Preconception Maternal and Paternal Exposure to Persistent Organic Pollutants and Birth Size: The LIFE Study

Background: Persistent organic pollutants (POPs) are developmental toxicants, but the impact of both maternal and paternal exposures on offspring birth size is largely unexplored. Objective: We examined associations between maternal and paternal serum concentrations of 63 POPs, comprising five major classes of pollutants, with birth size measures. Methods: Parental serum concentrations of 9 organochlorine pesticides, 1 polybrominated biphenyl (PBB), 7 perfluoroalkyl chemicals (PFCs), 10 polybrominated diphenyl ethers (PBDEs), and 36 polychlorinated biphenyls (PCBs) were measured before conception for 234 couples. Differences in birth weight, length, head circumference, and ponderal index were estimated using multiple linear regression per 1-SD increase in natural log-transformed (ln-transformed) chemicals. Models were estimated separately for each parent and adjusted for maternal age, maternal prepregnancy body mass index (kilograms per meter squared) and other confounders, and all models included an interaction term between infant sex and each chemical. Results: Among girls (n = 117), birth weight was significantly lower (range, 84–195 g) in association with a 1-SD increase in ln-transformed maternal serum concentrations of DDT, PBDE congeners 28 and 183, and paternal serum concentrations of PBDE-183 and PCB-167. Among boys (n = 113), maternal (PCBs 138, 153, 167, 170, 195, and 209 and perfluorooctane sulfonamide) and paternal (PCBs 172 and 195) serum concentrations of several POPs were statistically associated with lower birth weight (range, 98–170 g), whereas paternal concentrations of PBDEs (66, 99) were associated with higher birth weight. Differences in offspring head circumference, length, and ponderal index were also associated with parental exposures. Conclusions: Preconceptional maternal and paternal concentrations of several POPs were associated with statistically significant differences in birth size among offsprin

Maternal serum markers of lipid metabolism in relation to neonatal anthropometry

Objective: The objective of this study is to examine associations between lipids (high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides and lipoprotein (a)) measured on average three time points during pregnancy and neonatal anthropometrics. Study design: Stored samples from a preeclampsia trial measured as part of a case-control study from five US centers (1992 to 1995) were used. The sample included women without pregnancy complications (n=136) and cases of gestational diabetes (n=93), abnormal glucose tolerance (AGT; n=76), gestational hypertension (n=170) and preeclampsia (n=177). Linear regression and linear mixed-effects models estimated adjusted associations between lipids and birth weight z-score, ponderal index (PI), length and head circumference. Results: Among women without complications, cross-sectional associations between total cholesterol measured at different gestational ages increased PI 2.23 to 2.55 kg m-3 per-unit increase in cholesterol. HDL was inversely associated with birth length (β\u27s=-2.21 and -2.56 cm). For gestational hypertension, triglycerides were associated with birth weight z-score (β\u27s=0.24 to 0.31). For preeclampsia, HDL was associated with lower birth weight z-scores (β\u27s=-0.49 and -0.82). Women with gestational diabetes or AGT had inconsistent associations. Examining the level changes across pregnancy, each 0.0037 mmol l-1 increase in HDL was associated with decreased birth weight z-score (β=-0.22), length (β=-0.24 cm) and head circumference (β=-0.24 cm), whereas each 0.028 mmol l-1 increase in triglycerides was associated with increased birth weight z-score (β=0.13) and head circumference (β=0.19 cm). Conclusions: Although associations varied by complications, in general, growth-promoting fuels such as total cholesterol and triglycerides were associated with increased neonatal size, whereas high HDL was associated with smaller size. Maternal HDL that failed to decrease over pregnancy was associated with smaller neonate size

Developmental Origins of Cardiovascular Disease

Although cardiovascular disease has traditionally been viewed as a condition of aging individuals, increasing focus has turned to its developmental origins. Since birthweight has been related to cardiovascular disease risk, research into factors such as gravid conditions that affect fetal growth have grown. Associations between maternal diabetes and childhood obesity from sibling studies suggest a causal role but prospective studies of gestational diabetes remain mixed. Preeclampsia and increased offspring blood pressure has been consistently observed but evidence for other cardiovascular outcomes is lacking. While maternal obesity is associated with childhood obesity, causality remains unclear and paternal obesity should be investigated as an independent risk factor. Environmental chemical exposures in utero, particularly obesogens, are now emerging as another concern, as is conception by infertility treatment. Few studies have investigated subclinical measures of endothelial function or atherosclerosis and more research in these areas may help reveal the underlying pathogenesis

Examining the Prevalence Rates of Preexisting Maternal Medical Conditions and Pregnancy Complications by Source: Evidence to Inform Maternal and Child Research

