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BACKGROUND There is a lack of consensus in the literature about the association between meal patterning during pregnancy and birth outcomes. This study examined whether maternal meal patterning in the week before birth was associated with an increased likelihood of imminent spontaneous labor. METHODS Data came from 607 participants in the third phase of the Pregnancy, Infection, and Nutrition Study (PIN3). Data were collected through an interviewer-administered questionnaire after birth, before hospital discharge. Questions included the typical number of meals and snacks consumed daily, during both the week before labor onset and the 24-hour period before labor onset. A self-matched, case-crossover study design examined the association between skipping one or more meals and the likelihood of spontaneous labor onset within the subsequent 24 hours. RESULTS Among women who experienced spontaneous labor, 87.0% reported routinely eating three daily meals (breakfast, lunch, and dinner) during the week before their labor began, but only 71.2% reported eating three meals during the 24-hour period before their labor began. Compared with the week before their labor, the odds of imminent spontaneous labor were 5.43 times as high (95% CI: 3.41-8.65) within 24 hours of skipping 1 or more meals. The association between skipping 1 or more meals and the onset of spontaneous labor remained elevated for both pregnant individuals who birthed early (37

Background To evaluate pregnancy outcomes among women participating in the antiepileptic drug (AED) Levetiracetam Registry (LEV-Registry), and to review the impact of using two other registries' outcome definitions on the number of major congenital malformations (MCMs). Methods This US-based prospective study (ClinicalTrials.gov NCT00345475) was overseen by an independent Expert Panel. Women exposed to levetiracetam at any time during pregnancy enrolled, directly, or via their healthcare provider. The primary outcome was prevalence of MCMs, defined according to a modified version of the Metropolitan Atlanta Congenital Defects Program criteria. Results Of 491 women enrolled, 465 (94.7%) had a documented outcome. Most (92.3%) received levetiracetam for epilepsy; 323 (69.4%) as monotherapy and 142 (30.5%) as polytherapy. With three twin pregnancies, there were 468 outcomes-444 livebirths, 3 stillbirths, 19 miscarriages, and 2 terminations. Based on the MCM definition used by LEV-Registry, 46 infants among 444 livebirths had MCMs resulting in 10.4% (95% CI 7.7, 13.6) for overall prevalence, 9.4% (95% CI 6.4, 13.2) with monotherapy, and 12.6% (95% CI 7.5, 19.4) with polytherapy. When MCM reports were reviewed independently by staff at EURAP (International Registry of AEDs) and North American AED Pregnancy Registry according to their respective criteria, only 22 and 7 infants of the 46, respectively, were classified as having MCMs. Conclusion The LEV-Registry Expert Panel did not find evidence suggestive of teratogenic association with prenatal exposure to levetiracetam. The substantial differences in which physical findings were considered MCMs highlight the major impact of pregnancy registry methodology on MCM prevalence estimates.

Up to 25% of postpartum women experience psychological distress including stress, depressive, or anxiety symptoms during the postpartum period. The purpose of this study was to explore the extent to which social determinants of health and allostatic load score, a 10-item index of biologic measures of chronic stress, predict psychological distress in low-income pregnant women over the first postpartum year. We conducted a secondary data analysis of the Child Community Health Research Network data set. The psychological distress outcome variables were perceived stress (n = 842), depression ( n = 845), and anxiety ( n = 846) symptoms, all measured categorically over the first year postpartum (T1:1 month, T2: 24-29 weeks, and T3: 50-65 weeks). Our predictors were social determinants of health (e.g., demographics, maternal hardship, percent poverty level, interpersonal violence, and food security) and allostatic load score. Generalized linear mixed models were used to determine which predictors were significantly associated with psychological distress symptoms across the first postpartum year. Interpersonal violence was a statistically significant risk factor for stress, depression, and anxiety symptoms over the first year postpartum. Other significant risk factors included low-income level, nativity, and perceived food security. Receiving food stamps was a significant protective factor for stress symptoms. The significance of risk factors for psychological distress, both modifiable and nonmodifiable, can be used as potential targets for further research, screening, and intervention. Future work should explore why and in what conditions these risk factors vary over time.

