Hormones in infant rhesus monkeys' (Macaca mulatta) hair at birth provide a window into the fetal environment.

PubMed

Kapoor, Amita; Lubach, Gabriele; Hedman, Curtis; Ziegler, Toni E; Coe, Christopher L

2014-04-01

It is established that maternal parity can affect infant growth and risk for several disorders, but the prenatal endocrine milieu that contributes to these outcomes is still largely unknown. Recently, it has been shown that hormones deposited in hair can provide a retrospective reflection of hormone levels while the hair was growing. Taking advantage of this finding, our study utilized hair at birth to investigate if maternal parity affected fetal hormone exposure during late gestation. Hair was collected from primiparous and multiparous mother and infant monkeys at birth and used to determine steroid hormones embedded in hair while the infant was in utero. A high-pressure liquid chromatography-triple quadrupole mass spectrometry technique was refined, which enabled the simultaneous measurement of eight hormones. Hormone concentrations were dramatically higher in neonatal compared to maternal hair, reflecting extended fetal exposure as the first hair was growing. Further, hair cortisone was higher in primiparous mothers and infants when compared to the multiparous dyads. This research demonstrates that infant hair can be used to track fetal hormone exposure and a panel of steroid hormones can be quantified from hair specimens. Given the utility in nonhuman primates, this approach can be translated to a clinical setting with human infants.

Hormones in Infant Hair at Birth Provide a Window into the Fetal Environment

PubMed Central

Kapoor, Amita; Lubach, Gabriele; Hedman, Curtis; Ziegler, Toni E.; Coe, Christopher L.

2014-01-01

Background It is established that maternal parity can affect infant growth and risk for several disorders, but the prenatal endocrine milieu that contributes to these outcomes is still largely unknown. Recently, it has been shown that hormones deposited in hair can provide a retrospective reflection of hormone levels while the hair was growing. Taking advantage of this finding, our study utilized hair at birth to investigate if maternal parity affected fetal hormone exposure during late gestation. Methods Hair was collected from primiparous and multiparous mother and infant monkeys at birth and used to determine steroid hormones embedded in hair while the infant was in utero. An LC/MS/MS technique was refined, which enabled the simultaneous measurement of 8 hormones. Results Hormone concentrations were dramatically higher in neonatal compared to maternal hair, reflecting extended fetal exposure as the first hair was growing. Further, hair cortisone was higher in primiparous mothers and infants when compared to the multiparous dyads. Conclusion This research demonstrates that infant hair can be used to track fetal hormone exposure and a panel of steroid hormones can be quantified from hair specimens. Given the utility in nonhuman primates, this approach can be translated to a clinical setting with human infants. PMID:24418932

Electronic fetal heart rate monitoring and its relationship to neonatal and infant mortality in the United States.

PubMed

Chen, Han-Yang; Chauhan, Suneet P; Ananth, Cande V; Vintzileos, Anthony M; Abuhamad, Alfred Z

2011-06-01

To examine the association between electronic fetal heart rate monitoring and neonatal and infant mortality, as well as neonatal morbidity. We used the United States 2004 linked birth and infant death data. Multivariable log-binomial regression models were fitted to estimate risk ratio for association between electronic fetal heart rate monitoring and mortality, while adjusting for potential confounders. In 2004, 89% of singleton pregnancies had electronic fetal heart rate monitoring. Electronic fetal heart rate monitoring was associated with significantly lower infant mortality (adjusted relative risk, 0.75); this was mainly driven by the lower risk of early neonatal mortality (adjusted relative risk, 0.50). In low-risk pregnancies, electronic fetal heart rate monitoring was associated with decreased risk for Apgar scores <4 at 5 minutes (relative risk, 0.54); in high-risk pregnancies, with decreased risk of neonatal seizures (relative risk, 0.65). In the United States, the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity that lowered infant mortality. Copyright © 2011 Mosby, Inc. All rights reserved.

Prediction of fetal compromise in labor.

PubMed

Prior, Tomas; Mullins, Edward; Bennett, Phillip; Kumar, Sailesh

2014-06-01

The majority of intrapartum fetal hypoxia occurs in uncomplicated pregnancies. Current intrapartum monitoring techniques have not resulted in a reduction in the incidence of cerebral palsy in term neonates. We report the development of a composite risk score to allow risk stratification of normal pregnancies before labor. Six hundred one women were recruited to this prospective observational study. All women underwent an ultrasound examination before active labor, during which fetal biometry and fetal Doppler flow resistance indices were measured. A composite risk score, amalgamating data from the umbilical artery, middle cerebral artery, and umbilical vein, was then developed and correlated with intrapartum outcomes. In cases with the highest composite risk scores, the incidence of fetal compromise (the primary outcome) was 80.0% compared with just 15.3% in cases with the lowest risk scores (relative risk 5.2, 95% confidence interval 2.7-10.1). These cases were also at increased risk of cesarean delivery (53.3% compared with 3.4%, P<.001) and of developing a fetal heart rate pattern considered pathologic by National Institute for Health and Clinical Excellence criteria (P=.003). No significant variation in Apgar scores or umbilical artery pH was observed. Intrapartum fetal compromise remains a significant global health issue. The composite risk score reported here can identify fetuses at both high risk and low risk of a subsequent diagnosis of intrapartum fetal compromise. This may enable more judicious use of current intrapartum fetal monitoring techniques, which are hampered by low specificity. II.

High Tumor Volume to Fetal Weight Ratio Is Associated with Worse Fetal Outcomes and Increased Maternal Risk in Fetuses with Sacrococcygeal Teratoma.

PubMed

Gebb, Juliana S; Khalek, Nahla; Qamar, Huma; Johnson, Mark P; Oliver, Edward R; Coleman, Beverly G; Peranteau, William H; Hedrick, Holly L; Flake, Alan W; Adzick, N Scott; Moldenhauer, Julie S

2018-03-01

Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor outcome in fetuses with sacrococcygeal teratoma (SCT). We evaluated TFR in predicting poor fetal outcome and increased maternal operative risk in our cohort of SCT pregnancies. This is a retrospective, single-center review of fetuses seen with SCT from 1997 to 2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had initial evaluation at > 24 weeks were excluded. Receiver operating characteristic (ROC) analysis determined the optimal TFR to predict poor fetal outcome and increased maternal operative risk. Poor fetal outcome included fetal demise, neonatal demise, or fetal deterioration warranting open fetal surgery or delivery < 32 weeks. Increased maternal operative risk included cases necessitating open fetal surgery, classical cesarean delivery, or ex utero intrapartum treatment (EXIT). Of 139 pregnancies with SCT, 27 chose TOP, 14 delivered elsewhere, and 40 had initial evaluation at > 24 weeks. Thus, 58 fetuses were reviewed. ROC analysis revealed that at ≤24 weeks, TFR > 0.095 was predictive of poor fetal outcome and TFR > 0.12 was predictive of increased maternal operative risk. This study supports the use of TFR at ≤24 weeks for risk stratification of pregnancies with SCT. © 2018 S. Karger AG, Basel.

Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice.

PubMed

Watkins, Adam J; Sirovica, Slobodan; Stokes, Ben; Isaacs, Mark; Addison, Owen; Martin, Richard A

2017-06-01

Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development is largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal perception of fetal activity and late stillbirth risk: findings from the Auckland Stillbirth Study.

PubMed

Stacey, Tomasina; Thompson, John M D; Mitchell, Edwin A; Ekeroma, Alec; Zuccollo, Jane; McCowan, Lesley M E

2011-12-01

  Maternal perception of decreased fetal movements has been associated with adverse pregnancy outcomes, including stillbirth. Little is known about other aspects of perceived fetal activity. The objective of this study was to explore the relationship between maternal perception of fetal activity and late stillbirth (≥28 wk gestation) risk.   Participants were women with a singleton, late stillbirth without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two control women with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Detailed demographic and fetal movement data were collected by way of interview in the first few weeks after the stillbirth, or at the equivalent gestation for control women.   A total of 155/215 (72%) women who experienced a stillbirth and 310/429 (72%) control group women consented to participate in the study. Maternal perception of increased strength and frequency of fetal movements, fetal hiccups, and frequent vigorous fetal activity were all associated with a reduced risk of late stillbirth. In contrast, perception of decreased strength of fetal movement was associated with a more than twofold increased risk of late stillbirth (aOR: 2.37; 95% CI: 1.29-4.35). A single episode of vigorous fetal activity was associated with an almost sevenfold increase in late stillbirth risk (aOR: 6.81; 95% CI: 3.01-15.41) compared with no unusually vigorous activity.   Our study suggests that maternal perception of increasing fetal activity throughout the last 3 months of pregnancy is a sign of fetal well-being, whereas perception of reduced fetal movements is associated with increased risk of late stillbirth. © 2011, Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc.

Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure.

PubMed

Barrett, E S; Hoeger, K M; Sathyanarayana, S; Abbott, D H; Redmon, J B; Nguyen, R H N; Swan, S H

2018-06-01

Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls' AGD. In total, 300 mother-daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

The World Health Organization fetal growth charts: concept, findings, interpretation, and application.

PubMed

Kiserud, Torvid; Benachi, Alexandra; Hecher, Kurt; Perez, Rogelio González; Carvalho, José; Piaggio, Gilda; Platt, Lawrence D

2018-02-01

Ultrasound biometry is an important clinical tool for the identification, monitoring, and management of fetal growth restriction and development of macrosomia. This is even truer in populations in which perinatal morbidity and mortality rates are high, which is a reason that much effort is put onto making the technique available everywhere, including low-income societies. Until recently, however, commonly used reference ranges were based on single populations largely from industrialized countries. Thus, the World Health Organization prioritized the establishment of fetal growth charts for international use. New fetal growth charts for common fetal measurements and estimated fetal weight were based on a longitudinal study of 1387 low-risk pregnant women from 10 countries (Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) that provided 8203 sets of ultrasound measurements. The participants were characterized by median age 28 years, 58% nulliparous, normal body mass index, with no socioeconomic or nutritional constraints (median caloric intake, 1840 calories/day), and had the ability to attend the ultrasound sessions, thus essentially representing urban populations. Median gestational age at birth was 39 weeks, and birthweight was 3300 g, both with significant differences among countries. Quantile regression was used to establish the fetal growth charts, which also made it possible to demonstrate a number of features of fetal growth that previously were not well appreciated or unknown: (1) There was an asymmetric distribution of estimated fetal weight in the population. During early second trimester, the distribution was wider among fetuses <50th percentile compared with those above. The pattern was reversed in the third trimester, with a notably wider variation >50th percentile. (2) Although fetal sex, maternal factors (height, weight, age, and parity), and country had significant influence on fetal weight (1-4.5% each), their effect was graded across the percentiles. For example, the positive effect of maternal height on fetal weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the effects of treating dairy cows with meloxicam at calving on retained fetal membranes risk

PubMed Central

Newby, Nathalie C.; Renaud, David; Tremblay, Robert; Duffield, Todd F.

2014-01-01

Some non-steroidal anti-inflammatory drugs increase the risk of retained fetal membranes. This is the first study to investigate the effects of meloxicam on the risk of retained fetal membranes. Administration of meloxicam to dairy cattle immediately following calving revealed no differences in the incidence of retained fetal membranes between meloxicam-treated and untreated animals. There was no difference between the 2 groups in the incidence of periparturient diseases following calving. Meloxicam can be used on the day of calving in lactating cows without increasing the risk of retained fetal membranes. PMID:25477550

[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.

Fetal and neonatal outcomes of preterm infants born before 32 weeks of gestation according to antenatal vs postnatal assessments of restricted growth.

PubMed

Monier, Isabelle; Ancel, Pierre-Yves; Ego, Anne; Jarreau, Pierre-Henri; Lebeaux, Cécile; Kaminski, Monique; Goffinet, François; Zeitlin, Jennifer

2017-05-01

Fetal growth restriction is defined using ultrasound parameters during pregnancy or as a low birthweight for gestational age after birth, but these definitions are not always concordant. The purpose of this study was to investigate fetal and neonatal outcomes based on antenatal vs postnatal assessments of growth restriction. From the EPIPAGE 2 population-based prospective study of very preterm births in France in 2011, we included 2919 singleton nonanomalous infants 24-31 weeks gestational age. We constituted 4 groups based on whether the infant was suspected with fetal growth restriction during pregnancy and/or was small for gestational age with a birthweight <10th percentile of intrauterine norms by sex: 1) suspected with fetal growth restriction/small for gestational age 2) not suspected with fetal growth restriction/small for gestational age 3) suspected with fetal growth restriction/not small for gestational age and 4) not suspected with fetal growth restriction/not small for gestational age. We estimated relative risks of perinatal mortality and morbidity for these groups adjusting for maternal and neonatal characteristics. We found that 22.2% of infants were suspected with fetal growth restriction/small for gestational age, that 11.4% infants were not suspected with fetal growth restriction/small for gestational age, that 3.0% infants were suspected with fetal growth restriction/not small for gestational age, and that 63.4% infants were not suspected with fetal growth restriction/not small for gestational age. Compared with infants who were not suspected with fetal growth restriction/not small-for-gestational-age infants, small-for-gestational-age infants suspected and not suspected with fetal growth restriction had higher risks of stillbirth or termination of pregnancy (adjusted relative risk, 2.0 [95% confidence interval, 1.6-2.5] and adjusted relative risk, 2.8 [95% confidence interval, 2.2-3.4], respectively), in-hospital death (adjusted relative risk, 2.8 [95% confidence interval, 2.0-3.7] and adjusted relative risk, 2.0 [95% confidence interval, 1.5-2.8], respectively), and bronchopulmonary dysplasia (adjusted relative risk, 1.3 [95% confidence interval, 1.2-1.4] and adjusted relative risk, 1.3 [95% confidence interval, 1.1-1.4], respectively), but not severe brain lesions. Risks were not increased for infants suspected with fetal growth restriction but not small-for-gestational-age. Antenatal and postnatal assessments of fetal growth restriction were not concordant for 14% of very preterm infants. In these cases, birthweight appears to be the more relevant parameter for the identification of infants with higher risks of adverse short-term outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Reducing stillbirths: screening and monitoring during pregnancy and labour

PubMed Central

Haws, Rachel A; Yakoob, Mohammad Yawar; Soomro, Tanya; Menezes, Esme V; Darmstadt, Gary L; Bhutta, Zulfiqar A

2009-01-01

Background Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality. Methods The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome. Results We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress. Conclusion There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit. PMID:19426468

Perinatal and familial risk factors for acute lymphoblastic leukemia in a Swedish national cohort.

PubMed

Crump, Casey; Sundquist, Jan; Sieh, Weiva; Winkleby, Marilyn A; Sundquist, Kristina

2015-04-01

Perinatal factors including high birth weight have been found to be associated with acute lymphoblastic leukemia (ALL) in case-control studies. However, to the best of our knowledge, these findings have seldom been examined in large population-based cohort studies, and the specific contributions of gestational age and fetal growth remain unknown. The authors conducted a national cohort study of 3,569,333 individuals without Down syndrome who were born in Sweden between 1973 and 2008 and followed for the incidence of ALL through 2010 (maximum age, 38 years) to examine perinatal and familial risk factors. There were 1960 ALL cases with 69.7 million person-years of follow-up. After adjusting for potential confounders, risk factors for ALL included high fetal growth (incidence rate ratio [IRR] per additional 1 standard deviation, 1.07; 95% confidence interval [95% CI], 1.02-1.11 [P =.002]; and IRR for large vs appropriate for gestational age, 1.22; 95% CI, 1.06-1.40 [P =.005]), first-degree family history of ALL (IRR, 7.41; 95% CI, 4.60-11.95 [P<.001]), male sex (IRR, 1.20; 95% CI, 1.10-1.31 [P<.001]), and parental country of birth (IRR for both parents born in Sweden vs other countries, 1.13; 95% CI, 1.00-1.27 [P =.045]). These risk factors did not appear to vary by patient age at the time of diagnosis of ALL. Gestational age at birth, season of birth, birth order, multiple birth, parental age, and parental education level were not found to be associated with ALL. In this large cohort study, high fetal growth was found to be associated with an increased risk of ALL in childhood through young adulthood, independent of gestational age at birth, suggesting that growth factor pathways may play an important long-term role in the etiology of ALL. © 2014 American Cancer Society.

Maternal conditions and perinatal characteristics associated with autism spectrum disorder and intellectual disability.

PubMed

Langridge, Amanda T; Glasson, Emma J; Nassar, Natasha; Jacoby, Peter; Pennell, Craig; Hagan, Ronald; Bourke, Jenny; Leonard, Helen; Stanley, Fiona J

2013-01-01

As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities and overlap in diagnosis and aetiological pathways that may exist for both conditions. To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children. The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes. In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk. Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions.

Intrauterine fetal death and risk of shoulder dystocia at delivery.

PubMed

Larsen, Sandra; Dobbin, Joanna; McCallion, Oliver; Eskild, Anne

2016-12-01

Vaginal delivery is recommended after intrauterine fetal death. However, little is known about the risk of shoulder dystocia in these deliveries. We studied whether intrauterine fetal death increases the risk of shoulder dystocia at delivery. In this population-based register study using the Medical Birth Registry of Norway, we included all singleton pregnancies with vaginal delivery of offspring in cephalic presentation in Norway during the period 1967-2012 (n = 2 266 118). Risk of shoulder dystocia was estimated as absolute risk (%) and odds ratio with 95% confidence interval. Adjustment was made for offspring birthweight (in grams). We performed sub-analyses within categories of birthweight (<4000 and ≥4000 g) and in pregnancies with maternal diabetes. Shoulder dystocia occurred in 1.1% of pregnancies with intrauterine fetal death and in 0.8% of pregnancies without intrauterine fetal death (p < 0.0001) (crude odds ratio 1.5, 95% confidence interval 1.2-4.9). After adjustment for birthweight, the odds ratio was 5.9 (95% confidence interval 4.7-7.4). In pregnancies with birthweight ≥4000 g, shoulder dystocia occurred in 14.6% of pregnancies with intrauterine fetal death and in 2.8% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 5.9, 95% confidence interval 4.5-7.9). In pregnancies with birthweight ≥4000 g and concurrent maternal diabetes, shoulder dystocia occurred in 57.1% of pregnancies with intrauterine fetal death and 9.6% of pregnancies without intrauterine fetal death (p < 0.001) (crude odds ratio 12.6, 95% confidence interval 5.9-26.9). Intrauterine fetal death increased the risk of shoulder dystocia at delivery, and the absolute risk of shoulder dystocia was particularly high if offspring birthweight was high and the mother had diabetes. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Assessment of the concordance among 2-tier, 3-tier, and 5-tier fetal heart rate classification systems.

PubMed

Gyamfi Bannerman, Cynthia; Grobman, William A; Antoniewicz, Leah; Hutchinson, Maria; Blackwell, Sean

2011-09-01

In 2008, a National Institute of Child Health and Human Development/Society for Maternal-Fetal Medicine-sponsored workshop on electronic fetal monitoring recommended a new fetal heart tracing interpretation system. Comparison of this 3-tier system with other systems is lacking. Our purpose was to determine the relationships between fetal heart rate categories for the 3 existing systems. Three Maternal-Fetal Medicine specialists reviewed 120 fetal heart rates. All tracings were from term, singleton pregnancies with known umbilical artery pH. The fetal heart rates were classified by a 2-tier, 3-tier, and 5-tier system. Each Maternal-Fetal Medicine examiner reviewed 120 fetal heart rate segments. When compared with the 2-tier system, 0%, 54%, and 100% tracings in categories 1, 2, and 3 were "nonreassuring." There was strong concordance between category 1 and "green" as well as category 3 and "red" tracings. The 3-tier and 5-tier systems were similar in fetal heart rate interpretations for tracings that were either very normal or very abnormal. Whether one system is superior to the others in predicting fetal acidemia remains unknown. Copyright © 2011 Mosby, Inc. All rights reserved.

Sonographic large fetal head circumference and risk of cesarean delivery.

PubMed

Lipschuetz, Michal; Cohen, Sarah M; Israel, Ariel; Baron, Joel; Porat, Shay; Valsky, Dan V; Yagel, Oren; Amsalem, Hagai; Kabiri, Doron; Gilboa, Yinon; Sivan, Eyal; Unger, Ron; Schiff, Eyal; Hershkovitz, Reli; Yagel, Simcha

2018-03-01

Persistently high rates of cesarean deliveries are cause for concern for physicians, patients, and health systems. Prelabor assessment might be refined by identifying factors that help predict an individual patient's risk of cesarean delivery. Such factors may contribute to patient safety and satisfaction as well as health system planning and resource allocation. In an earlier study, neonatal head circumference was shown to be more strongly associated with delivery mode and other outcome measures than neonatal birthweight. In the present study we aimed to evaluate the association of sonographically measured fetal head circumference measured within 1 week of delivery with delivery mode. This was a multicenter electronic medical record-based study of birth outcomes of primiparous women with term (37-42 weeks) singleton fetuses presenting for ultrasound with fetal biometry within 1 week of delivery. Fetal head circumference and estimated fetal weight were correlated with maternal background, obstetric, and neonatal outcome parameters. Elective cesarean deliveries were excluded. Multinomial regression analysis provided adjusted odds ratios for instrumental delivery and unplanned cesarean delivery when the fetal head circumference was ≥35 cm or estimated fetal weight ≥3900 g, while controlling for possible confounders. In all, 11,500 cases were collected; 906 elective cesarean deliveries were excluded. A fetal head circumference ≥35 cm increased the risk for unplanned cesarean delivery: 174 fetuses with fetal head circumference ≥35 cm (32%) were delivered by cesarean, vs 1712 (17%) when fetal head circumference <35 cm (odds ratio, 2.49; 95% confidence interval, 2.04-3.03). A fetal head circumference ≥35 cm increased the risk of instrumental delivery (odds ratio, 1.48; 95% confidence interval, 1.16-1.88), while estimated fetal weight ≥3900 g tended to reduce it (nonsignificant). Multinomial regression analysis showed that fetal head circumference ≥35 cm increased the risk of unplanned cesarean delivery by an adjusted odds ratio of 1.75 (95% confidence interval, 1.4-2.18) controlling for gestational age, fetal gender, and epidural anesthesia. The rate of prolonged second stage of labor was significantly increased when either the fetal head circumference was ≥35 cm or the estimated fetal weight ≥3900 g, from 22.7% in the total cohort to 31.0%. A fetal head circumference ≥35 cm was associated with a higher rate of 5-minute Apgar score ≤7: 9 (1.7%) vs 63 (0.6%) of infants with fetal head circumference <35 cm (P = .01). The rate among fetuses with an estimated fetal weight ≥3900 g was not significantly increased. The rate of admission to the neonatal intensive care unit did not differ among the groups. Sonographic fetal head circumference ≥35 cm, measured within 1 week of delivery, is an independent risk factor for unplanned cesarean delivery but not instrumental delivery. Both fetal head circumference ≥35 cm and estimated fetal weight ≥3900 g significantly increased the risk of a prolonged second stage of labor. Fetal head circumference measurement in the last days before delivery may be an important adjunct to estimated fetal weight in labor management. Copyright © 2018 Elsevier Inc. All rights reserved.

ACR Appropriateness Criteria Assessment of Fetal Well-Being.

PubMed

Simpson, Lynn; Khati, Nadia J; Deshmukh, Sandeep P; Dudiak, Kika M; Harisinghani, Mukesh G; Henrichsen, Tara L; Meyer, Benjamin J; Nyberg, David A; Poder, Liina; Shipp, Thomas D; Zelop, Carolyn M; Glanc, Phyllis

2016-12-01

Although there is limited evidence that antepartum testing decreases the risk for fetal death in low-risk pregnancies, women with high-risk factors for stillbirth should undergo antenatal fetal surveillance. The strongest evidence supporting antepartum testing pertains to pregnancies complicated by intrauterine fetal growth restriction secondary to uteroplacental insufficiency. The main ultrasound-based modalities to determine fetal health are the biophysical profile, modified biophysical profile, and duplex Doppler velocimetry. In patients at risk for cardiovascular compromise, fetal echocardiography may also be indicated to ensure fetal well-being. Although no single antenatal test has been shown to be superior, all have high negative predictive values. Weekly or twice-weekly fetal testing has become the standard practice in high-risk pregnancies. The timing for the initiation of assessments of fetal well-being should be tailored on the basis of the risk for stillbirth and the likelihood of survival with intervention. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Plasma folate levels and risk of spontaneous abortion.

PubMed

George, Lena; Mills, James L; Johansson, Anna L V; Nordmark, Anna; Olander, Bodil; Granath, Fredrik; Cnattingius, Sven

2002-10-16

Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies. To study the association between plasma folate levels and the risk of spontaneous abortion. Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks. Risk of spontaneous abortion vs maternal plasma folate level. Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33). Low plasma folate levels were associated with an increased risk of early spontaneous abortion.

[RHD variant in RhD/-/ mother with anti-D makes noninvasive fetal RHD genotyping impossible].

PubMed

Orzińska, Agnieszka; Engel, Karina; Łakomy, Magdalena; Smolarczyk-Wodzyńska, Justyna; Lipińska, Anna; Pelc-Kłopotowska, Monika; Brojer, Ewa

2009-10-01

Noninvasive fetal RHD genotyping from maternal plasma of RhD(/-) pregnant women of Caucasian race may be used for predicting the risk of hemolytic disease because the RHD gene is usually absent in such populations. If detected in plasma of such women, the RHD gene originates from the RhD(+) fetus. The number of fetal copies of the gene in maternal plasma is extremely small. In the presented case of the RhD(/-) pregnant woman with anti-D it was impossible to give a fetal RHD result due to mother's RHD(+) genotype. The fetal RHD was determined from amniocytes. to present the difficulties related to the interpretation of results of invasive and noninvasive procedures. whole blood, plasma and amniotic fluid of the RhD(-) woman with anti-D (14 week of pregnancy) as well as whole blood of the newborn. RHD and RHCE*c were genotyped by real-time PCR in DNA isolated from maternal plasma and amniocytes and the RHD and d-genotypes were tested by SSP methods in DNA isolated from whole blood and amniocytes. RHD and RHCE*c were detected in DNA isolated from plasma. The high level of RHD suggested its origin from the mother's DNA therefore it was impossible to determine the fetal RHD. The d-little test identified a RHD(IVS3+ 1G>A) variant in the mother's genome. A weak signal of real-time PCR for the RHD was obtained in amniocytes but the RHD was not detected by SSP. The RHCE*c was detected by both methods. Results were inconclusive; the fetal RHD status remained unknown. The child was RhD(-) with RHD in its DNA undetected by either method. 1/The RHD(IVS3+ 1G>A) variant in the RhD(-) mother precluded formal noninvasive fetal RHD genotyping. 2/Real-time PCR is too sensitive for amniocyte testing and may lead to false results as it detects trace maternal DNA in amniotic fluid. 3/The frequency of RHD(IVS3+1G>A) occurrence in Poland requires further studies.

Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions

PubMed Central

Krakowiak, Paula; Walker, Cheryl K.; Tancredi, Daniel; Hertz-Picciotto, Irva; Van de Water, Judy

2016-01-01

Lay Abstract Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of antibodies to fetal brain tissue that have been detected in only 1% of mothers of typically developing children. However, it is unknown what causes these ASD-specific anti-fetal antibodies to be produced. We examined the relationship between ASD-specific anti-fetal antibodies and metabolic conditions during pregnancy in 227 mothers of 2–5 year old children with ASD, enrolled in the CHARGE (Childhood Autism Risk from Genetics and the Environment) Study, and who had blood samples measured for these anti-fetal brain antibodies after study enrollment. Metabolic conditions included diabetes, hypertensive disorders, and prepregnancy obesity or overweight. The presence of ASD-specific anti-fetal brain antibody patterns was more common among mothers diagnosed with diabetes, hypertensive disorders, or overweight during pregnancy compared to healthy mothers, but these differences did not reach statistical significance. In a subset of 145 mothers whose children exhibited severe ASD symptoms, those diagnosed with type 2 or gestational diabetes were nearly 3 times more likely to have ASD-specific anti-fetal antibodies compared to healthy mothers. Further, those diagnosed with gestational diabetes specifically were over 3 times more likely to have these anti-fetal brain antibodies. In this exploratory study, mothers whose children had severe ASD and who were diagnosed with diabetes were more likely to have anti-fetal brain autoantibodies 2–5 years later. Scientific Abstract Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD-specific maternal autoantibodies are poorly understood. We sought to determine whether ASD-specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation. Participants were 227 mothers of 2–5 year old children with confirmed ASD, enrolled in CHARGE (Childhood Autism Risk from Genetics and the Environment) between January 2003 and April 2008, and from whom blood samples were collected and analyzed for anti-fetal brain autoantibodies (Ab+). MCs included diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews. Log-linear regression models were performed to estimate prevalence ratios (PR) and 95% confidence intervals (CI) based on robust standard errors. Fifty-six (25%) mothers were Ab+. Ab+ prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant. In a subset of 145 mothers whose children exhibited severe ASD (31 Ab+), those diagnosed with type 2 or gestational diabetes were 2.7-fold more likely to be Ab+ (95% CI 1.1, 6.6), controlling for delivery payer and smoking. Gestational diabetes specifically was associated with a 3.2-fold increased Ab+ prevalence (95% CI 1.2, 8.6). In this exploratory study, mothers whose children had severe ASD and who experienced diabetes were more likely to have anti-fetal brain autoantibodies 2–5 years later. PMID:27312731

Care of HIV-Infected Pregnant Women in Maternal–Fetal Medicine Programs

PubMed Central

Bathgate, Susanne L.; Young, Heather A.; Parenti, David M.

2001-01-01

Objective: To survey the evolution over the past decade of attitudes and practices of obstetricians in maternal–fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV)-infected pregnant women. Methods: Directors of all 65 approved maternal–fetal medicine training programs were sent questionnaires, responses to which were to reflect the consensus among members of their faculties. Programs were stratified based upon the number of HIV-infected pregnant patients cared for in the previous year. Results: Responses reflect experience with over 1000 infected pregnantwomen per year, nearly one-quarter with advanced disease. Combination antiretroviral therapy was prescribed by all respondents, universally in the 2nd and 3rd trimesters. A three-drug regimen (often containing a protease inhibitor) was used more often by those who treated at least 20 HIV-infected pregnant patients per year than by those programs seeing a lower number of patients (80 vs 59%).Despite the known and unknown risks of the use of antiretrovirals during pregnancy, only half of all responding programs report adverse events to the Antiretroviral Pregnancy Registry; reporting was more common among the institutions seeing a higher number of patients (61 vs 45%). Seventy-eight percent of higher volume programs enroll their patients in clinical studies, usually multicenter, versus 35% of lower volume programs. Conclusions: Care for HIV² pregnant women has dramatically changed over the past decade. Antiretroviral therapy is now universally prescribed by physicians involved in maternal–fetal medicine training programs. Given limited experience with these agents in the setting of pregnancy, it is essential for maternal–fetal medicine practitioners to actively report on adverse events and participate in clinical trials. PMID:11495558

[Pregnancy in patients with renal transplantation: maternal and fetal morbidity].

PubMed

Romero Arauz, Juan Fernando; Ayala Méndez, José Antonio; Jiménez Solís, Guillermo

2008-11-01

Preeclampsia is a multisystemic syndrome with unknown etiology and characterized by abnormal vascular placentation response. Patients with renal transplantation restore them fertility 10 months after the intervention. To evaluate incidence of preeclampsia and maternal-perinatal outcome in patients with renal transplantation. Comparative, observational and retrospective study performed in pregnant patients with renal transplantation, from December 1999 to April 2008 at Perinatology of Hypertensive Diseases Department of the Unidad Medica de Alta Especialidad de Ginecoobstetricia Luis Castelazo Ayala, IMSS. Davison' guide, descriptive statistic, and Fischer exact test were used. Thirty patients were analyzed, 27 cases satisfy Davison's recommended guidelines, and the rest did not achieve these criteria (p = 0.001). Preeclampsia occurred in 15 cases (50%), preterm delivery in 15 (50%), and fetal growth restriction in 6 (20%). Among the 11 patients with previous chronic hypertension, 8 developed superimposed preeclampsia (72%), and 9 had delivery before 37 weeks of gestation (82%). Malfunction of renal transplantation, before pregnancy, was associated with maternal and perinatal poor outcome (p = 0.006). There were no maternal deaths, but one perinatal (3%) Successful pregnancy is possible in patients with renal transplantation, however there is a high risk of preeclampsia, infection, and fetal growth restriction. Patients with renal transplantation must fulfill Davison's pre-pregnancy guidelines.

Schizophrenia Risk Variation in the NRG1 gene Exerts Effects on NRG1-IV Splicing During Fetal and Early Postnatal Human Neocortical Development

PubMed Central

Paterson, Clare; Wang, Yanhong; Kleinman, Joel E.; Law, Amanda J.

2015-01-01

OBJECTIVE Neuregulin 1 (NRG1) is a multifunctional neurotrophin and a critical mediator of neurodevelopment and risk for schizophrenia. NRG1 undergoes extensive alternative splicing, and association of brain NRG1-IV isoform expression with the schizophrenia-risk polymorphism, rs6994992, is a potential molecular mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain. Because the developmental expression and genetic regulation of NRG1-IVNV in human brain and relationship to schizophrenia is unknown, the authors investigated the temporal dynamics of NRG1-IVNV transcription, compared to the major NRG1 isoforms (types I-IV), across human prenatal and postnatal prefrontal cortical development and examined the association of rs6994992 with NRG1-IVNV expression. METHOD NRG1, types I-IV and NRG1-IVNV isoform expression was evaluated using quantitative real-time PCR in prefrontal cortex during human fetal brain development (14-39 weeks gestation: N=41) and postnatally through aging (age range 0-83 years: N=195). The association of rs6994992 genotype with NRG1-IVNV expression was determined. In-vitro assays were performed to determine the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms. RESULTS Expression of NRG1, types I, II, III was temporally regulated during human prenatal and postnatal neocortical development and the trajectory of NRG1-IVNV was unique, being expressed from 16 weeks gestation until 3 years of age, after which it was undetectable. NRG1-IVNVs expression was associated with rs6994992 genotype, whereby homozygosity for the schizophrenia-risk allele (T) conferred lower cortical NRG1-IVNV levels. Finally, in-vitro cellular assays demonstrate that NRG1-IVNV is a novel nuclear enriched, truncated NRG1 protein that is resistant to proteolytic processing. CONCLUSION This study provides the first quantitative map of NRG1 isoform expression during human neocortical development and aging and identifies a potential mechanism of early developmental risk for schizophrenia at the NRG1 locus, involving a novel class of NRG1 proteins. PMID:24935406

Update on Fetal Monitoring: Overview of Approaches and Management of Category II Tracings.

PubMed

Raghuraman, Nandini; Cahill, Alison G

2017-12-01

Electronic fetal monitoring (EFM) is widely used to assess fetal status in labor. Use of intrapartum continuous EFM is associated with a lower risk of neonatal seizures but a higher risk of cesarean or operative delivery. Category II fetal heart tracings (FHTs) are indeterminate in their ability to predict fetal acidemia. Certain patterns of decelerations and variability within this category may be predictive of neonatal morbidity. Adjunct tests of fetal well-being can be used during labor to further triage patients. Intrauterine resuscitation techniques should target the suspected etiology of intrapartum fetal hypoxia. Clinical factors play a role in the interpretation of EFM. Copyright © 2017 Elsevier Inc. All rights reserved.

Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep

PubMed Central

Seedorf, Gregory J.; Brown, Alicia; Roe, Gates; O'Meara, Meghan C.; Gien, Jason; Tang, Jen-Ruey; Abman, Steven H.

2011-01-01

Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% (P < 0.005) in IUGR fetuses. Pulmonary vessel density was decreased 44% (P < 0.01) in IUGR fetuses. In vitro, insulin increased control PAEC migration, tube formation, and nitric oxide (NO) production. This response was absent in IUGR PAECs. VEGFA stimulated tube formation, and NO production also was absent. In control PAECs, insulin increased cell growth by 68% (P < 0.0001). Cell growth was reduced in IUGR PAECs by 29% at baseline (P < 0.01), and the response to insulin was attenuated (P < 0.005). Despite increased basal and insulin-stimulated Akt phosphorylation in IUGR PAECs, endothelial NO synthase (eNOS) protein expression as well as basal and insulin-stimulated eNOS phosphorylation were decreased in IUGR PAECs. Both VEGFA and VEGFR2 also were decreased in IUGR PAECs. We conclude that fetuses with IUGR are characterized by decreased alveolar and vascular growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR. PMID:21873446

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

PubMed

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Risk Factors for Brachial Plexus Birth Injury

PubMed Central

Louden, Emily; Marcotte, Michael; Mehlman, Charles; Lippert, William; Huang, Bin; Paulson, Andrea

2018-01-01

Over the course of decades, the incidence of brachial plexus birth injury (BPBI) has increased despite advances in healthcare which would seem to assist in decreasing the rate. The aim of this study is to identify previously unknown risk factors for BPBI and the risk factors with potential to guide preventative measures. A case control study of 52 mothers who had delivered a child with a BPBI injury and 132 mothers who had delivered without BPBI injury was conducted. Univariate, multivariable and logistic regressions identified risk factors and their combinations. The odds of BPBI were 2.5 times higher when oxytocin was used and 3.7 times higher when tachysystole occurred. The odds of BPBI injury are increased when tachysystole and oxytocin occur during the mother’s labor. Logistic regression identified a higher risk for BPBI when more than three of the following variables (>30 lbs gained during the pregnancy, stage 2 labor >61.5 min, mother’s age >26.4 years, tachysystole, or fetal malpresentation) were present in any combination. PMID:29596309

Risk of fetal death associated with maternal drug dependence and placental abruption: a population-based study.

PubMed

McDonald, Sarah D; Vermeulen, Marian J; Ray, Joel G

2007-07-01

Substance use in pregnancy is associated with placental abruption, but the risk of fetal death independent of abruption remains undetermined. Our objective was to examine the effect of maternal drug dependence on placental abruption and on fetal death in association with abruption and independent of it. To examine placental abruption and fetal death, we performed a retrospective population-based study of 1 854 463 consecutive deliveries of liveborn and stillborn infants occurring between January 1, 1995 and March 31, 2001, using the Canadian Institute for Health Information Discharge Abstract Database. Maternal drug dependence was associated with a tripling of the risk of placental abruption in singleton pregnancies (adjusted odds ratio [OR] 3.1; 95% confidence intervals [CI] 2.6-3.7), but not in multiple gestations (adjusted OR 0.88; 95% CI 0.12-6.4). Maternal drug dependence was associated with an increased risk of fetal death independent of abruption (adjusted OR 1.6: 95% CI 1.1-2.2) in singleton pregnancies, but not in multiples. Risk of fetal death was increased with placental abruption in both singleton and multiple gestations, even after controlling for drug dependence (adjusted OR 11.4 in singleton pregnancy; 95% CI 10.6-12.2, and 3.4 in multiple pregnancy; 95% CI 2.4-4.9). Maternal drug use is associated with an increased risk of intrauterine fetal death independent of placental abruption. In singleton pregnancies, maternal drug dependence is associated with an increased risk of placental abruption.

Obstetric risk indicators for labour dystocia in nulliparous women: A multi-centre cohort study

PubMed Central

Kjærgaard, Hanne; Olsen, Jørn; Ottesen, Bent; Nyberg, Per; Dykes, Anna-Karin

2008-01-01

Background In nulliparous women dystocia is the most common obstetric problem and its etiology is largely unknown. The frequency of augmentation and cesarean delivery related to dystocia is high although it is not clear if a slow progress justifies the interventions. Studies of risk factors for dystocia often do not provide diagnostic criteria for the diagnosis. The aim of the present study was to identify obstetric and clinical risk indicators of dystocia defined by strict and explicit criteria. Methods A multi-centre population based cohort study with prospectively collected data from 2810 nulliparous women in term spontaneous labour with a singleton infant in cephalic presentation. Data were collected by self-administered questionnaires and clinical data-records. Logistic regression analyses were used to estimate adjusted Odds Ratios (OR) and 95% confidence intervals (CI) are given. Results The following characteristics, present at admission to hospital, were associated with dystocia during labour (OR, 95% CI): dilatation of cervix < 4 cm (1.63, 1.38–1.92), tense cervix (1.31, 1.04–1.65), thick lower segment (1.32, 1.09–1.61), fetal head above the inter-spinal diameter (2.29, 1.80–2.92) and poor fetal head-to-cervix contact (1.83, 1.31–2.56). The use of epidural analgesia (5.65, 4.33–7.38) was also associated with dystocia. Conclusion Vaginal examinations at admission provide useful information on risk indicators for dystocia. The strongest risk indicator was use of epidural analgesia and if part of that is causal, it is of concern. PMID:18837972

Risk factors for fetal death after radiofrequency ablation for complicated monochorionic twin pregnancies.

PubMed

Sun, Luming; Zou, Gang; Yang, Yingjun; Zhou, Fenhe; Tao, Duan

2018-04-19

Radiofrequency ablation (RFA) is a management alternative for complicated monochorionic twin pregnancies. The purpose of this study is to evaluate risk factors for fetal death after RFA. An observational study was performed to document the perinatal outcomes of all cases undergoing fetal reduction using RFA from 2010 to 2016 at the Shanghai First Maternity and Infant Hospital. A multiple regression model was built to identify predictors of the death of the remaining fetus after RFA. A total of 183 patients treated with RFA for fetal reduction were analyzed, including 53 selective intrauterine growth restriction, 35 twin-twin transfusion syndrome, 36 dichorionic triamniotic triplets, 24 monochorionic twins discordant for fetal anomaly, and 35 twin reversed arterial perfusion. The prevalence of fetal death after RFA was 23% (43:183). The occurrence of fetal death after RFA was independently associated with more than 2 cycles of RFA coagulation (OR 3.46; 95% CI, 1.34-8.94; P = .01). More than 2 cycles of RFA coagulation is the only independent risk factors of fetal death after RFA. © 2018 John Wiley & Sons, Ltd.

Instrumenting a Fetal Membrane on a Chip as Emerging Technology for Preterm Birth Research.

PubMed

Gnecco, Juan S; Anders, Anjali P; Cliffel, David; Pensabene, Virginia; Rogers, Lisa M; Osteen, Kevin; Aronoff, David M

2017-01-01

Preterm birth (PTB) is clinically defined as process of giving birth before 37 weeks of gestation and is a leading cause of death among neonates and children under the age of five. Prematurity remains a critical issue in developed countries, yet our understanding of the pathophysiology of PTB remains largely unknown. Among pregnancy complications, subclinical infections such as chorioamnionitis (CAM) are implicated in up to 70% of PTB cases. Specifically, CAM is characterized by the infection of the fetal membranes that surround the developing fetus and extend from the placenta, and is often associated with preterm, premature rupture of the fetal membranes (PPROM). The fetal membrane plays a key structural role in maintaining the fetal and maternal compartments of the gravid uterus. However, our understanding of the mechanisms of PPROM and the spatio-temporal progress of CAM remains vastly unknown. A lack of human-derived models have hindered our understanding of the mechanism that govern spontaneous PTB. Thus, in this short review, we discuss the emerging microfabrication technologies, specifically, organ-on-chip (OoCs) models, that seek to recapitulate the cellular and molecular context of the gestational membranes in vitro. These models show promise to facilitate the investigation of pathologic mechanisms that drive these disease conditions by mimicking the interactive contribution of the major cell types that make up the microenvironment of the fetal membrane and enable high throughput screening. Herein, we histologically characterize the microenvironment of the fetal membrane as a metric for scaling to recapitulate the functional components of the human fetal membrane. We review the current OoC models of the gravid uterus and conceptualize an "Instrumented Fetal Membrane on a Chip" (IFMOC) design as a prototype for PPROM and CAM research. Lastly, we discuss further applications of these OoC models for toxicological or pharmacological screening and personalized medicine. Fetal membrane OoCs offer an innovative and valuable platform to explore complex interactions between multiple drug types, toxic substances, and/or pathogenic microbes and their potential impacts on pregnancy outcomes. Further work will be required by integrating technological and analytical capabilities in order to characterize the fetal membrane microenvironment for preterm birth research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Neonatal alloimmune thrombocytopenia with HLA alloimmunization: case report with immunohematologic and placental findings.

PubMed

De Tar, Michael W; Klohe, Ellen; Grosset, Alan; Rau, Thomas

2002-01-01

Severe neonatal thrombocytopenia is associated with a significant risk of neonatal bleeding complications. It may result from increased consumption, increased destruction, deficient production, or abnormal sequestration within the spleen. When immune mediated, most cases of clinically significant neonatal thrombocytopenia are due to maternal alloimmunization to paternally derived platelet antigens present on fetal platelets. We present the clinical, placental, and immunohematologic findings of a case of severe neonatal alloimmune thrombocytopenia (NAITP) complicated by additional HLA group alloimmunization. The placenta showed chronic villitis of unknown etiology (VUE) and diffuse microthrombi within the villous capillaries, indicating that abnormal thrombogenesis can be a complication of severe NAITP.

Placental mesenchymal dysplasia complicated by hydrops fetalis and fetal death: a case report.

PubMed

Akbarzadeh-Jahromi, Mojgan; Sari Aslani, Fatemeh; Parvari, Shams

2013-09-01

Placental mesenchymal dysplasia is a rare condition of the placenta and its true incidence and underlying cause has remained unknown till now due to its rarity. Its accurate diagnosis is essential, because placental mesenchymal dysplasia is usually compatible with a good fetal and maternal outcome. A precise ultrasonographic evaluation can contribute to the identification of characteristic features, particularly to discriminate it from partial hydatidiform mole, its main differential diagnosis. We report an early third-trimester pathologically- diagnosed case of placental mesenchymal dysplasia. It was complicated by fetal hydrops and death. 

Sonography in Fetal Birth Weight Estimation

ERIC Educational Resources Information Center

Akinola, R. A.; Akinola, O. I.; Oyekan, O. O.

2009-01-01

The estimation of fetal birth weight is an important factor in the management of high risk pregnancies. The information and knowledge gained through this study, comparing a combination of various fetal parameters using computer assisted analysis, will help the obstetrician to screen the high risk pregnancies, monitor the growth and development,…

Socioeconomic Status Accounts for Rapidly Increasing Geographic Variation in the Incidence of Poor Fetal Growth

PubMed Central

Ball, Stephen J.; Jacoby, Peter; Zubrick, Stephen R.

2013-01-01

Fetal growth is an important risk factor for infant morbidity and mortality. In turn, socioeconomic status is a key predictor of fetal growth; however, other sociodemographic factors and environmental effects may also be important. This study modelled geographic variation in poor fetal growth after accounting for socioeconomic status, with a fixed effect for socioeconomic status and a combination of spatially-correlated and spatially-uncorrelated random effects. The dataset comprised 88,246 liveborn singletons, aggregated within suburbs in Perth, Western Australia. Low socioeconomic status was strongly associated with an increased risk of poor fetal growth. An increase in geographic variation of poor fetal growth from 1999–2001 (interquartile odds ratio among suburbs = 1.20) to 2004–2006 (interquartile odds ratio = 1.40) indicated a widening risk disparity by socioeconomic status. Low levels of residual spatial patterns strengthen the case for targeting policies and practices in areas of low socioeconomic status for improved outcomes. This study indicates an alarming increase in geographic inequalities in poor fetal growth in Perth which warrants further research into the specific aspects of socioeconomic status that act as risk factors. PMID:23799513

Perceptions and use of electronic cigarettes in pregnancy

PubMed Central

McCubbin, Andrea; Fallin-Bennett, Amanda; Barnett, Janine; Ashford, Kristin

2017-01-01

Abstract Use of electronic cigarettes (e-cigs) is quickly growing in the United States, despite the unknown health implications and unregulated device contents. Although research is emerging around e-cigs in general, there continues to be a lack of scientific evidence regarding the safety and risks of e-cig use on maternal and fetal health, even though adverse health effects of nicotine on maternal and fetal outcomes are documented. This review summarizes existing perceptions of e-cig use in pregnancy, based on the limited number of publications available, and highlights the necessity of conducting additional research in this field of public health. Authors conducted a literature search of scientific peer-reviewed articles published from January 2006 to October 2016, comprising more than a decade of research. Search keywords include ‘tobacco use’, ‘electronic cigarette(s)’ and ‘pregnancy’. Fifty-seven publications were identified, narrowed to fifteen by screening title/abstract for potential relevance, with seven articles chosen for final inclusion. Of these seven studies, most participants not only believed e-cigs pose risks to maternal and child health but also perceived e-cigs as a safer and potentially healthier alternative to traditional cigarettes, and may assist with smoking cessation. Further research is needed to determine health implications and provide clinical guidelines for e-cig use in pregnancy. PMID:28158490

[Fetal echocardiography efficiency. Clinical experience].

PubMed

San Luis Miranda, Raúl; Arias Monroy, Laura Guadalupe; Gutiérrez González, Gladis Alicia; León Avila, José Luis; Cruz Rodríguez, Armando; Osornio Correa, Porfirio Rafael

2008-12-01

Congenital heart disease diagnostic has a high diagnostic precision with fetal echocardiography. This study has been reported in populations with high risk and with a sensibility of 86 to 99% and specificity of 91 to 100%. To know sensibility and specificity of fetal echocardiography in high-risk pregnancies, and to describe types and frequency of congenital heart disease in utero. 229 files of pregnant women with high-risk factors, more than 15 weeks of gestation, and at birth cardiovascular exam were analyzed. This analysis was made by means of simple frequencies, sensibility, specificity, positive and negative predictive value, and truth index calculation. We found 62 (27%) cases with fetal heart disease. Mean of maternal age was 27 +/- 5.5 years, and of gestational age 31 +/- 5 weeks. Risk factors that require study were: four-chamber abnormality in routine ultrasound, dysmorphy, fetal bradicardia, and poll and oligohydramnios. There were 55 (88.7%) high-risk heart diseases, and most frequent were Ebstein's anomaly, unique ventricle, hypoplastic left ventricle syndrome, and tumors. Sensibility was 98.41%, specificity was 97.59%, positive prognostic value was 97.59%, and negative prognostic value was 99.39%. Fetal echocardiography has a high diagnosis certainty in our hospital unit, thus, it has to be a normal prenatal exam in pregnant women with high-risk factors.

Cross-hemispheric functional connectivity in the human fetal brain.

PubMed

Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

2013-02-20

Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Maternal Conditions and Perinatal Characteristics Associated with Autism Spectrum Disorder and Intellectual Disability

PubMed Central

Langridge, Amanda T.; Glasson, Emma J.; Nassar, Natasha; Jacoby, Peter; Pennell, Craig; Hagan, Ronald; Bourke, Jenny; Leonard, Helen; Stanley, Fiona J.

2013-01-01

Background As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities and overlap in diagnosis and aetiological pathways that may exist for both conditions. Aims To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children. Methods The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes. Results In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk. Conclusion Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions. PMID:23308096

Socio-demographic characteristics and risk factors of ante-partum fetal death in a tertiary care hospital in Dhaka City.

PubMed

Azim, A K; Sultana, N; Chowdhury, S; Azim, E

2013-10-01

The objectives of this study were to assess the socio-demographic profile and to identify the risk factors of ante-partum fetal death which occurs after the age of viability of fetus. This prospective observational study was conducted in the Obstetrics and Gynaecology department of Ad-din Women Medical College Hospital from June 2009 to July 2010. A total of 14,015 pregnant patients were admitted in the study place after the age of viability, which was taken as 28 weeks of gestation for our facilities. Eighty-three (0.59%) of them were identified as intrauterine fetal death. Assessment of maternal socio-demographic characteristics and maternal-fetal risk factors were evaluated with a semi structured questionnaire which was pre-tested before executing in this study. Majority (81.92%, n=68) of the patients were below 30 years of age, 78.31% belonged to middle socioeconomic group. Almost 58% women had education below secondary school certificate (SSC) level and 28.91% took regular antenatal checkup. About 61.45% patients were multi-gravida. Most (59.04%) ante-partum deaths were identified below 32 weeks of pregnancy. Out of 83 patients, maternal risk factors were identified in 41(49.59%) cases where fetal risk factors were found in 16(19.27%) cases; no risk factors could be determined in rests. Hypertension (48.78%), diabetes (21.95%), hyperpyrexia (17.3%), abruptio placentae (4.88%) and UTI (7.36%) were identified as maternal factors; and congenital anomaly (37.5%), Rh incompatibility (37.5%), multiple pregnancy (12.5%) and post-maturity (12.5%) were the fetal risk factors. Here, proximal biological risk factors are most important in ante-partum fetal deaths. More investigations and facilities are needed to explain the causes of ante-partum deaths.

Maternal sociodemographic characteristics and risk factors of antepartum fetal death.

PubMed

Azim, M A; Sultana, N; Chowdhury, S; Azim, E

2012-04-01

The objectives of this study were to assess the sociodemographic profile and to identify the risk factors of ante-partum fetal death which occurs after the age of viability of fetus. This prospective observational study was conducted in the Obstetrics department of Ad-din Women Medical College Hospital during the period of June, 2009 to July, 2010. A total of 14,015 pregnant patients were admitted in the study place after the age of viability, which was taken as 28 weeks of gestation for our facilities. Eighty-three (0.59%) of them were identified as intrauterine fetal death. Assessment of maternal sociodemographic characteristics and maternal-fetal risk factors were evaluated with a semi structured questionnaire pretested. Majority (81.92%, n=68) of the patients were below 30 years of age, 78.31% belonged to middle socioeconomic group. Almost 58% women had education below SSC level and 28.91% took regular antenatal checkup. About 61.45% patients were multigravida. Most (59.04%) ante-partum deaths were identified below 32 weeks of pregnancy. Out of 83 patients, maternal risk factors were identified in 41(49.59%) cases where fetal risk factors were found in 16(19.27%) cases; no risk factors could be determined in rests. Hypertension (48.78%), diabetes (21.95%), hyperpyrexia (17.3%), abruptio placentae (4.88%) and UTI (7.36%) were identified as maternal factors; and congenital anomaly (37.5%), Rh incompatibility (37.5%), multiple pregnancy (12.5%) and post-maturity (12.5%) were the fetal risk factors. Here, proximal biological risk factors are most important in ante-partum fetal deaths. More investigations and facilities are needed to explain the causes of antepartum deaths.

The outcomes and risk factors of fetal bradycardia associated with external cephalic version.

PubMed

Suyama, Fumio; Ogawa, Kohei; Tazaki, Yukiko; Miwa, Terumi; Taniguchi, Kosuke; Nakamura, Noriyuki; Tanaka, Satomi; Tanigaki, Shinji; Sago, Haruhiko

2017-11-02

The objective of this study is to assess the outcomes and risk factors of fetal bradycardia after external cephalic version (ECV). We performed a retrospective study of women who underwent ECV after 35 weeks of gestation in 2010-2016. We assessed the birth outcomes, including umbilical cord artery pH, according to the duration of fetal bradycardia and the risk factors for bradycardia. Among 390 cases, 189 (48.5%) cases showed fetal bradycardia during or immediately after ECV. The duration of fetal bradycardia was <1 min (n = 82, 43.4%), <5 min (n = 168, 88.9%); and <10 min (n = 186, 98.4%). All cases showed a good prognosis. Fetal bradycardia lasting >10 min occurred in three cases; emergency cesarean section was performed in each case, with delivery after 12-4 min of bradycardia. Two of three cases showed low Apgar scores at 5 min, with an umbilical cord arterial pH of <7.1. Lower maternal BMI and a prolonged ECV procedure were significantly associated with bradycardia (p for trend: .016 and .015, respectively). Fetal bradycardia lasting >10 min after ECV was a risk factor for asphyxia. Thus, delivery should be completed within 10 min after bradycardia. A low maternal BMI and a prolonged ECV procedure were risk factors for bradycardia after ECV.

Obesity and Gestational Diabetes Mellitus Pathways for Programming in Mouse, Monkey, and Man—Where Do We Go Next? The 2014 Norbert Freinkel Award Lecture

PubMed Central

2015-01-01

Obesity and gestational diabetes mellitus continue to increase worldwide and span the spectrum of age, race, ethnicity, and socioeconomic status. Alarmingly, 1 in 10 infants and toddlers is obese, and 1 in 5 youths is both obese and at risk for metabolic syndrome prior to puberty. The mechanisms underlying how poor maternal health imparts risk for future metabolic disease in the offspring are beginning to emerge in deeply phenotyped human and nonhuman primate models. Maternal diet and obesity impact fuels, hormones, and inflammation with powerful effects on fetal metabolic systems. These are accompanied by persistent changes in the infant microbiome and epigenome and in offspring behavior. These results suggest that gestational and lactational dietary exposures are driving health risks in the next generation. Whether maternal diet can prevent changes in the womb to alter infant life-course disease risk is still unknown. Controlled, mechanistic studies to identify interventions are sorely needed for a healthier next generation. PMID:26207051

Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review.

PubMed

Raval, Donna B; Merideth, Melissa; Sloan, Jennifer L; Braverman, Nancy E; Conway, Robert L; Manoli, Irini; Venditti, Charles P

2015-09-01

Women with inherited metabolic disorders, including those with previously life-limiting conditions such as MMA, are reaching child-bearing age more often due to advances in early diagnosis and improved pediatric care. Information surrounding maternal and fetal complications associated with the underlying disorders remains largely unexplored. Pregnancies affected by maternal MMA were ascertained through study 04-HG-0127 "Clinical and Basic Investigations of Methylmalonic Acidemia and Related Disorders" (clinicaltrials.gov identifier: NCT00078078) and via literature review. Prenatal and delivery records in study participants were reviewed. Seventeen pregnancies were identified in women with isolated MMA, including three abortions, one termination, and 13 completed pregnancies [three cases with cblA (four pregnancies), four cases of mut- (one cobalamin responsive, three non-responsive), five cases with unknown type of MMA]. Seventeen percent (3/17) of the pregnancies resulted in a first trimester abortion, while 38.5% (5/13) of the completed pregnancies resulted in preterm deliveries. A cesarean delivery rate of 53.8% (7/13) was noted among the cohort. Fetal distress or nonreassuring fetal status was the indication for 57% (4/7) cesarean deliveries. One patient was reported to have metabolic crisis as well as episodes of mild hyperammonemia. Malformations or adverse outcomes in the progeny were not observed. Although there have been a small number of pregnancies identified in women with MMA, the cumulative results suggest that the majority of pregnancies can be complicated by cesarean delivery and increased risk of prematurity. A pregnancy registry could clarify perinatal complications and define management approaches needed to ensure optimal maternal and fetal outcomes in this growing patient population.

Adverse fetal outcome in road accidents: Injury mechanism study and injury criteria development in a pregnant woman finite element model.

PubMed

Auriault, F; Thollon, L; Pérès, J; Behr, M

2016-12-01

This study documents the development of adverse fetal outcome predictors dedicated to the analysis of road accidents involving pregnant women. To do so, a pre-existing whole body finite element model representative of a 50th percentile 26 weeks pregnant woman was used. A total of 8 accident scenarios were simulated with the model positioned on a sled. Each of these scenarios was associated to a risk of adverse fetal outcome based on results from real car crash investigations involving pregnant women from the literature. The use of airbags and accidents involving unbelted occupants were not considered in this study. Several adverse fetal outcome potential predictors were then evaluated with regard to their correlation to this risk of fetal injuries. Three predictors appeared strongly correlated to the risk of adverse fetal outcome: (1) the intra uterine pressure at the placenta fetal side area (r=0.92), (2) the fetal head acceleration (HIC) (r=0.99) and (3) area of utero-placental interface over a strain threshold (r=0.90). Finally, sensitivity analysis against slight variations of the simulation parameters was performed and assess robustness of these criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immune Thrombocytopenia in Pregnancy

PubMed Central

Stavrou, Evi; McCrae, Keith R.

2009-01-01

SYNOPSIS Management of ITP in pregnancy can be a complex and challenging task, and may be complicated by fetal/neonatal thrombocytopenia. Though fetal intracranial hemorrhage is a rare complication of ITP in pregnancy, invasive studies designed to determine the fetal platelet count before delivery are associated with greater risk than that of fetal intracranial hemorrhage, and therefore are discouraged. Moreover, the risk of neonatal bleeding complications does not correlate with the mode of delivery, and thus cesarean section should be reserved for obstetric indications only. PMID:19932435

Birthweight and thinness at birth independently predict symptoms of polycystic ovary syndrome in adulthood.

PubMed

Davies, M J; March, W A; Willson, K J; Giles, L C; Moore, V M

2012-05-01

The aetiology of polycystic ovary syndrome (PCOS) is unknown and contested. While it has been suggested that PCOS could have origins in perturbed development, epidemiological findings have been inconclusive. We aimed to examine potential fetal origins of PCOS. A retrospective birth cohort of 948 singleton female babies born at one hospital in South Australia in 1973-1975 was assembled. Birth characteristics were obtained from hospital records and PCOS symptoms were identified through interview and clinical examination when women were ~30 years old. Based on the combination of PCOS symptoms, women formed seven outcome groups. A multinomial logistic regression analysis was used to investigate associations between birth characteristics and these outcome groups. After adjusting for gestational age, two distinct birth characteristics were associated with two PCOS symptom groups. Each 100 g increase in birthweight increased the risk of hyperandrogenism (as a single symptom) in adulthood by 5% [relative risk ratio: 1.05, 95% confidence interval (CI): 1.01-1.09]. In contrast, each one unit increase in the ponderal index at birth decreased the risk of all three key PCOS symptoms (hyperandrogenism, menstrual dysfunction and polycystic ovaries) by 21% (0.79, 95% CI: 0.66-0.93). These results suggest two discrete fetal programming pathways (related to high birthweight and to thinness at birth) are operating. Our findings point to differing aetiologies for symptom clusters, and inform the debate over symptoms that best represent the disorder.

Genetic and Environmental Influences on Fetal Growth Vary during Sensitive Periods in Pregnancy.

PubMed

Workalemahu, Tsegaselassie; Grantz, Katherine L; Grewal, Jagteshwar; Zhang, Cuilin; Louis, Germaine M Buck; Tekola-Ayele, Fasil

2018-05-08

Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34-1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.

Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

PubMed Central

Solano, María Emilia; Kowal, Mirka Katharina; O’Rourke, Greta Eugenia; Horst, Andrea Kristina; Modest, Kathrin; Plösch, Torsten; Barikbin, Roja; Remus, Chressen Catharina; Berger, Robert G.; Jago, Caitlin; Ho, Hoang; Sass, Gabriele; Parker, Victoria J.; Lydon, John P.; DeMayo, Francesco J.; Hecher, Kurt; Karimi, Khalil; Arck, Petra Clara

2015-01-01

Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor– or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. PMID:25774501

Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

PubMed

Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-02-01

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of stillbirth, including fetal growth restriction. The development of "omic" technologies presents a huge opportunity to identify novel biomarkers for fetal growth restriction. The hope is that when such markers are measured alongside ultrasonic fetal biometry, the combination would have strong predictive power for fetal growth restriction and its related complications. However, a series of important methodological considerations in assessing the diagnostic effectiveness of new tests will have to be addressed. The challenge thereafter will be to identify novel disease-modifying interventions, which are the essential partner to an effective screening test to achieve clinically effective population-based screening. Copyright © 2017 Elsevier Inc. All rights reserved.

Gender- and parity-specific reference charts for fetal size in low risk singleton pregnancies at the onset of the third trimester.

PubMed

De Reu, Paul; Smits, Luc J; Oosterbaan, Herman P; Snijders, Rosalinde J; De Reu-Cuppens, Marga J; Nijhuis, Jan G

2007-01-01

To determine fetal growth in low risk pregnancies at the beginning of the third trimester and to assess the relative importance of fetal gender and maternal parity. Dutch primary care midwifery practice. Retrospective cohort study on 3641 singleton pregnancies seen at a primary care midwifery center in the Netherlands. Parameters used for analysis were fetal abdominal circumference (AC), fetal head circumference (HC), gestational age, fetal gender and maternal parity. Regression analysis was applied to describe variation in AC and HC with gestational age. Means and standard deviations in the present population were compared with commonly used reference charts. Multiple regression analysis was applied to examine whether gender and parity should be taken into account. The fetal AC and HC increased significantly between the 27th and the 33rd week of pregnancy (AC r2=0.3652, P<0.0001; HC r2=0.3301, P<0.0001). Compared to some curves, our means and standard deviations were significantly smaller (at 30+0 weeks AC mean=258+/-13 mm; HC mean=281+/-14 mm), but corresponded well with other curves. Fetal gender was a significant determinant for both AC (P<0.0001) and HC (P<0.0001). Parity contributed significantly to AC only but the difference was small (beta=0.00464). At the beginning of the third trimester, fetal size is associated with fetal gender and, to a lesser extent, with parity. Some fetal growth charts (e.g., Chitty et al.) are more suitable for the low-risk population in the Netherlands than others.

The effects of malaria and intermittent preventive treatment during pregnancy on fetal anemia in Malawi.

PubMed

Rogawski, Elizabeth T; Chaluluka, Ebbie; Molyneux, Malcolm E; Feng, Gaoqian; Rogerson, Stephen J; Meshnick, Steven R

2012-10-01

Fetal anemia is common in malarious areas and is a risk factor for infant morbidity and mortality. Malaria during pregnancy may cause decreased cord hemoglobin (Hb) and fetal anemia among newborns. Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is protective against malaria but may also affect hematopoiesis and contribute to fetal anemia. Peripheral, placental, and cord blood were examined for malaria parasitemia and Hb concentration in a cross-section of 3848 mothers and infants delivered at Queen Elizabeth Central Hospital in Blantyre, Malawi between 1997 and 2006. Unconditional linear and logistic regressions were performed with multiple imputation for missing covariates to assess the associations between malaria, IPTp with SP, and fetal anemia. The overall prevalence of fetal anemia was 7.9% (n = 304). Malaria parasitemia at delivery was associated with an adjusted decrease in cord Hb of -0.24 g/dL (95% confidence interval [CI], -.42 to -.05). The adjusted prevalence odds ratio for the effect of malaria on fetal anemia was 1.41 (95% CI, 1.05-1.90). Primigravidae who did not take IPTp had infants at highest risk for fetal anemia, and density of parasitemia was correlated with the decrease in cord Hb. There was no significant association between SP use and cord Hb or fetal anemia. Malaria during pregnancy, but not IPTp, decreases cord Hb and is a risk factor for fetal anemia in Malawi. Intermittent preventive treatment during pregnancy with SP may continue to be safe and effective in preventing malaria during pregnancy and fetal anemia despite development of SP resistance.