Objectives—We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research Methods—Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic (k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS Results—GHD was under-ascertained on birth certificates (5.7 %) and more frequently indicated by maternal report (11 %) and discharge data (8.2 %). PROM was indicated more on birth certificates (7.4 %) than maternal report (4.5 %) or discharge data (5.7 %). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor (kappa \u3c 0.4) to moderate (0.4 ≤ kappa \u3c 0.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment (kappa = 0.79, 95 % CI 0.74, 0.85). Conclusions for Practice—Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life-course

Preconception and early pregnancy air pollution exposures and risk of gestational diabetes Mellitus

Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5μm (PM2.5) and PM2.5 constituents, PM ≤ 10μm (PM10), nitrogen oxides (NOx), carbon monoxide, sulfur dioxide (SO2) and ozone (O3) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1-24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. Results: Preconception maternal exposure to NOX (RR=1.09, 95% CI: 1.04, 1.13) and SO2 (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O3 was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. Conclusion: Maternal exposures to NOx and SO2 preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O3 appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation

Adherence to the Mediterranean diet and body fat distribution in reproductive aged women

Background/Objectives Adherence to the Mediterranean Diet (MD) high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean Diet Score (aMED), anthropometry and measured adiposity by dual energy x-ray absorptiometry. Subjects/Methods This study included 248 healthy females, aged 18–44 years from the BioCycle Study. Each woman’s aMED (range 0–9) was calculated from up to eight 24-hr dietary recalls over 1–2 menstrual cycles (>97% had ≥7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake. Results: Participants had an average (SD) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist to hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95% CI:−0.09,−0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=−0.280, 95% CI:−0.550,−0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95% CI:0.002,0.117). Conclusions: Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD

Gestational Age at Birth and Risk of Developmental Delay: The Upstate KIDS Study

Objective—To model the association between gestational age at birth and early child development through 3 years of age. Study Design—Development of 5868 children in Upstate KIDS (New York State; 2008–2014) was assessed at 7 time-points using the Ages and Stages Questionnaire (ASQ). The ASQ was implemented using gestational age corrected dates of birth at 4, 8, 12, 18, 24, 30, and 36 months. Whether children were eligible for developmental services from the Early Intervention Program (EIP) was determined through linkage. Gestational age was based on vital records. Statistical models adjusted for covariates including sociodemographic factors, maternal smoking and plurality. Results——Compared to gestational age of 39 weeks, adjusted odds ratios (aOR) and 95% confidence intervals of failing the ASQ for children delivered at \u3c 32, 32–34, 35–36, 37, 38, and 40 weeks gestational age were: 5.32 (3.42, 8.28), 2.43 (1.60, 3.69), 1.38 (1.00, 1.90), 1.37 (0.98, 1.90), 1.29 (0.99, 1.67), 0.73 (0.55, 0.96), and 0.51 (0.32, 0.82). Similar risks of being eligible for EIP services were observed (aOR: 4.19, 2.10, 1.29, 1.20, 1.01, 1.00 (ref), 0.92, 0.78, respectively for \u3c 32, 32–34, 37, 38, 39 (ref), 40, 41 weeks). Conclusion—Gestational age was inversely associated with developmental delays for all gestational ages. Evidence from our study is potentially informative for low-risk deliveries at 39 weeks but it is notable that deliveries at 40 weeks exhibited further lower risk

Long-term risk of type 2 diabetes mellitus in relation to BMI and weight change among women with a history of gestational diabetes mellitus: a prospective cohort study

Aims/hypothesis—Women with a history of gestational diabetes mellitus (GDM) are advised to control their weight after pregnancy. We aimed to examine how adiposity and weight change influence the long-term risk of developing type 2 diabetes after GDM. Methods—We included 1,695 women who had incident GDM between 1991 and 2001, as part of the Diabetes & Women’s Health study, and followed them until the return of the 2009 questionnaire. Body weight and incident type 2 diabetic cases were reported biennially. We defined baseline as the questionnaire period when women reported an incident GDM pregnancy. We estimated HRs and 95% CIs using Cox proportional hazards models. Results—We documented 259 incident cases of type 2 diabetes during up to 18 years of follow-up. The adjusted HRs of type 2 diabetes associated with each 1 kg/m2 increase in BMI were 1.16 (95% CI 1.12, 1.19) for baseline BMI and 1.16 (95% CI 1.13, 1.20) for most recent BMI. Moreover, each 5 kg increment of weight gain after GDM development was associated with a 27% higher risk of type 2 diabetes (adjusted HR 1.27; 95% CI 1.04, 1.54). Jointly, women who had a BMI ≥30.0 kg/ m2 at baseline and gained ≥5 kg after GDM had an adjusted HR of 43.19 (95% CI 13.60, 137.11), compared with women who had a BMI Conclusions/interpretation—Baseline BMI, most recent BMI and weight gain after GDM were significantly and positively associated with risk of progression from GDM to type 2 diabetes

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV