0.81–0.98). These effects were even more pronounced in the subgroup analysis of preterm infants with birth weights below 1,000 g. Conclusion In order to reduce NEC and mortality in preterm infants, it is advisable to add routine prophylaxis with dual-strain probiotics to clinical practice in neonatal wards. PMID:27332554

Global report on preterm birth and stillbirth (6 of 7): ethical considerations

PubMed Central

2010-01-01

Introduction Despite the substantial global burden of preterm and stillbirth, little attention has been given to the ethical considerations related to research and interventions in the global context. Ethical dilemmas surrounding reproductive decisions and the care of preterm newborns impact the delivery of interventions, and are not well understood in low-resource settings. Issues such as how to address the moral and cultural attitudes surrounding stillbirths, have cross-cutting implications for global visibility of the disease burden. This analysis identifies ethical issues impacting definitions, discovery, development, and delivery of effective interventions to decrease the global burden of preterm birth and stillbirth. Methods This review is based on a comprehensive literature review; an ethical analysis of other articles within this global report; and discussions with GAPPS's Scientific Advisory Council, team of international investigators, and a community of international experts on maternal, newborn, and child health and bioethics from the 2009 International Conference on Prematurity and Stillbirth. The literature review includes articles in PubMed, Academic Search Complete (EBSCO), and Philosopher's Index with a range of 1995-2008. Results Advancements in discovery science relating to preterm birth and stillbirth require careful consideration in the design and use of repositories containing maternal specimens and data. Equally important is the need to improve clinical translation from basic science research to delivery of interventions, and to ensure global needs inform discovery science agenda-setting. Ethical issues in the development of interventions include a need to balance immediate versus long-term impacts—such as caring for preterm newborns rather than preventing preterm births. The delivery of interventions must address: women's health disparities as determinants of preterm birth and stillbirth; improving measurements of impact on equity in coverage; balancing maternal and newborn outcomes in choosing interventions; and understanding the personal and cross-cultural experiences of preterm birth and stillbirth among women, families and communities. Conclusion Efforts to improve visibility, funding, research and the successful delivery of interventions for preterm birth and stillbirth face a number of ethical concerns. Thoughtful input from those in health policy, bioethics and international research ethics helped shape an interdisciplinary global action agenda to prevent preterm birth and stillbirth. PMID:20233387

A whole brain morphometric analysis of changes associated with pre-term birth

NASA Astrophysics Data System (ADS)

Thomaz, C. E.; Boardman, J. P.; Counsell, S.; Hill, D. L. G.; Hajnal, J. V.; Edwards, A. D.; Rutherford, M. A.; Gillies, D. F.; Rueckert, D.

2006-03-01

Pre-term birth is strongly associated with subsequent neuropsychiatric impairment. To identify structural differences in preterm infants we have examined a dataset of magnetic resonance (MR) images containing 88 preterm infants and 19 term born controls. We have analyzed these images by combining image registration, deformation based morphometry (DBM), multivariate statistics, and effect size maps (ESM). The methodology described has been performed directly on the MR intensity images rather than on segmented versions of the images. The results indicate that the approach described makes clear the statistical differences between the control and preterm samples, showing a leave-one-out classification accuracy of 94.74% and 95.45% respectively. In addition, finding the most discriminant direction between the groups and using DBM features and ESM we are able to identify not only what are the changes between preterm and term groups but also how relatively relevant they are in terms of volume expansion and contraction.

Antenatal magnesium sulfate is beneficial or harmful in very preterm and extremely preterm neonates: a new insight.

PubMed

Garg, Bhawan Deep

2018-01-17

To evaluate whether antenatal MgSO 4 is beneficial or harmful in very preterm and extremely preterm neonates. We retrieved published literature through searches of PubMed or Medline, CINAHL, and the Cochrane Library. Results were restricted to systematic reviews, meta-analysis, randomized controlled trials (RCTs), and relevant observational studies. Evidence revealed that antenatal MgSO 4 has neuroprotective role in preterm neonates and it decreased the risk of cerebral palsy and gross motor dysfunction. Evidences regarding association of antenatal MgSO 4 with feed intolerance, NEC and SIP were from cohort studies and controversial. We should continue use antenatal MgSO 4 to all eligible patients according to protocol till the more robust evidence will suggest association with gastrointestinal complications. In the meantime, we should have a high index of suspicion of gastrointestinal complications in extremely preterms particularly <26 weeks of gestation.

Diethylstilbestrol: Potential health risks for women exposed in utero and their offspring.

PubMed

Conlon, J Leocadia

2017-02-01

Diethylstilbestrol (DES) is a synthetic estrogen given to pregnant women to prevent miscarriages and preterm labor; the drug was used between 1941 and 1971 in the United States and into the 1980s in other countries. DES exposure is associated with significant long-term health effects, including increased risk for breast cancer, cervical and vaginal clear cell adenocarcinoma, reproductive tract abnormalities, infertility, poor pregnancy outcomes, and early menopause. This article reviews the potential health risks associated with DES exposure, how to assess which patients are at risk, and management recommendations for patients exposed to DES.

New Resources for Childbirth Educators and Parents

PubMed Central

Shilling, Teri

2009-01-01

In this column, reviewers offer perspectives and comments on a variety of new media resources for childbirth educators and for expectant and new parents. The books and DVDs reviewed in this issue's column address the following topics: new directions for childbirth education classes; pregnancy tips for expectant mothers; empowering women to give birth naturally; midwifery care; breastfeeding; labyrinths and “laborinths” (an alternative approach to preparing for birth); preterm labor; understanding newborns' language cues; and exercise programs during pregnancy and the postnatal period, as well as exercises that strengthen the pelvic floor and help new mothers deal with incontinence. PMID:20514118

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.

Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth.

PubMed

Mwansa-Kambafwile, Judith; Cousens, Simon; Hansen, Thomas; Lawn, Joy E

2010-04-01

In high-income countries, administration of antenatal steroids is standard care for women with anticipated preterm labour. However, although >1 million deaths due to preterm birth occur annually, antenatal steroids are not routine practice in low-income countries where most of these deaths occur. To review the evidence for and estimate the effect on cause-specific neonatal mortality of administration of antenatal steroids to women with anticipated preterm labour, with additional analysis for the effect in low- and middle-income countries. We conducted systematic reviews using standardized abstraction forms. Quality of evidence was assessed using an adapted GRADE approach. Existing meta-analyses were reviewed for relevance to low/middle-income countries, and new meta-analysis was performed. We identified 44 studies, including 18 randomised control trials (RCTs) (14 in high-income countries) in a Cochrane meta-analysis, which suggested that antenatal steroids decrease neonatal mortality among preterm infants (<36 weeks gestation) by 31% [relative risk (RR) = 0.69; 95% confidence interval (CI) 0.58-0.81]. Our new meta-analysis of four RCTs from middle-income countries suggests 53% mortality reduction (RR = 0.47; 95% CI 0.35-0.64) and 37% morbidity reduction (RR = 0.63; 95% CI 0.49-0.81). Observational study mortality data were consistent. The control group in these equivalent studies was routine care (ventilation and, in many cases, surfactant). In low-income countries, many preterm babies currently receive little or no medical care. It is plausible that antenatal steroids may be of even greater effect when tested in these settings. Based on high-grade evidence, antenatal steroid therapy is very effective in preventing neonatal mortality and morbidity, yet remains at low coverage in low/middle-income countries. If fully scaled up, this intervention could save up to 500 000 neonatal lives annually.

