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Objective We examined mode of delivery among pregnant women with epilepsy (PWWE) versus pregnant controls (PC). We hypothesize that PWWE are more likely to deliver by cesarean. Study Design The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an observational, prospective, multicenter investigation of pregnancy outcomes funded by the National Institute of Health (NIH). MONEAD enrolled patients from December 2012 through January 2016. PWWE were matched to PC in a case:control ratio of 3:1. This analysis had 80% power to detect a 36% increase in cesarean frequency assuming a baseline rate of 30% among PC at an α = 0.05. Results This report analyzed 331 PWWE (76%) and 102 PC (24%) who gave birth while enrolled in the study. PWWE and PC had similar rates of cesarean delivery (34.7 vs. 28.6%; p = 0.27). Of women with cesarean, rates of cesarean without labor were similar between groups for those delivering in recruitment hospitals (48.2 vs. 50.0%) but in nonrecruitment hospitals, cesarean rates without labor were over two-fold higher among PWWE than those of PC (68.8 vs. 30.8%; p = 0.023). Receipt of a cesarean after labor did not differ for PWWE compared to PC or by type of antiepileptic drug among the PWWE. Conclusion These findings suggest that the obstetrical experiences of PWWE and PC are similar. An interesting deviation from this observation was the mode of delivery with higher unlabored cesarean rates occurring among PWWE in nonrecruitment hospitals. As the study recruitment hospitals were tertiary academic centers and nonrecruitment hospitals tended to be community-based institutions, differences in perinatal expertise might contribute to this difference. Key Points Unlabored cesarean rates higher among women with epilepsy. Provider preference may influence delivery mode among women with epilepsy. Type and amount of antiepileptic drug was not associated with mode of delivery. [ABSTRACT FROM AUTHOR]

Background: First deliveries in women older than 35, 40, or 45 years are at increased risk for adverse pregnancy outcomes compared with those in younger women. However, specific relationships between each additional year of maternal age and pregnancy risks remain unclear, and absolute risks at each maternal age are not known.Methods: Using a population-based cohort of nulliparous women in British Columbia, Canada, from 2004 to 2014 (n = 203,414), We examined relationships between maternal age (modeled flexibly to allow curvilinear shapes) and pregnancy outcomes using logistic regression. We plotted absolute predicted risks to display curves from age 20 to 50 estimated for two risk profiles: (1) population average values of all risk factors; (2) a low-risk profile without preexisting diabetes/hypertension, smoking, prior spontaneous/therapeutic abortion, diagnosed infertility, inadequate prenatal care, low income, rural residence, or obesity.Results: Risks of hypertensive disorders increased gradually until age 35, then accelerated. Risk of multiple gestations, major congenital anomalies, and maternal mortality or severe morbidity increased slowly until age 30, then accelerated. Cesarean delivery and gestational diabetes risks increased linearly with age. While indicated preterm delivery increased rapidly with maternal age, spontaneous preterm delivery did not. Stillbirth, neonatal mortality, and infant mortality had j-shaped relationships with maternal age, with nadirs near 30. Despite age-related increases, risks of severe outcomes remained low for women 35 and 40: < 1-2% for severe maternal morbidity and 5-7% for fetal-infant composite.Conclusions: This study provides risks for specific maternal ages to inform clinical counseling and public health messaging regarding the potential implications of delayed childbearing. [ABSTRACT FROM AUTHOR]

Background: The associations of individual antiepileptic drugs (AEDs) with pregnancy duration and size at birth, and potential dose relations, are not well characterized. Methods: This cohort study used nationwide Swedish register data (1996–2013). Adjusting for smoking, epilepsy and other AED indications, we used linear and quantile regression to explore associations with pregnancy duration, and birth weight, length, and head circumference (the last three operationalized as z-scores). We used logistic regression for preterm delivery, small for gestational age, and microcephaly. Lamotrigine was the reference drug. Results: 6,720 infants were exposed to AEDs in utero; AED exposure increased over the study period. Relative to lamotrigine-exposed infants, carbamazepine-exposed infants were born, on average, 1.3 days earlier (mean [95% confidence interval]: -1.3 [-2.3 to -0.3]); were 0.1 standard deviations (SDs) lighter (-0.1 [-0.2 to 0.0]); and had a head circumference that was 0.2 SDs smaller (-0.2 [-0.3 to -0.1]). Pregabalin-exposed infants were born, on average, 1.1 days earlier (-1.1 [-3.0 to 0.8]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had the same head circumference as lamotrigine-exposed infants. Levetiracetam-exposed infants were born, on average, 0.5 days earlier (-0.5 [-2.6 to 1.6]); were 0.1 SDs lighter (-0.1 [-0.3 to 0.0]); and had a head circumference 0.1 SDs smaller (-0.1 [-0.3 to 0.1]). Valproic acid–exposed infants had, on average, the same duration of gestation and birth weight z-score as lamotrigine-exposed infants, but had a head circumference 0.2 SDs smaller (-0.2 [-0.2 to -0.1]). Associations between carbamazepine exposure and pregnancy duration and between valproic acid exposure and pregnancy duration and birth weight z-score were more negative at the left than at the right tails of the outcome distributions. Effect-measure modification and dose-response relations were noted for some of the associations. Conclusions: Relative to lamotrigine, valproic acid and carbamazepine were associated with smaller head circumference. [ABSTRACT FROM AUTHOR]

Preterm birth is a major public health problem, especially in Puerto Rico where the rates are among the highest observed worldwide, reaching 18% in 2011. The Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) study is an ongoing investigation of environmental factors that contribute to this condition. In the present analysis, we sought to examine common risk factors for preterm birth and other adverse birth outcomes which have not been characterized previously in this unique population. Pregnant women from the PROTECT cohort are recruited from the heavily contaminated Northern coast of the island of Puerto Rico and are free of pre-existing conditions like diabetes. We examined associations between basic demographic, behavioral (e.g., tobacco and alcohol use), and pregnancy (e.g., season and year of delivery) characteristics as well as municipality of residence in relation to preterm birth (<37 weeks gestation), postterm birth (≥41 weeks gestation), and small and large for gestational age in univariate and multivariate logistic regression models. Between 2011 and 2017, 1028 live singleton births were delivered as part of the PROTECT cohort. Of these, 107 (10%) were preterm. Preterm birth rates were higher among women with low socioeconomic status, as indicated by education level and income, and among women with high pre-pregnancy body mass index (BMI). Odds ratios of small for gestational age delivery were higher for women who reported tobacco use in pregnancy and lower for women who delivered in the hurricane and dengue season (July-October). Overall, in pregnant women residing in Puerto Rico, socioeconomic status was associated with preterm birth but few other factors were associated with this or other adverse outcomes of pregnancy. Research to understand environmental factors that could be contributing to the preterm birth epidemic in Puerto Rico is necessary. [ABSTRACT FROM AUTHOR]

Study Question: Is there an increased risk of unplanned peripartum hysterectomy in pregnancies with assissted reproductive technology compared to those without ART?Summary Answer: Although the absolute risks are low, there is an almost five-fold increased risk of unplanned peripartum hysterectomy and 1.7 more unplanned peripartum hysterectomies occur per 1000 deliveries in pregnancies with ART compared to those without ART.What Is Known Already: It has been reported that pregnancies with ART was associated with increased risk of peripartum hysterectomy in one case-control study and in one cohort study.Study Design, Size, Duration: A retrospective cohort study was conducted using a birth cohort from 2014 and 2015 in the United States, which includes more than 7 million births. Propensity score (PS) matching was used to control for confounding.Participants/materials, Setting, Methods: Subjects were divided into two groups: pregnancies with and without ART. We calculated PSs with demographic, clinical and socioeconomic variables, and subjects were matched using the PS with a 1:1 ratio. Subjects comprised 43868 ART pregnancies and 43868 non-ART pregnancies after PS matching. The primary outcome of interest was the risk of unplanned peripartum hysterectomy which was compared by evaluating the relative risk and the risk difference between the two groups after PS matching.Main Results and the Role Of Chance: Baseline characteristics were similar between groups after PS matching. The risk of peripartum hysterectomy in women with ART was 4.947 times that of those without ART (0.0021 [94/43868] vs 0.0004 [19/43868]; 95% confidence interval [CI] 3.022-8.098). The risk difference between two groups was 0.0017 (95% CI 0.0012-0.0022).Limitations, Reasons For Caution: There is a possibility of bias due to unmeasured confounding such as fibroids, previous history of uterine surgery and intrauterine procedures. Misclassification of the exposure and/or the outcome could also influence the results.Wider Implications Of the Findings: Although we found a five-fold increased risk of unplanned peripartum hysterectomy in pregnancies with ART compared to those without ART, the results should be interpreted with caution in a clinical context as the overall number and the absolute risk of unplanned peripartum hysterectomy are very low in either group (1/2325 in the non-ART group, and 1/468 in the ART group). However, it would be appropriate as future research agenda to explore mechanisms and/or etiology underlying this finding.Study Funding/competing Interest(s): No external funding was used and there are no competing interests.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Pregnant women and their fetuses represent susceptible populations to environmental contaminants. Exposure to polycyclic aromatic hydrocarbons (PAHs) among pregnant women may contribute to adverse birth outcomes such as preterm birth. Multiple previous studies have assessed airborne sources of PAHs among pregnant women but few have measured urinary PAH metabolites which can capture total exposure through multiple routes. The aim of this study was to bridge this knowledge gap by assessing longitudinal urinary PAH metabolite concentrations over two time points in pregnancy cohorts in Boston (N = 200) and Puerto Rico (N = 50) to better understand exposure distributions throughout pregnancy and how they relate to demographic factors. Urine samples were analyzed for 1-NAP, 2-NAP, 2-FLU, 1-PHE, 2,3-PHE, 4-PHE, 9-PHE, and 1-PYR. Concentrations of 2-NAP, 1-PYR, and 4-PHE were higher in Puerto Rico, while all other metabolites were present in higher concentrations in Boston. In Puerto Rico, intraclass correlation coefficients (ICC) were weak to moderate, ranging from 0.06 to 0.42. PAH metabolite concentrations were significantly higher among younger, heavier (except 1-NAP and 9-PHE), and less educated individuals in Boston only. Consistent significant associations between PAH concentrations and measured covariates were not found in Puerto Rico. Our results suggest that potentially important differences in PAH exposure exist between these two populations. Additionally, our results indicate that multiple urinary measurements are required to accurately assess PAH exposure throughout pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Plasma glycated CD59 (pGCD59) is an emerging biomarker in diabetes. We assessed whether pGCD59 could predict the following: the results of the glucose challenge test (GCT) for screening of gestational diabetes mellitus (GDM) (primary analysis); and the diagnosis of GDM and prevalence of large for gestational age (LGA) newborns (secondary analyses).Research Design and Methods: Case-control study of 1,000 plasma samples from women receiving standard prenatal care, 500 women having a normal GCT (control subjects) and 500 women with a failed GCT and a subsequent oral glucose tolerance test (case patients).Results: Compared with control subjects, the median (interquartile range) pGCD59 value was 8.5-fold higher in case patients and 10-fold higher in GDM patients, as follows: control subjects 0.33 (0.19); case patients 2.79 (1.4); GDM patients 3.23 (1.43) (P < 0.001); area under the receiver operating characteristic curve 0.92. LGA prevalence was 4.3% in the lowest quartile and 13.5% in the highest quartile of pGCD59.Conclusions: One pGCD59 measurement during weeks 24-28 identifies pregnancy-induced glucose intolerance with high sensitivity and specificity and can potentially identify the risk for LGA. [ABSTRACT FROM AUTHOR]

