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Prenatal exposure to benzotriazoles and benzothiazoles (collectively as BTs) was associated with pregnancy complications. Identifying the metabolites associated with prenatal BTs exposure may help elucidate the mechanism and characterize the exposure risk. In this prospective study of 158 pregnant women from Wuhan, China, urinary BTs were repeatedly measured across three trimesters to provide an accurate estimation of exposure during pregnancy. We conducted high-throughput targeted metabolomics with great coverage and high accuracy to characterize the urinary metabolic profile in late pregnancy. We first identified the perturbed metabolites of cocktail BTs exposure and then pinned down to the pairwise associations between individual BTs and the identified metabolites. A total of 44 metabolites were identified as perturbed biomarkers of cocktail BTs exposure based on the variable influence on projection (VIP > 1.2) score. Further pairwise associations analysis showed positive association of BTs with oxidative stress related biomarkers and negative association of BTs with neuronal function metabolites. The shared metabolic signatures among BTs in the co-occurrence network of pairwise association analysis may partially be attributed to the correlation among cocktail BTs exposure. The findings provide the potential mechanisms of BTs-associated pregnancy complications and offer insight into the health implications for prenatal BTs exposure. Furthermore, the framework we employed, which integrates both cocktail exposure and individual exposure, may illuminate future epidemiological research that seeks to incorporate exposure to mixtures and omics scale data. [Display omitted] • Repeated measurements provided an accurate estimation of exposure during pregnancy. • High throughput targeted metabolomics ensures great coverage and high accuracy of metabolites. • Novel framework integrated the cocktail exposure and individual exposure was applied. • The framework may illuminate future studies integrating cocktail exposure and omics scale data. [ABSTRACT FROM AUTHOR]

• First study on maternal urinary levels of BTRs and BTHs and newborn mtDNAcn. • Exposure to BTRs and BTHs during first and third trimester were associated with newborn mtDNAcn alternation. • Sex-specific associations were observed between BTRs and BTHs exposure and newborn mtDNAcn. Mitochondria are sensitive to environmental toxicants due to the limited repair capacity. Exposure to benzotriazoles (BTRs) and benzothiazoles (BTHs) may contribute to adverse health outcomes through oxidative stress, which may interfere with mitochondrial function. However, the mitochondrial effects of exposure to BTs (BTRs and BTHs) have not yet been elucidated, particularly in human investigations. We examined the associations between trimester-specific urinary BTRs and BTHs concentrations and cord blood mitochondrial DNA copy number (mtDNAcn) in a prospective birth cohort. The present study included 742 mother-infant pairs who participated in a birth cohort between 2014 and 2015 in Wuhan and had data on urinary concentrations of BTRs and BTHs and mtDNAcn in cord blood. Concentrations of BTs were repeatedly measured in maternal urine samples at different trimesters using high performance liquid chromatography-tandem mass spectrometry. Relative mtDNAcn in umbilical cord blood was analyzed by quantitative real-time polymerase chain reaction. Generalized estimating equations were used to evaluate the associations between BTs exposure across gestation and mtDNAcn in cord blood. In the present study, we observed a positive association between urinary 2-methylthio-benzothiazole (2-MeS-BTH) concentrations in the first trimester and cord blood mtDNAcn, with marginal significance [percent changes (%Δ) = 3.97, 95% confidence interval (CI): −0.05, 8.16, p = 0.05], while urinary 2-amino-benzothiazole concentrations in the third trimester were significantly negatively associated with cord blood mtDNAcn (%Δ = −5.89, 95% CI: −10.32, −1.24). Similar patterns of associations were demonstrated between urinary 1-H-benzotriazole (1-H-BTR) and xylyltriazole concentrations in the third trimester and cord blood mtDNAcn (%Δ = −4.18 to −3.23). In sex-specific analysis, we identified that maternal urinary 1-H-BTR in the first trimester and 2-MeS-BTH in the third trimester were positively associated with cord blood mtDNAcn among male infants but not female (P for interaction = 0.05 for 1-H-BTR, P for interaction = 0.05 for 2-MeS-BTH, respectively). We found evidence that prenatal exposure to BTRs and BTHs were associated with cord blood mtDNAcn alternation, and these associations were modified by infant gender. Further investigations are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • Association between maternal phthalate exposure during pregnancy and cord glucocorticoids was evaluated for the first time. • Prenatal phthalate exposure during early and late trimester might disrupt the fetal steroidogenesis. • Fetal sex might modify the relationship of phthalate exposure and glucocorticoid levels. [ABSTRACT FROM AUTHOR]

