Triclosan (TCS) is an antibacterial chemical widely used in personal-care products and an endocrine disruptor. While TCS exposure is associated with insulin resistance and metabolic disorders in animals, few studies have assessed its effect on the risk of gestational diabetes mellitus (GDM) in humans. This study aimed to explore whether maternal urinary TCS level is associated with the risk of GDM and infant birthweight. We examined 620 pregnant women from Shanghai, China in 2012-2013. Urinary TCS level was measured with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and categorized into high, medium and low in tertiles. GDM was defined based on recommendation of International Association of Diabetes and Pregnancy Study Groups (IADPSG). The GDM rate was 12.7%. TCS was detectable (≥0.1 ng/mL) in 97.9% women (median 2.7 ng/mL). There was a positive, but statistically non-significant association between urinary TCS levels and GDM (adjusted odds ratio 1.17; 95%CI: 0.99, 1.39, with each unit increase of log (TCS) ng/mL) with adjustment for urinary creatinine, maternal age, education, passive smoking, parity and prepregnancy BMI categories. 48.1% of infants were females. Birthweight was 122.8 g higher (95% CI: 13.9, 231.6 g) for female infants of women in high TCS (median 13.3 ng/mL) versus low TCS (median 0.77 ng/mL), with adjustment for urinary creatinine, prepregnancy BMI, GDM and other confounders. No association was found between maternal TCS and birthweight in male infants. These results suggested the potential for TCS to be associated with increased risk of GDM and a gender-specific association with higher birthweight among female infants in a population with widespread but moderate exposure to TCS.

Background: Bisphenol A (BPA) has been associated with variable metabolic effects in animal models. It is unknown whether BPA exposure affects glucose tolerance in pregnancy. We aimed to investigate whether maternal urinary BPA concentration is associated with gestational diabetes mellitus (GDM). Methods: This study included 620 pregnant women from Shanghai, China 2012–2013. Maternal urinary BPA concentration was measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). GDM (n = 79) was diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Multivariate regressions were used to explore the relationships of urinary BPA with GDM, plasma glucose levels in the 75-g 2-hour oral glucose tolerance test (OGTT), birth weight, and ponder index. Results: The geometric mean of BPA was 1.32 μg/L. After adjustment for maternal age, education, husband smoking status, prepregnancy body mass index (BMI), and urinary creatinine concentration, plasma glucose at 2 hours in the 75-g OGTT was 0.36 mmol/L lower (95% confidence index [CI] = −0.73, 0.01) for women with urine BPA in the high versus the low tertile. For each unit increase in natural log-transformed BPA, the odds of GDM was reduced by 27% (odds ratio (OR) = 0.73; 95% CI = 0.56, 0.97), the birth weight decreased by 25.70 g (95% CI = −54.48, 3.07), and ponder index was decreased by 0.02 (100 g/cm³) (95% CI = −0.03, 0.00). Conclusions: Higher maternal urinary BPA concentrations were associated with reduced risk of GDM and marginally lower birth weight and ponder index.

Gestational diabetes mellitus (GDM) “program” an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate 0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.

Context: Thyroid hormones are essential for fetal brain development. The potential effects of maternal gestational thyroid dysfunction on offspring neuropsychological development remain inconclusive.Objective: This work aimed to estimate effects of maternal thyroid dysfunction during pregnancy on offspring neuropsychological development in the first 2 years.Methods: We prospectively examined 1903 mothers and their children from the Shanghai Birth Cohort. Thyroid hormones were assessed at about 12 gestational weeks. Maternal thyroid function was classified into 7 categories: euthyroid, overt/subclinical hyperthyroidism, overt/subclinical hypothyroidism, hyperthyroxinemia, and hypothyroxinemia. Neuropsychological development was assessed by the Ages and Stages Questionnaire at age 6 months, and Bayley Scales at age 24 months.Results: Compared with children of euthyroid mothers, maternal overt hypothyroidism was associated with 7.0 points (95% CI, 1.7-12.4) lower scores in personal-social domain in girls aged 6 months, 7.3 points (95% CI, 2.0-12.6) lower in motor domain, and 7.7 points (95% CI, 1.1-14.2) lower social-emotional scores in boys at age 24 months; maternal subclinical hypothyroidism was associated with 6.5 points (95% CI, 1.0-12.1) poorer social-emotional domain in boys at age 6 months, and 7.4 points (95% CI, 0.1-14.8) poorer adaptive behavior domain in boys at age 24 months; maternal hypothyroxinemia was associated with 9.3 points (95% CI, 3.5-15.1) lower motor scores in boys at age 24 months; and maternal subclinical hyperthyroidism was associated with 6.9 points (95% CI, 0.1-13.7) lower language scores in girls at age 24 months.Conclusion: Maternal overt hypothyroidism, subclinical hypothyroidism/hyperthyroidism, and hypothyroxinemia during early pregnancy were associated with weakened neuropsychological development in infancy, and some effects may be sex specific.

Exposure to endocrine disrupting chemicals during the first 1000 days of life may have long-lasting adverse effects on cardio-metabolic risk in later life. This study aimed to examine the associations between maternal prenatal Bisphenol A (BPA) exposure and child cardio-metabolic risk factors at age 2 years in a prospective cohort. During 2012-2013, 218 pregnant women were enrolled at late pregnancy from Shanghai, China. Urinary BPA concentration was measured in prenatal and child 2-year spot urine samples, and classified into high, medium and low tertiles. Child adiposity anthropometric measurements, random morning plasma glucose, serum insulin, and lipids (high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride), systolic (SBP) and diastolic blood pressure (DBP) were measured. Linear regression was used to evaluate the associations between prenatal BPA and each of the cardio-metabolic risk factors in boys and girls, respectively, adjusting for pertinent prenatal, perinatal and postnatal factors. BPA was detectable (>0.1 μg/L) in 98.2% of mothers prenatally and 99.4% of children at age 2 years. Compared to those with low prenatal BPA, mean SBP was 7.0 (95%CI: 2.9-11.2) mmHg higher, and DBP was 4.4 (95%CI: 1.2-7.5) mmHg higher in girls with high prenatal BPA levels, but these associations were not found in boys. In boys, medium maternal prenatal BPA level was associated with 0.36 (95% CI: 0.04-0.68) mmol/L higher plasma glucose. No associations were found between prenatal BPA and child BMI, skinfold thicknesses, serum lipids, or insulin in either girls or boys. There were no associations between concurrent child urinary BPA and cardio-metabolic risk factors. These results support that BPA exposure during prenatal period, susceptible time for fetal development, may be associated with increase in child BP and plasma glucose in a sex-specific manner. Further independent cohort studies are needed to confirm the findings.