Basic Information Processing Abilities at 11 years Account for Deficits in IQ Associated with Preterm Birth.

PubMed

Rose, Susan A; Feldman, Judith F; Jankowski, Jeffery J; Van Rossem, Ronan

2011-07-01

Although it is well established that preterms as a group do poorly relative to their full-term peers on tests of global cognitive functioning, the basis for this relative deficiency is less understood. The present paper examines preterm deficits in core cognitive abilities and determines their role in mediating preterm/full-term differences in IQ. The performance of 11-year-old children born preterm (birth weight <1750g) and their full-term controls were compared on a large battery of 15 tasks, covering four basic cognitive domains -- memory, attention, speed of processing and representational competence. The validity of these four domains was established using latent variables and confirmatory factor analysis (CFA). Preterms showed pervasive deficits within and across domains. Additionally, preterm deficits in IQ were completely mediated by these four cognitive domains in a structural equation model involving a cascade from elementary abilities (attention and speed), to more complex abilities (memory and representational competence), to IQ. The similarity of findings to those obtained with this cohort in infancy and toddlerhood suggest that preterm deficits persist - across time, across task, and from the non-verbal to the verbal period.

[Clinical features and magnetic resonance imaging evaluation of encephalopathy in high-risk late preterm infants].

PubMed

Zhu, Yan; Zhang, Ke; Hu, Lan; Xiao, Mi-Li; Li, Zhi-Hua; Chen, Chao

2017-05-01

To investigate the risk factors, clinical features, and magnetic resonance imaging (MRI) changes of encephalopathy in high-risk late preterm infants. Head MRI scan was performed for late preterm infants with high-risk factors for brain injury who were hospitalized between January 2009 and December 2014. The risk factors, clinical features, and head MRI features of encephalopathy in late preterm infants were analyzed. A total of 1 007 late preterm infants underwent MRI scan, among whom 313 (31.1%) had imaging features in accordance with the features of encephalopathy of prematurity. Of all infants, 76.7% had white matter damage. There was no association between the development of encephalopathy and gestational age in late preterm infants, but the detection rate of encephalopathy gradually increased with the increasing birth weight (P<0.05). The logistic regression analysis showed that a history of resuscitation was an independent risk factor for encephalopathy of prematurity (P<0.01). Encephalopathy of prematurity is commonly seen in high-risk late preterm infants, especially white matter damage. A history of resuscitation is an independent risk factor for encephalopathy in late preterm infants.

Basic Information Processing Abilities at 11 years Account for Deficits in IQ Associated with Preterm Birth

PubMed Central

Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.; Van Rossem, Ronan

2011-01-01

Although it is well established that preterms as a group do poorly relative to their full-term peers on tests of global cognitive functioning, the basis for this relative deficiency is less understood. The present paper examines preterm deficits in core cognitive abilities and determines their role in mediating preterm/full-term differences in IQ. The performance of 11-year-old children born preterm (birth weight <1750g) and their full-term controls were compared on a large battery of 15 tasks, covering four basic cognitive domains -- memory, attention, speed of processing and representational competence. The validity of these four domains was established using latent variables and confirmatory factor analysis (CFA). Preterms showed pervasive deficits within and across domains. Additionally, preterm deficits in IQ were completely mediated by these four cognitive domains in a structural equation model involving a cascade from elementary abilities (attention and speed), to more complex abilities (memory and representational competence), to IQ. The similarity of findings to those obtained with this cohort in infancy and toddlerhood suggest that preterm deficits persist – across time, across task, and from the non-verbal to the verbal period. PMID:21643482

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

[Influence of neonatal diseases and treatments on the development of cerebral palsy in preterm infant].

PubMed

Yu, Tao; Rong, Luo; Wang, Qiu; You, Yi; Fu, Jun-Xian; Kang, Lin-Min; Wu, Yan-Qiao

2013-03-01

To investigated the risk factors of cerebral palsy development in preterm infants. This study included 203 preterm infants (gestation age < 37 weeks) diagnosed with cerebral palsy (CP) and 220 preterm infants without cerebral palsy or any other severe neurological disorders during April 2005 to August 2011. The risk factors in the development of cerebral palsy, including the diseases of premature infants and the treatments in neonatal period, were analyzed by multiple logistic regression analysis. Multivariate logistic analysis for the risk factors associated with cerebral palsy in neonatal period found significant differences in the occurrence of periventricular leukomalacia (PVL, OR = 39.87, P < 0.05), hypoxia-ischemic encephalopathy (HIE, OR = 4.24, P < 0.05), hypoglycemia of neonatal (OR = 2.18, P < 0.05), neonatal hyperbilirubinemia (OR = 1.72, P < 0.05), continuous positive airway pressure (CPAP, OR = 0.21, P < 0.05). The factors including PLV, HIE, hypoglycemia, and neonatal jaundice may increase the risk in the development of CP in preterm infant, while CPAP may decrease the risk of cerebral palsy.

Preterm birth among African American and white women: a multilevel analysis of socioeconomic characteristics and cigarette smoking

PubMed Central

Ahern, J; Pickett, K; Selvin, S; Abrams, B

2003-01-01

Study objective: Research shows that neighbourhood socioeconomic factors are associated with preterm delivery. This study examined whether cigarette smoking and individual socioeconomic factors modify the effects of neighbourhood factors on preterm delivery. Design: Case-control study. Setting: Moffit Hospital in San Francisco, California. Participants: 417 African American and 1244 white women, including all preterm and a random selection of term deliveries 1980–1990, excluding non-singleton pregnancies, congenital anomolies, induced deliveries, and women transported for special care. US census data from 1980 and 1990 were used to characterise the women's neighbourhoods, defined as census tracts. Results: Cigarette smoking increased the risk of preterm delivery among both African American (OR=1.77, 95% confidence intervals (CI) (1.12 to 2.79)) and white women (OR=1.25, 95% CI (1.01 to 1.55)). However, cigarette smoking did not attenuate or modify the association of neighbourhood factors with preterm delivery. Among African American women, having public insurance modified the relation between neighbourhood unemployment and preterm delivery; among women without public insurance, the risk of preterm delivery was low in areas with low unemployment and high in areas with high unemployment, while among women with public insurance the risk of preterm delivery was highest at low levels of neighbourhood unemployment. Conclusions: Cigarette smoking was associated with preterm delivery, especially among African Americans. Adverse neighbourhood conditions had an influence on preterm delivery beyond that of cigarette smoking. The effects of some neighbourhood characteristics were different depending on individual socioeconomic status. Examining socioeconomic and behavioural/biological risk factors together may increase understanding of the complex causes of preterm delivery. PMID:12883067

PMTCT Option B+ Does Not Increase Preterm Birth Risk and May Prevent Extreme Prematurity: A Retrospective Cohort Study in Malawi.