Objective To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. Design A nested case–control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. Setting A multicentre study in 16 academic medical centres in the USA. Population Low-risk nulliparous women. Methods Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9–12, 15–18 and 23–26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. Main outcome measures Change in PlGF, sFlt-1 and sEng. Results Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64–99), 77% (95% CI 50–93) and 77% (95% CI 50–93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. Conclusion Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Please cite this paper as: Thorp J, Camargo C, McGee P, Harper M, Klebanoff M, Sorokin Y, Varner M, Wapner R, Caritis S, Iams J, Carpenter M, Peaceman A, Mercer B, Sciscione A, Rouse D, Ramin S, Anderson G. Vitamin D status and recurrent preterm birth: a nested case–control study in high-risk women. BJOG 2012;119:1617–1623. Objective To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. Design A nested case–control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. Setting Fourteen academic health centres in the USA. Population Women with prior spontaneous preterm birth. Methods In 131 cases (preterm delivery at

To evaluate the association between cerebral palsy (CP) or infant death and putative cord blood biomarkers of neurologic injury, we performed a nested case-control secondary analysis of a multicenter randomized trial of magnesium sulfate (MgSO(4)) versus placebo to prevent CP or death among offspring of women with anticipated delivery from 24 to 31 weeks' gestation. Cases were infants who died by 1 year (n=25) or developed CP (n=16), and were matched 1:2 to a control group (n=82) that survived without developing CP. Umbilical cord sera concentrations of S100B, neuron-specific enolase (NSE) and the total soluble form of the receptor for advanced glycation end-products (sRAGE) were measured by ELISA in duplicates. Maternal characteristics were similar between the 2 groups. Cases were born at a lower gestational age (GA) and had lower birth weight compared with controls. There were no differences in concentrations of the three biomarkers and the composite outcome of CP or infant death. However, S100B was higher (median 847.3 vs. 495.7 pg/ml; P=0.03) in infants who had CP and total sRAGE was lower (median 1259.3 vs. 1813.1 pg/ml; P=0.02) in those who died compared with the control group. When corrected for delivery GA and treatment group, both differences lost statistical significance. In conclusion, cord blood S100B level may be associated with CP, but this association was not significant after controlling for GA and MgSO(4) treatment.

Based on prediction models and expert opinion, most obstetric venous thromboembolism guidelines recommend low‐molecular‐weight heparin for many postpartum women, including most delivering by caesarean. Scrutiny reveals major oversights: prediction models are based on studies that report asymptomatic deep vein thrombosis; risk estimates are not adjusted for time exposure; and harm caused by heparin has been overlooked. The benefits of heparin are exaggerated and its harms are under‐appreciated. Estimates of the numbers‐needed‐to‐treat and harm are universally lacking. This paper critically reviews the evidence and quantifies the benefit and harm from low‐molecular‐weight heparin in postpartum women with common risk factors. Funding This work was unsponsored and unfunded. Tweetable abstract Randomised trials should demonstrate more benefit than harm before widespread postpartum low‐molecular‐weight heparin is recommended., Tweetable abstract Randomised trials should demonstrate more benefit than harm before widespread postpartum low‐molecular‐weight heparin is recommended.

Background The United States is moving toward active drug safety surveillance using sources such as administrative claims and electronic medical records, but use of these data for studying teratogenicity has been challenging, as they typically do not allow for the easy identification of pregnancies. Our goal was to develop and validate an algorithm for the identification of pregnancies in the general practice research database (GPRD) that could be used to study pregnancy outcomes. Methods The algorithm identified pregnancies in women 15–45-year-old that were pregnant between 1 January 1987 and 31 December 2006. We identified live births, stillbirths, and spontaneous and elective terminations within a woman's record. We validated the algorithm using the additional clinical details maternity (ACDM) file and de-identified free-text records. Results We analyzed 16 035 394 records from 3 093 927 individuals and identified 383 184 women who had a total of 580 356 pregnancies. There were 415 221 full-term live births, 3080 pre- or post-term births, 1834 multi-fetus deliveries, 86 408 spontaneous abortions or miscarriages, 72 164 elective terminations, and 1649 stillbirths or fetal deaths. A marker of pregnancy care was identifiable for 86.3% of the 580 356 pregnancies. The internal validation steps indicated that the algorithm produced consistent results with the ACDM file. Conclusions We were successful in identifying a large number of pregnancies in the GPRD. Our use of a hierarchical approach to identify pregnancy outcomes builds upon the methods suggested in previous work, while implementing additional steps to minimize potential misclassification of pregnancy outcomes. Copyright © 2009 John Wiley & Sons, Ltd.

