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Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 children conceived by ART and 205 children conceived spontaneously from two centers of the China National Birth Cohort, using whole-genome sequencing (WGS) data. One-year-old children conceived by ART had shorter LTLs than those conceived spontaneously (beta, -0.36; P = 1.29 × 10

Previous epidemiological studies have reported that prenatal exposure to metals might have influence on fetal growth. Most studies assessed the effect of individual metals, while the investigation on the relationship between multiple metal exposure and fetal growth is sparse. The objective of the present study is to assess the joint impact of metal mixtures on fetal growth during pregnancy. A total of 1275 maternal-infant pairs from the Jiangsu Birth Cohort (JBC) Study were included to investigate the effect of maternal metal exposure on fetal biometry measures at 22-24, 30-32, and 34-36 weeks of gestation. Lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), chromium (Cr), vanadium(V), thallium (Tl) and barium (Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in the first trimester. We used general linear models and restricted cubic splines to test dose-response relationships between single metals and fetal growth. The weighted quantile sum (WQS) models were then applied to evaluate the overall effect of all these metals. We observed inverse associations of exposure to Pb, V and Cr with estimated fetal weight (EFW) at 34-36 weeks of gestation. Notably, maternal exposure to metal mixtures was significantly associated with reduced EFW at 34-36 weeks of gestation after adjusting for some covariates and confounders (aβ -0.05 [95% CI: 0.09, -0.01], P = 0.023), and this association was mainly driven by Cr (30.41%), Pb (23.92%), and Tl (15.60%). These findings indicated that prenatal exposure to metal mixtures might impose adverse effects on fetal growth.

Emerging data have suggested the potential role of prenatal PM

It has been well recognized that antenatal administration of dexamethasone to pregnant women at risk of preterm delivery may markedly accelerate fetal maturation and reduce the risk of adverse perinatal outcomes in their preterm infants, particularly for births before 34 weeks of gestation. Since 2015, antenatal corticosteroid administration has been extended beyond 34 weeks of gestation by clinical guidelines, as it might have beneficial effects on fetal maturation and perinatal outcomes. However, concerns regarding the potential influence of antenatal corticosteroid treatment on offspring neurodevelopment have been raised.This study aimed to investigate whether maternal antenatal corticosteroid administration was associated with neurodevelopment in infants at 1 year of age.In this prospective and longitudinal birth cohort study, women were followed up throughout gestation, and their infants underwent a Bayley Scales of Infant and Toddler Development, Third Edition, screening test at 1 year of age between December 2018 and September 2020. Finally, 1609 pregnant women and 1759 infants were included in the current study. Using a generalized linear mixed model, we examined the association between antenatal corticosteroid exposure and infant neurodevelopment in cognitive, receptive communication, expressive communication, fine motor, and gross motor functions.Of the 1759 infants eligible for this study, 1453 (82.6%) were singletons. A total of 710 infants were exposed to antenatal corticosteroids, among whom 415 were dexamethasone exposed and 483 were prednisone exposed. Dexamethasone was prescribed most often in late pregnancy, whereas prednisone was often used before 8 weeks of gestation among women who conceived through assisted reproductive technology. Compared with those who had no exposure, antenatal corticosteroid exposure was associated with an increased risk of infants being noncompetent in the cognitive development domain after adjusting for conventional risk factors (adjusted risk ratio, 1.53; 95% confidence interval, 1.08-2.18; P=.017). For medication-specific exposure, those exposed vs not exposed to antenatal dexamethasone were 1.62-fold (95% confidence interval, 1.10-2.38; P=.014) more likely to be noncompetent in the cognitive development domain at 1 year. The association did not vary markedly between preterm and term infants, singletons and twins, or assisted reproductive technology-conceived and spontaneously conceived infants (all P.05 for heterogeneity). In contrast, a null association was observed for the risk of being noncompetent in any domain of neurodevelopment with antenatal prednisone exposure at early pregnancy.Here, antenatal corticosteroid, particularly dexamethasone exposure, was markedly associated with an increased risk of infants being noncompetent in the cognitive development domain at 1 year of age. These findings may provide new information when weighing the benefits and potential risks of maternal antenatal corticosteroid administration.