Premarital and Postmarital Conception and the Risk of Fetal and Infant Death. PHSB Studies, No. 10.

ERIC Educational Resources Information Center

North Carolina State Dept. of Human Resources, Raleigh. Div. of Health Services.

This report indicates relationships between the marital status of pregnant North Carolina women and mothers and the risk of fetal and infant death in the year 1974. No significant difference in the fetal mortality of the two legitimate groups (postmarital and premarital or pregnant brides) was found, although the illegitimate group had by far the…

Should apparently uncomplicated monochorionic twins be delivered electively at 32 weeks?

PubMed

Domingues, Ana Patrícia; Fonseca, Etelvina; Vasco, Elsa; Moura, Paulo

2009-11-01

We aimed to estimate the optimal time of delivery and investigated the residual risk of fetal death after viability in otherwise uncomplicated monochorionic diamniotic twin pregnancies. A database of 576 completed multiple pregnancies that were managed in our tertiary referral fetal medicine department between 1996 and 2007 was reviewed and the uncomplicated 111 monochorionic and the 290 dichorionic diamniotic twin pregnancies delivered after 24 weeks were selected. The rate of fetal death was derived for two-week periods starting at 24 weeks' gestation and the prospective risk of fetal death was calculated by determining the number of intrauterine fetal deaths that occurred within the two-week block divided by the number of continuing uncomplicated monochorionic twin pregnancies during that same time period. The unexpected single intrauterine deaths rate was 2.7% versus 2.8% in previously uncomplicated monochorionic and dichorionic diamniotic pregnancies, respectively. The prospective risk of unexpected stillbirth after 32 weeks of gestation was 1.3% for monochorionic and 0.8% for dichorionic pregnancies. In otherwise apparently uncomplicated monochorionic diamniotic pregnancies this prospective risk of fetal death after 32 weeks of gestation is lower than reported and similar to that of dichorionic pregnancies, so does not sustain the theory of elective preterm delivery.

Prepregnancy and early adulthood body mass index and adult weight change in relation to fetal loss.

PubMed

Gaskins, Audrey J; Rich-Edwards, Janet W; Colaci, Daniela S; Afeiche, Myriam C; Toth, Thomas L; Gillman, Matthew W; Missmer, Stacey A; Chavarro, Jorge E

2014-10-01

To examine prospectively the relationships of prepregnancy body mass index (BMI), BMI at age 18 years, and weight change since age 18 years with risk of fetal loss. Our prospective cohort study included 25,719 pregnancies reported by 17,027 women in the Nurses' Health Study II between 1990 and 2009. In 1989, height, current weight, and weight at age 18 years were self-reported. Current weight was updated every 2 years thereafter. Pregnancies were self-reported, with case pregnancies lost spontaneously and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. Incident fetal loss was reported in 4,494 (17.5%) pregnancies. Compared with those of normal BMI, the multivariate relative risks of fetal loss were 1.07 (95% CI [confidence interval] 1.00-1.15) for overweight women, 1.10 (95% CI 0.98-1.23) for class I obese women, and 1.27 (95% CI 1.11-1.45) for class II and class III obese women (P trend ≤ .001). Body mass index at age 18 years was not associated with fetal loss (P trend=.59). Compared with women who maintained a stable weight (± 4 kg) between age 18 years and before pregnancy, women who lost weight had a 20% (95% CI 9-29%) lower risk of fetal loss. This association was stronger among women who were overweight at age 18 years. Being overweight or obese before pregnancy was associated with higher risk of fetal loss. In women overweight or obese at age 18 years, losing 4 kg or more was associated with a lower risk of fetal loss. : II.

The "Fetal Reserve Index": Re-Engineering the Interpretation and Responses to Fetal Heart Rate Patterns.

PubMed

Eden, Robert D; Evans, Mark I; Evans, Shara M; Schifrin, Barry S

2018-01-01

Electronic fetal monitoring (EFM) correlates poorly with neonatal outcome. We present a new metric: the "Fetal Reserve Index" (FRI), formally incorporating EFM with maternal, obstetrical, fetal risk factors, and excessive uterine activity for assessment of risk for cerebral palsy (CP). We performed a retrospective, case-control series of 50 term CP cases with apparent intrapartum neurological injury and 200 controls. All were deemed neurologically normal on admission. We compared the FRI against ACOG Category (I-III) system and long-term outcome parameters against ACOG monograph (NEACP) requirements for labor-induced fetal neurological injury. Abnormal FRI's identified 100% of CP cases and did so hours before injury. ACOG Category III identified only 44% and much later. Retrospective ACOG monograph criteria were found in at most 30% of intrapartum-acquired CP patients; only 27% had umbilical or neonatal pH <7.0. In this initial, retrospective trial, an abnormal FRI identified all cases of labor-related neurological injury more reliably and earlier than Category III, which may allow fetal therapy by intrauterine resuscitation. The combination of traditional EFM with maternal, obstetrical, and fetal risk factors creating the FRI performed much better as a screening test than EFM alone. Our quantified screening system needs further evaluation in prospective trials. © 2017 S. Karger AG, Basel.

Fetal sex-based differences in maternal hormones, angiogenic factors, and immune mediators during pregnancy and the postpartum period.

PubMed

Enninga, Elizabeth Ann L; Nevala, Wendy K; Creedon, Douglas J; Markovic, Svetomir N; Holtan, Shernan G

2015-03-01

Several pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences. Using maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum. Male fetal sex was associated with higher levels of proinflammatory cytokines (G-CSF, IL-12p70, IL-21, and IL-33) and angiogenic factors (PlGF and VEGF-A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL-5, IL-9, IL-17, and IL-25). IL-27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex-based difference in analyte concentrations at the postpartum measurement. Women carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus. © 2014 The Authors. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.

Fetal Sex-Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period

PubMed Central

Enninga, Elizabeth Ann L; Nevala, Wendy K; Creedon, Douglas J; Markovic, Svetomir N; Holtan, Shernan G

2015-01-01

Problem Several pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences. Method of study Using maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum. Results Male fetal sex was associated with higher levels of proinflammatory cytokines (G-CSF, IL-12p70, IL-21, and IL-33) and angiogenic factors (PlGF and VEGF-A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL-5, IL-9, IL-17, and IL-25). IL-27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex-based difference in analyte concentrations at the postpartum measurement. Conclusion Women carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus. PMID:25091957

Fetal Research

NASA Astrophysics Data System (ADS)

Hansen, John T.; Sladek, John R.

1989-11-01

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

Fetal Substance Exposure and Cumulative Environmental Risk in an African American Cohort

ERIC Educational Resources Information Center

Yumoto, Chie; Jacobson, Sandra W.; Jacobson, Joseph L.

2008-01-01

Two models of vulnerability to socioenvironmental risk were examined in 337 African American children (M = 7.8 years) recruited to overrepresent prenatal alcohol or cocaine exposure: The cumulative risk model predicted synergistic effects from exposure to multiple risk factors, and the fetal patterning of disease model predicted that prenatal…

In Utero Alcohol Exposure and the Alteration of Histone Marks in the Developing Fetus: An Epigenetic Phenomenon of Maternal Drinking

PubMed Central

Mandal, Chanchal; Halder, Debasish; Jung, Kyoung Hwa; Chai, Young Gyu

2017-01-01

Ethanol is well known for its teratogenic effects during fetal development. Maternal alcohol consumption allows the developing fetus to experience the detrimental effects of alcohol exposure. Alcohol-mediated teratogenic effects can vary based on the dosage and the length of exposure. The specific mechanism of action behind this teratogenic effect is still unknown. Previous reports demonstrated that alcohol participates in epigenetic alterations, especially histone modifications during fetal development. Additional research is necessary to understand the correlation between major epigenetic events and alcohol-mediated teratogenesis such as that observed in fetal alcohol spectrum disorder (FASD). Here, we attempted to collect all the available information concerning alcohol-mediated histone modifications during gestational fetal development. We hope that this review will aid researchers to further examine the issues associated with ethanol exposure. PMID:29104501

IGF-I and NEFA concentrations in fetal fluids of term pregnancy dogs.

PubMed

Meloni, Tea; Comin, Antonella; Rota, Alessandro; Peric, Tanja; Contri, Alberto; Veronesi, Maria Cristina

2014-06-01

Insulin-like growth factor-I (IGF-I) and non-esterified fatty acids (NEFA) play an essential role in fetal growth and development. To date, fetal fluids IGF-I and NEFA levels at term canine pregnancy are unknown and could be related to the neonatal development and breed size. For these reasons, the aims of the present study were as follows: (1) to evaluate IGF-I and NEFA concentrations in fetal fluids collected from normally developed and viable newborn puppies born at term of normal pregnancies; (2) to assess possible differences between IGF-I and NEFA levels in amniotic compared with allantoic fluid; (3) to detect possible relationship between breed body size and IGF-I and NEFA amniotic and allantoic concentrations; (4) to evaluate possible differences in IGF-I fetal fluids levels between male and female puppies; and (5) to assess possible correlations between the two hormones in each type of fluid. The study enrolled 25 pure breed bitches submitted to elective Cesarean section at term because of the high risk of dystocia or previous troubles at parturition. At surgery, amniotic and allantoic fluids were collected and assayed for IGF-I and NEFA. IGF-I and NEFA amounts in both amniotic and allantoic fluids of different breed size bitches (small: ≤10 kg; medium: 11-25 kg; large: 26-40 kg) were detected, as well as the effect of gender on IGF-I levels. On a total of 73 amniotic and 76 allantoic samples collected by normal, viable, and mature newborns, the mean IGF-I concentration was significantly higher in amniotic than in allantoic fluid in all three groups, but the amniotic IGF-I levels were significantly lower in small and medium size bitches when compared with large ones. No significant differences were found in allantoic IGF-I concentrations among size groups. A significant effect of the puppy gender on IGF-I content in both fetal fluids was not reported. Regarding NEFA, in all the three groups, the mean NEFA concentration did not significantly differ between amnion and allantois, but in both fetal fluids, higher NEFA levels were detected in samples belonging to small breeds when compared with medium and large. These data strongly indicated that, also in the dog, a relation between fetal fluids IGF-I and NEFA concentrations and breed size exists. Further research is needed to elucidate the possible role of IGF-I and NEFA in the pathologic conditions related to canine fetal growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Proinflammatory cytokines: a link between chorioamnionitis and fetal brain injury.

PubMed

Patrick, Lindsay A; Smith, Graeme N

2002-09-01

To review the etiology of impaired fetal neurodevelopment - in particular, the relationship between chorioamnionitis, cytokines, and cerebral palsy. A MEDLINE search was performed for all clinical and basic science studies published in the English literature from 1966 to 2002. Key words or phrases used were chorioamnionitis, cerebral palsy, fetal brain damage, fetal CNS injury, infection in pregnancy, proinflammatory cytokines in pregnancy, proinflammatory cytokines in infection, and preterm labour or birth. All relevant human and animal studies were included. Fetal brain injury remains a major cause of lifelong morbidity, incurring significant societal and health care costs. It has been postulated that chorioamnionitis stimulates maternal/fetal proinflammatory cytokine release, which is damaging to the developing fetal nervous system. Elevated cytokine concentrations may interfere with glial cell development and proliferation in the late second trimester of pregnancy, when the central nervous system is most vulnerable. Increasing numbers of epidemiological and basic science studies found through MEDLINE searches support this hypothesis. Treatment options aimed at etiologic factors may lead to improved neurodevelopmental outcomes. Clearly, some relationship exists between chorioamnionitis, cytokines, and the development of cerebral palsy, but the severity and duration of exposure required to produce fetal damage remains unknown. Future research addressing these issues may aid in clinical decision-making. As well, the elucidation of mechanisms of cytokine action may aid in early treatment options to prevent or limit development of fetal brain injury.

Smoking in preeclamptic women is associated with higher birthweight for gestational age and lower soluble fms-like tyrosine kinase-1 levels: a nested case control study

PubMed Central

2011-01-01

Background Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers. Methods From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit. Results In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054). Conclusions Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1. PMID:22074109

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

PubMed

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

2017-05-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons

PubMed Central

McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas

2017-01-01

Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor–β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. PMID:28324053

The Potential Risks of Commonly Prescribed Antipsychotics

PubMed Central

Aneja, Alka; Rahman, Atiq; Megna, James; Freemont, Wanda; Shiplo, Mohammed; Nihilani, Nikil; Lee, Kathy

2005-01-01

Chlorpromazine, haloperidol, fluphenazine, clozapine, risperidone, quetiapine, olanzapine, ziprasidone, and aripiprazole are antipsychotics commonly used in psychiatric medicine. Approximately one third of pregnant women with psychotic symptoms use antipsychotics at least once. This review will discuss the effects of antipsychotic use during pregnancy and lactation on the fetus and infant. Although adequate and well-controlled studies have not been done in any one of these antipsychotic drugs, animal studies have revealed evidence of teratogenic or embryo/fetotoxic effects in all of them. Toxicities include skeletal malformations, central nervous system (CNS) defects, cleft palate, cardiac abnormalities, decreased fetal growth, and fetal death. For example, in pregnant women, congenital malformations and perinatal death have been reported with chlorpromazine use. Both chlorpromazine and fluphenazine in monotherapy have been shown to cause extrapyramidal symptoms and respiratory distress in infants born to mothers treated with these medications. Haloperidol use during pregnancy has been linked to severe limb reduction defects. Effects of antipsychotic use in lactating mothers are mostly unknown. However, the use of chlorpromazine has been reported to result in drowsiness and lethargy in breastfed infants. Additionally, clozapine has been reported to cause sedation, decreased suckling, restlessness, irritability, seizures, and cardiovascular instability of infants were also reported with clozapine use in lactating mother. Use of antipsychotic drugs by pregnant and lactating mother may only be justified if the potential benefit outweighs the potential risk to the fetus. PMID:21152171

Telemedicine for antenatal surveillance of high-risk pregnancies with ambulatory and home fetal heart rate monitoring--an update.

PubMed

Hod, Moshe; Kerner, Ram

2003-01-01

Antepartum fetal surveillance is routinely used to assess the risk of fetal death in high-risk pregnancies. Traditionally, testing is performed in the hospital or outpatient clinic by trained medical staff. New equipment is now available that is easy to operate and can be used for self-monitoring of the fetal heart rate (FHR) in the home setting. The tracings are transmitted by modem to a referral center for immediate interpretation by a health provider. The aim of this review was to assess the current data on the application of this new technology with regard to feasibility, access to care, maternal and neonatal outcome, patient and physician satisfaction, and cost-effectiveness.

The role of placental alpha microglobulin-1 amnisure in determining the status of the fetal membranes; its association with preterm birth. Traditions … traditions ….

PubMed

Mariona, Federico G; Roura, Lluis Cabero

2016-03-01

The integrity of the fetal amnion-chorion is an imperative for the preservation of a normal pregnancy in the human. The diagnosis of the status of the fetal membranes has traditionally been reduced to either intact or ruptured. In the last decades, evidence has accumulated demonstrating that this clinical approach may well be an over simplification. Practically, all maternal organs experienced physiologic or eventually pathologic changes during the length of the gestational period. We propose that the fetal membranes are also significantly impacted by those changes. The accurate, specific, simplified and low-cost diagnosis of the status of the fetal membranes is of critical importance for the assessment of risk to the pregnancy followed by efficient and prompt treatment. The presence of placental alpha macroglobulin-1 in the vagina specifically indicates a disruption in the integrity of the fetal membranes and may indirectly mean increased risk for preterm birth. Further research to properly characterize this marker and its importance in the care of pregnant woman at risk for preterm birth is strongly recommended.

Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

PubMed

Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

2018-04-01

Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of fetal well-being in cattle by ultrasonography in normal, high-risk, and cloned pregnancies

PubMed Central

Buczinski, Sébastien; Fecteau, Gilles; Lefebvre, Réjean C.; Smith, Lawrence C.

2011-01-01

This study determined ultrasonographic parameters of fetuses and uterine adnexa in late pregnancy in normal, cloned, and high-risk pregnancies in relation to perinatal and neonatal outcome. Ten cows with normal pregnancies (CONTROL, mean pregnancy length 273 d), 10 sick cows with potentially compromised pregnancies (HIGH-RISK, mean pregnancy length 267 d), and 10 heifers with cloned pregnancies (CLONED, mean pregnancy length 274 d) were examined at more than 260 d of gestation. There was no difference in mean fetal heart rates among the groups. The cloned calves were heavier (57 ± 8 kg) than calves from CONTROL group (36 ± 7 kg), and calves from HIGH-RISK group (37 ± 13 kg) (P = 0.003). The diameter of the thoracic aorta was positively correlated (R = 0.62) with fetal birth weight in the CONTROL group (P = 0.01). Fetal activity was not associated with survival. The results suggest that transabdominal ultrasonographic assessment of the fetal well-being may serve as a potential tool for evaluation of the fetoplacental unit. PMID:21532817

Consumption of PCB-contaminated sport fish and risk of spontaneous fetal death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendola, P.; Buck, G.M.; Vena, J.E.

1995-05-01

Spontaneous fetal death has been observed among various mammalian species after exposure to polychlorinated biphenyls (PCBs). Our exposure-based cohort study assessed the relationship between consumption of PCB-contaminated Lake Ontario sport fish and spontaneous fetal death using 1820 multigravid fertile women from the 1990-1991 New York State Angler Cohort Study. Fish consumption data were obtained from food frequency questionnaires and history of spontaneous fetal death from live birth certificates. Analyses were stratified by number of prior pregnancies and controlled for smoking and maternal age. No significant increases in risk for fetal death were observed across four measures of exposure: a lifetimemore » estimate of PCB exposure based on species-specific PCB levels; the number of years of fish consumption; kilograms of sport fish consumed in 1990-1991; and a lifetime estimate of kilograms eaten. A slight risk reduction was seen for women with two prior pregnancies at the highest level of PCB exposure (odds ratio = 0.36; 95% CI, 0.14-0.92) and for women with three or more prior pregnancies with increasing years of fish consumption (odds ratio = 0.97; 95% CI, 0.94-0.99). These findings suggest that consumption of PCB-contaminated sport fish does not increase the risk of spontaneous fetal death. 50 refs., 2 tabs.« less

Fetal Risks and Maternal Renal Complications in Pregnancy with Preexisting Chronic Glomerulonephritis.

PubMed

Li, Yuehong; Wang, Wei; Wang, Yujuan; Chen, Qi

2018-02-18

BACKGROUND Analysis the maternal and fetal risk predictors in pregnancy in conjunction with chronic glomerulonephritis (CGN) patients are helpful to understand the influence of kidney diseases on pregnancy and the effects of pregnancy on kidney diseases. The aim of this study was to determine the predictors of adverse maternal and fetal outcomes in CGN patients. MATERIAL AND METHODS Maternal and fetal outcomes in 64 pregnancies of CGN patients were retrospectively analyzed. We randomly selected 100 low-risk-pregnancy women without chronic kidney disease (CKD) at the same time as the control group. Clinical manifestations, laboratory data, medication, and outcomes during pregnancies of these patients were analyzed by univariate and logistic regression. RESULTS CGN patients were associated with higher adverse pregnancy outcomes versus general pregnancies. The gestational ages are shorter, and the incidence of preeclampsia, gestational hypertension, and abortion were increased. The rates of premature delivery, low birth weights, and intrauterine growth restriction were higher in the CGN group. Prenatal proteinuria and blood pressure were significantly increased compared with pre-pregnancy stage. Proteinuria (0.9±0.6 g/d vs. 0.5±0.3 g/d, P=0.032) and hypertension (6.9% vs. 3.4%, P=0.021) at 6 months after delivery were aggravated. Prenatal proteinuria ≥3.5 g/d (OR 12.22, 95%CI 3.16~47.32, P=0.001) was the maternal risk predictor in pregnancy. Prenatal blood pressure ≥160/110 mmHg (OR 8.97, 95%CI 1.69~47.53, P=0.010) and uric acid ≥363 μmol/L (OR 7.35, 95%CI 1.88~28.76, P=0.004) were the fetal risk predictors in pregnancy in conjunction with CGN patients. CONCLUSIONS Maternal-fetal risks are increased in pregnancies in conjunction with CGN patients. Prenatal proteinuria ≥3.5 g/d, BP ≥160/110 mmHg, and uric acid ≥363 μmol/L were the maternal and fetal risk predictors in pregnancy.

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.

Assessment of fetal sex chromosome aneuploidy using directed cell-free DNA analysis.

PubMed

Nicolaides, Kypros H; Musci, Thomas J; Struble, Craig A; Syngelaki, Argyro; Gil, M M

2014-01-01

To examine the performance of chromosome-selective sequencing of cell-free (cf) DNA in maternal blood for assessment of fetal sex chromosome aneuploidies. This was a case-control study of 177 stored maternal plasma samples, obtained before fetal karyotyping at 11-13 weeks of gestation, from 59 singleton pregnancies with fetal sex chromosome aneuploidies (45,X, n = 49; 47,XXX, n = 6; 47,XXY, n = 1; 47,XYY, n = 3) and 118 with euploid fetuses (46,XY, n = 59; 46,XX, n = 59). Digital analysis of selected regions (DANSR™) on chromosomes 21, 18, 13, X and Y was performed and the fetal-fraction optimized risk of trisomy evaluation (FORTE™) algorithm was used to estimate the risk for non-disomic genotypes. Performance was calculated at a risk cut-off of 1:100. Analysis of cfDNA provided risk scores for 172 (97.2%) samples; 4 samples (45,X, n = 2; 46,XY, n = 1; 46,XX, n = 1) had an insufficient fetal cfDNA fraction for reliable testing and 1 case (47,XXX) failed laboratory quality control metrics. The classification was correct in 43 (91.5%) of 47 cases of 45,X, all 5 of 47,XXX, 1 of 47,XXY and 3 of 47,XYY. There were no false-positive results for monosomy X. Analysis of cfDNA by chromosome-selective sequencing can correctly classify fetal sex chromosome aneuploidy with reasonably high sensitivity. © 2013 S. Karger AG, Basel.

Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study.

PubMed

Sovio, Ulla; White, Ian R; Dacey, Alison; Pasupathy, Dharmintra; Smith, Gordon C S

2015-11-21

Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15-24; 69 of 352 fetuses) for selective ultrasonography and 57% (51-62; 199 of 352 fetuses) for universal ultrasonography (relative sensitivity 2·9, 95% CI 2·4-3·5, p<0·0001). Of the 3977 fetuses, 562 (14·1%) were identified by universal ultrasonography with an estimated fetal weight of less than the 10th percentile and were at an increased risk of neonatal morbidity (relative risk [RR] 1·60, 95% CI 1·22-2·09, p=0·0012). However, estimated fetal weight of less than the 10th percentile was only associated with the risk of neonatal morbidity (pinteraction=0·005) if the fetal abdominal circumference growth velocity was in the lowest decile (RR 3·9, 95% CI 1·9-8·1, p=0·0001). 172 (4%) of 3977 pregnancies had both an estimated fetal weight of less than the 10th percentile and abdominal circumference growth velocity in the lowest decile, and had a relative risk of delivering an SGA infant with neonatal morbidity of 17·6 (9·2-34·0, p<0·0001). Screening of nulliparous women with universal third trimester fetal biometry roughly tripled detection of SGA infants. Combined analysis of fetal biometry and fetal growth velocity identified a subset of SGA fetuses that were at increased risk of neonatal morbidity. National Institute for Health Research, Medical Research Council, Sands, and GE Healthcare. Copyright © 2015 Sovio et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Ultrasonographic fetal well-being assessment, neonatal and postpartum findings of cloned pregnancies in cattle: A preliminary study on 10 fetuses and calves

PubMed Central

Buczinski, Sébastien; Fecteau, Gilles; Comeau, Geneviève; Boysen, Soren R.; Lefebvre, Réjean C.; Smith, Lawrence C.

2009-01-01

Cloned pregnancies in cattle are considered to be at risk due to a variety of fetal or adnexal abnormalities. Data is lacking concerning the possibility of transabdominal ultrasonography in the assessment of these high risk pregnancies. Transabdominal ultrasonography has rarely been reported in the assessment of bovine cloned pregnancies. Ten Holstein heifers carrying 8-month-old cloned fetuses were assessed by transabdominal ultrasonographic examination during the 3rd trimester of pregnancy. Fetal heart rates (FHR), movements, adnexal appearance, and placentome size were recorded. The outcome of the pregnancies was also noted and potential indicators of fetal demise recorded. Survival rate 1 week after birth was 30%. Mean FHR was 113 beats per minute (range: 92 to 128 bpm) during the fetal ultrasonography. No correlation between FHR and fetal activity was found. Fetal hyperactivity and imaging of hyperechoic particles in both allantoic and amniotic fluids were possible signs of fetal distress. Despite the size of the fetus and the deep bovine abdomen, fetal transabdominal ultrasonography can be performed in cattle. This preliminary study points to the necessity of further larger studies for defining normal and abnormal findings in bovine late pregnancy. PMID:19436477

Ultrasonographic fetal well-being assessment, neonatal and postpartum findings of cloned pregnancies in cattle: a preliminary study on 10 fetuses and calves.

PubMed

Buczinski, Sébastien; Fecteau, Gilles; Comeau, Geneviève; Boysen, Soren R; Lefebvre, Réjean C; Smith, Lawrence C

2009-03-01

Cloned pregnancies in cattle are considered to be at risk due to a variety of fetal or adnexal abnormalities. Data is lacking concerning the possibility of transabdominal ultrasonography in the assessment of these high risk pregnancies. Transabdominal ultrasonography has rarely been reported in the assessment of bovine cloned pregnancies. Ten Holstein heifers carrying 8-month-old cloned fetuses were assessed by transabdominal ultrasonographic examination during the 3rd trimester of pregnancy. Fetal heart rates (FHR), movements, adnexal appearance, and placentome size were recorded. The outcome of the pregnancies was also noted and potential indicators of fetal demise recorded. Survival rate 1 week after birth was 30%. Mean FHR was 113 beats per minute (range: 92 to 128 bpm) during the fetal ultrasonography. No correlation between FHR and fetal activity was found. Fetal hyperactivity and imaging of hyperechoic particles in both allantoic and amniotic fluids were possible signs of fetal distress. Despite the size of the fetus and the deep bovine abdomen, fetal transabdominal ultrasonography can be performed in cattle. This preliminary study points to the necessity of further larger studies for defining normal and abnormal findings in bovine late pregnancy.

Risk of ultrasound-detected neonatal brain abnormalities in intrauterine growth-restricted fetuses born between 28 and 34 weeks' gestation: relationship with gestational age at birth and fetal Doppler parameters.

PubMed

Cruz-Martinez, R; Tenorio, V; Padilla, N; Crispi, F; Figueras, F; Gratacos, E

2015-10-01

To estimate the value of gestational age at birth and fetal Doppler parameters in predicting the risk of neonatal cranial abnormalities in intrauterine growth-restricted (IUGR) fetuses born between 28 and 34 weeks' gestation. Fetal Doppler parameters including umbilical artery (UA), middle cerebral artery (MCA), aortic isthmus, ductus venosus and myocardial performance index were evaluated in a cohort of 90 IUGR fetuses with abnormal UA Doppler delivered between 28 and 34 weeks' gestation and in 90 control fetuses matched for gestational age. The value of gestational age at birth and fetal Doppler parameters in predicting the risk of ultrasound-detected cranial abnormalities (CUA), including intraventricular hemorrhage, periventricular leukomalacia and basal ganglia lesions, was analyzed. Overall, IUGR fetuses showed a significantly higher incidence of CUA than did control fetuses (40.0% vs 12.2%, respectively; P < 0.001). Within the IUGR group, all predictive variables were associated individually with the risk of CUA, but fetal Doppler parameters rather than gestational age at birth were identified as the best predictor. MCA Doppler distinguished two groups with different degrees of risk of CUA (48.5% vs 13.6%, respectively; P < 0.01). In the subgroup with MCA vasodilation, presence of aortic isthmus retrograde net blood flow, compared to antegrade flow, allowed identification of a subgroup of cases with the highest risk of CUA (66.7% vs 38.6%, respectively; P < 0.05). Evaluation of fetal Doppler parameters, rather than gestational age at birth, allows identification of IUGR preterm fetuses at risk of neonatal brain abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal growth: a review of terms, concepts and issues relevant to obstetrics.

PubMed

Mayer, C; Joseph, K S

2013-02-01

The perinatal literature includes several potentially confusing and controversial terms and concepts related to fetal size and growth. This article discusses fetal growth from an obstetric perspective and addresses various issues including the physiologic mechanisms that determine fetal growth trajectories, known risk factors for abnormal fetal growth, diagnostic and prognostic issues related to restricted and excessive growth and temporal trends in fetal growth. Also addressed are distinctions between fetal growth 'standards' and fetal growth 'references', and between fetal growth charts based on estimated fetal weight vs those based on birth weight. Other concepts discussed include the incidence of fetal growth restriction in pregnancy (does the frequency of fetal growth restriction increase or decrease with increasing gestation?), the obstetric implications of studies showing associations between fetal growth and adult chronic illnesses (such as coronary heart disease) and the need for customizing fetal growth standards. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Periconceptional intake of vitamins and fetal death: a cohort study on multivitamins and folate.

PubMed

Nohr, Ellen A; Olsen, Jorn; Bech, Bodil H; Bodnar, Lisa M; Olsen, Sjurdur F; Catov, Janet M

2014-02-01

Women planning to conceive are often advised to take multivitamins. Whether this affects the survival of the fetus is not known. We used data from 35 914 women in the Danish National Birth Cohort who at recruitment had reported the number of weeks of supplement use during a 12-week periconceptional period. A telephone interview provided information about maternal characteristics and data on fetal death came from registers. The associations between periconceptional multivitamin or folate-only use and early (<20 weeks) and late (≥20 weeks) fetal death were estimated by hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at 8 completed weeks of gestation, and comparisons were made with no supplement use at any time during the periconceptional period. Any multivitamin use was associated with a small increased crude risk of fetal death [HR 1.12 (1.01-1.25)], which was restricted to early losses [HR 1.18 (1.05-1.33)] compared with late losses [HR 0.82 (0.62-1.10)]. Adjustment for maternal factors increased this excess risk further. Whereas regular users of multivitamins (4-6 weeks of 6) before conception had more early losses [HR 1.29 (1.12-1.48)], a decreased risk of late losses was indicated when use started after conception [HR 0.65 (0.39-1.09)]. Folate-only use was not associated with fetal death. Multivitamin use was associated with a modest increased risk of early fetal death. For late fetal death, regular supplement use after conception may decrease risk, but numbers were small. Further studies on preconceptional multivitamin use are needed to guide public health recommendations.

Periconceptional intake of vitamins and fetal death: a cohort study on multivitamins and folate

PubMed Central

Nohr, Ellen A; Olsen, Jorn; Bech, Bodil H; Bodnar, Lisa M; Olsen, Sjurdur F; Catov, Janet M

2014-01-01

Background Women planning to conceive are often advised to take multivitamins. Whether this affects the survival of the fetus is not known. Methods We used data from 35 914 women in the Danish National Birth Cohort who at recruitment had reported the number of weeks of supplement use during a 12-week periconceptional period. A telephone interview provided information about maternal characteristics and data on fetal death came from registers. The associations between periconceptional multivitamin or folate-only use and early (<20 weeks) and late (≥20 weeks) fetal death were estimated by hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at 8 completed weeks of gestation, and comparisons were made with no supplement use at any time during the periconceptional period. Results Any multivitamin use was associated with a small increased crude risk of fetal death [HR 1.12 (1.01–1.25)], which was restricted to early losses [HR 1.18 (1.05–1.33)] compared with late losses [HR 0.82 (0.62–1.10)]. Adjustment for maternal factors increased this excess risk further. Whereas regular users of multivitamins (4–6 weeks of 6) before conception had more early losses [HR 1.29 (1.12–1.48)], a decreased risk of late losses was indicated when use started after conception [HR 0.65 (0.39–1.09)]. Folate-only use was not associated with fetal death. Conclusions Multivitamin use was associated with a modest increased risk of early fetal death. For late fetal death, regular supplement use after conception may decrease risk, but numbers were small. Further studies on preconceptional multivitamin use are needed to guide public health recommendations. PMID:24453235

2,3,7,8-tetrachlorodibenzo-p-dioxin potentially attenuates the gene expression of pituitary gonadotropin β-subunits in a fetal age-specific fashion: a comparative study using cultured pituitaries.

PubMed

Takeda, Tomoki; Yamamoto, Midori; Himeno, Masaru; Takechi, Shinji; Yamaguchi, Tadatoshi; Ishida, Takumi; Ishii, Yuji; Yamada, Hideyuki

2011-04-01

Our previous studies have demonstrated that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a reduction in gonadotropin biosynthesis in the fetal pituitary, resulting in the attenuated expression of steroidogenic proteins in the fetal gonads and the impairment of sexual behaviors in adulthood. However, the mechanism of the attenuation remains unknown. To address this issue, we investigated whether TCDD affects the pituitary production of gonadotropins, using cultured pituitary. In the absence of gonadotropin-releasing hormone (GnRH), a regulator of gonadotropin biosynthesis, TCDD did not affect the expression of gonadotropin mRNAs both in fetal and postnatal pituitaries. On the other hand, in the presence of GnRH, TCDD interfered with the synthesis of gonadotropin β-subunit mRNAs only in the fetal pituitary. A protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and a PKA activator (8-bromoadenosine-3' 5'-cyclic monophosphate) induced the expression of gonadotropin mRNAs in the fetal pituitary. Among the subunits, only the induction of β-subunit was reduced by TCDD treatment. These results suggest that TCDD reduces gonadotropin biosynthesis via damage to GnRH-stimulated PKC and PKA signaling in a β-subunit- and fetal age-specific manner.

Non-invasive risk assessment of fetal sex chromosome aneuploidy through directed analysis and incorporation of fetal fraction.

PubMed

Hooks, J; Wolfberg, A J; Wang, E T; Struble, C A; Zahn, J; Juneau, K; Mohseni, M; Huang, S; Bogard, P; Song, K; Oliphant, A; Musci, T J

2014-05-01

To assess the performance of a directed chromosomal analysis approach in the prenatal evaluation of fetal sex chromosome aneuploidy. We analyzed 432 frozen maternal plasma samples obtained from patients prior to undergoing fetal diagnostic testing. The cohort included women greater than 18 years of age with a singleton pregnancy of greater than 10 weeks gestation. Samples were analyzed using a chromosome-selective approach (DANSR(TM) ) and a risk algorithm that incorporates fetal fraction (FORTE(TM) ). The cohort included 34 cases of sex chromosome aneuploidy. The assay correctly identified 26 of 27 (92.6%) cases of Monosomy X, one case of XXX, and all six cases of XXY. There were four false positive cases of sex chromosome aneuploidy among 380 euploid cases for an overall false positive rate of less than 1%. Analysis of the risk for sex chromosome aneuploidies can be accomplished with a targeted assay with high sensitivity. © 2014 John Wiley & Sons, Ltd.

The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis.

PubMed

Roberge, Stéphanie; Nicolaides, Kypros; Demers, Suzanne; Hyett, Jon; Chaillet, Nils; Bujold, Emmanuel

2017-02-01

Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of preeclampsia, severe preeclampsia, and fetal growth restriction can be reduced by the prophylactic use of aspirin in high-risk women, but the appropriate dose of the drug to achieve this objective is not certain. We sought to estimate the impact of aspirin dosage on the prevention of preeclampsia, severe preeclampsia, and fetal growth restriction. We performed a systematic review and meta-analysis of randomized controlled trials comparing the effect of daily aspirin or placebo (or no treatment) during pregnancy. We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials up to December 2015, and study bibliographies were reviewed. Authors were contacted to obtain additional data when needed. Relative risks for preeclampsia, severe preeclampsia, and fetal growth restriction were calculated with 95% confidence intervals using random-effect models. Dose-response effect was evaluated using meta-regression and reported as adjusted R 2 . Analyses were stratified according to gestational age at initiation of aspirin (≤16 and >16 weeks) and repeated after exclusion of studies at high risk of biases. In all, 45 randomized controlled trials included a total of 20,909 pregnant women randomized to between 50-150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose-response effect for the prevention of preeclampsia (relative risk, 0.57; 95% confidence interval, 0.43-0.75; P < .001; R 2 , 44%; P = .036), severe preeclampsia (relative risk, 0.47; 95% confidence interval, 0.26-0.83; P = .009; R 2 , 100%; P = .008), and fetal growth restriction (relative risk, 0.56; 95% confidence interval, 0.44-0.70; P < .001; R 2 , 100%; P = .044) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66-0.99; P = .04) without relationship with aspirin dosage (R 2 , 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64-1.14; P = .28; R 2 , 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86-1.05; P = .34; R 2 , not available; P = .563). Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose-response effect. Low-dose aspirin initiated at >16 weeks' gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Maternal uterine NK cell–activating receptor KIR2DS1 enhances placentation

PubMed Central

Xiong, Shiqiu; Sharkey, Andrew M.; Kennedy, Philippa R.; Gardner, Lucy; Farrell, Lydia E.; Chazara, Olympe; Bauer, Julien; Hiby, Susan E.; Colucci, Francesco; Moffett, Ashley

2013-01-01

Reduced trophoblast invasion and vascular conversion in decidua are thought to be the primary defect of common pregnancy disorders including preeclampsia and fetal growth restriction. Genetic studies suggest these conditions are linked to combinations of polymorphic killer cell Ig-like receptor (KIR) genes expressed by maternal decidual NK cells (dNK) and HLA-C genes expressed by fetal trophoblast. Inhibitory KIR2DL1 and activating KIR2DS1 both bind HLA-C2, but confer increased risk or protection from pregnancy disorders, respectively. The mechanisms underlying these genetic associations with opposing outcomes are unknown. We show that KIR2DS1 is highly expressed in dNK, stimulating strong activation of KIR2DS1+ dNK. We used microarrays to identify additional responses triggered by binding of KIR2DS1 or KIR2DL1 to HLA-C2 and found different responses in dNK coexpressing KIR2DS1 with KIR2DL1 compared with dNK only expressing KIR2DL1. Activation of KIR2DS1+ dNK by HLA-C2 stimulated production of soluble products including GM-CSF, detected by intracellular FACS and ELISA. We demonstrated that GM-CSF enhanced migration of primary trophoblast and JEG-3 trophoblast cells in vitro. These findings provide a molecular mechanism explaining how recognition of HLA class I molecules on fetal trophoblast by an activating KIR on maternal dNK may be beneficial for placentation. PMID:24091323

Labor Induction

MedlinePlus

... many contractions may lead to changes in the fetal heart rate, umbilical cord problems, and other problems. Other risks of cervical ripening and labor induction include the following: • Infection in the mother or fetus • Uterine rupture • Increased risk of cesarean birth • Fetal ...

Coding update of the SMFM definition of low risk for cesarean delivery from ICD-9-CM to ICD-10-CM.

PubMed

Armstrong, Joanne; McDermott, Patricia; Saade, George R; Srinivas, Sindhu K

2017-07-01

In 2015, the Society for Maternal-Fetal Medicine developed a low risk for cesarean delivery definition based on administrative claims-based diagnosis codes described by the International Classification of Diseases, Ninth Revision, Clinical Modification. The Society for Maternal-Fetal Medicine definition is a clinical enrichment of 2 available measures from the Joint Commission and the Agency for Healthcare Research and Quality measures. The Society for Maternal-Fetal Medicine measure excludes diagnosis codes that represent clinically relevant risk factors that are absolute or relative contraindications to vaginal birth while retaining diagnosis codes such as labor disorders that are discretionary risk factors for cesarean delivery. The introduction of the International Statistical Classification of Diseases, 10th Revision, Clinical Modification in October 2015 expanded the number of available diagnosis codes and enabled a greater depth and breadth of clinical description. These coding improvements further enhance the clinical validity of the Society for Maternal-Fetal Medicine definition and its potential utility in tracking progress toward the goal of safely lowering the US cesarean delivery rate. This report updates the Society for Maternal-Fetal Medicine definition of low risk for cesarean delivery using International Statistical Classification of Diseases, 10th Revision, Clinical Modification coding. Copyright © 2017. Published by Elsevier Inc.

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.

Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study.

PubMed

Ay, L; Kruithof, C J; Bakker, R; Steegers, E A P; Witteman, J C M; Moll, H A; Hofman, A; Mackenbach, J P; Hokken-Koelega, A C S; Jaddoe, V W V

2009-06-01

We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. Population-based birth cohort study. Data of pregnant women and their children in Rotterdam, the Netherlands. In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.

Fetal head circumference, operative delivery, and fetal outcomes: a multi-ethnic population-based cohort study

PubMed Central

2013-01-01

Background Operative delivery procedures, such as primary cesarean section, vacuum-assisted, and forceps-assisted vaginal delivery increase maternal and fetal morbidity, and the cost of care. We evaluated whether large fetal head circumference (FHC) independently increases risk of such interventions, as well as fetal distress or low Apgar score, in anatomically normal infants. Methods We conducted a population-based retrospective cohort study using Washington State birth certificate data. We included singleton, term infants born to nulliparous mothers from 2003–2009. We compared mode of delivery and fetal outcomes in 10,750 large-FHC (37-41 cm) infants relative to 10,750 average-FHC (34 cm) infants, frequency matched by birth-year. Results Large-FHC infants were nearly twice as likely to be delivered by primary cesarean section as average-FHC infants (unadjusted relative risk [RR] 1.84, 95% confidence interval [CI]: 1.77, 1.92). The RR for primary cesarean section associated with large-FHC was largest for mothers aged 19 years or less (RR 2.28; 95% CI: 1.99, 2.61), and smallest for mothers aged 35 years or greater (RR 1.51; 95% CI: 1.37, 1.66) [test of homogeneity, p < 0.001]. Large-FHC infants were at increased risk of vacuum-assisted vaginal delivery (RR 1.55; 95% CI: 1.43, 1.69), and forceps-assisted vaginal delivery (RR 1.61; 95% CI: 1.32, 1.97). There was no difference in risk of fetal distress (RR 0.97; 95% CI: 0.89, 1.07) for large-FHC versus average-FHC infants. Risk estimates were unaffected by adjustment for potential confounders. Conclusions Nulliparous mothers of large-FHC infants are at increased risk of primary cesarean section, vacuum-assisted and forceps-assisted vaginal delivery relative to mothers of average-FHC infants. Maternal age modifies the association between FHC and primary cesarean section. PMID:23651454

Weighing the Social and Ethical Considerations of Maternal-Fetal Surgery.

PubMed

Antiel, Ryan M; Flake, Alan W; Collura, Christopher A; Johnson, Mark P; Rintoul, Natalie E; Lantos, John D; Curlin, Farr A; Tilburt, Jon C; Brown, Stephen D; Feudtner, Chris

2017-12-01

The ethics of maternal-fetal surgery involves weighing the importance of potential benefits, risks, and other consequences involving the pregnant woman, fetus, and other family members. We assessed clinicians' ratings of the importance of 9 considerations relevant to maternal-fetal surgery. This study was a discrete choice experiment contained within a 2015 national mail-based survey of 1200 neonatologists, pediatric surgeons, and maternal-fetal medicine physicians, with latent class analysis subsequently used to identify groups of physicians with similar ratings. Of 1176 eligible participants, 660 (56%) completed the discrete choice experiment. The highest-ranked consideration was of neonatal benefits, which was followed by consideration of the risk of maternal complications. By using latent class analysis, we identified 4 attitudinal groups with similar patterns of prioritization: "fetocentric" ( n = 232), risk-sensitive ( n = 197), maternal autonomy ( n = 167), and family impact and social support ( n = 64). Neonatologists were more likely to be in the fetocentric group, whereas surgeons were more likely to be in the risk-sensitive group, and maternal-fetal medicine physicians made up the largest percentage of the family impact and social support group. Physicians vary in how they weigh the importance of social and ethical considerations regarding maternal-fetal surgery. Understanding these differences may help prevent or mitigate disagreements or tensions that may arise in the management of these patients. Copyright © 2017 by the American Academy of Pediatrics.

A fetal cardiovascular score to predict infant hypertension and arterial remodeling in intrauterine growth restriction.

PubMed

Cruz-Lemini, Mónica; Crispi, Fátima; Valenzuela-Alcaraz, Brenda; Figueras, Francesc; Gómez, Olga; Sitges, Marta; Bijnens, Bart; Gratacós, Eduard

2014-06-01

Intrauterine growth restricted (IUGR) fetuses experience cardiovascular remodeling that persists into infancy and has been related to cardiovascular outcomes in adulthood. Hypertension in infancy has been demonstrated to be a strong risk factor for later cardiovascular disease. Close monitoring together with dietary interventions have shown to improve cardiovascular health in hypertensive children; however, not all IUGR infants show increased blood pressure. We evaluated the potential of fetal echocardiography for predicting hypertension and arterial remodeling in 6-month-old IUGR infants. One hundred consecutive IUGR and 100 control fetuses were observed into infancy. Fetal assessment included perinatal Doppler imaging, cardiac morphometry, ejection fraction, cardiac output, isovolumic relaxation time (IVRT), tricuspid annular-plane systolic excursion (TAPSE), and tissue Doppler imaging. Infant hypertension and arterial remodeling were defined as mean blood pressure of >95th percentile together with aortic intima-media thickness of >75th percentile at 6 months of age. Odds ratio were obtained for fetal parameters that were associated with infant outcomes. Fetal TAPSE, right sphericity index, IVRT, and cerebroplacental ratio were the strongest predictors for postnatal vascular remodeling. A cardiovascular risk score that was based on fetal TAPSE, cerebroplacental ratio, right sphericity index, and IVRT was highly predictive of infant hypertension and arterial remodeling (area under the curve, 0.87; 95% confidence interval, 0.79-0.93; P < .001). Fetal echocardiographic parameters identify a high-risk group within the IUGR fetuses who could be targeted for early screening of blood pressure and other cardiovascular risk factors and for promoting healthy diet and physical exercise. Copyright © 2014 Mosby, Inc. All rights reserved.

Third trimester fetal heart rate predicts phenotype and mutation burden in the type 1 long QT syndrome.

PubMed

Winbo, Annika; Fosdal, Inger; Lindh, Maria; Diamant, Ulla-Britt; Persson, Johan; Wettrell, Göran; Rydberg, Annika

2015-08-01

Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype. This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110 KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29-41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=-0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (-10 beats per minute per added mutation; P<1.0×10(-23)). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted -7 beats per minute, P<0.0001. In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias. © 2015 American Heart Association, Inc.

A placenta clinic approach to the diagnosis and management of fetal growth restriction.

PubMed

Kingdom, John C; Audette, Melanie C; Hobson, Sebastian R; Windrim, Rory C; Morgen, Eric

2018-02-01

Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening programs for placental complications. However, placental ultrasound can be diagnostic in the context of fetal growth restriction, for example in Breus' mole and triploidy, which in turn may enhance diagnosis and management. Several examples are illustrated in our figures and supplementary videos. Recent advances in the ability of multiparameter screening and intervention programs to reduce the risk of severe preeclampsia will likely increase efforts to deliver similar improvements for women at risk of fetal growth restriction. Placental pathology is important because the underlying pathologies associated with fetal growth restriction have a wide range of recurrence risks. Rare conditions such as massive perivillous fibrinoid deposition or chronic histolytic intervillositis may recur in >50% of subsequent pregnancies. Postpartum care in a placenta-focused program can provide effective counseling for modifiable maternal risk factors, and can assist in planning future pregnancy care based on the pathologic basis of fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantification of fetal magnetoencephalographic activity in low-risk fetuses using burst duration and interburst interval.

PubMed

Vairavan, Srinivasan; Govindan, Rathinaswamy B; Haddad, Naim; Preissl, Hubert; Lowery, Curtis L; Siegel, Eric; Eswaran, Hari

2014-07-01

To identify quantitative MEG indices of spontaneous brain activity for fetal neurological maturation in normal pregnancies and examine the effect of fetal state on these indices. Spontaneous MEG brain activity was examined in 22 low-risk fetal recordings with gestational age (GA) ranging from 30 to 37 weeks. As major quantitative characteristics of spontaneous activity, burst duration (BD) and interburst interval (IBI) were studied in correlation with GA and fetal state. IBI showed a decrease with gestational age (-0.21 s/week, P=0.0031). This trend was only maintained in the quiet-sleep state. With respect to BD, no significant trends were detected with GA and state. IBI can be quantified as a fetal brain maturational parameter. The decrease in IBI over gestation was similar to the trend reported in the preterm neonatal EEG studies. Quiet sleep could be the optimal state to study such MEG maturational indices. With further investigation, indices extracted from spontaneous fetal brain activity may serve as an early warning for fetal neurological distress. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial

PubMed Central

Al Wattar, Bassel H; Dodds, Julie; Placzek, Anna; Spyreli, Eleni; Moore, Amanda; Hooper, Richard; Beresford, Lee; Roseboom, Tessa J; Bes-Rastrollo, Maira; Hitman, Graham; Khan, Khalid S; Thangaratinam, Shakila

2016-01-01

Introduction Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and fetal complications in pregnant women with metabolic risk factors. Methods and analysis Pregnant women with a singleton pregnancy <18 weeks gestation, and without pre-existing diabetes, chronic renal disease and autoimmune diseases will be recruited. Women with metabolic risk factors will be randomised to receive a dietary intervention based on a Mediterranean pattern, supplemented with extra virgin olive oil and mixed nuts until delivery. The intervention will be delivered through a series of one to one and group sessions. The primary outcome is a composite maternal outcome of pre-eclampsia or gestational diabetes and a composite fetal outcome of stillbirth, small for gestational age fetus or admission to the neonatal intensive care unit. Secondary outcomes include maternal, fetal, dietary and laboratory outcomes. We aim to randomise 1230 eligible women with metabolic risk factors. We will also compare the outcomes in women with and without these risk factors. The sample size will provide us with 80% power at 5% significance, assuming a 20% loss to follow-up to detect a 30% reduction in maternal and fetal complications. Ethics and dissemination The ESTEEM trial is designed to provide a definitive estimate of the effects of Mediterranean dietary pattern in pregnancy on maternal and fetal outcomes. The pragmatic nature of ESTEEM ensures the applicability of its findings into clinical practice. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses. Ethical approval was granted by the NHS Research Ethics Committees (14/EE/1048). Trial registration number NCT02218931; Pre-results. PMID:27798035

Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

PubMed

Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

2018-02-01

Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy.

PubMed

Kim, Shin Young; Park, So Yeon; Choi, Ji Won; Kim, Do Jin; Lee, Shin Yeong; Lim, Ji Hyae; Han, Jung Yeol; Ryu, Hyun Mee; Kim, Min Hyoung

2011-10-01

PROBLEM  Polymorphisms in genes involved in folate metabolism are commonly associated with defects in folate-dependent homocysteine metabolism, which can result in DNA hypomethylation and chromosome nondisjunction. This prospective study aimed to investigate the associations between MTHFR 677C>T, MTHFR 1298A>C, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68 polymorphisms and spontaneous abortion (SA) with fetal chromosomal aneuploidy. METHOD OF STUDY  Subjects included 33 SA with normal fetal karyotype, 24 SA with fetal chromosomal aneuploidy and 155 normal controls. Polymorphisms were genotyped by PCR-RFLP and QF-PCR analysis. RESULTS  The frequencies of MTHFR 1298AC and combined 1298AC/CC genotypes were higher in SA with fetal chromosomal aneuploidy than in controls. The 1298C allele frequency was also significantly higher in SA with fetal chromosomal aneuploidy than in controls. Moreover, the 1298C allele frequency was higher in SA with fetal chromosomal aneuploidy than in SA with normal fetal karyotype. The combined 1298AC/CC genotype was significantly associated with the risk of SA with fetal chromosomal aneuploidy compared with that of the 1298AA genotype (adjusted OR = 2.93, 95% CI: 1.11-7.69). There was no association between SA with fetal chromosomal aneuploidy and other polymorphisms. CONCLUSIONS  Our findings indicate that MTHFR 1298A>C polymorphism may be an independent risk factor for SA with fetal chromosomal aneuploidy. © 2011 John Wiley & Sons A/S.

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.

Fetal growth velocity and body proportion in the assessment of growth.

PubMed

Hiersch, Liran; Melamed, Nir

2018-02-01

Fetal growth restriction implies failure of a fetus to meet its growth potential and is associated with increased perinatal mortality and morbidity. Therefore, antenatal detection of fetal growth restriction is of major importance in an attempt to deliver improved clinical outcomes. The most commonly used approach towards screening for fetal growth restriction is by means of sonographic fetal weight estimation, to detect fetuses small for gestational age, defined by an estimated fetal weight <10th percentile for gestational age. However, the predictive accuracy of this approach is limited both by suboptimal detection rate (as it may overlook non-small-for-gestational-age growth-restricted fetuses) and by a high false-positive rate (as most small-for-gestational-age fetuses are not growth restricted). Here, we review 2 strategies that may improve the diagnostic accuracy of sonographic fetal biometry for fetal growth restriction. The first strategy involves serial ultrasound evaluations of fetal biometry. The information obtained through these serial assessments can be interpreted using several different approaches including fetal growth velocity, conditional percentiles, projection-based methods, and individualized growth assessment that can be viewed as mathematical techniques to quantify any decrease in estimated fetal weight percentile, a phenomenon that many care providers assess and monitor routinely in a qualitative manner. This strategy appears promising in high-risk pregnancies where it seems to improve the detection of growth-restricted fetuses at increased risk of adverse perinatal outcomes and, at the same time, decrease the risk of falsely diagnosing healthy constitutionally small-for-gestational-age fetuses as growth restricted. Further studies are needed to determine the utility of this strategy in low-risk pregnancies as well as to optimize its performance by determining the optimal timing and interval between exams. The second strategy refers to the use of fetal body proportions to classify fetuses as either symmetric or asymmetric using 1 of several ratios; these include the head circumference to abdominal circumference ratio, transverse cerebellar diameter to abdominal circumference ratio, and femur length to abdominal circumference ratio. Although these ratios are associated with small for gestational age at birth and with adverse perinatal outcomes, their predictive accuracy is too low for clinical practice. Furthermore, these associations become questionable when other, potentially more specific measures such as umbilical artery Doppler are being used. Furthermore, these ratios are of limited use in determining the etiology underlying fetal smallness. It is possible that the use of the 2 gestational-age-independent ratios (transverse cerebellar diameter to abdominal circumference and femur length to abdominal circumference) may have a role in the detection of mild-moderate fetal growth restriction in pregnancies without adequate dating. In addition, despite their limited predictive accuracy, these ratios may become abnormal early in the course of fetal growth restriction and may therefore identify pregnancies that may benefit from closer monitoring of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Xanthine oxidase and the fetal cardiovascular defence to hypoxia in late gestation ovine pregnancy

PubMed Central

Kane, Andrew D; Hansell, Jeremy A; Herrera, Emilio A; Allison, Beth J; Niu, Youguo; Brain, Kirsty L; Kaandorp, Joepe J; Derks, Jan B; Giussani, Dino A

2014-01-01

Hypoxia is a common challenge to the fetus, promoting a physiological defence to redistribute blood flow towards the brain and away from peripheral circulations. During acute hypoxia, reactive oxygen species (ROS) interact with nitric oxide (NO) to provide an oxidant tone. This contributes to the mechanisms redistributing the fetal cardiac output, although the source of ROS is unknown. Here, we investigated whether ROS derived from xanthine oxidase (XO) contribute to the fetal peripheral vasoconstrictor response to hypoxia via interaction with NO-dependent mechanisms. Pregnant ewes and their fetuses were surgically prepared for long-term recording at 118 days of gestation (term approximately 145 days). After 5 days of recovery, mothers were infused i.v. for 30 min with either vehicle (n = 11), low dose (30 mg kg−1, n = 5) or high dose (150 mg kg−1, n = 9) allopurinol, or high dose allopurinol with fetal NO blockade (n = 6). Following allopurinol treatment, fetal hypoxia was induced by reducing maternal inspired O2 such that fetal basal decreased approximately by 50% for 30 min. Allopurinol inhibited the increase in fetal plasma uric acid and suppressed the fetal femoral vasoconstrictor, glycaemic and lactate acidaemic responses during hypoxia (all P < 0.05), effects that were restored to control levels with fetal NO blockade. The data provide evidence for the activation of fetal XO in vivo during hypoxia and for XO-derived ROS in contributing to the fetal peripheral vasoconstriction, part of the fetal defence to hypoxia. The data are of significance to the understanding of the physiological control of the fetal cardiovascular system during hypoxic stress. The findings are also of clinical relevance in the context of obstetric trials in which allopurinol is being administered to pregnant women when the fetus shows signs of hypoxic distress. PMID:24247986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freemark, M.; Comer, M.; Mularoni, T.

We have recently identified and purified from fetal liver a distinct receptor that mediates the effects of placental lactogen (PL) on amino acid transport, glycogen synthesis, and somatomedin production in fetal tissues. At present, the factors that regulate the number and affinity of PL receptors in the fetus are unknown. Since maternal nutrition plays a critical role in fetal metabolism and growth, we have examined the role of nutrition in the regulation of the PL receptor in fetal lambs. Pregnant ewes at 123-126 days gestation were fed ad libitum (FED), fasted for 3 days (FASTED), or fasted for 3 daysmore » and then refed for an additional 3 days (REFED). The ewes were then killed, and the binding of (125I)ovine (o) PL to hepatic microsomes from the fetal lambs was examined. Maternal fasting caused a 60-75% reduction in the specific binding of oPL to fetal liver; the effect of fasting was reversed in part by refeeding. The decrease in oPL binding resulted from an 80% reduction in the number of fetal oPL-binding sites (Scatchard analysis); there were no changes in the affinity of the oPL receptor (Kd, 0.6 nM), the subunit structure of the receptor, or the degree of occupancy of the receptor in vivo by endogenous fetal hormones. The specific bindings of GH (0.6%), PRL (0.3%), and insulin (35%) to fetal liver were not affected by maternal fasting, indicating that caloric restriction exerted a specific effect on oPL binding in the fetus. The number of fetal oPL-binding sites was positively correlated with the fetal liver glycogen content (r = 0.69; P less than 0.01) and the fetal plasma concentrations of glucose (r = 0.68; P less than 0.01) and insulin-like growth factor-I (r = 0.74; P less than 0.001), suggesting a role for the PL receptor in the regulation of fetal carbohydrate metabolism and growth.« less

Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123

PubMed Central

Huebner, Shane M; Blohowiak, Sharon E; Kling, Pamela J; Smith, Susan M

2016-01-01

Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disabilities, and gestational iron deficiency (ID) selectively worsens learning and neuroanatomical and growth impairments in PAE. It is unknown why ID worsens outcomes in alcohol-exposed offspring. Objective: We hypothesized that PAE alters maternal-fetal iron distribution or its regulation. Methods: Nulliparous, 10-wk-old, Long-Evans rats were mated and then fed iron-sufficient (100 mg Fe/kg) or iron-deficient (≤4 mg Fe/kg) diets. On gestational days 13.5–19.5, dams received either 5.0 g ethanol/kg body weight (PAE) or isocaloric maltodextrin by oral gavage. On gestational day 20.5, maternal and fetal clinical blood counts, tissue mineral and iron transport protein concentrations, and hepatic hepcidin mRNA expression were determined. Results: In fetal brain and liver (P < 0.001) and in maternal liver (P < 0.005), ID decreased iron (total and nonheme) and ferritin content by nearly 200%. PAE reduced fetal bodyweight (P < 0.001) and interacted with ID (P < 0.001) to reduce it by an additional 20%. Independent of maternal iron status, PAE increased fetal liver iron (30–60%, P < 0.001) and decreased brain iron content (total and nonheme, 15–20%, P ≤ 0.050). ID-PAE brains had lower ferritin, transferrin, and transferrin receptor content (P ≤ 0.002) than ID-maltodextrin brains. PAE reduced fetal hematocrit, hemoglobin, and red blood cell numbers (P < 0.003) independently of iron status. Unexpectedly, and also independent of iron status, PAE increased maternal and fetal hepatic hepcidin mRNA expression >300% (P < 0.001). Conclusions: PAE altered fetal iron distribution independent of maternal iron status in rats. The elevated iron content of fetal liver suggests that PAE may have limited iron availability for fetal erythropoiesis and brain development. Altered fetal iron distribution may partly explain why maternal ID substantially worsens growth and behavioral outcomes in PAE. PMID:27146918

Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

PubMed

Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

2011-04-01

Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2-1-kHz pulse-repetition rate and 10-16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus

PubMed Central

Phelan, Suzanne

2017-01-01

Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early life health complications and later disease. GDM recurrence is common, affecting 40–73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and pre-pregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify adiposity. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of inter-pregnancy or pre-pregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy. PMID:27487229

Regulatory Behaviors and Stress Reactivity among Infants at High Risk for Fetal Alcohol Spectrum Disorders: An Exploratory Study

ERIC Educational Resources Information Center

Jirikowic, Tracy; Chen, Maida; Nash, Jennifer; Gendler, Beth; Olson, Heather Carmichael

2016-01-01

Introduction: This article examines regulatory behaviors and physiological stress reactivity among 6-15 month-old infants with moderate to heavy prenatal alcohol exposure (PAE), a group at very high risk for fetal alcohol spectrum disorders and self-regulation impairments, compared to low risk infants with no/low exposure. Participants: Eighteen…

Fetal and perinatal exposure to drugs and chemicals: novel biomarkers of risk.

PubMed

Etwel, Fatma; Hutson, Janine R; Madadi, Parvaz; Gareri, Joey; Koren, Gideon

2014-01-01

Pregnant women are almost always excluded from randomized controlled clinical trials, as the risks to the fetus posed by most new chemical entities or approved drugs cannot be sufficiently ruled out. Hence, a major scientific challenge in this field is to discover and validate alternative tools that will fill the knowledge gap created by the lack of participation in gold-standard randomized trials. This review focuses on novel tools that allow estimation of fetal risks after exposure to therapeutic agents, such as placental perfusion studies, biomarkers of fetal exposure, and novel epidemiological and pharmacogenetic tools, all of which have been tested successfully in recent years.

Race and ethnic disparities in fetal mortality, preterm birth, and infant mortality in the United States: an overview.

PubMed

MacDorman, Marian F

2011-08-01

Infant mortality, fetal mortality, and preterm birth all represent important health challenges that have shown little recent improvement. The rate of decrease in both fetal and infant mortality has slowed in recent years, with little decrease since 2000 for infant mortality, and no significant decrease from 2003 to 2005 for fetal mortality. The percentage of preterm births increased by 36% from 1984 to 2006, and then decreased by 4% from 2006 to 2008. There are substantial race and ethnic disparities in fetal and infant mortality and preterm birth, with non-Hispanic black women at greatest risk of unfavorable birth outcomes, followed by American Indian and Puerto Rican women. Infant mortality, fetal mortality, and preterm birth are multifactorial and interrelated problems with similarities in etiology, risk factors and disease pathways. Preterm birth prevention is critical to lowering the infant mortality rate, and to reducing race and ethnic disparities in infant mortality. Published by Elsevier Inc.

Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

PubMed

Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

2015-06-01

Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by Elsevier Inc.

Can the season of birth risk factor for schizophrenia be prevented by bright light treatment for the second trimester mother around the winter solstice?

PubMed

Schwartz, Paul J

2014-12-01

The season of birth risk factor for schizophrenia exerts a pervasive effect on the global population, particularly at northerly latitudes. The winter infection hypothesis and the low vitamin D hypothesis are both compelling but lack conclusive clinical data. The present work develops a maternal-fetal chronobiological hypothesis for this season of birth risk factor and its prevention by maternal bright light treatment. Around the winter solstice, due to decreased sunlight, the chronobiological apparatus of the at-risk second trimester mother is characterized by a reduced amplitude circadian pacemaker, and a reduced maximum of her nocturnal plasma melatonin concentrations (MTmax) and an increased minimum of her nocturnal core body temperatures (Tmin)--both of which exert adverse effects on the fetal hippocampus and dorsal striatum. The consequences for the fetus include reduced volume and increased excitability of the hippocampus, ventral striatal dysfunction, increased presynaptic nigrostriatal dopamine transmission, and increased propensity for pathological nigrostriatal neuronal phasic firing. Thus, the maternal-fetal chronobiological hypothesis fully accounts for the fetal precursors of the major pathognomonic abnormalities in adults with schizophrenia. Bright light treatment for the second trimester mother around the winter solstice, by increasing maternal circadian amplitude, could possibly prevent the fetal hippocampal and striatal abnormalities and eliminate the season of birth risk factor for schizophrenia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predicting intrapartum fetal compromise using the fetal cerebro-umbilical ratio.

PubMed

Sabdia, S; Greer, R M; Prior, T; Kumar, S

2015-05-01

The aim of this study was to explore the association between the cerebro-umbilical ratio measured at 35-37 weeks and intrapartum fetal compromise. This retrospective cross sectional study was conducted at the Mater Mothers' Hospital in Brisbane, Australia. Maternal demographics and fetal Doppler indices at 35-37 weeks gestation for 1381 women were correlated with intrapartum and neonatal outcomes. Babies born by caesarean section or instrumental delivery for fetal compromise had the lowest median cerebro-umbilical ratio 1.60 (IQR 1.22-2.08) compared to all other delivery groups (vaginal delivery, emergency delivery for failure to progress, emergency caesarean section for other reasons or elective caesarean section). The percentage of infants with a cerebro-umbilical ratio <10th centile that required emergency delivery (caesarean section or instrumental delivery) for fetal compromise was 22%, whereas only 7.3% of infants with a cerebro-umbilical ratio between the 10th-90th centile and 9.6% of infants with a cerebro-umbilical ratio > 90th centile required delivery for the same indication (p < 0.001). A lower cerebro-umbilical ratio was associated with an increased risk of emergency delivery for fetal compromise, OR 2.03 (95% CI 1.41-2.92), p < 0.0001. This study suggests that a low fetal cerebro-umbilical ratio measured at 35-37 weeks is associated with a greater risk of intrapartum compromise. This is a relatively simple technique which could be used to risk stratify women in diverse healthcare settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal immune activation alters fetal brain development through interleukin-6.