PubMed

Chagomerana, Maganizo B; Miller, William C; Pence, Brian W; Hosseinipour, Mina C; Hoffman, Irving F; Flick, Robert J; Tweya, Hannock; Mumba, Soyapi; Chimbwandira, Frank; Powers, Kimberly A

2017-04-01

To estimate preterm birth risk among infants of HIV-infected women in Lilongwe, Malawi, according to maternal antiretroviral therapy (ART) status and initiation time under Option B+. A retrospective cohort study of HIV-infected women delivering at ≥27 weeks of gestation, April 2012 to November 2015. Among women on ART at delivery, we restricted our analysis to those who initiated ART before 27 weeks of gestation. We defined preterm birth as a singleton live birth at ≥27 and <37 weeks of gestation, with births at <32 weeks classified as extremely to very preterm. We used log-binomial models to estimate risk ratios and 95% confidence intervals for the association between ART and preterm birth. Among 3074 women included in our analyses, 731 preterm deliveries were observed (24%). Overall preterm birth risk was similar in women who had initiated ART at any point before 27 weeks and those who never initiated ART (risk ratio = 1.14; 95% confidence interval: 0.84 to 1.55), but risk of extremely to very preterm birth was 2.33 (1.39 to 3.92) times as great in those who never initiated ART compared with those who did at any point before 27 weeks. Among women on ART before delivery, ART initiation before conception was associated with the lowest preterm birth risk. ART during pregnancy was not associated with preterm birth, and it may in fact be protective against severe adverse outcomes accompanying extremely to very preterm birth. As preconception ART initiation appears especially protective, long-term retention on ART should be a priority to minimize preterm birth in subsequent pregnancies.

Preterm birth rates in Japan from 1979 to 2014: Analysis of national vital statistics.

PubMed

Sakata, Soyoko; Konishi, Shoko; Ng, Chris Fook Sheng; Watanabe, Chiho

2018-03-01

Secular trends of preterm birth in Japan between 1979 and 2014 were examined to determine whether changes could be explained by a shift in the distribution of maternal age at delivery and parity and/or by changes in age-specific preterm birth rates. Live birth data for 1979 to 2014 were obtained from the Japanese Ministry of Health, Labour and Welfare. Analyses were limited to singleton children born in Japan (n = 43 632 786). Preterm birth was defined using two cut-offs at < 37 or < 34 weeks of gestation. Crude and standardized rates of preterm birth were calculated for firstborn and later-born singletons by maternal age at delivery for specific time periods. Throughout the study period, the rates of preterm birth (both at < 37 and < 34 weeks of gestation) were higher among mothers aged 20 and younger, and mid-30s and older, compared to mothers in their 20s or early 30s. The rates of preterm birth at < 37 (but not at < 34) weeks decreased for mothers aged in their late 30s and 40s, and increased for mothers in their 20s and early 30s. Standardized rates of preterm birth showed a secular increase for preterm births at < 37 but not < 34 weeks of gestation. The rates of preterm birth among mothers aged in their 20s and early 30s increased between 1979 and 2014, which contributed to the secular increase in rates of preterm birth at < 37 weeks. © 2017 Japan Society of Obstetrics and Gynecology.

Endogenous Human Milk Peptide Release Is Greater after Preterm Birth than Term Birth123

PubMed Central

Dallas, David C; Smink, Christina J; Robinson, Randall C; Tian, Tian; Guerrero, Andres; Parker, Evan A; Smilowitz, Jennifer T; Hettinga, Kasper A; Underwood, Mark A; Lebrilla, Carlito B; German, J Bruce; Barile, Daniela

2015-01-01

Background: Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and enzymatic activity, thereby resulting in an altered peptide profile. Objective: This study examined differences in peptides present between milk from women delivering at term and women delivering prematurely. Methods: Nano-LC tandem mass spectrometry was employed to identify naturally occurring peptides and compare their abundances between term and preterm human milk samples at multiple time points over lactation. Term milk samples were collected from 8 mothers and preterm milk was collected from 14 mothers. The 28 preterm and 32 term human milk samples were divided into 4 groups based on day of collection (<14, 14–28, 29–41, and 42–58 d). Results: Preterm milk peptide counts, ion abundance, and concentration were significantly higher in preterm milk than term milk. Bioinformatic analysis of the cleavage sites for peptides identified suggested that plasmin was more active in preterm milk than term milk and that cytosol aminopeptidase and carboxypeptidase B2 likely contribute to extensive milk protein breakdown. Many identified milk peptides in both term and preterm milk overlapped with known functional peptides, including antihypertensive, antimicrobial, and immunomodulatory peptides. Conclusion: The high protein degradation by endogenous proteases in preterm milk might attenuate problems because of the preterm infant’s immature digestive system. This trial was registered at clinicaltrials.gov as NCT01817127. PMID:25540406

Perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios.

PubMed

Sahin, Erdem; Madendag, Yusuf; Tayyar, Ahter Tanay; Sahin, Mefkure Eraslan; Col Madendag, Ilknur; Acmaz, Gokhan; Unsal, Deniz; Senol, Vesile

2017-08-16

The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios. A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34 + 0-36 + 6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1-8 cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups. Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery <37 weeks, cesarean delivery for non-reassuring fetal heart-rate testing, meconium-stained amniotic fluid, Apgar 5 min <7, transient tachypnea of the newborn, respiratory distress syndrome, neonatal intensive care unit, and hyperbilirubinemia were not statistically different between the groups (p = .054, p = .134, p = .749, p = 0.858, p = .703, p = .320, p = .185, and p = .996, respectively). Although gestational age was full-term, induction of labor rates were significantly higher in the borderline AFI group (p = .040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p = .014). Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.

The ELGAN study of the brain and related disorders in extremely low gestational age newborns.

PubMed

O'Shea, T M; Allred, E N; Dammann, O; Hirtz, D; Kuban, K C K; Paneth, N; Leviton, A

2009-11-01

Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities. To identify factors that contribute to brain damage in ELGANs. Multi-center cohort study. We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots. Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age, i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders. ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery; greater neonatal illness severity; severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis. In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma.

Coagulase-Negative Staphylococci in Human Milk From Mothers of Preterm Compared With Term Neonates.

PubMed

Soeorg, Hiie; Metsvaht, Tuuli; Eelmäe, Imbi; Metsvaht, Hanna Kadri; Treumuth, Sirli; Merila, Mirjam; Ilmoja, Mari-Liis; Lutsar, Irja

2017-05-01

Human milk is the preferred nutrition for neonates and a source of bacteria. Research aim: The authors aimed to characterize the molecular epidemiology and genetic content of staphylococci in the human milk of mothers of preterm and term neonates. Staphylococci were isolated once per week in the 1st month postpartum from the human milk of mothers of 20 healthy term and 49 preterm neonates hospitalized in the neonatal intensive care unit. Multilocus variable-number tandem-repeats analysis and multilocus sequence typing were used. The presence of the mecA gene, icaA gene of the ica-operon, IS 256, and ACME genetic elements was determined by PCR. The human milk of mothers of preterm compared with term neonates had higher counts of staphylococci but lower species diversity. The human milk of mothers of preterm compared with term neonates more often contained Staphylococcus epidermidis mecA (32.7% vs. 2.6%), icaA (18.8% vs. 6%), IS 256 (7.9% vs. 0.9%), and ACME (15.4% vs. 5.1%), as well as Staphylococcus haemolyticus mecA (90.5% vs. 10%) and IS 256 (61.9% vs. 10%). The overall distribution of multilocus variable-number tandem-repeats analysis (MLVA) types and sequence types was similar between the human milk of mothers of preterm and term neonates, but a few mecA-IS 256-positive MLVA types colonized only mothers of preterm neonates. Maternal hospitalization within 1 month postpartum and the use of an arterial catheter or antibacterial treatment in the neonate increased the odds of harboring mecA-positive staphylococci in human milk. Limiting exposure of mothers of preterm neonates to the hospital could prevent human milk colonization with more pathogenic staphylococci.