The health effects of diet are long term and persistent. Few cohort studies have investigated the influence of maternal dietary patterns during different gestational periods on offspring’s health outcomes. This study investigated the associations between maternal dietary patterns in the mid- and late-gestation and infant’s neurodevelopment at 1 year of age in the Jiangsu Birth Cohort (JBC) Study. A total of 1178 mother–child pairs were available for analysis. A semiquantitative food frequency questionnaire (FFQ) was used to investigate dietary intake at 22–26 and 30–34 gestational weeks (GWs). Neurodevelopment of children aged 1 year old was assessed using Bayley-Ⅲ Screening Test. Principal component analysis (PCA) and Poisson regression were used to extract dietary patterns and to investigate the association between dietary patterns and infant neurodevelopment. After adjusting for potential confounders, the maternal ‘Aquatic products, Fresh vegetables and Homonemeae’ pattern in the second trimester was associated with a lower risk of being non-competent in cognitive and gross motor development, respectively (cognition: aRR = 0.84; 95% CI 0.74–0.94; gross motor: aRR = 0.80; 95% CI 0.71–0.91), and the similar pattern, ‘Aquatic products and Homonemeae’, in the third trimester also showed significant association with decreased risk of failing age-appreciate cognitive and receptive communication development (cognition: aRR = 0.89; 95% CI 0.80–0.98; receptive communication: aRR = 0.91; 95% CI 0.84–0.99). Notably, adherence to the dietary pattern with relatively high aquatic and homonemeae products in both trimesters demonstrated remarkable protective effects on child neurodevelopment with the risk of being non-competent in cognitive and gross motor development decreasing by 59% (95% CI 0.21–0.79) and 63% (95% CI 0.18–0.77), respectively. Our findings suggested that adherence to the ‘Aquatic products and Homonemeae’ dietary pattern during pregnancy may have optimal effects on offspring’s neurodevelopment.

Previous animal studies provided the evidence that prenatal titanium exposure can cause neurotoxicity in their offspring, while human data is vacant. Our aim was to identify the associations of prenatal titanium exposure with the child neurodevelopment. Participants in present study were recruited during early pregnancy between 2014 and 2017. Urinary concentrations of titanium at first trimester were determined. We assessed child neurodevelopment using the Chinese version of Gesell Developmental Schedules at first year follow-up. The multivariable linear regressions and the robust modified Poisson regressions were used to estimate the associations of specific gravity corrected urinary titanium concentrations with the child neurodevelopment. In adjusted models, children's developmental quotient scores in the language domain were 2.03 points (95% CI: -3.66, -0.40) lower in the highest tertile of prenatal urinary titanium than in the lowest tertile. Also, children with prenatal urinary titanium in the highest tertile had 1.42 times (95% CI: 1.17, 1.72) increased risk of language development delay compared to those in the lowest tertile. No statistically significant associations were observed between titanium exposure and child development delay in motor, adaptive and social areas. The findings indicated that prenatal higher titanium exposure was associated with impaired language development, suggesting that titanium might act as developmental neurotoxicants.

Well-designed birth cohorts are able to estimate prevalence/distribution of various health events/outcomes, and to link early-life origins with adult health and function. The past two decades have seen a surge in the establishment of new birth cohorts and their accompanying research. We discussed distinct designs of current birth cohort studies, reviewed their achievements, and highlighted insights obtained from birth cohort studies, as well as challenges we are facing. Birth cohort studies are providing increasing opportunities to identify determining factors for short- and long-term health, yielding substantial evidence to uncover biological mechanisms of diseases and phenotypes, and providing further insights for public health. Dynamic monitoring, accurate measurements, long-term follow-ups, and collaborative efforts are warranted in new birth cohorts to elucidate the nature of life course relationships in contemporary generation.

Background: Benzophenones (BPs), parabens, and triclosan (TCS) are widely used in personal care products and may be neurotoxic to children, but limited studies have estimated the associations between exposure to these potential endocrine disrupting chemicals during pregnancy and child neurocognitive development. Objective: Our aim was to evaluate the relationships of prenatal exposure to BPs, parabens and TCS with child neurocognitive development at age 2. Methods: From 2014 to 2015, 478 mother-child pairs from a longitudinal prenatal cohort in China were included in present study. We quantified BPs, parabens and TCS in three spot urine samples during pregnancy (in the first, second, and third trimester). The Bayley Scales of Infant Development (BSID) test to children was performed at 2 years. Multivariate linear regression models and generalized estimating equations were used to examine changes in mental developmental index (MDI) and psychomotor development index (PDI) per 2-fold increase in averaged and trimester-specific maternal urinary phenols, respectively. Results: In the adjusted models, each 2-fold increase in average prenatal paraben concentration was associated with lower MDI scores among girls [−1.08 (95% CI: −2.10, −0.06) and − 1.51 (95% CI: −2.69, −0.32) for methyl paraben (Mep) and Σparabens, respectively], but the association was not statistically significant among boys [−0.24 (95% CI: −1.46, 0.99), Psex-int = 0.37 and 0.18 (95% CI: −1.28, 1.64), Psex-int = 0.10 for Mep and Σparabens, respectively]. Increasing urinary 4-hydroxybenzophenone (4-OH-BP) concentration was associated with lower PDI scores among boys [−2.96 (95% CI: −4.48, −1.45)], not girls [−0.07 (95% CI: −1.57, 1.43)] and the association was significantly different in boys and girls (Psex-int = 0.01). No significant associations were observed between the average prenatal TCS exposure and BSID results. In trimester-specific analyses, increasing parabens was associated with lower girls' MDI only in the second trimester, while increasing 4-OH-BP was associated with lower boys' PDI in each trimester. Conclusion: Our results suggest that prenatal exposure to BPs and parabens may be associated with impairment in child cognitive abilities at 2 years. Further human and animal studies are needed to verify our results and elucidate the biological mechanisms involved in these associations. Keywords: Benzophenones, Parabens, Triclosan, Child neurocognitive development

Background: Widespread exposure to parabens has been a concern, especially among pregnant women. Only one study reported that parabens are associated with glucose levels among pregnant women. However, studies on parabens exposure and gestational diabetes mellitus (GDM) are lacking. Objectives: This study investigated whether exposure to parabens in early pregnancy is related to GDM. Methods: We conducted a prospective study of 1087 pregnant women from a single tertiary medical center between 2014 and 2015 in Wuhan, China. Parabens [methyl paraben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and benzylparaben (BzP)] concentrations were measured in spot urine samples collected between 8 and 16 gestational weeks. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations. We used the Poisson regression with a robust error variance with generalized estimating equations (GEE) estimation analyses to evaluate associations between parabens exposure and GDM risk. Results: A total of 103 (9.5%) women were diagnosed with GDM. We evaluated the associations of GDM risk with urinary MeP, EtP, and PrP (detection rate: >90%), but not with BuP and BzP due to the relatively low detection rate (

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): −0.11, −0.01) and 0.08 cm (95% CI: −0.15, −0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted β = −27.99 g, 95% CI: −50.66, −5.31 and −19.75 g, 95% CI: −37.31, −2.19, respectively) and length (adjusted β = −0.08 cm, 95% CI: −0.17, 0.00 and −0.08 cm, 95% CI: −0.15, −0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.

Previous studies have proven the endocrine-disrupting properties and health hazards of parabens, triclosan, and benzophenones, but their relationship with blood pressure during pregnancy remains unknown. Therefore, we investigated the associations of repeated measures of urinary parabens, triclosan, and benzophenones with blood pressure during pregnancy and evaluated whether the associations were modified by fetal sex. From a prospective birth cohort in Wuhan, China, we collected urine samples from 644 pregnant women in the first, second, and third trimesters between 2014 and 2015. Five parabens, triclosan, and three benzophenones were quantified in all urine samples. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in each trimester after urine sampling. Mixed linear models were used to estimate the associations between urinary chemical levels and blood pressure during pregnancy among all pregnant women and subgroups stratified by fetal sex. In the women carrying male fetuses, urinary triclosan and selected benzophenone concentrations were associated with a slight change of SBP during pregnancy. In the women carrying female fetuses, no chemical was associated with SBP, while urinary concentration of triclosan was inversely associated with DBP, though the magnitude was small. Urinary paraben levels weren't associated with blood pressure during pregnancy. Our results suggest that triclosan and selected benzophenone exposure might be associated with blood pressure during pregnancy in a potential fetal sex-different manner. Replicated research studies in pregnant women with higher triclosan and benzophenone exposure levels are needed in the future.

Background: Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with high production volume worldwide, which exhibit potential health risk to human. To date, little is known about the exposure of BTRs and BTHs (BTs) on human, especially in the context of pregnancy. Objectives: We aimed to characterize the exposure profiles, temporal variability, and potential predictors of urinary BTs during pregnancy. Methods: Between 2014 and 2015, we recruited 856 pregnant women in Wuhan who provided urine samples at three trimesters (13.1 ± 1.1, 23.7 ± 3.2, and 35.7 ± 3.4 gestational weeks). We measured the urinary concentrations of five BTRs (1‑H‑benzotriazole, 1‑hydroxy‑benzotriazole, xylyltriazole, tolyltriazole, 5‑chloro‑1‑H‑benzotriazole) and five BTHs (benzothiazole, 2‑hydroxy‑benzothiazole, 2‑methylthio‑benzothiazole, 2‑amino‑benzothiazole, 2‑thiocyanomethylthio‑benzothiazole) to characterize the exposure profiles of BTs. We calculated the intra-class correlation coefficients (ICCs) to assess the temporal variability and investigated potential predictors of urinary BTs by using the mixed models. Results: Most of the targeted BTs were detected in over 50% of urine samples, except for 5‑chloro‑1‑H‑benzotriazole (9.3%) and 2‑thiocyanomethylthio-benzothiazole (1.4%). The predominant BTRs in urine was 1‑hydroxy‑benzotriazole [Geometric Mean (GM): 0.77 ng/mL]. Benzothiazole was the major derivative in urine samples with a GM concentration of 1.6 ng/mL. Correlations among BTHs (r = 0.04–0.39) were higher than that among BTRs (r = 0.02–0.14). The exposure pattern was constant at low level and co-exposure to all the targeted compounds was infrequent during pregnancy. Urinary concentrations of BTRs exhibited considerable within-subject variation (ICCs: 0.12–0.56) during pregnancy. Relatively high temporal reliability was observed for urinary concentrations of BTHs with ICCs ranging from 0.42 to 0.85. It was found that parity, household income, pregnancy occupational status, sampling season and menstrual cycle were associated with urinary concentrations of BTs in pregnant women (P

Background: Previous studies have suggested that phthalates might disrupt fetal steroidogenesis. However, the evidence of the effects of prenatal phthalate exposure across pregnancy on fetal glucocorticoids was insufficient. Objective: We investigated the associations between urinary phthalate metabolites across pregnancy and cord blood glucocorticoids in a prospective birth cohort. Methods: Our study included 553 mother-infant pairs from a prospective birth cohort conducted in Wuhan, China. Maternal urine samples were collected at 14, 24 and 36 weeks of gestation (mean). Urinary phthalate metabolites and cord blood glucocorticoids (cortisol and cortisone) were measured. Generalized estimating equation models were conducted to explore the relationships of phthalate metabolite concentrations at each trimester and glucocorticoid levels. Results: Among the participants, mono‑benzyl phthalate (MBzP) in the first trimester was associated with higher cortisol/cortisone ratio concentrations, and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP) and mono‑(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP) measured in the third trimester were associated with decreased cortisone. Moreover, the associations between phthalates and glucocorticoids varied by sex. Among the female infants, each 10-fold increase in several maternal urinary phthalate metabolite concentrations in 1st and 3rd trimester was associated with the increased glucocorticoid levels with percent changes ranged from 16.2%–55.9%. However, among male infants, each 10-fold increase in maternal urinary MECPP, mono‑(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP) and MEOHP in 3rd trimester was associated with 20.8%–36.3% decreased cortisol and cortisone levels, respectively. Conclusion: We have shown that prenatal phthalate exposure during early and late trimester disrupted the infant steroidogenesis and these associations might be modified by infant sex. To the best of our knowledge, this is the first study to evaluate phthalate exposure at three trimesters during pregnancy in relation to infant glucocorticoids. Keywords: Phthalate, Glucocorticoid, Prenatal exposure, Trimester-specific

Background: Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with potential insulin modulation activities. Pregnancy exposure to BTs (BTRs and BTHs) may be a risk factor for the development of gestational diabetes mellitus (GDM). However, epidemiological studies are limited. Objectives: We prospectively investigated the associations of exposure to BTs at early pregnancy with the blood glucose levels and the risks of GDM. Methods: A prospective cohort of 1770 pregnant women who were free of diabetes at baseline was established between 2013 and 2015 in Wuhan, China. Urine samples collected at 13.1 ± 1.1 weeks of gestation were analyzed to estimate the exposure level of BTs. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) conducted at 26.4 ± 2.4 weeks of gestation. We examined the associations between urinary concentration of BTs and blood glucose levels by linear regression models. The associations of urinary BTs concentrations with the relative risk (RR) of GDM were evaluated by generalized estimating equations with Poisson regression. Effect modifications by fetus sex and pre-pregnancy body mass index (BMI) were further evaluated in the sensitivity analysis. Results:A total of 147 (8.31%) pregnant women were diagnosed with GDM. Median concentrations of urinary BTs did not differ significantly between pregnant women with and without GDM. It was found that urinary levels of benzothiazole and 2-hydroxy-benzothiazole (2-OH-BTH) were positively associated with 2-hour blood glucose (p for trend

Summary Background Identification of windows of heightened vulnerability to environmental factors has substantial public health implications. Prenatal exposure to vanadium has been linked to adverse birth outcomes; however, critical windows for such exposure during fetal growth remain unknown. We aimed to assess trimester-specific associations of vanadium exposure with ultrasound measures of fetal growth and birth size in a Chinese longitudinal cohort. Methods The present study was embedded in our ongoing prospective prenatal cohort study at the Wuhan Women and Children Medical Care Center (Wuhan, Hubei, China). Pregnant women were eligible for inclusion if they provided signed informed consent and were less than 16 weeks pregnant with a single gestation, and agreed to take in-person interviews, undergo ultrasound examinations, and provide blood and urine samples. We collected urine samples and measured urinary vanadium concentrations using inductively coupled plasma mass spectrometry. We calculated SD scores for ultrasound-measured biparietal diameter, head circumference, occipitofrontal diameter, abdominal circumference, femur length, and estimated fetal weight at 16, 24, and 31 weeks of gestation. We applied linear regressions with generalised estimating equations to estimate associations of urinary vanadium concentrations in each trimester with ultrasound-measured fetal growth parameters or neonatal size at birth. Findings As of Oct 12, 2016, we recruited 3075 women who were non-smokers and non-drinkers during pregnancy, provided up to three urine samples during the first, second, and third trimesters, and gave birth to live singletons without birth defects. We excluded women who did not provide information on ultrasound measurements (n=20) or who only had one ultrasound measurement of fetal crown–rump length at the first trimester (n=14). We excluded another 16 women because they had missing values for confounding variables, leaving 3025 women retained in the study. Every doubling of urinary vanadium concentration in the first trimester was associated with a significant increase in femur length (adjusted percentage change 6·4%, 95% CI 0·7 to 12·1) at 16 weeks of gestation and reductions in biparietal diameter (−4·2%, −8·2 to −0·1), head circumference (−6·0%, −10·1 to −1·9), occipitofrontal diameter (−5·7%, −9·9 to −1·5), and abdominal circumference (−5·3%, −9·4 to −1·2) at 31 weeks of gestation. Every doubling of urinary vanadium concentration in the second trimester was significantly associated with reductions in SD scores for head circumference (−7·2%, −14·1 to −0·3) and abdominal circumference (−6·9%, −13·8 to −0·1) at 31 weeks of gestation. The highest quartile of urinary vanadium concentration (>1·18 μg/L) in the first trimester, when compared with the lowest quartile (≤0·60 μg/L), was associated with a mean decrease in birthweight of 12·6 g (95% CI 2·5–22·8; ptrend=0·0055) and a mean decrease in ponderal index of 0·07 kg/m3 (0·01–0·12; ptrend=0·0053). Moreover, newborns with restricted birth size had higher vanadium exposure in the first and third trimesters. Interpretation Vanadium might be toxic to humans and impair fetal growth. The first, early second, and late third trimesters could be critical windows for heightened vulnerability to vanadium for fetal growth. Our findings require further investigation in other populations. Funding National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Huazhong University of Science and Technology.

The excess or deficiency of trace metals can cause adverse neurocognitive development. Evidence of health effect of trace metal mixtures on neurocognitive development is limited in children. We evaluated associations of prenatal exposure to trace metals and metal mixtures with neurocognitive development of 2-year-old children. A total of 544 mother-child pairs were included in the study. The concentrations of 10 trace metals in maternal urine were monitored before delivery. Neurocognitive development indexes, including mental development index (MDI) and psychomotor development index (PDI), were assessed using the Bayley Scales of Infant Development. Linear regression analysis was performed to explore the effects of single-metal and multi-metal exposures. Bayesian Kernel Machine regression (BKMR) was used to investigate overall effect of exposure to metal mixtures and potential interactions among mixture components. We found positive associations of urinary strontium (Sr) and Selenium (Se) levels with MDI scores among all children in the single-metal model. Sr was positively related to MDI, while Manganese (Mn) was negatively associated with PDI in the multi-metal model. The results from BKMR model in girls revealed that MDI scores were improved with the increasing concentrations of Sr, Se and Mn mixture until the concentrations reached their 30th percentiles (Sr: 149.49 μg/g creatinine, Se:18.38 μg/g creatinine, Mn:1.96 μg/g creatinine), with no effect after that threshold level. Sr played a positive role in mental development among mixture components, which was consistent with the results of Sr in the multi-metal models. No signification association of mixture with MDI/PDI was found in boys. The study suggested potential sex-specific association of Sr, Se and Mn mixture levels (at or below their 30th percentiles) with improved mental development, and beneficial role of Sr.

There is a proposed link between prenatal nickel (Ni) exposure and preterm low birth weight (PLBW); however, this association remains unclear. Selenium (Se) may modify this relationship by protecting against Ni toxicity. Concentrations of Ni and Se were measured in urine samples collected from 408 pregnant women (102 PLBW cases and 306 matched controls) in China. Conditional logistic regression was utilized to explore the association between Ni levels and PLBW, as well as the effect modification by Se on this association. A significant association was observed between higher maternal urinary Ni levels and risk of PLBW [adjusted odds ratio (OR) = 2.80 (95% confidence interval (CI): 1.44, 5.44) for the highest tertile], and this association was more apparent among female infants than that among male infants. Further analyses showed that mothers with high urinary Ni and low urinary Se levels had a significantly increased risk for PLBW [adjusted OR = 2.87 (95% CI: 1.09, 7.56)] compared with the mothers with low urinary Ni and high urinary Se levels. Our study indicates that prenatal exposure to Ni was a risk factor for PLBW. Se might provide protection against the toxicity of Ni.

Previous studies provided a strong evidence of the association between environmental exposure to cadmium (Cd) and hypertension in the general population. However, the role of Cd in pregnancy-induced hypertension (PIH) remains unclear. A total of 5429 pregnant women was selected from a birth cohort in Wuhan, China to investigate the association between Cd exposure and risk of PIH. Among them, 199 (3.7%) women were diagnosed with PIH. The Cd concentrations in maternal urine collected at delivery were measured by inductively coupled plasma mass spectrometry. Multivariable logistic regression was performed on Cd concentrations as a continuous variable (natural logarithm transformed) or as a categorical variable (tertiles). For about 3-fold increase in urinary Cd concentrations, there was 75% increase in the odds of PIH after adjusting for potential confounders (odds ratio (OR) =1.75; 95% confidence interval (CI): 1.45, 2.11). Women in the highest tertile of urinary Cd had 2.2-fold increased OR of PIH, compared with women in the lowest tertile (2.24; 95% CI: 1.47, 3.41). Furthermore, we found a significant interaction between Cd exposure and maternal socioeconomic status on PIH (P for interaction=0.04). Our findings indicate that higher Cd exposure might increase the risk of PIH, and the association might be modified by socioeconomic status.

Triclosan (TCS) is a suspected endocrine disrupting chemical which is widely used in consumer products as an antibacterial agent. But findings in human studies focusing on the fetal developmental effects of prenatal TCS exposure were rare and inconsistent. This study aimed to determine maternal urinary TCS and investigate its association with birth outcomes. Pregnant women (n = 1006) were randomly selected from the prospective Healthy Baby Cohort (HBC) enrolled in 2014. TCS levels were determined in maternal urine samples collected at delivery and recorded birth outcomes were obtained from the medical records. Multiple linear regressions were applied to evaluate associations of maternal urinary TCS levels with birth outcomes including birth weight, birth length, and gestational age. Logistic regressions were used to evaluate associations with preterm birth, late term birth, and low birth weight. The geometric mean concentrations for TCS and specific gravity (SG) adjusted TCS in maternal urines were 0.73, 0.78 ng/mL, respectively. In the crude model, one ln-unit increase of urinary SG-adjusted TCS concentration was associated with a 0.30-day [95% confidence interval (CI): 0.00, 0.60] increase in gestational age; however, the associations were not statistically significant after adjustment for covariates. No significant associations of SG-adjusted TCS concentrations with birth weight and birth length were observed. Maternal SG-adjusted TCS concentrations were not related to preterm birth, late term birth, and low birth weight (all p > 0.10). Our findings reported a relatively low level of TCS among Chinese pregnant women. With such exposure level, we did not find strong evidence for associations between maternal TCS exposure and birth outcomes. Longitudinal studies concerning about different potential effects of TCS on perinatal health are necessary.

Chromium exposure from increasing industrial releases has become a threat for pregnant women due to the potential health effects on vulnerable embryos. Previous studies have suggested that maternal chromium exposure is associated with adverse birth outcomes, but no epidemiological research has been conducted to examine the relationship between chromium exposure and premature rupture of membranes (PROM). This study aimed at investigating the association of maternal urinary chromium exposure levels with PROM and was performed with 5408 pregnant women recruited from 2012 to 2014 in the city of Wuhan, China. Maternal urinary chromium collected before labor was adjusted with creatinine, and its association with PROM was evaluated using logistic regression. Each one unit increase in the natural logarithm transformed maternal urinary chromium concentration (μg/g creatinine), an odds ratio (OR) of 1.47 [95% confidence interval (CI): 1.36, 1.58] for PROM was observed. Compared to the lowest tertile of maternal urinary chromium, PROM was positively correlated with increased urinary levels of chromium (adjusted OR = 1.42; 95% CI: 1.09, 1.84 for the medium tertile; adjusted OR = 2.77; 95% CI: 2.18, 3.52 for the highest tertile). Additionally, the association of chromium with PROM appeared to be more significant among male infants (adjusted OR = 3.52; 95% CI: 2.51, 4.94 for the highest tertile) than female infants (adjusted OR = 2.16; 95% CI: 1.52, 3.06 for the highest tertile) ( p for interaction = 0.05). Our large birth cohort showed an association between maternal urinary chromium levels and PROM, and the association may differ by infant gender. Further studies from different populations are needed to confirm the observed association.

Background Parabens are suspected to impair fetal growth because of their endocrine disrupting effects. Epidemiological studies regarding the effects of prenatal exposure to parabens on birth outcomes are limited. Objectives Our aim was to evaluate the association between prenatal paraben exposure and size of infants at birth. Methods Within the longitudinal Healthy Baby Cohort (HBC) in Hubei Province, China, we randomly selected 1006 mother-infant pairs recruited in Wuhan City in 2014. Concentrations of parabens were measured in maternal urine collected before delivery. General linear models were used to analyze the associations of maternal parabens exposure levels with birth weight and birth length. Results The specific gravity adjusted geometric means for urinary concentrations of methyl paraben (MeP), ethyl paraben (EtP), and propyl paraben (PrP) were 5.41, 0.11, and 0.94 ng/mL, respectively. Maternal urinary concentrations of parabens tended to be positively associated with birth weight in boys, while opposite trends were found in girls, though these associations were not significant. Higher maternal urinary levels of MeP were positively associated with birth length in boys (β = 0.30, 95% CI: 0.01, 0.58 for the medium tertile, and β = 0.30, 95% CI: 0.01, 0.58 for the highest tertile compared to the lowest tertile); however, no significant associations with birth length were observed in girls. Conclusions Maternal urinary levels of MeP were positively associated with length at birth in boys. Besides, we did not find strong associations of the current exposure levels of parabens in Chinese pregnant women with size of infants at birth.

While increasing evidence has shown that prenatal bisphenol A (BPA) exposure is adversely associated with child neurodevelopment, little is known about the neurodevelopmental effects of BPA alternatives, such as bisphenol S (BPS) and bisphenol F (BPF). We aimed to evaluate the relationships of repeated measurements of bisphenol exposure during pregnancy with child neurodevelopment. From 2014–2015, 456 mother-child pairs were included in the present study. Each had a spot urine sample in the first, second, and third trimester, respectively, during pregnancy for BPA, BPS, and BPF measurements. Children’s neurodevelopment was assessed using the Bayley Scales of Infant Development at 2 years. In adjusted models, children’s psychomotor development index scores decreased across quartiles of BPS concentrations [-5.52 (95 % CI: -10.06, -0.99) in the 4th quartile vs. 1 st quartile, P-trend = 0.01]. Each 10-fold increase in BPA concentrations was related to lower mental development index scores only in the second trimester [-2.87 (95 % CI: -4.98, -0.75), Ptrimester-int = 0.04]. However, prenatal BPF exposure was not significantly associated with child neurodevelopment. We provide evidence that prenatal exposure to BPA and BPS may affect child neurodevelopment.

BACKGROUND Pregnancy hypertensive disorders have impaired neurodevelopment in offspring. We aimed to explore the association of normal range maternal blood pressure (BP) with child neurodevelopment, as well as the possible role of placental 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) therein. METHODS Among 1,008 mother–child pairs recruited in Wuhan, China, in 2013–2015, we measured maternal third-trimester BP (systolic BP (SBP) and diastolic BP (DBP)) and cord glucocorticoids (cortisol and cortisone), a marker reflecting placental 11β-HSD2 activity. We evaluated child neurodevelopment using the Bayley Scales of Infant Development (BSID) with obtaining the Mental and Psychomotor Development Index (MDI and PDI). Multiple regression and mediation analysis were performed to estimate the effect. RESULTS Each 5 mm Hg increase in maternal third-trimester SBP was associated with 1.54 points decrease in MDI (95% confidence interval (CI) = –2.60, –0.48) and 1.23 points decrease in PDI (95% CI = –2.14, –0.31); similar association was observed between DBP and BSID (adjusted β = –1.32; 95% CI = –2.53, –0.10 for MDI and –1.37; 95% CI = –2.42, –0.33 for PDI). Also, we found significant associations between cord cortisol/cortisone ratio and PDI (adjusted β = 2.95; 95% CI = 0.91, 4.99), as well as between maternal BP and cord cortisol/cortisone ratio (adjusted β = –0.03; 95% CI = –0.06, –0.01 for both SBP and DBP). Mediation analysis revealed that cord cortisol/cortisone ratio explained 6.29% of the association between SBP and PDI, and 6.85% between DBP and PDI. CONCLUSIONS Increased maternal normal range BP may affect child neurodevelopment. Furthermore, placental 11β-HSD2 activity might be involved in the process.

Experimental studies suggested per- and polyfluoroalkyl substances (PFASs) may disrupt estrogens in animals, however, the epidemiological evidence on the associations of PFASs with estrogens is sparse. We investigated the associations of legacy PFASs and their alternatives, including F-53B, the perfluorooctane sulfonate (PFOS) replacement that is specifically and commonly used in China, with estrogen concentrations in newborns. We quantified six PFASs and three estrogens in the cord sera of 942 newborns from a birth cohort in Wuhan, China, between 2013 and 2014. After adjusting for confounders and correcting for multiple comparisons, we observed that both legacy PFASs and their alternatives were associated with higher serum levels of estradiol (E2). Some of the PFASs were associated with increasing levels of estrone (E1) and estriol (E3). Analysis of PFASs in mixture using weighted quantile sum regressions showed that F-53B contributed 20.1% and 48.5% to the associations between PFASs and E1 and E2, respectively. This study provided epidemiological data on the associations between common PFAS exposures and estrogens in newborns. Additional toxicology studies are needed to fully understand the effects of PFASs on estrogens and the mechanisms.

Increasing evidence shows that exposure to per- and polyfluoroalkyl substances (PFASs), common and persistent anthropogenic pollutants, may affect glucose homeostasis. However, data is limited for pregnant women, and it is less clear how novel fluorinated pollutants affect glucose homeostasis during pregnancy. Our goal was to investigate the relationships of exposure to13 PFASs including some novel fluorinated pollutants with blood glucose in 874 Chinese pregnant women from the general population. We measured blood glucose following an oral glucose tolerance test (OGTT) in the second trimester and quantified PFAS concentrations in umbilical cord blood. The associations of PFAS exposure with fasting, 1-h OGTT and 2-h OGTT glucose were examined using the general linear regression model. For every doubling of perfluorobutane sulfonate (PFBS), a short-chain PFAS, the 1-h and 2-h OGTT blood glucose increased 0.09 mmol/L (β = 0.09, 95%CI: 0.02, 0.17) and 0.07 mmol/L (β = 0.07, 95%CI: 0.01, 0.13), respectively. In addition, perfluoroheptanoate (PFHpA), an alternative of perfluorooctanoate (PFOA), was positively associated with fasting glucose (β = 0.07, 95%CI: 0.02, 0.13; high vs low). Higher levels of PFAS exposure were related to increased blood glucose in pregnant women, indicating PFAS exposure may impair glucose homeostasis during pregnancy.

ContextMaternal thyroid hormones during pregnancy play a critical role in fetal development. However, whether maternal heavy metal exposure affects their thyroid hormones and the effects on fetal growth are still unclear.ObjectiveTo explore the effect of heavy metal exposure on maternal thyroid hormones and the potential mediation role of thyroid hormones on birth outcomes.MethodsConcentrations of heavy metals in urine samples and thyroid hormones in blood samples of 675 pregnant women were measured during early pregnancy in a cohort study conducted in China. Multivariable linear regressions were applied to explore the associations of maternal urinary heavy metal levels with both maternal thyroid hormones and birth outcomes. Mediation analyses were performed to assess the mediation role of thyroid hormones in these associations.ResultsMaternal urinary vanadium (V) exhibited an inverse association with free T3 (FT3) and FT3/free T4 (FT4) ratio levels. Urinary arsenic (As) and lead (Pb) had inverse relationships with FT3. We also observed the positive associations of maternal FT3 and FT3/FT4 ratio with birthweight. The mediation analyses suggested that 5.33% to 30.57% of the associations among V, As, and Pb levels and birth size might be mediated by maternal FT3 or FT3/FT4 ratio.ConclusionsWe have shown that maternal exposures to V, As, and Pb at early pregnancy were associated with decreased maternal FT3 or FT3/FT4 ratio, which might contribute to reduced birthweight. Mediation analyses indicated that maternal thyroid hormone was a possible mediator of the association between urinary heavy metals and birth size.

Prenatal life exposure to fine particulate matter (aerodynamic diameter less than or equal to 2.5 µm, PM2.5) has been linked with increased risk of adverse fetal development and birth outcomes in previous studies. However, to our knowledge, no study has investigated the association of maternal PM2.5 with the risk of fetal distress, which is a harmful fetal status and may lead to fetal brain damage, even fetal death. Therefore, we conducted a study to determine the association between maternal PM2.5 and fetal distress among 7835 mother-infant pairs from a birth cohort, in Wuhan, China, 2013–2015. The individual daily PM2.5 level was assessed using land use regression model. We evaluated the association of maternal PM2.5 level over the whole pregnancy with fetal distress by logistic regression model, and estimated the risk between PM2.5 exposure in specific trimester and fetal distress using generalized estimating equations. We observed that per 10 µg/m3 change of maternal PM2.5 level over the whole pregnancy was associated with 25% increased risk of fetal distress (95% confidence interval: 1.09–1.44). Further, we found PM2.5 level in the 2nd trimester, but not in the 1st and 3rd trimesters, was associated with fetal distress. Stratified analyses indicated that the association was only significant among infants who were born in cold seasons. Our study suggested that PM2.5 exposure during the whole pregnancy exhibited significant associations with the risk of fetal distress, and exposure in the 2nd trimester maybe the susceptible window. Further stratified analyses indicated that birth season is a possible modifier in the association.

Heavy metal exposure has been indicated to be linked with reproductive and developmental toxicity. However, human studies on the association between heavy metal exposure and premature rupture of membranes (PROM) are limited. Thus, we aimed to evaluate the associations between urinary metal concentrations in pregnant women and the risk of PROM. The study was conducted among 7290 pregnant women from an ongoing cohort study in China. Levels of urinary metals were determined using an inductively coupled plasma-mass spectrometry and adjusted by creatinine concentration (μg/g creatinine). Adjusted odds ratios (OR) and 95% confidence intervals (CI) for PROM and preterm PROM were estimated using logistic regression models. Among 12 urinary metals detected, vanadium (V) have shown stable positive associations with PROM and preterm PROM. With one unit increase in natural logarithmically transformed urinary V concentration, adjusted OR of 1.57 (95% CI: 1.47, 1.66) for PROM was observed. Compared with the lowest tertile of urinary V, we also observed positive associations between V levels and PROM (for the medium tertile, adjusted OR = 1.66, 95% CI: 1.34, 2.05; for the highest tertile, adjusted OR = 3.75, 95% CI: 3.09, 4.54). In addition, higher adjusted ORs for preterm PROM were observed (for the highest tertile, adjusted OR = 8.14, 95% CI: 4.55, 14.55). Further stratified analysis suggested the associations were more pronounced among women delivering male infants than those with female infants. Our present epidemiological study indicated that pregnant women exposure to higher level of V might lead to an increased risk of PROM.

Background: Several studies have reported that cadmium (Cd) is associated with type 2 diabetes. However, little is known about Cd exposure and the risk of gestational diabetes mellitus (GDM). Objective: We examined the association between Cd body burden in early pregnancy and the risk of GDM. Methods: We conducted a prospective study of 2,026 pregnant women from a single tertiary medical center between 2013 and 2016 in Wuhan, China. Cd body burden was reflected by Cd concentrations in urine samples collected between gestational weeks 8 and 14. GDM was diagnosed according to International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations. Results: The geometric mean of Cd concentrations in maternal urine of all pregnant women was 0.59μg/L. A total of 198 (9.8%) women were diagnosed with GDM. After adjustment for potential confounders, the risk ratios (RRs) of GDM were 1.04 (95% CI: 0.74, 1.44) for the middle tertile of Cd levels and 1.36 (95%: CI: 0.98, 1.90) for the top tertile compared with the bottom tertile. In addition, we found a significant interaction between fetal sex and maternal Cd levels on the risk of GDM (p for interaction=0.03). Among women carrying male fetuses, the RR of GDM was 1.86 (95% CI: 1.14, 2.93) for the top tertile of Cd levels compared with the bottom tertile. Conclusions: To our knowledge, this is the first report of an association between urinary Cd levels in early pregnancy and GDM. Our findings suggest that Cd body burden increases the risk of GDM and that the association may be modified by fetal sex. https://doi.org/10.1289/EHP2716