Objectives To create a fetal size nomogram for use in sub-Saharan Africa and compare the derived centiles with reference intervals from developed countries. Methods Fetal biometric measurements were obtained at entry to antenatal care (11–22 weeks' gestation) and thereafter at 4-week intervals from pregnant women enrolled in a longitudinal ultrasound study in Kinshasa, Democratic Republic of Congo. The study population comprised 144 singleton gestations with ultrasound-derived gestational age within 14 days of the menstrual estimate. A total of 755 monthly ultrasound scans were included with a mean ± SD of 5 ± 1 (range, 2–8) scans per woman. Estimated fetal weight (EFW) was calculated at each ultrasound examination using the Hadlock algorithm. A general mixed-effects linear regression model that incorporated random effects for both the intercept and slope was fitted to log-transformed EFW to account for both mean growth and within-fetus variability in growth. Reference centiles (5th, 10th, 50th, 90th and 95th centiles) were derived from this model. Results Nomograms derived from developed populations consistently overestimated the 50th centile EFW value for Congolese fetuses by roughly 5–12%. Differences observed in the 10th and 90th centiles were inconsistent between nomograms, but generally followed a pattern of overestimation that decreased with advancing gestational age. Conclusions In low-resource settings, endemic malaria and maternal nutritional factors, including low prepregnancy weight and pregnancy weight gain, probably lead to lower fetal weight and utilization of nomograms derived from developed populations is not appropriate. This customized nomogram could provide more applicable reference intervals for diagnosis of intrauterine growth restriction in sub-Saharan African populations. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Fetal growth restriction is a leading cause of perinatal morbidity and mortality that could be reduced if high-risk infants are identified early in pregnancy. We propose a Bayesian model for aggregating 18 longitudinal ultrasound measurements of fetal size and blood flow into three underlying, continuous latent factors. Our procedure is more flexible than typical latent variable methods in that we relax the normality assumptions by allowing the latent factors to follow finite mixture distributions. Using mixture distributions also permits us to cluster individuals with similar observed characteristics and identify latent classes of subjects who are more likely to be growth or blood flow restricted during pregnancy. We also use our latent variable mixture distribution model to identify a clinically meaningful latent class of subjects with low birth weight and early gestational age. We then examine the association of latent classes of intrauterine growth restriction with latent classes of birth outcomes as well as observed maternal covariates including fetal gender and maternal race, parity, body mass index, and height. Our methods identified a latent class of subjects who have increased blood flow restriction and below average intrauterine size during pregnancy. These subjects were more likely to be growth restricted at birth than a class of individuals with typical size and blood flow.

Objectives To determine whether stress is associated with risk of bacterial vaginosis (BV) in pregnant women. Design Prospective cohort study. Setting The prenatal care clinics at the University of North Carolina. The residents’ clinic sees mostly government-insured and uninsured women, and the physicians’ clinic sees mostly those with private health insurance. Population A total of 897 women gave samples for BV analysis. Study participants were 22% African-American, 68% white; 24% unmarried and 44% nulliparous. More than half had completed college. Methods Women completed two questionnaires and two interviews reporting stress and psychological aspects of their lives. Measurement scales included the Sarason life events questionnaire, the Cohen perceived stress scale, Spielberger state–trait anxiety, the John Henryism coping style and the Medical Outcomes Study social support inventory. Two stress hormones, corticotrophin-releasing hormone and cortisol, were also measured. Main outcome measures BV at 15–19 and 24–29 weeks of gestation was diagnosed by Gram’s stain. Results Women in the highest quartile of stress measures, particularly state anxiety (OR = 2.0, 95% CI 1.2–3.3), perceived stress (OR = 2.4, 95% CI 1.5–3.9) and total life events (OR = 2.0, 95% CI 1.3–3.2), had the highest risk of BV. Adjustment for confounders, especially age, race, and income, reduced these associations (state anxiety: OR = 1.3, 95% CI 0.7–2.4; perceived stress: OR = 1.4, 95% CI 0.8–2.5; total life events: OR = 1.3, 95% CI 0.7–2.4). No clear pattern of association was seen between stress hormones and BV. Conclusions Few associations between stress and BV were seen after adjustment for confounders.

This study evaluates maternal age, race, cigarette smoking, prior spontaneous abortion, prior induced abortion, and prior preterm birth in relation to vaginal bleeding during the first two trimesters of pregnancy. Information on vaginal bleeding and predictors came from the Pregnancy, Infection, and Nutrition Study, which enrolled 2806 pregnant women at 24-29 weeks' gestation during 1995-2000 in central North Carolina, USA. Generalised estimating equations were applied to take into account repeated episodes of vaginal bleeding during pregnancy. Women with advanced maternal age and passive smoking exposure were more likely to experience more intense vaginal bleeding during pregnancy, as were women with prior preterm birth. More intense bleeding was also more likely to be reported among women with multiple prior spontaneous abortions or multiple prior induced abortions, but not among women with a single prior spontaneous or induced abortion. The combination of prior spontaneous and induced abortion showed a dose-response association with the occurrence of vaginal bleeding during pregnancy.

Summary Studies of pregnancy outcome are generally based either on geographically defined populations, often from birth records, or on clinic or hospital populations. We compared women recruited into a clinic-based study, the Pregnancy, Infection, and Nutrition (PIN) Study, with women who resided in the geographical area of the study (Alamance, Orange, and Wake Counties in North Carolina) and gave birth over the corresponding time period (1996–2000). Clinic participants were more likely to be Black, younger, have lower education, be unmarried, have a more frequent history of adverse pregnancy outcome, obtain prenatal care later, and smoke more cigarettes. Despite that profile, the proportion of clinic participants delivering preterm was somewhat lower than among area women overall (10.8% vs. 11.3%). Black/White risk ratios for preterm birth were markedly different for area (1.6) vs. clinic women (1.1), whereas other predictors were similar. Patterns may differ across groups for many reasons, including self-selection of clinics and varying clinical practices.

An increasing proportion of preterm births result from medical interventions, and the practice of aggregating all preterm births vs. splitting into spontaneous and medically indicated preterm births is inconsistent. While mechanistic and clinical arguments can be offered for either approach, we empirically evaluated the predictiveness of a range of risk factors for preterm birth in the Pregnancy, Infection, and Nutrition Study. Most influences were shared across the two subsets - African-American ethnicity, advancing age, delivery at a university medical centre, prior preterm birth and smoking. Medically indicated preterm births appeared to be associated with intensity of medical care, higher in the university medical centre and lower for the poorest women. Body mass index was positively associated with medically indicated preterm birth and inversely with spontaneous preterm birth. Given the complexity of the aetiological pathways, both aggregation and disaggregation are well justified and should be included in studies of the causes of preterm birth.

Objective: To identify the risk of preterm birth and possible determinants among women in Hanoi, Vietnam. Method: Prospective cohort study of 1709 women with singleton live births at Hanoi Obstetrics and Gynecology Hospital, Hanoi, Vietnam, June–October 2002. Logistic regression analysis was used to examine predictors of preterm birth (

Summary To determine whether the vaginal delivery rate is increased in nulliparous women who have positive fetal fibronectin (fFN) testing before elective induction of labour, we performed a decision analysis that tested three options: (1) spontaneous labour; (2) testing nulliparous candidates for elective induction of labour at 39 weeks gestation with fFN and inducing labour if fFN positive (women who are fFN negative are managed expectantly); (3) elective induction of labour for women who are at least 39 weeks. We found that spontaneous labour had a vaginal delivery rate of 90%, elective induction 79% and fFN screening 83%. At baseline, a mother must be willing to take an additional 7% risk of caesarean delivery to warrant fFN testing or an additional 11% risk of caesarean delivery to warrant elective induction. We conclude that spontaneous labour has the highest vaginal delivery rates. An fFN test in a nulliparous woman may help to raise her likelihood of a vaginal delivery in an elective induction.

Summary Preterm labour (PTL) is a major contributor to preterm delivery (PTD) but delivery is often not preventable by current therapies. We conducted this study to determine the proportion of women with PTL who were and who were not candidates for tocolytic therapy. The cohort comprised residents of Olmsted County, Minnesota who delivered at >20 weeks’ gestation in 1985–94 and who experienced PTL. Medical records were abstracted to identify episodes of PTL, its treatment and outcome. We developed an algorithm that accounted for gestation at delivery and pregnancy complications to determine the proportion of pregnancies complicated by PTL that were candidates for tocolytic therapy. Of 651 pregnancies complicated by PTL, a 50% probability sample, stratified by delivery year, were selected and abstracted. The cumulative incidence of PTL ranged from 3.6 to 6.4 per 100 deliveries of live or stillborn infants. Tocolysis was not contraindicated for 49.4% of all women with PTL and for a third of women with only one PTL episode. Delivery was delayed to >35 weeks in 53.8% of candidates for tocolysis. Only an additional 11.7% of women with one or more PTL episodes could have had their PTD delayed beyond 35 weeks if a perfect tocolytic therapy had been available. Many pregnancies complicated by PTL occurred at ≥35 weeks or involved maternal or obstetric factors that contraindicated tocolytic medications. The maximum incremental benefit that could be expected of a new safe and efficacious tocolytic therapy would be to reduce current PTD rates resulting from PTL by about 12%.

The proportion of preterm births associated with structural birth defects has not been adequately quantified. We explored the proportion of preterm infants with structural birth defects diagnosed in the first year of life, as well as the specific phenotypes of birth defects occurring among preterm infants. The data used were from the California Birth Defects Monitoring Program, a population-based registry, as well as data from California vital records corresponding to births and fetal deaths in the period 1984-96. The prevalence of structural birth defects exceeded 8% among deliveries with gestational agesor = 30 weeks, and prevalence decreased to 2% as gestational age increased toor = 37 weeks gestation. The decreasing prevalence pattern with increasing gestational age was observed for a variety of anatomically defined birth defect groups suggesting that certain birth defects were not the sole contributors to the elevated prevalences among preterm births. Decreasing prevalence with increasing gestational age was also observed across strata of maternal race/ethnicities, ages, infant's sex and each year studied. These data indicate that structural birth defects may contribute significantly to the proportion of infants who are delivered before 37 weeks gestation.

The objective of this study was to evaluate the effect of preeclampsia and its severity on maternal mean middle cerebral artery blood flow velocity (mean MCA-CBFV) using transcranial doppler sonography (TCD), as well as the effect of magnesium on mean MCA-CBFV in preeclampsia.This study used a prospective, comparative design. TCD was used to examine maternal mean MCA-CBFV in both healthy subjects (controls) and preeclamptic subjects (cases). The two groups were similar in age, gestational age, and parity. Healthy subjects were categorized into three groups: Group I, 6–14 weeks, n = 10; Group 11, 24–40 weeks, n = 27; Group HI, postpartum n = 15, 12–36 h. Serial TCD examinations of the middle cerebral artery were completed in 21 preeclamptic subjects at four different points in time: Time I is an initial measurement before delivery; Time 2 is also before delivery but after magnesium had been administered; Time 3 is postpartum while on magnesium (12–24 h), Time 4 is postpartum off magnesium, (24–48 h).Preecl...

A patient is described who had three consecutive fetuses with cystic hygroma and hydrops, two of which had documentation of normal karyotype. Some twenty percent of fetuses with cystic hygroma have a normal karyotype, and many of these have other major malformations. An autosomal recessive pattern of inheritance has been postulated, but cystic hygroma may also occur in association with a variety of syndromes, some of which have other patterns of inheritance.

Acute fatty liver of pregnancy (AFLP) is usually diagnosed at autopsy, with severe hepatic failure, or after the appearance of extrahepatic disease. We present an atypical patient with mild AFLP in whom hepatic biopsy allowed earlier diagnosis. A low threshold for liver biopsy in patients not experiencing fulminant disease can afford diagnostic information prior to the onset of serious sequelae.

Bilateral renal agenesis is a lethal congenital anomaly. It appears to be transmitted in a polygenic pattern. The prenatal ultrasound findings consist of severe oligohydramnios, absence of the fetal bladder, and failure to identify fetal kidneys. Twin gestations with renal agenesis have been described in the paediatric literature. We detail a case of a patient with two prior affected pregnancies with bilateral renal agenesis. Her latest pregnancy was diagnosed prenatally, with one fetus with bilateral and the other fetus with unilateral renal agenesis. The ultrasound findings should be differentiated from the stuck twin phenomenon.