Introduction: Overt thyroid disease in pregnancy is associated with numerous maternal and neonatal complications including preterm birth. Less is known about the contribution of trimester-specific subclinical alterations in individual thyroid hormones, especially in late gestation, on the risk of preterm birth. Herein, we examined the associations between subclinical changes in maternal thyroid hormone concentrations (TSH, total T3, free and total T4), measured at multiple time points in pregnancy, and the odds of preterm birth in pregnant women without clinical thyroid disease. Participants and Methods: Data were obtained from pregnant women participating in a nested case-control study of preterm birth within on ongoing birth cohort study at Brigham and Women’s Hospital in Boston, MA (N = 439; 116 cases and 323 controls). We measured thyroid hormones in plasma collected at up to four time points in pregnancy (median = 10, 18, 26, and 35 weeks). We used multivariate logistic regression models stratified by study visit of sample collection to examine associations. To reveal potential biological pathways, we also explored these relationships by obstetric presentation of preterm birth (e.g., spontaneous preterm delivery) that have been previously hypothesized to share common underlying mechanisms. Results: In samples collected at median 10 and 26 weeks of gestation, we found inverse associations between FT4 and the odds of overall preterm birth (odds ratio [OR] = 0.57, 95% confidence interval (CI) = 0.33, 1.00; and OR = 0.53, 95% CI = 0.34, 0.84, respectively). Positive associations were detected for total T3 at these same time points (OR = 2.52, 95% CI = 1.20, 5.31; and OR = 3.40, 95% CI = 1.56, 7.40, respectively). These effect estimates were stronger for spontaneous preterm birth. Conclusions: Our results suggest that subclinical alterations in individual maternal thyroid hormones may influence the risk of preterm birth, and the strength of these associations vary by gestational age. [ABSTRACT FROM AUTHOR]

Problem We assess whether inflammatory and oxidative stress markers early in pregnancy are associated with decreasing cervical length in the second trimester. Method of study This is a secondary analysis of a nested case-control study of preterm birth conducted at a tertiary care center from 2006 to 2008. Plasma inflammatory markers included the following: interleukin-6 ( IL-6), interleukin-10 ( IL-10), interleukin-1 beta ( IL-1β), tumor necrosis factor alpha ( TNF-α), and C-reactive protein ( CRP); and urine oxidative stress markers included the following: 8-hydroxydeoxyguanosine (8- OHdG) and 8-isoprostane, measured at two study visits (median 10 and 18 weeks of gestation). The primary outcome was cervical length<10th percentile measured between 16 and 24 weeks of gestation. Logistic regression models were used, adjusting for body mass index, age, race, parity, tobacco use, education, and gestational age at cervical length measurement. Results Among 384 observed women, the 10th percentile cervical length was 3.0 cm. IL-10 levels were significantly higher among women with a cervical length<10th percentile compared to women with a longer cervix (mean IL-10: 95.5 vs 25.8 pg/mL, P<.01). Similarly, IL-6 levels were significantly higher among women with a cervical length<10th percentile (mean IL-6: 25.2 vs 4.3 pg/mL, P<.01). After controlling for potential confounders, an increase in IL-10 was significantly associated with a cervical length<10th percentile at both 10 and 18 weeks (adjusted odd ratio [ AOR]: 1.74; 95% CI: 1.18-2.58; P=.005). At 18 weeks, only IL-6 was also significantly associated with a cervical length<10th percentile ( AOR: 1.54; 95% CI: 1.11-2.13; P=.009). Other inflammatory biomarkers, including CRP, IL-1β, TNF-α, and oxidative stress biomarkers, 8- OHdG and 8-isoprostane, were not associated with cervical length. Conclusion There was a significant association between the cytokines IL-6 and IL-10 early in pregnancy and decreased cervical length, suggesting an imbalance of immune regulation could impact cervical length. [ABSTRACT FROM AUTHOR]

Background Previous studies have shown an association between total excessive gestational weight gain and hypertension in pregnancy. However, this may be a reflection of excessive water retention associated with the pathophysiology of hypertensive disorders of pregnancy. Early excessive weight gain, prior to the third trimester, results in greater maternal fat deposition and inflammation, which has also been associated with the development of hypertension. By focusing on early excessive weight gain, the association between maternal weight gain and the future development of hypertension can be examined. Objective To evaluate the association between early excessive maternal weight gain and the development of hypertension during pregnancy. Study Design This was a secondary analysis of a longitudinal cohort study of 1,441 women without chronic hypertension who were enrolled in a prospective study evaluating maternal angiogenic factors and the prediction of preeclampsia. Initial body mass index (BMI) was calculated by weight and height at the first study visit. Early excessive maternal weight gain was defined as weight gain by 28 weeks that exceeded the Institute of Medicine (IOM) guidelines and was calculated utilizing the maximum amount of weight gain per week recommended by the IOM based on the patient's starting BMI (normal: 0.45 kg; overweight: 0.32 kg; obese: 0.27 kg). Hypertension was defined as a sustained systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg. Logistic regression was used to determine the association between early excessive weight gain, initial BMI, and the development of hypertension, including gestational hypertension and preeclampsia, during pregnancy. Results Of 1,441 women, 767 (53.2%) had weight gain that exceeded the IOM guidelines in the first 28 weeks and 154 (10.8%) developed hypertension during pregnancy. Women whose weight gain exceeded the IOM guidelines were more likely to develop hypertension even after adjusting for relevant confounders (12.5 vs. 8.6%; p = 0.02; adjusted odds ratio [OR] = 1.70; 95% confidence interval [CI]: 1.18-2.44; p < 0.01). Obese women had a 2.4-fold increased risk of developing hypertension, even after controlling for excessive weight gain (adjusted OR = 2.44; 95% CI: 1.66-3.59; p < 0.01) Conclusions Early excessive maternal weight gain and initial BMI are independently associated with the diagnosis of a hypertensive disorder of pregnancy. Women should be counseled regarding the benefits of achieving a normal BMI prior to pregnancy and appropriate weight gain during pregnancy, as well as the potential harms of excessive weight gain related to perinatal outcomes. [ABSTRACT FROM AUTHOR]

Impaired or suboptimal fetal growth is associated with an increased risk of perinatal morbidity and mortality. By utilizing readily available clinical data on the relative size of the fetus at multiple points in pregnancy, including delivery, future epidemiological research can improve our understanding of the impacts of maternal, fetal, and environmental factors on fetal growth at different windows during pregnancy. This study presents mean and standard deviation ultrasound measurements from a clinically representative US population that can be utilized for creating Z-scores to this end. Between 2006 and 2012, 18, 904 non-anomalous pregnancies that received prenatal care, first and second trimester ultrasound evaluations, and ultimately delivered singleton newborns at Brigham and Women’s hospital in Boston were used to create the standard population. To illustrate the utility of this standard, we created Z-scores for ultrasound and delivery measurements for a cohort study population and examined associations with factors known to be associated with fetal growth. In addition to cross-sectional regression models, we created linear mixed models and generalized additive mixed models to illustrate how these scores can be utilized longitudinally and for the identification of windows of susceptibility. After adjustment for a priori confounders, maternal BMI was positively associated with increased fetal size beginning in the second trimester in cross-sectional models. Female infants and maternal smoking were associated with consistently reduced fetal size in the longitudinal models. Maternal age had a non-significant association with increased size in the first trimester that was attenuated as gestation progressed. As the growth measurements examined here are widely available in contemporary obstetrical practice, these data may be abstracted from medical records by investigators and standardized with the population means presented here. This will enable easy extension of clinical data to epidemiologic studies investigating novel maternal, fetal, and environmental factors that may impact fetal growth. [ABSTRACT FROM AUTHOR]

Background: We designed and tested the validity of a questionnaire to characterize maternal recall of pregnancy complications associated with increased future cardiovascular disease risk, based on the 2011 American Heart Association (AHA) guidelines. Methods: A maternal recall questionnaire of pregnancy history was administered to 971 patients who had participated in a previous cohort study of 1,608 pregnant women. Medical records from the study pregnancy served as the gold standard. Prevalence, sensitivity (sens), specificity (spec), positive predictive value (PPV), negative predictive value (NPV), and/or Spearman's correlation coefficients ( r) were calculated for each question. Results: A total of 526 (54%) individuals recontacted responded. Respondents were more likely to be older, white, educated, and nulliparous and were less likely to deliver low-birthweight infants in the study pregnancy than were individuals who did not respond. Mean length of recall was 4.35 years (standard deviation [SD] 0.46) postpartum. Maternal recall was most accurate for gestational diabetes (sens: 92%, spec: 98%, PPV: 79%, NPV: 99%), infant birthweight ( r=0.95), and gestation length ( r=0.85). Maternal recall was modest for preeclampsia (sens: 79%, spec: 97%, PPV: 68%, NPV: 98%) and pregnancy-associated hypertension, including preeclampsia or gestational hypertension (sens: 60%, spec: 95%, PPV: 64%, NPV: 94%). Conclusions: This validation study demonstrated that the majority of women could accurately recall a history of gestational diabetes, infant birthweight, and gestational age at delivery, 4 years postpartum on average. Recall of preeclampsia and pregnancy-associated hypertension overall was modest. Maternal report of these pregnancy conditions may help clinicians identify women at increased risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: It is of critical importance to evaluate the role of environmental chemical exposures in premature birth. While a number of studies investigate this relationship, most utilize single exposure measurements during pregnancy in association with the outcome. The studies with repeated measures of exposure during pregnancy employ primarily cross-sectional analyses that may not be fully leveraging the power and additional information that the data provide. Methods: We examine 9 statistical methods that may be utilized to estimate the relationship between a longitudinal exposure and a binary, non-time-varying outcome. To exemplify these methods we utilized data from a nested case-control study examining repeated measures of urinary phthalate metabolites during pregnancy in association with preterm birth. Results: The methods summarized may be useful for: 1) Examining sensitive windows of exposure in association with an outcome; 2) Summarizing repeated measures to estimate the relationship between average exposure and an outcome; 3) Identifying acute exposures that may be relevant to the outcome; and 4) Understanding the contribution of temporal patterns in exposure levels to the outcome of interest. In the study of phthalates, changes in urinary metabolites over pregnancy did not appear to contribute significantly to preterm birth, making summary of average exposure across gestation optimal given the current design. Conclusions: The methods exemplified may be of great use in future epidemiologic research projects intended to: 1) Elucidate the complex relationships between environmental chemical exposures and preterm birth; 2) Investigate biological mechanisms in prematurity using repeated measures of maternal factors throughout pregnancy; and 3) More generally, address the relationship between a longitudinal predictor and a binary, non-time-varying outcome. [ABSTRACT FROM AUTHOR]

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

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

Objective: To explore (1) whether extremely low gestational age newborns exposed to inflammation-associated pregnancy disorders differ in retinopathy of prematurity (ROP) risk from infants exposed to placenta dysfunction-associated disorders, and (2) whether ROP risk associated with postnatal hyperoxemia and bacteremia differs among infants exposed to these disorders. Methods: Pregnancy disorders resulting in preterm birth include inflammation-associated: preterm labor, prelabor premature rupture of membranes (pPROM), cervical insufficiency, and abruption and placenta dysfunction-associated: preeclampsia and fetal indication. The risk of severe ROP associated with pregnancy disorders was evaluated by multivariable analyses in strata defined by potential effect modifiers, postnatal hyperoxemia and bacteremia. Results: Compared to preterm labor, infants delivered after pPROM were at reduced risk of plus disease (Odds ratio = 0.4, 95% confidence interval: 0.2-0.8) and prethreshold/threshold ROP (0.5, 0.3-0.8). Infants delivered after abruption had reduced risk of zone I ROP (0.2, 0.1-0.8) and prethreshold/threshold ROP (0.3, 0.1-0.7). In stratified analyses, infants born after placenta dysfunction had higher risks of severe ROP associated with subsequent postnatal hyperoxemia and bacteremia than infants born after inflammation-associated pregnancy disorders. Conclusion: Infants exposed to placenta dysfunction have an increased risk of severe ROP following postnatal hyperoxemia and bacteremia compared to infants exposed to inflammation-associated pregnancy disorders. [ABSTRACT FROM AUTHOR]

Citation Faupel-Badger JM, Fichorova RN, Allred EN, Hecht JL, Dammann O, Leviton A, McElrath TF. Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation. Am J Reprod Immunol 2011; 66: 488-494 Problem Inflammation within the preterm placenta is common and leads to adverse outcomes for premature infants. The risks of complications are different between iatrogenic (e.g. PE) and spontaneous (e.g. PL and membrane rupture) causes of preterm delivery, suggesting different underlying biology contributes to these placental conditions. Method of study Thirty preterm singleton placentas from the following groups were analyzed: (i) severe PE, (ii) preterm premature membrane rupture (pPROM), and (iii) PL. Proinflammatory and anti-inflammatory cytokines, adhesion and angiogenic molecules were measured in placental lysates using a multiplex assay. K-means cluster analysis was used to generate patterns of protein level intensity. Results Three cluster patterns were apparent. Placentas from PE had high levels of vascular endothelial growth factor (VEGF) combined with low levels of acute inflammatory proteins (IL-1β, IL-18, IL-6, TNF-α), low IL-1 RA, and high transforming growth factor β (TGF-β). PL and pPROM had higher anti-inflammatory IL-1 RA and thrombomodulin combined with lower VEGF, regardless of proinflammatory cytokines and adhesion molecules. Half of the PL and pPROM cases had clusters of heightened inflammatory responses (lower TGF-β clustered with higher intensity of inflammatory mediators). Conclusion Discriminating protein patterns were elucidated and may serve as a foundation from which to understand the biologic mechanisms underlying these pregnancy complications. [ABSTRACT FROM AUTHOR]

In a 2002–2004 prospective cohort study of deliveries of infants at <28 weeks at 14 US centers, the authors sought the antecedents of white matter damage evident in newborn cranial ultrasound scans (ventriculomegaly and an echolucent lesion) and of cerebral palsy diagnoses at age 2 years. Of the 1,455 infants enrolled, those whose mothers received an antenatal steroid tended to have lower risks of ventriculomegaly and an echolucent lesion than their peers (10% vs. 23%, P < 0.001 and 7% vs. 11%, P = 0.06, respectively). Risk of ventriculomegaly was increased for infants delivered because of preterm labor (adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI): 1.1, 4.9), preterm premature rupture of fetal membranes (OR = 3.6, 95% CI: 1.5, 8.7), and cervical insufficiency (OR = 2.8, 95% CI: 1.4, 5.5) when compared with infants delivered because of preeclampsia. Risk of an echolucent lesion was increased for infants delivered because of preterm labor (OR = 2.7, 95% CI: 1.2, 5.7) and intrauterine growth retardation (OR = 3.3, 95% CI: 1.2, 9.4). The doubling of diparesis risk associated with preterm labor and with preterm premature rupture of fetal membranes did not achieve statistical significance, nor did the doubling of quadriparesis risk and the tripling of diparesis risk associated with cervical insufficiency. [ABSTRACT FROM PUBLISHER]