PubMed

Smith, Stephen E P; Li, Jennifer; Garbett, Krassimira; Mirnics, Karoly; Patterson, Paul H

2007-10-03

Schizophrenia and autism are thought to result from the interaction between a susceptibility genotype and environmental risk factors. The offspring of women who experience infection while pregnant have an increased risk for these disorders. Maternal immune activation (MIA) in pregnant rodents produces offspring with abnormalities in behavior, histology, and gene expression that are reminiscent of schizophrenia and autism, making MIA a useful model of the disorders. However, the mechanism by which MIA causes long-term behavioral deficits in the offspring is unknown. Here we show that the cytokine interleukin-6 (IL-6) is critical for mediating the behavioral and transcriptional changes in the offspring. A single maternal injection of IL-6 on day 12.5 of mouse pregnancy causes prepulse inhibition (PPI) and latent inhibition (LI) deficits in the adult offspring. Moreover, coadministration of an anti-IL-6 antibody in the poly(I:C) model of MIA prevents the PPI, LI, and exploratory and social deficits caused by poly(I:C) and normalizes the associated changes in gene expression in the brains of adult offspring. Finally, MIA in IL-6 knock-out mice does not result in several of the behavioral changes seen in the offspring of wild-type mice after MIA. The identification of IL-6 as a key intermediary should aid in the molecular dissection of the pathways whereby MIA alters fetal brain development, which can shed new light on the pathophysiological mechanisms that predispose to schizophrenia and autism.

Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

PubMed Central

Houin, Satya S.; Rozance, Paul J.; Brown, Laura D.; Hay, William W.; Wilkening, Randall B.

2014-01-01

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 (P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 (P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia (P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia. PMID:25516551

Sertoli Cell Wt1 Regulates Peritubular Myoid Cell and Fetal Leydig Cell Differentiation during Fetal Testis Development.

PubMed

Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C Yan; Liu, Yi-Xun

2016-01-01

Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms' tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization.

Real-time fetal ECG system design using embedded microprocessors

NASA Astrophysics Data System (ADS)

Meyer-Baese, Uwe; Muddu, Harikrishna; Schinhaerl, Sebastian; Kumm, Martin; Zipf, Peter

2016-05-01

The emphasis of this project lies in the development and evaluation of new robust and high fidelity fetal electrocardiogram (FECG) systems to determine the fetal heart rate (FHR). Recently several powerful algorithms have been suggested to improve the FECG fidelity. Until now it is unknown if these algorithms allow a real-time processing, can be used in mobile systems (low power), and which algorithm produces the best error rate for a given system configuration. In this work we have developed high performance, low power microprocessor-based biomedical systems that allow a fair comparison of proposed, state-of-the-art FECG algorithms. We will evaluate different soft-core microprocessors and compare these solutions to other commercial off-the-shelf (COTS) hardcore solutions in terms of price, size, power, and speed.

Accuracy of Down syndrome risks produced in a first-trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry.

PubMed

Spencer, Kevin

2002-03-01

Over the past three years approximately 12 000 women have been screened in the first trimester through our OSCAR programme, which utilizes fetal NT and maternal serum free beta-hCG and PAPP-A. During this time 30 cases of Down syndrome were identified either prenatally or postnatally. Using an established procedure the accuracy of predicted risk for Down syndrome was assessed in a population of 30 cases of Down syndrome and 11 758 unaffected pregnancies. The correlation between predicted risk and prevalence of Down syndrome was very high (r=0.9995). It is concluded that risks produced by the Fetal Medicine Foundation combined risk algorithm agree very closely with Down syndrome prevalence and can be used with confidence when counselling women of their risk. Copyright 2002 John Wiley & Sons, Ltd.

Maternal caffeine intake during pregnancy and risk of fetal growth restriction: a large prospective observational study.

PubMed

2008-11-03

To examine the association of maternal caffeine intake with fetal growth restriction. Prospective longitudinal observational study. Two large UK hospital maternity units. 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy. Investigations Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations. Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations. Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06). Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy.

Two-stage approach for risk estimation of fetal trisomy 21 and other aneuploidies using computational intelligence systems.

PubMed

Neocleous, A C; Syngelaki, A; Nicolaides, K H; Schizas, C N

2018-04-01

To estimate the risk of fetal trisomy 21 (T21) and other chromosomal abnormalities (OCA) at 11-13 weeks' gestation using computational intelligence classification methods. As a first step, a training dataset consisting of 72 054 euploid pregnancies, 295 cases of T21 and 305 cases of OCA was used to train an artificial neural network. Then, a two-stage approach was used for stratification of risk and diagnosis of cases of aneuploidy in the blind set. In Stage 1, using four markers, pregnancies in the blind set were classified into no risk and risk. No-risk pregnancies were not examined further, whereas the risk pregnancies were forwarded to Stage 2 for further examination. In Stage 2, using seven markers, pregnancies were classified into three types of risk, namely no risk, moderate risk and high risk. Of 36 328 unknown to the system pregnancies (blind set), 17 512 euploid, two T21 and 18 OCA were classified as no risk in Stage 1. The remaining 18 796 cases were forwarded to Stage 2, of which 7895 euploid, two T21 and two OCA cases were classified as no risk, 10 464 euploid, 83 T21 and 61 OCA as moderate risk and 187 euploid, 50 T21 and 52 OCA as high risk. The sensitivity and the specificity for T21 in Stage 2 were 97.1% and 99.5%, respectively, and the false-positive rate from Stage 1 to Stage 2 was reduced from 51.4% to ∼1%, assuming that the cell-free DNA test could identify all euploid and aneuploid cases. We propose a method for early diagnosis of chromosomal abnormalities that ensures that most T21 cases are classified as high risk at any stage. At the same time, the number of euploid cases subjected to invasive or cell-free DNA examinations was minimized through a routine procedure offered in two stages. Our method is minimally invasive and of relatively low cost, highly effective at T21 identification and it performs better than do other existing statistical methods. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fetal monitoring during nonobstetric surgery: revisiting guidelines: a case report.

PubMed

Rothschild, Tod J; Morel, Bruce; Pace, Benjamin; Fuks, Aleksandr M

2015-01-01

Nonobstetric surgery during pregnancy is not an infrequent occurrence. Guidelines for fetal monitoring during nonobstetric surgery are limited. We describe a case of appendectomy during third trimester, complicated by in utero fetal demise (IUFD). A 30-year-old, Caucasian woman underwent open appendectomy for suspected acute appendicitis. The procedure was complicated by IUFD. Fetal monitoring was done prior to but not during surgery. Guidelines for fetal monitoring were revised, recommending continuous electronic fetal monitoring when possible during third trimester nonobstetric surgery after appropriate patient counseling. A subsequent series of 5 uncomplicated appendectomies demonstrated no difficulty in implementing these guidelines. Continuous electronic fetal monitoring during third trimester nonobstetric surgery should be available and implemented after appropriate patient counseling. This approach reduces the risk of fetal mortality.

Fetal growth trajectory and risk for eczema in a Saudi population.

PubMed

AlMakoshi, Amel; Ellahi, Awaiss; Sallout, Bala; Devereux, Graham; Turner, Steve

2015-12-01

Recent studies in Western cohorts have identified associations between increasing fetal abdominal circumference (AC) during mid-pregnancy and increased risk for eczema and atopy. We sought to replicate these findings in a Saudi population where antenatal environmental exposures are different compared with Western countries. A Saudi birth cohort was recruited to relate maternal dietary intake and fetal growth to wheeze, eczema, and rhinitis in the first 2 yrs. Fetal size was determined from routine ultrasound scan measurements in the second and third trimesters and birthweight was noted. Parent-reported outcomes during the first 2 yrs were acquired by telephone-administered questionnaire. There were 1076 mothers recruited. AC was determined in 562 for the second, in 632 for the third, and in 281 for both second and third trimesters. A history of eczema was determined in 814 children at 2 yrs of age. There was an inverse relationship between change in abdominal circumference between the second and third trimesters for eczema (OR 0.66 per z score increase in AC [95% CI 0.49, 0.89]), and the quartile with the greatest faltering growth were at increased risk compared with other groups (p ≤ 0.045). Change in fetal size between the third trimester and birth was not associated with altered eczema risk. There were no associations between fetal growth and wheeze at the age of 2 yrs. Our findings contrast observations made in Western populations but nonetheless suggest that factors associated with changing fetal growth trajectory in the second half of pregnancy are also relevant to atopy development on the global setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Severe hydramnios and preterm delivery in association with transient maternal diabetes insipidus.

PubMed

Weinberg, Lori E; Dinsmoor, Mara J; Silver, Richard K

2010-08-01

Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.

Effects of Cremation on Fetal Bones.

PubMed

Zana, Michela; Magli, Francesca; Mazzucchi, Alessandra; Castoldi, Elisa; Gibelli, Daniele; Caccia, Giulia; Cornacchia, Francesca; Gaudio, Daniel A; Mattia, Mirko; Cattaneo, Cristina

2017-09-01

The charring process is a weak point of anthropological analysis as it changes bone morphology and reduces information obtainable, specially in fetuses. This experiment aims at verifying the conservation of fetal bones after cremation. A total of 3138 fetuses of unknown sex and age were used, deriving from legal and therapeutic abortions from different hospitals of Milan. Cremations took place in modern crematoria. Nine cremation events were analyzed, each ranging from 57 to 915 simultaneously cremated fetuses. During the cremations, 4356 skeletal remains were recovered, 3756 of which (86.2%) were morphologically distinguishable. All types of fetal skeletal elements were found, with the exception of some cranial bones. Only 3.4% of individuals could be detected after the cremation process, because of the prevalence of abortions under 12 lunar weeks. All fire alterations were observed and the results were statistically analyzed. This pilot study confirmed the possibility of preservation of fetal skeletal elements after cremation. © 2017 American Academy of Forensic Sciences.

The effect of abused substances on antenatal and intrapartum fetal testing and well-being.

PubMed

Kopel, Ellen; Hill, Washington C

2013-03-01

Recognition that use and abuse of substances by pregnant patients perpetuates, despite ongoing efforts to educate the public, necessitates clinicians to integrate understanding of potential effects on antepartum and intrapartum fetal testing into their interpretation and implementation of clinical findings. This includes acknowledging some anticipated alterations in results and selecting the appropriate type and frequency of testing methods and interventions. Certain substances are well documented in terms of expected variations in test results; others are not as clearly defined. An overview of information that may be helpful to the clinician is presented to promote understanding of fetal evaluation performed through common tests such as contraction stress test, the nonstress test, the biophysical profile, the modified biophysical profile, fetal movement counting, and Doppler velocimetry. What evidence is available should be used to assist in defining the actual status of the fetus as best as possible, even when the effects of substances may be unknown or have obscure results.

Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

PubMed

Cooke, Gerard M

2014-01-01

The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

Fetal growth curves for an ethnically diverse military population: the American Institute of Ultrasound in Medicine-accredited platform experience.

PubMed

Elliott, Dawn; Patience, Troy; Boyd, Emily; Hume, Roderick F; Calhoun, Byron C; Napolitano, Peter G; Apodaca, Christina C

2006-06-01

To determine which fetal growth curve provided the best estimates of fetal weight for a cohort of ethnically diverse patients at sea level. The study consisted of a population of 1,729 fetuses examined at sea level between January 1, 1997, and June 30, 2000, at 18 weeks, 28 weeks, and term. Gestational age (GA) based on menstrual dates was confirmed or adjusted by crown-rump length or early second-trimester biometry. Fetal weight was estimated by using biparietal diameter, head circumference, abdominal circumference, and femur length. Our fetal growth curves were analyzed with fourth-order polynomial regression analysis, applying four previously defined formulae for fetal growth. Fetal growth curves for estimated fetal weight demonstrated the expected parabolic shape, which varied according to the formulae used. Our curve best fit the following equation: estimated fetal weight = 4.522 - 0.22 x GA age + 0.25 x GA(2) - 0.001 x GA(3) + 5.248 x 10(-6) x GA(4) (R2 = 0.976). SD increased in concordance with GA. Madigan Army Medical Center serves a racially mixed, culturally diverse, military community with unrestricted access to prenatal care. Determination of the optimal population-appropriate growth curve at the correct GA assists clinicians in identifying fetuses at risk for growth restriction or macrosomia and therefore at risk for increased perinatal morbidity and death.

Factors affecting fetal bradycardia following combined spinal epidural for labor analgesia: a matched case-control study.

PubMed

Cheng, Su Lin Maureen; Bautista, Dianne; Leo, Serene; Sia, Tiong Heng Alex

2013-04-01

The combined spinal epidural (CSE) technique for labor analgesia has become increasingly popular owing to its rapid onset of analgesia. However, incidences of fetal bradycardia following CSE have been reported. This study aimed to identify predictors of fetal bradycardia post CSE, such as a decrease in pain scores, the block height, Prostin (dinoprostone; Pfizer) use, and dosage of oxytocin. From May 2008 to October 2008, 29 patients were identified to have had an episode of fetal bradycardia. Each case was then matched to three controls, according to age and American Society of Anesthesiology status, selected from 2345 parturients who received a CSE during this period. A unit improvement in the pain score was associated with an increase in the odds of fetal bradycardia by 1.28 (95 % confidence interval [CI]: 1.02-1.60). In a second logistic regression model including sensory level higher than T9, the effect size remained consistent with an odds ratio of 1.22 (95 % CI: 0.97-1.53), supporting the theory that a higher level of sympathetic block (with a higher sensory block taken as a surrogate marker) results in an increased risk of fetal bradycardia. The dosage of oxytocin and the quantity of Prostin used were not found to be risk factors. The difference between pre- and post-CSE pain scores, and a higher sensory block height, which are surrogates for a greater degree of sympatholysis, were found to be risk factors for fetal bradycardia post CSE.

Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

PubMed

Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

2015-01-01

To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and infant death: a population-based study.

PubMed

Tennant, Peter W G; Glinianaia, Svetlana V; Bilous, Rudy W; Rankin, Judith; Bell, Ruth

2014-02-01

Pre-existing diabetes is associated with an increased risk of stillbirth, but few studies have excluded the effect of congenital anomalies. This study used data from a long-standing population-based survey of women with pre-existing diabetes to investigate the risks of fetal and infant death and quantify the contribution of glycaemic control. All normally formed singleton offspring of women with pre-existing diabetes (1,206 with type 1 diabetes and 342 with type 2 diabetes) in the North of England during 1996-2008 were identified from the Northern Diabetes in Pregnancy Survey. RRs of fetal death (≥20 weeks of gestation) and infant death were estimated by comparison with population data from the Northern Perinatal Morbidity and Mortality Survey. Predictors of fetal and infant death in women with pre-existing diabetes were examined by logistic regression. The prevalence of fetal death in women with diabetes was over four times greater than in those without (RR 4.56 [95% CI 3.42, 6.07], p < 0.0001), and for infant death it was nearly doubled (RR 1.86 [95% CI 1.00, 3.46], p = 0.046). There was no difference in the prevalence of fetal death (p = 0.51) or infant death (p = 0.70) between women with type 1 diabetes and women with type 2 diabetes. There was no evidence that the RR of fetal and infant death had changed over time (p = 0.95). Increasing periconception HbA1c concentration above 49 mmol/mol (6.6%) (adjusted odds ratio [aOR] 1.02 [95% CI 1.00, 1.04], p = 0.01), prepregnancy retinopathy (aOR 2.05 [95% CI 1.04, 4.05], p = 0.04) and lack of prepregnancy folic acid consumption (aOR 2.52 [95% CI 1.12, 5.65], p = 0.03) were all independently associated with increased odds of fetal and infant death. Pre-existing diabetes is associated with a substantially increased risk of fetal and infant death in normally formed offspring, the effect of which is largely moderated by glycaemic control.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

PubMed

Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

2013-01-01

Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

PubMed

Anton, Lauren; Olarerin-George, Anthony O; Schwartz, Nadav; Srinivas, Sindhu; Bastek, Jamie; Hogenesch, John B; Elovitz, Michal A

2013-11-01

Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P < 0.0001, area under the receiver operator curve = 0.89). Hence, we conclude that aberrant expression of miR-210 may contribute to trophoblast function and that miR-210 is a novel predictive serum biomarker for preeclampsia that can help in identifying at-risk women for monitoring and treatment. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

PubMed Central

Goetzl, Laura

2010-01-01

Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons1

PubMed Central

Pantham, Priyadarshini; Rosario, Fredrick J.; Weintraub, Susan T.; Nathanielsz, Peter W.; Powell, Theresa L.; Li, Cun; Jansson, Thomas

2016-01-01

Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n = 8) or MNR diet (70% of control diet, n = 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P = 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P < 0.05) in MNR fetuses compared to controls. In this primate model of IUGR, placental MVM system A amino acid transporter activity is decreased prior to the onset of reduction in the fetal growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced placental amino acid transport may be a cause rather than a consequence of IUGR due to inadequate maternal nutrition. PMID:27605346

Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons.

PubMed

Pantham, Priyadarshini; Rosario, Fredrick J; Weintraub, Susan T; Nathanielsz, Peter W; Powell, Theresa L; Li, Cun; Jansson, Thomas

2016-11-01

Intrauterine growth restriction (IUGR) is an important risk factor for perinatal complications and adult disease. IUGR is associated with down-regulation of placental amino acid transporter expression and activity at birth. It is unknown whether these changes are a cause or a consequence of human IUGR. We hypothesized that placental amino acid transport capacity is reduced prior to onset of reduced fetal growth in baboons with maternal nutrient restriction (MNR). Pregnant baboons were fed either a control (n = 8) or MNR diet (70% of control diet, n = 9) from Gestational Day 30. At Gestational Day 120 (0.65 of gestation), fetuses and placentas were collected. Microvillous (MVM) and basal (BM) plasma membrane vesicles were isolated. System A and system L transport activity was determined in MVM, and leucine transporter activity was assessed in BM using radiolabeled substrates. MVM amino acid transporter isoform expression (SNAT1, SNAT2, and SNAT4 and LAT1 and LAT2) was measured using Western blots. LAT1 and LAT2 expression were also determined in BM. Maternal and fetal plasma amino acids concentrations were determined using mass spectrometry. Fetal and placental weights were unaffected by MNR. MVM system A activity was decreased by 37% in MNR baboon placentas (P = 0.03); however MVM system A amino acid transporter protein expression was unchanged. MVM system L activity and BM leucine transporter activity were not altered by MNR. Fetal plasma concentrations of essential amino acids isoleucine and leucine were reduced, while citrulline increased (P < 0.05) in MNR fetuses compared to controls. In this primate model of IUGR, placental MVM system A amino acid transporter activity is decreased prior to the onset of reduction in the fetal growth trajectory. The reduction in plasma leucine and isoleucine in MNR fetuses may be caused by reduced activity of MVM system A, which is strongly coupled with system L essential amino acid uptake. Our findings indicate that reduced placental amino acid transport may be a cause rather than a consequence of IUGR due to inadequate maternal nutrition. © 2016 by the Society for the Study of Reproduction, Inc.

Isolated Complete Heart Block in the Fetus.

PubMed

Ho, Andrew; Gordon, Patrick; Rosenthal, Eric; Simpson, John; Miller, Owen; Sharland, Gurleen

2015-07-01

Isolated congenital complete heart block (CCHB) is a rare disease with significant associated morbidity and mortality. A diagnosis is often made in fetal life, but data regarding long-term outcomes are limited, and fetal therapy to improve prognosis is controversial. In our institution, 85 fetuses were diagnosed with CCHB from 1981 to 2013 in 80 mothers. There were 37 anti-Ro-positive pregnancies, 36 both anti-Ro and anti-La positive, 10 antibody negative, and 2 of unknown antibody status. Antenatal treatments were given in 14 fetuses, with 8 given fluorinated steroids, 4 beta sympathomimetics, and both in 2. Of the original 85, 74 babies survived to delivery. Fetal hydrops was the only risk factor found to be significantly associated with intrauterine death (p <0.001). Four babies died before pacemaker implantation, 56 have had pacemakers implanted, and 14 are pacemaker free. The Kaplan-Meier estimate for median time to pacemaker implantation was 2.6 years, with 15 implanted in the neonatal period. There have been 14 postnatal deaths, with a Kaplan-Meier estimate of survival at 30 years of 76.8% (95% confidence interval 65% to 90%). Dilated cardiomyopathy was uncommon, occurring in 6 patients. Prematurity and hydrops were associated with increased postnatal mortality (p = 0.02 and 0.005, respectively). In conclusion, we present the largest single-unit experience of prenatally diagnosed CCHB in the published literature. Our cohort was conservatively managed, with survival similar to those previously published. These data offer insight into the long-term natural history of CCHB. Copyright © 2015 Elsevier Inc. All rights reserved.

Electronic fetal monitoring: family medicine obstetrics.

PubMed

Rodney, John R M; Huntley, Benjamin J F; Rodney, Wm Macmillan

2012-03-01

Electronic fetal monitoring assesses fetal health during the prenatal and intrapartum process. Intermittent auscultation does not detect key elements of fetal risk, such as beat-to-beat variability. Family medicine obstetric fellowships have contributed new knowledge to this process by articulating a method of analysis that builds on evidence-based recommendations from the American College of Obstetrics and Gynecology as well as the National Institute of Child Health and Development. This article summarizes the development, interpretation, and management of electronic fetal heart rate patterns and tracings. Copyright © 2012 Elsevier Inc. All rights reserved.

The Contribution of Fetal Drug Exposure to Temperament: Potential Teratogenic Effects on Neuropsychiatric Risk

ERIC Educational Resources Information Center

Weiss, Sandra J.; St. Jonn-Seed, Mary; Harris-Muchell, Carolyn

2007-01-01

Background: Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. Methods: High risk children (n = 120) were followed from…

Intelligent Structured Intermittent Auscultation (ISIA): evaluation of a decision-making framework for fetal heart monitoring of low-risk women

PubMed Central

2014-01-01

Background Research-informed fetal monitoring guidelines recommend intermittent auscultation (IA) for fetal heart monitoring for low-risk women. However, the use of cardiotocography (CTG) continues to dominate many institutional maternity settings. Methods A mixed methods intervention study with before and after measurement was undertaken in one secondary level health service to facilitate the implementation of an initiative to encourage the use of IA. The intervention initiative was a decision-making framework called Intelligent Structured Intermittent Auscultation (ISIA) introduced through an education session. Results Following the intervention, medical records review revealed an increase in the use of IA during labour represented by a relative change of 12%, with improved documentation of clinical findings from assessments, and a significant reduction in the risk of receiving an admission CTG (RR 0.75, 95% CI, 0.60 – 0.95, p = 0.016). Conclusion The ISIA informed decision-making framework transformed the practice of IA and provided a mechanism for knowledge translation that enabled midwives to implement evidence-based fetal heart monitoring for low risk women. PMID:24884597

Human prenatal diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filkins, K.; Russo, J.F.

Advances in the field of prenatal diagnosis have been rapid during the past decade. Moreover, liberal use of birth control methods and restriction of family size have placed greater emphasis on optimum outcome of each pregnancy. There are many prenatal diagnostic techniques of proven value; the risks, including false negatives and false positives, are known. With the rapid proliferation of new and experimental techniques, many disorders are potential diagnosable or even treatable; however, risk factors are unknown and issues relating to quality control have not been resolved. These problems are readily appreciated in the dramatic new techniques involving recombinant DNA,more » chorion villus sampling, and fetal surgery. Unfortunately, clinicians may not appreciate the difficulties that may also be encountered in the more mundane prenatal diagnostic tests such as ultrasonography or enzymatic testing. The aim of this volume is to clarify and rationalize certain aspects of diagnosis, genetic counseling, and intervention. New and experimental techniques are presented in the light of current knowledge.« less

Amnioinfusion for umbilical cord compression in labour.

PubMed

Hofmeyr, G J

2000-01-01

Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by infusing a solution into the uterine cavity. The objective of this review was to assess the effects of amnioinfusion on maternal and perinatal outcome for potential or suspected umbilical cord compression or potential amnionitis. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials of amnioinfusion compared with no amnioinfusion in women with babies at risk of umbilical cord compression; and women at risk of intrauterine infection. Eligibility and trial quality were assessed by the reviewer. Twelve studies were included. Transcervical amnioinfusion for potential or suspected umbilical cord compression was associated with the following reductions: fetal heart rate decelerations (relative risk 0.54, 95% confidence interval 0.43 to 0.68); caesarean section for suspected fetal distress (relative risk 0.35, 95% confidence interval 0.24 to 0.52); neonatal hospital stay greater than 3 days (relative risk 0.40, 95% confidence interval 0. 26 to 0.62); maternal hospital stay greater than 3 days (relative risk 0.46, 95% 0.29 to 0.74). Transabdominal amnioinfusion showed similar results. Transcervical amnioinfusion to prevent infection in women with membranes ruptured for more than 6 hours was associated with a reduction in puerperal infection (relative risk 0.50, 95% confidence interval 0.26 to 0.97). Amnioinfusion appears to reduce the occurrence of variable heart rate decelerations and lower the use of caesarean section. However the studies were done in settings where fetal distress was not confirmed by fetal blood sampling. The results may therefore only be relevant where caesarean sections are commonly done for abnormal fetal heart rate alone. The trials reviewed are too small to address the possibility of rare but serious maternal adverse effects of amnioinfusion.

PP032. Apolipoprotein profiling in umbilical cord blood of intrauterine growth restricted (IUGR) neonates.

PubMed

Pecks, Ulrich; Wölter, Manja; Borchers, Christoph; Smith, Derek; Maass, Nicolai; Glocker, Michael; Rath, Werner

2013-04-01

Fetal umbilical cord HDL concentration is lower in IUGR neonates as compared to gestational age matched controls (CTRL). The causes by now are unknown. A full apolipoprotein analysis of cord blood might help in understanding the changes in lipid metabolism seen in IUGR. To characterize cord blood apolipoprotein profile of IUGR neonates. Serum of venous umbilical cord blood (15 IUGR vs. 15 CTRL) was analyzed by Multiple Reaction Monitoring (MRM). 15 different known apolipoproteins were profiled. HDL and LDL were measured by colorimetric methods in fetal cord blood and their corresponding mothers. Fetal HDL (p<0.0001), ApoC1 (p<0.0001), and ApoE (p=0.0001) levels were lower in IUGR as compared to CTRL. Fetal HDL levels were positive correlated to ApoE, ApoC1, and ApoA2 (r=0.79, r=0.74, r=0.56). Fetal LDL levels were positive correlated to ApoB, ApoE, ApoA2, and ApoC3 (r=0.74, r=0.67, r=0.57, r=0.55). Maternal LDL concentrations correlated positive to fetal ApoC1, ApoC2, and LCAT-concentration (r=0.54, r=0.52, r=0.52). The results underlines the relevance of ApoE in fetal development. Moreover, we speculate that maternal lipid profile has an impact on fetal lipid metabolisms as evidenced by the association of maternal LDL levels and fetal ApoC1, ApoC2, and LCAT concentrations. This observation requires further confirmation and is worth to be analyzed since it provides a mechanistic link for therapeutic options. Copyright © 2013. Published by Elsevier B.V.

[Zika virus infection during pregnancy].

PubMed

Picone, O; Vauloup-Fellous, C; D'Ortenzio, E; Huissoud, C; Carles, G; Benachi, A; Faye, A; Luton, D; Paty, M-C; Ayoubi, J-M; Yazdanpanah, Y; Mandelbrot, L; Matheron, S

2016-05-01

A Zika virus epidemic is currently ongoing in the Americas. This virus is linked to congenital infections with potential severe neurodevelopmental dysfunction. However, incidence of fetal infection and whether this virus is responsible of other fetal complications are still unknown. National and international public health authorities recommend caution and several prevention measures. Declaration of Zika virus infection is now mandatory in France. Given the available knowledge on Zika virus, we suggest here a review of the current recommendations for management of pregnancy in case of suspicious or infection by Zika virus in a pregnant woman. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Fetal Neurobehavioral Development: A Tale of Two Cities.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Caulfield, Laura; Costigan, Kathleen A.; Merialdi, Mario; Nguyen, Ruby H. N.; Zavaleta, Nelly; Gurewitsch, Edith D.

2004-01-01

Longitudinal neurobehavioral development was examined in 237 fetuses of low-risk pregnancies from 2 distinct populations-Baltimore, Maryland, and Lima, Peru-at 20, 24, 28, 32, 36, and 38 weeks gestation. Data were based on digitized Doppler-based fetal heart rate (FHR) and fetal movement (FM). In both groups, FHR declined while variability,…

Cholera in pregnancy: outcomes from a specialized cholera treatment unit for pregnant women in Léogâne, Haiti.

PubMed

Ciglenecki, Iza; Bichet, Mathieu; Tena, Javier; Mondesir, Erneau; Bastard, Mathieu; Tran, Nguyen-Toan; Antierens, Annick; Staderini, Nelly

2013-01-01

The association between cholera in pregnancy and negative fetal outcome has been described since the 19(th) century. However, there is limited published literature on the subject. We describe pregnancy outcomes from a specialized multidisciplinary hospital unit at the onset of a large cholera outbreak in Haiti in 2010 and 2011. Pregnant women with cholera were hospitalized in a specialized unit within the MSF hospital compound in Léogâne and treated using standard cholera treatment guidelines but with earlier, more intense fluid replacement. All women had intravenous access established at admission regardless of their hydration status, and all received antibiotic treatment. Data were collected on patient demographics, pregnancy and cholera status, and pregnancy outcome. In this analysis we calculated risk ratios for fetal death and performed logistic regression analysis to control for confounding factors. 263 pregnant women with cholera were hospitalized between December 2010 and July 2011. None died during hospitalization, 226 (86%) were discharged with a preserved pregnancy and 16 (6%) had live fullterm singleton births, of whom 2 died within the first 5 days postpartum. The remaining 21 pregnancies (8%) resulted in intrauterine fetal death. The risk of fetal death was associated with factors reflecting severity of the cholera episode: after adjusting for confounding factors, the strongest risk factor for fetal death was severe maternal dehydration (adjusted risk ratio for severe vs. mild dehydration was 9.4, 95% CI 2.5-35.3, p = 0.005), followed by severe vomiting (adjusted risk ratio 5.1, 95% 1.1-23.8, p = 0.041). This is the largest cohort of pregnant women with cholera described to date. The main risk factor identified for fetal death was severity of dehydration. Our experience suggests that establishing specialized multidisciplinary units which facilitate close follow-up of both pregnancy and dehydration status due to cholera could be beneficial for patients, especially in large epidemics.

Prenatal diagnosis of congenital fetal heart abnormalities and clinical analysis.

PubMed

Li, Hui; Wei, Jun; Ma, Ying; Shang, Tao

2005-09-01

To study the value of detecting fetal congenital heart disease (CHD) using the five transverse planes technique of fetal echocardiography. Nine hundred and eighty-two high-risk pregnancies for fetal CHD were included in this study, the fetal heart was scanned with the five transverse planes technique of fetal echocardiography described by Yagel, autopsy was conducted when pregnancy was terminated. Blood from fetal heart was collected for fetal chromosome analysis. A close follow-up was given for normal fetal heart pregnancies and neonatal echocardiography was performed to check the accuracy of prenatal diagnosis. (1) Forty-six cases (4.68%) were found to have fetal heart abnormalities in this study, 69.56% of them were diagnosed by single four-chamber view, another 30.43% fetal CHD were found by combining other views; (2) Forty-one parents of prenatal fetuses with CHD chose to terminate pregnancy, thirty-two of them gave consent to conduct autopsy, 93.75% of which yielded unanimous conclusion between prenatal fetal echocardiography and autopsy; (3) Thirty-two of 46 cases underwent fetal chromosome analysis, 8 cases (25%) were found to have abnormal chromosome; (4) Five cases were found to have right ventricle and atrium a little bigger than those on the left side, with the unequal condition being the same after birth, but there were no clinical manifestations and they are healthy for the time being; (5) Nine hundred and thirty-six cases were not found with abnormality in this study, but one case was diagnosed with ventricular septal defect after birth, one case was diagnosed with patent ductus arteriosus, one case had atrial septal defect after birth. (1) The detected CHD rate was 4.68% by screening fetal heart with five transverse planes according to Yagel's description of high risk population basis for CHD. The coinciding rate of prenatal diagnosis and autopsy was 93.75%; (2) The sensitivity of detecting fetal heart abnormality is 92%, the specificity is 99.6% using the five transverse planes technique of fetal echocardiography; (3) Fetuses with mild or moderate disproportion of right and left side in the heart are potentially healthy babies.

Radiotherapy for glioma during pregnancy: fetal dose estimates, risk assessment and clinical management.

PubMed

Haba, Y; Twyman, N; Thomas, S J; Overton, C; Dendy, P; Burnet, N G

2004-05-01

Cancer in pregnancy is relatively uncommon, but constitutes a major problem. We report the measurement of scatter dose to the fetus and the estimated fetal risk from that exposure in an illustrative case of a patient, 20 weeks pregnant, with a grade 3 anaplastic astrocytoma. A clinical decision was made to withhold radiotherapy, if possible, until after delivery. Sequential magnetic resonance imaging (MRI) showed no progression during the pregnancy. In the event, she was managed conservatively until the successful completion of her pregnancy. In case radiotherapy was required, an estimation of the fetal risk was made. Phantom measurements were undertaken to assess the likely fetal dose. Film badges were used to estimate the scattered radiation energy. Measurements were made on a Varian 600C at 6 MV and Asea Brown Boveri (ABB) accelerator at 8 and 16 MV. Doses were measured at 30, 45 and 60 cm from the isocentre; the fetus was assumed to lie at about 60 cm and not closer than 45 cm from the isocentre. Estimated doses to the position of the fetus were lowest with the 6 MV Varian accelerator. Using this machine without additional abdominal shielding, the estimated dose on the surface at 45 cm from the tumour volume was 2.2 cGy for a tumour dose of 54 Gy; using the ABB accelerator, the dose varied between 49-59 cGy. The energy of scattered radiation was in the range 208-688 keV, so that additional shielding would be practical to further reduce the fetal dose. The risk of cancer up to the age of 15 years attributable to radiation is 1 in 1700 per cGy, of which half will be fatal (i.e. 1 in 3300 per cGy). A dose of 2.2 cGy adds a risk of fatal cancer by the age 15 years of only 1 in 1500. Because the addition of shielding might halve the fetal dose, this risk should be reduced to 1 in 3000. For comparison, the overall UK risk of cancer up to the age 15 years is 1 in 650. In conclusion, careful choice of linear accelerator for the treatment of a pregnant woman and the use of additional shielding is valuable, as this can dramatically affect fetal dose.

Putting intelligent structured intermittent auscultation (ISIA) into practice.

PubMed

Maude, Robyn M; Skinner, Joan P; Foureur, Maralyn J

2016-06-01

Fetal monitoring guidelines recommend intermittent auscultation for the monitoring of fetal wellbeing during labour for low-risk women. However, these guidelines are not being translated into practice and low-risk women birthing in institutional maternity units are increasingly exposed to continuous cardiotocographic monitoring, both on admission to hospital and during labour. When continuous fetal monitoring becomes routinised, midwives and obstetricians lose practical skills around intermittent auscultation. To support clinical practice and decision-making around auscultation modality, the intelligent structured intermittent auscultation (ISIA) framework was developed. The purpose of this discussion paper is to describe the application of intelligent structured intermittent auscultation in practice. The intelligent structured intermittent auscultation decision-making framework is a knowledge translation tool that supports the implementation of evidence into practice around the use of intermittent auscultation for fetal heart monitoring for low-risk women during labour. An understanding of the physiology of the materno-utero-placental unit and control of the fetal heart underpin the development of the framework. Intelligent structured intermittent auscultation provides midwives with a robust means of demonstrating their critical thinking and clinical reasoning and supports their understanding of normal physiological birth. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep.

PubMed

Wang, Qiming; Gold, Nathan; Frasch, Martin G; Huang, Huaxiong; Thiriet, Marc; Wang, Xiaogang

2015-12-01

Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation.

Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2.

PubMed

Rosario, Fredrick J; Dimasuay, Kris Genelyn; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

2016-04-01

Changes in placental amino acid transfer directly contribute to altered fetal growth, which increases the risk for perinatal complications and predisposes for the development of obesity, diabetes and cardiovascular disease later in life. Placental amino acid transfer is critically dependent on the expression of specific transporters in the plasma membrane of the trophoblast, the transporting epithelium of the human placenta. However, the molecular mechanisms regulating this process are largely unknown. Nedd4-2 is an ubiquitin ligase that catalyses the ubiquitination of proteins, resulting in proteasomal degradation. We hypothesized that inhibition of mechanistic target of rapamycin complex 1 (mTORC1) decreases amino acid uptake in primary human trophoblast (PHT) cells by activation of Nedd4-2, which increases transporter ubiquitination resulting in decreased transporter expression in the plasma membrane. mTORC 1 inhibition increased the expression of Nedd4-2, promoted ubiquitination and decreased the plasma membrane expression of SNAT2 (an isoform of the System A amino acid transporter) and LAT1 (a System L amino acid transporter isoform), resulting in decreased cellular amino acid uptake. Nedd4-2 silencing markedly increased the trafficking of SNAT2 and LAT1 to the plasma membrane, which stimulated cellular amino acid uptake. mTORC1 inhibition by silencing of raptor failed to decrease amino acid transport following Nedd4-2 silencing. In conclusion, we have identified a novel link between mTORC1 signalling and ubiquitination, a common posttranslational modification. Because placental mTORC1 is inhibited in fetal growth restriction and activated in fetal overgrowth, we propose that regulation of placental amino acid transporter ubiquitination by mTORC1 and Nedd4-2 constitutes a molecular mechanisms underlying abnormal fetal growth. © 2016 Authors; published by Portland Press Limited.

[Prenatal diagnosis and treatment of fetal choroid plexus cysts].

PubMed

Liang, Mei-Ying; Wang, Hong-Bin; Huang, Xin; Wei, Yan-Qiu

2007-09-01

To discuss the clinical management and significance of the prenatal diagnosis of Fetal Choroid Plexus Cysts (CPC). From May 2004 to March 2007, 55 cases of fetal CPC diagnosed by B-ultrasound during second trimester were prospectively studied. Each case was studied regarding fetal chromosome karyotype, disappearance weeks of the cyst, the clinical outcome and follow-up results respectively. The cases were diagnosed during 16 - 25 gestational weeks. The diameters of the cysts varied from 0.2 cm to 2.4 cm. There were 25 cases of bilateral cysts and 30 cases of unilateral or 50 cases of isolated CPC and 5 cases of complicated CPC. The cysts of all cases who continued pregnancy disappeared before 28 weeks. Fetal chromosome karyotypes were obtained in 50 cases. Among them, two cases were 18-trisomy, and one case was 21-trisomy. Five cases were terminated pregnancy because of abnormal chromosome karyotype or malformation during second trimester. One neonate was diagnosed as ventricular septal defect among 50 cases of follow up. Among these six cases, three were from advanced-age pregnant women, five cases were with abnormal fetal structure and five cases were with the diameter of bilateral or unilateral cysts more than 1.0 cm. (1) Fetal CPC can be diagnosed during second trimester, and the majority disappear before 28 gestational weeks. (2) High risk factors for fetal abnormal chromosome karyotype may be: advanced-age pregnant women, abnormal structure of fetus, and the diameter of bilateral or unilateral cyst more than 1.0 cm. It is suggested that fetal CPC with the high risks should receive fetal chromosome karyotype test during pregnancy.

Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study.

PubMed

Parvez, S; Gerona, R R; Proctor, C; Friesen, M; Ashby, J L; Reiter, J L; Lui, Z; Winchester, P D

2018-03-09

Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = - 0.28, p = 0.02). This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.

Maternal predictive factors for fetal congenital heart block in pregnant mothers positive for anti-SS-A antibodies.

PubMed

Tsuboi, Hiroto; Sumida, Takayuki; Noma, Hisashi; Yamagishi, Kazumasa; Anami, Ai; Fukushima, Kotaro; Horigome, Hitoshi; Maeno, Yasuki; Kishimoto, Mitsumasa; Takasaki, Yoshinari; Nakayama, Masahiro; Waguri, Masako; Sago, Haruhiko; Murashima, Atsuko

2016-07-01

To determine the maternal predictive factors for fetal congenital heart block (CHB) in pregnancy in mothers positive for anti-SS-A antibodies. The Research Team for Surveillance of Autoantibody-Exposed Fetuses and Treatment of Neonatal Lupus Erythematosus, the Research Program of the Japan Ministry of Health, Labor and Welfare, performed a national survey on pregnancy of mothers positive for anti-SS-A antibodies. We analyzed 635 pregnant mothers who tested positive for anti-SS-A antibodies before conception but had no previous history of fetal CHB. We performed univariate and multivariate analysis (models 1, 2, and 3 using different set of independent variables) investigated the relation between risk of fetal CHB and maternal clinical features. Of the 635 pregnant mothers, fetal CHB was detected in 16. Univariate analysis showed that fetal CHB associated with use of corticosteroids before conception (OR 3.72, p = 0.04), and negatively with use of corticosteroids (equivalent doses of prednisolone (PSL), at ≥10 mg/day) after conception before 16-week gestation (OR 0.17, p = 0.03). In multivariate analysis, model 1 identified the use of corticosteroids before conception (OR 4.28, p = 0.04) and high titer of anti-SS-A antibodies (OR 3.58, p = 0.02) as independent and significant risk factors, and model 3 identified use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as independent protective factor against the development of fetal CHB (OR 0.16, p = 0.03). Other maternal clinical features did not influence the development of fetal CHB. The results identified high titers of anti-SS-A antibodies and use of corticosteroids before conception as independent risk factors, and use of corticosteroids (equivalent doses of PSL, at ≥10 mg/day) after conception before 16-week gestation as an independent protective factor for fetal CHB.

Accidental fetal lacerations during cesarean delivery: experience in an Italian level III university hospital.

PubMed

Dessole, Salvatore; Cosmi, Erich; Balata, Antonio; Uras, Luisa; Caserta, Donatella; Capobianco, Giampiero; Ambrosini, Guido

2004-11-01

The purpose of this study was to investigate the incidence, type, location, and risk factors of accidental fetal lacerations during cesarean delivery. Total deliveries, cesarean deliveries, and neonatal records for documented accidental fetal lacerations were reviewed retrospectively in our level III university hospital. The gestational age, the presenting part of the fetus, the cesarean delivery indication, the type of incision, and the surgeon who performed the procedure were recorded. Cesarean deliveries were divided into scheduled, unscheduled, and emergency procedures. Fetal lacerations were divided into mild, moderate, and severe. Neonatal follow-up examinations regarding laceration sequelae were available for 6 months. Of 14926 deliveries, 3108 women were delivered by cesarean birth (20.82%). Neonatal records documented 97 accidental fetal lacerations. Of these accidental lacerations, 94 were mild; 2 were moderate, and 1 was severe. The overall rate of accidental fetal laceration per cesarean delivery was 3.12%; the accidental laceration rate in the cohort of fetuses was 2.46%. The crude odds ratios were 0.34 for scheduled procedures, 0.57 for unscheduled procedures, and 1.7 for emergency procedures. The risk for fetal accidental lacerations was higher in fetuses who underwent emergency cesarean birth and lower for unscheduled and scheduled cesarean births (P < .001). Fetal accidental laceration may occur during cesarean delivery; the incidence is significantly higher during emergency cesarean delivery compared with elective procedures. The patient should be counseled about the occurrence of fetal laceration during cesarean delivery to avoid litigation.

Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

PubMed

Spiroski, A-M; Oliver, M H; Harding, J E; Bloomfield, F H

2016-01-01

Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

[The effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction: a cohort study].

PubMed

Shi, M Y; Wang, Y F; Huang, K; Yan, S Q; Ge, X; Chen, M L; Hao, J H; Tong, S L; Tao, F B

2017-12-06

Objective: To investigate the effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Methods: From May 2013 to September 2014, a total of 3 474 pregnant women who took their first antenatal care and willing to undergo their prenatal care and delivery in Ma 'anshan Maternity and Child Care Centers were recruited in the cohort study. Excluding subjects without weight data before delivery ( n= 54), pregnancy termination ( n= 162), twins live births ( n= 39), without fetal birth weight data ( n= 7), 3 212 maternal-singleton pairs were enrolled for the final data analysis. Demographic information of pregnant woman, pregnancy history, disease history, height and weight were collected. In the 24(th)-28(th), 32(nd)-36(th) gestational week and childbirth, three follow-up visits were undertaken to collect data of pregnancy weight, pregnancy vomiting, gestational hypertension, gestational diabetes mellitus, newborn gender and birth weight. χ(2) test was used to compare the detection rate of fetal growth restriction in different groups. Multivariate unconditional logistic regression model and spreadsheet were used to analyze the independent and interaction effect of pre-pregnancy weight and the increase of gestational weight on fetal growth restriction. Results: The incidence of fetal growth restriction was 9.7%(311/3 212). The incidence of fetal growth restriction in pre-pregnancy underweight group was 14.9% (90/603), higher than that in normal pre-pregnancy weight group (8.7% (194/2 226)) (χ(2)=24.37, P< 0.001). The incidence of fetal growth restriction in inadequate increase of gestational weight group was 17.9% (50/279), higher than the appropriate increase of weight group (11.8% (110/932)) (χ(2)=36.89, P< 0.001). Multivariate unconditional logistic regression analysis showed that compared with normal pre-pregnancy weight group, pre-pregnancy underweightwas a risk factor for fetal growth restriction, with RR (95 %CI ) at 1.76 (1.34-2.32); Compared with the appropriate increase of gestational weight group, inadequate weight increase during pregnancy was a risk factor for fetal growth restriction, with the RR (95 %CI ) at 1.70 (1.17-2.48). No additive model interaction [relative excess risk of interaction, attributable proportions of interaction, the synergy index and their 95 %CI were 0.75 (-2.14-3.63), 0.21 (-0.43-0.86) and 1.43 (0.45-4.53), respectively] or multiplication model interaction ( RR (95 %CI ): 1.00 (0.44-2.29)) existed between pre-pregnancy underweight and inadequate increase of gestational weight on fetal growth restriction. Conclusion: Pre-pregnancy underweight and inadequate increase of gestational weight would increase the risk of fetal growth restriction without interaction.

Fetal-maternal erythrocyte distribution

MedlinePlus

... under the skin) Infection (a slight risk any time the skin is broken) Alternative Names Kleihauer-Betke stain; Flow cytometry - fetal-maternal erythrocyte distribution; Rh incompatibility - erythrocyte distribution References Chernecky CC, Berger ...

Anesthesia for fetal surgery.

PubMed

Hoagland, Monica A; Chatterjee, Debnath

2017-04-01

Fetal therapy is an exciting and growing field of medicine. Advances in prenatal imaging and continued innovations in surgical and anesthetic techniques have resulted in a wide range of fetal interventions including minimally invasive, open mid-gestation, and ex-utero intrapartum treatment procedures. The potential for maternal morbidity is significant and must be carefully weighed against claimed benefits to the fetus. Appropriate patient selection is critical, and a multidisciplinary team-based approach is strongly recommended. The anesthetic management should focus on maintaining uteroplacental circulation, achieving profound uterine relaxation, optimizing surgical conditions, monitoring fetal hemodynamics, and minimizing maternal and fetal risk. © 2017 John Wiley & Sons Ltd.

Fetal metabolic influences of neonatal anthropometry and adiposity.

PubMed

Donnelly, Jean M; Lindsay, Karen L; Walsh, Jennifer M; Horan, Mary; Molloy, Eleanor J; McAuliffe, Fionnuala M

2015-11-10

Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring. Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity. Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant. Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

Noninvasive Antenatal Determination of Fetal Blood Group Using Next-Generation Sequencing

PubMed Central

Rieneck, Klaus; Clausen, Frederik Banch; Dziegiel, Morten Hanefeld

2016-01-01

Hemolytic disease of the fetus and newborn (HDFN) is a condition characterized by a decreased lifespan of fetal red blood cells caused by maternally produced allospecific antibodies transferred to the fetus during pregnancy. The antibodies bind to the corresponding blood group antigens on fetal red blood cells and induce hemolysis. Cell-free DNA derived from the conceptus circulates in maternal blood. Using next-generation sequencing (NGS), it can be determined if this cell-free fetal DNA encodes the corresponding blood group antigen that is the target of the maternal allospecific antibodies. This determination carries no risk to the fetus. It is important to determine if the fetus is at risk of hemolysis to enable timely intervention. Many tests for blood groups are based solely on the presence or absence of a single nucleotide polymorphism (SNP). Antenatal determination of fetal blood group by NGS analysis holds advantages over polymerase chain reaction (PCR) determination based on allele specific amplification. PMID:26511760

Customized Versus Population Approach for Evaluation of Fetal Overgrowth

PubMed Central

COSTANTINE, Maged M.; MELE, Lisa; LANDON, Mark B.; SPONG, Catherine Y.; RAMIN, Susan M.; CASEY, Brian; WAPNER, Ronald J.; VARNER, Michael W.; ROUSE, Dwight J.; THORP, John M.; SCISCIONE, Anthony; CATALANO, Patrick; CARITIS, Steve N.; SOROKIN, Yoram; PEACEMAN, Alan M.; TOLOSA, Jorge E.; ANDERSON, Garland D.

2013-01-01

Objective To compare the ability of customized versus normalized population fetal growth norms in identifying neonates at risk for adverse perinatal outcomes (APOs) associated with fetal overgrowth and gestational diabetes (GDM). Study Design Secondary analysis of a multicenter treatment trial of mild GDM. The primary outcome was a composite of neonatal outcomes associated with fetal overgrowth and GDM. Birthweight percentiles were calculated using ethnicity- & gender-specific population norms and customized norms (Gardosi). Results 203 (9.8%) and 288 (13.8%) neonates were LGA by population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and LGAcust were associated with the primary outcome and neonatal hyperinsulinemia, while neither was associated with hypoglycemia or hyperbilirubinemia. The ability of customized and population birthweight percentiles for predicting APOs were poor (receiver operating characteristic area under the curve <0.6 for 6 out of 8 APOs). Conclusion Neither customized nor normalized-population norms better identify neonates at risk of APOs related to fetal overgrowth and GDM. PMID:23147078

Intermittent auscultation of fetal heart rate during labour - a widely accepted technique for low risk pregnancies: but are the current national guidelines robust and practical?

PubMed

Sholapurkar, S L

2010-01-01

Intermittent auscultation of fetal heart rate is an accepted practice in low risk labours in many countries. National guidelines on intrapartum fetal monitoring were critically reviewed regarding timing and frequency of intermittent auscultation. Hypothetical but plausible examples are presented to illustrate that it may be possible to miss significant fetal distress with strict adherence to current guidelines. Opinion is forwarded that intermittent auscultation should be performed for 60 seconds before and after three contractions over about 10 min every half an hour in the first stage of labour. Reasons are put forward to show how this could be more practical and patient friendly and at the same time could improve detection of fetal distress. The current recommendation of intermittent auscultation every 15 min in the first stage is associated with poor compliance and leads to unnecessary burden, stress and medicolegal liability for birth attendants. Modification of current national guidelines would be desirable.

Naturally conceived twins with monochorionic placentation have the highest risk of fetal loss.

PubMed

Sperling, L; Kiil, C; Larsen, L U; Qvist, I; Schwartz, M; Jørgensen, C; Skajaa, K; Bang, J; Tabor, A

2006-10-01

The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception. In a prospective multicenter observational study women with a twin pregnancy had an ultrasound scan before 14 + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the perinatal, neonatal and infant mortality rates and the frequency of very preterm labor were estimated for the different types of twin. Among the 495 pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%) by assisted reproduction (AR). Outcome data for 945 liveborn babies were obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9% (7/64) among naturally conceived MC compared to 3.0% (5/165) for naturally conceived DC twins (P < 0.05). For twins conceived by AR the corresponding figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm birth-before 28 weeks' gestation-was 4.2 for MC twins compared to DC twins. The relative risk of fetal loss or death among DC twins was 20% of the risk for MC twins. The risk of fetal loss, very preterm delivery and neonatal/infant death is significantly higher among twins with MC compared to DC placentation. Twins conceived by AR have a much lower risk of MC placentation. The risk of losing one or both twins seems higher among naturally conceived twins compared to twins conceived by AR, despite the fact that the maternal age was higher among the mothers of the AR twins. Copyright 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal cerebro-placental ratio and adverse perinatal outcome: systematic review and meta-analysis of the association and diagnostic performance.

PubMed

Nassr, Ahmed Abobakr; Abdelmagied, Ahmed M; Shazly, Sherif A M

2016-03-01

The objective of this meta-analysis is to assess the value of fetal cerebro-placental Doppler ratio (CPR) in predicting adverse perinatal outcome in pregnancies with fetal growth restriction (FGR). Three databases were used: MEDLINE, EMBASE (with online Ovid interface) and SCOPUS and studies from inception to April 2015 were included. Studies that reported perinatal outcomes of fetuses at risk of FGR or sonographically diagnosed FGR that were evaluated with CPR were considered eligible. Perinatal outcomes include cesarean section (CS) for fetal distress, APGAR scores at 5 min, neonatal complications and admission to neonatal intensive care unit (NICU). Pooled data were expressed as odds ratio (OR) and confidence intervals (CI), and the summary receiver operating characteristic (SROC) curve was used to illustrate the diagnostic accuracy of CPR. Seven studies were eligible (1428 fetuses). Fetuses with abnormal CPR were at higher risk of CS for fetal distress (OR=4.49, 95% CI [1.63, 12.42]), lower APGAR scores (OR=4.01, 95% CI [2.65, 6.08]), admission to NICU (OR=9.65, 95% CI [3.02, 30.85]), and neonatal complications (OR=11.00, 95% [3.64, 15.37]) than fetuses who had normal CPR. These risks were higher among studies that included fetuses diagnosed with FGR than fetuses at risk of FGR. Abnormal CPR had higher diagnostic accuracy for adverse perinatal outcomes among "sonographically diagnosed FGR" studies than "at risk of FGR" studies. Abnormal CPR is associated with substantial risk of adverse perinatal outcomes. The test seems to be particularly useful for follow up of fetuses with sonographically diagnosed FGR.

Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature.

PubMed

Chan, W S; Anand, S; Ginsberg, J S

2000-01-24

The management of women with prosthetic heart valves during pregnancy poses a particular challenge as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulants such as warfarin sodium cause fetal embryopathy; subcutaneous administration of heparin sodium has been reported to be ineffective in preventing thromboembolic complications. To identify the risks of maternal and fetal complications in women with mechanical heart valves treated with different anticoagulation regimens during pregnancy. We performed a systematic review of the literature to determine pooled estimates of maternal and fetal risks associated with the 3 commonly used approaches: (1) oral anticoagulants (OA) throughout pregnancy, (2) replacing OA with heparin in the first trimester (from 6-12 weeks' gestation), and (3) heparin use throughout pregnancy. Fetal outcomes included spontaneous abortions and fetopathic effects, and maternal outcomes were major bleeding, thromboembolic complications, and death. The use of OA throughout pregnancy is associated with warfarin embryopathy in 6.4% (95% confidence interval [CI], 4.6%-8.9%) of livebirths. The substitution of heparin at or prior to 6 weeks, and continued until 12 weeks, eliminated this risk. Overall risks for fetal wastage (spontaneous abortion, stillbirths, and neonatal deaths) were similar in women treated with OA throughout, compared with women treated with heparin in the first trimester. Maternal mortality was 2.9% (95% CI, 1.9%-4.2%). Maj or bleeding events occurred in 2.5% (95% CI, 1.7%-3.5%) of all pregnancies, most at the time of delivery. The regimen associated with the lowest risk of valve thrombosis (3.9%; 95% CI, 2.9-5.9%) was the use of OA throughout; using heparin only between 6 and 12 weeks' gestation was associated with an increased risk of valve thrombosis (9.2%; 95% CI, 5.9%-13.9%). Thromboembolic prophylaxis of women with mechanical heart valves during pregnancy is best achieved with OA; however, this increases the risk of fetal embryopathy. Substituting OA with heparin between 6 and 12 weeks reduces the risk of fetopathic effects, but with an increased risk of thromboembolic complications. The use of low-dose heparin is definitely inadequate; the use of adjusted-dose heparin warrants aggressive monitoring and appropriate dose adjustment. Large prospective trials to determine the best regimen for these women are needed.

Prenatal Diagnosis Procedures and Techniques to Obtain a Diagnostic Fetal Specimen or Tissue: Maternal and Fetal Risks and Benefits.

PubMed

Wilson, R Douglas; Gagnon, Alain; Audibert, François; Campagnolo, Carla; Carroll, June

2015-07-01

To provide maternity care providers and their patients with current evidence-based guidelines for maternal risk/benefit counselling for a prenatally identified at-risk pregnancy that requires ultrasound-guided prenatal diagnostic procedures and/or techniques for a genetic diagnosis and for subsequent pregnancy management decisions on questions such as level of obstetrical care provider, antenatal surveillance, location of care and delivery, and continuation or termination of pregnancy. This guideline is limited to maternal risk/benefit counselling and pregnancy management decisions for women who require, or are considering, an invasive ultrasound-guided procedure or technique for prenatal diagnosis. Pregnant women identified as having an increased risk of a fetal genetic abnormality secondary to the process of established prenatal screening protocols (maternal serum±imaging, high-risk cell-free DNA results, abnormal diagnostic fetal imaging, or a positive family history of an inherited condition). These women may require or request counselling about pregnancy risks and benefits of an invasive ultrasound-guided procedure to determine the etiology, diagnosis, and/or pathology for the possible fetal anomaly or anomalies. Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to June 2014 using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, cordocentesis) and key words (prenatal screening, prenatal genetic counselling, post-procedural pregnancy loss rate). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1985 to June 2014. Searches were updated on a regular basis and incorporated in the guideline to June 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical speciality societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Health benefits, side effects, and risks: Patient informed consent, knowledge translation, genetic prenatal risk assessment, anxiety relief, anxiety creation, advocacy, understanding or limitation for fetal testing, pregnancy management choice, pregnancy complication or loss, timely and improved care for birth of a neonate with recognized morbidity. Recommendations 1. The health care provider should counsel the at-risk pregnant woman on the different levels of genetic fetal testing in order for her to have a clear understanding and expectation of the level of testing and type of results that are offered. (III-B) 2. As part of the informed consent process, the health care provider should review with the at-risk pregnant woman the risks and benefits of in utero genetic diagnostic techniques associated with fetal genetic testing options. (III-A) 3. During risk/benefit counselling, the health care provider should advise that the best estimate of the pregnancy loss rate related to: a.amniocentesis is 0.5% to 1.0% (range 0.17 to 1.53%) (I) b.chorionic villus sampling is 0.5% to 1.0% (I) and c.cordocentesis or percutaneous umbilical blood sampling is 1.3% for fetuses with no anomalies and 1.3% to 25% for fetuses with single or multiple anomalies or intrauterine growth restriction. (II-2A).

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.

Risk Factors for Dystocia in Pigtailed Macaques (Macaca nemestrina)

PubMed Central

Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

2011-01-01

Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources. PMID:21535929

Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus.

PubMed

Phelan, Suzanne

2016-11-01

Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early-life health complications and later disease. GDM recurrence is common, affecting 40 to 73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and prepregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify body weight. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of interpregnancy or prepregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Should we recommend universal aspirin for all pregnant women?

PubMed

Mone, Fionnuala; Mulcahy, Cecilia; McParland, Peter; McAuliffe, Fionnuala M

2017-02-01

Low-dose aspirin has been demonstrated to reduce the incidence of preeclampsia and fetal growth restriction in at-risk populations. Its role in low-risk populations is as yet unknown. Novel preeclampsia screening tests are emerging that can predict the risk of the development of preeclampsia from as early as 11 weeks of gestation. It may be more efficacious, acceptable, and cost-effective to prescribe low-dose aspirin to all pregnant women from the first trimester as opposed to performing a screening test in the first instance. There is variation in opinion: the American College of Obstetricians and Gynecologists suggests the use of aspirin only in women who are at risk of preeclampsia, based on patient history; the National Institute for Health and Clinical Excellence, UK, and the US Preventative Services Task Force recommend the use of low-dose aspirin if there is 1 major or 2 moderate risk factors. This point-counterpoint discussion shall address (1) controversies regarding the real impact of low-dose aspirin; (2) controversies in the actual guidelines among the different national societies; (3) controversies regarding emerging preeclampsia screening tests in terms of cost-effectiveness and efficacy, and (4) points in favor of the provision of universal vs screened-positive women. Copyright © 2016 Elsevier Inc. All rights reserved.

[Design and Application of High-risk Pregnancy Monitoring & Warning Internet Platform Based on Internet of Things].

PubMed

Lu, Heqing; Zhang, Xiaofeng; Li, Bin

2017-09-30

Through illustrating the designing of high-risk pregnancy maternal-fetal monitoring system based on the internet of things, this paper introduced the specific application of using wearable medical devices to provide maternal-fetal mobile medical services. With the help of big data and cloud obstetrics platform, the monitoring and warning network was further improved, the level-to-level administration of high-risk pregnancy was realized, the level of perinatal health care was enhanced and the risk of critical emergency of pregnancy decreased.

Significantly higher number of fetal cells in the maternal circulation of women with pre-eclampsia.

PubMed

Jansen, M W; Korver-Hakkennes, K; van Leenen, D; Visser, W; in 't Veld, P A; de Groot, C J; Wladimiroff, J W

2001-12-01

Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two-color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre-eclampsia (0.61+/-1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02+/-0.04 XY cells/ml blood) (Mann-Whitney U-test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre-eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease. Copyright 2001 John Wiley & Sons, Ltd.

Fetal and post-natal lung defects reveal a novel and required role for Fgf8 in lung development

PubMed Central

Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah; Albertine, Kurt H.; Fenton, Stephen; Garg, Vidu; Moon, Anne M.

2016-01-01

The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. PMID:20727874

Assessing effects of BL67 points stimulation on fetal heart rate parameters and fetal movements during nonstress test.

PubMed

Pirhadi, Masume; Valiani, Mahboube

2017-01-01

One of the main goals of antenatal testing is to identify fetuses at the risk of neurologic injury or death so that these adverse outcomes can be prevented. We want to assess the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements during nonstress test (NST). We did a quasi-experimental design in Shahid Beheshti Hospital in Isfahan in 2011. This study aims to assessment of the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements. We did a randomized controlled clinical trial in Shahid Beheshti Hospital in Isfahan in 2011. This study is a quasi-experimental design that was conducted in one group and the two steps (before-after study). Participants were pregnant women (primigravida) who were 35-18 years that refer to Shahid Beheshti Hospital in Isfahan in 2011 to receive routine prenatal care. The 32 pregnant women were selected for acupressure during the second NST. The statistical processing was performed by descriptive, paired t -test through SPSS version 20. There was no significant difference in mean number of accelerations in fetal heart rate and mean number of fetal movement before and after intervention; however, there was a significant difference in mean time to the second acceleration before and after the intervention ( P = 0.04). No difference between parameters of the fetal heart rate before and after stimulation and lack of uterine response by this method is a significant advantage and is probably why stimulating this point could not create a risk to the fetuses.

Reference charts of fetal biometric parameters in 31,476 Brazilian singleton pregnancies.

PubMed

Araujo Júnior, Edward; Martins Santana, Eduardo Félix; Martins, Wellington P; Júnior, Julio Elito; Ruano, Rodrigo; Pires, Claudio Rodrigues; Filho, Sebastião Marques Zanforlin

2014-07-01

The purpose of this study was to establish reference charts of fetal biometric parameters measured by 2-dimensional sonography in a large Brazilian population. A cross-sectional retrospective study was conducted including 31,476 low-risk singleton pregnancies between 18 and 38 weeks' gestation. The following fetal parameters were measured: biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. To assess the correlation between the fetal biometric parameters and gestational age, polynomial regression models were created, with adjustments made by the determination coefficient (R(2)). The means ± SDs of the biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight measurements at 18 and 38 weeks were 4.2 ± 2.34 and 9.1 ± 4.0 cm, 15.3 ± 7.56 and 32.3 ± 11.75 cm, 13.3 ± 10.42 and 33.4 ± 20.06 cm, 2.8 ± 2.17 and 7.2 ± 3.58 cm, and 256.34 ± 34.03 and 3169.55 ± 416.93 g, respectively. Strong correlations were observed between all fetal biometric parameters and gestational age, best represented by second-degree equations, with R(2) values of 0.95, 0.96, 0.95, 0.95, and 0.95 for biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. Fetal biometric parameters were determined for a large Brazilian population, and they may serve as reference values in cases with a high risk of intrauterine growth disorders. © 2014 by the American Institute of Ultrasound in Medicine.

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

PubMed

Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

2015-10-13

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

PubMed Central

Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

2015-01-01

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

Fetal Programming and Cardiovascular Pathology

PubMed Central

Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

2016-01-01

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

Maternal amino acid supplementation for intrauterine growth restriction

PubMed Central

Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J

2011-01-01

Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387

Perinatal and Family Risk Factors for Non-Hodgkin Lymphoma in Early Life: A Swedish National Cohort Study

PubMed Central

Sundquist, Kristina; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Jan

2012-01-01

Background The incidence of non-Hodgkin lymphoma (NHL) in early life has increased in recent decades, but the relevant risk factors remain largely unknown. We examined perinatal and family risk factors for NHL in childhood through young adulthood. Methods We conducted a national cohort study of 3 571 574 individuals born in Sweden in 1973–2008 who were followed for incidence of NHL through 2009 (ages 0–37 years). Detailed information on perinatal and family characteristics and NHL diagnoses were obtained from national birth and cancer registries. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between perinatal and family variables and NHL; P values are from two-sided tests. Results There were 936 NHL case patients identified in 66.3 million person-years of follow-up. Independent risk factors for NHL included family history of NHL in either a sibling (adjusted HR = 9.84; 95% CI = 2.46 to 39.41; P = .001) or parent (adjusted HR = 2.36; 95% CI = 1.27 to 4.38; P = .007); high fetal growth (for ≥2 SDs relative to 0 to <1 SD from the mean: adjusted HR = 1.64; 95% CI = 1.19 to 2.25; P = .002); older maternal age (adjusted HR for each 5-year increment = 1.11; 95% CI = 1.04 to 1.19; P trend = .004); low birth order (adjusted HR for each increment of one birth = 0.91; 95% CI = 0.84 to 0.99; P trend = .02); and male sex (adjusted HR = 1.58; 95% CI = 1.38 to 1.80; P < .001). Male sex was associated with onset of NHL before 15 years of age but not with later-onset NHL, whereas the other risk factors did not vary by age at diagnosis. No association was found between gestational age at birth, twinning, paternal age, or parental education and NHL. Conclusion In this large national cohort study, family history of NHL, high fetal growth, older maternal age, low birth order, and male sex were independent risk factors for NHL in early life. PMID:22623506

Informative priors on fetal fraction increase power of the noninvasive prenatal screen.

PubMed

Xu, Hanli; Wang, Shaowei; Ma, Lin-Lin; Huang, Shuai; Liang, Lin; Liu, Qian; Liu, Yang-Yang; Liu, Ke-Di; Tan, Ze-Min; Ban, Hao; Guan, Yongtao; Lu, Zuhong

2017-11-09

PurposeNoninvasive prenatal screening (NIPS) sequences a mixture of the maternal and fetal cell-free DNA. Fetal trisomy can be detected by examining chromosomal dosages estimated from sequencing reads. The traditional method uses the Z-test, which compares a subject against a set of euploid controls, where the information of fetal fraction is not fully utilized. Here we present a Bayesian method that leverages informative priors on the fetal fraction.MethodOur Bayesian method combines the Z-test likelihood and informative priors of the fetal fraction, which are learned from the sex chromosomes, to compute Bayes factors. Bayesian framework can account for nongenetic risk factors through the prior odds, and our method can report individual positive/negative predictive values.ResultsOur Bayesian method has more power than the Z-test method. We analyzed 3,405 NIPS samples and spotted at least 9 (of 51) possible Z-test false positives.ConclusionBayesian NIPS is more powerful than the Z-test method, is able to account for nongenetic risk factors through prior odds, and can report individual positive/negative predictive values.Genetics in Medicine advance online publication, 9 November 2017; doi:10.1038/gim.2017.186.

Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

PubMed

Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

2016-05-08

Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

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.

The effect of fetal sex on customized fetal growth charts.

PubMed

Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

2016-12-01

To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

Optimizing hidden layer node number of BP network to estimate fetal weight

NASA Astrophysics Data System (ADS)

Su, Juan; Zou, Yuanwen; Lin, Jiangli; Wang, Tianfu; Li, Deyu; Xie, Tao

2007-12-01

The ultrasonic estimation of fetal weigh before delivery is of most significance for obstetrical clinic. Estimating fetal weight more accurately is crucial for prenatal care, obstetrical treatment, choosing appropriate delivery methods, monitoring fetal growth and reducing the risk of newborn complications. In this paper, we introduce a method which combines golden section and artificial neural network (ANN) to estimate the fetal weight. The golden section is employed to optimize the hidden layer node number of the back propagation (BP) neural network. The method greatly improves the accuracy of fetal weight estimation, and simultaneously avoids choosing the hidden layer node number with subjective experience. The estimation coincidence rate achieves 74.19%, and the mean absolute error is 185.83g.

Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and 5 mo of age

USDA-ARS?s Scientific Manuscript database

Effects of prenatal iron supplementation on maternal postpartum iron status and early infant iron homeostasis remain largely unknown. We examined iron absorption and growth in exclusively breastfed infants in relation to fetal iron exposure and iron status during early infancy. Longitudinal, paired ...

Gestational diabetes mellitus and macrosomia: a literature review.

PubMed

Kc, Kamana; Shakya, Sumisti; Zhang, Hua

2015-01-01

Fetal macrosomia, defined as a birth weight ≥ 4,000 g, may affect 12% of newborns of normal women and 15-45% of newborns of women with gestational diabetes mellitus (GDM). The increased risk of macrosomia in GDM is mainly due to the increased insulin resistance of the mother. In GDM, a higher amount of blood glucose passes through the placenta into the fetal circulation. As a result, extra glucose in the fetus is stored as body fat causing macrosomia, which is also called 'large for gestational age'. This paper reviews studies that explored the impact of GDM and fetal macrosomia as well as macrosomia-related complications on birth outcomes and offers an evaluation of maternal and fetal health. Fetal macrosomia is a common adverse infant outcome of GDM if unrecognized and untreated in time. For the infant, macrosomia increases the risk of shoulder dystocia, clavicle fractures and brachial plexus injury and increases the rate of admissions to the neonatal intensive care unit. For the mother, the risks associated with macrosomia are cesarean delivery, postpartum hemorrhage and vaginal lacerations. Infants of women with GDM are at an increased risk of becoming overweight or obese at a young age (during adolescence) and are more likely to develop type II diabetes later in life. Besides, the findings of several studies that epigenetic alterations of different genes of the fetus of a GDM mother in utero could result in the transgenerational transmission of GDM and type II diabetes are of concern.

Clinical relevance of fetal hemodynamic monitoring: Perinatal implications.

PubMed

Pruetz, Jay D; Votava-Smith, Jodie; Miller, David A

2015-08-01

Comprehensive assessment of fetal wellbeing involves monitoring of fetal growth, placental function, central venous pressure, and cardiac function. Ultrasound evaluation of the fetus using 2D, color Doppler, and pulse-wave Doppler techniques form the foundation of antenatal diagnosis of structural anomalies, rhythm abnormalities and altered fetal circulation. Accurate and timely prenatal identification of the fetus at risk is critical for appropriate parental counseling, antenatal diagnostic testing, consideration for fetal intervention, perinatal planning, and coordination of postnatal care delivery. Fetal hemodynamic monitoring and serial assessment are vital to ensuring fetal wellbeing, particularly in the setting of complex congenital anomalies. A complete hemodynamic evaluation of the fetus gives important information on the likelihood of a smooth postnatal transition and contributes to ensuring the best possible outcome for the neonate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prenatal diagnosis and management of an intestinal volvulus with meconium ileus and peritonitis.

PubMed

Takacs, Z F; Meier, C M; Solomayer, E-F; Gortner, L; Meyberg-Solomayer, G

2014-08-01

Fetal intestinal volvulus is a rare but serious finding with a high risk of potential life threatening fetal complications. Delay in diagnosis or treatment can increase mortality and morbidity. We report a case of mild fetal bowel dilatation at 30 weeks of gestation and intestinal volvulus presented by the 'whirl-sign', intestinal perforation and meconium peritonitis with fetal ascites and polyhydramnios at 33 weeks of gestation. This case emphasizes the role of examination of the bowel in third trimester ultrasound and the importance of quick decision to delivery and interdisciplinary perinatal management at suspected fetal volvulus with bowel necrosis and intraabdominal bleeding.

Predictive factors for intrauterine growth restriction.

PubMed

Albu, A R; Anca, A F; Horhoianu, V V; Horhoianu, I A

2014-06-15

Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies.

Antenatal management of at-risk pregnancies from a distance.

PubMed

Ivey, Tesa L; Hughes, Dawn; Dajani, Nafisa K; Magann, Everett F

2015-02-01

This study was undertaken to determine whether antenatal care can be achieved in women with at-risk pregnancies residing in rural areas with limited access to antenatal care and maternal fetal medicine (MFM) specialists. Over a period of 15 months, 156 women with high-risk pregnancies (diabetes, hypertensive disorders, suspected fetal anomalies, prior caesarean complications) from six different healthcare units had 350 visits managed by telemedicine. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

[Fetal programming and the etiology of osteoporosis].

PubMed

Pieńkowski, Wojciech; Wolski, Hubert; Drews, Krzysztof; Seremak-Mrozikiewicz, Agnieszka

2015-08-01

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.

Hyperparathyroidism in pregnancy: options for localization and surgical therapy.

PubMed

McMullen, Todd P W; Learoyd, Diana L; Williams, David C; Sywak, Mark S; Sidhu, Stan B; Delbridge, Leigh W

2010-08-01

Hyperparathyroidism in pregnancy is a threat to the health of both mother and fetus. The mothers suffer commonly from nephrolithiasis, hyperemesis, or even hypercalcemic crisis. Untreated disease will commonly complicate fetal development and fetal death is a significant risk. Treatment options, including medical and surgical therapy, are debated in the literature. This is a case series comprising seven patients with primary hyperparathyroidism in pregnancy. Data collected included symptoms at diagnosis, biochemical abnormalities, pathologic findings, treatment regimes, and subsequent maternal and fetal outcomes. Seven women, aged 20 to 39 years, presented with hyperparathyroidism during pregnancy. The earliest presented at 8 weeks and the latest at 38 weeks. Four of seven patients experienced renal calculi. Calcium levels were 2.7-3.5 mmol/l. All were found to have solitary parathyroid adenomas, of which two were in ectopic locations. Fetal complications included three preterm deliveries and one fetal death with no cases of neonatal tetany. Maternal and fetal complications could not be predicted based on duration or severity of hypercalcemia. Three patients were treated during pregnancy with surgery, and two of these had ectopic glands that required reoperations with a novel approach using Tc-99m sestamibi scanning during pregnancy to assist in localizing the abnormal gland. Four cases were treated postpartum with a combination of open and minimally invasive approaches after localization. No operative complications or fetal loss related to surgery were observed in this cohort. Primary hyperparathyroidism in pregnancy represents a significant risk for maternal and fetal complications that cannot be predicted by duration of symptoms or serum calcium levels. Surgical treatment should be considered early, and a minimally invasive approach with ultrasound is best suited to mitigating risk to mother and fetus. Equally important, Tc-99m sestamibi imaging may be used safely for localization of the parathyroids after negative cervical explorations.

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

PubMed Central

Simmons, Heather A.; Salamat, M. Shahriar; Thoong, Troy H.; Weiler, Andrea M.; Barry, Gabrielle L.; Weisgrau, Kim L.; Vosler, Logan J.; Mohns, Mariel S.; Breitbach, Meghan E.; Stewart, Laurel M.; Newman, Christina M.; Graham, Michael E.; Turski, Patrick A.; Post, Jennifer; Hayes, Jennifer M.; Schotzko, Michele L.; Permar, Sallie R.; Rakasz, Eva G.; Capuano, Saverio; Tarantal, Alice F.; Osorio, Jorge E.; O’Connor, Shelby L.

2017-01-01

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated. PMID:28542585

Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace.

PubMed

East, Christine E; Leader, Leo R; Sheehan, Penelope; Henshall, Naomi E; Colditz, Paul B; Lau, Rosalind

2015-05-01

Fetal scalp blood sampling for lactate estimation may be considered following identification of an abnormal or non-reassuring fetal heart rate pattern. The smaller volume of blood required for this test, compared with the more traditional pH estimation, may improve sampling rates. The appropriate use of this practice mandates systematic review of its safety and clinical effectiveness prior to widespread introduction. To evaluate the effectiveness and risks of fetal scalp lactate sampling in the assessment of fetal well-being during labour, compared with no testing or alternative testing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015). All published and unpublished randomised and quasi-randomised trials that compared fetal scalp lactate testing with no testing or alternative testing to evaluate fetal status in the presence of a non-reassuring cardiotocograph during labour. We used the standard methodological procedures of the Cochrane Pregnancy and Childbirth Group. Two review authors independently assessed the studies. The search identified two completed randomised controlled trials (RCTs) and two ongoing trials. The two published RCTs considered outcomes for 3348 mother-baby pairs allocated to either lactate or pH estimation of fetal blood samples when clinically indicated in labour. Overall, the published RCTs were of low or unclear risk of bias. There was a high risk of performance bias, because it would not have been feasible to blind clinicians or participants.No statistically significant between-group differences were found for neonatal encephalopathy (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.32 to 3.09, one study, 2992 infants) or death. No studies reported neonatal seizures. We had planned to report death with other morbidities, for example, neonatal encephalopathy; however, the data were not available in a format suitable for this, therefore death due to congenital abnormality was considered alone. The three reported neonatal deaths occurred in babies with diaphragmatic hernias (n = 2) or congenital cardiac fibrosis (n = 1). All three babies had been randomised to the pH group and were not acidaemic at birth.There were no statistically significant differences for any of the pre-specified secondary fetal/neonatal/infant outcomes for which data were available. This included low Apgar score at five minutes (RR 1.13, 95% CI 0.76 to 1.68, two studies, 3319 infants) and admission to neonatal intensive care units (RR 1.02, 95% CI 0.83 to 1.25, one study, 2992 infants), or metabolic acidaemia (RR 0.91, 95% CI 0.60 to 1.36, one study, 2675 infants) considered within the studies, either overall or where data were available for those where fetal blood sampling had occurred within 60 minutes of delivery.Similar proportions of fetuses underwent additional tests to further evaluate well-being during labour, including scalp pH if in the lactate group or scalp lactate if in the pH group (RR 0.22, 95% CI 0.04 to 1.30, two studies, 3333 infants;Tau² 1.00, I² = 58%). Fetal blood sampling attempts for lactate and pH estimation were successful in 98.7% and 79.4% of procedures respectively in the one study that reported this outcome.There were no significant between-group differences in mode of birth or operative birth for non-reassuring fetal status, either for all women, or within the group where the fetal blood sample had been taken within 60 minutes of delivery (for example, caesarean section for all enrolled, RR 1.09, 95% CI 0.97 to 1.22, two studies, 3319 women; operative delivery for non-reassuring fetal status for all enrolled RR 1.02, 95% CI 0.93 to 1.11, one study, 2992 women).Neither study reported on adverse effects of fetal scalp lacerations or maternal anxiety. When further testing to assess fetal well-being in labour is indicated, fetal scalp blood lactate estimation is more likely to be successfully undertaken than pH estimation. Further studies may consider subgroup analysis by gestational age, the stage of labour and sampling within a prolonged second stage of labour. Additionally, we await the findings from the ongoing studies that compare allocation to no fetal blood sample with sampling for lactate and address longer-term neonatal outcomes, maternal satisfaction with intrapartum fetal monitoring and an economic analysis.

Pregnancy Loss and Maternal Methemoglobin Levels: An Indirect Explanation of the Association of Environmental Toxics and Their Adverse Effects on the Mother and the Fetus

PubMed Central

Mohorovic, Lucijan; Petrovic, Oleg; Haller, Herman; Micovic, Vladimir

2010-01-01

The aim of this epidemiologic study was to point out a relationship between the exposure to products of coal combustion, and complications in pregnancy where one third of causes of stillbirth are still unknown. In the town of Labin (Croatia) a coal-powered thermoelectric power plant is the single major air polluter. We compared the records of miscarriages, premature births and stillbirths in two periods: the control and the exposure period. Data on reproductive loss was based on the records of pregnant women visiting for regular monthly pregnancy checkups. At the time of the epidemiological prospective study, 260 women (n = 138 in the clean period and n = 122 in the dirty period) were considered representative. The data were processed using Chi square and correlation tests. The frequencies of miscarriages and stillbirths were significantly lower in the control than in the exposure period (p < 0.05). Methemoglobinemia and stillbirths recorded over the “exposure” period are significantly higher than in the “control” period (p = 0.0205). The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics’ adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin. Methemoglobin and heme, having prooxidant properties, also cause the early and late endothelial dysfunction of vital organs. Despite our retrospective epidemiological study findings, we emphasize that the rate of reproductive loss represents a hypothetical risk, which needs to be confirmed with further fetal clinical and anatomopatholgical researches about the effects of methemoglobin catabolism products on the fetal CNS. PMID:21318003

Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells.

PubMed

Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

2013-02-01

Abnormal fetal growth increases the risk for perinatal complications and predisposes for the development of obesity, diabetes and cardiovascular disease later in life. Emerging evidence suggests that changes in placental amino acid transport directly contribute to altered fetal growth. However, the molecular mechanisms regulating placental amino acid transport are largely unknown. Here we combined small interfering (si) RNA-mediated silencing approaches with protein expression/localization and functional studies in cultured primary human trophoblast cells to test the hypothesis that mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) regulate amino acid transporters by post-translational mechanisms. Silencing raptor (inhibits mTORC1) or rictor (inhibits mTORC2) markedly decreased basal System A and System L amino acid transport activity but had no effect on growth factor-stimulated amino acid uptake. Simultaneous inhibition of mTORC1 and 2 completely inhibited both basal and growth factor-stimulated amino acid transport activity. In contrast, mTOR inhibition had no effect on serotonin transport. mTORC1 or mTORC2 silencing markedly decreased the plasma membrane expression of specific System A (SNAT2, SLC38A2) and System L (LAT1, SLC7A5) transporter isoforms without affecting global protein expression. In conclusion, mTORC1 and mTORC2 regulate human trophoblast amino acid transporters by modulating the cell surface abundance of specific transporter isoforms. This is the first report showing regulation of amino acid transport by mTORC2. Because placental mTOR activity and amino acid transport are decreased in human intrauterine growth restriction our data are consistent with the possibility that dysregulation of placental mTOR plays an important role in the development of abnormal fetal growth.

Brain Development in Fetuses of Mothers with Diabetes: A Case-Control MR Imaging Study.

PubMed

Denison, F C; Macnaught, G; Semple, S I K; Terris, G; Walker, J; Anblagan, D; Serag, A; Reynolds, R M; Boardman, J P

2017-05-01

Offspring exposed to maternal diabetes are at increased risk of neurocognitive impairment, but its origins are unknown. With MR imaging, we investigated the feasibility of comprehensive assessment of brain metabolism ( 1 H-MRS), microstructure (DWI), and macrostructure (structural MRI) in third-trimester fetuses in women with diabetes and determined normal ranges for the MR imaging parameters measured. Women with singleton pregnancies with diabetes ( n = 26) and healthy controls ( n = 26) were recruited prospectively for MR imaging studies between 34 and 38 weeks' gestation. Data suitable for postprocessing were obtained from 79%, 71%, and 46% of women for 1 H-MRS, DWI, and structural MRI, respectively. There was no difference in the NAA/Cho and NAA/Cr ratios (mean [SD]) in the fetal brain in women with diabetes compared with controls (1.74 [0.79] versus 1.79 [0.64], P = .81; and 0.78 [0.28] versus 0.94 [0.36], P = .12, respectively), but the Cho/Cr ratio was marginally lower (0.46 [0.11] versus 0.53 [0.10], P = .04). There was no difference in mean [SD] anterior white, posterior white, and deep gray matter ADC between patients and controls (1.16 [0.12] versus 1.16 [0.08], P = .96; 1.54 [0.16] versus 1.59 [0.20], P = .56; and 1.49 [0.23] versus 1.52 [0.23], P = .89, respectively) or volume of the cerebrum (243.0 mL [22.7 mL] versus 253.8 mL [31.6 mL], P = .38). Acquiring multimodal MR imaging of the fetal brain at 3T from pregnant women with diabetes is feasible. Further study of fetal brain metabolism in maternal diabetes is warranted. © 2017 by American Journal of Neuroradiology.

Maternal dietary free or bound fructose diversely influence developmental programming of lipogenesis.

PubMed

Yuruk, Armagan Aytug; Nergiz-Unal, Reyhan

2017-12-01

Maternal dietary choices throughout preconception, pregnancy, and lactation irreversibly affect the development of fetal tissues and organs, known as fetal programming. Recommendations tend to emphasize reducing added sugars. However, the impact of maternal dietary free or bound fructose in added sugars on developmental programming of lipogenesis is unknown. Virgin Sprague-Dawley rats were randomly divided into five groups. Rats were given feed and plain water (control) or water containing maltodextrin (vehicle), fructose, high-fructose corn syrup (HFCS) containing 55% fructose, sucrose (20% w/v) for 12 weeks before mating and throughout the pregnancy and lactation periods. Body weight, water, and feed intake were measured throughout the study. At the end of the lactation period, blood was drawn to determine the fasting levels of glucose, insulin, triglycerides, and non-esterified fatty acids (NEFA) in blood. Triglycerides and acetyl Co-A Carboxylase-1 (ACC1) levels in livers were analyzed, and insulin resistance was calculated. The energy intake of dams in the HFCS group was higher than in the fructose group, while weight gain was less in the HFCS group than in the fructose group. HFCS resulted in greater insulin resistance in dams, whereas free fructose had a robust effect on the fetal programming of insulin resistance. Free fructose and HFCS in the maternal diet increased blood and liver triglycerides and NEFA content in pups. Furthermore, fructose and HFCS exposure increased phosphorylated ACC1 as compared to maltodextrin and control, indicating greater fatty acid synthesis in pups and dams. Different types of added sugar in the maternal diet have different metabolic effects on the developmental programming of lipogenesis. Consequently, high fructose intake via processed foods may increase the risk for chronic diseases, and free fructose might contribute to developmental programming of chronic diseases more than bound fructose.

Relationships of maternal and paternal anthropometry with neonatal body size, proportions and adiposity in an Australian cohort.

PubMed

Pomeroy, Emma; Wells, Jonathan C K; Cole, Tim J; O'Callaghan, Michael; Stock, Jay T

2015-04-01

The patterns of association between maternal or paternal and neonatal phenotype may offer insight into how neonatal characteristics are shaped by evolutionary processes, such as conflicting parental interests in fetal investment and obstetric constraints. Paternal interests are theoretically served by maximizing fetal growth, and maternal interests by managing investment in current and future offspring, but whether paternal and maternal influences act on different components of overall size is unknown. We tested whether parents' prepregnancy height and body mass index (BMI) were related to neonatal anthropometry (birthweight, head circumference, absolute and proportional limb segment and trunk lengths, subcutaneous fat) among 1,041 Australian neonates using stepwise linear regression. Maternal and paternal height and maternal BMI were associated with birthweight. Paternal height related to offspring forearm and lower leg lengths, maternal height and BMI to neonatal head circumference, and maternal BMI to offspring adiposity. Principal components analysis identified three components of variability reflecting neonatal "head and trunk skeletal size," "adiposity," and "limb lengths." Regression analyses of the component scores supported the associations of head and trunk size or adiposity with maternal anthropometry, and limb lengths with paternal anthropometry. Our results suggest that while neonatal fatness reflects environmental conditions (maternal physiology), head circumference and limb and trunk lengths show differing associations with parental anthropometry. These patterns may reflect genetics, parental imprinting and environmental influences in a manner consistent with parental conflicts of interest. Paternal height may relate to neonatal limb length as a means of increasing fetal growth without exacerbating the risk of obstetric complications. © 2014 The Authors American Journal of Physical Anthropology Published by Wiley Periodicals, Inc.

Relationships of maternal and paternal anthropometry with neonatal body size, proportions and adiposity in an Australian cohort

PubMed Central

Pomeroy, Emma; Wells, Jonathan CK; Cole, Tim J; O'Callaghan, Michael; Stock, Jay T

2015-01-01

The patterns of association between maternal or paternal and neonatal phenotype may offer insight into how neonatal characteristics are shaped by evolutionary processes, such as conflicting parental interests in fetal investment and obstetric constraints. Paternal interests are theoretically served by maximizing fetal growth, and maternal interests by managing investment in current and future offspring, but whether paternal and maternal influences act on different components of overall size is unknown. We tested whether parents' prepregnancy height and body mass index (BMI) were related to neonatal anthropometry (birthweight, head circumference, absolute and proportional limb segment and trunk lengths, subcutaneous fat) among 1,041 Australian neonates using stepwise linear regression. Maternal and paternal height and maternal BMI were associated with birthweight. Paternal height related to offspring forearm and lower leg lengths, maternal height and BMI to neonatal head circumference, and maternal BMI to offspring adiposity. Principal components analysis identified three components of variability reflecting neonatal “head and trunk skeletal size,” “adiposity,” and “limb lengths.” Regression analyses of the component scores supported the associations of head and trunk size or adiposity with maternal anthropometry, and limb lengths with paternal anthropometry. Our results suggest that while neonatal fatness reflects environmental conditions (maternal physiology), head circumference and limb and trunk lengths show differing associations with parental anthropometry. These patterns may reflect genetics, parental imprinting and environmental influences in a manner consistent with parental conflicts of interest. Paternal height may relate to neonatal limb length as a means of increasing fetal growth without exacerbating the risk of obstetric complications. Am J Phys Anthropol 156:625–636, 2015. PMID:25502164

Measurement of fetal fraction in cell-free DNA from maternal plasma using a panel of insertion/deletion polymorphisms.

PubMed

Barrett, Angela N; Xiong, Li; Tan, Tuan Z; Advani, Henna V; Hua, Rui; Laureano-Asibal, Cecille; Soong, Richie; Biswas, Arijit; Nagarajan, Niranjan; Choolani, Mahesh

2017-01-01

Cell-free DNA from maternal plasma can be used for non-invasive prenatal testing for aneuploidies and single gene disorders, and also has applications as a biomarker for monitoring high-risk pregnancies, such as those at risk of pre-eclampsia. On average, the fractional cell-free fetal DNA concentration in plasma is approximately 15%, but can vary from less than 4% to greater than 30%. Although quantification of cell-free fetal DNA is straightforward in the case of a male fetus, there is no universal fetal marker; in a female fetus measurement is more challenging. We have developed a panel of multiplexed insertion/deletion polymorphisms that can measure fetal fraction in all pregnancies in a simple, targeted sequencing reaction. A multiplex panel of primers was designed for 35 indels plus a ZFX/ZFY amplicon. cfDNA was extracted from plasma from 157 pregnant women, and maternal genomic DNA was extracted for 20 of these samples for panel validation. Sixty-one samples from pregnancies with a male fetus were subjected to whole genome sequencing on the Ion Proton sequencing platform, and fetal fraction derived from Y chromosome counts was compared to fetal fraction measured using the indel panel. A total of 157 cell-free DNA samples were sequenced using the indel panel, and informativity was assessed, along with the proportion of fetal DNA. Using gDNA we optimised the indel panel, removing amplicons giving rise to PCR bias. Good correlation was found between fetal fraction using indels and using whole genome sequencing of the Y chromosome (Spearmans r = 0.69). A median of 12 indels were informative per sample. The indel panel was informative in 157/157 cases (mean fetal fraction 14.4% (±0.58%)). Using our targeted next generation sequencing panel we can readily assess the fetal DNA percentage in male and female pregnancies.

Measurement of fetal fraction in cell-free DNA from maternal plasma using a panel of insertion/deletion polymorphisms

PubMed Central

Xiong, Li; Tan, Tuan Z.; Advani, Henna V.; Hua, Rui; Laureano-Asibal, Cecille; Soong, Richie; Biswas, Arijit; Nagarajan, Niranjan; Choolani, Mahesh

2017-01-01

Objective Cell-free DNA from maternal plasma can be used for non-invasive prenatal testing for aneuploidies and single gene disorders, and also has applications as a biomarker for monitoring high-risk pregnancies, such as those at risk of pre-eclampsia. On average, the fractional cell-free fetal DNA concentration in plasma is approximately 15%, but can vary from less than 4% to greater than 30%. Although quantification of cell-free fetal DNA is straightforward in the case of a male fetus, there is no universal fetal marker; in a female fetus measurement is more challenging. We have developed a panel of multiplexed insertion/deletion polymorphisms that can measure fetal fraction in all pregnancies in a simple, targeted sequencing reaction. Methods A multiplex panel of primers was designed for 35 indels plus a ZFX/ZFY amplicon. cfDNA was extracted from plasma from 157 pregnant women, and maternal genomic DNA was extracted for 20 of these samples for panel validation. Sixty-one samples from pregnancies with a male fetus were subjected to whole genome sequencing on the Ion Proton sequencing platform, and fetal fraction derived from Y chromosome counts was compared to fetal fraction measured using the indel panel. A total of 157 cell-free DNA samples were sequenced using the indel panel, and informativity was assessed, along with the proportion of fetal DNA. Results Using gDNA we optimised the indel panel, removing amplicons giving rise to PCR bias. Good correlation was found between fetal fraction using indels and using whole genome sequencing of the Y chromosome (Spearmans r = 0.69). A median of 12 indels were informative per sample. The indel panel was informative in 157/157 cases (mean fetal fraction 14.4% (±0.58%)). Conclusions Using our targeted next generation sequencing panel we can readily assess the fetal DNA percentage in male and female pregnancies. PMID:29084245

Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

PubMed

Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning

2010-07-01

The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

Improving Perinatal Care in the Rural Regions Worldwide by Wireless Enabled Antepartum Fetal Monitoring: A Demonstration Project

PubMed Central

Tapia-Conyer, Roberto; Lyford, Shelley; Saucedo, Rodrigo; Casale, Michael; Gallardo, Hector; Becerra, Karen; Mack, Jonathan; Mujica, Ricardo; Estrada, Daniel; Sanchez, Antonio; Sabido, Ramon; Meier, Carlos; Smith, Joseph

2015-01-01

Background. Fetal and neonatal morbidity and mortality are significant problems in developing countries; remote maternal-fetal monitoring offers promise in addressing this challenge. The Gary and Mary West Health Institute and the Instituto Carlos Slim de la Salud conducted a demonstration project of wirelessly enabled antepartum maternal-fetal monitoring in the state of Yucatán, Mexico, to assess whether there were any fundamental barriers preventing deployment and use. Methods. Following informed consent, high-risk pregnant women at 27–29 weeks of gestation at the Chemax primary clinic participated in remote maternal-fetal monitoring. Study participants were randomized to receive either prototype wireless monitoring or standard-of-care. Feasibility was evaluated by assessing technical aspects of performance, adherence to monitoring appointments, and response to recommendations. Results. Data were collected from 153 high-risk pregnant indigenous Mayan women receiving either remote monitoring (n = 74) or usual standard-of-care (n = 79). Remote monitoring resulted in markedly increased adherence (94.3% versus 45.1%). Health outcomes were not statistically different in the two groups. Conclusions. Remote maternal-fetal monitoring is feasible in resource-constrained environments and can improve maternal compliance for monitoring sessions. Improvement in maternal-fetal health outcomes requires integration of such technology into sociocultural context and addressing logistical challenges of access to appropriate emergency services. PMID:25691900

The introduction of the absolute risk for the detection of fetal aneuploidies in the first-trimester screening.

PubMed

Padula, Francesco; Laganà, Antonio Simone; Vitale, Salvatore Giovanni; D'Emidio, Laura; Coco, Claudio; Giannarelli, Diana; Cariola, Maria; Favilli, Alessandro; Giorlandino, Claudio

2017-05-01

Maternal age is a crucial factor in fetal aneuploidy screening, resulting in an increased rate of false-positive cases in older women and false-negative cases in younger women. The absolute risk (AR) is the simplest way to eliminate the background maternal age risk, as it represents the amount of improvement of the combined risk from the maternal background risk. The aim of this work is to assess the performance of the AR in the combined first-trimester screening for aneuploidies. A retrospective validation of the AR in the combined first-trimester screening for fetal aneuploidies, in an unselected population at Altamedica Fetal-Maternal Medical Center in Rome, between March 2007 and December 2008. Of 3845 women included in the study, we had a complete follow-up on 2984. We evaluated that an AR < 3 would individuate 22 of 23 cases of aneuploidy with a detection rate of 95.7% (95%CI 87.3-100), a false-positive rate of 8.7% (95%CI 7.7-9.7) and a false-negative rate of 4.3% (95%CI 0-12.7). In our study, the AR ameliorates the detection rate for aneuploidy. Further research and a prospective study on a larger population would help us to improve the AR in detecting most cases of aneuploidy.

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

PubMed Central

De Kleer, Ismé; Henri, Sandrine; Post, Sijranke; Vanhoutte, Leen; De Prijck, Sofie; Deswarte, Kim; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N.

2013-01-01

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life. PMID:24043763

Monitoring fetal electrocortical activity during labour for predicting worsening acidemia: a prospective study in the ovine fetus near term.

PubMed

Frasch, Martin G; Keen, Ashley E; Gagnon, Robert; Ross, Michael G; Richardson, Bryan S

2011-01-01

Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24 ± 0.04, 52 ± 13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23 ± 2 Hz from 3 ± 1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001). The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such "adaptive brain shutdown," the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring.

Monitoring Fetal Electrocortical Activity during Labour for Predicting Worsening Acidemia: A Prospective Study in the Ovine Fetus Near Term

PubMed Central

Frasch, Martin G.; Keen, Ashley E.; Gagnon, Robert; Ross, Michael G.; Richardson, Bryan S.

2011-01-01

Background Severe fetal acidemia during labour with arterial pH below 7.00 is associated with increased risk of hypoxic-ischemic brain injury. Electronic fetal heart rate (FHR) monitoring, the mainstay of intrapartum surveillance, has poor specificity for detecting fetal acidemia. We studied brain electrical activity measured with electrocorticogram (ECOG) in the near term ovine fetus subjected to repetitive umbilical cord occlusions (UCO) inducing FHR decelerations, as might be seen in human labour, to delineate the time-course for ECOG changes with worsening acidemia and thereby assess the potential clinical utility of fetal ECOG. Methodology/Principal Findings Ten chronically catheterized fetal sheep were studied through a series of mild, moderate and severe UCO until the arterial pH was below 7.00. At a pH of 7.24±0.04, 52±13 min prior to the pH dropping <7.00, spectral edge frequency (SEF) increased to 23±2 Hz from 3±1 Hz during each FHR deceleration (p<0.001) and was correlated to decreases in FHR and in fetal arterial blood pressure during each FHR deceleration (p<0.001). Conclusions/Significance The UCO-related changes in ECOG occurred in advance of the pH decreasing below 7.00. These ECOG changes may be a protective mechanism suppressing non-essential energy needs when oxygen supply to the fetal brain is decreased acutely. By detecting such “adaptive brain shutdown,” the need for delivery in high risk pregnant patients may be more accurately predicted than with FHR monitoring alone. Therefore, monitoring fetal electroencephalogram (EEG, the human equivalent of ECOG) during human labour may be a useful adjunct to FHR monitoring. PMID:21789218

Role of fetal sex in amniotic fluid alphafetoprotein screening.

PubMed

Knippel, Alexander Johannes

2002-10-01

Previous studies have shown that fetal gender has influence on various pregnancy complications and prenatal diagnostic biochemical markers. We have evaluated, whether elevation of amniotic fluid alphafetoprotein (AF AFP) is associated with fetal sex and whether a sex-related difference can help to identify pregnancies with AFP-associated malformations or fetal loss. From our database we obtained 6461 singleton gestations with AF AFP measurements for the period April 1997-March 1999. Patients with AF AFP >1.9 MoM were identified, details of pregnancy outcome were obtained and compared to matched-pair controls having AF AFP <2 MoM. In 232 of 262 patients having AF AFP levels >1.9 MoM outcome information was available. Of these fetuses, significantly more had male gender (147 male fetuses versus 85 female). Having a screen-positive result the risk of AFP-associated malformations was significantly higher for female fetuses (25 female fetuses (29.4%) versus 22 male fetuses (15%) with AFP-associated malformations). Adjusting the cut-off MoM to 2.5 for male and to 2.0 for female fetuses halves the false positive rate from 3.4 to 1.7% without affecting the detection rate of 95%. Pregnancies with false positive AF AFP had a significantly higher risk for fetal loss compared with pregnancies having normal AF AFP (ten fetal losses from 185 versus two fetal losses from 232), but fetal gender had no significant influence. Adjusting AF AFP MoM cut-offs for fetal gender could increase performance of AF-AFP screening. Larger studies are required to determine suitable sex-adjusted cut-off levels. Copyright 2002 John Wiley & Sons, Ltd.

Maternal high-fat diet is associated with impaired fetal lung development

PubMed Central

Mayor, Reina S.; Finch, Katelyn E.; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D.; Frank, Aaron P.; Hahner, Lisa D.; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F.; Rosenfeld, Charles R.; Savani, Rashmin C.

2015-01-01

Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development. PMID:26092997

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

Perinatal and Family Risk Factors for Hodgkin Lymphoma in Childhood Through Young Adulthood

PubMed Central

Crump, Casey; Sundquist, Kristina; Sieh, Weiva; Winkleby, Marilyn A.; Sundquist, Jan

2012-01-01

The incidence of Hodgkin lymphoma has increased among adolescents and young adults in recent decades, but the relevant risk factors in early life are still unknown. A national cohort study was conducted of 3,571,574 individuals born in Sweden in 1973–2008 and followed up for Hodgkin lymphoma incidence through 2009, to examine perinatal and family risk factors for Hodgkin lymphoma in childhood through young adulthood (ages 0–37 years). There were 943 Hodgkin lymphoma cases identified in 66.3 million person-years of follow-up. High fetal growth was associated with an increased risk of Hodgkin lymphoma after adjustment for gestational age at birth and other potential confounders (Ptrend = 0.005). Family history of Hodgkin lymphoma in a sibling or parent also was strongly associated with an increased risk, with adjusted hazard ratios = 8.83 (95% confidence interval: 3.67, 21.30) and 7.19 (95% confidence interval: 3.58, 14.44), respectively. No association was found between gestational age at birth, birth order, twinning, parental age, or parental education and Hodgkin lymphoma. These findings did not vary by age at Hodgkin lymphoma diagnosis. Similar associations were found for nodular sclerosis and mixed cellularity subtypes. These findings suggest that perinatal factors including possible growth factor pathways may contribute to the risk of Hodgkin lymphoma in childhood through young adulthood. PMID:23171883

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

PubMed

Buck Louis, Germaine M; Grewal, Jagteshwar; Albert, Paul S; Sciscione, Anthony; Wing, Deborah A; Grobman, William A; Newman, Roger B; Wapner, Ronald; D'Alton, Mary E; Skupski, Daniel; Nageotte, Michael P; Ranzini, Angela C; Owen, John; Chien, Edward K; Craigo, Sabrina; Hediger, Mary L; Kim, Sungduk; Zhang, Cuilin; Grantz, Katherine L

2015-10-01

Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were: humerus and femur lengths (10 weeks), abdominal circumference (16 weeks), head circumference (21 weeks), and biparietal diameter (27 weeks). The study-derived standard based solely on the white group erroneously classifies as much as 15% of non-white fetuses as growth restricted (EFW <5th percentile). Significant differences in fetal growth were found among the 4 groups. Racial/ethnic-specific standards improve the precision in evaluating fetal growth. Published by Elsevier Inc.

Spontaneous fetal death among multigravid fertile women in relation to sport fish consumption and PCB exposure, New York State Angler Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendola, P.

1994-01-01

Spontaneous fetal death, a sentinel event for environmental reproductive toxicity, has been observed among various mammalian species following polychlorinated biphenyl (PCB) exposure. This exposure-based cohort study assessed the relationship between PCB exposure due to consumption of contaminated Lake Ontario sport fish and spontaneous fetal death. Using 1,820 women from the 1990-1991 New York State Angler Study, fish consumption data were obtained from food frequency questionnaires and reproductive histories from live birth certificates. A reliability study demonstrated an excellent level of agreement between the exact number of spontaneous fetal deaths recorded on the birth certificate compared with telephone interview data (kappamore » = 0.83). Women who had never eaten Lake Ontario sport fish were unexposed (n = 979) and 841 women reported various levels of exposure. Analyses were stratified by maternal gravidity and controlled for smoking status and maternal age. No significant increases in risk for spontaneous fetal death were seen for any estimate of PCB exposure including lifetime estimate of PCB exposure based on species-specific PCB levels, years of fish consumption, and kilograms of fish consumed, either in the 1990-1991 season or in a lifetime estimate. The only significant finding was a slight risk reduction for women of gravidity three or more with years of fish consumption (odds ratio = 0.97; p = 0.03; 95% confidence interval = 0.94-0.99). These findings suggest that PCB exposure from contaminated sport fish does not increase the risk of spontaneous fetal death.« less

Fetal oxidative stress mechanisms of neurodevelopmental deficits and exacerbation by ethanol and methamphetamine.

PubMed

Wells, Peter G; Bhatia, Shama; Drake, Danielle M; Miller-Pinsler, Lutfiya

2016-06-01

In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108-130, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders.

PubMed

Nuttall, Johnathan R

2017-05-01

Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development. The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD. This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD. Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants. These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD.

Asymptomatic bacteriuria in pregnancy: maternal and fetal complications.

PubMed

Grio, R; Porpiglia, M; Vetro, E; Uligini, R; Piacentino, R; Minì, D; Marchino, G L

1994-12-01

From an analysis of the data reported in the literature it is clear that pregnancy is a predisposing factor for urinary tract infection and that pregnant women with this pathology are exposed to dangerous risks which may influence maternal wellbeing and fetal prognosis. Authors do not concur on the specific risks to the mother and fetus, one reason being that the statistics reported to date reveal discrepancies relating to the presence of disorders prior to pregnancy and the environmental, working and socio-hygienic conditions of the populations studied. The apparently paradoxical finding of a higher incidence of perinatal problems in pregnant women with asymptomatic bacteriuria compared to manifest forms can be attributed to the fact that the latter are treated with adequate therapies whereas asymptomatic bacteriuria, which is difficult to diagnose, may persist throughout pregnancy. This underlines the importance of early diagnosis using a protocol which entails the execution of serial urine tests and urine cultures and adequate treatment of all cases of asymptomatic bacteriuria in order to reduce the incidence of urinary tract infections and materno-fetal complications. Non-treated asymptomatic bacteriuria in fact represents a considerable risk factor since it may lead to the onset of acute pyelonephritis in approximately 5% of pregnant women and may increase the risk of fetal mortality.

Fetal heart rate abnormalities during and after external cephalic version: Which fetuses are at risk and how are they delivered?

PubMed

Kuppens, Simone M; Smailbegovic, Ida; Houterman, Saskia; de Leeuw, Ingrid; Hasaart, Tom H

2017-10-17

Fetal heart rate abnormalities (FHR) during and after external cephalic version (ECV) are relatively frequent. They may raise concern about fetal wellbeing. Only occasionally they may lead to an emergency cesarean section. Prospective cohort study in 980 women (> 34 weeks gestation) with a singleton fetus in breech presentation. During and after external cephalic version (ECV) FHR abnormalities were recorded. Obstetric variables and delivery outcome were evaluated. Primary outcome was to identify which fetuses are at risk for FHR abnormalities. Secondary outcome was to identify a possible relationship between FHR abnormalities during and after ECV and mode of delivery and fetal distress during subsequent labor. The overall success rate of ECV was 60% and in 9% of the attempts there was an abnormal FHR pattern. In two cases FHR abnormalities after ECV led to an emergency CS. Estimated fetal weight per 100 g (OR 0.90, CI: 0.87-0.94) and longer duration of the ECV-procedure (OR 1.13, CI: 1.05-1.21) were factors significantly associated with the occurrence of FHR abnormalities. FHR abnormalities were not associated with the mode of delivery or the occurrence of fetal distress during subsequent labor. FHR abnormalities during and after ECV are more frequent with lower estimated fetal weight and longer duration of the procedure. FHR abnormalities during and after ECV have no consequences for subsequent mode of delivery. They do not predict whether fetal distress will occur during labor. The Eindhoven Breech Intervention Study, NCT00516555 . Date of registration: August 13, 2007.

Determinants and outcome of fetal macrosomia in a Nigerian tertiary hospital.

PubMed

Olokor, Oghenefegor Edwin; Onakewhor, Joseph Ubini; Aderoba, Adeniyi Kolade

2015-01-01

To determine the incidence and risk factors of fetal macrosomia and maternal and perinatal outcome. This was a 1-year prospective case-control study of singleton pregnancies in a Nigerian tertiary hospital. Only women who gave consent were recruited for the study. The maternal and perinatal outcomes in women who delivered macrosomic infants (birth weight ≥ 4000 g) were compared with the next consecutive delivery of normal birth weight (2500-3999 g) infants. The total deliveries for the study period were 2437, of which 135 were macrosomic babies. The incidence of fetal macrosomia was 5.5%. The mean birth weights of macrosomic and nonmacrosomic babies were 4.26 ± 0.29 kg and 3.20 ± 0.38 kg, respectively, P = 0.000. Mothers with macrosomic babies were more likely to be older (P = 0.047), of higher parity (0.001), taller (P = 0.007), and weighed more at delivery (P = 0.000). Previous history of fetal macrosomia (P = 0.000) and maternal diabetes (P = 0.007) were factors strongly associated with the delivery of macrosomic infants. Pregnancies associated with fetal macrosomia had increased duration of labor (P = 0.007), interventional deliveries (P = 0.000), shoulder dystocia, and genital laceration (P = 0.000). There was no significant difference in the incidence of primary postpartum hemorrhage (P = 0.790), birth asphyxia, and perinatal mortality (P = 0.197). Fetal macrosomia is associated with maternal and fetal morbidities. The presence of the observed risk factors should elicit the suspicion of a macrosomic fetus and the need for appropriate management to reduce maternal and fetal morbidities.

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses.

PubMed

Zamora, Irving J; Sheikh, Fariha; Cassady, Christopher I; Olutoye, Oluyinka O; Mehollin-Ray, Amy R; Ruano, Rodrigo; Lee, Timothy C; Welty, Stephen E; Belfort, Michael A; Ethun, Cecilia G; Kim, Michael E; Cass, Darrell L

2014-06-01

The purpose of this study was to evaluate fetal magnetic resonance imaging (MRI) as a modality for predicting perinatal outcomes and lung-related morbidity in fetuses with congenital lung masses (CLM). The records of all patients treated for CLM from 2002 to 2012 were reviewed retrospectively. Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated. Multivariate regression and receiver operating characteristic analyses were applied to determine the predictive accuracy of prenatal imaging. Of 128 fetuses with CLM, 93% (n=118) survived. MRI data were available for 113 fetuses. In early gestation (<26weeks), MRI measurements of LMVR and LLV correlated with risk of fetal hydrops, mortality, and/or need for fetal intervention. In later gestation (>26weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal respiratory distress, intubation, NICU admission and need for neonatal surgery. On multivariate regression, LMVR was the strongest predictor for development of fetal hydrops (OR: 6.97, 1.58-30.84; p=0.01) and neonatal respiratory distress (OR: 12.38, 3.52-43.61; p≤0.001). An LMVR >2.0 predicted worse perinatal outcome with 83% sensitivity and 99% specificity (AUC=0.94; p<0.001). Fetal MRI volumetric measurements of lung masses and residual normal lung are predictive of perinatal outcomes in fetuses with CLM. These data may assist in perinatal risk stratification, counseling, and resource utilization. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical outcomes and predictors of fetal and maternal consequences of pregnancy in lupus nephritis patients.

PubMed

Lv, Jiaxuan; Wang, Wei; Li, Yuehong

2015-08-01

To define the outcomes and risk predictors of fetal and maternal consequences of pregnancy in lupus nephritis (LN) patients. Maternal and fetal outcomes of pregnancy in 52 systemic lupus erythematosus (SLE) patients were observed. Patients were allocated into two groups according to the presence or absence of LN. LN patients were subject to a higher risk of fetal complications, including fetal loss (7/24, 29.2 %, P = 0.001), lower birth weight (2548.2 ± 540.8 vs. 2949.1 ± 592.6 g, P = 0.028) and a higher frequency of small for gestational age births (33.3 vs. 10.7 %, P = 0.002). Higher rates of lupus flares (83.3 vs. 21.4 %, P = 0.001) and increased LAI-P scores (0.65 ± 0.36 vs. 0.21 ± 0.27, P = 0.001) during pregnancy were observed in LN patients. Multivariate analysis showed that increased SLE activity (P = 0.02, OR 4.2, 95 % CI 1.2-14.5), renal damage (P = 0.001, OR 8.4, 95 % CI 2.2-31.8), hypocomplementemia (P = 0.05, OR 3.23, 95 % CI 1.0-10.7), hypoalbuminemia (P = 0.011, OR 5.62, 95 % CI 1.4-23.0) and hypertension (P = 0.021, OR 6.0, 95 % CI 1.5-24.2) during pregnancy were predictors of adverse fetal outcomes. Pregnancy in LN patients should be monitored before and during pregnancy because of poor fetal and maternal outcomes. Increased LAI-P scores, renal damage, hypocomplementemia, hypoalbuminemia and hypertension are predictors of adverse fetal outcomes for SLE patients.

Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

PubMed

Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

2018-01-01

Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

Sex Differences in Fetal Habituation

ERIC Educational Resources Information Center

Hepper, Peter G.; Dornan, James C.; Lynch, Catherine

2012-01-01

There is some evidence for sex differences in habituation in the human fetus, but it is unknown whether this is due to differences in central processing (habituation) or in more peripheral processes, sensory or motor, involved in the response. This study examined whether the sex of the fetus influenced auditory habituation at 33 weeks of…

Influenza and its treatment during pregnancy: A review.

PubMed

Ghulmiyyah, L M; Alame, M M; Mirza, F G; Zaraket, H; Nassar, A H

2015-01-01

The influenza viral infection has dramatic effects during pregnancy on the mother and the fetus. We present a review article on the prevention and treatment recommendations of influenza infection in pregnant women, and the effects of antiviral medications on maternal-fetal outcomes. This viral infection not only leads to miscarriages, preterm deliveries and a high maternal mortality rate, but it also poses negative risks to the fetus including small-for-gestational age infants, and admissions to neonatal intensive care units. Vaccination is the most effective strategy for preventing influenza infection during pregnancy whereby can protect both maternal and fetal immunities. The safety profiles of antiviral drugs during pregnancy are limited. Available risk-benefit evidence has indicated that pregnant women with suspected or confirmed influenza should receive prompt antiviral therapy where these medications reduce the risk of complications among pregnant women, and attenuate the teratogenic effects of the influenza infection. Post-exposure prophylaxis is not recommended for most pregnant women, but it may be prescribed in pandemic settings, particularly to non-vaccinated women. Although some ex vivo models for pharmacokinetic studies have revealed that the transplacental transfer of oseltamivir to fetal circuits may occur, there is no evidence of adverse fetal outcomes as a result of most in utero exposures to neuraminidase inhibitors. Due to the large number of confounding variables, large, population-based studies are needed to assess the association between in utero oseltamivir exposure and fetal outcome.

Does corticosteroid therapy impact fetal pulmonary artery blood flow in women at risk for preterm birth?

PubMed

Lindsley, William; Hale, Richard; Spear, Ashley; Adusumalli, Jasvant; Singh, Jasbir; DeStefano, Kimberly; Haeri, Sina

2015-09-01

Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB). We prospectively evaluated main fetal pulmonary artery (MPA) blood flow in pregnant women at risk for PTB and treated with corticosteroids (betamethasone), compared to an uncomplicated cohort without steroid therapy. The Doppler indices of interest included Peak Systolic Velocity (PSV), Resistive Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D ratio), Acceleration Time (AT), and Acceleration Time/Ejection Time Ratio (AT/ET ratio), with the latter serving as the primary outcomes due to its stability irrespective of gestational age. When compared with controls, fetuses treated with corticosteroids demonstrated significantly decreased pulmonary artery acceleration time (median: 28.89 (22.22-51.11) vs. 33.33 (22.20-57.00), p=0.006), while all other indices remained similar. We found no difference in pulmonary blood flow between fetuses who developed respiratory distress syndrome (RDS) and those that did not (31.56 +/- 6.842 vs. 32.36 +/- 7.265, p= 0.76). Our data demonstrate altered fetal pulmonary blood flow with corticosteroid therapy, possibly due to increased arterial elastance brought on by medication effect, which leads to the decreased acceleration time or possible gestational age affect. Contrary to a recent report, we did not observe any Doppler differences in fetuses with RDS, which underscores the need for further examination of this proposed association.

Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study

PubMed Central

Carroli, Guillermo; Zavaleta, Nelly; Donner, Allan; Wojdyla, Daniel; Faundes, Anibal; Velazco, Alejandro; Bataglia, Vicente; Langer, Ana; Narváez, Alberto; Valladares, Eliette; Shah, Archana; Campodónico, Liana; Romero, Mariana; Reynoso, Sofia; de Pádua, Karla Simônia; Giordano, Daniel; Kublickas, Marius; Acosta, Arnaldo

2007-01-01

Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery. Design Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health. Setting 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data Participants 106 546 deliveries reported during the three month study period, with data available for 97 095 (91% coverage). Main outcome measures Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics. Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective. Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations. PMID:17977819

UK NHS pilot study on cell-free DNA testing in screening for fetal trisomies: factors affecting uptake.

PubMed

Gil, M M; Giunta, G; Macalli, E A; Poon, L C; Nicolaides, K H

2015-01-01

This study reports on the clinical implementation of cell-free DNA (cfDNA) testing, contingent on the results of the combined test, in screening for fetal trisomies 21, 18 and 13 in two UK National Health Service hospitals. Women with a combined-test risk of ≥ 1:100 (high risk) were offered the options of chorionic villus sampling (CVS), cfDNA testing or no further testing and those with a risk of 1:101 to 1:2500 (intermediate risk) were offered cfDNA or no further testing. The objective of the study was to examine the factors affecting patient decisions concerning their options. Combined screening was performed in 6651 singleton pregnancies in which the risk for trisomies was high in 260 (3.9%), intermediate in 2017 (30.3%) and low in 4374 (65.8%). Logistic regression analysis was used to determine which factors among maternal characteristics, fetal nuchal translucency thickness (NT) and risk for trisomies were significant predictors of opting for CVS in the high-risk group and opting for cfDNA testing in the intermediate-risk group. In the high-risk group, 104 (40.0%) women opted for CVS; predictors for CVS were increasing fetal NT and increasing risk for trisomies, while the predictor against CVS was being of Afro-Caribbean racial origin (r = 0.366). In the intermediate-risk group, 1850 (91.7%) women opted for cfDNA testing; predictors for cfDNA testing were increasing maternal age, increasing risk for trisomies and university education, while predictors against cfDNA testing were being of Afro-Caribbean racial origin, smoking and being parous (r = 0.105). This study has identified factors that can influence the decision of women undergoing combined screening in favor of or against CVS and in favor of or against cfDNA testing. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

The added predictive value of biphasic events in ST analysis of the fetal electrocardiogram for intrapartum fetal monitoring.

PubMed

Becker, Jeroen H; Krikhaar, Anniek; Schuit, Ewoud; Mårtendal, Annika; Maršál, Karel; Kwee, Anneke; Visser, Gerard H A; Amer-Wåhlin, Isis

2015-02-01

To study the predictive value of biphasic ST-events for interventions for suspected fetal distress and adverse neonatal outcome, when using ST-analysis of the fetal electrocardiogram (FECG) for intrapartum fetal monitoring. Prospective cohort study. Three academic hospitals in Sweden. Women in labor with a high-risk singleton fetus in cephalic position beyond 36 weeks of gestation. In women in labor who were monitored with conventional cardiotocography, ST-waveform analysis was recorded and concealed. Traces with biphasic ST-events of the FECG (index) were compared with traces without biphasic events of the FECG. The ability of biphasic events to predict interventions for suspected fetal distress and adverse outcome was assessed using univariable and multivariable logistic regression analyses. Interventions for suspected fetal distress and adverse outcome (defined as presence of metabolic acidosis (i.e. umbilical cord pH <7.05 and base deficit in extracellular fluid >12 mmol), umbilical cord pH <7.00, 5-min Apgar score <7, admittance to neonatal intensive care unit or perinatal death). Although the presence of biphasic events of the FECG was associated with more interventions for fetal distress and an increased risk of adverse outcome compared with cases with no biphasic events, the presence of significant (i.e. intervention advised according to cardiotocography interpretation) biphasic events showed no independent association with interventions for fetal distress [odds ratio (OR) 1.71, 95% confidence interval (CI) 0.65-4.50] or adverse outcome (OR 1.96, 95% CI 0.74-5.24). The presence of significant biphasic events did not discriminate in the prediction of interventions for fetal distress or adverse outcome. Therefore, biphasic events in relation to ST-analysis monitoring during birth should be omitted if future studies confirm our findings. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Risks to the fetus from diagnostic imaging during pregnancy: review and proposal of a clinical protocol.

PubMed

Gomes, Mafalda; Matias, Alexandra; Macedo, Filipe

2015-12-01

Every day, medical practitioners face the dilemma of exposing pregnant or possibly pregnant patients to radiation from diagnostic examinations. Both doctors and patients often have questions about the risks of radiation. The most vulnerable period is between the 8th and 15th weeks of gestation. Deterministic effects like pregnancy loss, congenital malformations, growth retardation and neurobehavioral abnormalities have threshold doses above 100-200 mGy. The risk is considered negligible at 50 mGy and in reality no diagnostic examination exceeds this limit. The risk of carcinogenesis is slightly higher than in the general population. Intravenous iodinated contrast is discouraged, except in highly selected patients. Considering all the possible noxious effects of radiation exposure, measures to diminish radiation are essential and affect the fetal outcome. Nonionizing procedures should be considered whenever possible and every radiology center should have its own data analysis on fetal radiation exposure. In this review, we analyze existing literature on fetal risks due to radiation exposure, producing a clinical protocol to guide safe radiation use in a clinical setting.

Troponin T and Pro–B-Type Natriuretic Peptide in Fetuses of Type 1 Diabetic Mothers

PubMed Central

Russell, Noirin E.; Higgins, Mary F.; Amaruso, Michael; Foley, Michael; McAuliffe, F.M.

2009-01-01

OBJECTIVE Cardiomyopathy is noted in up to 40% of infants of diabetic mothers, and the exact mechanisms are unknown. The aim of this study was to determine whether fetal serum markers of cardiac function differ between normal and type 1 diabetic pregnancies and to examine the relationship between these markers and fetal cardiac structure and function. RESEARCH DESIGN AND METHODS This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro–B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester. RESULTS Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05). CONCLUSIONS Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants. PMID:19690080

Mother's educational level and fetal growth: the genesis of health inequalities.

PubMed

Silva, Lindsay M; Jansen, Pauline W; Steegers, Eric A P; Jaddoe, Vincent W V; Arends, Lidia R; Tiemeier, Henning; Verhulst, Frank C; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

2010-10-01

Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.

Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

PubMed

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

2009-10-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

Is fetal brain monoamine oxidase inhibition the missing link between maternal smoking and conduct disorders?

PubMed Central

Baler, Ruben D.; Volkow, Nora D.; Fowler, Joanna S.; Benveniste, Helene

2008-01-01

Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development — but not during adult life — is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke–induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke. PMID:18592036

Maternal influences on fetal microbial colonization and immune development

PubMed Central

Romano-Keeler, Joann; Weitkamp, Jörn-Hendrik

2014-01-01

While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization. PMID:25310759

SU-F-I-36: In-Utero Dose Measurements Within Postmortem Subjects for Estimating Fetal Doses in Pregnant Patients Examined with Pulmonary Embolism, Trauma, and Appendicitis CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipnharski, I; Quails, N; Carranza, C

Purpose: The imaging of pregnant patients is medically necessary in certain clinical situations. The purpose of this work was to directly measure uterine doses in a cadaver scanned with CT protocols commonly performed on pregnant patients in order to estimate fetal dose and assess potential risk. Method: One postmortem subject was scanned on a 320-slice CT scanner with standard pulmonary embolism, trauma, and appendicitis protocols. All protocols were performed with the scan parameters and ranges currently used in clinical practice. Exams were performed both with and without iterative reconstruction to highlight the dose savings potential. Optically stimulated luminescent dosimeters (OSLDs)more » were inserted into the uterus in order to approximate fetal doses. Results: In the pulmonary embolism CT protocol, the uterus is outside of the primary beam, and the dose to the uterus was under 1 mGy. In the trauma and appendicitis protocols, the uterus is in the primary beam, the fetal dose estimates were 30.5 mGy for the trauma protocol, and 20.6 mGy for the appendicitis protocol. Iterative reconstruction reduced fetal doses by 30%, with uterine doses at 21.3 for the trauma and 14.3 mGy for the appendicitis protocol. Conclusion: Fetal doses were under 1 mGy when exposed to scatter radiation, and under 50 mGy when exposed to primary radiation with the trauma and appendicitis protocols. Consistent with the National Council on Radiation Protection & Measurements (NCRP) and the International Commission on Radiological Protection (ICRP), these doses exhibit a negligible risk to the fetus, with only a small increased risk of cancer. Still, CT scans are not recommended during pregnancy unless the benefits of the exam clearly outweigh the potential risk. Furthermore, when possible, pregnant patients should be examined on CT scanners equipped with iterative reconstruction in order to keep patient doses as low as reasonable achievable.« less

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction.

PubMed

Groom, Katie M; David, Anna L

2018-02-01

Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology. This renders the study findings less reliable for determining clinical significance. For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0.90, 95% confidence interval, 0.81-1.00) and that a dose of ≥100 mg should be recommended and to start at or before 16 weeks of gestation. These findings support national clinical practice guidelines. In vitro and in vivo studies suggest that low-molecular-weight heparin may prevent fetal growth restriction; however, evidence from randomized control trials is inconsistent. A meta-analysis of multicenter trial data does not demonstrate any positive preventative effect of low-molecular-weight heparin on a primary composite outcome of placenta-mediated complications including fetal growth restriction (18% vs 18%; absolute risk difference, 0.6%; 95% confidence interval, 10.4-9.2); use of low-molecular-weight heparin for the prevention of fetal growth restriction should remain in the research setting. There are even fewer treatment options once fetal growth restriction is diagnosed. At present the only management option if the risk of hypoxia, acidosis, and intrauterine death is high is iatrogenic preterm birth, with the use of peripartum maternal administration of magnesium sulphate for neuroprotection and corticosteroids for fetal lung maturity, to prevent adverse neonatal outcomes. The pipeline of potential therapies use different strategies, many aiming to increase fetal growth by improving poor placentation and uterine blood flow. Phosphodiesterase type 5 inhibitors that potentiate nitric oxide availability such as sildenafil citrate have been extensively researched both in preclinical and clinical studies; results from the Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction consortium of randomized control clinical trials are keenly awaited. Targeting the uteroplacental circulation with novel therapeutics is another approach, the most advanced being maternal vascular endothelial growth factor gene therapy, which is being translated into the clinic via the doEs Vascular endothelial growth factor gene therapy safEly impRove outcome in seveRe Early-onset fetal growth reSTriction consortium. Other targeting approaches include nanoparticles and microRNAs to deliver drugs locally to the uterine arterial endothelium or trophoblast. In vitro and in vivo studies and animal models have demonstrated effects of nitric oxide donors, dietary nitrate, hydrogen sulphide donors, statins, and proton pump inhibitors on maternal blood pressure, uteroplacental resistance indices, and angiogenic/antiangiogenic factors. Data from human pregnancies and, in particular, pregnancies with fetal growth restriction remain very limited. Early research into melatonin, creatine, and N-acetyl cysteine supplementation in pregnancy suggests they may have potential as neuro- and cardioprotective agents in fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement.

PubMed

Brown, Rebecca; Higgins, Lucy E; Johnstone, Edward D; Wijekoon, Jayawan H; Heazell, Alexander E P

2016-01-01

A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.

Doppler flowmetry in preeclampsia.

PubMed

Zahumensky, J

2009-01-01

The purpose of this study was to summarize the new published data on the Doppler flowmetry in preeclampsia. We summarize the new published data on the Doppler flowmetry in uteroplacental, fetoplacental and fetal circulation in preeclampsia. The present review summarized the results of clinical research on the Doppler flowmetry in the screening of risk of preclampsia, in the diagnosis of preclampsia and in the fetal risk in preclampsia (Ref. 19). Full Text (Free, PDF) www.bmj.sk.

An environment-dependent transcriptional network specifies human microglia identity.

PubMed

Gosselin, David; Skola, Dylan; Coufal, Nicole G; Holtman, Inge R; Schlachetzki, Johannes C M; Sajti, Eniko; Jaeger, Baptiste N; O'Connor, Carolyn; Fitzpatrick, Conor; Pasillas, Martina P; Pena, Monique; Adair, Amy; Gonda, David D; Levy, Michael L; Ransohoff, Richard M; Gage, Fred H; Glass, Christopher K

2017-06-23

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.

PubMed

Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi

2015-01-01

Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

Cesarean section among immigrants in Norway.

PubMed

Vangen, S; Stoltenberg, C; Skrondal, A; Magnus, P; Stray-Pedersen, B

2000-07-01

We studied prevalences and risk factors for cesarean section among different groups of immigrants from countries outside Western Europe and North America in comparison to ethnic Norwegians. The study is population based using data from the Medical Birth Registry of Norway. A total of 553,491 live births during the period 1986-1995 were studied, including 17,891 births to immigrant mothers. The prevalences of cesarean section ranged from 10.1% among women from Vietnam to 25.8% in the group of Filipino origin. The use of abdominal delivery was also high in the groups from Sri Lanka/India (21.3%), Somalia/Eritrea/Ethiopia (20.5%) and Chile/Brazil (24.3%), while the frequency among women from Turkey/Morocco (12.6%) and Pakistan (13.2%) was approximately the same as among ethnic Norwegians (12.4%). Feto-pelvic disproportion, fetal distress and prolonged labor were the most important diagnoses associated with the high prevalences, but the significance of these diagnoses differed among the groups. Other unknown factors come into play, particularly among women from Somalia/Eritrea/Ethiopia and Chile/Brazil. There was substantial variation in the use of cesarean section among ethnic groups in Norway. The diagnoses feto-pelvic disproportion, fetal distress and prolonged labor may be confounded by a number of factors including maternal request for cesarean section and difficulties in handling the delivery. Further research is needed to explain the observed differences.

Legionnaire's disease complicating pregnancy: a case report with intrauterine fetal demise.

PubMed

Vimercati, A; Greco, P; Bettocchi, S; Resta, L; Selvaggi, L

2000-01-01

Legionnaire's disease complicating pregnancy is an unusual event that can seriously compromise both the mother and the fetus. We describe one case of such association, with an unfavourable intrauterine fetal outcome, secondary to acute placental insufficiency, related to infection. It is important in these high risk pregnancies complicated by acute pneumonia to take into consideration the diagnosis, as early as possible, and the appropriate treatment or the careful monitoring of fetal wellbeing.

Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver.

PubMed

Kakinuma, Sei; Ohta, Haruhiko; Kamiya, Akihide; Yamazaki, Yuji; Oikawa, Tsunekazu; Okada, Ken; Nakauchi, Hiromitsu

2009-07-01

Hepatic stem/progenitor cells possess active proliferative ability and the capacity for differentiation into hepatic and cholangiocytic lineages. Our group and others have shown that a prospectively defined population in mid-gestational fetal liver contains hepatic stem/progenitor cells. However, the phenotypes of such cells are incompletely elucidated. We analyzed the profile of cell-surface molecules on primary hepatic stem/progenitor cells. Expression of cell surface molecules on primary hepatic stem/progenitor cells in mouse mid-gestational fetal liver was analyzed using flow cytometric multicolor analyses and colony-formation assays. The potential of the cells for liver repopulation was examined by transplantation assay. We found that CD13 (aminopeptidase N) was detected on the cells of the previously reported (Dlk/Pref-1(+)) hepatic stem/progenitor fraction. Colony-formation assays revealed that the CD13(+) fraction, compared with the Dlk(+) fraction, of non-hematopoietic cells in fetal liver was enriched in hepatic stem/progenitor cells. Transplantation assay showed the former fraction exhibited repopulating potential in regenerating liver. Moreover, flow cytometric analysis for over 90 antigens demonstrated enrichment of hepatic stem/progenitor cells using several positive selection markers, including (hitherto unknown) CD13, CD73, CD106, and CD133. Our data indicated that CD13 is a positive selection marker for hepatic stem/progenitor cells in mid-gestational fetal liver.

Nestin is highly expressed in fetal spinal cord isolated from placenta previa patients and promotes inflammation by enhancing NF-κB activity.

PubMed

Li, Ling; Zhang, Jing; Gao, Huahe; Ma, Yuyan

2018-04-26

Purpose Nestin is expressed in various tissues of the embryo in patients with placenta previa, while the regulatory mechanism still unknown. Materials and methods All participants terminated pregnancy. Among them, 75 patients with placenta previa were assigned to the case group and 80 healthy pregnant women with normal placenta were assigned to the control group. Expression of nestin and CDK5 in fetal spinal cord tissues was detected by Western Blot and RT-qPCR methods. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum expression of some pro-inflammatory cytokines in placenta previa patients. The interaction between nestin and CDK5 was evaluated by immunoprecipitation and siRNA inhibition of nestin was performed to estimate its effect on NF-κB activity in fetal spinal cord tissues. Results Along with increased expression of nestin and CDK5 in fetal spinal cord tissues in the case group, IL-1β, IL-6, TNF-α, and IFN-γ were increased in the serum of placenta previa patients. siRNA inhibition analysis indicated that nestin interacted with CDK5 and regulated NF-κB activity in fetal spinal cord tissues. Conclusions Nestin is highly expressed and the interaction between nestin and CDK5 might lead to the progress of placenta previa through its regulation on NF-κB.

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

PubMed

Orlandini, Cinzia; Torricelli, Michela; Spirito, Nicoletta; Alaimo, Lucia; Di Tommaso, Mariarosaria; Severi, Filiberto Maria; Ragusa, Antonio; Petraglia, Felice

2017-07-01

Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

PubMed

Liu, Hai Lun; Garzoni, Luca; Herry, Christophe; Durosier, Lucien Daniel; Cao, Mingju; Burns, Patrick; Fecteau, Gilles; Desrochers, André; Patey, Natalie; Seely, Andrew J E; Faure, Christophe; Frasch, Martin G

2016-04-01

Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. Prospective animal study. University research laboratory. Chronically instrumented near-term fetal sheep (n = 21). Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals, correlated uniquely to M1 ileum macrophages increasing due to lipopolysaccharide. We identified a unique subset of fetal heart rate variability measures reflecting 1.5 days ahead of time the levels of macrophage activation and increased leakiness in terminal ileum. We propose that such subset of fetal heart rate variability measures reflects brain-gut communication via the vagus nerve. Detecting such noninvasively obtainable organ-specific fetal heart rate variability signature of inflammation would alarm neonatologists about neonates at risk of developing necrotizing enterocolitis and sepsis. Clinical validation studies are required.

Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction

EPA Science Inventory

Fetal growth restriction is a major underlying cause of infant mortality worldwide. Despite knowledge of risk factors for adverse pregnancy outcomes, the mechanisms that drive compromised growth during pregnancy have not been well established. Placental maladaptation, particularl...

Correlation of fetal oxygen saturation to fetal heart rate patterns. Evaluation of fetal pulse oximetry with two different oxisensors.

PubMed

Luttkus, A K; Friedmann, W; Homm-Luttkus, C; Dudenhausen, J W

1998-03-01

The purpose of this study was the correlation of fetal oxygen saturation values to various fetal heart rate patterns, as well as to oxygen saturation values obtained by fetal blood analysis. These objectives need to be evaluated from the perspective that two generations of fetal oxisensors have been used. Two different oxisensor systems (FS10: 660+890 nm and FS14: 735+890 nm) and a blinded pulse oximeter (type N400, Nellcor Puritan Bennett) were utilized to monitor 112 fetuses. All data, including oxygen saturation, fetal heart rate patterns, signal and contact quality were stored on a personal computer and evaluated after delivery. The following median fetal oxygen saturation values were obtained: during reassuring fetal heart rate sequences 54% with the oxisensor FS10 and 48% with the newer FS14 oxisensor, during intervals of variable decelerations 43% with the FS10 oxisensor and 40% with the FS14 oxisensor. These differences between values obtained during normal and abnormal fetal heart rate patterns are significant. Due to non-reassuring fetal heart rate patterns 81 fetal blood analyses were performed. The values of pulse oximetry were 9% higher (6% for the FS14) than those of spectrophotometry. Correlation of both methods was r=0.66 (0.74 for the FS14). In combination with fetal heart rate monitoring, fetal pulse oximetry promises a better differentiation between low and high risk heart rate patterns. Oxygen saturation values from intermittent fetal blood sampling reassure the clinician concerning the accuracy of this new method of intrapartum fetal surveillance and underline the increased quality of the new generation of oxisensor using light of a wavelength of 735 and 890 nm.

[Per partum acidosis: Interest and feasibility of cerebral Doppler during labor].

PubMed

Barrois, M; Chartier, M; Lecarpentier, E; Goffinet, F; Tsatsaris, V

2016-09-01

To evaluate feasibility and interest of fetal cerebral Doppler during labor and the link with fetal pH to predict perinatal fetal asphyxia. Our prospective study in a university perinatal center, included patients during labor. There were no risk factors during pregnancy and patients were included after 37 weeks of pregnancy. For each patient an ultrasound with cerebral Doppler was done concomitant to a fetal scalp blood sample. We collected maternal and fetal characteristics as well as cervix dilatation, fetal heart rate analysis and fetal presentation. Among 49 patients included over a period of 4 months, cerebral Doppler failed in 7 cases (11%). Majority of failure occurred at 10cm of dilatation (P=0.007, OR=14.1 [1.483; 709.1275]). Others factors like: maternal age, body mass index, parity, history of C-Section were not associated with higher rate of failure. We did not found either significant correlation between cerebral fetal Doppler and pH on fetal scalp blood sample (r=0.15) nor pH at cord blood sample (r=0.13). No threshold of cerebral Doppler is significant for fetal asphyxia prediction. Fetal cerebral Doppler is feasible during labor with a low rate of failure but not a good exam to predict fetal acidosis and asphyxia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

External cephalic version facilitation for breech presentation at term.

PubMed

Hofmeyr, G J

2001-01-01

Tocolytic drugs to relax the uterus as well as other methods have been also used in an attempt to facilitate external cephalic version at term. The objective of this review is to assess the effects of routine tocolysis, fetal acoustic stimulation, epidural or spinal analgesia and transabdominal amnioinfusion for external cephalic version at term on successful version and measures of pregnancy outcome. The Cochrane Pregnancy and Childbirth Group Trials Register and the Cochrane Controlled Trials Register were searched. Date of last search: April 2001. Randomised and quasi-randomised trials comparing routine versus selective tocolysis; fetal acoustic stimulation in midline fetal spine positions versus dummy or no stimulation; epidural or spinal analgesia versus no regional analgesia; or transabdominal amnioinfusion versus no amnioinfusion for external cephalic version at term. Eligibility and trial quality were assessed by the reviewer. In seven trials, routine tocolysis was associated with fewer failures of external cephalic version (relative risk 0.74, 95% confidence interval 0.64 to 0.87). There were no significant differences between non-cephalic presentations at birth. Caesarean sections were reduced (relative risk 0.85, confidence interval 0.72-0.99). Fetal acoustic stimulation in midline fetal spine positions was associated with fewer failures of external cephalic version at term (relative risk 0.17, 95% confidence interval 0.05 to 0.60). With epidural or spinal analgesia, external cephalic version failure, non-cephalic births and caesarean sections were reduced in one trial but not the other. The overall differences were not statistically significant. No randomised trials of transabdominal amnioinfusion for external cephalic version at term were located. Routine tocolysis appears to reduce the failure rate of external cephalic version at term. Although promising, there is not enough evidence to evaluate the use of fetal acoustic stimulation in midline fetal spine positions, nor of epidural or spinal analgesia. Large volume intravenous preloading may have contributed to the effectiveness demonstrated in one of the latter trials. No randomised trials of transabdominal amnioinfusion for external cephalic version at term were found.

Gender mix in twins and fetal growth, length of gestation and adult cancer risk.

PubMed

Luke, Barbara; Hediger, Mary; Min, Sung-Joon; Brown, Morton B; Misiunas, Ruta B; Gonzalez-Quintero, Victor Hugo; Nugent, Clark; Witter, Frank R; Newman, Roger B; Hankins, Gary D V; Grainger, David A; Macones, George A

2005-01-01

This study evaluated the effect of gender mix (the gender combinations of twin pairs) on fetal growth and length of gestation, and reviewed the literature on the long-term effects of this altered fetal milieu on cancer risk. In singletons, it is well established that females weigh less than males at all gestations, averaging 125-135 g less at full term. This gender difference is generally believed to be the result of the effect of androgens on fetal growth. The gender difference in fetal growth is greater before the third trimester and less towards term, with males growing not only more, but also earlier than females. Plurality is a known risk factor for reduced fetal growth and birthweight. Compared with singletons, the mean birthweight percentiles of twins fall substantially (by 10% or more) below the singleton 10th percentile by 28 weeks, below the singleton 50th percentile by 30 weeks, and below the singleton 90th percentile by 34 weeks. In unlike-gender twin pairs, it has been reported that the female prolongs gestation for her brother, resulting in a higher birthweight for the male twin than that of like-gender male twins. Other researchers have demonstrated that females in unlike-gender pairs had higher birthweights than females in like-gender pairs. Analyses from our consortium on 2491 twin pregnancies with known chorionicity showed longer gestations and faster rates of fetal growth in both males and females in unlike-gender pairs compared with like-gender male or female pairs, although these differences were not statistically significant. The post-natal effects for females growing in an androgenic-anabolic environment include increased sensation-seeking behaviour and aggression, lowered visual acuity, more masculine attitudes and masculinising effects of the auditory system and craniofacial growth. In contrast, there is no evidence to suggest that there might be a similar feminising effect on males from unlike-gender pairs. This hormonal exposure in utero may influence adult body size and susceptability to breast cancer.

Management and outcomes of 27 pregnancies in women with myeloproliferative neoplasms.

PubMed

Lapoirie, Joëlle; Contis, Anne; Guy, Alexandre; Lifermann, François; Viallard, Jean-François; Sentilhes, Loïc; James, Chloé; Duffau, Pierre

2018-06-26

Philadelphia-negative myeloproliferative neoplasms (MPNs) greatly increase the risk of maternal and fetal complications during pregnancy. Currently, international agreements regarding the management of these women are lacking. Our study aimed to assess the current management and outcomes of MPN pregnancies in a French cohort. We retrospectively analyzed 27 pregnancies in women with MPNs that were associated with a specific mutation. Nineteen pregnancies in nine women with essential thrombocythemia and eight pregnancies in five women with polycythemia vera were identified. Our study showed 70% live births, but only 30% uneventful pregnancies. Fetal complications were mainly early spontaneous abortions (22%), fetal growth restriction (15%), and premature delivery (15%). Maternal issues were divided between thrombosis (15%) and hemorrhages (11%). High rates of preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome (15%) were reported. Uterine artery Doppler was performed in 70% pregnancies. Abnormal Doppler results were found in 43% pregnancies. Pregnancies with high platelet counts and packed cell volume remaining static or increasing ended with fetal death and utero-placental dysfunction. According to expert consensus, most of the pregnancies (67%) could be stratified in the high risk group and had a bad obstetrical outcome, with 50% standard-risk pregnancies versus 22% high-risk pregnancies that were uneventful. Higher risk pregnancies were prescribed heparin and/or interferon α in 72%. The prognosis of these pregnancies remains very bad and may be improved by a more effective collaboration between specialists as well as a therapeutic intensification including heparin and interferon α.

Impact of fetal death reporting requirements on early neonatal and fetal mortality rates and racial disparities.

PubMed

Tyler, Crystal P; Grady, Sue C; Grigorescu, Violanda; Luke, Barbara; Todem, David; Paneth, Nigel

2012-01-01

Racial disparities in infant and neonatal mortality vary substantially across the U.S. with some states experiencing wider disparities than others. Many factors are thought to contribute to these disparities, but state differences in fetal death reporting have received little attention. We examined whether such reporting requirements may explain national variation in neonatal and fetal mortality rates and racial disparities. We used data on non-Hispanic white and non-Hispanic black infants from the U.S. 2000-2002 linked birth/infant death and fetal death records to determine the degree to which state fetal death reporting requirements explain national variation in neonatal and fetal mortality rates and racial disparities. States were grouped depending upon whether they based the lower limit for fetal death reporting on birthweight alone, gestational age alone, both birthweight and gestational age, or required reporting of all fetal deaths. Traditional methods and the fetuses-at-risk approach were used to calculate mortality rates, 95% confidence intervals, and relative and absolute racial disparity measures in these four groups. States with birthweight-alone fetal death thresholds substantially underreported fetal deaths at lower gestations and slightly overreported neonatal deaths at older gestations. This finding was reflected by these states having the highest neonatal mortality rates and disparities, but the lowest fetal mortality rates and disparities. Using birthweight alone as a reporting threshold may promote some shift of fetal deaths to newborn deaths, contributing to racial disparities in neonatal mortality. The adoption of a uniform national threshold for reporting fetal deaths could reduce systematic differences in live birth and fetal death reporting.

Digital PCR analysis of maternal plasma for noninvasive detection of sickle cell anemia.

PubMed

Barrett, Angela N; McDonnell, Thomas C R; Chan, K C Allen; Chitty, Lyn S

2012-06-01

Cell-free fetal DNA (cffDNA) constitutes approximately 10% of the cell-free DNA in maternal plasma and is a suitable source of fetal genetic material for noninvasive prenatal diagnosis (NIPD). The objective of this study was to determine the feasibility of using digital PCR for NIPD in pregnancies at risk of sickle cell anemia. Minor-groove binder (MGB) TaqMan probes were designed to discriminate between wild-type hemoglobin A and mutant (hemoglobin S) alleles encoded by the HBB (hemoglobin, beta) gene in cffDNA isolated from maternal plasma samples obtained from pregnancies at risk of sickle cell anemia. The fractional fetal DNA concentration was assessed in male-bearing pregnancies with a digital PCR assay for the Y chromosome-specific marker DYS14. In pregnancies with a female fetus, a panel of biallelic insertion/deletion polymorphism (indel) markers was developed for the quantification of the fetal DNA fraction. We used digital real-time PCR to analyze the dosage of the variant encoding hemoglobin S relative to that encoding wild-type hemoglobin A. The sickle cell genotype was correctly determined in 82% (37 of 45) of male fetuses and 75% (15 of 20) of female fetuses. Mutation status was determined correctly in 100% of the cases (25 samples) with fractional fetal DNA concentrations >7%. The panel of indels was informative in 65% of the female-bearing pregnancies. Digital PCR can be used to determine the genotype of fetuses at risk for sickle cell anemia. Optimization of the fractional fetal DNA concentration is essential. More-informative indel markers are needed for this assay's comprehensive use in cases of a female fetus.

Physically demanding work, fetal growth and the risk of adverse birth outcomes. The Generation R Study.

PubMed

Snijder, Claudia A; Brand, Teus; Jaddoe, Vincent; Hofman, Albert; Mackenbach, Johan P; Steegers, Eric A P; Burdorf, Alex

2012-08-01

Work-related risk factors, such as long work hours, and physically demanding work have been suggested to adversely influence pregnancy outcome. The authors aimed to examine associations between various aspects of physically demanding work with fetal growth in different trimesters during pregnancy and the risks of adverse birth outcomes. Associations between physically demanding work and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in The Netherlands (2002-2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment) were included if they conducted paid employment and had a spontaneously conceived singleton live born pregnancy. Questions on physical workload were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on lifting, long periods of standing or walking, night shifts and working hours. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. There were no consistent significant associations between physically demanding work nor working hours in relation to small for gestational age, low birth weight or preterm delivery. Women exposed to long periods of standing had lower growth rates for fetal head circumference (HC), resulting in a reduction of approximately 1 cm (3%) of the average HC at birth. Compared with women working <25 h/week, women working 25-39 h/week and >40 h/week had lower growth rates for both fetal weight and HC, resulting in a difference of approximately 1 cm in HC at birth and a difference of 148-198 g in birth weight. Long periods of standing and long working hours per week during pregnancy seem to negatively influence intrauterine growth.

Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ao, Ying; Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071; Sun, Zhaoxia

Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well asmore » interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits fetal kidney development. • Prenatal caffeine exposure causes low functional programming of renal AT{sub 2}R.« less

Accelerated fetal growth in early pregnancy and risk of severe large-for-gestational-age and macrosomic infant: a cohort study in a low-risk population.

PubMed

Simic, Marija; Wikström, Anna-Karin; Stephansson, Olof

2017-10-01

Our objective was to examine the association between fetal growth in early pregnancy and risk of severe large-for-gestational-age (LGA) and macrosomia at birth in a low-risk population. Cohort study that included 68 771 women with non-anomalous singleton pregnancies, without history of diabetes or hypertension, based on an electronic database on pregnancies and deliveries in Stockholm-Gotland Region, Sweden, 2008-2014. We performed multivariable logistic regression to estimate the association between accelerated fetal growth occurring in the first through early second trimester as measured by ultrasound and LGA and macrosomia at birth. Restricted analyses were performed in the groups without gestational diabetes and with normal body mass index (18.5-24.9 kg/m 2 ). When adjusting for confounders, the odds of having a severely LGA or macrosomic infant were elevated in mothers with fetuses that were at least 7 days larger than expected as compared with mothers without age discrepancy at the second-trimester scan (adjusted odds ratio 1.80; 95% CI 1.23-2.64 and adjusted odds ratio 2.15; 95% CI 1.55-2.98, respectively). Additionally, mothers without gestational diabetes and mothers with normal weight had an elevated risk of having a severely LGA or macrosomic infant when the age discrepancy by second-trimester ultrasound was at least 7 days. In a low-risk population, ultrasound-estimated accelerated fetal growth in early pregnancy was associated with an increased risk of having a severely LGA or macrosomic infant. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Effect of Fetal Sex on Maternal and Obstetric Outcomes

PubMed Central

Al-Qaraghouli, Mohammed; Fang, Yu Ming Victor

2017-01-01

Fetal sex plays an important role in modifying the course and complications related to pregnancy and may also have an impact on maternal health and well-being both during and after pregnancy. The goal of this article is to review and summarize the findings from published research on physiologic and pathologic changes that may be affected by fetal sex and the effect of these changes on the maternal and obstetrical outcomes. This will help create awareness that fetal sex is not just a random chance event but an interactive process between the mother, the placenta, and the fetus. The reported effects of male sex on the course of pregnancy and delivery include higher incidence of preterm labor in singletons and twins, failure of progression in labor, true umbilical cord knots, cord prolapse, nuchal cord, higher cesarean section rate, higher heart rate variability with increased frequency, and duration of decelerations without acidemia and increased risk of gestational diabetes mellitus through the poor beta cells function. Similarly, female fetal sex has been reported to modify pregnancy and delivery outcomes including altered fetal cardiac hemodynamics, increased hypertensive diseases of pregnancy, higher vulnerability of developing type 2 DM after pregnancy possibly because of influences on increased maternal insulin resistance. Placental function is also influenced by fetal sex. Vitamin D metabolism in the placenta varies by fetal sex; and the placenta of a female fetus is more responsive to the relaxing action of magnesium sulfate. Male and female feto-placental units also vary in their responses to environmental toxin exposure. The association of fetal sex with stillbirths is controversial with many studies reporting higher risk of stillbirth in male fetuses; although some smaller and limited studies have reported more stillbirths with female fetus pregnancies. Maternal status such as BMI may in turn also affect the fetus and the placenta in a sex-specific manner. There is probably a sex-specific maternal–placental–fetal interaction that has significant biological implications of which the mechanisms may be genetic, epigenetic, or hormonal. Determination of fetal sex may therefore be an important consideration in management of pregnancy and childbirth. PMID:28674684

Effect of Fetal Sex on Maternal and Obstetric Outcomes.

PubMed

Al-Qaraghouli, Mohammed; Fang, Yu Ming Victor

2017-01-01

Fetal sex plays an important role in modifying the course and complications related to pregnancy and may also have an impact on maternal health and well-being both during and after pregnancy. The goal of this article is to review and summarize the findings from published research on physiologic and pathologic changes that may be affected by fetal sex and the effect of these changes on the maternal and obstetrical outcomes. This will help create awareness that fetal sex is not just a random chance event but an interactive process between the mother, the placenta, and the fetus. The reported effects of male sex on the course of pregnancy and delivery include higher incidence of preterm labor in singletons and twins, failure of progression in labor, true umbilical cord knots, cord prolapse, nuchal cord, higher cesarean section rate, higher heart rate variability with increased frequency, and duration of decelerations without acidemia and increased risk of gestational diabetes mellitus through the poor beta cells function. Similarly, female fetal sex has been reported to modify pregnancy and delivery outcomes including altered fetal cardiac hemodynamics, increased hypertensive diseases of pregnancy, higher vulnerability of developing type 2 DM after pregnancy possibly because of influences on increased maternal insulin resistance. Placental function is also influenced by fetal sex. Vitamin D metabolism in the placenta varies by fetal sex; and the placenta of a female fetus is more responsive to the relaxing action of magnesium sulfate. Male and female feto-placental units also vary in their responses to environmental toxin exposure. The association of fetal sex with stillbirths is controversial with many studies reporting higher risk of stillbirth in male fetuses; although some smaller and limited studies have reported more stillbirths with female fetus pregnancies. Maternal status such as BMI may in turn also affect the fetus and the placenta in a sex-specific manner. There is probably a sex-specific maternal-placental-fetal interaction that has significant biological implications of which the mechanisms may be genetic, epigenetic, or hormonal. Determination of fetal sex may therefore be an important consideration in management of pregnancy and childbirth.

Association between congenital anomalies and paternal exposure to agricultural pesticides depending on mother's employment status.

PubMed

Ronda, Elena; Regidor, Enrique; García, Ana M; Domínguez, Vicente

2005-08-01

We analyzed the association between fetal death from congenital anomalies and paternal agricultural occupation in mothers who were employed and in housewives. The data consist of individual records from the Spanish Birth Register (1995-1999). The adjusted relative risk of fetal death in agricultural workers compared with nonagricultural was 1.24 (95% confidence interval = 0.38- 4.02) in mothers who were employed and 1.68 (95% confidence interval = 1.03-2.73) in housewives. The risk of fetal death in the offspring of agricultural workers exposed to pesticides around the time of conception was higher than in the offspring of nonagricultural workers in mothers who were housewives but not in mothers who worked outside the home.

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

PubMed

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

1995-08-01

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

Coxsackie Virus A16 Infection of Placenta with Massive Perivillous Fibrin Deposition Leading to Intrauterine Fetal Demise at 36 Weeks Gestation.

PubMed

Yu, Weiming; Tellier, Raymond; Wright, James R

2015-01-01

Massive perivillous fibrin deposition (MPFD) is an uncommon placental disorder, associated with significant fetal morbidity, mortality, and recurrence; its etiology is unknown. We describe a 31-year-old mother, diagnosed with Coxsackievirus infection and hand-foot-and-mouth disease at 35 weeks gestation. Ultrasound at 35 weeks revealed a normal fetus and placenta. One week later, the mother experienced decreased fetal movement and ultrasound demonstrated intrauterine demise. The autopsy showed mild, acute pericarditis and hypoxic-ischemic encephalopathy. Placenta examination showed MPFD involving 80% of the parenchyma. Molecular viral analysis and serotyping showed Coxsackie A16 virus. The mother had an uneventful pregnancy 15 months later. Coxsackievirus infections in pregnant mothers are often asymptomatic. Transplacental Coxsackievirus infection is very rare but is associated with spontaneous abortion, intrauterine demise, or serious neonatal morbidity. Mild, nonspecific histologic changes have been reported in the placenta. To our knowledge, this is the first report of MPFD associated with Coxsackievirus infection.

Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection.

PubMed

Yockey, Laura J; Varela, Luis; Rakib, Tasfia; Khoury-Hanold, William; Fink, Susan L; Stutz, Bernardo; Szigeti-Buck, Klara; Van den Pol, Anthony; Lindenbach, Brett D; Horvath, Tamas L; Iwasaki, Akiko

2016-08-25

Zika virus (ZIKV) can be transmitted sexually between humans. However, it is unknown whether ZIKV replicates in the vagina and impacts the unborn fetus. Here, we establish a mouse model of vaginal ZIKV infection and demonstrate that, unlike other routes, ZIKV replicates within the genital mucosa even in wild-type (WT) mice. Mice lacking RNA sensors or transcription factors IRF3 and IRF7 resulted in higher levels of local viral replication. Furthermore, mice lacking the type I interferon (IFN) receptor (IFNAR) became viremic and died of infection after a high-dose vaginal ZIKV challenge. Notably, vaginal infection of pregnant dams during early pregnancy led to fetal growth restriction and infection of the fetal brain in WT mice. This was exacerbated in mice deficient in IFN pathways, leading to abortion. Our study highlights the vaginal tract as a highly susceptible site of ZIKV replication and illustrates the dire disease consequences during pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of fetal birth weight on perinatal outcome in planned vaginal births.

PubMed

Temerinac, Dunja; Chen, Xi; Sütterlin, Marc; Kehl, Sven

2014-02-01

The aim of this study was to provide information for better obstetric counseling by analyzing the impact of fetal birth weight (BW) on fetal and maternal outcome when vaginal birth is planned in a university hospital. In this retrospective study from January 1st 2006 to December 31st 2011, 5,177 singleton, alive deliveries at or >37 gestational weeks were assessed with regard to the fetal BW when vaginal birth was attempted. The normal BW group was defined as ≥2,500 <4,500 g. For comparison, further BW groups were defined as: group 1 <2,500 g, group 2 ≥4,000 <4,250 g, group 3 ≥4,250 <4,500 g and group 4 ≥4,500 g. Outcome criteria were mode of delivery and perineal lacerations as well as the pH and base excess of the umbilical cord artery, the Apgar score after 5 min and occurrence of shoulder dystocia. The set of controlling variables included maternal height, maternal weight, maternal age, gestational age, neonatal sex and parity. Second stage caesarean section is significantly more likely when fetal BW is under 2,500 g (30.7 vs. 15.5 % in the normal BW group, odds ratio 3.01, 95 % confidence interval 2.03-4.46, p value < 0.001). Shoulder dystocia occurred significantly more often when fetal BW was over 4,250 g (group 3: odds ratio 4.95, 95 % confidence interval 1.74-14.10, p value 0.003, group 4: odds ratio 19.96, 95 % confidence interval 7.61-52.38, p value < 0.001). The risk of an Apgar score after 5 min below 7 increased, when fetal BW was below 2,500 g (odds ratio 9.28, 95 % confidence interval 3.15-27.35, p value < 0.001) or above 4,500 g (odds ratio 5.65, 95 % confidence interval 1.22-26.24, p value 0.027). All groups were comparable to the normal group regarding pH and base excess of the umbilical cord artery as well as the risk for severe (third and fourth degree) perineal lacerations. Although a fetal birth weight under 2,500 g and a birth weight over 4,250 g are associated with some risks, there is no general contraindication for an attempt to deliver vaginally in a university hospital with regard to fetal birth weight.

The contribution of fetal drug exposure to temperament: potential teratogenic effects on neuropsychiatric risk.

PubMed

Weiss, Sandra J; St Jonn-Seed, Mary; Harris-Muchell, Carolyn

2007-08-01

Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. High risk children (n = 120) were followed from birth to 6 months of age to determine the effects of fetal drug exposure on temperament, after controlling for the child's gender, gestational age, medical morbidity, ethnicity, and maltreatment as well as the mother's stress, income adequacy, and quality of caregiving. Methods included medical chart review, questionnaires, and videotapes of mother-child interaction. Preliminary analyses indicated that fetal drug exposure was associated with both distractibility and intensity of children's responses to the environment at 6 months of age. After adjusting for potentially confounding variables, drug exposure accounted for 12% of the variance in distractibility but was not a significant predictor in the regression model for intensity. Findings suggest that drug-exposed children may experience difficulty sustaining their focus of attention and be more easily distracted by environmental stimuli than non-drug-exposed children. Results converge with previous research to implicate cortical hyperarousal, stemming from teratogenic effects on the dopaminergic system during fetal development.

Understanding fetal physiology and second line monitoring during labor.

PubMed

Garabedian, C; De Jonckheere, J; Butruille, L; Deruelle, P; Storme, L; Houfflin-Debarge, V

2017-02-01

Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition and is one of the most common obstetric procedures. Second line methods of fetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography and to better identify fetuses at risk of intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal blood scalp samples, the modification of the myocardial oxygenation by the fetal ECG ST-segment analysis (STAN) and the autonomic nervous system by the power spectral analysis of the fetal heart variability. To correctly interpret the features observed on CTG traces or second line methods, it seems important to understand normal physiology during labor and the compensatory mechanisms of the fetus in case of hypoxemia. Therefore, the aim of this review is first to describe fetal physiology during labor and then to explain the modification of the second line monitoring during labor. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Zhengqi

Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showedmore » a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. - Highlights: • Glucocorticoid but not ethanol enhanced the expression of OPG in chondrocytes. • PEE reduced osteoclast differentiation relative with over-expression of OPG. • PEE inhibited endochondral ossification in fetal long bones of rats. • Endochondral ossification delay is regarded as the thrifty phenotype induced by PEE.« less

Developmental regulation of neuroligin genes in Japanese rice fish (oryzias latipes) embryogenesis maintains the rhythym during ethanol-in

USDA-ARS?s Scientific Manuscript database

Although prenatal alcohol exposure is the potential cause of fetal alcohol spectrum disorder (FASD) in humans, the molecular mechanism(s) of FASD is yet unknown. We have used Japanese rice fish (Oryzias latipes) embryogenesis as an animal model of FASD and reported that this model has effectively ge...

Incidence of fetal bradycardia and effect of placental injury on fetal heart rate during second-trimester genetic amniocentesis.

PubMed

Hanprasertpong, T; Petpichetchian, C; Ponglopisit, S; Suksai, M; Kor-Anantakul, O; Geater, A; Pruksanusak, N; Hanprasertpong, J

2016-05-01

A prospective study was conducted for comparing the incidence of fetal bradycardia and level of fetal heart rate change following a second-trimester genetic amniocentesis with and without placental injury. A total of 257 and 495 participants in injured and non-injured groups were analysed. The incidence of fetal bradycardia following amniocentesis was not statistically different between the two groups (1.17%, [95% CI 0.24, 3.37] and 0.20%, [95% CI 0.005, 1.12]) in injured and non-injured placenta groups, respectively; p = 0.118). The mean change in baseline fetal heart rate before and after amniocentesis was also not significantly different between the two groups (p = 0.844). No fetal death or pregnancy loss occurred within 4 weeks after the procedure. All 4 bradycardia participants were normal and healthy and had an appropriate weight for their gestational age. We conclude that placental injury during a second-trimester genetic amniocentesis due to advanced maternal age poses only a low risk of fetal bradycardia, and there is no evidence of differences between subjects with injured and non-injured placenta in the changes in fetal heart rate.

The Fetal Care Team: Care for Pregnant Women Carrying a Fetus with a Serious Diagnosis.

PubMed

Loyet, Margaret; McLean, Amy; Graham, Karen; Antoine, Cheryl; Fossick, Kathy

Women carrying a fetus with a suspected or known fetal anomaly have complex needs such as emotional and informational support and help with the logistical aspects of arranging care and treatment from numerous specialists. IMPROVEMENT IN QUALITY OF CARE FOR WOMEN CARRYING A FETUS WITH A SUSPECTED OR KNOWN FETAL ANOMALY:: Our fetal care team was initiated in 2012 to meet the needs of this high-risk pregnant population. The fetal care team nurse coordinator supports the woman and her family through all aspects of care during the pregnancy and neonatal period including scheduling appointments with multiple specialists, being there with her as a support person, keeping her updated, making sure she has accurate information about the fetal diagnosis, and helping her to navigate the complex healthcare system. Since the program was started, the number of women enrolled has nearly doubled. Women overwhelmingly are satisfied with the various services and care provided by the nurse coordinators and believe the fetal care team has value for them. We present the development and operations of our fetal care team with a focus on the role of the fetal care team nurse coordinator.

Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province.

PubMed Central

May, P A; Brooke, L; Gossage, J P; Croxford, J; Adnams, C; Jones, K L; Robinson, L; Viljoen, D

2000-01-01

OBJECTIVES: This study determined the characteristics of fetal alcohol syndrome in a South African community, and methodology was designed for the multidisciplinary study of fetal alcohol syndrome in developing societies. METHODS: An active case ascertainment, 2-tier methodology was used among 992 first-grade pupils. A case-control design, using measures of growth, development, dysmorphology, and maternal risk, delineated characteristics of children with fetal alcohol syndrome. RESULTS: A high rate of fetal alcohol syndrome was found in the schools--40.5 to 46.4 per 1000 children aged 5 to 9 years--and age-specific community rates (ages 6-7) were 39.2 to 42.9. These rates are 18 to 141 times greater than in the United States. Rural residents had significantly more fetal alcohol syndrome. After control for ethnic variation, children with fetal alcohol syndrome had traits similar to those elsewhere: poor growth and development, congruent dysmorphology, and lower intellectual functioning. CONCLUSIONS: This study documented the highest fetal alcohol syndrome rate to date in an overall community population. Fetal alcohol syndrome initiatives that incorporate innovative sampling and active case ascertainment methods can be used to obtain timely and accurate data among developing populations. PMID:11111264

Prospective chromosome analysis of 3429 amniocentesis samples in China using copy number variation sequencing.

PubMed

Wang, Jing; Chen, Lin; Zhou, Cong; Wang, Li; Xie, Hanbin; Xiao, Yuanyuan; Zhu, Hongmei; Hu, Ting; Zhang, Zhu; Zhu, Qian; Liu, Zhiying; Liu, Shanlin; Wang, He; Xu, Mengnan; Ren, Zhilin; Yu, Fuli; Cram, David S; Liu, Hongqian

2018-05-28

Next generation sequencing (NGS) is emerging as a viable alternative to chromosome microarray analysis for the diagnosis of chromosome disease syndromes. One NGS methodology, copy number variation sequencing (CNV-Seq), has been shown to deliver high reliability, accuracy and reproducibility for detection of fetal CNVs in prenatal samples. However, its clinical utility as a first tier diagnostic method has yet to be demonstrated in a large cohort of pregnant women referred for fetal chromosome testing. To evaluate CNV-Seq as a first tier diagnostic method for detection of fetal chromosome anomalies in a general population of pregnant women with high-risk prenatal indications. Prospective analysis of 3429 pregnant women referred for amniocentesis and fetal chromosome testing for different risk indications, including advanced maternal age (AMA), high-risk maternal serum screening (HR-MSS), and positivity for an ultrasound soft marker (USM). Amniocentesis was performed by standard procedures. Amniocyte DNA was analyzed by CNV-Seq with a chromosome resolution of 0.1 Mb. Fetal chromosome anomalies including whole chromosome aneuploidy and segmental imbalances were independently confirmed by gold standard cytogenetic and molecular methods and their pathogenicity determined following guidelines of the American College of Medical Genetics for sequence variants. Clear interpretable CNV-Seq results were obtained for all 3429 amniocentesis samples. CNV-Seq identified 3293 (96%) samples with a normal molecular karyotype and 136 samples (4%) with an altered molecular karyotype. A total of 146 fetal chromosome anomalies were detected, comprising 46 whole chromosome aneuploidies (pathogenic), 29 submicroscopic microdeletions/microduplications with known or suspected associations with chromosome disease syndromes (pathogenic), 22 other microdeletions/microduplications (likely pathogenic) and 49 variants of uncertain significance (VUS). Overall, the cumulative frequency of pathogenic/likely pathogenic and VUS chromosome anomalies in the patient cohort was 2.83% and 1.43%, respectively. In the three high-risk AMA, HR-MSS and USM groups, the most common whole chromosome aneuploidy detected was trisomy 21, followed by sex chromosome aneuploidies, trisomy 18 and trisomy 13. Across all clinical indications, there was a similar incidence of submicroscopic CNVs, with approximately equal proportions of pathogenic/likely pathogenic and VUS CNVs. If karyotyping had been used as an alternate cytogenetics detection method, CNV-Seq would have returned a 1% higher yield of pathogenic or likely pathogenic CNVs. In a large prospective clinical study, CNV-Seq delivered high reliability and accuracy for identifying clinically significant fetal anomalies in prenatal samples. Based on key performance criteria, CNV-Seq appears to be a well-suited methodology for first tier diagnosis of pregnant women in the general population at risk of having a fetal chromosome abnormality. Copyright © 2018. Published by Elsevier Inc.

Fetal Alcohol Syndrome: Diagnostic Features and Psychoeducational Risk Factors.

ERIC Educational Resources Information Center

Phelps, LeAdelle; Grabowski, Jo-Anne

1992-01-01

Discusses Fetal Alcohol Syndrome (FAS), accepted as leading known cause of mental retardation. Relates chronicity, timing, and severity of alcohol exposure to age-specific developmental and behavioral consequences. Delineates specific interventions with infants, preschoolers, school-age children, and adolescents. Advocates for accurate diagnosis…

Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

PubMed

Santos, Ana Paula Caires Dos; Couto, Ricardo David

2018-05-16

Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

[Recent advances in prenatal diagnostics].

PubMed

Lapaire, O; Holzgreve, W; Miny, P; Hösli, I; Hahn, S; Tercanli, S

2006-11-01

During the last years, technical improvements have increased the possibilities in prenatal ultrasound. During the eighties and nineties, fetal malformations were increasingly detected and specified. Since a few years, the measurement of the fetal nuchal translucency between 11 and 14 weeks of gestation has been implemented to calculate the individual risk, in combination with most recent biochemical markers. Today, the sonographic measurement of the nuchal translucency is regarded as a valuable screening tool for chromosomal anomalies in prenatal medicine. Beside standardized examinations, a profound information and counseling of the pregnant women should be emphasized. With the improvement of the specific maternal risk calculation, using the sonographic measurement of the nuchal translucency, the biochemical markers and the maternal age, unnecessary invasive examinations may be prevented and their overall number can significantly be reduced. The same trend is seen in the whole field of prenatal medicine, illustrated by the detection of the fetal rhesus D status from the maternal blood and the use of Doppler ultrasound in the management of fetal anemia.

Disruption of Fetal Hormonal Programming (Prenatal Stress) Implicates Shared Risk for Sex Differences in Depression and Cardiovascular Disease

PubMed Central

Goldstein, JM; Handa, RJ; Tobet, SA

2014-01-01

Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) represents the fourth leading cause of morbidity and mortality worldwide, and women have a two times greater risk than men. Thus understanding the pathophysiology has widespread implications for attenuation and prevention of disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from alterations in fetal programming consequent to the prenatal maternal environments that produce excess glucocorticoids, which then drive sex-dependent developmental alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry impacting mood, stress regulation, autonomic nervous system (ANS), and the vasculature in adulthood. Evidence is consistent with the hypothesis that disruptions of pathways associated with gamma aminobutyric acid (GABA) in neuronal and vascular development and growth factors have critical roles in key developmental periods and adult responses to injury in heart and brain. Understanding the potential fetal origins of these sex differences will contribute to development of novel sex-dependent therapeutics. PMID:24355523

Effect of Placenta Previa on Fetal Growth

PubMed Central

HARPER, Lorie M.; ODIBO, Anthony O.; MACONES, George A.; CRANE, James P.; CAHILL, Alison G.

2011-01-01

Objective To estimate the association between placenta previa and abnormal fetal growth. Study Design Retrospective cohort study of consecutive women undergoing ultrasound between 15–22 weeks. Groups were defined by the presence or absence of complete or partial placenta previa. The primary outcome was intrauterine growth restriction (IUGR), defined as a birth weight <10th percentile by the Alexander growth standard. Univariable, stratified and multivariable analyses were used to estimate the effect of placenta previa on fetal growth restriction. Results Of 59,149 women, 724 (1.2%) were diagnosed with a complete or partial previa. After adjusting for significant confounding factors (black race, gestational diabetes, preeclampsia, and single umbilical artery,), the risk of IUGR remained similar (adjusted odds ratio 1.1, 95% CI 0.9–1.5). The presence of bleeding did not impact the risk of growth restriction. Conclusion Placenta previa is not associated with fetal growth restriction. Serial growth ultrasounds are not indicated in patients with placenta previa. PMID:20599185

[The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

PubMed

Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

2014-06-01

Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

Predicting the Future: Delivery Room Planning of Congenital Heart Disease Diagnosed by Fetal Echocardiography.

PubMed

Donofrio, Mary T

2018-05-01

Advances in prenatal imaging have improved the examination of the fetal cardiovascular system. Fetal echocardiography facilitates the prenatal diagnosis of congenital heart disease (CHD) and through sequential examination, allows assessment of fetal cardiac hemodynamics, predicting the evolution of anatomical and functional cardiovascular abnormalities in utero and during the transition to a postnatal circulation at delivery. This approach allows detailed diagnosis with prenatal counseling and enables planning to define perinatal management, selecting the fetuses at a risk of postnatal hemodynamic instability who are likely to require a specialized delivery plan. The prenatal diagnosis and management of critical neonatal CHD has been shown to play an important role in improving the outcome of newborns with these conditions, allowing timely stabilization of the circulation prior to cardiac intervention or surgery, thus reducing the risk of perioperative morbidity and mortality. Diagnostic protocols aimed at risk-stratifying severity and potential postnatal compromise in fetuses with CHD have been developed to identify those who may require special intervention at birth or within the first days of life. In addition, new methodologies are being studied to improve the accuracy of prediction of disease severity. Perinatal management of neonates with a prenatal diagnosis of CHD requires a close collaboration between obstetric, neonatal, and cardiology services. In this article, the management of fetuses with CHD will be discussed, along with summarizing the in utero and fetal echocardiographic findings used for risk stratification of newborns with CHD and reviewing the basic principles used for planning for neonatal resuscitation and initial transitional care of these complex newborns. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Interpretation of false positive results of biochemical prenatal tests].

PubMed

Sieroszewski, Piotr; Słowakiewicz, Katarzyna; Perenc, Małgorzata

2010-03-01

Modern, non-invasive prenatal diagnostics based on biochemical and ultrasonographic markers of fetal defects allows us to calculate the risk of fetal chromosomal aneuploidies with high sensitivity and specificity An introduction of biochemical, non-invasive prenatal tests turned out to result in frequent false positive results of these tests in cases when invasive diagnostics does not confirm fetal defects. However prospective analysis of these cases showed numerous complications in the third trimester of the pregnancies.

Transabdominal amnioinfusion to avoid fetal demise and intestinal damage in fetuses with gastroschisis and severe oligohydramnios.

PubMed

Sapin, E; Mahieu, D; Borgnon, J; Douvier, S; Carricaburu, E; Sagot, P

2000-04-01

Despite dramatic improvement in survival rate for neonates with gastroschisis, significant postoperative morbidity and a low mortality rate still occur. Furthermore, even in recent publications, some fetal death has been reported. Does this mean that antenatal diagnosis of gastroschisis is a missed opportunity? In fact, decreased amniotic fluid (AF) volume is observed in some fetuses with gastroschisis. However, oligohydramnios is associated with an increased risk of fetal suffering. When severe oligohydramnios is observed, intrapartum amnioinfusion, to restore AF volume, may help avoid fetal complications. Two fetuses with gastroschisis and severe oligohydramnios were treated antenatally with amnioinfusion of saline solution. In one case, fetal heart beat decelerations were observed at 27 weeks' gestation among with the oligohydroamnios and serial transabdominal amnioinfusions were performed. In the second case, severe oligohydramnios was observed at 31, weeks and an amnioinfusion was performed. The 2 babies were delivered at 31 and 34 weeks, respectively. In both cases, exteriorized bowel was nearly normal at birth, and primary closure could be performed. Outcome was favorable, and they were discharged home on day 43 and day 54, respectively. Because fetuses with gastroschisis and oligohydramnios are part of a particular high-risk group, serial ultrasound examination and computerized fetal heart beat monitoring are necessary during the third trimester. In selected cases of gastroschisis associated with severe oligohydramnios, serial amnioinfusion may be required.

Customized Fetal Growth Charts for Parents' Characteristics, Race, and Parity by Quantile Regression Analysis: A Cross-sectional Multicenter Italian Study.

PubMed

Ghi, Tullio; Cariello, Luisa; Rizzo, Ludovica; Ferrazzi, Enrico; Periti, Enrico; Prefumo, Federico; Stampalija, Tamara; Viora, Elsa; Verrotti, Carla; Rizzo, Giuseppe

2016-01-01

The purpose of this study was to construct fetal biometric charts between 16 and 40 weeks' gestation that were customized for parental characteristics, race, and parity, using quantile regression analysis. In a multicenter cross-sectional study, 8070 sonographic examinations from low-risk pregnancies between 16 and 40 weeks' gestation were analyzed. The fetal measurements obtained were biparietal diameter, head circumference, abdominal circumference, and femur diaphysis length. Quantile regression was used to examine the impact of parental height and weight, parity, and race across biometric percentiles for the fetal measurements considered. Paternal and maternal height were significant covariates for all of the measurements considered (P < .05). Maternal weight significantly influenced head circumference, abdominal circumference, and femur diaphysis length. Parity was significantly associated with biparietal diameter and head circumference. Central African race was associated with head circumference and femur diaphysis length, whereas North African race was only associated with femur diaphysis length. In this study we constructed customized biometric growth charts using quantile regression in a large cohort of low-risk pregnancies. These charts offer the advantage of defining individualized normal ranges of fetal biometric parameters at each specific percentile corrected for parental height and weight, parity, and race. This study supports the importance of including these variables in routine sonographic screening for fetal growth abnormalities.

Twins less frequent than expected among male births in risk averse populations.

PubMed

Karasek, Deborah; Goodman, Julia; Gemmill, Alison; Falconi, April; Hartig, Terry; Magganas, Aristotle; Catalano, Ralph

2015-06-01

Male twin gestations exhibit higher incidence of fetal morbidity and mortality than singleton gestations. From an evolutionary perspective, the relatively high rates of infant and child mortality among male twins born into threatening environments reduce the fitness of these gestations, making them more vulnerable to fetal loss. Women do not perceive choosing to spontaneously abort gestations although the outcome may result from estimates, made without awareness, of the risks of continuing a pregnancy. Here, we examine whether the non-conscious decisional biology of gestation can be linked to conscious risk aversion. We test this speculation by measuring the association between household surveys in Sweden that gauge financial risk aversion in the population and the frequency of twins among live male births. We used time-series regression methods to estimate our suspected associations and Box-Jenkins modeling to ensure that autocorrelation did not confound the estimation or reduce its efficiency. We found, consistent with theory, that financial risk aversion in the population correlates inversely with the odds of a twin among Swedish males born two months later. The odds of a twin among males fell by approximately 3.5% two months after unexpectedly great risk aversion in the population. This work implies that shocks that affect population risk aversion carry implications for fetal loss in vulnerable twin pregnancies.

Linear Phase Sharp Transition BPF to Detect Noninvasive Maternal and Fetal Heart Rate.

PubMed

Marchon, Niyan; Naik, Gourish; Pai, K R

2018-01-01

Fetal heart rate (FHR) detection can be monitored using either direct fetal scalp electrode recording (invasive) or by indirect noninvasive technique. Weeks before delivery, the invasive method poses a risk factor to the fetus, while the latter provides accurate fetal ECG (FECG) information which can help diagnose fetal's well-being. Our technique employs variable order linear phase sharp transition (LPST) FIR band-pass filter which shows improved stopband attenuation at higher filter orders. The fetal frequency fiduciary edges form the band edges of the filter characterized by varying amounts of overlap of maternal ECG (MECG) spectrum. The one with the minimum maternal spectrum overlap was found to be optimum with no power line interference and maximum fetal heart beats being detected. The improved filtering is reflected in the enhancement of the performance of the fetal QRS detector (FQRS). The improvement has also occurred in fetal heart rate obtained using our algorithm which is in close agreement with the true reference (i.e., invasive fetal scalp ECG). The performance parameters of the FQRS detector such as sensitivity (Se), positive predictive value (PPV), and accuracy (F 1 ) were found to improve even for lower filter order. The same technique was extended to evaluate maternal QRS detector (MQRS) and found to yield satisfactory maternal heart rate (MHR) results.

Maternal serum pregnancy-associated plasma protein A and fetal nuchal translucency thickness for the prediction of fetal trisomies in early pregnancy.

PubMed

Brizot, M L; Snijders, R J; Bersinger, N A; Kuhn, P; Nicolaides, K H

1994-12-01

To determine if the risk for fetal trisomies during the first trimester of pregnancy can be derived by combining data from maternal serum pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency thickness. Pregnancy-associated plasma protein A was measured in samples from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy 21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four triploidies) and 348 chromosomally normal controls at 10-13 weeks' gestation. Likelihood ratios for trisomies 21, 18, and 13 in relation to PAPP-A, in multiples of the normal median (MoM) for crown-rump length, were derived from the overlapping gaussian frequency distribution curves for normal and abnormal pregnancies. In the chromosomally normal group, maternal serum PAPP-A correlated significantly with fetal crown-rump length (r = 0.421, P < .0001). In the chromosomally abnormal group, the median PAPP-A was significantly lower than in the normal controls. The respective median values expressed in MoM for trisomies 21, 18, and 13 and other aneuploidies were 0.5 MoM (90% confidence interval [CI] 0.09-1.67, z = 6.0, P < .001), 0.17 MoM (90% CI 0.06-1.45, z = 6.6, P < .001), 0.25 MoM (90% CI 0.10-0.62, z = 4.5, P < .001), and 0.72 MoM (90% CI 0.09-2.48, z = 2.2, P < .05), respectively. There was no significant linear association between PAPP-A and fetal nuchal translucency thickness in either the chromosomally normal (r = -0.01, P = .89) or abnormal groups (r = -0.19, P = .08). The risks for fetal trisomies at 10-13 weeks' gestation can be derived by combining data on maternal age, maternal serum PAPP-A, and fetal nuchal translucency thickness.

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

PubMed Central

Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

2015-01-01

Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

Stress matters! Psychophysiological and emotional loadings of pregnant women undergoing fetal magnetic resonance imaging.

PubMed

Derntl, Birgit; Krajnik, Jacqueline; Kollndorfer, Kathrin; Bijak, Manfred; Nemec, Ursula; Leithner, Katharina; Prayer, Daniela; Schöpf, Veronika

2015-02-13

While the application of fetal MRI in high-risk pregnant women is steadily rising, little is known about the psychological consequences of this procedure. The aim of the present study was to investigate emotional and psychophysiological reactions of females undergoing fetal MRI. Sixty women (17-44 ys), assigned for fetal MRI, were included. Affective state was assessed by standardized measures of anxiety, emotional states and depressive symptoms. Stress coping strategies were assessed using a self-report questionnaire. Stress responses were determined using skin conductance levels (SCL) during fetal MRI as well as measurement of salivary cortisol levels immediately before and after fetal MRI. Analysis of fast and slow physiological stress measures revealed significant differences between women with and without a supporting person accompanying them to the examination. For SCLs, lower levels of stress during MRI emerged in accompanied women. Women with well-marked stress-coping-strategies experienced lower levels of stress during the examination. Although fast and slow stress measures before and after MRI did not show significant correlations, a significant difference of SCLs pre and post examination was clearly detectable, as well as a trend of decreased cortisol levels for both time points. The results imply that the elevation of SCLs is an accurate instrument to assess fast stress alterations in patients during fetal MRI. Stress coping strategies and whether women are accompanied or not play an important role in the experience of anxiety and depressive symptoms. These factors should be considered especially in patients with high-risk-pregnancies to improve patient care.

The consequences of high-risk behaviors: trauma during pregnancy.

PubMed

Patteson, Stephen K; Snider, Carolyn C; Meyer, David S; Enderson, Blaine L; Armstrong, Janice E; Whitaker, Gregory L; Carroll, Roger C

2007-04-01

Trauma during pregnancy places two lives at risk. Knowledge of risk factors for trauma during pregnancy may improve outcomes. We reviewed the charts of 188 such patients admitted to a Level I trauma center from 1996 to 2004. A comparison was made of injury severity and outcome from a cohort of nonpregnant female trauma patients selected with a similar temporal occurrence and age range. Motor vehicle collisions comprised 160 cases, 67 using a restraint device. Of 84 patients tested, 45 tested positive for intoxicants, 16 positive for 2 or more intoxicants. A significant trend toward less testing through the study period was observed (p = 0.0002). Injury severity was assessed by Revised Trauma Score (RTS). RTS <11 or admission to operating room or intensive care units (OR/ICU) classified patients as severely injured. The six maternal fatalities had an RTS <11 or OR/ICU disposition. Fetal outcomes included 155 live in utero, 18 live births, and 15 fatalities correlating with injury severity by either criteria (p < 0.0001). Of the fetal fatalities, 7 occurred with RTS = 12, but only 3 fatalities occurred in the 147 cases not admitted to OR/ICU. Gestational age correlated (p < 0.0001) with fetal outcomes. The 18 live births had mean gestational ages of 35 +/- 4 weeks as compared with fetal fatalities at 20 +/- 9 weeks, and fetuses alive in utero at 22 +/- 9 weeks gestation. Coagulation tests prothrombin time (PT), international normalized ratio (INR) (both p < 0.008), and partial thromboplastin time (PTT) (p < 0.0001) correlated with maternal outcome. A matched cohort of nonpregnancy trauma cases during the same time frame indicated that, despite a significantly higher percentage of severely injured patients, fewer fatalities occurred. This might reflect a greater risk for the pregnant trauma patient. This study of trauma in pregnancy cases revealed a high percentage with risk behaviors. There was a significant trend toward less intoxicant testing in recent years. Coagulation tests were the most predictive of outcomes. Lower gestational age correlated with fetal demise.

Fetal well-being: nonimaging assessment and the biophysical profile.

PubMed

Jackson, G M; Forouzan, I; Cohen, A W

1991-01-01

All of the testing methods described above are very good at predicting continued fetal health when test results are reassuring. Each test also suffers from a very poor ability to predict compromise when results are abnormal. Thus, the primary value of antepartum fetal monitoring is in identifying those pregnancies that do not require immediate intervention and may be allowed to continue. Certainly, all pregnant women (regardless of risk status) should monitor fetal movement as part of their fetal surveillance. For patients at risk, a variety of testing schemes are available using combinations of the NST, CST and BPP. There are several reasons for using the NST as the primary testing method for those at risk. Even a small antenatal testing area can accommodate three or four FHR monitors, and a single antenatal testing nurse can perform several NSTs at a time. Because the BPP requires an ultrasound machine and a trained technician to perform, and because only one BPP can be done at a time, many obstetricians who do their own in-office fetal testing are unable to adopt BPP testing as their primary means of surveillance. Additionally, it is more economical to use the NST than the BPP for first-line testing. Assuming charges of $150 and $300 for the NST and BPP, respectively, and assuming that 20% of NSTs are nonreactive and require a BPP for second-line testing, the weekly cost of testing 100 patients is $21,000 for the NST and $37,500 for the BPP. This increase-in-testing cost must be balanced against the small improvement in perinatal mortality rates achieved with the use of the BPP. Because it must be performed in a hospital setting and takes an average of 90 minutes to complete, the CST is more expensive and time-consuming than either the NST or BPP and it is less frequently used as the primary method of fetal testing. In the past the CST was the most commonly used secondary test after a nonreactive NST, but use of the BPP in this situation has now become commonplace. Although the CST still has an important role in fetal testing, the BPP is better suited for use in this setting because of its technical ease and low incidence of abnormal results. Thus, many centers use the NST as the primary mode of testing for the fetus at risk, often with a sonographic assessment of AFV.(ABSTRACT TRUNCATED AT 400 WORDS)

Management of varicella infection (chickenpox) in pregnancy.

PubMed

Shrim, Alon; Koren, Gideon; Yudin, Mark H; Farine, Dan

2012-03-01

To review the existing data regarding varicella zoster virus infection (chickenpox) in pregnancy, interventions to reduce maternal complications and fetal infection, and antepartum and peripartum management. The maternal and fetal outcomes in varicella zoster infection were reviewed, as well as the benefit of the different treatment modalities in altering maternal and fetal sequelae. Medline was searched for articles and clinical guidelines published in English between January 1970 and November 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). 1. Varicella immunization is recommended for all non-immune women as part of pre-pregnancy and postpartum care. (II-3B) 2. Varicella vaccination should not be administered in pregnancy. However, termination of pregnancy should not be advised because of inadvertent vaccination during pregnancy. (II-3D) 3. The antenatal varicella immunity status of all pregnant women should be documented by history of previous infection, varicella vaccination, or varicella zoster immunoglobulin G serology. (III-C) 4. All non-immune pregnant women should be informed of the risk of varicella infection to themselves and their fetuses. They should be instructed to seek medical help following any contact with a person who may have been contagious. (II-3B) 5. In the case of a possible exposure to varicella in a pregnant woman with unknown immune status, serum testing should be performed. If the serum results are negative or unavailable within 96 hours from exposure, varicella zoster immunoglobulin should be administered. (III-C) 6. Women who develop varicella infection in pregnancy need to be made aware of the potential adverse maternal and fetal sequelae, the risk of transmission to the fetus, and the options available for prenatal diagnosis. (II-3C) 7. Detailed ultrasound and appropriate follow-up is recommended for all women who develop varicella in pregnancy to screen for fetal consequences of infection. (III-B) 8. Women with significant (e.g., pneumonitis) varicella infection in pregnancy should be treated with oral antiviral agents (e.g., acyclovir 800 mg 5 times daily). In cases of progression to varicella pneumonitis, maternal admission to hospital should be seriously considered. Intravenous acyclovir can be considered for severe complications in pregnancy (oral forms have poor bioavailability). The dose is usually 10 to 15 mg/kg of BW or 500 mg/m² IV every 8 h for 5 to 10 days for varicella pneumonitis, and it should be started within 24 to 72 h of the onset of rash. (III-C) 9. Neonatal health care providers should be informed of peripartum varicella exposure in order to optimize early neonatal care with varicella zoster immunoglobulin and immunization. (III-C) Varicella zoster immunoglobulin should be administered to neonates whenever the onset of maternal disease is between 5 days before and 2 days after delivery. (III-C).

Reproductive health indicators and fetal medicine - many things will change.

PubMed

Olsen, Jørn; Pedersen, Lars Henning

2016-06-01

Reproductive epidemiologists study disease outcomes over three time periods: (i) from conception, or before, to birth, (ii) from birth to death and (iii) from death and into the next generations. They have traditionally been short of data from the time of conception to birth, and we use data at birth to estimate fetal growth or the incidence of congenital malformations. Although we are interested in incidence data for defects that start early in gestation, we have to use prevalence data at birth. Cumulative incidence will only be similar to prevalence at birth given no competing risks - or no fetal death after the onset of the lesion. Routinely use of ultrasound methods in fetal medicine will change our monitoring of structural birth defects. We may now be able to link exposures to events with the right time sequence, for example on fetal growth deviations and get better data on fetal deaths also for twins and triplets. The scientific challenges will mainly come from induced abortions following ultrasound examinations. Ultrasound data from the time of pregnancy will be of crucial importance for studies on fetal programming or "developmental origins of health and disease" (DOHaD). In humans, babies that are small at birth have an increased risk of, eg, cardiovascular disease, as shown by DJ Barker in the 1980s (1), but this association is probably not a direct consequence of the low birth weight but rather caused by external or internal exposures during fetal life. DOHaD studies that use outcomes at birth, including weight, as exposures or intermediates may be biased. One notorious example is the apparent protective effect of smoking on the mortality of children with a low birth weight (2). This bias, partly related to collider stratification bias, is potentially less important in studies using direct ultrasound assessments. The risk of reverse causation may also be reduced in longitudinal studies based on ultrasound data. Fetal ultrasound examinations are also done to detect fetal structural abnormalities in order to start early treatment or terminate an effected pregnancy if that is permitted and requested by the parents. This change in timing and validity of determining congenital abnormalities (CA) will have substantial consequences for our monitoring of CA over time. Most of the existing monitoring systems are based on measuring prevalence of CA at time of birth, often allowing for a time period of detection from months to years since some of the CA are not detected at birth. They may be detected by ultrasound during gestation, but even for CA detectable in gestational weeks 20-24 and at birth, the sensitivity and specificity of times of diagnosing may differ so much that the measures are not comparable. Furthermore, the time from ultrasound to birth is sometimes interrupted by late fetal deaths and some of these deaths may be induced on indication. In any case, it will be difficult to reestablish long-term monitoring trends by applying birth correcting factors that will differ by the type of CA. We probably have to accept that long-term time trends need years to be reestablished and will have to be based on updated diagnostic facilities that will change over time. It may be difficult to spot increases in the incidence of CA in the future. An increase could be real or related to better diagnostic facilities operating in the time period from conception to birth. Fetal medicine will sometimes make it possible to study causes and events in the proper time sequence, which is important since a cause has to precede an event as the only sine qua non causal criteria. Measurements of recurrence "risks" of CA in families have always been complicated. It is well known that several CA have a tendency to be repeated in a subsequent pregnancy, most likely related to genetic factors or other time stable environmental exposures. Better diagnostic facilities with an option for an induced abortion may encourage high-risk parents to try to become pregnant and this may affect estimates of recurrence risk. In any case, calculating recurrence risk for newborns following siblings with the CA in question will probably no longer work (maybe it never worked) since the desire to reach a given family size depends on many factors, including the perceived risk of a CA. Access to prenatal diagnostic data may therefore well produce data closer to recurrence risk than data recorded at the time of birth. Pediatrics and Perinatal Epidemiology recently published a series of papers initiated by Olga Basso (3, 4) addressing in part the problem of moving from time scale one (starting at conception) to time scale two (starting at birth). Part of the addressed problems relate to a lack of options for starting observations on causal factors at the onset of exposure or, at best, before exposure. If that exposure happens early in fetal life, outcomes will be complicated by fetal deaths that probably end observation for ≥30% of subjects. That equals mortality rates we see for ≥95-year-olds or equals a cumulative death risk seen for newborns from birth to ≥65 years of age. If the exposure of interest is related to fetal death that opens up for strong collider stratification bias and selection when we condition on survival in our analyses for observations at the beginning of the second time scale (5). A negative association on that time scale need not reflect "prevention" in any sense other than suicides early in life will prevent later cancer deaths. It is difficult to imagine a counterfactual comparison to an exposed had he/she not been exposed and had survived fetal life. Those who were susceptible did not all survive. If we study fetal programming of adult diseases, we have to "condition on birth" in our studies, but we should be aware of the selection bias that follows. Fetal medicine will in many ways produce better data or data we never have had before, but it will change the conditions in many aspects of reproductive epidemiology. The main advantage in analytical epidemiology is to get the time sequence right from exposure to outcome to avoid the problem of reverse causation and to do proper mediation analyses. Conflict of interest The authors declare no conflicts of interest.

MicroRNA-20b-5p inhibits platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3.

PubMed

Tang, Jin; Luo, Lingying

2018-06-01

Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF). Here, we showed that miR-20b-5p was significantly decreased in fetal ASM cells treated with PDGF. Biological experiments showed that the overexpression of miR-20b-5p inhibited the proliferation while miR-20b-5p inhibition markedly promoted the proliferation of fetal ASM cells. Bioinformatics analysis and luciferase reporter assay showed that miR-20b-5p directly targeted the 3'-UTR of signal transducer and activator of transcription 3 (STAT3). Further data showed that miR-20b-5p negatively regulated the expression of STAT3 in fetal ASM cells. Moreover, miR-20b-5p regulates the transcriptional activity of STAT3 in fetal ASM cells. Overexpression of STAT3 reversed the inhibitory effect of miR-20b-5p overexpression on fetal ASM cell proliferation while the knockdown of STAT3 abrogated the promoted effect of miR-20b-5p inhibition on fetal ASM cell proliferation. Overall, our results show that miR-20b-5p impedes PDGF-induced proliferation of fetal ASM cells through targeting STAT3. Our study suggests that miR-20b-5p may play an important role in airway remodeling during asthma and suggests that miR-20b-5p may serve as a potential therapeutic target for pediatric asthma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pregnancy and contraception in systemic and cutaneous lupus erythematosus.

PubMed

Guettrot-Imbert, G; Morel, N; Le Guern, V; Plu-Bureau, G; Frances, C; Costedoat-Chalumeau, N

2016-10-01

A causal link has long been described between estrogen and systemic lupus erythematosus activity. Contraceptive and pregnancy management is now common for lupus patients, but pregnancy continues to be associated with higher maternal and fetal mortality/morbidity in systemic lupus erythematosus patients than among the general population. Potential complications include lupus flares, obstetric complications (fetal loss, in utero growth retardation, premature birth) and neonatal lupus syndrome. Association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetric complications. Anti-SSA and/or anti-SSB antibodies put fetuses at risk for neonatal lupus. Improving the outcome of such pregnancies depends upon optimal systematic planning of pregnancy at a preconception counseling visit coupled with a multidisciplinary approach. Absence of lupus activity, use of appropriate medication during pregnancy based on the patient's medical history and risk factors, and regular monitoring constitute the best tools for achieving a favorable outcome in such high-risk pregnancies. The aim of this review is to provide an update on the management of contraception and pregnancy in systemic lupus erythematosus, cutaneous lupus and/or antiphospholipid syndrome in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interventions to help external cephalic version for breech presentation at term.

PubMed

Hofmeyr, G J

2002-01-01

Breech presentation places a fetus at increased risk. The outcome for the baby is improved by planned caesarean section compared with planned vaginal delivery. External cephalic version attempt reduces the chance of breech presentation at birth, but is not always successful. Tocolytic drugs to relax the uterus as well as other methods have been also used in an attempt to facilitate external cephalic version at term. The objective of this review is to assess the effects of routine tocolysis, fetal acoustic stimulation, epidural or spinal analgesia and transabdominal amnioinfusion for external cephalic version at term on successful version and measures of pregnancy outcome. The Cochrane Pregnancy and Childbirth Group Trials Register (searched December 2001) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001) were searched. Randomised and quasi-randomised trials comparing routine versus selective or no tocolysis; fetal acoustic stimulation in midline fetal spine positions versus dummy or no stimulation; epidural or spinal analgesia versus no regional analgesia; or transabdominal amnioinfusion versus no amnioinfusion for external cephalic version at term. Eligibility and trial quality were assessed by the reviewer. In six trials, routine tocolysis was associated with fewer failures of external cephalic version (relative risk 0.74, 95% confidence interval 0.64 to 0.87). The reduction in non-cephalic presentations at birth was not statistically significant. Caesarean sections were reduced (relative risk 0.85, 95% confidence interval 0.72 to 0.99). Fetal acoustic stimulation in midline fetal spine positions was associated with fewer failures of external cephalic version at term (relative risk 0.17, 95% confidence interval 0.05 to 0.60). With epidural or spinal analgesia, external cephalic version failure, non-cephalic births and caesarean sections were reduced in two trials but not the other. The overall differences were not statistically significant. No randomised trials of transabdominal amnioinfusion for external cephalic version at term were located. Routine tocolysis appears to reduce the failure rate of external cephalic version at term. Although promising, there is not enough evidence to evaluate the use of fetal acoustic stimulation in midline fetal spine positions, nor of epidural or spinal analgesia. Large volume intravenous preloading may have contributed to the effectiveness demonstrated in two of the latter trials. No randomised trials of transabdominal amnioinfusion for external cephalic version at term were found.

Developmental effects of antiepileptic drugs and the need for improved regulations

PubMed Central

Loring, David W.

2016-01-01

Antiepileptic drugs (AEDs) are among the most common teratogenic drugs prescribed to women of childbearing age. AEDs can induce both anatomical (malformations) and behavioral (cognitive/behavioral deficits) teratogenicity. Only in the last decade have we begun to truly discriminate differential AED developmental effects. Fetal valproate exposure carries a special risk for both anatomical and behavioral teratogenic abnormalities, but the mechanisms and reasons for individual variability are unknown. Intermediate anatomical risks exist for phenobarbital and topiramate. Several AEDs (e.g., lamotrigine and levetiracetam) appear to possess low risks for both anatomical and behavioral teratogenesis. Despite advances in the past decade, our knowledge of the teratogenic risks for most AEDs and the underlying mechanisms remain inadequate. Further, the long-term effects of AEDs in neonates and older children remain uncertain. The pace of progress is slow given the lifelong consequences of diminished developmental outcomes, exposing children unnecessarily to potential adverse effects. It is imperative that new approaches be employed to determine risks more expediently. Our recommendations include a national reporting system for congenital malformations, federal funding of the North American AED Pregnancy Registry, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of AED prescription practices for women, routine preclinical testing of all new AEDs for neurodevelopmental effects, more specific Food and Drug Administration requirements to establish differential AED cognitive effects in children, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for AED-induced anatomical and behavioral teratogenesis. PMID:26519545

Customized versus Population Fetal Growth Norms and Adverse Outcomes Associated with Small for Gestational Age Infants in a High-Risk Cohort.

PubMed

Moussa, Hind N; Wu, Zhao Helen; Han, Yimei; Pacheco, Luis D; Blackwell, Sean C; Sibai, Baha M; Saade, George; Costantine, Maged M

2015-06-01

To compare population versus customized fetal growth norms in identifying neonates at risk for adverse perinatal and neonatal outcomes (AOs) associated with small for gestational age (SGA) in high-risk women. Secondary analysis to a multicenter treatment trial of pregnant women at high risk for preeclampsia using low-dose aspirin versus placebo. The associations between SGA by population (SGApop) and customized (SGAcust) norms and AOs were evaluated. A total of 2,289 mother/infant pairs were included in the analysis. The rates of SGA in the aspirin and placebo groups were similar by the customized (22.8% vs 23.9%; p = 0.55) or population (8.7% vs 7.5%; p = 0.54) norms; however, they were lower using population norms compared with customized norms (p < 0.001). SGAcust, but not SGApop, was associated with spontaneous preterm birth (odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.15-1.81; p < 0.001), preterm premature rupture of membranes (OR 1.42 95% CI 1.05-1.92; p = 0.02), and cesarean delivery (OR: 1.35, 95% CI: 1.11-1.64; p = 0.002). Both SGAcust and SGApop were associated with the composite neonatal outcome, indicated preterm delivery before 32, 35, and 37 weeks, oligohydramnios, fetal distress, as well as decreased risk of oxygen requirement. Neither was associated with preeclampsia. Customized approach for assessment of fetal growth was associated with higher SGA rates and better identification of SGA neonates at risk for AOs. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study.

PubMed

Gaillard, Romy; Eilers, Paul H C; Yassine, Siham; Hofman, Albert; Steegers, Eric A P; Jaddoe, Vincent W V

2014-05-01

To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy. In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals. Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7). In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications. © 2014 John Wiley & Sons Ltd.

Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences.

PubMed

Abel, E L; Hannigan, J H

1995-01-01

We present an hypothesis integrating epidemiological, clinical case, and basic biomedical research to explain why only relatively few women who drink alcohol during pregnancy give birth to children with alcohol-related birth defects (ARBDs), in particular, Fetal Alcohol Syndrome (FAS). We argue that specific sociobehavioral risk factors, e.g., low socioeconomic status, are permissive for FAS in that they provide the context for increased vulnerability. We illustrate how these permissive factors are related to biological factors, e.g., decreased antioxidant status, which in conjunction with alcohol, provoke FAS/ARBDs in vulnerable fetuses. We propose an integrative heuristic model hypothesizing that these permissive and provocative factors increase the likelihood of FAS/ARBDs because they potentiate two related mechanisms of alcohol-induced teratogenesis, specifically, maternal/fetal hypoxia and free radical formation.

Fetal Alcohol Syndrome (FAS)--A Review.

ERIC Educational Resources Information Center

Holzman, Ian R.

1982-01-01

At least 30 percent of newborn children of alcoholic mothers are affected severely by the fetal alcohol syndrome and 40-45 percent show some stigmata. Risks to offspring of mothers who drink occasionally or binge drink are not clear, but the danger is probably greatest in the first trimester of pregnancy. (CMG)

Fetal Origins of Child Non-Right-Handedness and Mental Health

ERIC Educational Resources Information Center

Rodriguez, Alina; Waldenstrom, Ulla

2008-01-01

Background: Environmental risk during fetal development for non-right-handedness, an index of brain asymmetry, and its relevance for child mental health is not fully understood. Methods: A Swedish population-based prospective pregnancy-offspring cohort was followed-up when children were five years old (N = 1714). Prenatal environmental risk…

Macrosomia Predictors in Infants Born to Cuban Mothers with Gestational Diabetes.

PubMed

Cruz, Jeddú; Grandía, Raiden; Padilla, Liset; Rodríguez, Suilbert; Hernández García, Pilar; Lang Prieto, Jacinto; Márquez-Guillén, Antonio

2015-07-01

INTRODUCTION Fetal macrosomia is the most important complication in infants of women with diabetes, whether preconceptional or gestational. Its occurrence is related to certain maternal and fetal conditions and negatively affects maternal and perinatal outcomes. The definitive diagnosis is made at birth if a newborn weighs >4000 g. OBJECTIVE Identify which maternal and fetal conditions could be macrosomia predictors in infants born to Cuban mothers with gestational diabetes. METHODS A case-control study comprising 236 women with gestational diabetes who bore live infants (118 with macrosomia and 118 without) was conducted in the América Arias University Maternity Hospital, Havana, Cuba, during 2002-2012. The dependent variable was macrosomia (birth weight >4000 g). Independent maternal variables included body mass index at pregnancy onset, overweight or obesity at pregnancy onset, gestational age at diabetes diagnosis, pregnancy weight gain, glycemic control, triglycerides and cholesterol. Fetal variables examined included third-semester fetal abdominal circumference, estimated fetal weight at ≥28 weeks (absolute and percentilized by Campbell and Wilkin, and Usher and McLean curves). Chi square was used to compare continuous variables (proportions) and the student t test (X ± SD) for categorical variables, with significance threshold set at p <0.05. ORs and their 95% CIs were calculated. RESULTS Significant differences between cases and controls were found in most variables studied, with the exception of late gestational diabetes diagnosis, total fasting cholesterol and hypercholesterolemia. The highest OR for macrosomia were for maternal hypertriglyceridemia (OR 4.80, CI 2.34-9.84), third-trimester fetal abdominal circumference >75th percentile (OR 7.54, CI 4.04-14.06), and estimated fetal weight >90th percentile by Campbell and Wilkin curves (OR 4.75, CI 1.42-15.84) and by Usher and McLean curves (OR 8.81, CI 4.25-18.26). CONCLUSIONS Most variables assessed were predictors of macrosomia in infants of mothers with gestational diabetes. They should therefore be taken into account for future studies and for patient management. Wide confidence intervals indicate uncertainty about the magnitude of predictive power. KEYWORDS Fetal macrosomia, fetal diseases, gestational diabetes, risk factors, risk prediction, Cuba.

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.

PubMed

Ridha, Fatnassi; Houssem, Ragmoun; Latifa, Marzougui; Ines, Mkhinini; Sabra, Hammami

2017-01-01

The delivery of a macrosomic infant is a relatively common situation. It can put mother and fetus at high risk. The main maternal complications are the increase in cesarean rates, postpartum hemorrhage and cervicovaginal traumatic lacerations. The main fetal complication is shoulder dystocia increasing the risk of brachial plexus. The objective was to identify risk factors and maternal-fetal complications associated with fetal macrosomia. Comparative retrospective study conducted at Kairouan University Hospital maternity unit in 2010. We compared a group of 820 cases of macrosomic infants to a control group of 800 cases of infants born in the same period of time. During the study period we collected clinical data of 820 macrosomic cases on a total of 7.495 deliveries, corresponding to a total incidence of 10.94%. Several factors predisposing to fetal macrosomia were highlighted: Maternal age> 35 years was present in 28.5% of cases; Maternal obesity was found in 45% of cases; A personal history of macrosomia was noted in 28,8% of cases; Prolonged pregnancies > 41 weeks of amenorrhoea was noted in 35.6% of cases; Multiparity was found in 47% of cases. Maternal complications were essentially postpartum hemorrhage: 71 cases and genital traumas: 24 cases. Perinatal complications were dominated by shoulder dystocia: 27 cases (3.3%). Traumatic postpartum complications were found in 11.6%.

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark.

PubMed

Basu, Millie Nguyen; Johnsen, Iben Birgit Gade; Wehberg, Sonja; Sørensen, Rikke Guldberg; Barington, Torben; Nørgård, Bente Mertz

2018-02-23

We examined the causes of death amongst full term stillbirths and early neonatal deaths. Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20-34 years and with a normal body mass index (BMI). Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

Maternal exercise, season and sex modify the daily fetal heart rate rhythm.

PubMed

Sletten, J; Cornelissen, G; Assmus, J; Kiserud, T; Albrechtsen, S; Kessler, J

2018-05-13

The knowledge on biological rhythms is rapidly expanding. We aimed to define the longitudinal development of the daily (24-hour) fetal heart rate rhythm in an unrestricted, out-of-hospital setting and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Daily rhythms in fetal heart rate and fetal heart rate variation were detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant daily rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (P < .001) and nonlinearly in males (quadratic function, P = .001). At 32 and 36 weeks, interindividual rhythm diversity was found in male fetuses during higher maternal physical activity and during the summer season. The dynamic development of the daily fetal heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Novel insights into host responses and reproductive pathophysiology of porcine reproductive and respiratory syndrome caused by PRRSV-2.

PubMed

Harding, John C S; Ladinig, Andrea; Novakovic, Predrag; Detmer, Susan E; Wilkinson, Jamie M; Yang, Tianfu; Lunney, Joan K; Plastow, Graham S

2017-09-01

A large challenge experiment using North American porcine reproductive and respiratory virus (PRRSV-2) provided new insights into the pathophysiology of reproductive PRRS. Deep phenotyping of dams and fetuses identified maternal and fetal predictors of PRRS severity and resilience. PRRSV infection resulted in dramatic decreases in all leukocyte subsets by 2days post inoculation. Apoptosis in the interface region was positively related to endometrial vasculitis, viral load in endometrium and fetal thymus, and odds of meconium staining. Viral load at the maternal-fetal interface was a strong predictor of viral load in fetal thymus and odds of fetal death. However, interferon-alpha suppression, a consequence of PRRSV infection, was protective against fetal death. Although the prevalence of fetal lesions was low, their presence in fetal organs and umbilical cord was strongly associated with fetal compromise. Fetal death and viral load clustered in litters suggesting inter-fetal transmission starting from a limited number of index fetuses. Factors associated with index fetal infection are unclear, but large fetuses appear at greater risk. Disease progression in fetuses was associated with an up-regulation of genes associated with inflammation, innate immunity, and cell death signaling, and down-regulation of genes associated with cell cycle and lymphocyte quality. A number of maternal transcriptomic responses were associated with PRRS resilience including higher basal gene expression correlated with platelet function, interferon and pro-inflammatory responses. Twenty-one genomic regions across 10 chromosomes were associated with important traits including fetal viral load, fetal death and viability suggesting that selection for reproductive PRRS resilience may be possible. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges

PubMed Central

Epstein, Richard A; Moore, Katherine M; Bobo, William V

2015-01-01

Treating pregnant women with bipolar disorder is among the most challenging clinical endeavors. Patients and clinicians are faced with difficult choices at every turn, and no approach is without risk. Stopping effective pharmacotherapy during pregnancy exposes the patient and her baby to potential harms related to bipolar relapses and residual mood symptom-related dysfunction. Continuing effective pharmacotherapy during pregnancy may prevent these occurrences for many; however, some of the most effective pharmacotherapies (such as valproate) have been associated with the occurrence of congenital malformations or other adverse neonatal effects in offspring. Very little is known about the reproductive safety profile and clinical effectiveness of atypical antipsychotic drugs when used to treat bipolar disorder during pregnancy. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated or undertreated maternal bipolar disorder during pregnancy, the effectiveness of interventions for bipolar disorder management during pregnancy, and potential obstetric, fetal, and neonatal risks associated with core foundational pharmacotherapies for bipolar disorder. PMID:25565896

Occiput posterior fetal head position increases the risk of anal sphincter injury in vacuum-assisted deliveries.

PubMed

Wu, Jennifer M; Williams, Kathryn S; Hundley, Andrew F; Connolly, AnnaMarie; Visco, Anthony G

2005-08-01

The purpose of this study was to determine whether an occiput posterior (OP) fetal head position increases the risk for anal sphincter injury when compared with an occiput anterior (OA) position in vacuum-assisted deliveries. We conducted a retrospective cohort study of 393 vacuum-assisted singleton vaginal deliveries. Maternal demographics and obstetric and neonatal data were collected from an obstetric database and chart review. Within the OP group, 41.7% developed a third- or fourth-degree laceration compared with 22.0% in the OA group (OR 2.5, 95% CI 1.4-4.7). In a logistic regression model that controlled for BMI, race, nulliparity, length of second stage, episiotomy, birth weight, head circumference, and fetal head position, OP position was 4.0 times (95% CI 1.7-9.6) more likely to be associated with an anal sphincter injury than OA position. Among vacuum deliveries, an OP head position confers an incrementally increased risk for anal sphincter injury over an OA position.

Pregnancy in patients with chronic renal disease.

PubMed Central

Bear, R. A.

1978-01-01

Pregnancy is not invariably contra-indicated in patients with pre-existing renal disease. Clinical data now exist that permit the clinician to distinguish such patients who are likely to experience difficulty during pregnancy from those in whom pregnancy can be undertaken with high expectation of success. Patients suffering from systemic lupus erythematosus, active or inactive, with or without lupus nephritis, should avoid pregnancy. Patients with other forms of chronic renal disease in whom the serum creatinine concentration prior to pregnancy is less than 1.5 mg/dL are not exposed to increased maternal or fetal risk. On the other hand, patients with serum creatinine values exceeding 1.6 mg/dL experience a high incidence of maternal and fetal complications and should avoid pregnancy. The life expectancy of recipients of a renal transplant is uncertain, and these patients should receive counselling as to the advisability of undertaking pregnancy. The maternal risk in such patients is not inordinately high, but the fetal risk is considerable. PMID:350371

Placenta previa and long-term morbidity of the term offspring.

PubMed

Walfisch, Asnat; Beharier, Ofer; Shoham-Vardi, Ilana; Sergienko, Ruslan; Landau, Daniella; Sheiner, Eyal

2016-08-01

The long-term impact of placenta previa on term infants is unknown. We aimed to investigate whether abnormal placentation increases the risk for long-term morbidity of the term offspring. A population-based cohort study compared the incidence of long-term hospitalizations up to the age of 18 due to cardiovascular, endocrine, neurological, hematological, respiratory and urinary morbidity of children born at term in pregnancies diagnosed with placenta previa and those without. Deliveries occurred between the years 1991-2013 in a tertiary medical center. Multiple pregnancies, and fetal congenital malformations were excluded. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence over time. A multivariable generalized estimating equation (GEE) logistic regression model analysis was used to control for confounders and for maternal clusters. During the study period 233,123 term deliveries met the inclusion criteria; 0.2% (n=502) of the children were born to mothers with placenta previa. During the follow-up period, children born to mothers with placenta previa did not have an increased risk for long-term cardiovascular, endocrine, hematological, neurological, respiratory, and urinary morbidity. Term offsprings of mothers diagnosed with placenta previa do not appear to be at an increased risk for long-term morbidity up to the age of 18. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluation of fetal anthropometric measures to predict the risk for shoulder dystocia.

PubMed

Burkhardt, T; Schmidt, M; Kurmanavicius, J; Zimmermann, R; Schäffer, L

2014-01-01

To evaluate the quality of anthropometric measures to improve the prediction of shoulder dystocia by combining different sonographic biometric parameters. This was a retrospective cohort study of 12,794 vaginal deliveries with complete sonographic biometry data obtained within 7 days before delivery. Receiver-operating characteristics (ROC) curves of various combinations of the biometric parameters, namely, biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference, abdominal diameter (AD), abdominal circumference (AC) and femur length were analyzed. The influences of independent risk factors were calculated and their combination used in a predictive model. The incidence of shoulder dystocia was 1.14%. Different combinations of sonographic parameters showed comparable ROC curves without advantage for a particular combination. The difference between AD and BPD (AD - BPD) (area under the curve (AUC) = 0.704) revealed a significant increase in risk (odds ratio (OR) 7.6 (95% CI 4.2-13.9), sensitivity 8.2%, specificity 98.8%) at a suggested cut-off ≥ 2.6 cm. However, the positive predictive value (PPV) was low (7.5%). The AC as a single parameter (AUC = 0.732) with a cut-off ≥ 35 cm performed worse (OR 4.6 (95% CI 3.3-6.5), PPV 2.6%). BPD/OFD (a surrogate for fetal cranial shape) was not significantly different between those with and those without shoulder dystocia. The combination of estimated fetal weight, maternal diabetes, gender and AD - BPD provided a reasonable estimate of the individual risk. Sonographic fetal anthropometric measures appear not to be a useful tool to screen for the risk of shoulder dystocia due to a low PPV. However, AD - BPD appears to be a relevant risk factor. While risk stratification including different known risk factors may aid in counseling, shoulder dystocia cannot effectively be predicted. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Performance of a wearable acoustic system for fetal movement discrimination

PubMed Central

Lai, Jonathan; Woodward, Richard; Alexandrov, Yuriy; ain Munnee, Qurratul; Lees, Christoph C.

2018-01-01

Fetal movements (FM) are a key factor in clinical management of high-risk pregnancies such as fetal growth restriction. While maternal perception of reduced FM can trigger self-referral to obstetric services, maternal sensation is highly subjective. Objective, reliable monitoring of fetal movement patterns outside clinical environs is not currently possible. A wearable and non-transmitting system capable of sensing fetal movements over extended periods of time would be extremely valuable, not only for monitoring individual fetal health, but also for establishing normal levels of movement in the population at large. Wearable monitors based on accelerometers have previously been proposed as a means of tracking FM, but such systems have difficulty separating maternal and fetal activity and have not matured to the level of clinical use. We introduce a new wearable system based on a novel combination of accelerometers and bespoke acoustic sensors as well as an advanced signal processing architecture to identify and discriminate between types of fetal movements. We validate the system with concurrent ultrasound tests on a cohort of 44 pregnant women and demonstrate that the garment is capable of both detecting and discriminating the vigorous, whole-body ‘startle’ movements of a fetus. These results demonstrate the promise of multimodal sensing for the development of a low-cost, non-transmitting wearable monitor for fetal movements. PMID:29734344

Performance of a wearable acoustic system for fetal movement discrimination.

PubMed

Lai, Jonathan; Woodward, Richard; Alexandrov, Yuriy; Ain Munnee, Qurratul; Lees, Christoph C; Vaidyanathan, Ravi; Nowlan, Niamh C

2018-01-01

Fetal movements (FM) are a key factor in clinical management of high-risk pregnancies such as fetal growth restriction. While maternal perception of reduced FM can trigger self-referral to obstetric services, maternal sensation is highly subjective. Objective, reliable monitoring of fetal movement patterns outside clinical environs is not currently possible. A wearable and non-transmitting system capable of sensing fetal movements over extended periods of time would be extremely valuable, not only for monitoring individual fetal health, but also for establishing normal levels of movement in the population at large. Wearable monitors based on accelerometers have previously been proposed as a means of tracking FM, but such systems have difficulty separating maternal and fetal activity and have not matured to the level of clinical use. We introduce a new wearable system based on a novel combination of accelerometers and bespoke acoustic sensors as well as an advanced signal processing architecture to identify and discriminate between types of fetal movements. We validate the system with concurrent ultrasound tests on a cohort of 44 pregnant women and demonstrate that the garment is capable of both detecting and discriminating the vigorous, whole-body 'startle' movements of a fetus. These results demonstrate the promise of multimodal sensing for the development of a low-cost, non-transmitting wearable monitor for fetal movements.

Prenatal Depression Restricts Fetal Growth

PubMed Central

Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

2009-01-01

Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

MYSTERIES OF THE HUMAN FETUS REVEALED

PubMed Central

SANDMAN, CURT A

2015-01-01

The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Lacey's, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk.. PMID:26303720

Fetal transesophageal echocardiography: clinical introduction as a monitoring tool during cardiac intervention in a human fetus.

PubMed

Kohl, T; Müller, A; Tchatcheva, K; Achenbach, S; Gembruch, U

2005-12-01

Because of insufficient imaging by maternal transabdominal fetal echocardiography (TAE) in a human fetus with aortic atresia, imperforate atrial septum and progressive cardiac failure, we assessed the feasibility of fetal transesophageal echocardiography (TEE) as a monitoring tool during fetal cardiac intervention at 24 + 6 weeks of gestation. Percutaneous fetoscopic intraesophageal deployment of the ultrasound catheter was achieved and did not result in any maternal or fetal complications. Fetal TEE permitted substantially clearer definition of fetal cardiac anatomy and intracardiac device manipulations than conventional maternal TAE. Despite the employment of various devices, no sufficiently large opening could be achieved within the atrial septum. Although the fetus tolerated the procedure remarkably well and satisfactory fetoplacental flow could be documented at the end of the procedure, the fetus died from progressive cardiac failure 3 days after the intervention. Fetoscopic TEE is feasible in the human fetus and permits substantially clearer definition of fetal cardiac anatomy and intracardiac manipulations than conventional maternal TAE. Based on the observation of spontaneous closure of multiple iatrogenic perforations of the atrial septum, specialized devices are required in order to improve the technical success rate of septoplasty methods and hence the survival odds of these high-risk patients.

Does the Use of Diagnostic Technology Reduce Fetal Mortality?

PubMed

Grytten, Jostein; Skau, Irene; Sørensen, Rune; Eskild, Anne

2018-01-19

To examine the effect that the introduction of new diagnostic technology in obstetric care has had on fetal death. The Medical Birth Registry of Norway provided detailed medical information for approximately 1.2 million deliveries from 1967 to 1995. Information about diagnostic technology was collected directly from the maternity units, using a questionnaire. The data were analyzed using a hospital fixed-effects regression with fetal mortality as the outcome measure. The key independent variables were the introduction of ultrasound and electronic fetal monitoring at each maternity ward. Hospital-specific trends and risk factors of the mother were included as control variables. The richness of the data allowed us to perform several robustness tests. The introduction of ultrasound caused a significant drop in fetal mortality rate, while the introduction of electronic fetal monitoring had no effect on the rate. In the population as a whole, ultrasound contributed to a reduction in fetal deaths of nearly 20 percent. For post-term deliveries, the reduction was well over 50 percent. The introduction of ultrasound made a major contribution to the decline in fetal mortality at the end of the last century. © Health Research and Educational Trust.

Role of fetal DNA in preeclampsia (review).

PubMed

Konečná, Barbora; Vlková, Barbora; Celec, Peter

2015-02-01

Preeclampsia is an autoimmune disorder characterized by hypertension. It begins with abnormal cytotrophoblast apoptosis, which leads to inflammation and an increase in the levels of anti-angiogenic factors followed by the disruption of the angiogenic status. Increased levels of fetal DNA and RNA coming from the placenta, one of the most commonly affected organs in pregnancies complicated by preeclampsia, have been found in pregnant women with the condition. However, it remains unknown as to whether this is a cause or a consequence of preeclampsia. Few studies have been carried out on preeclampsia in which an animal model of preeclampsia was induced by an injection of different types of DNA that are mimic fetal DNA and provoke inflammation through Toll-like receptor 9 (TLR9) or cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). The specific mechanisms involved in the development of preeclampsia are not yet fully understood. It is hypothesized that the presence of different fragments of fetal DNA in maternal plasma may cause for the development of preeclampsia. The function of DNase during preeclampsia also remains unresolved. Studies have suggested that its activity is decreased or the DNA is protected against its effects. Further research is required to uncover the pathogenesis of preeclampsia and focus more on the condition of patients with the condition.

Fetal electrocardiogram (ECG) for fetal monitoring during labour.

PubMed

Neilson, James P

2015-12-21

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average fewer fetal scalp samples taken during labour (average RR 0.61, 95% CI 0.41 to 0.91; four trials, 9671 babies; high quality evidence) although the findings were heterogeneous and there were no data from the largest trial (from the USA). There were marginally fewer operative vaginal births (RR 0.92, 95% CI 0.86 to 0.99; six trials, 26,446 women); but no obvious difference in the number of babies with low Apgar scores at five minutes or babies requiring neonatal intubation, or babies requiring admission to the special care unit (RR 0.96, 95% CI 0.89 to 1.04, six trials, 26,410 babies; high quality evidence). There was little evidence that monitoring by PR interval analysis conveyed any benefit of any sort. The modest benefits of fewer fetal scalp samplings during labour (in settings in which this procedure is performed) and fewer instrumental vaginal births have to be considered against the disadvantages of needing to use an internal scalp electrode, after membrane rupture, for ECG waveform recordings. We found little strong evidence that ST waveform analysis had an effect on the primary outcome measures in this systematic review.There was a lack of evidence showing that PR interval analysis improved any outcomes; and a larger future trial may possibly demonstrate beneficial effects.There is little information about the value of fetal ECG waveform monitoring in preterm fetuses in labour. Information about long-term development of the babies included in the trials would be valuable.

Maternal and fetal safety of fluid-restrictive general anesthesia for endoscopic fetal surgery in monochorionic twin gestations.

PubMed

Duron, Vincent D; Watson-Smith, Debra; Benzuly, Scott E; Muratore, Christopher S; O'Brien, Barbara M; Carr, Stephen R; Luks, Francois I

2014-05-01

To review our experience with general anesthesia in endoscopic fetal surgery for twin-to-twin transfusion syndrome (TTTS), and to compare fetomaternal outcome before and after protocol implementation. Retrospective impact study. University-affiliated medical center. Data from 85 consecutive patients who underwent endoscopic laser ablation of placenta vessels for severe TTTS were studied. Outcomes were compared in patients before (2000-2007) and after (2008-2012) a change to strict intraoperative intravenous (IV) fluid and liberal vasopressor management. Perioperative parameters (IV fluid administration, vasopressor use, maternal hemoglobin [Hb] concentration); maternal complication rate (respiratory, hemorrhagic); pregnancy outcome; and fetal and neonatal survival were recorded. Patients in the early group (2000-2007; n = 55) received 1634 ± 949 mL of crystalloid fluid intraoperatively, compared with 485 ± 238 mL (P < 0.001; Student's t test) given to the late group (2008-2012; n = 30). Maternal pulmonary edema and any respiratory distress were seen in 5.5% and 12.7% of patients in the early group, respectively, and in none of the late group patients (P < 0.05; Chi-square analysis). A significant risk of maternal respiratory complications exists after general anesthesia for endoscopic fetal surgery. Judicious fluid management significantly decreases this risk. Copyright © 2014 Elsevier Inc. All rights reserved.

Predictive factors for intrauterine growth restriction

PubMed Central

Albu, AR; Anca, AF; Horhoianu, VV; Horhoianu, IA

2014-01-01

Abstract Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. Abbreviations: SGA = small for gestational age; IUGR = intrauterine growth restriction; FGR = fetal growth restriction; IUFD = intrauterine fetal demise; HIV = human immunodeficiency virus; PAPP-A = pregnancy associated plasmatic protein A; β-hCG = beta human chorionic gonadotropin; MoM = multiple of median; ADAM-12 = A-disintegrin and metalloprotease 12; PP-13 = placental protein 13; VEGF = vascular endothelial growth factor; PlGF = placental growth factor; sFlt-1 = soluble fms-like tyrosine kinase-1; UAD = uterine arteries Doppler ultrasound; RI = resistence index; PI = pulsatility index; VOCAL = Virtual Organ Computer–Aided Analysis software; VI = vascularization index; FI = flow index; VFI = vascularization flow index; PQ = placental quotient PMID:25408721

Fetal programming of infant neuromotor development: the generation R study.

PubMed

van Batenburg-Eddes, Tamara; de Groot, Laila; Steegers, Eric A P; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning

2010-02-01

The objective of the study was to examine whether infant neuromotor development is determined by fetal size and body symmetry in the general population. This study was embedded within the Generation R Study, a population-based cohort in Rotterdam. In 2965 fetuses, growth parameters were measured in mid-pregnancy and late pregnancy. After birth, at age 9 to 15 wks, neuromotor development was assessed with an adapted version of Touwen's Neurodevelopmental Examination. Less optimal neuromotor development was defined as a score in the highest tertile. We found that higher fetal weight was beneficial to infant neurodevelopment. A fetus with a 1-SD score higher weight in mid-pregnancy had an 11% lower risk of less optimal neuromotor development (OR: 0.89; 95% CI: 0.82-0.97). Similarly, a fetus with a 1-SD score larger abdominal-to-head circumference (AC/HC) ratio had a 13% lower risk of less optimal neuromotor development (OR: 0.87; 95% CI: 0.79-0.96). These associations were also present in late pregnancy. Our findings show that fetal size and body symmetry in pregnancy are associated with infant neuromotor development. These results suggest that differences in infant neuromotor development, a marker of behavioral and cognitive problems, are at least partly caused by processes occurring early in fetal life.

Signs of fetal brain sparing are not related to umbilical cord blood gases at birth.

PubMed

Cheema, Riffat; Dubiel, Mariusz; Gudmundsson, Saemundur

2009-07-01

Fetal chronic hypoxia leads to centralization of circulation in order to spare the vital organs brain, adrenals and the heart. This can be documented by Doppler ultrasound. Increased blood velocity in the fetal middle cerebral artery (MCA) is an acknowledged sign of centralization of circulation in chronic hypoxia, and is called brain sparing. Our aim was to assess the relationship between signs of brain sparing in the MCA and umbilical cord blood gases at birth. A prospective study. Singleton 57 high-risk pregnancies (outcome was compared with 21 normal pregnancies). MCA Doppler was performed within 24 h of elective caesarean section in high-risk pregnancies. Umbilical cord blood gases were analysed at birth. Cord blood gases were related to signs of centralization of fetal circulation in the MCA. No correlation between signs of brain sparing in the MCA and cord blood gases. Apgar score at 5'<7 was seen in three newborns, but only one of these had antenatal signs of brain sparing. Newborns with antenatal brain sparing were admitted more often (p<0.04) and had a longer duration of stay in NICU (p<0.03) compared to newborns without brain sparing. Decreased pulsatility index in MCA is an acknowledged sign of fetal centralization of circulation during chronic hypoxia. However, signs of brain sparing are not related to cord blood gases at birth, which might suggest that redistribution of fetal circulation can maintain normal blood gases for a long time during chronic hypoxia.

Prognostic factors of premature closure of the ductus arteriosus in utero: a systematic literature review.

PubMed

Ishida, Hidekazu; Kawazu, Yukiko; Kayatani, Futoshi; Inamura, Noboru

2017-05-01

A number of case reports show various outcomes of premature closure of the ductus arteriosus in utero, including persistent pulmonary hypertension of the newborn and fetal or neonatal death; however, no study clarifies the clinical observations that are related to their prognoses. We aimed to clarify the prognostic factors of intrauterine ductal closure by a systematic literature review. Data sources We searched PubMed database (1975-2014) to identify case reports and studies on intrauterine closure of the ductus arteriosus, including maternal, fetal, and neonatal clinical information and their prognoses. We analysed the data of 116 patients from 39 articles. Of these, 12 (10.3%) died after birth or in utero. Fetal or neonatal death was significantly correlated with fetal hydrops (odds ratio=39.6, 95% confidence interval=4.6-47.8) and complete closure of the ductus arteriosus (odds ratio=5.5, 95% confidence interval=1.2-15.1). Persistent pulmonary hypertension was observed in 33 cases (28.4%), and was also correlated with fetal hydrops (odds ratio=4.2, 95% confidence interval=1.3-4.6) and complete closure of the ductus arteriosus (odds ratio=5.5, 95% confidence interval=1.6-6.0). Interestingly, maternal drug administration was not correlated with the risk of death and persistent pulmonary hypertension. Fetal hydrops and complete ductal closure are significant risk factors for both death and persistent pulmonary hypertension. Cardiac or neurological prognoses could be favourable if the patients overcome right heart failure during the perinatal period.

Fetal immune response to chorioamnionitis

PubMed Central

Kallapur, Suhas G.; Presicce, Pietro; Rueda, Cesar M.; Jobe, Alan H.; Chougnet, Claire A.

2014-01-01

Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, GI tract, brain and other fetal organs. Chorioamnionitis is a polymicrobial non-traditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis induced injury in different fetal compartments. Since chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses. PMID:24390922

Fetal evaluation for transport by ultrasound performed by air medical teams: A case series.

PubMed

Polk, James D; Merlino, James I; Kovach, Betty L; Mancuso, Charlene; Fallon, William F

2004-01-01

The air medical team has limited options when evaluating the obstetrical patient and assessing fetal health during air transport to a high-risk obstetrical unit. Traditionally, physical examination and a Doppler stethoscope have been used to determine fetal heart rates and movement. However, with the advent of portable ultrasound technology, new information about the mother and child are available to the air medical crew. The Fetal Evaluation for Transport with Ultrasound (FETUS) is a screening examination that consists of an evaluation of the fetal heart rate, position, and movement and general condition of the placenta. The examination can be repeated in flight with no acoustic distortion from rotor noise. The additional information can be advantageous when transport decisions need to be made or when conditions do not allow Doppler stethoscope use.

Intrinsic catch-up growth of hypoplastic fetal lungs is mediated by interleukin-6.

PubMed

Nogueira-Silva, Cristina; Moura, Rute S; Esteves, Nuno; Gonzaga, Sílvia; Correia-Pinto, Jorge

2008-07-01

Fetal lung hypoplasia is a common finding in several fetal conditions such as congenital diaphragmatic hernia (CDH). Interestingly, previous studies have demonstrated that hypoplastic lungs have the ability to recover to normal size, when relieved from mechanical factors. However, the underlying mechanisms remain largely unknown. Recently, interleukin-6 (IL-6) has been involved in catch-up growth phenomenon in children. Thus, we hypothesized that IL-6 could mediate fetal growth recover from hypoplastic lungs. Control and nitrofen-induced hypoplastic lung explants were cultured either in normal conditions or with IL-6 neutralizing antibodies. The total number of peripheral airway buds, epithelial perimeter, and total explant area were analyzed and daily branching rates were calculated. Additionally, IL-6 mRNA and protein expression was assessed both in qualitative (by in situ hybridization and immunohistochemistry) and in quantitative (by real-time PCR and Western blot) approaches, in control and hypoplastic lungs (nitrofen and CDH groups). Nitrofen-induced hypoplastic lungs showed in vitro, out of systemic environment, the ability to recover from hypoplasia and presented daily branching rates significantly higher than controls. Blocking IL-6 activity significantly diminished the intrinsic capacity of hypoplastic fetal lungs to recover from hypoplasia and attenuated their daily branching rates. Although more exacerbated in CDH, both nitrofen-exposed lungs presented significant IL-6 mRNA and protein over-expression throughout all studied gestational ages. The present study suggests, for the first time, that fetal lung is able to recover from growth retardation through a way that resembles the catch-up growth phenomenon, and it seems to be, at least partially, orchestrated by intrinsic mechanisms implicating IL-6.

IGF2 DNA methylation is a modulator of newborn's fetal growth and development.

PubMed

St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

2012-10-01

The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.

IGF2 DNA methylation is a modulator of newborn’s fetal growth and development

PubMed Central

St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

2012-01-01

The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn’s fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn’s weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn’s fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity. PMID:22907587

Type I interferons instigate fetal demise after Zika virus infection.

PubMed

Yockey, Laura J; Jurado, Kellie A; Arora, Nitin; Millet, Alon; Rakib, Tasfia; Milano, Kristin M; Hastings, Andrew K; Fikrig, Erol; Kong, Yong; Horvath, Tamas L; Weatherbee, Scott; Kliman, Harvey J; Coyne, Carolyn B; Iwasaki, Akiko

2018-01-05

Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout ( Ifnar1 -/- ) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling. The role of type I IFNs in limiting or mediating ZIKV disease within this congenital infection model remains unknown. In this study, we challenged Ifnar1 -/- dams mated with Ifnar1 +/- sires with ZIKV. This breeding scheme enabled us to examine pregnant dams that carry a mixture of fetuses that express ( Ifnar1 +/- ) or do not express IFNAR ( Ifnar1 -/- ) within the same uterus. Virus replicated to a higher titer in the placenta of Ifnar1 -/- than within the Ifnar1 +/- concepti. Yet, rather unexpectedly, we found that only Ifnar1 +/- fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1 -/- littermates continue to develop. Analyses of the fetus and placenta revealed that, after ZIKV infection, IFNAR signaling in the conceptus inhibits development of the placental labyrinth, resulting in abnormal architecture of the maternal-fetal barrier. Exposure of midgestation human chorionic villous explants to type I IFN, but not type III IFNs, altered placental morphology and induced cytoskeletal rearrangements within the villous core. Our results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Prenatal choline and the development of schizophrenia

PubMed Central

FREEDMAN, Robert; ROSS, Randal G.

2015-01-01

Background The primary prevention of illness at the population level, the ultimate aim of medicine, seems out of reach for schizophrenia. Schizophrenia has a strong genetic component, and its pathogenesis begins long before the emergence of psychosis, as early as fetal brain development. Cholinergic neurotransmission at nicotinic receptors is a pathophysiological mechanism related to one aspect of this genetic risk. Choline activates these nicotinic receptors during fetal brain development. Dietary supplementation of maternal choline thus emerges as a possible intervention in pregnancy to alter the earliest developmental course of the illness. Aim Review available literature on the relationship of choline supplementation or choline levels during pregnancy and fetal brain development. Methods A Medline search was used to identify studies assessing effects of choline in human fetal development. Studies of other prenatal risk factors for schizophrenia and the role of cholinergic neurotransmission in its pathophysiology were also identified. Results Dietary requirements for choline are high during pregnancy because of its several uses, including membrane biosynthesis, one-carbon metabolism, and cholinergic neurotransmission. Its ability to act directly at high concentrations as a nicotinic agonist is critical for normal brain circuit development. Dietary supplementation in the second and third trimesters with phosphatidyl-choline supports these functions and is associated generally with better fetal outcome. Improvement in inhibitory neuronal functions whose deficit is associated with schizophrenia and attention deficit disorder has been observed. Conclusion Prenatal dietary supplementation with phosphatidyl-choline and promotion of diets rich in choline-containing foods (meats, soybeans, and eggs) are possible interventions to promote fetal brain development and thereby decrease the risk of subsequent mental illnesses. The low risk and short (sixmonth) duration of the intervention makes it especially conducive to population-wide adoption. Similar findings with folate for the prevention of cleft palate led to recommendations for prenatal pharmacological supplementation and dietary improvement. However, definitive proof of the efficacy of prenatal choline supplementation will not be available for decades (because of the 20-year lag until the onset of schizophrenia), so public health officials need to decide whether or not promoting choline supplementation is justified based on the limited information available. PMID:26120259

Investigations of Crashes Involving Pregnant Occupants

PubMed Central

Klinich, Kathleen DeSantis; Schneider, Lawrence W.; Moore, Jamie L.; Pearlman, Mark D.

2000-01-01

Case reports of 16 crashes involving pregnant occupants are presented that illustrate the main conclusions of a crash-investigation program that includes 42 crashes investigated to date. Some unusual cases that are exceptions to the overall trends are also described. The study indicates a strong association between adverse fetal outcome and both crash severity and maternal injury. Proper restraint use, with and without airbag deployment, generally leads to acceptable fetal outcomes in lower severity crashes, while it does not affect fetal outcome in high-severity crashes. Compared to properly restrained pregnant occupants, improperly restrained occupants have a higher risk of adverse fetal outcome in lower severity crashes, which comprise the majority of all motor-vehicle collisions. PMID:11558095

[Measles and pregnancy].

PubMed

Anselem, Olivia; Tsatsaris, Vassilis; Lopez, Emmanuel; Krivine, Anne; Le Ray, Camille; Loulergue, Pierre; Floret, Daniel; Goffinet, Francois; Launay, Odile

2011-11-01

Because of insufficient vaccine coverage, there is an outbreak of measles since 2008 in France with an increasing incidence of cases, most of them among children less than 1 year old or young adults. When measles occurs during pregnancy, maternal and fetal morbidity is increased. Particularly pregnant women are exposed to a higher risk of severe respiratory distress that might cause death. Measles virus can be detected in the placenta. Placental infection appears to be involved in some cases of fetal death. The virus is not responsible for congenital defects but can induce histologic damages inside the placenta which may lead to fetal death. Major perinatal risks are also miscarriage and prematurity. When measles occurs in late pregnancy, congenital infection is possible with variable expression and a risk of subacute sclerosing panencephalitis. Non immune pregnant women or neonates exposed to measles should receive an immunoglobulin prophylaxis within 6 days after contact in order to reduce the risk of infection and severe morbidity. In case of declared measles infection, symptomatic treatment can be proposed and tocolysis can be used if preterm labor is associated. Daily fetal monitoring during the 14 days following the beginning of the eruption can be offered when the fetus is viable. Vaccination is recommended for the people born in France after 1980 with 2 doses of vaccine against measles, rubeola and mumps. Measles vaccine, an attenuated living vaccine, should not be administered during pregnancy but must be proposed before pregnancy or during the post-partum period. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Reengineering Electronic Fetal Monitoring Interpretation: Using the Fetal Reserve Index to Anticipate the Need for Emergent Operative Delivery.

PubMed

Eden, Robert D; Evans, Mark I; Evans, Shara M; Schifrin, Barry S

2018-04-01

The near-ubiquitous use of electronic fetal monitoring has failed to lower the rates of both cerebral palsy and emergency operative deliveries (EODs). Its performance metrics have low sensitivity, specificity, and predictive values for both. There are many EODs, but the vast majority have normal outcomes. The EODs, however, cause serious disruption in the delivery suite routine with increased complications, anxiety, and concern for all. We developed the fetal reserve index (FRI) as multicomponent algorithm including 4 FHR components (analyzed individually), uterine activity, and maternal, obstetrical, and fetal risk factors to assess risk of cerebral palsy and EOD. Scores were categorized into green, yellow, and red zones. Here, we studied 300 patients by the FRI, all of whom had normal neonatal outcomes. We attempted to distinguish the clinical course of those cases which required an EOD versus controls which did not. 51 cases with EOD had FRIs much lower than 249 non-EOD cases. The red zone was reached more frequently ( P < .001) and lasted longer (1.06 vs 0.05 hours; P < .001). Reaching the red zone had a sensitivity of 92% for EOD, with a positive predictive value of 64% and a false positive rate of 10.4%. Our data suggest the FRI can significantly lower the incidence of EODs by identifying the opportunity for intrauterine resuscitation. Our approach can reduce the disruptive effects of EODs and their concomitant increased risks of complications. The FRI may provide a metric that can refine labor management to reduce CP and EODs.

Acetaminophen and pregnancy: short- and long-term consequences for mother and child.

PubMed

Thiele, Kristin; Kessler, Timo; Arck, Petra; Erhardt, Annette; Tiegs, Gisa

2013-03-01

Counter-intuitively, over-the-counter medication is commonly taken by pregnant women. In this context, acetaminophen (APAP, e.g. Paracetamol, Tylenol) is generally recommended by physicians to treat fever and pain during pregnancy. Thus, APAP ranks at the top of the list of medications taken prenatally. Insights on an increased risk for pregnancy complications such as miscarriage, stillbirth, preterm birth or fetal malformations upon APAP exposure are rather ambiguous. However, emerging evidence arising from human trials clearly reveals a significant correlation between APAP use during pregnancy and an increased risk for the development of asthma in children later in life. Pathways through which APAP increases this risk are still elusive. APAP can be liver toxic and since APAP appears to freely cross the placenta, therapeutic and certainly toxic doses could not only affect maternal, but also fetal hepatocytes. It is noteworthy that during fetal development, the liver transiently functions as the main hematopoietic organ. We here review the effect of APAP on metabolic and immunological parameters in pregnant women and on fetal development and immune ontogeny in order to delineate novel, putative and to date underrated pathways through which APAP use during pregnancy can impair maternal, fetal and long term children's health. We conclude that future studies are urgently needed to reconsider the safety and dosage of APAP during pregnancy and - based on the advances made in the field of reproduction as well as APAP metabolism - we propose pathways, which should be addressed in future research and clinical endeavors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors

PubMed Central

Habert, René; Muczynski, Vincent; Grisin, Tiphany; Moison, Delphine; Messiaen, Sébastien; Frydman, René; Benachi, Alexandra; Delbes, Géraldine; Lambrot, Romain; Lehraiki, Abdelali; N'Tumba-Byn, Thierry; Guerquin, Marie-Justine; Levacher, Christine; Rouiller-Fabre, Virginie; Livera, Gabriel

2014-01-01

Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk. PMID:24497529

Birthweight below the tenth percentile: the relative and attributable risks of maternal tobacco consumption and other factors.

PubMed

Morrison, J; Williams, G M; Najman, J M; Andersen, M J; Keeping, J D

1993-10-01

Analysis of 7776 singleton births defined a cohort of babies with birthweight below the 10th percentile after adjusting for gestational age and sex. The relative risk of a baby being small for gestational age in respect to a number of factors, such as parental anthropometry, demographic factors, behavior patterns (tobacco, cannabis, alcohol, and caffeine consumption), maternal pathology, and fetal abnormality, was calculated. The highest relative risks are associated with severe antepartum hemorrhage, severe pre-eclampsia, and severe fetal abnormality. As these are relatively rare events, a more accurate calculation of overall risk to the population as opposed to the individual can be obtained by studying the percent attributable risk of each of the factors. This demonstrates that maternal tobacco consumption is the major environmental risk factor in our population.

External cephalic version facilitation for breech presentation at term.

PubMed

Hofmeyr, G J

2000-01-01

Successful external cephalic version at a late stage of pregnancy was considered to be possible only with the use of tocolytic drugs to relax the uterus. Other methods are also used in an attempt to facilitate external cephalic version at term. The objective of this review was to assess the effects of routine tocolysis, fetal acoustic stimulation, epidural anaesthesia and transabdominal amnioinfusion for external cephalic version at term on successful version and measures of pregnancy outcome. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Date of last search: February 1999. Randomised and quasi-randomised trials comparing routine versus selective tocolysis; fetal acoustic stimulation in midline fetal spine positions versus dummy or no stimulation; epidural analgesia versus no epidural analgesia; or transabdominal amnioinfusion versus no amnioinfusion for external cephalic version at term. Eligibility and trial quality were assessed by the reviewer. Six trials were included. Routine tocolysis was associated with fewer failures of external cephalic version (relative risk 0.77, 95% confidence interval 0.64 to 0.92). There were no significant differences between non-cephalic presentations and caesarean sections. Fetal acoustic stimulation in midline fetal spine positions was associated with fewer failures of external cephalic version at term (relative risk 0.17, 95% confidence interval 0.05 to 0.60). No randomised trials of epidural analgesia or transabdominal amnioinfusion for external cephalic version at term were located. Routine tocolysis appears to reduce the failure rate of external cephalic version at term. Although promising, there is not enough evidence to evaluate the use of fetal acoustic stimulation in midline fetal spine positions. There is not enough evidence to evaluate the use of epidural analgesia or transabdominal amnioinfusion for external cephalic version at term.

Paternal Metabolic and Cardiovascular Risk Factors for Fetal Growth Restriction

PubMed Central

Hillman, Sara; Peebles, Donald M.; Williams, David J.

2013-01-01

OBJECTIVE Fathers of low–birth weight offspring are more likely to have type 2 diabetes and cardiovascular disease in later life. We investigated whether paternal insulin resistance and cardiovascular risk factors were evident at the time that fetal growth–restricted offspring were born. RESEARCH DESIGN AND METHODS We carried out a case-control study of men who fathered pregnancies affected by fetal growth restriction, in the absence of recognized fetal disease (n = 42), compared with men who fathered normal–birth weight offspring (n = 77). All mothers were healthy, nonsmoking, and similar in age, BMI, ethnicity, and parity. Within 4 weeks of offspring birth, all fathers had measures of insulin resistance (HOMA index), blood pressure, waist circumference, endothelial function (flow-mediated dilatation), lipid profile, weight, and smoking habit. Comparison was made using multivariable logistical regression analysis. RESULTS Fathers of fetal growth–restricted offspring [mean (SD) 1.8th (2.2) customized birth centile] were more likely to have insulin resistance, hypertension, central adiposity, and endothelial dysfunction and to smoke cigarettes compared with fathers of normal grown offspring. After multivariable analysis, paternal insulin resistance and smoking remained different between the groups. Compared with fathers of normal grown offspring, men who fathered pregnancies affected by fetal growth restriction had an OR 7.68 (95% CI 2.63–22.40; P < 0.0001) of having a 1-unit higher log HOMA-IR value and 3.39 (1.26–9.16; P = 0.016) of being a smoker. CONCLUSIONS Men who recently fathered growth-restricted offspring have preclinical evidence of the insulin resistance syndrome and are more likely to smoke than fathers of normal grown offspring. Paternal lifestyle may influence heritable factors important for fetal growth. PMID:23315598

Fetal growth and risk of childhood asthma and allergic disease

PubMed Central

Tedner, S G; Örtqvist, A K; Almqvist, C

2012-01-01

Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep

PubMed Central

Cowie, R. V.; Stone, P. R.; Barrett, R.; Naylor, A. S.; Blood, A. B.; Gunn, A. J.

2010-01-01

Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 ± 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide. PMID:20484698

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep.

PubMed

Bennet, L; Cowie, R V; Stone, P R; Barrett, R; Naylor, A S; Blood, A B; Gunn, A J

2010-08-01

Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 +/- 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide.

Diet quality in early pregnancy and its effects on fetal growth outcomes: the Infancia y Medio Ambiente (Childhood and Environment) Mother and Child Cohort Study in Spain.

PubMed

Rodríguez-Bernal, Clara L; Rebagliato, Marisa; Iñiguez, Carmen; Vioque, Jesús; Navarrete-Muñoz, Eva M; Murcia, Mario; Bolumar, Francisco; Marco, Alfredo; Ballester, Ferran

2010-06-01

Maternal diet has been associated with fetal growth outcomes; however, evidence is scarce on the role of dietary quality. The objective was to assess the effect of diet quality during the first trimester of pregnancy, as measured by the Alternate Healthy Eating Index (AHEI) adapted for pregnancy, on fetal growth. We studied 787 women and their newborns from a Spanish cohort study. Diet quality was assessed by using a modification of the AHEI. Adjusted birth weight, birth length, and head circumference were used as continuous outcomes. We used a customized model to define fetal growth restriction in weight, length, and head circumference. After adjustment of multivariate models, a positive association was observed between diet quality and adjusted birth weight and adjusted birth length. The greatest differences were found between the fourth and first quintiles of the AHEI. Newborns of women in the fourth quintile were on average 126.3 g (95% CI: 38.5, 213.9 g) heavier and 0.47 cm (95% CI: 0.08, 0.86 cm) longer than those in the lowest quintile (P for trend = 0.009 and 0.013, respectively). Women with the highest AHEI scores had a significantly lower risk of delivering a fetal growth-restricted infant for weight (odds ratio: 0.24; 95% CI: 0.10, 0.55; P for trend = 0.001) than did women in the lowest quintile, but this was not the case for fetal growth restriction in length (P for trend = 0.538) or head circumference (P for trend = 0.070). A high-quality diet in the first trimester of pregnancy is associated with birth size and the risk of fetal growth restriction.

Effects of prenatal maternal stress on serotonin and fetal development.

PubMed

St-Pierre, Joey; Laurent, Laetitia; King, Suzanne; Vaillancourt, Cathy

2016-12-01

Fetuses are exposed to many environmental perturbations that can influence their development. These factors can be easily identifiable such as drugs, chronic diseases or prenatal maternal stress. Recently, it has been demonstrated that the serotonin synthetized by the placenta was crucial for fetal brain development. Moreover, many studies show the involvement of serotonin system alteration in psychiatric disease during childhood and adulthood. This review summarizes existing studies showing that prenatal maternal stress, which induces alteration of serotonin systems (placenta and fetal brain) during a critical window of early development, could lead to alteration of fetal development and increase risks of psychiatric diseases later in life. This phenomenon, termed fetal programming, could be moderated by the sex of the fetus. This review highlights the need to better understand the modification of the maternal, placental and fetal serotonin systems induced by prenatal maternal stress in order to find early biomarkers of psychiatric disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low-complexity R-peak detection for ambulatory fetal monitoring.

PubMed

Rooijakkers, Michael J; Rabotti, Chiara; Oei, S Guid; Mischi, Massimo

2012-07-01

Non-invasive fetal health monitoring during pregnancy is becoming increasingly important because of the increasing number of high-risk pregnancies. Despite recent advances in signal-processing technology, which have enabled fetal monitoring during pregnancy using abdominal electrocardiogram (ECG) recordings, ubiquitous fetal health monitoring is still unfeasible due to the computational complexity of noise-robust solutions. In this paper, an ECG R-peak detection algorithm for ambulatory R-peak detection is proposed, as part of a fetal ECG detection algorithm. The proposed algorithm is optimized to reduce computational complexity, without reducing the R-peak detection performance compared to the existing R-peak detection schemes. Validation of the algorithm is performed on three manually annotated datasets. With a detection error rate of 0.23%, 1.32% and 9.42% on the MIT/BIH Arrhythmia and in-house maternal and fetal databases, respectively, the detection rate of the proposed algorithm is comparable to the best state-of-the-art algorithms, at a reduced computational complexity.

PP096. The effect of preterm placental calcification on uteroplacental blood flow, fetal growth and perinatal outcome in hypertension complicating pregnancy.

PubMed

Chen, K-H; Chen, L-R

2012-07-01

Placental calcification is often found in pregnancy at term and regarded as a physiological aging process. However, its earlier presence, before 36weeks' gestation (preterm placental calcification) may have an unusual pathological implication [1-3]. This prospective cohort study aims to examine the effect of preterm placental calcification on uteroplacental blood flow, fetal growth and perinatal death (including intrauterine fetal death and neonatal death) in hypertension complicating pregnancy. Monthly ultrasound was performed starting at 28weeks' gestation to establish the diagnosis of Grade III placental calcification, with measurement of fetal growth and uteroplacental blood flow by Doppler velocimetry on the umbilical vessels at 34weeks' gestation. Participants (n=105) were classified into Group A (n=44), a hypertensive study group with notable preterm placental calcification at 28-36weeks' gestation, and Group B (n=61), a hypertensive control group without notable preterm placental calcification prior to 36weeks' gestation. Women who smoked or drank alcohol during their pregnancies, had multifetal gestations, or major fetal congenital anomalies were all excluded. In addition to the measurement of S/D ratio, poor uteroplacental blood flow was confirmed by absent or reversed end-diastolic velocity (AREDV). Logistic regression analysis was used to estimate the risks of AREDV, poor fetal growth (IUGR) and perinatal death by calculating odds ratios (OR) and 95% confidence intervals (CI), adjusted by maternal age, body mass index, economic status, co-morbidities (e.g. diabetes, marked anemia and placenta previa), type of delivery, and parity. In Group A, there is significant higher mean S/D ratio (3.80 Vs 3.28), as well as higher incidences of AREDV (28.2% Vs 10.5%), IUGR (45.5% Vs 26.2%), and perinatal deaths (20.5% Vs 6.6%) than those in Group B (p<0.05). The risks of AREDV (OR 3.28; 95%CI 1.04-10.37), IUGR (OR 3.24; 95%CI 1.26-8.29), and perinatal death (OR 4.78; 95%CI 1.23-18.67) were greater in Group A than those in Group B (the control group). In hypertension complicating pregnancy, the presence of preterm placental calcification is associated with a higher incidence of poor uteroplacental blood flow, fetal growth and perinatal death. Being an ominous sign, it may precede poor uteroplacental blood flow, fetal growth and adverse fetal outcome and can serve as a predictor of such findings when noted on ultrasonography. The affected baby is at greater risk, thus requiring closer antepartum surveillance for fetal well-being. Copyright © 2012. Published by Elsevier B.V.

Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats

EPA Science Inventory

Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the curren...

Identifying Risk and Promoting Resilience in Infants and Toddlers with Fetal Alcohol Spectrum Disorders

ERIC Educational Resources Information Center

Shah, Prachi; Milgrom, Tedi; Munzer, Tiffany; Hoyme, H. Eugene

2015-01-01

Fetal alcohol spectrum disorders (FASDs) is an umbrella term that describes a variety of conditions characterized by a pattern of atypical facial features, growth restriction, structural physical abnormalities, and brain dysfunction resulting from prenatal alcohol exposure. Studies suggest that the prevalence of FASDs ranges between 2-5% (of the…

Is There Evidence To Show That Fetal Alcohol Syndrome Can Be Prevented?

ERIC Educational Resources Information Center

Murphy-Brennan, Majella G.; Oei, Tian P. S.

1999-01-01

Reviews the effectiveness of prevention programs in reducing Fetal Alcohol Syndrome (FAS). Results reveal that prevention programs, to date, have been successful in raising awareness of FAS; however this awareness has not been translated into behavioral changes in high-risk drinkers as consumption levels in this group have increased. (Author/MKA)

Dose additive effects of simvastatin and dipentyl phthalate on testosterone production in the fetal testis: A cummulative risk perspective

EPA Science Inventory

Sex differentiation of the mammalian reproductive tract is a highly regulated process that is driven, in part, by fetal testosterone (T) production. In utero exposure to phthalate esters (PE) during sex differentiation can cause reproductive tract malformations in rats. PE alter ...

[Evaluation of neonatal prognosis using Doppler velocimeter in cases of a high risk fetus].

PubMed

Ferchiou-Cherif, M; Zhioua, F; Hafsia, S; Hamdoun, L; Jedoui, A; Slim, R; Meriah, S

1993-01-01

The authors describe the main characteristics of the Doppler method in the early diagnosis of chronic fetal distress, and report their personal results in the study of 51 high risk pregnancies. In their study the fetal doppler ultrasound findings were correlated with birth weight related to gestational age, and neonatal morbidity. The parameters established from the doppler ultrasound assessment were the placenta resistance (calculated from the formula of Pourcelot: R = S-D/S applied to the umbilical artery) and the cerebro-placental index, Rp/Rc, Rc being the index of cerebral arterial resistance. The diagnosis performance of the method appeared very good: the Rp index was found to be highly specific for hypotrophy (85,7%) and for neonatal morbidity (90%), the RCP index adding its own good sensitivity (85% for hypotrophy and 83,3% for neonatal morbidity). The authors conclude upon the interest to study simultaneously the fetal umbilical and cerebral arterial circulations. The pathological significance of the two indexes appears different so that they are to be complementary in the evaluation of fetal distress.

Check the Head: Emergency Ultrasound Diagnosis of Fetal Anencephaly

PubMed Central

Hall, John W.; Denne, Nicolas; Minardi, Joseph J.; Williams, Debra; Balcik, BJ

2016-01-01

Background Early pregnancy complaints in emergency medicine are common. Emergency physicians (EP) increasingly employ ultrasound (US) in the evaluation of these complaints. As a result, it is likely that rare and important diagnoses will be encountered. We report a case of fetal anencephaly diagnosed by bedside emergency US in a patient presenting with first-trimester vaginal bleeding. Case Report A 33-year-old patient at 10 weeks gestation presented with vaginal bleeding. After initial history and physical examination, a bedside US was performed. The EP noted the abnormal appearance of the fetal cranium and anencephaly was suspected. This finding was confirmed by a consultative high-resolution fetal US. Making the diagnosis at the point of care allowed earlier detection and more comprehensive maternal counseling about pregnancy options. This particular patient underwent elective abortion which was able to be performed at an earlier gestation, thus decreasing maternal risk. If this diagnosis would not have been recognized by the EP at the point of care, it may not have been diagnosed until the second trimester, and lower-risk maternal options would not have been available. PMID:27429697

Cell-free fetal nucleic acid testing: a review of the technology and its applications.

PubMed

Sayres, Lauren C; Cho, Mildred K

2011-07-01

Cell-free fetal nucleic acids circulating in the blood of pregnant women afford the opportunity for early, noninvasive prenatal genetic testing. The predominance of admixed maternal genetic material in circulation demands innovative means for identification and analysis of cell-free fetal DNA and RNA. Techniques using polymerase chain reaction, mass spectrometry, and sequencing have been developed for the purposes of detecting fetal-specific sequences, such as paternally inherited or de novo mutations, or determining allelic balance or chromosome dosage. Clinical applications of these methods include fetal sex determination and blood group typing, which are currently available commercially although not offered routinely in the United States. Other uses of cell-free fetal DNA and RNA being explored are the detection of single-gene disorders, chromosomal abnormalities, and inheritance of parental polymorphisms across the whole fetal genome. The concentration of cell-free fetal DNA may also provide predictive capabilities for pregnancy-associated complications. The roles that cell-free fetal nucleic acid testing assume in the existing framework of prenatal screening and invasive diagnostic testing will depend on factors such as costs, clinical validity and utility, and perceived benefit-risk ratios for different applications. As cell-free fetal DNA and RNA testing continues to be developed and translated, significant ethical, legal, and social questions will arise that will need to be addressed by those with a stake in the use of this technology. Obstetricians & Gynecologists and Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to evaluate techniques and tools for analyzing cell-free fetal nucleic acids, assess clinical applications of prenatal testing, using cell-free fetal nucleic acids and barriers to implementation, and distinguish between relevant clinical features of cell-free fetal nucleic acid testing and existing prenatal genetic screening and diagnostic procedures.

The association between angiogenic markers and fetal sex: Implications for preeclampsia research.

PubMed

Andersen, L B; Jørgensen, J S; Herse, F; Andersen, M S; Christesen, H T; Dechend, R

2016-09-01

Current research suggests sexual dimorphism between the male and female fetoplacental units, but with unknown relevance for preeclampsia. We investigated the association between fetal sex and concentrations of the angiogenic markers soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in first and second-third trimester in women with/without preeclampsia, and the impact of fetal sex on the prognostic value of angiogenic markers for preeclampsia. Observational study in a prospective, population-based cohort of 2110 singleton pregnancies with 150 preeclampsia cases. Higher sFlt-1 concentrations were observed for women carrying female fetuses in first trimester (all, 1107.65 vs. 992.27pg/ml; preeclampsia cases, 1118.79 vs. 934.49pg/ml, p<0.05) and in second-third trimester (all, 1130.03 vs. 1043.15pg/ml; preeclampsia, 1480.30 vs. 1152.86pg/ml, p<0.05), with similar findings for the sFlt-1/PlGF ratio concentrations in first (29.67 vs. 27.39 p<0.05) and second-third trimester (3.56 vs. 3.22, p<0.05). In first trimester, log transformed concentrations of PlGF, sFlt-1 and sFlt-1/PlGF (all participants) and sFlt-1 (preeclampsia cases) associated with fetal sex in adjusted analyses (p<0.05). In second-third trimester, only log(sFlt-1) associated with fetal sex (all, p=0.028; preeclampsia, p=0.067) In receiver operating curve analysis, prediction of early-onset preeclampsia by sFlt-1/PlGF tended to be superior in pregnancies with female vs. male fetuses (p=0.06). Sexual dimorphism was observed for concentrations of angiogenic markers. Female fetal sex was associated to higher sFlt-1 and sFlt-1/PlGF ratio concentrations in both healthy pregnancies and women developing preeclampsia. Fetal sex should be considered in research and clinical use of angiogenic markers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prenatal Exposure to Traffic Pollution: Associations with Reduced Fetal Growth and Rapid Infant Weight Gain

PubMed Central

Fleisch, Abby F.; Rifas-Shiman, Sheryl L.; Koutrakis, Petros; Schwartz, Joel D.; Kloog, Itai; Melly, Steven; Coull, Brent A.; Zanobetti, Antonella; Gillman, Matthew W.; Gold, Diane R.; Oken, Emily

2014-01-01

Background Prenatal air pollution exposure inhibits fetal growth, but implications for postnatal growth are unknown. Methods We assessed weights and lengths of US infants in the Project Viva cohort at birth and 6 months. We estimated third-trimester residential air pollution exposures using spatiotemporal models. We estimated neighborhood traffic density and roadway proximity at birth address using geographic information systems. We performed linear and logistic regression adjusted for sociodemographic variables, fetal growth, and gestational age at birth. Results Mean birth weight-for-gestational age z-score (fetal growth) was 0.17 (SD = 0.97; n=2,114), 0-6 month weight-for-length gain was 0.23 z-units (SD = 1.11; n=689), and 17% had weight-for-length ≥95th percentile at 6 months of age. Infants exposed to the highest (vs. lowest) quartile of neighborhood traffic density had lower fetal growth (−0.13 units [95% confidence interval (CI) = −0.25 to −0.01]), more rapid 0-6 month weight-for-length gain (0.25 units [95% CI = 0.01 to 0.49]), and higher odds of weight-for-length ≥95th percentile at 6 months (1.84 [95% CI = 1.11 to 3.05]). Neighborhood traffic density was additionally associated with an infant being in both the lowest quartile of fetal growth and highest quartile of 0-6 month weight-for-length gain (Q4 vs. Q1, OR = 3.01 [95% CI = 1.08 to 8.44]). Roadway proximity and third-trimester black carbon exposure were similarly associated with growth outcomes. For third-trimester PM2.5, effect estimates were in the same direction, but smaller and imprecise. Conclusions Infants exposed to higher traffic-related pollution in early life may exhibit more rapid postnatal weight gain in addition to reduced fetal growth. PMID:25437317

Prenatal exposure to traffic pollution: associations with reduced fetal growth and rapid infant weight gain.