Altered Network Oscillations and Functional Connectivity Dynamics in Children Born Very Preterm.

PubMed

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

2015-09-01

Structural brain connections develop atypically in very preterm children, and altered functional connectivity is also evident in fMRI studies. Such alterations in brain network connectivity are associated with cognitive difficulties in this population. Little is known, however, about electrophysiological interactions among specific brain networks in children born very preterm. In the present study, we recorded magnetoencephalography while very preterm children and full-term controls performed a visual short-term memory task. Regions expressing task-dependent activity changes were identified using beamformer analysis, and inter-regional phase synchrony was calculated. Very preterm children expressed altered regional recruitment in distributed networks of brain areas, across standard physiological frequency ranges including the theta, alpha, beta and gamma bands. Reduced oscillatory synchrony was observed among task-activated brain regions in very preterm children, particularly for connections involving areas critical for executive abilities, including middle frontal gyrus. These findings suggest that inability to recruit neurophysiological activity and interactions in distributed networks including frontal regions may contribute to difficulties in cognitive development in children born very preterm.

Association of maternal depression with dietary intake, growth, and development of preterm infants: a cohort study in Beijing, China.

PubMed

Wang, Han; Zhou, Hong; Zhang, Yan; Wang, Yan; Sun, Jing

2017-11-27

This study aimed to explore the association of maternal depression with nutrient intake, growth, and development of preterm infants. A cohort study of 201 infants was conducted in Beijing. Based on the gestational age of an infant and status of the mother, the infants were divided into four groups: non-depression-fullterm (64), non-depression-preterm (70), depression-fullterm (36), and depression-preterm (31). Data on sociodemographic characteristics, nutritional intake, growth, and developmental status of children at 8 months (corrected ages) were collected using a quantitative questionnaire, a 24-Hour Dietary Recall, anthropometric measurements, and the Bayley-III scale. A multivariate analysis was used to evaluate the effects of maternal depression and preterm birth on infant growth and development. The energy, protein, and carbohydrate intake in the depression group was lower than the recommended amounts. The depression preterm groups indicated the lowest Z-scores for length and weight and the lowest Bayley-III scores. Preterm infants of depressed mothers are at high risks of poor growth and development delay.

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.

Relation between sleep status of preterm infants aged 1-2 years and mothers' parenting stress.

PubMed

Asaka, Yoko; Takada, Satoshi

2013-08-01

The aim of this study was to compare infants' sleep measures through an actigraph and maternal parenting stress among preterm and full-term mothers, and to explore the factors affecting maternal parenting stress in relation to infants' sleep. The subjects were 44 pairs of mothers and children. Twenty-one were in the preterm group, and 23 were in the full-term group. Inclusion criteria for preterm infants were born at less than 36 weeks and birthweight of less than 2500 g. The Parenting Stress Index (PSI) Short Form assesses maternal perception of the degree of parenting stress: the children's domain, and the parent's domain. An actigraph was applied to assess the infants' sleep measures. The PSI showed significant differences, with high scores in parenting stress in the preterm group. Also, the number of mothers who complained about their infant's sleep issues was significantly higher in the preterm group. Most of the sleep measures showed improvement by their age in both preterm and full-term infants. Multiple linear regression analysis showed that sleep efficiency, longest sleep duration at nighttime accounted for 71% of stress in the children's domain of the PSI of the preterm group. The parenting stress among mothers of preterm infants was significantly higher than that of mothers of full-term infants. The mothers of preterm infants were concerned about their infant's nocturnal sleep quality. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

The effects of preterm birth on mother-infant interaction and attachment during the infant's first two years.

PubMed

Korja, Riikka; Latva, Reija; Lehtonen, Liisa

2012-02-01

Early mother-infant relationships in preterm populations were evaluated in the context of a systematic review of the literature. A systematic search of three electronic databases (PsychINFO, PubMed and Cochrane Library) was undertaken. Three studies of maternal attachment, 18 studies of mother-preterm infant interaction and eight studies of infant attachment were included. Studies of preterm infant attachment were also evaluated using a meta-analysis. Studies of mother-preterm infant interactions showed that the differences in maternal interaction behavior between mothers of preterm infants and mothers of full-term infants seem to be most evident during the first six months of life. Differences in the preterm infant's interaction behavior seem also to continue for six months after birth. However, five of 18 studies showed an equal or even higher quality of mother-infant interaction in groups of preterm compared to groups of full-term infants. Studies of maternal and infant attachment indicated that preterm infants and their mothers are not at higher risk of insecure attachment than full-term infants and their mothers. The mother-preterm infant relationship is complex, and some relational patterns forecast greater psychological risk than others. It is important to decrease maternal stress and early separation in every possible way during hospitalization as well as after discharge. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

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

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.

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.

Change-point analysis data of neonatal diffusion tensor MRI in preterm and term-born infants.

PubMed

Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

2017-06-01

The data presented in this article are related to the research article entitled "Mapping the Critical Gestational Age at Birth that Alters Brain Development in Preterm-born Infants using Multi-Modal MRI" (Wu et al., 2017) [1]. Brain immaturity at birth poses critical neurological risks in the preterm-born infants. We used a novel change-point model to analyze the critical gestational age at birth (GAB) that could affect postnatal development, based on diffusion tensor MRI (DTI) acquired from 43 preterm and 43 term-born infants in 126 brain regions. In the corresponding research article, we presented change-point analysis of fractional anisotropy (FA) and mean diffusivities (MD) measurements in these infants. In this article, we offered the relative changes of axonal and radial diffusivities (AD and RD) in relation to the change of FA and FA-based change-points, and we also provided the AD- and RD-based change-point results.

Developmental exposure to terbutaline and chlorpyrifos: pharmacotherapy of preterm labor and an environmental neurotoxicant converge on serotonergic systems in neonatal rat brain regions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aldridge, Justin E.; Meyer, Armando; Centro de Estudos da Saude do Trabalhador e Ecologia Humana, Escola Nacional de Saude Publica, Fundacao Oswaldo Cruz, Rio de Janeiro

2005-03-01

Developmental exposure to unrelated neurotoxicants can nevertheless produce similar neurobehavioral outcomes. We examined the effects of developmental exposure to terbutaline, a tocolytic {beta}{sub 2}-adrenoceptor agonist used to arrest preterm labor, and chlorpyrifos (CPF), a widely used organophosphate pesticide, on serotonin (5HT) systems. Treatments were chosen to parallel periods typical of human developmental exposures, terbutaline (10 mg/kg) on postnatal days (PN) 2-5 and CPF (5 mg/kg) on PN11-14, with assessments conducted on PN45, comparing each agent alone as well as sequential administration of both. Although neither treatment affected growth or viability, each elicited similar alterations in factors that are critical tomore » the function of the 5HT synapse: 5HT{sub 1A} receptors, 5HT{sub 2} receptors, and the presynaptic 5HT transporter (5HTT). Either agent elicited global increases in 5HT receptors and the 5HTT in brain regions possessing 5HT cell bodies (midbrain, brainstem) as well as in the hippocampus, which contains 5HT projections. For both terbutaline and CPF, males were affected more than females, although there were some regional disparities in the sex selectivity between the two agents. Both altered 5HT receptor-mediated cell signaling, suppressing stimulatory effects on adenylyl cyclase and enhancing inhibitory effects. When animals were exposed sequentially to both agents, the outcomes were no more than additive and, for many effects, less than additive, suggesting convergence of the two agents on a common set of developmental mechanisms. Our results indicate that 5HT systems represent a target for otherwise unrelated neuroteratogens.« less

Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus.

PubMed

Clowse, Megan E B; Grotegut, Chad

2016-10-01

Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step. © 2016, American College of Rheumatology.

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.

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

Interleukin-6 is an essential determinant of on-time parturition in the mouse.

PubMed

Robertson, Sarah A; Christiaens, Inge; Dorian, Camilla L; Zaragoza, Dean B; Care, Alison S; Banks, Anke M; Olson, David M

2010-08-01

IL-6 abundance in amniotic fluid and uterine tissues increases in late gestation or with infection-associated preterm labor. A role in regulation of labor onset is suggested by observations that IL-6 increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether IL-6 is essential for normal parturition is unknown. To evaluate the physiological role of IL-6 in parturition in mice, we investigated the effect of Il6 null mutation on the timing of parturition and expression of genes associated with uterine activation. Il6 null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. Il6 null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce preterm delivery in wild-type mice. The characteristic late-gestation elevation in uterine expression of Oxtr mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in Il6 null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in Il6 null mutant mice. Administration of recombinant IL-6 from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that IL-6 has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade.

Management of Labor and Delivery After Fetoscopic Repair of an Open Neural Tube Defect.

PubMed

Kohn, Jaden R; Rao, Vibha; Sellner, Allison A; Sharhan, Dina; Espinoza, Jimmy; Shamshirsaz, Alireza A; Whitehead, William E; Belfort, Michael A; Sanz Cortes, Magdalena

2018-06-01

To report labor, delivery, and neonatal outcomes in a cohort of women delivering neonates who had undergone fetoscopic neural tube defect repair. We conducted a retrospective cohort study from April 2014 to January 2018. All patients met Management of Myelomeningocele Study eligibility criteria. We included patients with completed second-trimester fetoscopic neural tube defect repair (laparotomy, uterine exteriorization, and minimally invasive access through two or three uterine ports) followed by standardized management of labor and delivery at our institution. Outcomes included rates of vaginal delivery, term delivery, and intrapartum cesarean delivery as well as obstetric and neonatal outcomes after oxytocin. Complications of interest included preterm prelabor rupture of membranes, chorioamnionitis, uterine dehiscence or rupture, 5-minute Apgar score less than 7, and neonatal acidosis (umbilical artery pH less than 7.15). Thirty-four patients had fetoscopic repair, followed by 17 vaginal deliveries (50%, 95% CI 32-68%). Median gestational age was 38 1/7 weeks at vaginal delivery (range 26 0/7-40 2/7 weeks of gestation) and 37 1/7 weeks of gestation at cesarean delivery (range 25 5/7-40 5/7 weeks of gestation); 62% of deliveries occurred at term. Eight patients had prelabor cesarean delivery: three nonurgent and five urgent (for nonreassuring fetal heart tracings). Twenty-six patients labored; six were induced and 20 labored spontaneously. Of the latter, five were augmented. Of 26 laboring patients, 17 delivered vaginally and nine underwent urgent cesarean delivery (35%, 95% CI 17-56%; seven nonreassuring fetal heart tracings and two breech). There were no cases of uterine rupture or dehiscence. Most (94%, 95% CI 80-99%) had normal 5-minute Apgar scores; one neonate (3%, 95% CI 0-15%) had acidosis but normal Apgar scores. Our data regarding trial of labor, use of low-dose oxytocin, and vaginal delivery after prenatal fetoscopic neural tube defect repair are reassuring. Importantly, fetoscopic repair may permit delivery at advanced gestational ages.

Human trophoblast cell during first trimester after IVF-ET differs from natural conceived pregnancy in development and function.

PubMed

Yang, Rui; Liu, Ying-Ying; Zhao, Liang; Wang, Ying; Li, Rong; Liu, Ping; Ma, Cai-Hong; Chen, Xin-Na; Qiao, Jie

2017-03-01

To explore the differences of the trophoblast cell function in first trimester between natural pregnancy and pregnancy after IVF-ET therapy. 102 cases with twin to singleton fetal reduction after IVF-ET treatment from July 2010 to August 2013 in Peking University Third Hospital were involved in analysis, and eight specimens were obtained from this group. 10 natural-pregnancy cases undergoing artificial abortion with unwanted pregnancy were recruited as control. Semi-quantitative immunohistochemical method was used to detect the expression of EGFR, Bcl-2, tubulin-α, metallothionein and AFP in villi in both groups. Of the 102 cases, 14 cases (13.73%) were aborted. Preterm birth occurred in seven cases (7.86%). Low birth weight occurred in three patients (3.37%), and extremely low birth weight occurred in four cases (4.49%). The expression of EGFR, tubulin-α, Bcl-2, and metallothionein in the IVF-ET group was significantly lower than that in the control group (P<0.05). However, AFP expression was significantly higher in IVF-ET group than in control group (P<0.05). In IVF-ET group, the miscarriage case had weaker EGFR, tubulin-α, and metallothionein expression than full-term pregnancy; the early preterm labor case had weaker Bcl-2, tubulin-α, and metallothionein expression; and velamentous cord insertion case had weaker tubulin-α expression. The trophoblast cell function of IVF-ET group in first trimester is different from control group in proliferation, invasion, apoptosis and vascular development, and optimal pregnancy outcome depends on the self-healing balance of trophoblast cells.

Using Geographic Information Science to Explore Associations between Air Pollution, Environmental Amenities, and Preterm Births

PubMed Central

Ogneva-Himmelberger, Yelena; Dahlberg, Tyler; Kelly, Kristen; Simas, Tiffany A. Moore

2015-01-01

The study uses geographic information science (GIS) and statistics to find out if there are statistical differences between full term and preterm births to non-Hispanic white, non-Hispanic Black, and Hispanic mothers in their exposure to air pollution and access to environmental amenities (green space and vendors of healthy food) in the second largest city in New England, Worcester, Massachusetts. Proximity to a Toxic Release Inventory site has a statistically significant effect on preterm birth regardless of race. The air-pollution hazard score from the Risk Screening Environmental Indicators Model is also a statistically significant factor when preterm births are categorized into three groups based on the degree of prematurity. Proximity to green space and to a healthy food vendor did not have an effect on preterm births. The study also used cluster analysis and found statistically significant spatial clusters of high preterm birth volume for non-Hispanic white, non-Hispanic Black, and Hispanic mothers. PMID:29546120

Using Geographic Information Science to Explore Associations between Air Pollution, Environmental Amenities, and Preterm Births.

PubMed

Ogneva-Himmelberger, Yelena; Dahlberg, Tyler; Kelly, Kristen; Simas, Tiffany A Moore

2015-01-01

The study uses geographic information science (GIS) and statistics to find out if there are statistical differences between full term and preterm births to non-Hispanic white, non-Hispanic Black, and Hispanic mothers in their exposure to air pollution and access to environmental amenities (green space and vendors of healthy food) in the second largest city in New England, Worcester, Massachusetts. Proximity to a Toxic Release Inventory site has a statistically significant effect on preterm birth regardless of race. The air-pollution hazard score from the Risk Screening Environmental Indicators Model is also a statistically significant factor when preterm births are categorized into three groups based on the degree of prematurity. Proximity to green space and to a healthy food vendor did not have an effect on preterm births. The study also used cluster analysis and found statistically significant spatial clusters of high preterm birth volume for non-Hispanic white, non-Hispanic Black, and Hispanic mothers.

Social Support Provision: Perspective of Fathers With Preterm Infants.

PubMed

Kim, Hyung Nam

Today's social support systems for parents of preterm infants tend to pay more attention to mothers than fathers. As a father also plays a critical role in caring for a preterm infant, there is a need to advance understanding of paternal concerns and needs about social supports that should better support fathers. Interviews were conducted with 18 parents of preterm infants (i.e., 10 mothers and 8 fathers) who have been discharged from the NICU to home. All interviews were audio-recorded and subsequently transcribed verbatim for analysis. The fathers' primary resources are healthcare professionals, their partners, and peer fathers of preterm infants. The fathers expressed various social support needs associated with informational, belonging, and emotional supports. It is recommended that a social support system be customized accordingly to better accommodate paternal needs. Healthcare professionals may refer to the study results in designing the educational materials for fathers of preterm infants. Copyright © 2018 Elsevier Inc. All rights reserved.

Preventing preterm births: trends and potential reductions with current interventionsin 39 very high human development index countries

PubMed Central

Chang, Hannah H.; Larson, Jim; Blencowe, Hannah; Spong, Catherine Y.; Howson, Christopher P.; Cairns-Smith, Sarah; Lackritz, Eve M.; Lee, Shoo K.; Mason, Elizabeth; Serazin, Andrew C.; Walani, Salimah; Simpson, Joe Leigh; Lawn, Joy E.

2013-01-01

Summary Background Each year,1.1 million babies die from prematurity, andmany survivors are disabled. Worldwide, 15 million babies are preterm(<37 weeks’ gestation),withtwo decades of increasing ratesinalmost all countries with reliable data. Improved care of babies has reduced mortality in high-income countries, although effective interventions have yet to be scaled-up in most low-income countries. A 50% reduction goal for preterm-specific mortality by 2025 has been set in the “Born Too Soon” report. However, for preterm birth prevention,understanding of drivers and potential impact of preventive interventions is limited. We examine trends and estimate the potential reduction in preterm birthsforvery high human development index (VHHDI) countries if current evidence-based interventions were widely implemented. This analysis is to inform a “Born Too Soon” rate reduction target. Methods Countries were assessed for inclusion based on availability and quality ofpreterm prevalence data (2000-2010), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1998-2004. For 39 VHHDI countrieswith >10,000 births, country-by-country analyses were performed based on target population, incremental coverage increase,and intervention efficacy. Cost savings were estimated based on reported costs for preterm care in the USAadjusted usingWorld Bank purchasing power parity. Findings From 2010, even if all VHHDI countries achieved annual preterm birth rate reductions of the best performers, (Sweden and Netherlands), 2000-2010 or 2005-2010(Lithuania, Estonia)), rates would experience a relative reduction of<5% by 2015 on average across the 39 countries.Our analysis of preterm birth rise 1998-2004 in USA suggests half the change is unexplained, but important drivers includeinductions/cesareandelivery and ART.For all 39 VHHDI countries, five interventionsmodeling at high coveragepredicted 5%preterm birth rate relative reduction from 9.59 to 9.07% of live births:smoking cessation (0.01 rate reduction), decreasing multiple embryo transfers during assisted reproductive technologies (0.06), cervical cerclage (0.15), progesterone supplementation (0.01), and reduction of non-medically indicated labour induction or caesarean delivery (0.29).These translate to 58,000 preterm births averted and total annual economic cost savings of ~US$ 3 billion. Interpretation Even with optimal coverage of current interventions, many being complex to implement, the estimated potential reduction in preterm birth is tiny. Hence we recommenda conservative target of 5% preterm birth rate relative reductionby 2015. Our findings highlight the urgent need for discovery research into underlying mechanisms of preterm birth, and developmentof innovative interventions. Furthermore, the highest preterm birth rates occur in low-income settings where the causes of prematurity may differand have simpler solutions, such as birth spacing and treatment of infections in pregnancy. Urgent focus on these settings also is critical to reduce preterm births worldwide. PMID:23158883

The inner state differences of preterm birth rates in Brazil: a time series study.

PubMed

de Oliveira, Rosana Rosseto; Melo, Emiliana Cristina; Fujimori, Elizabeth; Mathias, Thais Aidar de Freitas

2016-05-17

Preterm birth is a serious public health problem, as it is linked to high rates of neonatal and child morbidity and mortality. The prevalence of premature births has increased worldwide, with regional differences. The objective of this study was to analyze the trend of preterm births in the state of Paraná, Brazil, according to Macro-regional and Regional Health Offices (RHOs). This is an ecological time series study using preterm births records from the national live birth registry system of Brazil's National Health Service - Live Birth Information System (Sinasc), for residents of the state of Paraná, Brazil, between 2000 and 2013. The preterm birth rates was calculated on a yearly basis and grouped into three-year periods (2000-2002, 2003-2005, 2006-2008, 2009-2011) and one two-year period (2012-2013), according to gestational age and mother's Regional Health Office of residence. The polynomial regression model was used for trend analysis. The predominance of preterm birth rate increased from 6.8 % in 2000 to 10.5 % in 2013, with an average increase of 0.20 % per year (r(2) = 0.89), and a greater share of moderate preterm births (32 to <37 weeks), which increased from 5.8 % to 9 %. The same pattern was observed for all Macro-regional Health Offices, with highlight to the Northern Macro-Regional Office, which showed the highest average rate of prematurity and average annual growth during that period (7.55 % and 0.35 %, respectively). The trend analysis of preterm birth rates according to RHO showed a growing trend for almost all RHOs - except for the 7(th) RHO where a declining trend was observed (-0.95 a year); and in the 20(th), 21(st) and 22(nd) RHOs which remained unchanged. In the last three-year of the study period (2011-2013), no RHO showed preterm birth rates below 7.3 % or prevalence of moderate preterm birth below 9.4 %. The results show an increase in preterm births with differences among Macro-regional and RHOs, which indicate the need to improve actions during the prenatal period according to the specificities of each region.

Pregnant Women With Posttraumatic Stress Disorder and Risk of Preterm Birth

PubMed Central

Yonkers, Kimberly Ann; Smith, Megan V.; Forray, Ariadna; Epperson, C. Neill; Costello, Darce; Lin, Haiqun; Belanger, Kathleen

2014-01-01

IMPORTANCE Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions. OBJECTIVE To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth. DESIGN, SETTING, AND PARTICIPANTS Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts. EXPOSURES Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications. MAIN OUTCOMES AND MEASURES Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview. RESULTS Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27–13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0–110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02–2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98–4.03]). CONCLUSIONS AND RELEVANCE Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms. PMID:24920287

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.

Prenatal stress alters amygdala functional connectivity in preterm neonates.

PubMed

Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

2016-01-01

Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

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.

Association of external cephalic version before term with late preterm birth.

PubMed

Poole, Kristie L; McDonald, Sarah D; Griffith, Lauren E; Hutton, Eileen K

2017-08-01

While evidence suggests that beginning an external cephalic version (ECV) before term (34 0/7 to 36 6/7 weeks) compared with after term may be associated with an increase in late preterm birth (34 0/7 to 36 6/7 weeks), it remains unknown what might account for this risk. The objective of the present study is to further investigate the association between ECV before term and late preterm birth. Secondary analysis of data collected from the international, multicenter Early ECV trials. We evaluated the relation between ECV exposure and late preterm birth (34 0/7 to 36 6/7 weeks), as well as whether additional risk factors for preterm birth (such as maternal age, height, body mass index, parity, placental location, and perinatal mortality rate) moderated this relation. Generalized linear mixed methods were used to account for center effect and adjust for covariates. Among 1765 women with breech pregnancies and without a prior preterm birth, 749 (42.4%) received at least one ECV before term. Exposure to an ECV before term was not associated significantly independently with odds of preterm birth. However, placenta location moderated the association between early ECV exposure and late preterm birth. The odds of preterm birth in women who were exposed to an ECV before term and who also had an anterior placenta were doubled (OR 2.05; 95% CI 1.12-3.71; p = 0.02). In a large cohort of women without known risks for preterm birth, those with an anterior placenta who undergo an ECV before term constitute a subgroup at particular risk for late preterm birth. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Preterm newborns show slower repair of oxidative damage and paternal smoking associated DNA damage.

PubMed

Vande Loock, Kim; Ciardelli, Roberta; Decordier, Ilse; Plas, Gina; Haumont, Dominique; Kirsch-Volders, Micheline

2012-09-01

Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common etiological factor for certain neonatal diseases in preterm infants. The aim of this study was to assess background DNA damage; in vitro H(2)O(2) induced oxidative DNA damage and repair capacity (residual DNA damage) in peripheral blood mononucleated cells from 25 preterm newborns and their mothers. In addition, demographic data were taken into account and repair capacity of preterm was compared with full-term newborns. Multivariate linear regression analysis revealed that preterm infants from smoking fathers have higher background DNA damage levels than those from non-smoking fathers, emphasizing the risk of paternal smoking behaviour for the progeny. Significantly higher residual DNA damage found after 15-min repair in preterm children compared to their mothers and higher residual DNA damage after 2 h compared to full-term newborns suggest a slower DNA repair capacity in preterm children. In comparison with preterm infants born by caesarean delivery, preterm infants born by vaginal delivery do repair more slowly the in vitro induced oxidative DNA damage. Final impact of passive smoking and of the slower DNA repair activity of preterm infants need to be confirmed in a larger study population combining transgenerational genetic and/or epigenetic effects, antioxidant levels, genotypes, repair enzyme efficiency/levels and infant morbidity.

Nurses' perspectives on the suffering of preterm infants.

PubMed

Korhonen, Anne; Haho, Annu; Pölkki, Tarja

2013-11-01

The concept of suffering is discussed among those who are cognitively aware and verbally capable to express their suffering. Due to immaturity, preterm infants' abilities to express suffering are limited. Relieving suffering is an ethical and juridical demand of good nursing care. The purpose of this study is to describe nurses' perceptions of the suffering of preterm infants. A descriptive qualitative approach was selected. Data were collected from essays written by nurses (n = 19) working in the neonatal intensive care unit. Inductive content analysis guided by the research question was performed. The nurses described individually determined suffering of the preterm infants according to four categories: suffering ruled by maturation, existence of suffering, individual threshold of suffering and interpreting the cues of suffering. Suffering of preterm infants is manifested by population-specific features, emphasising the need to develop sensitive interventions for relieving their suffering.

[Neonatal behavioural assessment of pre-term and full-term infants as experienced by parents].

PubMed

Kiepura, Eliza; Kmita, Grażyna; Cieślak-Osik, Bożena; Urmańska, Wanda; Lewandowska, Dorota

2011-01-01

The analysis of similarities and differences of parental experience of observing preterm versus full term babies assessed with the Neonatal Behavioural Assessment Scale (NBAS). 95 pairs of parents participated in the study, including 33 mothers and fathers of babies born before 29th gestational week, 31 - between 29th and 34th week and 31 - at term. All infants were assessed with the NBAS in the first month of life (or corrected age) in the presence of both parents. Semi-structured clinical interviews were conducted with each parental pair and the qualitative analysis of the obtained co-constructed narratives was carried out. Seven common categories of parental experience related to the NBAS were empirically discerned in all groups of parents. There were also two categories of experience related to the NBAS that were different in the group of parents of preterm versus full term babies. Apart from that, three specific categories characteristic of the parental narratives in the two preterm groups were identified: parental tendency to compare NBAS assessment with medical examination, hope for having the child's health confirmed and parental tendency to compare preterm with full term babies. Mothers and fathers of preterm vs full term babies experience the observation of NBAS assessment differently. Parents of preterm babies are extremely sensitive to any information regarding their child. Therefore specialists should pay a special attention to the process of communicating with the family. Effective support of any family in the perinatal period requires special appreciation of the individual parental needs.

[Relationship between the thyroid autoimmunity and the risk of preterm birth in pregnant women: a meta-analysis].

PubMed

Li, M; Wang, S W; Huang, S; Mao, Y

2016-05-25

To evaluate the relationship between thyroid autoimmunity and the risk of preterm birth. Literature search was done among PubMed, Embase, Wanfang Medical Database, China Academic Journal Network Publishing Database and China Biology Medicine disc from Jan. 1(st) 1980 to July 31(st), 2015. (1) Literature were extracted according to inclusion and exclusion standards, and the quality of the extracted literature were evaluated by Newcastle-Ottawa Scale (NOS). (2) Meta-analysis was performed by RevMan 5 software formulated by using the Cochrane library databases. Various heterogeneity of the research was inspected firstly. According to the results of the inspection a certain effect model was selected (including fixed effects model, the random effects model) to be utilized in merger analysis. In this study pregnant women with both thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin (TG-Ab) positive were defined as thyroid antibody positive pregnant women. Pregnant women with only TPO-Ab positive were defined as TPO-Ab positive pregnant women. Then the relationship of antibody positive and the risk of a preterm birth was analyzed respectively. (1) Ten cohort studies were enrolled, of which NOS scale score were 7 or higher. All the studies are of medium quality and above. A total of 1 322 cases of preterm birth occurred among 19 910 pregnant women. (2) Positive thyroid autoantibodies did not increase the risk of preterm birth in euthyroid pregnant women (OR=1.41, 95%CI: 0.83-2.40, P=0.200) or in pregnant women with hypothyroidism (OR=0.68, 95% CI: 0.32-1.44, P=0.310) . Positive TPO-Ab in euthyroid pregnant women increase the risk of preterm birth significantly (OR=2.08, 95%CI: 1.09-3.97, P=0.030), but positive TPO-Ab in pregnant women with hypothyroidism did not increase the risk of preterm birth significantly (OR=1.21, 95%CI: 0.65-2.24, P=0.550). Positive TPO-Ab is an independent risk factor of preterm birth in euthyroid pregnant women.

Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

PubMed

Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

2016-10-23

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; β = -89.6, 95% CI = -131.5; -47.7; p < 0.0001; β = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

[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.

Increased aortic wave reflection contributes to higher systolic blood pressure in adolescents born preterm.

PubMed

Kowalski, Remi R; Beare, Richard; Mynard, Jonathan P; Cheong, Jeanie L Y; Doyle, Lex W; Smolich, Joseph J; Cheung, Michael M H

2018-03-29

To evaluate the wave reflection characteristics in the aortic arch and common carotid artery of ex-preterm adolescents and assess their relationship to central blood pressure in a cohort followed prospectively since birth. Central blood pressures, pulse wave velocity, augmentation index, microvascular reactive hyperemia, arterial distensibility, compliance and stiffness index, and also aortic and carotid wave intensity were measured in 18-year-olds born extremely preterm at below 28 weeks' gestation (n = 76) and term-born controls (n = 42). Compared with controls, ex-preterm adolescents had higher central systolic (111 ± 11 vs. 105 ± 10 mmHg; P < 0.001) and diastolic blood pressures (73 ± 7 vs. 67 ± 7 mmHg; P < 0.001). Although conventional measures of arterial function and biomechanics such as pulse wave velocity and augmentation index were no different between groups, wave intensity analysis revealed elevated backward compression wave area (-0.39 ± 0.21 vs. -0.29 ± 0.17 W/m/s × 10; P = 0.03), backward compression wave pressure change (9.0 ± 3.5 vs. 6.6 ± 2.5 mmHg; P = 0.001) and reflection index (0.44 ± 0.15 vs. 0.32 ± 0.08; P < 0.001) in the aorta of ex-preterm adolescents compared with controls. These changes were less pronounced in the carotid artery. On multivariable analysis, forward and backward compression wave areas were the only biomechanical variables associated with central systolic pressure. Ex-preterm adolescents demonstrate elevated wave reflection indices in the aortic arch, which correlate with central systolic pressure. Wave intensity analysis may provide a sensitive novel marker of evolving vascular dysfunction in ex-preterm survivors.

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

OVER-EXPRESSION OF THE THROMBIN RECEPTOR (PAR-1) IN THE PLACENTA IN PREECLAMPSIA: A MECHANISM FOR THE INTERSECTION OF COAGULATION AND INFLAMMATION

PubMed Central

EREZ, OFFER; ROMERO, ROBERTO; KIM, SUNG-SU; KIM, JUNG-SUN; KIM, YEON MEE; WILDMAN, DEREK E; THAN, NANDOR GABOR; MAZAKI-TOVI, SHALI; GOTSCH, FRANCESCA; PINELES, BETH; KUSANOVIC, JUAN PEDRO; ESPINOZA, JIMMY; MITTAL, POOJA; MAZOR, MOSHE; HASSAN, SONIA S.; KIM, CHONG JAI

2008-01-01

Objective Preeclampsia (PE) is characterized by excessive thrombin generation that has been implicated in the multiple organ damage associated with the disease. The biological effects of thrombin on coagulation and inflammation are mediated by protease activated receptor-1 (PAR-1), a G-protein coupled receptor. The aim of this study was to determine whether preterm preeclampsia (PE) is associated with changes in placental expression of PAR-1. Study design This cross-sectional study included two groups matched for gestational age at delivery: 1) patients with preterm PE (<37 weeks of gestation; n=26) and 2) a control group of patients with preterm labor without intraamniotic infection (n=26). Placental tissue microarrays were immunostained for PAR-1. Immunoreactivity of PAR-1 in the villous trophoblasts was graded as negative, weak-positive, or strong-positive. Results 1) The proportion of cases with strong PAR-1 immunoreactivity was significantly higher in placentas of patients with preeclampsia than in placentas from the control group [37.5% (9/24) vs. 8.7% (2/23); p=0.036, respectively]. 2) PAR-1 immunoreactivity was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells. 3) PAR-1 was detected in 92.3% (24/26) of the placentas of women with preeclampsia and in 88.5% (23/26) of the placentas from the control group (p=1). Conclusion Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous PTL. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in preeclampsia. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme. PMID:18570113

Effect of Vocalization of the Holy Quran With and Without Translation on Pregnancy Outcomes: A Randomized Clinical Trial.

PubMed

Mirghafourvand, Mojgan; Sehhati Shafaie, Fahimeh; Mohammad-Alizadeh-Charandabi, Sakineh; Jabbari, Batoul

2016-09-01

During recent decades, research in Iran in the area of the Quran and medical science has been seriously engaged in. With respect to the tendency toward spirituality and alternative medicine, we tried to find other aspects of the influence of the Quran. This study aimed to determine the effect of vocalizations of the Holy Quran with and without translation on the consequences of pregnancy (the prevalence of preterm delivery, caesarean delivery, and neonatal anthropometric indices) in women admitted to health care centers in Urmia, Iran. This was a three-armed parallel-group randomized clinical trial in which 168 pregnant women (25-28 weeks) in their first and second pregnancies were divided into three groups of 56 (Holy Quran with translation, Holy Quran without translation, and control group) by randomized blocking. The intervention was implemented once a week for three weeks in the health center, and on other days of the week, the participants listened at home to a CD they were given. The intervention and the control groups all received routine pregnancy care once a week. These mothers were tracked during their labor. Outcomes including gestational age at delivery, delivery type, and neonatal anthropometric indices were recorded based on the mother's records. There was no statistically significant difference between the groups in terms of demographic and obstetric characteristics before the intervention. In comparison with the control group, the probability of preterm delivery was lower in the Holy Quran with translation group (odds ratio: 0.3, CI 95%: 0.1-1.2) and in the Holy Quran without translation group (0.6, 0.2-1.9) as compared to the control group. However, this difference was not statistically significant. Similarly, the probability of caesarean delivery was lower in the Holy Quran with translation group (0.6, 0.3-1.4) and the Holy Quran without translation group (0.5, 0.2-1.2) as compared to the control group. Based on one-way ANOVA, there was no statistically significant difference between the study groups regarding the infants' anthropometric indices. Based on the results of this study, despite the lower prevalence of preterm labor and caesarean section in the intervention groups as compared to the control group, no statistically significant effect was seen. This was apparently due to the small sample size.

[Risk factors for patent ductus arteriosus in early preterm infants: a case-control study].

PubMed

Du, Jin-Feng; Liu, Tian-Tian; Wu, Hui

2016-01-01

To investigate the risk factors for the occurrence of patent ductus arteriosus (PDA) and to provide a clinical basis for reducing the occurrence of PDA in early preterm infants. A total of 136 early preterm infants (gestational age≤32 weeks) who were hospitalized between January 2013 and December 2014 and diagnosed with hemodynamicalhy significant PDA (hs-PDA) were enrolled as the case group. Based on the matched case-control principle, 136 early preterm infants without hs-PDA were selected among those who were hospitalized within the same period at a ratio of 1:1 and enrolled as the control group. The two groups were matched for sex and gestational age. The basic information of neonates and maternal conditions during the pregnancy and perinatal periods were collected. Logistic regression analysis was performed to identify the risk factors for the development of PDA. Univariate analysis showed that neonatal infectious diseases, neonatal respiratory distress syndrome, decreased platelet count within 24 hours after birth, and low birth weight were associated with the development of hs-PDA (P<0.05). Multivariate conditional logistic regression analysis revealed that neonatal infectious diseases (OR=2.368) and decreased platelet count within 24 hours after birth (OR=0.996) were independent risk factors for hs-PDA. Neonatal infectious diseases and decreased platelet count within 24 hours after birth increase the risk of hs-PDA in early preterm infants.