Exposure to chromium is increasing due to environmental pollution from industrial processes. Several epidemiological studies have investigated chromium exposure and reproductive outcomes, but few studies have investigated the association of chromium exposure and low birth weight (LBW). This study was designed to investigate whether maternal exposure to chromium during pregnancy is associated with an increased risk of LBW. Chromium concentrations in maternal urine samples collected at delivery were measured in 204 LBW cases and 612 matched controls recruited between 2012 and 2014 in Hubei Province, China. Risk of LBW was associated with higher levels of chromium in maternal urine [adjusted odds ratio (OR) = 1.77 for the medium tertile, 95% confidence interval (CI): 0.95, 3.29; adjusted OR = 2.48 for the highest tertile, 95% CI: 1.33, 4.61; P trend = 0.01]. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile, 95% CI: 1.50, 8.97) than among male infants (adjusted OR = 1.22 for the highest tertile, 95% CI = 0.48, 3.11) ( p heterogeneity = 0.06). Our findings suggest that maternal exposure to higher levels of chromium during pregnancy may potentially increase the risk of delivering LBW infants, particularly for female infants. [ABSTRACT FROM AUTHOR]

We investigated the association between prenatal exposure to lead (Pb) and the risk of preterm low birth weight (PLBW). Pb concentrations in maternal urine collected at birth from 408 subjects (102 cases and 306 matched controls) were analyzed and adjusted by creatinine. The median Pb concentration in the PLBW cases (10.60 μg Pb/g creatinine) was higher than that of the controls (7.28 μg Pb/g creatinine). An adjusted odds ratio (OR) of 2.96 (95% CI = 1.49–5.87) for PLBW was observed when the highest tertile was compared to the lowest tertile of Pb levels. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile; 95% CI = 1.35–9.93) than male infants (adjusted OR = 1.91 for the highest tertile; 95% CI = 0.74–4.95). Our study suggests that prenatal exposure to levels of Pb encountered today in China is associated with an elevated risk of PLBW. [ABSTRACT FROM AUTHOR]

Phthalates are a family of endocrine disruptors with short elimination half-lives in the human body. To date, few epidemiological studies have examined repeated measures of maternal urinary phthalates and the combined effects of prenatal exposure to multiple phthalates on children's neurocognitive development. We aimed to investigate the association between children's neurocognitive development at 2 years of age and prenatal phthalate exposure, as assessed by repeated measurements during pregnancy, and to further examine the effects of co-exposure to multiple phthalates using cumulative risk assessment. Within a prenatal cohort in Wuhan, China, we measured five high-molecular-weight (HMW) phthalates and three low-molecular-weight (LMW) phthalate metabolites' concentrations in three urine samples collected in the 1st, 2nd, and 3rd trimester of pregnancy from each mother. We assessed neurocognitive development by Bayley Scales of Infant and Toddler Development (BSID) at 2 years of age (n = 476) to obtain the children's mental development index (MDI) and psychomotor development index (PDI). Higher exposure levels to LMW phthalates compared to HMW phthalates were observed in our population. Ln-transformed averaged concentration of mono- n -butyl phthalate (MnBP), a metabolite of the LMW phthalate di- n -butyl phthalate (DnBP) during pregnancy, was associated with decreased PDI scores in all children (β = −1.90, 95% CI: −3.43, −0.37). Similarly, the averaged sum concentration of ∑dibutyl phthalate (∑DBP) was associated with decreased PDI scores in all children (β = −1.89, 95% CI: −3.63, −0.15). A negative trend of association between exposure to HMW phthalates and PDI scores was observed in girls, while a positive association was found in boys. In cumulative risk assessment analyses, we consistently observed that the hazard quotient of DnBP (the parent compound of MnBP) was inversely associated with PDI scores in all children, whereas the hazard quotient of di-2-ethylhexyl phthalate (DEHP), an HMW phthalate, was positively associated with PDI scores in boys only. This study is the first to use repeated measurement of maternal urinary phthalates in all three trimesters to assess prenatal exposure in relation to children's neurodevelopment. Our study suggested a negative association between prenatal exposure to MnBP and children's psychomotor development, and potentially sex-specific associations between HMW phthalates and neurocognitive development among boys and girls. These findings warrant further confirmation. • We first evaluated the effect of repeated measurements of maternal urinary phthalates on child neurocognitive development. • Prenatal exposure to mono-n-butyl phthalate was negatively associated with children's psychomotor development. • The sex-specific effect may exist between phthalates and neurocognitive development. [ABSTRACT FROM AUTHOR]