PubMed

Fleisch, Abby F; Rifas-Shiman, Sheryl L; Koutrakis, Petros; Schwartz, Joel D; Kloog, Itai; Melly, Steven; Coull, Brent A; Zanobetti, Antonella; Gillman, Matthew W; Gold, Diane R; Oken, Emily

2015-01-01

Prenatal air pollution exposure inhibits fetal growth, but implications for postnatal growth are unknown. We assessed weights and lengths of US infants in the Project Viva cohort at birth and 6 months. We estimated 3rd-trimester residential air pollution exposures using spatiotemporal models. We estimated neighborhood traffic density and roadway proximity at birth address using geographic information systems. We performed linear and logistic regression adjusted for sociodemographic variables, fetal growth, and gestational age at birth. Mean birth weight-for-gestational age z-score (fetal growth) was 0.17 (standard deviation [SD] = 0.97; n = 2,114), 0- to 6-month weight-for-length gain was 0.23 z-units (SD = 1.11; n = 689), and 17% had weight-for-length ≥95th percentile at 6 months of age. Infants exposed to the highest (vs. lowest) quartile of neighborhood traffic density had lower fetal growth (-0.13 units [95% confidence interval (CI) = -0.25 to -0.01]), more rapid 0- to 6-month weight-for-length gain (0.25 units [95% CI = 0.01 to 0.49]), and higher odds of weight-for-length ≥95th percentile at 6 months (1.84 [95% CI = 1.11 to 3.05]). Neighborhood traffic density was additionally associated with an infant being in both the lowest quartile of fetal growth and the highest quartile of 0- to 6-month weight-for-length gain (Q4 vs. Q1, odds ratio = 3.01 [95% CI = 1.08 to 8.44]). Roadway proximity and 3rd-trimester black carbon exposure were similarly associated with growth outcomes. For 3rd-trimester particulate matter (PM2.5), effect estimates were in the same direction, but smaller and imprecise. Infants exposed to higher traffic-related pollution in early life may exhibit more rapid postnatal weight gain in addition to reduced fetal growth.

Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes.

PubMed

Prieto-Sánchez, María T; Ruiz-Palacios, María; Blanco-Carnero, José E; Pagan, Ana; Hellmuth, Christian; Uhl, Olaf; Peissner, Wolfgang; Ruiz-Alcaraz, Antonio J; Parrilla, Juan J; Koletzko, Berthold; Larqué, Elvira

2017-04-01

Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers. Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers. Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P = 0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P = 0.029) and lyso-PL (P = 0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r = 0.388, P = 0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference. In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Does maternal race influence the short-term variation of the fetal heart rate? An historical cohort study.

PubMed

Marie, Cécile; Sinoquet, Céline; Barasinski, Chloé; Lémery, Didier; Vendittelli, Françoise

2015-10-01

The main aim of this article was to analyze short-term variation (STV) of the fetal heart rate according to maternal race. The secondary aim was to study the baseline fetal heart rate according to this factor. This single-center historical cohort study covered the period from November 2008 through December 2011 (n=182). The inclusion criteria were: black women from sub-Saharan Africa or white European women, with a singleton pregnancy ≥34 weeks and fetal heart rate recorded by computerized analysis (Oxford Sonicaid System 8002) at a prenatal visit. The exclusion criteria were: medication likely to modify fetal heart rate, abnormal fetal heart rate tracing, and being in labor. A multiple linear regression analysis was used to study the association between maternal race and STV. STV was lower by 2.6ms in fetuses of black women (n=55) compared to those of white women (n=127) (8.9±2.1ms vs. 11.4±3.4ms) (p<0.001). The basal fetal heart rate was higher (p=0.001), and the recording criteria were met less often for the black women (p=0.04). After adjustment for maternal age, body mass index at the beginning of pregnancy, maternal cigarette smoking, parity, gestational diabetes, gestational age at the time of the fetal heart rate recording, and the time between the last meal and the recording, mean STV was lower by 3.1±0.6ms in fetuses of black compared with white women (p<0.001). STV is lower in fetuses of black women compared to those of white women in a low-risk population. A study of black and white women with high-risk pregnancies is necessary to assess the impact of medical practices on perinatal outcome after STV analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The role of steroids in the development of post-partum mental disorders.

PubMed

Paskova, Andrea; Jirak, Roman; Mikesova, Michaela; Adamcova, Karolina; Fartakova, Zdenka; Horakova, Vladimira; Koucky, Michal; Hill, Martin; Hruskovicova, Hana; Starka, Luboslav; Duskova, Michaela; Parizek, Antonin

2014-09-01

Unfavorable post-partum changes to mental well-being affect more than half of all women, and are a risk to the health of both mother and baby. Their effects place strains on health and social systems. Currently, no generally accepted theory exists of the causes and mechanisms of post-partum mental disorders. Literature search up to 2012, using PubMed and search words: neuroactive steroids, post-partum mental disorders, depression, corticotropin-releasing hormone and estrogens. There are several theories for post-partum depression. One is that autoimmune diseases are involved. Others revolve around genes responsible or that lead to increased disposition to the disorder. It is likely however that the process is associated with the separation of the placenta and the fetal zone of fetal adrenal gland, the main sources of corticotropin-releasing hormone and sexual and neuroactive steroids during pregnancy, and the ability of the receptor system to adapt to these changes. The central nervous system is able to produce neurosteroids, but the drop in levels of peripheral steroids likely leads to a sudden deficit in neuroinhibitory steroids modulating ionotropic receptors in the brain. Post-partum depression is a multifactorial disease with unknown etiology. It is probably associated with sudden changes in the production of hormones influencing the nervous system, and on the other hand the ability of the receptor system to adapt to these changes. When the relative changes in concentrations of hormones, rather than their absolute levels, is likely more important.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

PubMed

Murphy, Kellie E; Willan, Andrew R; Hannah, Mary E; Ohlsson, Arne; Kelly, Edmond N; Matthews, Stephen G; Saigal, Saroj; Asztalos, Elizabeth; Ross, Susan; Delisle, Marie-France; Amankwah, Kofi; Guselle, Patricia; Gafni, Amiram; Lee, Shoo K; Armson, B Anthony

2012-05-01

To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. II.

Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

PubMed

Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

2015-09-01

Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. Copyright © 2015. Published by Elsevier Inc.

Perinatal Bisphenol A Exposure and Adult Glucose Homeostasis: Identifying Critical Windows of Exposure

PubMed Central

Liu, Jingli; Yu, Pan; Qian, Wenyi; Li, Yan; Zhao, Jingjing; Huan, Fei; Wang, Jun; Xiao, Hang

2013-01-01

Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day) at different time of perinatal stage: 1) on days 1–6 of pregnancy (P1–P6, preimplantation exposure); 2) from day 6 of pregnancy until postnatal day (PND) 0 (P6–PND0, fetal exposure); 3) from lactation until weaning (PND0–PND21, neonatal exposure); and 4) from day 6 of gestation until weaning (P6–PND21, fetal and neonatal exposure). At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure. PMID:23675523

Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth.

PubMed

Hinkle, Stefanie N; Johns, Alicia M; Albert, Paul S; Kim, Sungduk; Grantz, Katherine L

2015-07-01

Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at 17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed models. Second, the association between maternal weight changes (per 5 kg) and corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. From 0 to 17 weeks, changes in maternal weight were most strongly associated with changes in BPD [β=0.51 per 5 kg (95%CI 0.26, 0.76)] and FL [β=0.46 per 5 kg (95%CI 0.26, 0.65)]. From 17 to 28 weeks, AC [β=2.92 per 5 kg (95%CI 1.62, 4.22)] and EFW [β=58.7 per 5 kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29 kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67 kg/w (90th percentile). Among women at high-risk for SGA, maternal weight gain was associated with fetal growth throughout pregnancy, but had a differential relationship with specific biometrics across gestation. For women with fetal SGA identified mid-pregnancy, increased antenatal weight gain was associated with a decreased probability of fetal SGA approximately 7 weeks later. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fetal response to maternal hunger and satiation - novel finding from a qualitative descriptive study of maternal perception of fetal movements.

PubMed

Bradford, Billie; Maude, Robyn

2014-08-26

Maternal perception of decreased fetal movements is a specific indicator of fetal compromise, notably in the context of poor fetal growth. There is currently no agreed numerical definition of decreased fetal movements, with the subjective perception of a decrease on the part of the mother being the most significant definition clinically. Both qualitative and quantitative aspects of fetal activity may be important in identifying the compromised fetus.Yet, how pregnant women perceive and describe fetal activity is under-investigated by qualitative means. The aim of this study was to explore normal fetal activity, through first-hand descriptive accounts by pregnant women. Using qualitative descriptive methodology, interviews were conducted with 19 low-risk women experiencing their first pregnancy, at two timepoints in their third trimester. Interview transcripts were later analysed using qualitative content analysis and patterns of fetal activity identified were then considered along-side the characteristics of the women and their birth outcomes. This paper focuses on a novel finding; the description by pregnant women of fetal behaviour indicative of hunger and satiation. Full findings will be presented in later papers. Most participants (74% 14 of 19) indicated mealtimes were a time of increased fetal activity. Eight participants provided detailed descriptions of increased activity around meals, with seven (37% 7 of 19) of these specifying increased fetal activity prior to meals or in the context of their own hunger. These movements were interpreted as a fetal demand for food often prompting the mother to eat. Interestingly, the women who described increased fetal activity in the context of hunger subsequently gave birth to smaller infants (mean difference 364 gm) than those who did not describe a fetal response to hunger. Food seeking behaviour may have a pre-birth origin. Maternal-fetal interaction around mealtimes could constitute an endocrine mediated communication, in the interests of maintaining optimal intrauterine conditions. Further research is warranted to explore this phenomenon and the potential influence of feeding on the temporal organisation of fetal activity in relation to growth.

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

Polynomial Chaos decomposition applied to stochastic dosimetry: study of the influence of the magnetic field orientation on the pregnant woman exposure at 50 Hz.

PubMed

Liorni, I; Parazzini, M; Fiocchi, S; Guadagnin, V; Ravazzani, P

2014-01-01

Polynomial Chaos (PC) is a decomposition method used to build a meta-model, which approximates the unknown response of a model. In this paper the PC method is applied to the stochastic dosimetry to assess the variability of human exposure due to the change of the orientation of the B-field vector respect to the human body. In detail, the analysis of the pregnant woman exposure at 7 months of gestational age is carried out, to build-up a statistical meta-model of the induced electric field for each fetal tissue and in the fetal whole-body by means of the PC expansion as a function of the B-field orientation, considering a uniform exposure at 50 Hz.

Cost Analysis of Following Up Incomplete Low-Risk Fetal Anatomy Ultrasounds.

PubMed

O'Brien, Karen; Shainker, Scott A; Modest, Anna M; Spiel, Melissa H; Resetkova, Nina; Shah, Neel; Hacker, Michele R

2017-03-01

To examine the clinical utility and cost of follow-up ultrasounds performed as a result of suboptimal views at the time of initial second-trimester ultrasound in a cohort of low-risk pregnant women. We conducted a retrospective cohort study of women at low risk for fetal structural anomalies who had second-trimester ultrasounds at 16 to less than 24 weeks of gestation from 2011 to 2013. We determined the probability of women having follow-up ultrasounds as a result of suboptimal views at the time of the initial second-trimester ultrasound, and calculated the probability of detecting an anomaly on follow-up ultrasound. These probabilities were used to estimate the national cost of our current ultrasound practice, and the cost to identify one fetal anomaly on follow-up ultrasound. During the study period, 1,752 women met inclusion criteria. Four fetuses (0.23% [95% CI 0.06-0.58]) were found to have anomalies at the initial ultrasound. Because of suboptimal views, 205 women (11.7%) returned for a follow-up ultrasound, and one (0.49% [95% CI 0.01-2.7]) anomaly was detected. Two women (0.11%) still had suboptimal views and returned for an additional follow-up ultrasound, with no anomalies detected. When the incidence of incomplete ultrasounds was applied to a similar low-risk national cohort, the annual cost of these follow-up scans was estimated at $85,457,160. In our cohort, the cost to detect an anomaly on follow-up ultrasound was approximately $55,000. The clinical yield of performing follow-up ultrasounds because of suboptimal views on low-risk second-trimester ultrasounds is low. Since so few fetal abnormalities were identified on follow-up scans, this added cost and patient burden may not be warranted. © 2016 Wiley Periodicals, Inc.

The lived experience of pregnancy complications in single older women.

PubMed

Mandel, Deborah

2010-01-01

To explore the lived experience of single older women (35 years or older at time of birth) who experienced complications in their planned pregnancy. Phenomenology, using semistructured interviews with 11 women between the ages of 35 to 48 years. Six themes emerged: (a) motherhood now or never, (b) the known and unknown, (c) importance of support, (d) the stigma of single motherhood, (e) changing priorities, and (f) long-term concerns for themselves and child/children. Nurses who work with pregnant women should understand as much as possible about the issues affecting older single women who choose pregnancy; this offers the best opportunity to provide comprehensive care. These women can be at increased risk for many pregnancy complications, and should receive counseling about their risks for both fetal and maternal complications. Nurses should also conduct a thorough psychosocial assessment to determine what support systems are in place and what resources are available if complications arise. In the intrapartum and postpartum settings, nurses can offer not only appropriate physical caregiving but also a supportive and caring attitude with women in this circumstance. Helping women maintain a sense of control by helping them to participate in their care planning is essential.

Complications of shoulder dystocia.

PubMed

Dajani, Nafisa K; Magann, Everett F

2014-06-01

Complications of shoulder dystocia are divided into fetal and maternal. Fetal brachial plexus injury (BPI) is the most common fetal complication occurring in 4-40% of cases. BPI has also been reported in abdominal deliveries and in deliveries not complicated by shoulder dystocia. Fractures of the fetal humerus and clavicle occur in about 10.6% of cases of shoulder dystocia and usually heal with no sequel. Hypoxic ischemic brain injury is reported in 0.5-23% of cases of shoulder dystocia. The risk correlates with the duration of head-to-body delivery and is especially increased when the duration is >5 min. Fetal death is rare and is reported in 0.4% of cases. Maternal complications of shoulder dystocia include post-partum hemorrhage, vaginal lacerations, anal tears, and uterine rupture. The psychological stress impact of shoulder dystocia is under-recognized and deserves counseling prior to home discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

Simultaneous use of intrapartum fetal pulse oximetry and amnioinfusion in meconium stained amniotic fluid.

PubMed

Halvax, László; Szabó, István; Vizer, Miklós; Csermely, Tamás; Ertl, Tibor

2002-09-10

Fetal pulse oximetry is a minimally invasive, simple technique which continuously helps to reflect in utero well-being. The presence of meconium in the amniotic fluid may be a clinical sign of fetal hypoxaemia. Amnioinfusion has a beneficial effect on the incidence of meconium aspiration syndrome (MAS), and the presence of meconium below the level of the vocal cords. We studied the impact of amnioinfusion combined with fetal pulse oximetry on the incidence of meconium aspiration syndrome and operative delivery. The retrospective analysis revealed that the presence of meconium below the level of vocal cords was significantly reduced. The frequency of cesarean section is decreased, however, it did not reach statistical significance. Fetal pulse oximetry may be used in combination with amnioinfusion and cardiotocography (CTG) to reduce the risk of meconium aspiration syndrome and the number of instrumental deliveries and improve perinatal outcome. Copyright 2002 Elsevier Science Ireland Ltd.

Piracetam for fetal distress in labour.

PubMed

Hofmeyr, G Justus; Kulier, Regina

2012-06-13

Piracetam is thought to promote the metabolism of brain cells when they are hypoxic. It has been used to prevent adverse effects of fetal distress. The objective of this review was to assess the effects of piracetam for suspected fetal distress in labour on method of delivery and perinatal morbidity. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 February 2012). Randomised trials of piracetam compared with placebo or no treatment for suspected fetal distress in labour. Both review authors assessed eligibility and trial quality. One study of 96 women was included. Piracetam compared with placebo was associated with a trend to reduced need for caesarean section (risk ratio 0.57, 95% confidence interval 0.32 to 1.03). There were no statistically significant differences between the piracetam and placebo group for neonatal morbidity (measured by neonatal respiratory distress) or Apgar score. There is not enough evidence to evaluate the use of piracetam for fetal distress in labour.

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

PubMed

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

2017-10-01

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

Health effects of prenatal radiation exposure.

PubMed

Williams, Pamela M; Fletcher, Stacy

2010-09-01

Pregnant women are at risk of exposure to nonionizing and ionizing radiation resulting from necessary medical procedures, workplace exposure, and diagnostic or therapeutic interventions before the pregnancy is known. Nonionizing radiation includes microwave, ultrasound, radio frequency, and electromagnetic waves. In utero exposure to nonionizing radiation is not associated with significant risks; therefore, ultrasonography is safe to perform during pregnancy. Ionizing radiation includes particles and electromagnetic radiation (e.g., gamma rays, x-rays). In utero exposure to ionizing radiation can be teratogenic, carcinogenic, or mutagenic. The effects are directly related to the level of exposure and stage of fetal development. The fetus is most susceptible to radiation during organogenesis (two to seven weeks after conception) and in the early fetal period (eight to 15 weeks after conception). Noncancer health effects have not been detected at any stage of gestation after exposure to ionizing radiation of less than 0.05 Gy (5 rad). Spontaneous abortion, growth restriction, and mental retardation may occur at higher exposure levels. The risk of cancer is increased regardless of the dose. When an exposure to ionizing radiation occurs, the total fetal radiation dose should be estimated and the mother counseled about the potential risks so that she can make informed decisions about her pregnancy management.

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.

Functional adaptations of the coronary microcirculation to anaemia in fetal sheep.

PubMed

Jonker, Sonnet S; Davis, Lowell; Soman, Divya; Belcik, J Todd; Davidson, Brian P; Atkinson, Tamara M; Wilburn, Adrienne; Louey, Samantha; Giraud, George D; Lindner, Jonathan R

2016-11-01

In fetuses, chronic anaemia stimulates cardiac growth; simultaneously, blood flow to the heart muscle itself is increased, and reserve blood flow capacity of the coronary vascular bed is preserved. Here we examined functional adaptations of the capillaries and small blood vessels responsible for delivering oxygen to the anaemic fetal heart muscle using contrast-enhanced echocardiography. We demonstrate that coronary microvascular flux rate doubled in anaemic fetuses compared to control fetuses, both at rest and during maximal flow, suggesting reduced microvascular resistance consistent with capillary widening. Cardiac fractional microvascular blood volume was not greater in anaemic fetuses, suggesting that growth of new microvascular vessels does not contribute to the increased flow per volume of myocardium. These unusual changes in microvascular function during anaemia may indicate novel adaptive strategies in the fetal heart. Fetal anaemia causes cardiac adaptations that have immediate and life-long repercussions on heart function and health. It is known that resting and maximal coronary conductance both increase during chronic fetal anaemia, but the coronary microvascular changes responsible for the adaptive response are unknown. Until recently, technical limitations have prevented quantifying functional capillary-level adaptations in the in vivo fetal heart. Our objective was to characterise functional microvascular adaptations in chronically anaemic fetal sheep. Chronically instrumented fetuses were randomized to a control group (n = 11) or were made anaemic by isovolumetric haemorrhage (n = 12) for 1 week prior to myocardial contrast echocardiography at 85% of gestation. Anaemia augmented cardiac mass by 23% without changing body weight. In anaemic fetuses, microvascular blood flow per volume of myocardium was twice that of control fetuses at rest, during vasodilatory hyperaemia, and during hyperaemia plus increased aortic pressure. The elevated blood flow was attributable almost entirely to an increase in microvascular blood flux rate whereas microvascular blood volumes were not different between groups at baseline, during hyperaemia, or with hyperaemia plus increased aortic pressure. Increased coronary microvascular flux rate in response to chronic fetal anaemia is consistent with expected reductions in capillary resistance from capillary diameter widening detected in earlier histological studies. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.

PubMed

McMillen, I C; Muhlhausler, B S; Duffield, J A; Yuen, B S J

2004-08-01

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

Early fetal heart ultrasonography as additional indicator for chromosomopathies.

PubMed

Dmitrovic, A; Jeremic, K; Babic, U M; Perovic, M; Mihailovic, T; Opric, D; Zecevic, N; Gojnić-Dugalić, M

2016-01-01

First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still required.

Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

PubMed

Crew, Rachael C; Mark, Peter J; Clarke, Michael W; Waddell, Brendan J

2016-09-01

Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids. © 2016 by the Society for the Study of Reproduction, Inc.

Gestational and Fetal Outcomes in B19 Maternal Infection: a Problem of Diagnosis▿

PubMed Central

Bonvicini, Francesca; Puccetti, Chiara; Salfi, Nunzio C. M.; Guerra, Brunella; Gallinella, Giorgio; Rizzo, Nicola; Zerbini, Marialuisa

2011-01-01

Parvovirus B19 infection during pregnancy is a potential hazard to the fetus because of the virus' ability to infect fetal erythroid precursor cells and fetal tissues. Fetal complications range from transitory fetal anemia and nonimmune fetal hydrops to miscarriage and intrauterine fetal death. In the present study, 72 pregnancies complicated by parvovirus B19 infection were followed up: fetal and neonatal specimens were investigated by serological and/or virological assays to detect fetal/congenital infection, and fetuses and neonates were clinically evaluated to monitor pregnancy outcomes following maternal infection. Analysis of serological and virological maternal B19 markers of infection demonstrated that neither B19 IgM nor B19 DNA detected all maternal infections. IgM serology correctly diagnosed 94.1% of the B19 infections, while DNA testing correctly diagnosed 96.3%. The maximum sensitivity was achieved with the combined detection of both parameters. B19 vertical transmission was observed in 39% of the pregnancies, with an overall 10.2% rate of fetal deaths. The highest rates of congenital infections and B19-related fatal outcomes were observed when maternal infections occurred by the gestational week 20. B19 fetal hydrops occurred in 11.9% of the fetuses, and 28.6% resolved the hydrops with a normal neurodevelopment outcome at 1- to 5-year follow-up. In conclusion, maternal screening based on the concurrent analysis of B19 IgM and DNA should be encouraged to reliably diagnose maternal B19 infection and correctly manage pregnancies at risk. PMID:21849687

Quantification of fetal and total circulatory DNA in maternal plasma samples before and after size fractionation by agarose gel electrophoresis.

PubMed

Hromadnikova, I; Zejskova, L; Doucha, J; Codl, D

2006-11-01

Fetal extracellular DNA is mainly derived from apoptotic bodies of trophoblast. Recent studies have shown size differences between fetal and maternal extracellular DNA. We have examined the quantification of fetal (SRY gene) and total (GLO gene) extracellular DNA in maternal plasma in different fractions (100-300, 300-500, 500-700, 700-900, and >900 bp) after size fractionation by agarose gel electrophoresis. DNA was extracted from maternal plasma samples from 11 pregnant women carrying male foetuses at the 16th week of gestation. Fetal circulatory DNA was mainly detected in the 100-300 bp fraction with the median concentration being 14.4 GE/ml. A lower median amount of 4.9 GE/ml was also found in the 300-500 bp fraction. Circulatory DNA extracted from the 100-300 bp fraction contained 4.2 times enriched fetal DNA when compared with unseparated DNA sample. Fetal DNA within the 300-500 bp fraction was 2.5 times enriched. Circulatory fetal DNA is predominantly present in a fraction with molecular size <500 bp, which can be used for the detection of paternally inherited alleles. However, the usage of size-separated DNA is not suitable for routine clinical applications because of risk of contamination.

MYSTERIES OF THE HUMAN FETUS REVEALED.

PubMed

Sandman, Curt A

2015-09-01

The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al. open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Laceys, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk. © 2015 The Society for Research in Child Development, Inc.

Fetal alcohol-spectrum disorders: identifying at-risk mothers

PubMed Central

Montag, Annika C

2016-01-01

Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. PMID:27499649

Changes in Doppler blood flow velocity in middle cerebral artery in response to airborne sound in low- and high-risk human fetuses.

PubMed

Dobrijević, Lj J; Ljubić, Aleksandar; Sovilj, Mirjana; Ribarić-Jankes, Ksenija; Miković, Zeljko; Cerović, Nikola

2009-10-01

To examine fetal auditory perception in low- and high-risk pregnancies in period from 27 to 31 weeks gestational age with the aim to establish diagnostic parameters in prenatal detection of the degree of hearing development in a fetus. Method of prenatal hearing screening was applied on 80 women divided in two groups: Control group (C=22), consisted of pregnant women with low-risk pregnancies, and Experimental group (E=58), consisted of pregnant women with high-risk pregnancies (pregnancies with diagnosis of: preterm delivery, hypertension and/or intrauterine growth restriction (IUGR), diabetes). PHS was applied in period from 27 to 31 weeks gestational age. Brain circulation changes in fetal middle cerebral artery (MCA) caused by defined sound stimulus, as the indicator of fetal auditory reactions, were registered on Doppler ultrasound apparatus. After visualization of MCA, a sound stimulus was delivered. The stimulus consisted of one defined sound which is a digitally produced sound with the intensity of 90 dB, frequency range of 1500-4500 Hz, and duration of 0.2s (click) and it was presented only once. Measurements in observed artery were taken before (baseline) and after defined sound stimulation. Results showed that the absolute and relative difference in Pulsatility index (baseline and after sound stimulation) were greater for the high-risk group compared to the low-risk group (absolute difference: mean=0.36 vs mean=0.36) (relative difference: mean = ∼ 18% vs mean = ∼ 12%). When the low-risk group and the three high-risk group mean pairs were compared using multiple t-test, the diabetic group differed from the low-risk and two other high-risk groups; the low-risk and the two other high-risk groups did not differ from each other. Fetuses from pregnancies with diagnosis of diabetes demonstrated the most expressive reactibility and significantly higher absolute and relative changes of Pi values (absolute difference: mean=0.54, relative difference: mean=25.49%). The values of Pulsatility index (Pi) registered by PHS in low- and high-risk pregnancies may be used as differential and diagnostic parameters in fetal auditory perception examination. Fetuses from pregnancies with diagnosis of diabetes demonstrated significantly higher absolute and relative changes of Pi values compared to other groups of examined fetuses.

Maternal Obesity Accelerates Fetal Pancreatic Beta Cell but not Alpha Cell Development in the Sheep: Prenatal and Postnatal Consequences

USDA-ARS?s Scientific Manuscript database

Maternal obesity affects offspring weight, body composition and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high energy diet on fetal pancreatic development. Sixty days prior to breeding. ewes were assigned to control (C, 100% of N...

Maternal hemodynamics early in labor: a possible link with obstetric risk?

PubMed

Valensise, H; Tiralongo, G M; Pisani, I; Farsetti, D; Lo Presti, D; Gagliardi, G; Basile, M R; Novelli, G P; Vasapollo, B

2018-04-01

To determine if hemodynamic assessment in 'low-risk' pregnant women at term with an appropriate-for-gestational age (AGA) fetus can improve the identification of patients who will suffer maternal or fetal/neonatal complications during labor. This was a prospective observational study of 77 women with low-risk term pregnancy and AGA fetus, in the early stages of labor. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor (USCOM ® ) system. Patients were followed until the end of labor to identify fetal/neonatal and maternal outcomes, and those which developed complications of labor were compared with those delivering without complications. Eleven (14.3%) patients had a complication during labor: in seven there was fetal distress and in four there were maternal complications (postpartum hemorrhage and/or uterine atony). Patients who developed complications during labor had lower cardiac output (5.6 ± 1.0 vs 6.7 ± 1.3 L/min, P = 0.01) and cardiac index (3.1 ± 0.6 vs 3.5 ± 0.7 L/min/m 2 , P = 0.04), and higher total vascular resistance (1195.3 ± 205.3 vs 1017.8 ± 225.6 dynes × s/cm 5 , P = 0.017) early in labor, compared with those who did not develop complications. Receiver-operating characteristics curve analysis to determine cut-offs showed cardiac output ≤ 5.8 L/min (sensitivity, 81.8%; specificity, 69.7%), cardiac index ≤ 2.9 L/min/m 2 (sensitivity, 63.6%; specificity, 76.9%) and total vascular resistance > 1069 dynes × s/cm 5 (sensitivity, 81.8%; specificity, 63.6%) to best predict maternal or fetal/neonatal complications. The study of maternal cardiovascular adaptation at the end of pregnancy could help to identify low-risk patients who may develop complications during labor. In particular, low cardiac output and high total vascular resistance are apparently associated with higher risk of fetal distress or maternal complications. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Non-invasive prenatal diagnosis for fetal sex determination: benefits and disadvantages from the service users' perspective.

PubMed

Lewis, Celine; Hill, Melissa; Skirton, Heather; Chitty, Lyn S

2012-11-01

Prenatal fetal sex determination is clinically indicated for women who are at risk of having a child with a serious genetic disorder affecting a particular sex. Ultrasound has been the traditional method used, but early fetal sex determination using non-invasive prenatal diagnosis (NIPD) can now be performed using cell-free fetal DNA in maternal plasma. The study aim was to assess the views and experiences of service users who had used NIPD for fetal sex determination. In this paper, we report on the perceived benefits and disadvantages. A qualitative approach using semi-structured interviews was used. A total of 44 participants (38 women and 6 partners of participating women) were recruited. Participants' views and experiences of NIPD were overwhelmingly positive. Concerning benefits over traditional methods, three themes emerged: (1) technical aspects of technology; (2) timing; and (3) enhanced decision-making. Practical advantages of NIPD included avoiding miscarriage, and there were a number of psychological advantages associated with timing such as perceived control, early re-engagement, normalization of pregnancy and peace of mind. Participants also valued NIPD as it enabled a stepwise approach to decision-making. A number of disadvantages were discussed including concerns about social sexing and increased bonding at a time in pregnancy when miscarriage risk is high. However, participants felt these were fairly minor in comparison with the advantages of NIPD. Until definitive genetic diagnosis using NIPD is available, NIPD for fetal sex determination is perceived as a good interim measure with a number of notable advantages over traditional methods.

Maternal pelvic dimensions and neonatal size: Implications for growth plasticity in early life as adaptation.

PubMed

Wells, Jonathan C K; Figueiroa, José N; Alves, Joao G

2017-01-01

Patterns of fetal growth predict non-communicable disease risk in adult life, but fetal growth variability appears to have a relatively weak association with maternal nutritional dynamics during pregnancy. This challenges the interpretation of fetal growth variability as 'adaptation'. We hypothesized that associations of maternal size and nutritional status with neonatal size are mediated by the dimensions of the maternal pelvis. We analysed data on maternal height, body mass index (BMI) and pelvic dimensions (conjugate, inter-spinous and inter-cristal diameters) and neonatal gestational age, weight, length, thorax girth and head girth ( n = 224). Multiple regression analysis was used to identify independent maternal predictors of neonatal size, and the mediating role of neonatal head girth in these associations. Pelvic dimensions displaced maternal BMI as a predictor of birth weight, explaining 11.6% of the variance. Maternal conjugate and inter-spinous diameters predicted neonatal length, thorax girth and head girth, whereas inter-cristal diameter only predicted neonatal length. Associations of pelvic dimensions with birth length, but not birth weight, were mediated by neonatal head girth. Pelvic dimensions predicted neonatal size better than maternal BMI, and these associations were mostly independent of maternal height. Sensitivity of fetal growth to pelvic dimensions reduces the risk of cephalo-pelvic disproportion, potentially a strong selective pressure during secular trends in height. Selection on fetal adaptation to relatively inflexible components of maternal phenotype, rather than directly to external ecological conditions, may help explain high levels of growth plasticity during late fetal life and early infancy.

Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine.

PubMed

Gentile, Salvatore; Bellantuono, Cesario

2009-03-01

To analyze all studies reporting primary data on the rate of fetal malformations after early in utero exposure to paroxetine, investigated either specifically or jointly with other antidepressant medications. Medical literature was identified through searches of MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library (1980 through September 2008). Search terms were pregnancy, antidepressants, SSRIs, paroxetine, and fetal malformations. Additional studies were identified from the reference lists of published articles. Twenty-five articles reporting primary data on the rate of fetal structural malformations following exposure to paroxetine or selective serotonin reuptake inhibitors as a group during the first trimester of pregnancy were electronically or manually selected. Studies on the teratogenic risk of paroxetine show a high degree of heterogeneity. Moreover, research studies performed with the same methodology and thus showing the same level of evidence report conflicting results. Given the inconsistency of the findings and limitations of the methodology of the published studies, the teratogenic potential of paroxetine that has been reported in some studies remains unproven. This relevant safety question is likely to remain unanswered until large, prospective studies are conducted. Such studies should be designed to include a control group of untreated mothers with similar psychiatric diagnosis so as to differentiate effects of drug exposure from impact of underlying mental disorder on the fetus. Moreover, further experimental studies are warranted to definitively assess clinical consequences of the impact on fetal development related to physiologic effects of prenatal paroxetine exposure on different maternal and fetal parameters. ©Copyright 2009 Physicians Postgraduate Press, Inc.

Non-invasive prenatal diagnosis for fetal sex determination: benefits and disadvantages from the service users' perspective

PubMed Central

Lewis, Celine; Hill, Melissa; Skirton, Heather; Chitty, Lyn S

2012-01-01

Prenatal fetal sex determination is clinically indicated for women who are at risk of having a child with a serious genetic disorder affecting a particular sex. Ultrasound has been the traditional method used, but early fetal sex determination using non-invasive prenatal diagnosis (NIPD) can now be performed using cell-free fetal DNA in maternal plasma. The study aim was to assess the views and experiences of service users who had used NIPD for fetal sex determination. In this paper, we report on the perceived benefits and disadvantages. A qualitative approach using semi-structured interviews was used. A total of 44 participants (38 women and 6 partners of participating women) were recruited. Participants' views and experiences of NIPD were overwhelmingly positive. Concerning benefits over traditional methods, three themes emerged: (1) technical aspects of technology; (2) timing; and (3) enhanced decision-making. Practical advantages of NIPD included avoiding miscarriage, and there were a number of psychological advantages associated with timing such as perceived control, early re-engagement, normalization of pregnancy and peace of mind. Participants also valued NIPD as it enabled a stepwise approach to decision-making. A number of disadvantages were discussed including concerns about social sexing and increased bonding at a time in pregnancy when miscarriage risk is high. However, participants felt these were fairly minor in comparison with the advantages of NIPD. Until definitive genetic diagnosis using NIPD is available, NIPD for fetal sex determination is perceived as a good interim measure with a number of notable advantages over traditional methods. PMID:22453293

Human chorionic gonadotropin, fetal sex and risk of hypertensive disorders of pregnancy: A nested case-control study.

PubMed

Zheng, Qizhen; Deng, Yuqing; Zhong, Shilin; Shi, Yu

2016-01-01

To assess whether human chorionic gonadotropin (HCG) and fetal sex are two independent risk factors for hypertensive pregnancy in the early second-trimester of pregnancy. This was a retrospective nested case-control study based on a cohort of 2521 singleton pregnancies, among whom we recruited 98 hypertensive pregnancies (subdivided into severe preeclampsia, n=34; mild preeclampsia, n=29 and gestational hypertension, n=35) and 196 normotensive pregnancies. Maternal serum HCG levels were measured at 15-20 weeks of gestation and fetal sex was determined from the neonatal record. Mann-Whitney U and chi-square tests were performed to assess differences of HCG levels and fetal sex between groups. Logistic regressions were performed to evaluate the effect of HCG and fetal sex on hypertensive pregnancy. There were 35 male and 63 female fetuses in the hypertensive group, and 102 male and 94 female fetuses in the normotensive group (p=0.008). HCG (MoM) levels were significantly higher in only severe preeclamptic pregnancies (n=34) (p=0.013). There were no significant differences of the HCG (MoM) levels between male and female fetuses in each sub-group. aOR for increased maternal HCG levels and female fetus were 2.4 (95% CI: 1.434-3.954) and 2.9 (95% CI: 1.227-6.661) respectively in severe preeclamptic pregnancies compared with normotensive pregnancies. There is a female preponderance in hypertensive pregnancies. Increased HCG levels and female fetus are two independent risk factors for severe preeclampsia in the early second-trimester of pregnancy. Copyright © 2016 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Maternal diabetes alters the development of ductus venosus shunting in the fetus.

PubMed

Lund, Agnethe; Ebbing, Cathrine; Rasmussen, Svein; Kiserud, Torvid W; Kessler, Jörg

2018-05-11

Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous (UV) distribution, including increased ductus venosus (DV) shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on UV and DV flow is not known. In this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36. The blood velocity and the mean diameters of the UV and DV were used for calculating blood flow volumes. The development of the UV flow, DV flow and DV shunt fraction (% of UV blood shunted through the DV) was compared with a reference population, and the effect of HbA 1c on the DV flow was assessed. The UV flow was larger in pregnancies with pregestational diabetes mellitus than in low-risk pregnancies (p<0.001), but smaller when normalized for fetal weight (p=0.036). The distributional pattern of the DV flow developed differently in diabetic pregnancies, particularly during the third trimester, being smaller (p=0.007), also when normalized for fetal weight (p<0.001). Correspondingly the DV shunt fraction was reduced (p<0.0001), most prominently at 36 weeks. There were negative relations between the maternal HbA 1c and the DV flow velocity, flow volume and shunt fraction. In pregnancies with pregestational diabetes mellitus, prioritized UV distribution to the fetal liver, and lower DV shunt capacity, both reduce the compensatory capability of the fetus and may represent an augmented risk during hypoxic challenges during late pregnancy and birth. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Glucocorticoid-induced changes in glucocorticoid receptor mRNA and protein expression in the human placenta as a potential factor for altering fetal growth and development.

PubMed

Bivol, Svetlana; Owen, Suzzanne J; Rose'Meyer, Roselyn B

2016-02-05

Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth.

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

PubMed

Miranda, Joana O; Ramalho, Carla; Henriques-Coelho, Tiago; Areias, José Carlos

2017-11-01

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

Disproportionate Fetal Growth and the Risk for Congenital Cerebral Palsy in Singleton Births

PubMed Central

Streja, Elani; Miller, Jessica E.; Wu, Chunsen; Bech, Bodil H.; Pedersen, Lars Henning; Schendel, Diana E.; Uldall, Peter; Olsen, Jørn

2015-01-01

Objective To investigate the association between proportionality of fetal and placental growth measured at birth and the risk for congenital cerebral palsy (CP). Study Design We identified all live-born singletons born in Denmark between 1995 and 2003 and followed them from 1 year of age until December 31st, 2008. Information on four indices of fetal growth: ponderal index, head circumference/ abdominal circumference ratio, cephalization index and birth weight/ placenta weight ratio was collected. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). All measurements were evaluated as gestational age and sex specific z-scores and in z-score percentile groups, adjusted for potential confounders, and stratified on gestational age groups (<32, 32-36, 37-38, 39, 40, ≥41 weeks). Results We identified 503,784 singleton births, of which 983 were confirmed cases of CP. Head/ abdominal circumference ratio (aHR:1.12; 95%CI:1.07-1.16) and cephalization index (aHR:1.14; 95%CI:1.11-1.16) were associated with the risk of CP irrespective of gestational age. Birth weight-placental weight ratio was also associated with CP in the entire cohort (aHR:0.90; 95%CI:0.83-0.97). Ponderal index had a u-shaped association with CP, where both children with low and high ponderal index were at higher risk of CP. Conclusions CP is associated with disproportions between birth weight, birth length, placental weight and head circumference suggesting pre and perinatal conditions contribute to fetal growth restriction in children with CP. PMID:25974407

Identification of trisomy 18, trisomy 13, and Down syndrome from maternal plasma.

PubMed

Gekas, Jean; Langlois, Sylvie; Ravitsky, Vardit; Audibert, François; van den Berg, David-Gradus; Haidar, Hazar; Rousseau, François

2014-01-01

Current prenatal diagnosis for fetal aneuploidies (including trisomy 21 [T21]) generally relies on an initial biochemical serum-based noninvasive prenatal testing (NIPT) after which women who are deemed to be at high risk are offered an invasive confirmatory test (amniocentesis or chorionic villi sampling for a fetal karyotype), which is associated with a risk of fetal miscarriage. Recently, genomics-based NIPT (gNIPT) was proposed for the analysis of fetal genomic DNA circulating in maternal blood. The diffusion of this technology in routine prenatal care could be a major breakthrough in prenatal diagnosis, since initial research studies suggest that this novel approach could be very effective and could reduce substantially the number of invasive procedures. However, the limitations of gNIPT may be underappreciated. In this review, we examine currently published literature on gNIPT to highlight advantages and limitations. At this time, the performance of gNIPT is relatively well-documented only in high-risk pregnancies for T21 and trisomy 18. This additional screening test may be an option for women classified as high-risk of aneuploidy who wish to avoid invasive diagnostic tests, but it is crucial that providers carefully counsel patients about the test's advantages and limitations. The gNIPT is currently not recommended as a first-tier prenatal screening test for T21. Since gNIPT is not considered as a diagnostic test, a positive gNIPT result should always be confirmed by an invasive test, such as amniocentesis or chorionic villus sampling. Validation studies are needed to optimally introduce this technology into the existing routine workflow of prenatal care.

Corticosterone alters materno-fetal glucose partitioning and insulin signalling in pregnant mice

PubMed Central

Vaughan, O R; Fisher, H M; Dionelis, K N; Jefferies, E C; Higgins, J S; Musial, B; Sferruzzi-Perri, A N; Fowden, A L

2015-01-01

Glucocorticoids affect glucose metabolism in adults and fetuses, although their effects on materno-fetal glucose partitioning remain unknown. The present study measured maternal hepatic glucose handling and placental glucose transport together with insulin signalling in these tissues in mice drinking corticosterone either from day (D) 11 to D16 or D14 to D19 of pregnancy (term = D21). On the final day of administration, corticosterone-treated mice were hyperinsulinaemic (P < 0.05) but normoglycaemic compared to untreated controls. In maternal liver, there was no change in glycogen content or glucose 6-phosphatase activity but increased Slc2a2 glucose transporter expression in corticosterone-treated mice, on D16 only (P < 0.05). On D19, but not D16, transplacental 3H-methyl-d-glucose clearance was reduced by 33% in corticosterone-treated dams (P < 0.05). However, when corticosterone-treated animals were pair-fed to control intake, aiming to prevent the corticosterone-induced increase in food consumption, 3H-methyl-d-glucose clearance was similar to the controls. Depending upon gestational age, corticosterone treatment increased phosphorylation of the insulin-signalling proteins, protein kinase B (Akt) and glycogen synthase-kinase 3β, in maternal liver (P < 0.05) but not placenta (P > 0.05). Insulin receptor and insulin-like growth factor type I receptor abundance did not differ with treatment in either tissue. Corticosterone upregulated the stress-inducible mechanistic target of rapamycin (mTOR) suppressor, Redd1, in liver (D16 and D19) and placenta (D19), in ad libitum fed animals (P < 0.05). Concomitantly, hepatic protein content and placental weight were reduced on D19 (P < 0.05), in association with altered abundance and/or phosphorylation of signalling proteins downstream of mTOR. Taken together, the data indicate that maternal glucocorticoid excess reduces fetal growth partially by altering placental glucose transport and mTOR signalling. Key points Glucocorticoids regulate fetal and adult glucose metabolism, in part by influencing the actions of insulin. However, their effects on materno-fetal glucose partitioning remain largely unknown. In the present study, when pregnant mice were given the natural glucocorticoid, corticosterone, plasma insulin concentrations and liver insulin-signalling increased but the blood glucose concentration remained normal. However, in the placenta, glucose transport was reduced in association with the lower activity of some insulin signalling proteins, depending on the day of pregnancy and maternal food intake. In both liver and placenta, there was increased expression of the Redd1 (Ddit4) gene when the plasma corticosterone concentration was raised. The results show that maternal glucocorticoids interact with signalling pathways in the placenta to limit materno-fetal glucose partitioning. PMID:25625347

The effect of in vitro tracheal occlusion on branching morphogenesis in fetal lung explants from the rat nitrofen model of congenital diaphragmatic hernia.

PubMed

Grushka, Jeremy R; Al-Abbad, Saleh; Baird, Robert; Puligandla, Pramod; Kaplan, Feige; Laberge, Jean-Martin

2010-05-01

Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia. Tracheal occlusion has been shown to accelerate lung growth, but its effect on bronchial branching is unknown. In this study, we characterize the effects of in vitro TO on bronchial branch development in fetal lung explants derived from the nitrofen rat model of congenital diaphragmatic hernia. Rat dams were gavaged nitrofen on gestational day 9.5, and fetal lungs were harvested for explant culture on gestational day 14 (term, 22 days). Four experimental groups were investigated, with TO performed ex vivo using cautery: control, control + TO, nitrofen, and nitrofen + TO. Explants were incubated for 72 hours. Representative photographs were taken at 0, 24, 48, and 72 hours from the time of culture, and the number of distal branches was counted for each explant. The Student t test was used to compare distal branch measurements. A minimum of 12 fetal lung explants were cultured for each group. By 24 hours, all explants undergoing TO had more branch iterations than explants that did not. Moreover, TO in nitrofen-exposed explants increased bronchial branching to control levels by 24 hours in culture. Our results suggest that TO at day 14 increases branching in normal and nitrofen-exposed lung explants. In addition, TO increases airway branching in nitrofen-exposed explants to control levels suggesting that early TO reverses the lung hypoplasia seen in this model. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Structural development of human brain white matter from mid-fetal to perinatal stage

NASA Astrophysics Data System (ADS)

Ouyang, Austin; Yu, Qiaowen; Mishra, Virendra; Chalak, Lina; Jeon, Tina; Sivarajan, Muraleedharan; Jackson, Greg; Rollins, Nancy; Liu, Shuwei; Huang, Hao

2015-03-01

The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.

Antenatal Workup of Early Megacystis and Selection of Candidates for Fetal Therapy.

PubMed

Fontanella, Federica; Duin, Leonie; Adama van Scheltema, Phebe N; Cohen-Overbeek, Titia E; Pajkrt, Eva; Bekker, Mireille; Willekes, Christine; Bax, Caroline J; Oepkes, Dick; Bilardo, Catia M

2018-05-17

To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks' gestation (early megacystis). In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts. © 2018 The Author(s) Published by S. Karger AG, Basel.

Diagnosis and Management of IUGR in Pregnancy Complicated by Type 1 Diabetes Mellitus.

PubMed

Gutaj, Paweł; Wender-Ozegowska, Ewa

2016-05-01

This review discusses available literature on the diagnosis and management of intrauterine growth restriction (IUGR) in women with type 1 diabetes. IUGR is diagnosed when ultrasound-estimated fetal weight is below the 10th percentile for gestational age. IUGR diagnosis implies a pathologic process behind low fetal weight. IUGR in pregnancy complicated by type 1 diabetes is usually caused by placental dysfunction related to maternal vasculopathy. Prevention of IUGR should ideally start before pregnancy. Strict glycemic control and intensive treatment of nephropathy and hypertension are essential. Low-dose aspirin initiated before 16 gestational weeks can also reduce IUGR risk in women with vasculopathy. Umbilical and uterine artery Doppler studies can guide diagnosis and surveillance of fetuses with IUGR. Decisions regarding the timing of delivery should be based on assessment of umbilical artery Doppler. The risk of prematurity and impaired fetal lung maturation should always be considered, especially in fetuses younger than 32 weeks.

What can be done to lessen morbidity associated with fetal alcohol spectrum disorders?

PubMed

Mukherjee, Raja; Cook, Penny A; Fleming, Kate M; Norgate, Sarah H

2017-05-01

Fetal alcohol syndrome and its wider spectrum of presentation fetal alcohol spectrum disorders represent a range of disorders that are sometimes difficult to recognise as they may present in a way that overlaps with other conditions. This makes identification and recognition challenging, which increases the burden associated with the disorder. When considering the reduction in morbidity, both prevention of exposure to alcohol by the fetus and early identification of cases are required. This selective review seeks to highlight some of the complexities involved as well as highlighting the challenges. By considering populations particularly at risk to exploring the reality of alcohol risk it will seek to offer some solutions to begin the process of change. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Postpartum posttraumatic stress disorder in a fetal high-risk maternity hospital in the city of Rio de Janeiro, Brazil.

PubMed

Henriques, Tatiana; Moraes, Claudia Leite de; Reichenheim, Michael E; Azevedo, Gustavo Lobato de; Coutinho, Evandro Silva Freire; Figueira, Ivan Luiz de Vasconcellos

2015-12-01

The objectives of this study were to estimate the prevalence of postpartum posttraumatic stress disorder (PTSD) in a maternity hospital for fetal high-risk pregnancies and to identify vulnerable subgroups. This was a cross-sectional study at a fetal high-risk maternity hospital in Rio de Janeiro, Brazil, with a sample of 456 women who had given birth at this hospital. The Trauma History Questionnaire and Post-Traumatic Stress Disorder Checklist were used to screen for lifetime traumatic events and PTSD symptoms, respectively. Overall prevalence of PTSD was 9.4%. Higher PTSD prevalence was associated with three or more births, a newborn with a 1-minute Apgar score of seven or less, history of mental disorder prior to or during the index pregnancy, postpartum depression, physical or psychological intimate partner violence during the pregnancy, a history of unwanted sexual experience, and lifetime exposure to five or more traumas. Rapid diagnosis and treatment of PTSD are essential to improve the mother's quality of life and the infant's health.

Risk factors for antepartum fetal death.

PubMed

Oron, T; Sheiner, E; Shoham-Vardi, I; Mazor, M; Katz, M; Hallak, M

2001-09-01

To determine the demographic, maternal, pregnancy-related and fetal risk factors for antepartum fetal death (APFD). From our perinatal database between the years 1990 and 1997, 68,870 singleton birth files were analyzed. Fetuses weighing < 1,000 g at birth and those with structural malformations and/or known chromosomal anomalies were excluded from the study. In order to determine independent factors contributing to APFD, a multiple logistic regression model was constructed. During the study period there were 246 cases of APFD (3.6 per 1,000 births). The following obstetric factors significantly correlated with APFD in a multiple logistic regression model: preterm deliveries: small size for gestational age (SGA), multiparity (> 5 deliveries), oligohydramnios, placental abruption, umbilical cord complications (cord around the neck and true knot of cord), pathologic presentations (nonvertex) and meconium-stained amniotic fluid. APFD was not significantly associated with advanced maternal age. APFD was significantly associated with several risk factors. Placental and umbilical cord pathologies might be the direct cause of death. Grand multiparity, oligohydramnios, meconium-stained amniotic fluid, pathologic presentations and suspected SGA should be carefully evaluated during pregnancy in order to decrease the incidence of APFD.

Shoulder Dystocia: Incidence and Risk Factors.

PubMed

Ouzounian, Joseph G

2016-12-01

Shoulder dystocia complicates ∼1% of vaginal births. Although fetal macrosomia and maternal diabetes are risk factors for shoulder dystocia, for the most part its occurrence remains largely unpredictable and unpreventable.

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

PubMed

Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

2015-12-01

Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

Blood-derived small Dot cells reduce scar in wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kong, Wuyi; Li Shaowei; Longaker, Michael T.

2008-04-15

Wounds in fetal skin heal without scar, however the mechanism is unknown. We identified a novel group of E-cadherin positive cells in the blood of fetal and adult mice and named them 'Dot cells'. The percentage of Dot cells in E16.5 fetal mice blood is more than twenty times higher compared to adult blood. Dot cells also express integrin {beta}1, CD184, CD34, CD13{sup low} and Sca1{sup low}, but not CD45, CD44, and CD117. Dot cells have a tiny dot shape between 1 and 7 {mu}m diameters with fast proliferation in vitro. Most of the Dot cells remain positive for E-cadherinmore » and integrin {beta}1 after one month in culture. Transplantation of Dot cells to adult mice heals skin wounds with less scar due to reduced smooth muscle actin and collagen expression in the repair tissue. Tracking GFP-positive Dot cells demonstrates that Dot cells migrate to wounds and differentiate into dermal cells, which also express strongly to FGF-2, and later lose their GFP expression. Our results indicate that Dot cells are a group of previously unidentified cells that have strong wound healing effect. The mechanism of scarless wound healing in fetal skin is due to the presence of a large number of Dot cells.« less

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone

PubMed Central

Pearson, Helen; Britt, Rodney D.; Pabelick, Christine M.; Prakash, Y.S.; Amrani, Yassine; Pandya, Hitesh C.

2016-01-01

Background Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Methods Cultured fetal human ASM cells stimulated with TNF-α (0–20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. Results CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Conclusion Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases. PMID:26331770

Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes.

PubMed

Coppola, Danielle; Russo, Leo J; Kwarta, Robert F; Varughese, Ruana; Schmider, Juergen

2007-01-01

A significant number of women of childbearing age have schizophrenia or other psychoses. This means that there is a considerable risk of in utero exposure to risperidone due to maternal use. To determine whether in utero exposure to the atypical antipsychotic risperidone is associated with poor pregnancy and fetal/neonatal outcomes. A search of the Benefit Risk Management Worldwide Safety database, using a selection of preferred terms from the Medical Dictionary of Regulatory Activities, was performed to identify all cases of pregnancy or fetal/neonatal outcomes reported in association with risperidone treatment from its first market launch (international birth date, 1 June 1993) to 31 December 2004. The main measures were the patterns and reporting rates of pregnancy (stillbirth and spontaneous and induced abortion) and fetal/neonatal outcomes (congenital abnormalities, perinatal syndromes and withdrawal symptoms) for women administered risperidone during pregnancy. Overall, 713 pregnancies were identified in women who were receiving risperidone. Data were considered prospective in 516 of these, and retrospective in the remaining 197 cases. The majority of the known adverse pregnancy and fetal/neonatal outcomes were retrospectively reported. Of the 68 prospectively reported pregnancies with a known outcome, organ malformations and spontaneous abortions occurred 3.8% and 16.9% (when the 15 induced abortions were excluded from the denominator, as they were predominantly undertaken for nonmedical reasons), respectively, a finding consistent with background rates of the general population. There were 12 retrospectively reported pregnancies involving major organ malformations, the most frequently reported of which affected the heart, brain, lip and/or palate. There were 37 retrospectively reported pregnancies involving perinatal syndromes, of which 21 cases involved behavioural or motor disorders. In particular, there was a cluster of cases reporting tremor, jitteriness, irritability, feeding problems and somnolence, which may represent a withdrawal-emergent syndrome. This comprehensive review of the Benefit Risk Management Worldwide Safety database for case reports of risperidone exposure during pregnancy represents the largest ever published dataset documenting pregnancy outcomes for women taking the atypical antipsychotic risperidone. It indicates that in utero exposure to risperidone does not appear to increase the risk of spontaneous abortions, structural malformations and fetal teratogenic risk above that of the general population. Self-limited extrapyramidal effects in neonates were observed after maternal exposure to risperidone during the third trimester of pregnancy. Risperidone should only be used during pregnancy if the benefits outweigh the potential risks.

Cerebral palsy litigation: change course or abandon ship.

PubMed

Sartwelle, Thomas P; Johnston, James C

2015-06-01

The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds' labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule-the Daubert doctrine that excludes "junk science" from the courtroom-as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring's 40-year masquerade as science. © The Author(s) 2014.

Cerebral Palsy Litigation

PubMed Central

Sartwelle, Thomas P.

2015-01-01

The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds’ labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule—the Daubert doctrine that excludes “junk science” from the courtroom—as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring’s 40-year masquerade as science. PMID:25183322

A prospective clinical trial to compare the performance of dried blood spots prenatal screening for Down's syndrome with conventional non-invasive testing technology.

PubMed

Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun

2017-03-01

To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. Results demonstrate that fetal cfDNA can significantly reduce false-positive rate close to none while distinguishing all true positives. Thus, we recommend that fetal cfDNA analysis to be utilized as a secondary screening tool atop of the primary blood protein screening to further minimize the capacity of undesirable invasive diagnostic operations.

Fetal ascites and oligohydramnios: prenatal diagnosis of a sialic acid storage disease (index case).

PubMed

Poulain, P; Odent, S; Maire, I; Milon, J; Proudhon, J F; Jouan, H; Le Marec, B

1995-09-01

In a 20-year-old primiparous patient, a routine ultrasound scan performed at 28 weeks revealed fetal ascites, bilateral talipes, and oligohydramnios. This woman, married to possibly her first cousin, was at risk for an autosomal recessive disease, a metabolic disorder. At 29 weeks, an amniotic fluid biochemical study revealed the presence of an abnormal band of free sialic acid, leading to a diagnosis of a congenital form of sialic acid storage disease. Termination of pregnancy was performed at 30 weeks. Measurement of free sialic acid in cultured fetal skin fibroblasts confirmed the diagnosis.

Acute Lung Injury: Making the Injured Lung Perform Better and Rebuilding Healthy Lungs

DTIC Science & Technology

2014-04-01

A. Derivation Lung Mesenchymal Lineages from the Fetal Mesothelium Requires Hedgehog Signaling for Mesothelial Cell Entry. Development 140:4398-4405...mesothelial cell entry into the developing lung are largely unknown. The importance of the hedgehog (Hh) signaling pathway in mesenchymal...et al., 1997; Weaver et al., 2003; Polizio et al., 2011; Yoo et al., 2011). Mammals express three Hh ligands: Indian hedgehog (IHH), desert hedgehog

Evaluation of dexamethasone on fetal maturation and delivery in mares when administered on days 305 to 307 of gestation

USDA-ARS?s Scientific Manuscript database

In many species corticosteroids are administered to the dam to induce precocious fetal maturation when the pregnancy is at risk; however in the mare this has met with mixed results. Previously we showed that 24 mg betamethasone administered to pregnant mares on d305 to 307 of pregnancy tended to...

Intrauterine transfusion with the use of phased array ultrasonography: a new technique.

PubMed

Frigoletto, F D; Birnholz, J C; Rothchild, S B; Finberg, H J; Umansky, I

1978-06-01

Continuous ultrasonic observation of needle placement for aspiration, biopsy, or catheter placement is a novel and specific use of phased array imaging. In the case of IUTx, catheter placement into the fetal peritoneal space is accomplished rapidly, with reduced risk of fetal trauma, and without exposure to ionizing radiation. Experience with 27 transfusions in 11 patients is presented.

The Feasibility of Screening for Fetal Alcohol Spectrum Disorders Risk in Early Intervention Settings: A Pilot Study of Systems Change

ERIC Educational Resources Information Center

Watson, Enid; Finkelstein, Norma; Gurewich, Deborah; Morse, Barbara

2011-01-01

Prenatal alcohol exposure can result in fetal alcohol spectrum disorders (FASD), which can include physical and neurobehavioral disorders, including cognitive, social, language, and motor impairments that can persist throughout life. In order for children with FASD to receive the full benefit of services, recognition of their disability needs to…

Fetal Heart Rate Reactivity Differs by Women's Psychiatric Status: An Early Marker for Developmental Risk?

ERIC Educational Resources Information Center

Monk, Catherine; Sloan, Richard P.; Myers, Michael M.; Ellman, Lauren; Werner, Elizabeth; Jeon, Jiyeon; Tager, Felice; Fifer, William P.

2004-01-01

Objective: To determine whether there are differences in fetal heart rate (FHR) reactivity associated with women's psychiatric status. Method: In 57 women in their 36th to 38th week of pregnancy (mean age 27 [+ or -] 6 years), electrocardiogram, blood pressure (BP), respiration (RSP), and FHR were measured during baseline and a psychological…

Maternal exposure to hurricane destruction and fetal mortality.

PubMed

Zahran, Sammy; Breunig, Ian M; Link, Bruce G; Snodgrass, Jeffrey G; Weiler, Stephan; Mielke, Howard W

2014-08-01

The majority of research documenting the public health impacts of natural disasters focuses on the well-being of adults and their living children. Negative effects may also occur in the unborn, exposed to disaster stressors when critical organ systems are developing and when the consequences of exposure are large. We exploit spatial and temporal variation in hurricane behaviour as a quasi-experimental design to assess whether fetal death is dose-responsive in the extent of hurricane damage. Data on births and fetal deaths are merged with Parish-level housing wreckage data. Fetal outcomes are regressed on housing wreckage adjusting for the maternal, fetal, placental and other risk factors. The average causal effect of maternal exposure to hurricane destruction is captured by difference-in-differences analyses. The adjusted odds of fetal death are 1.40 (1.07-1.83) and 2.37 (1.684-3.327) times higher in parishes suffering 10-50% and >50% wreckage to housing stock, respectively. For every 1% increase in the destruction of housing stock, we observe a 1.7% (1.1-2.4%) increase in fetal death. Of the 410 officially recorded fetal deaths in these parishes, between 117 and 205 may be attributable to hurricane destruction and postdisaster disorder. The estimated fetal death toll is 17.4-30.6% of the human death toll. The destruction caused by Hurricanes Katrina and Rita imposed significant measurable losses in terms of fetal death. Postdisaster migratory dynamics suggest that the reported effects of maternal exposure to hurricane destruction on fetal death may be conservative. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pumps and warmers during amnioinfusion: is either necessary?

PubMed

Glantz, J C; Letteney, D L

1996-01-01

To determine if there is evidence from published reports that the use of infusion pumps or solution warmers during amnioinfusion is beneficial. We identified all English-language amnioinfusion reports published since 1983 through Medline and references. Fourteen prospective papers with at least 40 subjects were identified. For the amnioinfusion and control groups in each study, odds ratios (OR) were calculated for cesarean delivery, fetal distress, meconium below the cords, low 5-minute Apgar score, and endometritis. Cumulative ORs were calculated using the Mantel-Haenszel inverse variance method. This process was repeated after separation into pump-gravity and warmed-unwarmed groups. Multiple regression analyses were performed. Amnioinfusion improved the ability of the fetus to tolerate labor (fetal distress OR 0.40), decreased the incidence of meconium below the cords (OR 0.16), and decreased the rate of cesarean delivery (OR 0.56). There were no demonstrable benefits associated with the use of warmers or pumps. In multiple regression analysis, infusion pumps were associated with a significantly increased risk of fetal distress (P = .01). The use of amnioinfusion is associated with a decreased risk of fetal distress, meconium below the cords, and cesarean delivery. To date, there is no demonstrable benefit using infusion pumps or solution warmers during amnioinfusion.

Current understanding of the toxicological risk posed to the fetus following maternal exposure to nanoparticles.

PubMed

Zhang, Yanli; Wu, Junrong; Feng, Xiaoli; Wang, Ruolan; Chen, Aijie; Shao, Longquan

2017-12-01

With the broad use of nanotechnology, the number and variety of nanoparticles that humans can be exposed to has further increased. Consequently, there is growing concern about the potential effect of maternal exposure to various nanoparticles during pregnancy on a fetus. However, the nature of this risk is not fully known. Areas covered: In this review, materno-fetal transfer of nanoparticles through the placenta is described. Both prenatal and postnatal adverse effects, such as fetal resorption, malformation and injury to various organs in mice exposed to nanoparticles are reviewed. The potential mechanisms of toxicity are also discussed. Expert opinion: The toxicology and safe application of recently developed nanoparticles has attracted much attention in the past few years. Although many studies have demonstrated the toxicology of nanoparticles in various species, only a small number of studies have examined the effect on a fetus after maternal exposure to nanoparticles. This is particularly important, because the developing fetus is especially vulnerable to the toxic effects of nanoparticles during fetal development due to the unique physical stage of the fetus. Nanoparticles may directly or indirectly impair fetal development and growth after maternal exposure to nanoparticles.

Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour.

PubMed

Novikova, Natalia; Hofmeyr, G Justus; Essilfie-Appiah, George

2012-09-12

Amnioinfusion aims to relieve umbilical cord compression during labour by infusing a liquid into the uterine cavity. The objective of this review was to assess the effects of prophylactic amnioinfusion for women in labour with oligohydramnios, but not fetal heart deceleration, compared with therapeutic amnioinfusion only if fetal heart rate decelerations or thick meconium-staining of the liquor occur. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2012). Randomised trials comparing prophylactic amnioinfusion in women in labour with oligohydramnios but not fetal heart rate deceleration in labour with therapeutic amnioinfusion. The authors assessed trial quality and extracted data. One randomized trial of 116 women was included. No differences were found in the rate of caesarean section (risk ratio 1.29, 95% confidence interval 0.60 to 2.74). There were no differences in cord arterial pH, oxytocin augmentation, neonatal pneumonia or postpartum endometritis. Prophylactic amnioinfusion was associated with increased intrapartum fever (risk ratio 3.48, 95% confidence interval 1.21 to 10.05). There appears to be no advantage of prophylactic amnioinfusion over therapeutic amnioinfusion carried out only when fetal heart rate decelerations or thick meconium-staining of the liquor occur.

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

Birth weight and mortality: causality or confounding?

PubMed

Basso, Olga; Wilcox, Allen J; Weinberg, Clarice R

2006-08-15

The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality.

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.

Coagulation disorders in pregnancy: acquired and inherited thrombophilias.

PubMed

Benedetto, Chiara; Marozio, Luca; Tavella, Anna Maria; Salton, Loredana; Grivon, Sara; Di Giampaolo, Francesca

2010-09-01

Both acquired and inherited thrombophilias are associated with an increased risk of pregnancy-related venous thromboembolism (VTE) as well as with adverse pregnancy outcome. However, the extension of attributable risk for each thrombophilia and outcome is still a question of debate. Thrombophilias have been investigated in connection with VTE and pregnancy complications such as: recurrent and nonrecurrent early pregnancy loss, late fetal death, placental abruption, fetal growth restriction, and preeclampsia. This review discusses the evidence of association between thrombophilias and pregnancy outcome together with issues as to clinical management and preventive strategies. © 2010 New York Academy of Sciences.

Maternal abetalipoproteinemia resulting in multiple fetal anomalies.

PubMed

Seckeler, Michael D; Linden, Jennifer

2008-01-01

Abetalipoproteinemia is a rare genetic condition that results in an inability of the body to absorb dietary fats, including fat-soluble vitamins. Deficiencies of these vitamins are known to cause a wide range of clinical effects ranging from blindness to coagulopathy and neuropathy. We present the case of a child with multisystem anomalies born to a mother with abetalipoproteinemia and provide a brief review of the literature about vitamin A and fetal development. Mothers at high risk for vitamin deficiencies should be screened and counseled on the potential benefits, and risks, of vitamin supplementation. Copyright 2008 S. Karger AG, Basel.

[In case of fetal macrosomia, the best strategy is the induction of labor at 38 weeks of gestation].