Objectives: Few studies have examined factors associated with compliance with a postpartum visit (PPV). The identification of such factors is of particular importance in populations with high rates of unintended pregnancies and medical complications of pregnancy. This study seeks to determine factors associated with compliance with a PPV among low-income women in the population served by fourteen Healthy Start sites. Methods: Data from the Healthy Start Survey of Postpartum Women were reviewed to identify variables associated with compliance with a PPV at or beyond 6 weeks. Multiple logistic regression models were created, based on a sociobehavioral model of health services use, to examine which types of factors (demographic, social, enabling or need) are most strongly associated with the use of a PPV. Results: The study population consisted of survey respondents interviewed six weeks or more following delivery. Eighty-five percent of respondents had had a PPV at time of interview. In a multiple regression analysis, enabling factors such as multiple moves (OR (95% CI)=0.34 (0.18, 0.67)), trouble understanding the provider (OR (95% CI)=0.65 (0.43, 0.99)) and appointment reminders (OR (95% CI)=2.37 (1.40, 4.02)) were most strongly associated with a PPV. Conclusions: This work finds that women with unstable housing, transportation barriers, and difficulties communicating with providers are at risk for not receiving a PPV. This suggests that access to postpartum health services in the Healthy Start communities studied may not be entirely equitable. Policies aimed at improving interconception care will need to address these barriers to accessing health services. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Neonatal respiratory distress syndrome (RDS) affects approximately 1% of live births, and the probability of RDS continues to be a major determinant in the timing of delivery. This study was designed to investigate the optimal gestational age-specific cutoff value for a surfactant-to-albumin ratio assay for predicting RDS. METHODS: Amniotic fluid surfactant-to-albumin ratio data were collected prospectively for a 2-year period. Women were included in the study if they delivered within 72 hours of surfactant-to-albumin ratio estimation. RDS was defined by the presence of 2 or more of the following criteria: evidence of respiratory compromise shortly after delivery and a persistent oxygen requirement for more than 24 hours, administration of exogenous pulmonary surfactant, and/or radiographic evidence of hyaline membrane disease. RESULTS: A total of 415 mother-neonate pairs (28 RDS, 387 non-RDS) met criteria for analysis. Both gestational age and surfactant-to-albumin ratio values were independent predictors of RDS. By modeling the odds of RDS by using a logistic regression with gestational age and surfactant-to-albumin ratio values as continuous variables, a probability of RDS of 150/0 or less can be achieved with a surfactant-to-albumin ratio cutoff of 60 mg or more surfactant-to-albumin at 28 weeks of gestation, 50 or more at 30 weeks, 40 or more at 33 weeks, 30 or more at 35 weeks, and 20 or more at 37 weeks. CONCLUSIONS: These data describe a means of stratifying the probability of neonatal RDS using both gestational age and surfactant-to-albumin ratio value and may be a useful model for clinical decision-making. [ABSTRACT FROM AUTHOR]

Examines the impact of retention of cerclage after premature rupture of the membranes occurring before 34 weeks' gestation on pregnancy outcomes. Association between retention of cervical cerclage after premature rupture of membranes occurring before 34 weeks' gestation and comparable clinical outcomes with respect to latency and perinatal outcome.

The article discusses various reports published within the issue, including one on the population-level examination of cervical insufficiency and one on pregnancy complications on birth certificates.

Several studies have linked maternal asthma, excess BMI, and low vitamin D status with increased risk of Preeclampsia (PE) development. Given prior evidence in the literature and our observations from the subjects in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we hypothesized that PE, maternal asthma, vitamin D insufficiency, and excess body mass index (BMI) might share both peripheral blood and placental gene signatures that link these conditions together. We used samples collected in the VDAART to investigate relationships between these four conditions and gene expression patterns in peripheral blood obtained at early pregnancy. We identified a core set of differentially expressed genes in all comparisons between women with and without these four conditions and confirmed them in two separate sets of samples. We confirmed the differential expression of the shared gene signatures in the placenta from an independent study of preeclampsia cases and controls and constructed the preeclampsia module using protein–protein interaction networks. CXC chemokine genes showed the highest degrees of connectivity and betweenness centrality in the peripheral blood and placental modules. The shared gene signatures demonstrate the biological pathways involved in preeclampsia at the pre-clinical stage and may be used for the prediction of preeclampsia. [ABSTRACT FROM AUTHOR]

Problem: Perturbations in normal fetal growth during pregnancy are associated with poor child and adult health outcomes. Inflammation and oxidative stress are recognized as important mechanisms in preeclampsia and preterm birth but have been examined less in relation to fetal growth. We hypothesized that maternal inflammation and oxidative stress in pregnancy would be associated with reduced fetal growth and sought to identify windows of vulnerability. Method of study: In a secondary analysis of 482 women from the LIFECODES birth cohort study, we measured inflammation (C‐reactive protein [CRP] and the cytokines IL‐1β, IL‐6, IL‐10, and TNF‐α) and oxidative stress (8‐isoprostane and 8‐hydroxydeoxyguanosine [8‐OHdG]) biomarkers in plasma and urine, respectively, at four time points during pregnancy. We examined associations between repeated measures of each marker and ultrasound (head and abdominal circumference, femur length, and a summary measure of estimated fetal weight) as well as delivery (birthweight) metrics of growth. Results: In adjusted repeated‐measures models, an interquartile range (IQR) increase in CRP was associated with a 0.12 standard deviation decrease in fetal weight z‐score (95% confidence interval, CI, −0.21, −0.02), which corresponds to approximately 50 g at 40‐week gestation. The association was greatest in magnitude (ie, most negative) with CRP measured later in pregnancy. Oxidative stress markers were not associated with fetal weight, although both were inversely associated with head circumference and femur length. Conclusion: Inflammation and oxidative stress markers measured later in pregnancy were associated with reduced fetal growth as measured by repeated ultrasound scans. [ABSTRACT FROM AUTHOR]

Background: Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of preeclampsia (PE) remains elusive. The pathophysiology of PE is believed to involve aberrant placentation and an associated increase in systemic inflammation. In this conceptualization, PE becomes more likely when the level of systemic inflammatory burden inherent in pregnancy itself exceeds the maternal capacity to compensate for this additional stress. If this is the case, then it is possible to hypothesize that conditions, such as infectious disease, that increase systemic inflammatory burden should also increase the risk of PE. As urinary tract infection (UTI) represents a common source of inflammation during pregnancy, we tested whether presence of UTI during pregnancy increased the odds of developing PE. Prior work has documented this association. However many of these studies were limited by small cohort sizes and insufficient control for covariates. Objective: The present study is a secondary analysis of a robust contemporary obstetrical cohort recruited to examine the ability of longitudinally sampled maternal angiogenic concentrations to predict PE. We hypothesize that the occurrence of UTI during a pregnancy is associated with the later occurrence of PE in that pregnancy. As PE is believed to be associated with aberrations in systemic angiogenic levels (placental growth factor and soluble isoform of VEGF receptor), we further hypothesize that there will be significant interactions between maternal angiogenic protein levels and the occurrence of UTI. Study Design: Women aged ≥18 years (n = 2607) were recruited and followed up prospectively from the initiation of prenatal care through delivery at 3 regional academic centers. PE was defined by American Congress of Obstetricians and Gynecologists criteria and was independently validated by a panel of physicians. UTI was defined by the presence of clinical symptoms necessitating treatment in addition to supportive laboratory evidence. Multivariate logistic regression models were used and controlled for maternal age, race, parity, body mass index, hypertension, diabetes, in vitro fertilization, and smoking status. Results: There were 129 women with diagnosed UTIs and 235 with PE. Patients with UTI in pregnancy had higher rates of PE (31.1% vs 7.8%, P < .001) compared to those without reported UTI. The mean gestational age (SD) for UTI diagnosis in PE cases and controls was 25.6 (10.4) and 21.9 (10.9) weeks, respectively (P = .08). The unadjusted odds ratio for PE in the setting of UTI was 5.29 (95% confidence interval, 3.54-7.89). After controlling for confounders, UTI was associated with an odds ratio for PE of 3.2 (95% confidence interval, 2.0-5.1). Conclusion: Presence of UTI in pregnancy, particularly in the third trimester, is strongly associated with PE. This association supports the hypothesis that the risk of PE is enhanced by an increased maternal inflammatory burden. Prophylaxis against UTI represents a potentially low-cost global intervention to slow or halt the development of PE. [ABSTRACT FROM AUTHOR]

Objective Pregnancies that have been conceived through in vitro fertilization (IVF) have been associated with higher rates of preeclampsia and other complications that are associated with placental dysfunction. We evaluated whether IVF pregnancies, when compared with those conceived spontaneously, would be associated with alterations in serum angiogenic markers. Study Design This was a retrospective cohort study from 3 US academic institutions (2006-2008). Women with singleton pregnancies who conceived via IVF or spontaneously were included. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 4 time points throughout gestation. Pregnancy outcomes that included diagnosis of preeclampsia or other obstetric complications were ascertained from the medical record. The relationship among IVF status, PlGF, and sFlt-1 were modeled over gestation and stratified by clinical pregnancy outcome. Results Of the included 2392 singleton pregnancies, 4.5% (108 pregnancies) were conceived though IVF. IVF pregnancies were significantly more likely to be complicated by preeclampsia (15.7% vs 7.7%). IVF pregnancies had significantly higher levels of sFlt-1 at 18, 26, and 35 weeks of gestation ( P = .04, P = .004, P < .0001, respectively) and lower levels of PlGF at 18 and 35 weeks of gestation ( P = .007 and .0006, respectively). These differences persisted even after being controlled for maternal comorbidities or obstetric outcomes such as preeclampsia. Conclusion Pregnancies conceived via IVF were found to have an increased antiangiogenic profile (elevated sFlt-1 and decreased PlGF) at multiple time points throughout gestation when compared with spontaneously conceived pregnancies. Alterations in the angiogenic profile persisted even after we controlled for maternal comorbidities of clinically evident disorders of abnormal placentation such as preeclampsia. The increased antiangiogenic profile suggests fundamentally aberrant placentation related to in vitro fertilization, which may warrant closer fetal surveillance in these pregnancies. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine whether longitudinally sampled maternal angiogenic concentrations predict preeclampsia. Study Design: Plasma sFlt-1 and placental growth factor (PlGF) concentrations in healthy pregnant women were quantified at 10, 17, 25, and 35 weeks'' gestation. Preeclampsia was diagnosed with criteria from the American College of Obstetricians and Gynecologists. Results: In the first trimester, sensitivity/specificity for PlGF and sFlt-1 were 55/43% and 57/40%, respectively, and did not improve appreciably as the pregnancy progressed. Among pregnancies that later experienced preeclampsia, median PlGF was lower beginning in the second trimester, but sFlt-1 was not higher until the third trimester. Analyte positive predictive values approached 10% in the third trimester. Negative predictive values were >90% for the entire pregnancy. Conclusion: Prediction of preeclampsia in early pregnancy was not possible with the use of maternal angiogenic protein concentrations. Even in late pregnancy, positive predictive values were not useful clinically. Negative predictive values are similarly unlikely to prove useful as a tool with which to a rule out suspected disease. [Copyright &y& Elsevier]

Objective: Disorders that lead to preterm delivery influence the fetal inflammatory response. Study Design: We calculated odds ratios of elevated concentrations of 25 blood proteins on the first postnatal day in 798 infants born before the 28th week and classified by the pregnancy disorder that lead to preterm delivery. Results: Concentrations of cytokines (IL-1β, IL-6, TNFα), cytokine receptors (IL-6R, TNF-R1, TNF-R2), systemic inflammatory proteins (CRP, SAA, MPO), chemokines (IL-8, MCP-1, MCP-4, MIP-1β, RANTES, I-TAC), adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin), and metalloproteinases (MMP-1, MMP-9) were elevated in children delivered after preterm labor, membrane rupture, abruption, and cervical insufficiency, whereas such a pattern was not seen after preeclampsia or fetal indication/growth restriction. Inflammatory profiles were also associated with maternal vaginitis. Conclusion: The patterns of blood proteins in the newborn support the division of pregnancy disorders that lead to preterm delivery into those associated, and those not associated, with inflammation. [ABSTRACT FROM AUTHOR]

Objective: Patients with transabdominal cerclage in place present a management challenge in the setting of undesired pregnancy, pregnancy failure, or pre-viable pregnancy complications. Literature that guides safe surgical technique for uterine evacuation is sparse. This study sought to describe the management and safety profile of dilation and curettage (D&C) and dilation and evacuation (D&E) in patients with transabdominal cerclage.Study Design: We used hospital billing records to identify patients with history of transabdominal cerclage placed between January 1998 and August 2019. We subsequently described the patient characteristics and surgical techniques of the procedures among those who underwent uterine evacuation.Results: Of the 142 patients with an abdominal cerclage placed at our institution, fourteen had subsequent uterine aspiration for a total of 19 procedures over the study period. We describe fifteen D&C procedures in 11 patients between 5- and 12-weeks gestation, and four D&E procedures in three patients between 17- and 19-weeks gestation. Surgeons used osmotic dilators for cervical preparation and standard surgical techniques. There was one minor complication and no major complications. Three patients had procedures other than uterine evacuation.Conclusions: Dilation and curettage and D&E are reasonable potential methods of uterine evacuation in women with transabdominal cerclage.Implications Statement: This chart review suggests D&C and D&E are reasonable management options in the setting of transabdominal cerclage. Current practice guidelines should reflect the utilization of these procedures as potentially less invasive means of uterine evacuation. [ABSTRACT FROM AUTHOR]

Background Pregnancy exposure to bisphenol-A (BPA) may be associated with gestational diabetes (GDM), but evidence from human studies is limited. Moreover, adiposity is associated with both higher BPA concentrations and GDM risk, and may act as a confounder or an effect modifier of the association. Methods We included 350 term births from the Lifecodes pregnancy cohort (Boston, MA), who had 1st and 2nd trimester measures of urinary BPA concentrations available. BPA measures were SG-adjusted and categorized into quartiles (Q). Multivariable-adjusted linear regressions were used to determine the association between BPA, at both 1st and 2nd trimester, and glucose, in the overall population and by categories of 1st trimester BMI. Results No clear associations were seen between BPA and glucose levels in the overall population. From stratified analyses there was suggestive evidence of effect modification by maternal 1st trimester BMI, with significant associations observed among obese/overweight participants (1st trimester BPA concentrations for Q3 vs Q1: adj.β = 14.1 mg/dL; 95% CI: 1.5, 26.6) (2nd trimester BPA concentrations for Q2 vs Q1: adj. β = 16.9 mg/dL; 95% CI: 2.6, 31.2). Conclusion No associations were found between BPA and glucose levels in the overall population. However, moderately high BPA concentrations were associated with increased glucose levels among overweight/obese women—a subgroup at high-risk of elevated glucose levels in pregnancy. [ABSTRACT FROM AUTHOR]

Background Maternal supply of thyroid hormones during pregnancy serves a critical role in fetal development. Although animal and in vitro studies provide evidence for thyroid hormone disruption as a result of bisphenol A (BPA) exposure, there is still a lack of evidence in human studies, particularly in the context of pregnancy. Objectives We aimed to explore the associations between urinary BPA concentrations and plasma thyroid hormone parameters during gestation in pregnant women, and also investigated potential windows of vulnerability during gestation. Methods Our study population included 116 cases of preterm birth and 323 controls from a nested case-control study. We measured BPA in urine and thyroid hormone parameters in plasma samples collected at up to four study visits during pregnancy (median for each visit: 9.64, 17.9, 26.0, and 35.1 weeks gestation). We used linear mixed models for repeated measures analyses, and multivariate linear regression models stratified by study visit to explore potential windows of susceptibility. Results In our repeated measures analysis, BPA and thyrotropin (TSH) were inversely associated. An interquartile range (IQR) increase in BPA was associated with an 8.21% decrease in TSH (95% confidence interval [CI]: − 14.2, − 1.83), and a 4.79% increase in free T4 (95% CI: 0.82, 8.92). BPA and TSH were also inversely associated in our cross-sectional analyses at visits 3 and 4. Conclusions Our results suggest that TSH is inversely associated with urinary BPA in a consistent manner across pregnancy. Disruption of TSH levels during pregnancy can potentially impact child development and interfere with normal birth outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the evidence guiding management of multiple sclerosis (MS) in reproductive-aged women. DATA SOURCES: We conducted an electronic literature search using PubMed, ClinicalTrials.gov, and other available resources. The following keywords were used: "multiple sclerosis" and "pregnancy." We manually searched the reference lists of identified studies. METHODS OF STUDY SELECTION: Two reviewers categorized all studies identified in the search by management topic, including effect of pregnancy on MS course, fetal risks associated with disease-modifying treatments during pregnancy, and management of patients off disease-modifying treatment. We categorized studies by strength of evidence and included prior meta-analyses and systematic studies. These studies were then summarized and discussed by an expert multidisciplinary team. TABULATION, INTEGRATION, AND RESULTS: The risk of MS relapses is decreased during pregnancy and increased postpartum. Data are lacking regarding the risks of disease-modifying treatments during pregnancy. There may be an increased risk of MS relapses after use of assisted reproductive techniques. There does not appear to be a major increase in adverse outcomes in newborns of mothers with MS. CONCLUSION: Although there are many unmet research needs, the reviewed data support the conclusion that in the majority of cases, women with MS can safely choose to become pregnant, give birth, and breastfeed children. Clinical management should be individualized to optimize both the mother's reproductive outcomes and MS course. [ABSTRACT FROM AUTHOR]