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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]

Maternal exposure to phthalates may cause some adverse health effects on both mother and fetus, but variations of phthalate exposure and metabolism during pregnancy have not been thoroughly characterized. A total of 946 participants were selected from a cohort study conducted in Wuhan between 2014 and 2015 through which they had provided a complete set of urine samples at three trimesters. Eight phthalate metabolites were analyzed in 2838 urine samples. Based on urinary concentrations, various parameters (i.e. phthalate metabolite concentrations, ratios of metabolites of bis(2-ethylhexyl) phthalate (DEHP) in DEHP, and percentages of individual metabolites in total phthalates) were compared over three visits. We observed that levels of phthalate metabolites showed a U-shaped trend across three trimesters. The significant variations in the ratios of DEHP metabolites indicated that the efficiency in metabolizing DEHP declined during pregnancy and less recent exposure occurred in mid-pregnancy. The changes of percentages of individual compound in total phthalates suggested the inconsistent pattern over trimesters. This longitudinal study found that the exposure pattern, exposure timing and metabolic susceptibility varied by trimesters, which suggests that urine samples should be collected at multiple time points and mothers should be especially careful in the early pregnancy. Image 1 • Phthalate metabolite concentrations demonstrated U-trend over three trimesters. • The efficiency in metabolizing di-2-ethylhexyl phthalate decreased during pregnancy. • More recent exposure occurred on early and late gestational periods. • Mothers were more susceptive to DEHP in the early stages of pregnancy. • Multiple samples were needed to evaluate phthalate exposure throughout pregnancy. Urinary concentrations of phthalate metabolites showed a U-shaped trend across three trimesters. Mothers were more susceptive to phthalate exposure in the early stages of pregnancy. [ABSTRACT FROM AUTHOR]

Abstract As endocrine disrupting chemicals, hexachlorocyclohexane (HCH) isomers were reported to impair the intrauterine growth. Although the findings of HCHs with preterm birth were well established, the associations with gestational age were limited. In the present study, we examined whether exposure to HCHs would influence gestational age. The study population included 1028 pregnant women and their offspring who were born in 2014–2015 from a birth cohort in Wuhan, China. Associations of the cord serum HCH levels with gestational age were estimated using generalized linear models. We found higher HCH levels in pregnant women, who were elder, had higher body mass index (BMI) before pregnancy, received higher education, or were exposed to smoking passively. For term birth, the 3rd tertiles of α-HCH and γ-HCH were significantly associated with shorter gestational age [crude β = −1.017, confidence interval (CI): − 2.017, − 0.018 for α-HCH, crude β = −1.068, CI: − 2.067, − 0.070 for γ-HCH], and relationships were similar after adjusted by covariates. Stratified analysis showed positive associations between α-HCH and gestational age for mothers younger than 25 years old (adjusted β = 0.610, CI: 0.061, 1.158), while showing negative relationships for mothers elder than 35 years old (adjusted β = −1.365, CI: −2.414, −0.317). In summary, our results indicated cord serum levels of HCHs were associated with gestational age at birth. Highlights • Associations between HCH exposure and gestational age were evaluated. • Opposite associations of α-HCH and gestational age were found between youngest and eldest women. • Shorter gestational age with elevated γ-HCH was observed in women with excessive weight gain. • No significant relationships were found between β-HCH and gestational age. [ABSTRACT FROM AUTHOR]

Abstract 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 (<50%). After adjustment for potential confounders, urinary EtP was associated with GDM. The risk ratios (RRs) = 1.12 (95% CI: 0.63, 2.01) for the second quartile, RRs = 1.11 (95% CI: 0.64, 1.93) for the third quartile, and RRs = 1.70 (95% CI: 1.02, 2.82) for the highest quartile, compared with the lowest quartile. There was no evidence of associations between urinary MeP or PrP and GDM. Conclusions To the best of our knowledge, this is the first report of an association between urinary paraben levels in early pregnancy and GDM. Our findings suggest that exposure to EtP may increase the risk of GDM. Highlights • 2 parabens out of 5 were not studied because they were detected in <43% of the population. • Higher urinary ethylparaben levels were associated with increased risks of GDM. • Age and pre-pregnancy BMI might modify the association of ethylparaben with GDM. [ABSTRACT FROM AUTHOR]

Bisphenol A and its alternatives are frequently detected in environmental and human samples, but studies associated with the pattern of combined health hazards from the exposure to the bisphenol mixtures are lacking, particularly for pregnant women. Here, we recruited 941 pregnant women with a full set of urine samples in the three trimesters collected under a cohort study project in Wuhan, China, between 2014 and 2015. We measured the concentrations of 8 bisphenols in 2823 urine samples, and calculated the average concentrations of bisphenols, which were detected in over 50% of samples, once during each trimester of pregnancy. We calculated the maximum cumulative ratio (MCR) on basis of estimated daily intake (EDI), hazard quotient (HQ), hazard index (HI) of three major bisphenols, including bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), to find which one or mixtures drive risks. Participants were categorized into four groups according to their maximum HQ, HI and MCR values. We found negative relationships between log(MCR-1) and log(HI) with the slope (−0.6431). Percentage of HQ of BPA in HI ranged from 37.1% (<25th percentiles of HI) to 75.5% (>95th percentiles of HI) indicating the upward trend of dominance by BPA at increasing HI ranges. The cumulative health risks of bisphenol exposures largely originated from the health hazards of BPA and BPS, particularly BPA. The intervention for regulation on the production and application of BPA and its alternatives are urgent, and China should consider national regulation on these chemicals based on its risk to human health. Image 1 • Inverse relationships between MCR and HI of bisphenol exposure were noted. • Major health hazard was induced by exposure to high dose of BPS or BPA. • BPA was dominating the combined health hazards of bisphenol exposure. • Regulation of BPS production and application should be considered in China. BPA still dominates the cumulative health risks induced by exposure to bisphenols, although the application of BPA has been restricted. [ABSTRACT FROM AUTHOR]

• Prenatal exposure to benzotriazoles and benzothiazoles were measured in urine samples collected across three trimesters. • Repeated ultrasound measurements of fetal size in combination with birth size were used to characterize fetal growth. • We investigated the associations of prenatal exposure to benzotriazoles and benzothiazoles with fetal and birth size. • We observed sex-specific associations and further explored the window of susceptibility. The presence of benzotriazoles and benzothiazoles (BTs) in maternal urine and amniotic fluid indicated the widespread fetal exposure to the contaminants. We investigated the associations of prenatal BTs exposure with fetal and birth size and explored the window of susceptibility. Participants consisted of 856 mother-infant pairs drawn from a prospective birth cohort between 2014 and 2015 in Wuhan, China. Prenatal BTs exposure were measured in multiple urine samples collected across three trimesters. We observed positive associations between prenatal exposure to specific BTs (e.g., 1-H-benzotriazole, 1-hydroxy-benzotriazole and 2-amino-benzothiazole) and femur length (FL) and birth length z-scores among girls. In boys, a 2-fold increase of averaged concentration of urinary benzothiazole (BTH) was associated with decrement in FL (β = -0.068, p < 0.001) and birth length (β = -0.055, p = 0.005) z-scores. Further analysis indicated that the negative associations between urinary concentrations of BTH and birth length z-score among boys were observed at exposure measurement in 25–35 gestational weeks. This study reported the associations between prenatal exposure to BTs and fetal and birth size, suggests the associations maybe in a sex-specific manner and the window of exposure may influence susceptibility. These findings require replication in future research. [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]

• The associations of urinary BTs with the blood glucose levels were investigated. • Urinary levels of 2-OH-BTH were positively associated with 2-hour blood glucose. • Higher urinary levels of 2-OH-BTH were associated with increased risk of GDM. 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. We prospectively investigated the associations of exposure to BTs at early pregnancy with the blood glucose levels and the risks of GDM. 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 < 0.050). Comparing the high exposure group with the low exposure group of 2-OH-BTH, the adjusted RR of GDM was 1.79 (95% CI = 1.18 to 2.69, p for trend = 0.012). Sensitivity analysis indicated that the positive association of the urinary 2-OH-BTH level with the RR of GDM remained significant among pregnant women who had a male fetus (RR = 1.76, 95% CI = 1.02 to 3.03, p for trend = 0.041) and those with a normal pre-pregnancy BMI (RR = 1.85, 95% CI = 1.09 to 3.11, p for trend = 0.034). These findings suggested that higher urinary level of 2-OH-BTH in early pregnancy was associated with impaired glucose homeostasis and the increased risk of GDM. The results underscore the need of follow-up studies to validate the findings and elucidate the underlying biological mechanism. [ABSTRACT FROM AUTHOR]

Phthalates are endocrine disrupting chemicals (EDCs) that pose a serious hazard to the human health. Many epidemiological studies revealed a relationship between phthalates exposure and blood pressure in general population, while the relationship in pregnant women remains unknown. Aimed to elucidate whether phthalate exposure is associated with blood pressure among pregnant women. This study included 636 participants from Wuhan, China. Urine samples were conducted repeatedly in three trimesters, and 9 phthalates were measured in these samples. After each urine was sampled, all the participants completed blood pressure measurements. Associations between repeated measurements of phthalate concentration and blood pressure were evaluated by using generalized estimating equations. Stratified analysis by fetus gender was conducted. Among the pregnant women with male fetuses, mono-i-butyl phthalate (MiBP) exposed in the 1st trimester was associated with the increased diastolic blood pressure (DBP) measured in the 2nd trimester, while the environmental risk score (ERS) measured in the 1st and 2nd trimester was positively associated with systolic blood pressure (SBP) and DBP in the 2nd trimester. No significant relationships were observed among all the population or pregnant women with female fetuses. Exposure to higher levels of MiBP may be related to increased blood pressure during pregnancy in pregnant women with male fetuses. • Repeated measures of urinary metabolites and blood pressure in three trimesters were carried out to cover the whole pregnancy. • Exposure to phthalates was significantly related to the increment of blood pressure in pregnant women with male fetus. • The effects of multi-phthalate risk score were more prominent than single phthalate, which may indicate greater harm to human health. [ABSTRACT FROM AUTHOR]

Concerns on minimizing health risks of phthalates have been raised due to their widespread exposure and well-documented endocrine disrupting properties, but the determinants of levels, metabolism, and health risks of phthalate exposures have not been thoroughly characterized among the Chinese population, particularly pregnant women. The metabolites of five phthalates were analyzed: diethyl (DEP), diisobutyl (DiBP), di-n-butyl (DnBP), di-(2-ethylhexyl) (DEHP), and benzyl butyl phthalate (BBzP) were analyzed in urine samples collected from 946 mothers in Wuhan during 2014–2015. We applied linear mixed models to investigate the relationships between biomarkers (e.g., urinary concentrations of phthalate metabolites, phthalates, and ratios of metabolites) and factors including sampling seasons and epidemiological characteristics. We calculated estimated daily intake (EDI) using average phthalate concentrations over three trimesters and hazard index (HI) by dividing EDI by tolerance daily intake. About 24.9% of participants were at health risks with HI > 1. The largest health risks were driven by one specific phthalate (DnBP or DEHP). We observed lower urinary levels of phthalate metabolites in winter. Elevated levels were found in mothers with higher education levels or those employed. Mothers who got pregnant on purpose had lower phthalate concentrations than those got pregnant by accident. More recent exposure to phthalates was observed among groups of mothers giving birth to girls, or those who got excessive gestational weight gain. Younger mothers were more susceptible to phthalate exposure. This repeated measurement study suggests that the intervention should be taken to limit application and production of DnBP and DEHP, and highlights that typical demographic factors should be taken into account in demographic studies. • Phthalate levels were associated with sampling seasons, education levels, and employment. • Mothers who got pregnant on purpose had lower phthalate concentrations. • More recent exposure was observed among mothers who gave birth to girls. • More recent exposure was observed among mothers who gained excessive weight. • Younger mothers were more susceptible to phthalate exposure. [ABSTRACT FROM AUTHOR]

Background: The sequencing platform BGISEQ-500 is based on DNBSEQ technology and provides high throughput with low costs. This sequencer has been widely used in various areas of scientific and clinical research. A better understanding of the sequencing process and performance of this system is essential for stabilizing the sequencing process, accurately interpreting sequencing results and efficiently solving sequencing problems. To address these concerns, a comprehensive database, SEQdata-BEACON, was constructed to accumulate the run performance data in BGISEQ-500. Results: A total of 60 BGISEQ-500 instruments in the BGI-Wuhan lab were used to collect sequencing performance data. Lanes in paired-end 100 (PE100) sequencing using 10 bp barcode were chosen, and each lane was assigned a unique entry number as its identification number (ID). From November 2018 to April 2019, 2236 entries were recorded in the database containing 65 metrics about sample, yield, quality, machine state and supplies information. Using a correlation matrix, 52 numerical metrics were clustered into three groups signifying yield-quality, machine state and sequencing calibration. The distributions of the metrics also delivered information about patterns and rendered clues for further explanation or analysis of the sequencing process. Using the data of a total of 200 cycles, a linear regression model well simulated the final outputs. Moreover, the predicted final yield could be provided in the 15th cycle of the early stage of sequencing, and the corresponding R2 of the 200th and 15th cycle models were 0.97 and 0.81, respectively. The model was run with the test sets obtained from May 2019 to predict the yield, which resulted in an R2 of 0.96. These results indicate that our simulation model was reliable and effective. Conclusions: Data sources, statistical findings and application tools provide a constantly updated reference for BGISEQ-500 users to comprehensively understand DNBSEQ technology, solve sequencing problems and optimize run performance. These resources are available on our website http://seqBEACON.genomics.cn:443/home.html. [ABSTRACT FROM AUTHOR]

• Non-monotonic relationships between BPA and estrogen were noted among mothers. • Gender-specific associations of BPA with estrogen were observed. • Trimester-specific associations between BPA and estrogen were observed. • BPA was non-linearly associated with estrogen even under the safety threshold. Bisphenol A (BPA) may cause some adverse effects on human health by mimicking estrogen activities. In vitro and animal studies have observed the non-monotonic associations between BPA and natural estrogens, but the evidence in human study is lacking, particularly at multiple points in time during pregnancy. We aimed to examine the relationships between BPA and estrogens in the three trimesters among Chinese pregnant women and their gender variations. This study included 851 participants from a birth cohort conducted in Wuhan, China between 2014 and 2015. We measured concentrations of BPA and three estrogens (estrone (E1), 17β-estradiol (E2) and estriol (E3)) in urine samples collected in the three trimesters of pregnancy (mean for each visit: 13.0, 23.6, and 35.9 weeks' gestation). We calculated the estimated daily intakes using urinary BPA concentrations and compared them with the tolerable intake value to assess potential health risks. We used multivariate linear regression models stratified by trimester and gender to explore trimester-specific and gender-specific associations of BPA with E1, E2, and E3. We found the decreased levels of estrogens (β < 0, P < 0.05) in the upper BPA quartiles over three trimesters, except for the elevated levels of E3 (β = 0.20, 95% CI: 0.02, 0.38) in the highest BPA quartile in the 2nd trimester. There were significant non-linear associations (overall associations P < 0.05, non-linear associations P < 0.05) between BPA and E3 in the three trimesters. In the gender-stratified analysis, we observed significant negative relationships (β < 0, P < 0.05) between BPA and E2 among mothers carrying male fetuses in the 1st trimester and significant associations between BPA and E3 among mothers carrying female fetuses in the 2nd trimester. However, we found no significant relationship between BPA and E2 among mothers carrying female fetuses over three trimesters. Our findings support experimental evidence of non-monotonic relationships between BPA and three major estrogens, even at low doses of BPA. Mothers delivering male fetuses may be more sensitive to E2 at early pregnancy, and those delivering female fetuses may be more susceptive to E3 at mid-pregnancy. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) and its substitute bisphenol S (BPS) are endocrine-disrupting chemicals and metabolized rapidly in human body. BPA exposure in late pregnancy has been suggested to be associated with preterm birth (PTB), but the associations of trimester BPA and BPS exposures with gestational age have been rarely studied. We aimed to examine maternal urinary BPA and BPS levels longitudinally measured across pregnancy in relation to gestational age and PTB. A prenatal cohort study was conducted between 2014 and 2015 in Wuhan, China. Maternal urinary BPA and BPS concentrations were measured in a complete series of urine samples collected in the 1st, 2nd and 3rd trimesters from 850 pregnant women and corrected by specific gravity. In comparison with the lowest tertile of maternal urinary BPA, higher levels of averaged BPA concentration across pregnancy was associated with a 1.97-day decrease in gestation (95% CI: 3.25, −0.68) and an adjusted odds ratio of 3.19 (95% CI: 1.00, 10.45) for PTB. Higher BPA concentrations in three trimesters were also negatively associated with gestational age and positively correlated with PTB. In contrast, only a positive association of third-trimester BPS with gestational age was found, but the significant association disappeared in the adjusted models. Both maternal trimester and averaged BPA exposure across pregnancy were significantly associated with shortened gestation and increased risk of PTB. However, the results showed little evidence of a relationship between BPS and PTB. • Urinary BPA and BPS were measured in each trimester from 850 pregnant women. • Both trimester and averaged BPA exposure were associated with decreased gestation. • BPA exposure was related to increased risk of preterm birth (PTB) across pregnancy. • BPS exposure across pregnancy was not related to pregnancy duration or PTB. [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]