PubMed

Rozenberg, P

2016-11-01

Macrosomic fetuses are at increased risk of obstetric complications, and notably shoulder dystocia, responsible for a severe neonatal morbidity. In case of fetal macrosomia, three options are: (i) the elective cesarean delivery, but this is recommended only when the estimated fetal weight is≥4500g for diabetic women and 5000g for non-diabetic women; (ii) the expectative management, but children with birth weight≥4500 had significantly increased risk of perinatal mortality, neonatal asphyxia, trauma, and cesarean delivery; (iii) the induction of labor which, reducing the possibility of fetal growth, reduce the risk of cesarean delivery for cephalopelvic disproportion and shoulder dystocia. As 2 former trials did not show maternal or neonatal benefit with induction of labor for fetal macrosomia, it was therefore not recommended. However, these 2 studies had small sample size (273 and 40 women) and a methodology limiting their ability to show a difference, justifying to achieve a large multicentre randomized controlled trial. This trial was performed by Boulvain et al. and the results published in 2015 in the Lancet. Inclusion criteria were: a singleton pregnancy in cephalic presentation and a suspected fetal macrosomia defined by an ultrasound estimated weight>95th percentile between 36 and 38 weeks. Women were randomly assigned to receive induction of labor within 3 days between 37 +0  and 38 +6  weeks of gestation, or expectant management. Expectant management continued until either spontaneous labour or diagnosis of a condition necessitating induction. The primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. Baseline characteristics were similar between groups. The mean birth weight (±SD) was 3831 (±324) g in the induction group 4118 (±392) g in the expectant group. Induction of labor significantly reduced the risk of shoulder dystocia or associated morbidity (8/407; 2 %) compared with expectant management (25/411; 6 %); P=0.004. The number needed to treat was 25 (95 % CI: 15-70). The incidence of caesarean section and operative vaginal delivery did not differ significantly between the groups. The likelihood of spontaneous vaginal delivery increased significantly in the induction of labor group (59 % vs. 52 %, RR: 1.14; 95 % CI: 1.01-1.29). In all, the results of the Boulvain et al. trial justify to propose an induction of labor in cases of suspected macrosomia>95th percentile: the induction of labor reduced the risk of severe shoulder dystocia, and does not increase the risk of cesarean section. It even increases the likelihood of spontaneous vaginal delivery. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation.

PubMed

Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J

2017-06-01

Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation. The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life. The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas. Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T 3 ), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation in vitro was reduced by T 3 in a dose-dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T 3 , insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Risk factors and adverse pregnancy outcomes among births affected by velamentous umbilical cord insertion: a retrospective population-based register study.

PubMed

Räisänen, Sari; Georgiadis, Leena; Harju, Maija; Keski-Nisula, Leea; Heinonen, Seppo

2012-12-01

To identify risk factors associated with velamentous cord insertion (VCI) and to evaluate the association between adverse pregnancy outcomes and VCI in singleton pregnancies. The total population of women (n=26,849) with singleton pregnancies delivered in Kuopio University Hospital during the study period between 2000 and 2011 was reviewed. Risk factors and the risk of adverse pregnancy outcomes (admission to a neonatal unit, fetal death, preterm delivery, low birth weight (LBW< 2500 g), the infant being small for its gestation age (SGA), low Apgar scores (<7) at 1 and 5 min and fetal venous pH<7.15) were evaluated separately among women with and without VCI by means of logistic regression analyses. The incidence of VCI among women with singleton pregnancies was 2.4% (n=633 of 26,849). Independent risk factors for VCI were nulliparity, obesity, fertility problems, placenta previa and maternal smoking. VCI was associated with a 1.38-, 2.01-, 3.93- and 1.39-fold increased risk of admission to a neonatal unit, preterm delivery (<37 gestation weeks), LBW and SGA, respectively compared to pregnancies involving normal cord insertion. Of the women with VCI, 15.3% underwent non-elective cesarean section compared to 8.3% (p ≤ 0.001) of women without VCI. The results suggest that the incidence of VCI increases along with an increase in fertility problems and maternal obesity. VCI is a moderate risk condition increasing the risks of prematurity and impaired fetal growth. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy.

PubMed

McCowan, Lesley M; Figueras, Francesc; Anderson, Ngaire H

2018-02-01

Small for gestational age is usually defined as an infant with a birthweight <10th centile for a population or customized standard. Fetal growth restriction refers to a fetus that has failed to reach its biological growth potential because of placental dysfunction. Small-for-gestational-age babies make up 28-45% of nonanomalous stillbirths, and have a higher chance of neurodevelopmental delay, childhood and adult obesity, and metabolic disease. The majority of small-for-gestational-age babies are not recognized before birth. Improved identification, accompanied by surveillance and timely delivery, is associated with reduction in small-for-gestational-age stillbirths. Internationally and regionally, detection of small for gestational age and management of fetal growth problems vary considerably. The aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines; and identify future research priorities in this field. A search of MEDLINE, Google, and the International Guideline Library identified 6 national guidelines on management of pregnancies complicated by fetal growth restriction/small for gestational age published from 2010 onwards. There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency. All highlight the importance of smoking cessation to prevent small for gestational age. While there is consensus in recommending fundal height measurement in the third trimester, 3 specify the use of a customized growth chart, while 2 recommend McDonald rule. Routine third-trimester scanning is not recommended for small-for-gestational-age screening, while women with major risk factors should have serial scanning in the third trimester. Umbilical artery Doppler studies in suspected small-for-gestational-age pregnancies are universally advised, however there is inconsistency in the recommended frequency for growth scans after diagnosis of small for gestational age/fetal growth restriction (2-4 weekly). In late-onset fetal growth restriction (≥32 weeks) general consensus is to use cerebral Doppler studies to influence surveillance and/or delivery timing. Fetal surveillance methods (most recommend cardiotocography) and recommended timing of delivery vary. There is universal agreement on the use of corticosteroids before birth at <34 weeks, and general consensus on the use of magnesium sulfate for neuroprotection in early-onset fetal growth restriction (<32 weeks). Most guidelines advise using cardiotocography surveillance to plan delivery in fetal growth restriction <32 weeks. The recommended gestation at delivery for fetal growth restriction with absent and reversed end-diastolic velocity varies from 32 to ≥34 weeks and 30 to ≥34 weeks, respectively. Overall, where there is high-quality evidence from randomized controlled trials and meta-analyses, eg, use of umbilical artery Doppler and corticosteroids for delivery <34 weeks, there is a high degree of consistency between national small-for-gestational-age guidelines. This review discusses areas where there is potential for convergence between small-for-gestational-age guidelines based on existing randomized controlled trials of management of small-for-gestational-age pregnancies, and areas of controversy. Research priorities include assessing the utility of late third-trimester scanning to prevent major morbidity and mortality and to investigate the optimum timing of delivery in fetuses with late-onset fetal growth restriction and abnormal Doppler parameters. Prospective studies are needed to compare new international population ultrasound standards with those in current use. Copyright © 2017. Published by Elsevier Inc.

Duration of second stage of labor and instrumental delivery as risk factors for severe perineal lacerations: population-based study.

PubMed

Simic, Marija; Cnattingius, Sven; Petersson, Gunnar; Sandström, Anna; Stephansson, Olof

2017-02-21

We sought to investigate the impact of the duration of second stage of labor on risk of severe perineal lacerations (third and fourth degree). This population based cohort study was conducted in the Stockholm/Gotland region, Sweden, 2008-2014. Study population included 52 211 primiparous women undergoing vaginal delivery with cephalic presentation at term. Unconditional logistic regression analysis was used to calculate crude and adjusted odds ratios (OR), using 95% confidence intervals (CI). Main exposure was duration of second stage of labor, and main outcome was risks of severe perineal lacerations (third and fourth degree). Risk of severe perineal lacerations increased with duration of second stage of labor. Compared with a second stage of labor of 1 h or less, women with a second stage of more than 2 h had an increased risk (aOR 1.42; 95% CI 1.28-1.58). Compared with non-instrumental vaginal deliveries, the risk was elevated among instrumental vaginal deliveries (aOR 2.24; 95% CI 2.07-2.42). The risk of perineal laceration increased with duration of second stage of labor until less than 3 h in both instrumental and non-instrumental vaginal deliveries, but after 3 h, the ORs did not further increase. After adjustments for potential confounders, macrosomia (birth weight > 4 500 g) and occiput posterior fetal position were risk factors of severe perineal lacerations. The risk of severe perineal laceration increases with duration until the third hour of second stage of labor. Instrumental delivery is the most significant risk factor for severe lacerations, followed by duration of second stage of labor, fetal size and occiput posterior fetal position.

A new biosensor for noninvasive determination of fetal RHD status in maternal blood of RhD negative pregnant women.

PubMed

Dündar Yenilmez, Ebru; Kökbaş, Umut; Kartlaşmış, Kezban; Kayrın, Levent; Tuli, Abdullah

2018-01-01

Prenatal detection of the fetal RHD status can be useful in the management of RhD incompatibility to identify fetuses at risk of hemolytic disease. Hemolytic disease causes morbidity and mortality of the fetus in the neonatal period. The routine use of antenatal and postnatal anti-D prophylaxis has reduced the incidence of hemolytic disease of the fetus and newborn. This study describe the detection of fetal RhD antigens in blood of RhD negative pregnant women using a nanopolymer coated electrochemical biosensor for medical diagnosis. Cell free fetal DNA in maternal plasma was also used to genotyping fetal RHD status using multiplex real-time PCR. Twenty-six RhD negative pregnant women in different gestational ages were included in the study. RhD positive fetal antibodies detected with a developed biosensor in maternal blood of RhD negative mothers. The electrochemical measurements were performed on a PalmSens potentiostat, and corundum ceramic based screen printed gold electrode combined with the reference Ag/AgCl electrode, and the auxiliary Au/Pd (98/2%) electrode. Fetal RHD genotyping performed using fluorescence-based multiplex real-time PCR exons 5 and 7 of the RHD gene. The fetal RHD status of 26 RhD negative cases were detected 21 as RhD positive and 5 as RhD negative with electrochemical biosensor. Fetal RHD status confirmed with extracted fetal DNA in maternal plasma using multiplex real-time PCR RHD genotyping and by serological test after delivery. The new method for fetal RhD detection in early pregnancy is useful and can be carry out rapidly in clinical diagnosis. Using automated biosensors are reproducible, quick and results can be generated within a few minutes compared to noninvasive fetal RHD genotyping from maternal plasma with real-time PCR-based techniques. We suggest the biosensor techniques could become an alternative part of fetal RHD genotyping from maternal plasma as a prenatal screening in the management of RhD incompatibility.

The effects of own fetal growth on reported hypertension in parous women aged 33.

PubMed

Hennessy, E; Alberman, E

1997-06-01

Data from the study of the British 1958 birth cohort, National Child Development Study (NCDS), has allowed wider investigation of the relationship between retarded fetal growth and risk of adult hypertension. A history of self-reported hypertension was related to fetal growth in 3308 parous cohort members. Fetal growth, the measure used, is the difference in actual birthweight from that expected for the gestational age and subsequent adult height. The relationships were investigated both linearly and non-linearly adjusting for potential confounders. After adjustment for confounding factors, including adult weight for height, retarded fetal growth was associated with reported hypertension particularly when not confined to pregnancy. The latter was also associated with accelerated fetal growth, moderate or severe hypertension in the mother when pregnant with the cohort member, being relatively taller than your mother, and lack of educational qualifications. Hypertension confined to pregnancy was more likely among women who were themselves firstborn or older at childbirth. Neither maternal smoking during cohort's gestation nor cohort member's gestational age had a significant effect. The results are consistent with previous reports that fetal growth effects are less marked if gestation is short. The relationships between fetal growth and subsequent hypertension are extremely complex and variable, and need to be studied allowing for deviations from growth potential. Adult weight for height remains the strongest predictor of hypertension. The results suggest that losing weight is likely to have the same proportional benefit in women with and without a history of retarded fetal growth.

[Evaluation of medication risk in pregnant women: methodology of evaluation and risk management].

PubMed

Eléfant, E; Sainte-Croix, A

1997-01-01

This round table discussion was devoted to the description of the tools currently available for the evaluation of drug risks and management during pregnancy. Five topics were submitted for discussion: pre-clinical data, methodological tools, benefit/risk ratio before prescription, teratogenic or fetal risk evaluation, legal comments.

The pharmacokinetic profile of synthetic cathinones in a pregnancy model.

PubMed

Strange, Lauren G; Kochelek, Kerri; Keasling, Robert; Brown, Stacy D; Pond, Brooks B

2017-09-01

In recent years, the abuse of synthetic cathinones or 'bath salts' has become a major public health concern. Although these compounds were initially sold legally and labeled "not for human consumption", the 'bath salts' are psychostimulants, with similar structures and pharmacologic mechanisms to cocaine, the amphetamines, and 3,4 methylendioxymethamphetamine (MDMA, Molly, or Ecstasy). The reported use of these substances by women of child-bearing age highlights the necessity of studies seeking to delineate risks of prenatal exposure. Three popular drugs of this type are methylone, mephedrone, and 3, 4-methylenedioxypyrovalerone (MDPV). Unfortunately, there is currently no information available on the teratogenicity of these compounds, or of the extent to which they cross the placenta. As such, the purpose of this study was to examine the pharmacokinetic profile of the 'bath salts' in a pregnancy model. Pregnant mice (E17.5 gestation) were injected intraperitoneally with a cocktail of 5mg/kg methylone, 10mg/kg mephedrone, and 3mg/kg (MDPV) dissolved in sterile saline. Maternal brain, maternal plasma, placenta, and fetal brain were collected at 30s, 1min, 5min, 10min, 15min, 30min, 1h, 2h, 4h, and 8h following injection. Methylone, mephedrone, and MDPV were extracted from tissue by solid phase extraction, and concentrations were determined using a previously validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Interestingly, all 3 cathinones reached measurable concentrations in the placenta, as well as the fetal brain; in fact, for MDPV, the maximal concentration (Cmax) was highest in fetal brain, while mephedrone's highest Cmax value was achieved in placenta. Additionally, the total drug exposure for all 3 compounds (as represented by area under the curve, AUC) was higher in fetal matrices (placenta and fetal brain) than in maternal matrices (maternal brain and plasma), and the half-lives for the drugs were longer. Given the extensive presence of methylone, mephedrone, and MDPV in the fetal brain following prenatal exposure, fetal risk is definitely a concern. As there are currently no prenatal studies available on the teratogenicity of these agents, pregnant patients should be informed about the potential risks that these substances may have. Copyright © 2017 Elsevier Inc. All rights reserved.

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

PubMed

Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

2013-07-01

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

PubMed Central

Stewart, Laurel M.; Koenig, Michelle; Semler, Matthew; Breitbach, Meghan E.; Zeng, Xiankun; Weiler, Andrea M.; Barry, Gabrielle L.; Thoong, Troy H.; Wiepz, Gregory J.; Dudley, Dawn M.; Simmons, Heather A.; Mejia, Andres; Morgan, Terry K.; Salamat, M. Shahriar; Kohn, Sarah; Antony, Kathleen M.; Mohns, Mariel S.; Hayes, Jennifer M.; Schultz-Darken, Nancy; Schotzko, Michele L.; Peterson, Eric; Capuano, Saverio; Osorio, Jorge E.; O’Connor, Shelby L.; O’Connor, David H.; Golos, Thaddeus G.

2018-01-01

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. PMID:29381706

Evaluation of prenatal risk factors for prediction of outcome in right heart lesions: CVP score in fetal right heart defects.

PubMed

Neves, Ana Luisa; Mathias, Leigh; Wilhm, Marilyn; Leshko, Jennifer; Linask, Kersti K; Henriques-Coelho, Tiago; Areias, José C; Huhta, James C

2014-09-01

To determine the prenatal variables predicting the risk of perinatal death in congenital right heart defects. Retrospective analysis of 28 fetuses with right heart defects was performed. Logistic regression analyses were performed to obtain odds ratios (OR) for the relationship between the risk of death and echocardiographic parameters. The parameters that correlated with the outcome were incorporated in an attempt to devise a disease-specific cardiovascular profile score. Fetal echocardiograms (143) from 28 patients were analyzed. The cardiovascular profile score predicted the risk of death. A lower right ventricle (RV) pressure was associated with mortality (OR 0.959; 95% confidence intervals (CI) 0.940-0.978). Higher peak aortic velocity through the aortic valve (OR 0.104; 95% CI 0.020-0.529) was associated with a better outcome. These cardiac function parameters were incorporated in a modified disease-specific CVP Score. Patients with a mean modified cardiovascular profile score of ≤ 6 were over 3.7 times more likely to die than those with scores of 7-10. The original Cardiovascular Profile Score predicted the risk of death in right heart defects. The modified score was not validated as a good prediction tool by this study. Fetal RV pressure estimate and peak aortic velocity can be used as independent prognostic predictors.

Exposure to the Chinese famine in early life and the risk of anaemia in adulthood.

PubMed

Shi, Zumin; Zhang, Cuilin; Zhou, Minghao; Zhen, Shiqi; Taylor, Anne W

2013-10-01

Famine exposure during the early stage of life is related to a number of adulthood diseases. The objective of this study was to examine the association of early life exposure to the famine in China (1959-1961) with the risk of anaemia in adulthood. We used the data of 2007 adults born between 1954 and 1964 in Jiangsu province from the 2002 Chinese National Nutrition and Health Survey. Anaemia was defined as haemoglobin concentration <12 g/dl in women and <13 g/dl in men. Prevalence of anaemia in adulthood in nonexposed, fetal-exposed, early-childhood, mid-childhood, and late-childhood exposed to famine groups were 26.0%, 33.8%, 28.1%, 28.2% and 29.7%, respectively. Overall, fetal-exposed to famine was associated with 37% increased risk of anaemia as compared with those non-exposed after adjusting for income, education, place of residence, smoking, alcohol drinking, job, hypertension and BMI; relative risk (95% confidence interval) (RR (95% CI)) was 1.37 (1.09, 1.71). In general, this association appeared to be stronger among men, those who were currently overweight or obese, or those of lower educational levels. Corresponding RR (95% CI) was 1.87 (1.21-2.87), 1.75 (1.20-2.56), and 2.07 (1.37-3.12), respectively. Fetal exposure to the Chinese famine was associated with an increased risk of anaemia in adulthood.

Predictive value of late decelerations for fetal acidemia in unselective low-risk pregnancies.

PubMed

Sameshima, Hiroshi; Ikenoue, Tsuyomu

2005-01-01

We evaluated the clinical significance of late decelerations (LD) of intrapartum fetal heart rate (FHR) monitoring to detect low pH (< 7.1) in low-risk pregnancies. We selected two secondary and two tertiary-level institutions where 10,030 women delivered. Among them, 5522 were low-risk pregnancies. The last 2 hours of FHR patterns before delivery were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlation between the incidence of LD (occasional, < 50%; recurrent, > or = 50%) and severity (reduced baseline FHR accelerations and variability) of LD, and low pH (< 7.1) were evaluated. Statistical analyses included a contingency table with chi2 and the Fisher test, and one-way analysis of variance with the Bonferroni/Dunn test. In the 5522 low-risk pregnancies, 301 showed occasional LD and 99 showed recurrent LD. Blood gases and pH values deteriorated as the incidence of LD increased and as baseline accelerations or variability was decreased. Positive predictive value for low pH (< 7.1) was exponentially elevated from 0% at no deceleration, 1% in occasional LD, and > 50% in recurrent LD with no baseline FHR accelerations and reduced variability. In low-risk pregnancies, information on LD combined with acceleration and baseline variability enables us to predict the potential incidence of fetal acidemia.

Overlap Chronic Placental Inflammation Is Associated with a Unique Gene Expression Pattern.

PubMed

Raman, Kripa; Wang, Huaqing; Troncone, Michael J; Khan, Waliul I; Pare, Guillaume; Terry, Jefferson

2015-01-01

Breakdown of the balance between maternal pro- and anti-inflammatory pathways is thought to allow an anti-fetal maternal immune response that underlies development of chronic placental inflammation. Chronic placental inflammation is manifested by the influx of maternal inflammatory cells, including lymphocytes, histiocytes, and plasma cells, into the placental membranes, villi, and decidua. These infiltrates are recognized pathologically as chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. Each of these histological entities is associated with adverse fetal outcomes including intrauterine growth restriction and preterm birth. Studying the gene expression patterns in chronically inflamed placenta, particularly when overlapping histologies are present, may lead to a better understanding of the underlying mechanism(s). Therefore, this study compared tissue with and without chronic placental inflammation, manifested as overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis. RNA expression profiling was conducted on formalin fixed, paraffin embedded placental tissue using Illumina microarrays. IGJ was the most significant differentially expressed gene identified and had increased expression in the inflamed tissue. In addition, IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the inflamed placental samples. These differentially expressed genes are associated with T follicular helper cells, natural killer cells, and B cells. Furthermore, these genes differ from those typically associated with the individual components of chronic placental inflammation, such as chronic villitis, suggesting that the inflammatory infiltrate associated with overlapping chronic chorioamnionitis, chronic villitis of unknown etiology, and chronic deciduitis differs is unique. To further explore and validate gene expression findings, we conducted immunohistochemical assessment of protein level expression and demonstrate that IgJ expression was largely attributable to the presence of plasma cells as part of chronic deciduitis and that IgA positive plasma cells are associated with chronic deciduitis occurring in combination with chronic chorioamnionitis and chronic villitis of unknown etiology but not with isolated chronic deciduitis.

Fetal laceration during caesarean section and its medico-legal sequelae.

PubMed

Esposito, Ciro; Escolino, Maria; Paternoster, Mariano; Buccelli, Claudio; Graziano, Vincenzo; Falco, Marianna; Alicchio, Francesca; Cerulo, Mariapina; Settimi, Alessandro; Savanelli, Antonio

2015-04-01

Fetal laceration is a recognized complication of caesarean delivery. The aim of this study was to investigate the incidence, type, location, risk factors and long-term consequences of accidental fetal incised wounds during caesarean delivery. During a five-year period, we observed 25 cases of fetal lacerations caused by the scalpel during hysterotomy. In 20 of these cases, we observed these lesions as consultants for the Neonatologic Care Unit; the other five cases came under our care after an insurance claim for damages against the gynaecologist. All the infants had a lesion located to the head. In only 5 of the 25 cases the lesion was reported in the operative summary, and only 16 of the 25 mothers had signed an informed consent before surgery. With regard to the 20 cases diagnosed at the Neonatologic Care Unit, the lesion was closed using single stitches in nine cases, and with biological glue in 11 cases. Concerning the five cases that underwent legal proceedings against the gynaecologist, a clinical examination was performed by an expert in Public Health and Social Security in collaboration with a paediatric surgeon to evaluate the degree of biological damage. In all five cases, the result of the legal challenge was monetary compensation for the physical and moral damage caused by the gynaecologists to the patients and their parents. Accidental fetal lesions may occur during caesarean delivery; the incidence is significantly higher during emergency caesarean delivery compared to elective procedures. Patients should sign an informed consent in which they should be informed about the risk of the occurrence of fetal lacerations during caesarean delivery in order to avoid legal complications. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Cost-effectiveness of cardiotocography plus ST analysis of the fetal electrocardiogram compared with cardiotocography only.

PubMed

Vijgen, Sylvia M C; Westerhuis, Michelle E M H; Opmeer, Brent C; Visser, Gerard H A; Moons, Karl G M; Porath, Martina M; Oei, Guid S; Van Geijn, Herman P; Bolte, Antoinette C; Willekes, Christine; Nijhuis, Jan G; Van Beek, Erik; Graziosi, Giuseppe C M; Schuitemaker, Nico W E; Van Lith, Jan M M; Van Den Akker, Eline S A; Drogtrop, Addy P; Van Dessel, Hendrikus J H M; Rijnders, Robbert J P; Oosterbaan, Herman P; Mol, Ben Willem J; Kwee, Anneke

2011-07-01

To assess the cost-effectiveness of addition of ST analysis of the fetal electrocardiogram (ECG; STAN) to cardiotocography (CTG) for fetal surveillance during labor compared with CTG only. Cost-effectiveness analysis based on a randomized clinical trial on ST analysis of the fetal ECG. Obstetric departments of three academic and six general hospitals in The Netherlands. Population. Laboring women with a singleton high-risk pregnancy, a fetus in cephalic presentation, a gestational age >36 weeks and an indication for internal electronic fetal monitoring. A trial-based cost-effectiveness analysis was performed from a health-care provider perspective. Primary health outcome was the incidence of metabolic acidosis measured in the umbilical artery. Direct medical costs were estimated from start of labor to childbirth. Cost-effectiveness was expressed as costs to prevent one case of metabolic acidosis. The incidence of metabolic acidosis was 0.7% in the ST-analysis group and 1.0% in the CTG-only group (relative risk 0.70; 95% confidence interval 0.38-1.28). Per delivery, the mean costs per patient of CTG plus ST analysis (n= 2 827) were €1,345 vs. €1,316 for CTG only (n= 2 840), with a mean difference of €29 (95% confidence interval -€9 to €77) until childbirth. The incremental costs of ST analysis to prevent one case of metabolic acidosis were €9 667. The additional costs of monitoring by ST analysis of the fetal ECG are very limited when compared with monitoring by CTG only and very low compared with the total costs of delivery. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

Early Life Stages

EPA Pesticide Factsheets

Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

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

Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child Characteristics, and Maternal Risk Factors in a Second Sample of Rural Communities in South Africa.

PubMed

May, Philip A; De Vries, Marlene M; Marais, Anna-Susan; Kalberg, Wendy O; Buckley, David; Adnams, Colleen M; Hasken, Julie M; Tabachnick, Barbara; Robinson, Luther K; Manning, Melanie A; Bezuidenhout, Heidre; Adam, Margaret P; Jones, Kenneth L; Seedat, Soraya; Parry, Charles D H; Hoyme, H Eugene

2017-05-12

Background : Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods : Active case ascertainment focused on children with height, weight and/or head circumference ≤25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results : Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 9-129 per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children in these communities. Conclusions : Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.

Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: Differential influences of fetal sex.

PubMed

Fineberg, Anna M; Ellman, Lauren M; Schaefer, Catherine A; Maxwell, Seth D; Shen, Ling; H Chaudhury, Nashid; Cook, Aundrea L; Bresnahan, Michaeline A; Susser, Ezra S; Brown, Alan S

2016-02-28

Exposure to adverse life events during pregnancy has been linked to increased risk of schizophrenia spectrum disorders (SSD) in offspring. Nevertheless, much of the previous work inferred maternal stress from severe life events rather than directly assessing maternal reports of stress. The present study aimed to examine maternal reports of stress during pregnancy and risk for offspring SSD. Participants were 95 SSD cases and 206 controls who were offspring from a large birth cohort study that followed pregnant women from 1959 to 1966. During pregnancy interviews, women were asked if anything worrisome had occurred recently. Interviews were qualitatively coded for stress-related themes, including reports of daily life stress, by two independent raters. None of the maternal psychosocial stress themes were significantly associated with increased odds of offspring SSD in analyses of the full sample. However, results indicated a significant daily life stress by infant sex interaction. Maternal daily life stress during pregnancy was associated with significantly increased odds of SSD among male offspring. Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy. Published by Elsevier Ireland Ltd.

A systematic review and meta-analysis of fetal outcomes following the administration of influenza A/H1N1 vaccination during pregnancy.

PubMed

Zhang, Chuan; Wang, Xiaodong; Liu, Dan; Zhang, Lingli; Sun, Xin

2018-05-01

Pregnant women were identified as a population of priority for vaccination during the H1N1 influenza pandemic outbreak in 2009. To assess adverse fetal outcomes following the administration of H1N1 pandemic vaccination during pregnancy. PubMed, Embase, and Cochrane Library were searched up to January 2017. Cohort studies investigating fetal outcomes after H1N1 influenza vaccination during pregnancy were eligible. The language was limited to English. Pairs of reviewers independently screened studies for eligibility, assessed the risk of bias, and extracted data from the included studies. A total of 19 cohort studies were eligible. The use of vaccines during any period of pregnancy was associated with lower risk of stillbirth (adjusted hazard ratio 0.80, 95% confidence interval 0.69-0.92). No significant differences were found between the vaccinated versus unvaccinated groups in terms of the risks of spontaneous abortion, premature birth, and small for gestational age. The administration of H1N1 vaccines during pregnancy might reduce the risk of stillbirth, a complication associated with H1N1 infection. The quality of evidence was, however, not adequate to reach a definitive conclusion. © 2017 International Federation of Gynecology and Obstetrics.

Contribution of Leptospira, Neospora caninum and bovine viral diarrhea virus to fetal loss of beef cattle in New Zealand.

PubMed

Sanhueza, J M; Heuer, C; West, D

2013-10-01

The profitability of beef breeding farms in New Zealand depends principally on optimal reproductive performance. The aim of this study was to estimate the impact of four major pathogens, bovine viral diarrhea virus (BVDV), Neospora caninum (N. caninum), Leptospira borgpetersenii serovar Hardjo (Hardjo), and Leptospira interrogans serovar Pomona (Pomona), on rates of fetal loss in commercial beef breeding herds. Farms reporting fetal loss were recruited, and a blood sample from aborting cows (cases) was collected. Controls were normally calving cows from the same farm. At least four controls were selected from each farm contributing cases. Samples were tested using ELISA for detection of antibodies against BVDV and N. caninum, and microscopic agglutination test (MAT) for detection of antibody against Hardjo and Pomona. A selection of titer cut-offs was conducted to evaluate the relationship between fetal loss and seropositivity to each pathogen using conditional logistic regression. The cut-off titer with the strongest association with fetal loss was included in the multivariate model. A significant increased risk of fetal loss was found for animals seropositive to N. caninum (odds ratio (OR)=3.36; 95% confidence interval (95% CI)=1.27-8.89), Hardjo (OR=1.84; 95% CI=1.01-3.33), and Pomona in non-vaccinated cows (OR=14.91, 95% CI=1.73-128.84) at the ELISA titer ≥ 30, and MAT titers of ≥ 1:384 and ≥ 1:768 for a positive sample, respectively. A marginally non-significant increased risk of fetal loss was found for animals exposed to BVDV (OR=2.01; 95% CI=0.99-4.11) at the ELISA titer of ≤ 1. Vaccination did not affect ORs for Hardjo or BVDV and no herd vaccinated against N. caninum. Approximately 14.0% of all fetal loss in the beef breeding cattle population in New Zealand may be attributable to BVDV (3.5%), N. caninum (3.0%), Hardjo (4.7%), and Pomona (3.6%). Copyright © 2013 Elsevier B.V. All rights reserved.

Cardiotocography versus intermittent auscultation of fetal heart on admission to labour ward for assessment of fetal wellbeing.

PubMed

Devane, Declan; Lalor, Joan G; Daly, Sean; McGuire, William; Smith, Valerie

2012-02-15

The admission cardiotocograph (CTG) is a commonly used screening test consisting of a short (usually 20 minutes) recording of the fetal heart rate (FHR) and uterine activity performed on the mother's admission to the labour ward. To compare the effects of admission CTG with intermittent auscultation of the FHR on maternal and infant outcomes for pregnant women without risk factors on their admission to the labour ward. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 May 2011) (CENTRAL) (The Cochrane Library 2011 Issue 2 of 4), MEDLINE (1966 to 17 May 2011), CINAHL (1982 to 17 May 2011), Dissertation Abstracts (1980 to 17 May 2011) and the reference list of retrieved papers. All randomised and quasi-randomised trials comparing admission CTG with intermittent auscultation of the FHR for pregnant women between 37 and 42 completed weeks of pregnancy and considered to be at low risk of intrapartum fetal hypoxia and of developing complications during labour. Two authors independently assessed trial eligibility and quality, and extracted data. Data were checked for accuracy. We included four trials involving more than 13,000 women. All four studies included women in labour. Overall, the studies were at low risk of bias. Although not statistically significant using a strict P < 0.05 criterion, data are consistent with women allocated to admission CTG having, on average, a higher probability of an increase in incidence of caesarean section than women allocated to intermittent auscultation (risk ratio (RR) 1.20, 95% confidence interval (CI) 1.00 to 1.44, four trials, 11,338 women, T² = 0.00, I² = 0%). There was no significant difference in the average treatment effect across included trials between women allocated to admission CTG and women allocated to intermittent auscultation in instrumental vaginal birth (RR 1.10, 95% CI 0.95 to 1.27, four trials, 11,338 women, T² = 0.01, I² = 38%) and fetal and neonatal deaths (RR 1.01, 95% CI 0.30 to 3.47, four trials, 11339 infants, T² = 0.00, I² = 0%).Women allocated to admission CTG had, on average, significantly higher rates of continuous electronic fetal monitoring during labour (RR 1.30, 95% CI 1.14 to 1.48, three trials, 10,753 women, T² = 0.01, I² = 79%) and fetal blood sampling (RR 1.28, 95% CI 1.13 to 1.45, three trials, 10,757 women, T² = 0.00, I² = 0%) than women allocated to intermittent auscultation. There were no differences between groups in other secondary outcome measures. Contrary to continued use in some clinical areas, we found no evidence of benefit for the use of the admission cardiotocograph (CTG) for low-risk women on admission in labour.We found no evidence of benefit for the use of the admission CTG for low-risk women on admission in labour. Furthermore, the probability is that admission CTG increases the caesarean section rate by approximately 20%. The data lacked power to detect possible important differences in perinatal mortality. However, it is unlikely that any trial, or meta-analysis, will be adequately powered to detect such differences. The findings of this review support recommendations that the admission CTG not be used for women who are low risk on admission in labour. Women should be informed that admission CTG is likely associated with an increase in the incidence of caesarean section without evidence of benefit.

The Association Between Maternal Subclinical Hypothyroidism and Growth, Development, and Childhood Intelligence: A Meta-analysis

PubMed

Liu, Yahong; Chen, Hui; Jing, Chen; Li, FuPin

2018-06-01

To explore the association between maternal subclinical hypothyroidism (SCH) in pregnancy and the somatic and intellectual development of their offspring. Using RevMan 5.3 software, a meta-analysis of cohort studies published from inception to May 2017, focusing on the association between maternal SCH in pregnancy and childhood growth, development and intelligence, was performed. Sources included the Cochrane Library, Pub-Med, Web of Science, China National Knowledge Infrastructure and Wan Fang Data. Analysis of a total of 15 cohort studies involving 1.896 pregnant women with SCH revealed that SCH in pregnancy was significantly associated with the intelligence (p=0.0007) and motor development (p<0.00001) of the offspring. SCH was also significantly associated with the child’s weight in four studies involving 222 women (p=0.02). Maternal SCH in pregnancy was identified as a risk factor for fetal growth restriction with a combined relative risk (RR) value of 2.4 [95% confidence interval (CI): 1.56, 3.7]. Meta-analysis of 10 studies that provided numbers of preterm infants revealed a significant association between maternal SCH in pregnancy and premature delivery, with a combined RR of 1.96 (95% CI: 1.34, 2.88). There was a significant effect of maternal SCH in pregnancy on fetal distress in utero (p=0.003). Maternal SCH in pregnancy is associated with increased risk of adverse neonatal outcomes, including delayed intellectual and motor development, low birth weight, premature delivery, fetal distress and fetal growth restriction.

Cardiovascular outcomes of pregnancy in Marfan's syndrome patients: A literature review.

PubMed

Kim, So Yeon; Wolfe, Diana S; Taub, Cynthia C

2018-03-01

Pregnancy in patients with Marfan's syndrome (MFS) carries an increased risk of cardiovascular complications, resulting in increased maternal and fetal mortality and morbidity. Literature on MFS pregnant patients is relatively sparse, and there has yet to be a concrete consensus on the management of this unique patient population. The purpose of our paper is to provide a literature review of case reports and studies on MFS during pregnancy (published between 2005 and 2015) and to explore cardiovascular outcomes of patients with MFS. Of the 852 women in our review, there were 1112 pregnancies, with an aortic dissection rate of 7.9% and mortality of 1.2%. Data demonstrated a trend that patients whose aortic diameter ≥40 mm had a greater rate of dissection than MFS patients whose aortic diameter <40 mm (Fisher's exact test, P = .0504). Fetal outcome included a 5.6% mortality rate and 41% of births were cesarean deliveries and of those reported, 75% secondary to cardiac emergencies. Patients with MFS, especially those whose initial aortic diameters ≥40 mm, planning a pregnancy or currently pregnant should be carefully counseled about the maternal and fetal risks throughout pregnancy. MFS patients whose aortic diameters ≥40 mm should be advised to ideally await pregnancy until prophylactic aortic surgery. As MFS varies in its phenotypic expression, each patient's risk of adverse cardiac events should be assessed individually through a joint Maternal Fetal Medicine and Cardiology Center. © 2017 Wiley Periodicals, Inc.

Ultrasound diagnosis of bilateral cataracts in a fetus with possible cerebro-ocular congential muscular dystrophy during the routine second trimester anomaly scan

PubMed Central

Wimalasundera, Ruwan; Holder, Susan

2015-01-01

The finding of bilateral congenital cataracts in the fetus is rare. We report bilateral congenital cataracts detected during the routine second trimester anomaly scan, which subsequently were found to be associated with other congenital anomalies and the parents opted for a termination of pregnancy. At post-mortem, Muscle–Eye Brain disease or Walker–Warburg Syndrome was considered likely, which are autosomal recessive congenital muscular dystrophy disorders associated with cerebral, cerebellar, muscle and eye anomalies. On ultrasound, bilateral cataracts appear as echogenic, solid areas within the fetal orbits. The examination of the fetal face and orbits plays an important role in confirming fetal well-being antenatally. We propose that it should become a routine part of the structural survey of fetal anatomy during the obstetric anomaly scan. This is especially important in pregnancies previously affected by fetal cataracts or pregnancies at risk of rare genetic syndromes. PMID:27433255

A phantom with pulsating artificial vessels for non-invasive fetal pulse oximetry.

PubMed

Laqua, Daniel; Pollnow, Stefan; Fischer, Jan; Ley, Sebastian; Husar, Peter

2014-01-01

Arterial oxygen saturation of the fetus is an important parameter for monitoring its physical condition. During labor and delivery the transabdominal non-invasive fetal pulse oximetry could minimize the risk for mother and fetus, compared to other existing invasive examination methods. In this contribution, we developed a physical-like phantom to investigate new sensor circuits and algorithms of a non-invasive diagnostic method for fetal pulse oximetry. Hence, the developed artificial vascular system consists of two independent tube systems representing the maternal and fetal vessel system. The arterial blood pressure is reproduced with a pre-pressure and an artificial vascular system. Each pulse wave can be reproduced, by digital control of a proportional valve, adjustable viscoelastic elements, and resistances. The measurements are performed by pressure transducers, optical sensor units, and a coplanar capacitive sensor. Transmission and reflection measurements have shown that the fetal and maternal pulse waves can be reproduced qualitatively. The measured light represents the transabdominal modulated signal on an abdomen of a pregnant woman.

Safe fetal platelet genotyping: new developments.

PubMed

Le Toriellec, Emilie; Chenet, Christophe; Kaplan, Cecile

2013-08-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal management strategies have been developed to avoid complications such as intracranial hemorrhage. The aim of this study was to set up two reliable, noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in which the father is heterozygous for the offending antigen. This study focused on human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in Caucasians. Two assays based on cell-free fetal DNA extracted from maternal blood samples and on real-time polymerase chain reaction (QPCR) were developed: an allele-specific QPCR specifically targeting the polymorphic sequence in HPA-1 and the study of the variation in the high-resolution melting curve of amplicons containing the polymorphic region. All results from the 49 samples obtained from 29 pregnant women were consistent with expectations. Six women were compatible with their fetuses (three HPA-1aa women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their fetuses, as were two HPA-1aa women. Two fetal PLT genotyping assays on maternal blood samples proved to be reliable as of 15 weeks of gestation, thereby avoiding invasive techniques such as amniocentesis. © 2012 American Association of Blood Banks.

Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

PubMed

Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

2017-08-29

Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

Autism spectrum disorders and fetal hypoxia in a population-based cohort: Accounting for missing exposures via Estimation-Maximization algorithm

PubMed Central

2011-01-01

Background Autism spectrum disorders (ASD) are associated with complications of pregnancy that implicate fetal hypoxia (FH); the excess of ASD in male gender is poorly understood. We tested the hypothesis that risk of ASD is related to fetal hypoxia and investigated whether this effect is greater among males. Methods Provincial delivery records (PDR) identified the cohort of all 218,890 singleton live births in the province of Alberta, Canada, between 01-01-98 and 12-31-04. These were followed-up for ASD via ICD-9 diagnostic codes assigned by physician billing until 03-31-08. Maternal and obstetric risk factors, including FH determined from blood tests of acidity (pH), were extracted from PDR. The binary FH status was missing in approximately half of subjects. Assuming that characteristics of mothers and pregnancies would be correlated with FH, we used an Estimation-Maximization algorithm to estimate HF-ASD association, allowing for both missing-at-random (MAR) and specific not-missing-at-random (NMAR) mechanisms. Results Data indicated that there was excess risk of ASD among males who were hypoxic at birth, not materially affected by adjustment for potential confounding due to birth year and socio-economic status: OR 1.13, 95%CI: 0.96, 1.33 (MAR assumption). Limiting analysis to full-term males, the adjusted OR under specific NMAR assumptions spanned 95%CI of 1.0 to 1.6. Conclusion Our results are consistent with a weak effect of fetal hypoxia on risk of ASD among males. E-M algorithm is an efficient and flexible tool for modeling missing data in the studied setting. PMID:21208442

[Study of 178 ante partum deaths in 2001-2004 in the southern part of Reunion Island].

PubMed

Randrianaivo, H; Robillard, P-Y; Barau, G; Gérardin, P; Heisert, M; Kauffmann, E; Laffite, A; Fourmaintraux, A

2006-11-01

The perinatal mortality rate is 18.5 in the southern part of the Reunion Island (Indian Ocean), of which 2/3 are due to antepartum fetal deaths (APFD). During a 4-year period (2001-2004) all APFD from 22 weeks gestation were recorded and analyzed with placental histology, bacteriological samples and autopsies in 27% of cases. The Australasian and New-Zealand classification PSANZ-PDC (2000) was used. Risk factors of fetal death with monofetal pregnancies are determined in comparison with live births. Out of 21.495 total births, 178 APFD were recorded. The main obstetrical risk factors were primiparity (OR 1.6, p = 0.002), maternal age over 34 years (OR 1.6, p = 0.01), hypertensive disorders of pregnancy (OR 3.0, p < .001) and multiple births (OR 2.5, p < 0.001). The great majority of APFD (76%) involved preterm fetuses, of which 61% of very preterm (<33 weeks), and 25% of fetuses were growth retarded (OR 3.9, p < 0.001). Only 8% of cases were considered unexplained. The main etiologies were infectious causes in 26% of cases, vascular fetal growth restriction (18%), specific perinatal conditions (14%) of which one-third were due to cord anomalies, preeclampsia (10%), maternal conditions (8%), congenital anomalies (8%) and ante-partum hemorrhage (7%). We discuss the interests and the limitations of using the Australian and New-Zealand classification PSANZ 2000. Intra-uterine growth retardation is one of the principal risk factors of fetal death. Besides well-known obstetrical risk factors such as diabetes, hypertension, multiple pregnancies, all screening of intra-uterine growth retardation in the second trimester of pregnancy should include a special survey in order to minimize the incidence of APFDs.

Immortalization of Human Fetal Hepatocyte by Ectopic Expression of Human Telomerase Reverse Transcriptase, Human Papilloma Virus (E7) and Simian Virus 40 Large T (SV40 T) Antigen Towards Bioartificial Liver Support.

PubMed

Giri, Shibashish; Bader, Augustinus

2014-09-01

Generation of genetically stable and non-tumoric immortalization cell line from primary cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. It is now universal acceptance that immortalization of human fetal hepatocytes based on recent advances of telomerase biology and oncogene, lead to unlimited population doubling could be the possible source for bioartificial liver device. Immortalization of human fetal hepatocytes cell line by ectopic expression of human telomerase reverse transcriptase (hTERT), human papilloma virus gene (E7) and simian virus 40 large T (SV40 T) antigens is main goal of present study. We used an inducible system containing human telomerase and E7, both of which are cloned into responder constructs controlled by doxycycline transactivator. We characterized the immortalized human fetal hepatocyte cells by analysis of green fluorescent cells (GFP) positive cells using flow cytometry (FACs) cell sorting and morphology, proliferative rate and antigen expression by immunohistochemical analysis. In addition to we analysized lactate formation, glucose consumption, albumin secretion and urea production of immortalized human fetal hepatocyte cells. After 25 attempts for transfection of adult primary hepatocytes by human telomerase and E7 to immortalize them, none of the transfection systems resulted in the production of a stable, proliferating cell line. Although the transfection efficiency was more than 70% on the first day, the vast majority of the transfected hepatocytes lost their signal within the first 5-7 days. The remaining transfected hepatocytes persisted for 2-4 weeks and divided one or two times without forming a clone. After 10 attempts of transfection human fetal hepatocytes using the same transfection system, we obtained one stable human fetal hepatocytes cell line which was able albumin secretion urea production and glucose consumption. We established a conditional human fetal hepatocytes cell line with mesenchymal characteristics. Thus immortalization of human fetal hepatocytes cell line by telomerase biology offers a great challenge to examine basic biological mechanisms which are directly related to human and best cell source having unlimited population doubling for bioartificial support without any risk of replicative senescence and pathogenic risks.

A State of Double Jeopardy: Impact of Prenatal Alcohol Exposure and Adverse Environments on the Social Communicative Abilities of School-Age Children with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Coggins, Truman E.; Timler, Geralyn R.; Olswang, Lesley B.

2007-01-01

Purpose: This article is a retrospective examination of environmental risk, language performance, and narrative discourse data from a clinical database of school-age children with fetal alcohol spectrum disorder (FASD). Method: A case-defined diagnostic approach for measuring and reporting the full spectrum of disabilities in children with…

Canadian Children and Youth in Care: The Cost of Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Popova, Svetlana; Lange, Shannon; Burd, Larry; Rehm, Jürgen

2014-01-01

Background: A high prevalence of prenatal alcohol exposure has been reported among children in care and thus, the risk of fetal alcohol spectrum disorder (FASD) in this population is high. Objective: The purpose of the current study was to estimate the number of children (0-18 years) in care with FASD and to determine the associated cost by age…

A health priority for developing countries: the prevention of chronic fetal malnutrition.

PubMed

Villar, J; Altobelli, L; Kestler, E; Beliźan, J

1986-01-01

A prospective study of 3557 consecutively born neonates from a lower middle class district in Guatemala City documented a 23.8% incidence of intrauterine growth retardation due to fetal malnutrition. Those infants whose weights are below the 10th percentile of a sex- and race-specific birthweight and gestational age distribution, based on a developed country population, were considered to manifest intrauterine growth retardation. Ponderal index values were then used to further classify this population as having chronic fetal malnutrition (above the 10th percentile of the standard distribution) or subacute fetal malnutrition (below the 10th percentile); the incidences of these conditions were 79.1% and 20.8%, respectively. The results of numerous studies carried out in various populations suggest that developing countries have a higher incidence of chronically malnourished infants within the intrauterine growth retardation population, while subacute fetal malnutrition is more prevalent in developed countries. Moreover, it has been shown that chronically malnourished infants do not recover from their intrauterine damage and score the lowest in mental development tests even up to school age. They remain lighter, shorter, and with a smaller head circumference until at least 3 years of age. Based on the incidence rates ascertained in this study, it can be estimated that at least 2 million infants born each year in Latin America are at risk of chronic intrauterine growth retardation. Screening programs are needed to identify at-risk mothers early in pregnancy so that medical and nutritional interventions can be implemented.

Prenatal detection of structural cardiac defects and presence of associated anomalies: a retrospective observational study of 1262 fetal echocardiograms.

PubMed

Mone, Fionnuala; Walsh, Colin; Mulcahy, Cecelia; McMahon, Colin J; Farrell, Sinead; MacTiernan, Aoife; Segurado, Ricardo; Mahony, Rhona; Higgins, Shane; Carroll, Stephen; McParland, Peter; McAuliffe, Fionnuala M

2015-06-01

The aim of this study is to document the detection of fetal congenital heart defect (CHD) in relation to the following: (1) indication for referral, (2) chromosomal and (3) extracardiac abnormalities. All fetal echocardiograms performed in our institution from 2007 to 2011 were reviewed retrospectively. Indication for referral, cardiac diagnosis based on the World Health Organization International Classification of Diseases tenth revision criteria and the presence of chromosomal and extracardiac defects were recorded. Of 1262 echocardiograms, 287 (22.7%) had CHD. Abnormal anatomy scan in pregnancies originally considered to be at low risk of CHD was the best indicator for detecting CHD (91.2% of positive cardiac diagnoses), compared with other indications of family history (5.6%) or maternal medical disorder (3.1%). Congenital anomalies of the cardiac septa comprised the largest category (n = 89), within which atrioventricular septal defects were the most common anomaly (n = 36). Invasive prenatal testing was performed for 126 of 287 cases, of which 44% (n = 55) had a chromosomal abnormality. Of 232 fetuses without chromosomal abnormalities, 31% had an extracardiac defect (n = 76). Most CHDs occur in pregnancies regarded to be at low risk, highlighting the importance of a routine midtrimester fetal anatomy scan. Frequent association of fetal CHD and chromosomal and extracardiac pathology emphasises the importance of thorough evaluation of any fetus with CHD. © 2015 John Wiley & Sons, Ltd.

Fetal anomalies and long-term effects associated with substance abuse in pregnancy: a literature review.

PubMed

Viteri, Oscar A; Soto, Eleazar E; Bahado-Singh, Ray O; Christensen, Carl W; Chauhan, Suneet P; Sibai, Baha M

2015-04-01

Substance abuse in pregnancy remains a major public health problem. Fetal teratogenicity results from the effect of these substances during fetal development, particularly when used in combination. This review will focus on and attempt to clarify the existing literature regarding the association of substance abuse on the development of congenital anomalies and the long-term implications in exposed offspring. Systematic review of available English literature using the PubMed database of all peer-reviewed articles on the subject. A total of 128 articles were included in this review. Alcohol was the most common substance associated with fetal anomalies, particularly facial dysmorphisms and alterations in the central nervous system development. Adverse maternal environments associated with risky behaviors and lack of adequate prenatal care precludes the timely detection of fetal anomalies, confounding most studies linking causality. In addition, although methodological differences and limited availability of well-designed trials exist, substance abuse in pregnancy has been associated with adverse long-term outcomes in infant growth, behavior, cognition, language and achievement. The literature summarized in this review suggests that drug exposure during pregnancy may increase the risk of congenital anomalies and long-term adverse effects in exposed children and adolescents. These conclusions must be tempered by the many confounders associated with drug use. A multidisciplinary approach is paramount for appropriate counseling regarding the known immediate and long-term risks of substance abuse in pregnancy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice.

PubMed

Chin, Eunice H; Schmidt, Kim L; Martel, Kaitlyn M; Wong, Chi Kin; Hamden, Jordan E; Gibson, William T; Soma, Kiran K; Christians, Julian K

2017-01-01

Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS) diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.

Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study

PubMed Central

Kessler, Jörg

2018-01-01

Objectives To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length. Design Population based registry study. Setting Medical Birth Registry of Norway 1999–2013. Population All singleton births (gestational age>22weeks<45 weeks) (n = 856 300). Methods Descriptive statistics and odds ratios of risk factors for extreme cord length and adverse outcomes based on logistic regression adjusted for confounders. Main outcome measures Short or long cord (<10th or >90th percentile), cord knot and entanglement, adverse pregnancy outcomes including perinatal and intrauterine death. Results Increasing parity, maternal height and body mass index, and diabetes were associated with increased risk of a long cord. Large placental and birth weight, and fetal male sex were factors for a long cord, which again was associated with a doubled risk of intrauterine and perinatal death, and increased risk of adverse neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were associated with a short cord, which was associated with increased risk of fetal malformations, placental complications, caesarean delivery, non-cephalic presentation, perinatal and intrauterine death. At term, cord knot was associated with a quadrupled risk of perinatal death. The combination of a cord knot and entanglement had a more than additive effect to the association to perinatal death. There was a more than doubled risk of recurrence of a long or short cord, knot and entanglement in a subsequent pregnancy of the same woman. Conclusion Cord length is influenced both by maternal and fetal factors, and there is increased risk of recurrence. Extreme cord length, entanglement and cord knot are associated with increased risk of adverse outcomes including perinatal death. We provide population based reference ranges for umbilical cord length. PMID:29584790

Intrauterine growth retardation promotes fetal intestinal autophagy in rats via the mechanistic target of rapamycin pathway

PubMed Central

WANG, Chao; ZHANG, Ruiming; ZHOU, Le; HE, Jintian; HUANG, Qiang; SIYAL, Farman A; ZHANG, Lili; ZHONG, Xiang; WANG, Tian

2017-01-01

Intrauterine growth retardation (IUGR) impairs fetal intestinal development, and is associated with high perinatal morbidity and mortality. However, the mechanism underlying this intestinal injury is largely unknown. We aimed to investigate this mechanism through analysis of intestinal autophagy and related signaling pathways in a rat model of IUGR. Normal weight (NW) and IUGR fetuses were obtained from primiparous rats via ad libitum food intake and 50% food restriction, respectively. Maternal serum parameters, fetal body weight, organ weights, and fetal blood glucose were determined. Intestinal apoptosis, autophagy, and the mechanistic target of rapamycin (mTOR) signaling pathway were analyzed. The results indicated that maternal 50% food restriction reduced maternal serum glucose, bilirubin, and total cholesterol and produced IUGR fetuses, which had decreased body weight; blood glucose; and weights of the small intestine, stomach, spleen, pancreas, and kidney. Decreased Bcl-2 and increased Casp9 mRNA expression was observed in IUGR fetal intestines. Analysis of intestinal autophagy showed that the mRNA expression of WIPI1, MAP1LC3B, Atg5, and Atg14 was also increased, while the protein levels of p62 were decreased in IUGR fetuses. Compared to NW fetuses, IUGR fetuses showed decreased mTOR protein levels and enhanced mRNA expression of ULK1 and Beclin1 in the small intestine. In summary, the results indicated that maternal 50% food restriction on gestational days 10–21 reduced maternal serum glucose, bilirubin, and total cholesterol contents, and produced IUGR fetuses that had low blood glucose and reduced small intestine weight. Intestinal injury of IUGR fetuses caused by maternal food restriction might be due to enhanced apoptosis and autophagy via the mTOR signaling pathway. PMID:28855439

Altered autonomic control of heart rate variability in the chronically hypoxic fetus.

PubMed

Shaw, C J; Allison, B J; Itani, N; Botting, K J; Niu, Y; Lees, C C; Giussani, D A

2018-03-31

Fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, and a decrease in FHRV is associated with fetal compromise. However, the mechanisms by which FHRV is reduced in the chronically hypoxic fetus have yet to be established. The sympathetic and parasympathetic influences on heart rate mature at different rates throughout fetal life, and can be assessed by time domain and power spectral analysis of FHRV. In this study of chronically instrumented fetal sheep in late gestation, we analysed FHRV daily over a 16 day period towards term, and compared changes between fetuses of control and chronically hypoxic pregnancy. We show that FHRV in sheep is reduced by chronic hypoxia, predominantly due to dysregulation of the sympathetic control of the fetal heart rate. This presents a potential mechanism by which a reduction in indices of FHRV predicts fetuses at increased risk of neonatal morbidity and mortality in humans. Reduction in overall FHRV may therefore provide a biomarker that autonomic dysregulation of fetal heart rate control has taken place in a fetus where uteroplacental dysfunction is suspected. Although fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, the mechanisms by which it is reduced in the chronically hypoxic fetus have yet to be established. In particular, the physiological mechanism underlying the reduction of short term variation (STV) in fetal compromise remains unclear. In this study, we present a longitudinal study of the development of autonomic control of FHRV, assessed by indirect indices, time domain and power spectral analysis, in normoxic and chronically hypoxic, chronically catheterised, singleton fetal sheep over the last third of gestation. We used isobaric chambers able to maintain pregnant sheep for prolonged periods in hypoxic conditions (stable fetal femoral arterial PO2 10-12 mmHg), and a customised wireless data acquisition system to record beat-to-beat variation in the fetal heart rate. We determined in vivo longitudinal changes in overall FHRV and the sympathetic and parasympathetic contribution to FHRV in hypoxic (n = 6) and normoxic (n = 6) ovine fetuses with advancing gestational age. Normoxic fetuses show gestational age-related increases in overall indices of FHRV, and in the sympathetic nervous system contribution to FHRV (P < 0.001). Conversely, gestational age-related increases in overall FHRV were impaired by exposure to chronic hypoxia, and there was evidence of suppression of the sympathetic nervous system control of FHRV after 72 h of exposure to hypoxia (P < 0.001). This demonstrates that exposure to late gestation isolated chronic fetal hypoxia has the potential to alter the development of the autonomic nervous system control of FHRV in sheep. This presents a potential mechanism by which a reduction in indices of FHRV in human fetuses affected by uteroplacental dysfunction can predict fetuses at increased risk. © 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Non-invasive management of fetal goiter during maternal treatment of hyperthyroidism in Grave's disease.

PubMed

Lembet, Arda; Eroglu, Derya; Kinik, Sibel Tulgar; Gurakan, Berkan; Kuscu, Esra

2005-01-01

There is an increased risk of fetal goiter in patients who have a history of Grave's disease and undergo propylthiouracil (PTU) treatment during pregnancy. In this report, we describe a case of a fetal goiter detected by antenatal ultrasound at the 26th week of gestation in a mother treated with PTU for Grave's disease. A 32 x 38 x 20 mm fetal goiter was detected, each lobe measured 30 x 18 x 18 mm and estimated volume was 10 cm3. Subsequently, fetal thyroid function was assessed by umbilical fetal blood sampling. Cord blood showed elevated serum TSH (40.2 mU/l) and normal concentrations of free T4 (9.5 pmol/l) and free T3 (2.6 pmol/l). There were no other ultrasonographic signs of fetal hypothyroidism. Based on the above findings, the mother's PTU dosage was reduced to 50 mg daily from a total of 150 mg and weekly ultrasonographic examinations were performed. Six weeks after the initial ultrasound, a complete regression of the fetal goiter was noted. At the 34th week of gestation, the patient was delivered due to intrauterine growth restriction and oligohydramnios and gave birth to a male, weighing 1,920 g. The newborn thyroid was not palpable and thyroid ultrasonography was normal. Cord blood TSH was normal (8.4 mU/l) and free T4 was within lower normal limit (9.03 pmol/l). Ten days later, newborn thyroid function was normal and the baby did well afterwards. In conclusion, after the evaluation of fetal thyroid status, selected cases with fetal goiter can be initially managed without intrauterine treatment. (c) 2005 S. Karger AG, Basel

Fetal and maternal dose assessment for diagnostic scans during pregnancy

NASA Astrophysics Data System (ADS)

Rafat Motavalli, Laleh; Miri Hakimabad, Hashem; Hoseinian Azghadi, Elie

2016-05-01

Despite the concerns about prenatal exposure to ionizing radiation, the number of nuclear medicine examinations performed for pregnant women increased in the past decade. This study attempts to better quantify radiation doses due to diagnostic nuclear medicine procedures during pregnancy with the help of our recently developed 3, 6, and 9 month pregnant hybrid phantoms. The reference pregnant models represent the adult female international commission on radiological protection (ICRP) reference phantom as a base template with a fetus in her gravid uterus. Six diagnostic scintigraphy scans using different radiopharmaceuticals were selected as typical diagnostic nuclear medicine procedures. Furthermore, the biokinetic data of radioiodine was updated in this study. A compartment representing iodide in fetal thyroid was addressed explicitly in the biokinetic model. Calculations were performed using the Monte Carlo transport method. Tabulated dose coefficients for both maternal and fetal organs are provided. The comparison was made with the previously published fetal doses calculated for stylized pregnant female phantoms. In general, the fetal dose in previous studies suffers from an underestimation of up to 100% compared to fetal dose at organ level in this study. A maximum of difference in dose was observed for the fetal thyroid compared to the previous studies, in which the traditional models did not contain the fetal thyroid. Cumulated activities of major source organs are primarily responsible for the discrepancies in the organ doses. The differences in fetal dose depend on several other factors including chord length distribution between fetal organs and maternal major source organs, and anatomical differences according to gestation periods. Finally, considering the results of this study, which was based on the realistic pregnant female phantoms, a more informed evaluation of the risks and benefits of the different procedures could be made.

Parvovirus B19 infection during pregnancy and risks to the fetus.

PubMed

Ornoy, Asher; Ergaz, Zivanit

2017-03-15

Parvovirus B19 infects 1 to 5% of pregnant women, generally with normal pregnancy outcomes. During epidemics, the rate of infection is higher. Major congenital anomalies among offspring of infected mothers are rare, as the virus does not appear to be a significant teratogen. However, parvovirus B19 infection may cause significant fetal damage, and in rare cases, brain anomalies and neurodevelopmental insults, especially if infection occurs in the first 20 weeks of pregnancy. Parvovirus B19 is also an important cause of fetal loss, especially in the second half of pregnancy when spontaneous fetal loss from other causes is relatively rare. Parvovirus B19 infection may affect many fetal organs and can cause severe anemia, following fetal erythroid progenitor cells infection and apoptosis, especially in fetuses, that have shortened half-life of erythrocytes. Severe anemia may cause high output cardiac failure and nonimmune hydrops fetalis. In addition, parvovirus B19 may directly infect myocardial cells and produce myocarditis that further aggravates the cardiac failure. Intrauterine fetal transfusion is commonly used for the treatment of severe fetal anemia with survival rates of 75 to 90% and significant reduction of fetal morbidity. Only 66 cases were evaluated neurodevelopmentally, of which 10 (16%) had slight or severe neurodevelopmental problems. Because parvovirus B19 infection can cause severe fetal morbidity and mortality, it should be part of the routine work-up of pregnant women who have been exposed to the virus or of pregnancies with suspected fetal hydrops. Assessment for maternal infection during pregnancy is especially important during epidemics, when sero-conversion rates are high. Birth Defects Research 109:311-323, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

PubMed

Satterfield, M Carey; Bazer, Fuller W; Spencer, Thomas E; Wu, Guoyao

2010-02-01

Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

Fetal distress and the condition of newborn infants.

PubMed Central

Sykes, G S; Molloy, P M; Johnson, P; Stirrat, G M; Turnbull, A C

1983-01-01

In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth. PMID:6412897

Comparative proteomics analysis of placenta from pregnant women with intrahepatic cholestasis of pregnancy.

PubMed

Zhang, Ting; Guo, Yueshuai; Guo, Xuejiang; Zhou, Tao; Chen, Daozhen; Xiang, Jingying; Zhou, Zuomin

2013-01-01

Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and associated with increased risks in fetal complications. Currently, the exact cause of this disease is unknown. In this study we aim to investigate the potential proteins in placenta, which may participate in the molecular mechanisms of ICP-related fetal complications using iTRAQ-based proteomics approach. The iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to separate differentially expressed placental proteins from 4 pregnant women with ICP and 4 healthy pregnant women. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three apoptosis related proteins ERp29, PRDX6 and MPO that resulted from iTRAQ-based proteomics were further verified in placenta by Western blotting and immunohistochemistry. Placental apoptosis was also detected by TUNEL assay. Proteomics results showed there were 38 differentially expressed proteins from pregnant women with ICP and healthy pregnant women, 29 were upregulated and 9 were downregulated in placenta from pregnant women with ICP. Bioinformatics analysis showed most of the identified proteins was functionally related to specific cell processes, including apoptosis, oxidative stress, lipid metabolism. The expression levels of ERp29, PRDX6 and MPO were consistent with the proteomics data. The apoptosis index in placenta from ICP patients was significantly increased. This preliminary work provides a better understanding of the proteomic alterations of placenta from pregnant women with ICP and may provide us some new insights into the pathophysiology and potential novel treatment targets for ICP.

[Prenatal diagnosis. Review, personal and prospective studies].

PubMed

Engel, E; Empson, J; DeLozier, D; McGee, B; da Costa Woodson, E; Engel-de Montmollin, M; Carter, T; Lorber, C; Cassidy, S B; Millis, J; Heller, R M; Boehm, F; Vanhooydonk, J

1979-07-07

1. In a review of methods developed for the identification of fetal malformations, the technique, risks and results of amniocentesis are presented. 2. Large series already published have demonstrated the relative simplicity and feasibility of the procedure as well as current indications for its utilization. These include the detection of chromosomal anomalies, the determination of sex (in certain sex-linked disorders), documentation of enzymatic and metabolic deficiencies, and the demonstration of open lesions of the neural tube by appropriate techniques. 3. Experience with over 500 cases personally tested by the authors entirely confirms the major indications for and benefits of this modern method for the detection and prevention of severe congenital anomalies during early pregnancy. 4. The identification of chromosomal alterations is currently the major objective of the method. Increased risks are associated with pregnancies involving a maternal age of 35 years or older (which account for 1-3% of aneuploidies), the birth of a previous infant with free trisomy 21 (1% recurrence risk) or secondary to a parental chromosome translocation (as much as 10% risk of aneuploidy). Fetal karyotyping for determination of sex, in cases where the mother is a carrier of an X-linked recessive gene (on average, 50% of male offspring will be affected), is an inadequate method of diagnosis to be utilized only until alternative techniques render possible specific diagnosis of the anomalies under consideration (hemophilias A and B, muscular dystrophy, etc). 5. Several of these techniques are now nearing development through the advent of fetoscopy and advanced ultrasound methodology, and have already been applied to the detection of certain sex-linked disorders and also for diagnosis of hemoglobinopathies (thalassemias, sickel cell anemia) and other conditions requiring the obtaining of fetal blood for diagnosis. Technology allowing direct examination of fetal parts by means of optical instruments is particularly useful in cases where a severe fetal morphologic malformation cannot currently be identified by indirect visualization (ultrasound) or by analysis of cytogenetic or molecular markers. 6. Pathological accumulations of alpha-fetoprotein which are associated with diverse feto-placental abnormalities (particularly open malformations of the neural tube) can be detected in the amniotic fluid and/or maternal blood. In extension of this approach, it is foreseeable that conditions existing prenatally will be diagnosed in a growing number of cases from the study of fetal cells and molecules which can be isolated from the venous blood of pregnant women. This will become feasible as a result of some well-developed techniques which allow separation of fetal from maternal cells and metabolites, and also to some extremely fine analytic techniques, notably examination of the DNA itself by means of restriction enzymes.

Neuromyelitis optica in pregnancy complicated by posterior reversible encephalopathy syndrome, eclampsia and fetal death.

PubMed

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-03-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable.