Thomas McElrath

Between 0.3% and 0.5% of all pregnancies occur among women with epilepsy. Evidence suggests an increase in perinatal morbidity and mortality among women with epilepsy. However, these risks have not been quantified in large population-based samples. To report on the risk for death and adverse outcomes at the time of delivery for women with epilepsy in the United States. Retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007-2011 Nationwide Inpatient Sample. From this representative sample of 20% of all US hospitals, we obtained a weighted sample of delivery hospitalizations from 69 385 women with epilepsy and 20 449 532 women without epilepsy. Obstetrical outcomes including maternal death, cesarean delivery, length of stay, preeclampsia, preterm labor, and stillbirth. Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100 000 pregnancies, significantly higher than the 6 deaths per 100 000 pr...

Despite decades of research, and much progress in discernment of biomarkers in the maternal circulation, the pathogenesis of PE remains elusive. The pathophysiology of preeclampsia (PE) is believed to involve aberrant placentation and an associated increase in systemic inflammation. In this conceptualization, preeclampsia 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 a UTI during pregnancy increased the odds of developing PE. Prior work has documented this association (11-15). However many of these studies were limited by small cohort sizes and insufficient contro...

ABSTRACT Phthalates and bisphenol-a (BPA) are endocrine disrupting compounds with widespread exposure that have been linked to adverse birth outcomes and developmental effects. We hypothesized that these associations may be mediated in part through altered placental development and function consequent to exposure. To investigate this question, we examined associations between plasma biomarkers of angiogenesis and urinary biomarkers of exposure to phthalates and bisphenol-a (BPA) measured at repeated time points across pregnancy. We utilized a nested case-control population of 130 mothers who delivered preterm and 352 who delivered term from a prospective birth cohort. Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured in plasma samples collected from up to four visits during pregnancy (median 10, 18, 26, and 35 weeks). Phthalate metabolites and BPA were measured in urine samples collected at the same visits as indices of exposure. In linear mixed effects models adjusted for urine dilution and gestational age at sample collection, oxidized di-2-ethylhexyl phthalate (DEHP) metabolites were associated with decreases in PlGF as well as increases in the sFlt-1 to PlGF ratio. These results were slightly attenuated in fully adjusted models. Other phthalate metabolites did not show consistent relationships with either sFlt-1 or PlGF. BPA, however, was associated with increased sFlt-1 as well as the sFlt-1 to PlGF ratio in both crude and adjusted models. We observed associations between urinary DEHP metabolites and BPA and biomarkers of angiogenesis during pregnancy that may be indicative of disrupted placental development and/or function during gestation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phthalate exposure is prevalent in populations worldwide, including pregnant women. Maternal urinary metabolite concentrations have been associated with adverse reproductive outcomes, but underlying mechanisms remain unclear. Here we investigate inflammation as a possible pathway by examining phthalates in association with inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (IL-1β, IL-6, IL-10, and TNF-α) in a repeated measures analysis of pregnant women (N = 480). Urinary phthalate metabolites and plasma inflammation biomarkers were measured from samples collected at up to four visits per subject during gestation (median 10, 18, 26, and 35 weeks). Associations were examined using mixed models to account for within-individual correlation of measures. Few statistically significant associations or clear trends were observed, although in full models mono-carboxypropyl phthalate (MCPP) was significantly (percent change with interquartile range increase in exposure [%Δ] = 8.89, 95% confidence interval [CI] = 3.28, 14.8), and mono-benzyl phthalate (MBzP) was suggestively (%Δ = 6.79, 95%CI = -1.21, 15.4) associated with IL-6. Overall these findings show little evidence of an association between phthalate exposure and peripheral inflammation in pregnant women. To investigate inflammation as a mechanism of phthalate effects in humans, biomarkers from target tissues or fluids, though difficult to measure in large-scale studies, may be necessary to detect effects.

2-methoxyestradiol (2ME2) is a potent antiangiogenic molecule that inhibits the expression of hypoxia-inducible factor (HIF)-1alpha and, consequently, of VEGF and other HIF-1alpha target genes. Although 2ME2 is elevated during pregnancy in maternal serum, its presence in fetal fluids and its impact in neonatal health are unknown. In this study, we 1) described normal levels of 2ME2 in maternal blood, cord blood, breast milk, and amniotic fluid, and 2) compared a composite measure of perinatal outcome between infants born with high and low levels of 2ME2. We found that 2ME2 was significantly decreased in all fluids compared with prepartum maternal serum. After stratifying babies by 2ME2 exposure levels, we observed no differences in the vulnerability to impaired lung development or to complications involving aberrant angiogenesis or vascular leak, such as necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), posthemorrhagic hydrocephalus (PHH), and retinopathy of premat...

Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regards to PTB. In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB. A nested case-control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston during 2006-2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as "spontaneous", which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or "placental", which was preceded by preeclampsia or intrauterine growth restriction. Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant's sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males. These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.

To determine if epidural analgesia is associated with differences in rates of severe perineal trauma during vaginal deliveries. We studied 1942 consecutive, low-risk, term, vaginal deliveries in nulliparas, including spontaneous and induced labors, at a single institution from December 1994 to August 1995. The rate of third- and fourth-degree lacerations was compared for women who had and did not have epidural analgesia for labor-pain relief. Statistical significance was determined using chi2. Logistic regression analyses were used to evaluate associations while controlling for possible confounding variables. Overall rates of third- and fourth-degree lacerations were 10.8% (n = 210) and 3.4% (n = 63), respectively. Epidural analgesia was given to 1376 (70.9%) women. Among women who had epidurals, 16.1% (221 of 1376) had severe perineal lacerations compared with 9.7% (n = 55) of the 566 women who did not have epidurals (P < .001; odds ratio [OR] 1.8, 95% confidence interval [CI] 1...

We sought to validate several clinical risk factors previously described for preeclampsia in a large contemporary multicenter prospective cohort. We enrolled women from three sites before 15 weeks of gestation. Demographic and clinical risk factors were collected through standardized chart review. The main outcome of preeclampsia was diagnosed using the American College of Obstetricians and Gynecologists definitions from 2002. Multivariable logistic regression was used to control for confounders. Two thousand six hundred thirty-seven women are included in this analysis; 237 (9.0%) developed preeclampsia. In adjusted analysis, chronic hypertension (adjusted odds ratio [OR] 2.72; 95% confidence interval 1.78-4.13), pregestational diabetes (adjusted OR 3.88; 2.08-7.26), multiple gestation (adjusted OR 2.96; 1.74-5.03), African American race (adjusted OR 1.91; 1.35-2.71), prior preeclampsia (adjusted OR 3.63; 2.29-5.73), nulliparity (adjusted OR 1.73; 1.26-2.38), assisted reproductive techniques (adjusted OR: 1.72; 1.10-2.68), and being overweight (adjusted OR for body mass index [BMI, kg/m] greater than 25-30: 1.65; 1.13-2.41) or obese (adjusted OR for BMI greater than 30-35: 2.34, 1.51-3.61; adjusted OR for BMI greater than 35-40: 3.59, 2.13-6.03; adjusted OR for BMI greater than 40: 6.04, 3.56-10.24) were associated with preeclampsia, but advanced maternal age was not. Similar associations were found for severe preeclampsia. A dose-response effect was observed in the relationship between BMI and both preeclampsia and severe preeclampsia. Being overweight or obese was the most important risk factor for both preeclampsia and severe preeclampsia with an attributable risk percent of 64.9% and 64.4%, respectively. In this contemporary cohort, increasingly prevalent and potentially modifiable factors were confirmed as significant risk factors for preeclampsia and severe preeclampsia, the most important being overweight or obese. This information is important to guide public health efforts in preeclampsia prevention. : II.

To assess antenatal and early postnatal antecedents of attention problems identified by the Child Behavior Checklist in extremely preterm children. In a cohort of 826 children born between 23 and 27 weeks' gestation, we collected demographic, birth, and postnatal information. We then identified behavior problems by using parent ratings from the Child Behavior Checklist at 2 years' adjusted age. We created time-oriented logistic regression risk models to identify significant risk factors for attention problems and Diagnostic and Statistical Manual of Mental Disorders-compatible attention deficit/hyperactivity problems (ADHP(DSM)). Children were at increased risk of both attention problems if they were born to a woman who had no formal education beyond high school and/or a woman who was exposed to secondhand smoke. Recovery of a single organism from the placenta was associated with increased risk of an attention problem, and fetal stem vessel thrombosis and recovery of Mycoplasma species were associated with increased risk of ADHP(DSM). Infants of multifetal gestations were at reduced risk of both attention problems. The only postnatal risk factor for an attention problem was recovery of bacteria from a tracheal aspirate. Among extremely preterm infants, several potentially modifiable antenatal and perinatal antecedents are associated with increased risk for attention problems and ADHP(DSM) at 2 years adjusted age.

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. 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. 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). 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.

Preterm birth is a leading cause of neonatal mortality, with a variety of contributing causes and risk factors. Environmental exposures represent a group of understudied, but potentially important, factors. Phthalate diesters are used extensively in a variety of consumer products worldwide. Consequently, exposure in pregnant women is highly prevalent. To assess the relationship between phthalate exposure during pregnancy and preterm birth. This nested case-control study was conducted at Brigham and Women's Hospital, Boston, Massachusetts. Women were recruited for a prospective observational cohort study from 2006-2008. Each provided demographic data, biological samples, and information about birth outcomes. From within this group, we selected 130 cases of preterm birth and 352 randomly assigned control participants, and we analyzed urine samples from up to 3 time points during pregnancy for levels of phthalate metabolites. Phthalate exposure during pregnancy. We examined associations between average levels of phthalate exposure during pregnancy and preterm birth, defined as fewer than 37 weeks of completed gestation, as well as spontaneous preterm birth, defined as preterm preceded by spontaneous preterm labor or preterm premature rupture of the membranes (n = 57). Geometric means of the di-2-ethylhexyl phthalate (DEHP) metabolites mono-(2-ethyl)-hexyl phthalate (MEHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), as well as mono-n-butyl phthalate (MBP), were significantly higher in cases compared with control participants. In adjusted models, MEHP, MECPP, and  Σ DEHP metabolites were associated with significantly increased odds of preterm birth. When spontaneous preterm births were examined alone, MEHP, mono-(2-ethyl-5-oxohexyl) phthalate, MECPP,  Σ DEHP, MBP, and mono-(3-carboxypropyl) phthalate metabolite levels were all associated with significantly elevated odds of prematurity. Women exposed to phthalates during pregnancy have significantly increased odds of delivering preterm. Steps should be taken to decrease maternal exposure to phthalates during pregnancy.

Placental analytes are traditionally used for aneuploidy screening, although may be replaced by cell-free fetal DNA. Abnormal analytes also identify women at risk for small for gestational age (SGA). We sought to quantify the proportion of women at risk for SGA by low pregnancy-associated plasma protein-A (PAPP-A) or βhCG who would not otherwise be identified by maternal risk factors. We studied first-trimester PAPPA-A and βhCG from 658 euploid singleton pregnancies from a prospective longitudinal cohort. Analytes were standardized for gestational age in multiples of the median (MoM). SGA was defined as birthweight z-score ≤-1.28. Maternal risk factors included chronic hypertension, pre-gestational diabetes and age ≥40. Mean GA was 38.8 ± 1.9 weeks; 6.8% had a SGA infant. Low PAPP-A and βhCG were identified in 48 (7.4%) and 9 (1.4%) of pregnancies, respectively, of whom 18.9% were SGA (OR 3.0, 95% CI 1.4-6.3). 88% did not have risk factors for SGA. Among women with no risk factors, low PAPP-A was a significant predictor of SGA (OR 3.3, 95% CI 1.5-7.4). Most women with abnormal analytes did not have risk factors for SGA. Eliminating PAPP-A and βhCG may present missed opportunities to identify women at risk for SGA.

Recent studies have revealed increased morbidity and mortality rates in term neonates without birth defects who were delivered before 39 weeks of completed gestation. We sought to determine if a similar association exists between gestational age at delivery and adverse outcomes in neonates with critical congenital heart disease, with particular interest in those born at 37 to 38 weeks' gestation. We studied 971 consecutive neonates who had critical congenital heart disease and a known gestational age and were admitted to our cardiac ICU from 2002 through 2008. Gestational age was stratified into 5 groups: >41, 39 to 40, 37 to 38, 34 to 36, and…

Our goal is to study the triggers of spontaneous preterm delivery using a case-crossover design. In a pilot study, we enrolled 50 women with spontaneous preterm labour (PTL) and 50 with preterm premature rupture of membranes (PPROM) between 2011 and 2012. To assess non-transient risk factors, we also enrolled a control group of 158 pregnant women at their regular prenatal care visits matched to cases by gestational age and calendar time. The index time was defined as the onset of PTL/PPROM (for cases) or interview (for controls). Detailed data were collected through structured interviews regarding factors of interest during the 72 h that preceded the index time. Within case subjects, we compared the frequency of transient factors from 0 to 24 h before index time with that from 48 to 72 h before index time, and estimated matched odds ratios (OR) and 95% confidence intervals (CI). Previously hypothesised chronic risk factors for spontaneous preterm delivery, including mood disorders and stressful events, were more common among cases than among controls. Within cases, skipped meals [OR 4.3, 95% CI 1.2, 15.2], disturbed sleep [OR 4.5, 95% CI 1.5, 13.3], sexual activity [OR 6.0, 95% CI 0.7, 69.8], and intake of spicy foods [OR 7.0, 95% CI 1.6, 30.8] were associated with an increased risk for PTL/PPROM within the subsequent 24 h. For physical exertion and other potential risk factors evaluated, the OR was close to the null. Skipping meals and disturbed sleep may be associated with imminent PTL/PPROM; sexual activity and spicy food may trigger PTL/PPROM in susceptible women. Larger case-crossover studies will be able to evaluate the impact of modifiable risk factors and acute predictors of PTL/PPROM, and might help guide obstetrical management.

Several groups, including ours, have developed probabilistic models that incorporate both the surfactant-to-albumin ratio (TDx-FLM II) and gestational age to more accurately predict the risk of neonatal respiratory distress syndrome (RDS) and eliminate the current categorical "immature"/"indeterminate"/"mature" interpretation. We validate our model using a separate data set, with the goal of providing the clinician with a risk score. The medical records of all women who had TDx-FLM II testing performed at Brigham and Women's Hospital between January 1, 2003, and December 31, 2005, were reviewed to gather a population upon which to validate our previous logistic regression model. Receiver operating characteristic curve and Hosmer-Lemeshow analysis was conducted to determine the performance of our model and another model in this new population. A total of 233 mother-neonate pairs (21 RDS, 212 non-RDS) met criteria for analysis. The receiver operating characteristic analysis illustrated that our previous formula was a strong predictor of the risk of RDS with an area under the curve of 0.902 (95% confidence interval 0.849-0.955). In addition, using the Hosmer-Lemeshow analysis, our formula produced an excellent overall fit (P=.95), whereas another published model was a poor fit to our data (P=.002). Our previously derived logistic regression model formula incorporating TDx-FLM II results and gestational age to predict risk of neonatal respiratory distress syndrome was robust and stable over time in an independent data set. The results suggest that the equation can be implemented clinically to assist physicians and patients and used by other institutions after their own internal validation. III.

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. 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. 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 15% or less can be achieved with a surfactant-to-albumin ratio cutoff of 60 mg or more surfactant/g 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. 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. II-2

To determine the neonatal outcome in accurately dated 23-week deliveries. We reviewed the records of consecutive births between 23 0/7 and 23 6/7 weeks at Brigham & Women's Hospital, Boston, Massachusetts, from January 1995 to December 1999. Women were excluded if they presented for elective termination or had known fetal death or poor dating criteria. Neonatal records were abstracted for mortality and short-term morbidity, including the respiratory distress syndrome (RDS), intraventricular hemorrhage, chronic lung disease, necrotizing enterocolitis, periventricular leukomalacia, and retinopathy of prematurity. Survival was defined as discharge from neonatal intensive care. Thirty-three singleton pregnancies met criteria for inclusion, 11 of whom survived to discharge (survival rate 0.33; 95% CI 0.18, 0.52). More advanced gestational age was associated with increased likelihood of survival: 0 of 12 at 23 0/7 to 23 2/7 weeks, 4 of 10 at 23 3/7 to 23 4/7 weeks, and 7 of 11 at 23 5/7 to 23 6/7 weeks (P =.02). All 11 survivors developed RDS and chronic lung disease. One of 11 survivors had necrotizing enterocolitis, and 2 of 11 had severe retinopathy of prematurity. One survivor had periventricular leukomalacia on head ultrasonography, compared with 7 of the nonsurvivors who had head ultrasonography (P =.03). One survivor developed severe intraventricular hemorrhage (grade 3 or 4) compared with 8 of the 12 at-risk nonsurvivors who had head ultrasonography (P =.01). About one third of infants delivered at 23 weeks' gestation survived to be discharged from neonatal intensive care. More advanced gestational age was associated with increased likelihood of survival. No neonates survived free of substantial morbidity.

To test the hypothesis of an association between maternal infertility therapy and the risk of very low birth weight (VLBW), defined as birth weight less than 1500 g, independent of the risk of multiple births, and to estimate the contribution of infertility therapy to the national incidence of VLBW. The National Maternal and Infant Health Survey conducted in 1988 was used to develop statistics describing outcomes among this birth cohort and to construct logistic regression models evaluating fertility therapy as an independent risk factor for VLBW. An estimated 10.1% of live births and 18.2% of VLBW births nationally were associated with either maternal subfertility or infertility therapy (6.8% and 11.4%, respectively). The risk of VLBW among women concerned with subfertility (i.e., receiving diagnostic testing or advice on timing intercourse) was 1.4 (95% confidence interval [CI] 1.1, 1.9), whereas that for women undergoing therapeutic interventions (ie, ovarian stimulation, surgery, in vitro fertilization, or artificial insemination) was 2.6 (95% CI 2.1, 3.2). Accounting for effects of multiple gestation, maternal age, and a history of miscarriage, the odds ratios for the concerned and therapy groups were 1.5 (95% CI 1.1, 1.9) and 2.0 (95% CI 1.5, 2.5), respectively. Black women were less likely to use fertility therapy but more likely to experience a therapy-related VLBW. Fertility therapy is associated with an important portion of all VLBW and with an elevated risk of VLBW, related only in part to an increased risk of multiple gestations. Women expressing concern about subfertility but not receiving therapy are also at increased risk of VLBW, suggesting that a history of infertility may mediate part of the risk associated with fertility therapy.

Because prior work suggests an association between high insulin concentrations in early pregnancy and excess gestational weight gain, we examined such associations in a prospective cohort. Multivariate regression analysis of early pregnancy insulin homeostasis and gestational weight gain among 434 women enrolled in the MGH Obstetrical Maternal Study. We found that the association between insulin quartile and gestational weight gain varied depending on maternal body mass index (BMI) in early pregnancy (P for interaction <0.0001). Among women with a BMI of 20, high fasting insulin was associated with greater gestational weight gain (multivariate-adjusted predicted mean 39.6, 95% CI 30.9-40.3 lbs for Quartile 4 (Q4) vs. 31.3, 95% CI 28.6-34.1 lbs for Q1) and higher risk of excessive weight gain. By contrast, among women with a BMI of 35, higher fasting insulin was associated with lower total gain (multivariate-adjusted predicted mean 25.7, 95% CI 22.6-28.7 lbs for Q4 vs. 33.2, 95% CI 10.5-55.9 lbs for Q1) and lower risk of excessive gain. In our cohort, early pregnancy BMI modified the association between insulin homeostasis and gestational weight gain. These associations suggest that the physiologic consequences of hyperinsulinemia differ between normal weight and obese women.

Bisphenol A (BPA) is one of the environmental endocrine-disrupting chemicals used widely in common consumer products. There is an increasing concern about human exposure to BPA, particularly in fetuses, due to the potential adverse effects related to the estrogenic activity of BPA. In assessing environmental exposure to BPA, it is essential to have a sensitive, accurate, and specific analytical method, particularly for low BPA levels in complex sample matrices. In this study, we developed and validated an accurate, sensitive, and robust liquid chromatography-mass spectrometry (LC-MS) method for determining the BPA concentrations in human amniotic fluid (AF). In this method, BPA and the internal standards (13)C(12) -BPA were extracted from 500 μL of human AF using solid-phase extraction. Calibration curves were linear over a concentration range of 0.3-100 ng/mL for BPA. The analytes were quantitatively determined using LC-MS operated in a negative electrospray ionization selected ion monitoring mode. This validated method has been used successfully in the clinical sample analysis of BPA in second-trimester AF specimens.

To test the hypothesis that exposure to preeclampsia is associated with an increased risk of bronchopulmonary dysplasia (BPD). A prospective cohort study of 107 babies born between 23 and 32 weeks gestation, collecting maternal, neonatal, and placental data. Of the 107 infants studied, 27 (25%) developed BPD. The bivariate odds ratio (OR) for the relationship between pre-eclampsia and BPD was 2.96 (95% confidence interval [CI] = 1.17 to 7.51; P = .01). When controlling for gestational age, birth weight z-score, chorioamnionitis, and other clinical confounders, the OR of developing BPD was 18.7 (95% CI = 2.44 to 144.76). Including the occurrence of preeclampsia, clinical chorioamnionitis, male sex, and maternal tobacco use in addition to gestational age and birth weight z-score accounted for 54% of the variability of the odds of developing BPD. BPD is increased for infants exposed to preeclampsia. This has possible implications for the prevention of BPD with proangiogenic agents, such as vascular endothelial growth factor.

We sought to use a novel case-selection methodology to identify antenatal or intrapartum risk factors associated with neonatal neurological impairment following non-reassuring fetal heart rate patterns during labour. We used a retrospective case-control design with bivariate and multivariate conditional logistic regression. Cases were births in which electronic fetal monitoring (EFM) showed non-reassuring patterns and the infant had neurological disability. Controls were births in which EFM was non-reassuring but the infant was born healthy. We identified 36 cases from among malpractice claims filed with a liability insurer in Massachusetts between 1985 and 2001 and randomly selected 70 controls, matching them to cases by hospital, birth date and gestational age. More cases had maternal antenatal vaginal bleeding (P = 0.004), a prolonged latent phase or protracted dilation during the first stage of labour (P = 0.03), and protracted descent or prolonged second stage (P = 0.01). More cases also had minimal variability on EFM on admission (P = 0.02) and during the second stage (P = 0.02). Multivariate analysis highlighted three significant predictors of neurological injury following complicated labour: antenatal vaginal bleeding (OR = 27.1), prolonged latent phase or protracted dilation in the first stage (OR = 4.0) and EFM showing minimal variability in the first stage (OR = 4.3). These promising initial findings suggest that future research into outcomes from complicated labour with non-reassuring heart rate patterns should focus on maternal history of vaginal bleeding, slow labour and minimal variability on EFM.