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Background: Recently, many studies have shown that the progress of conversion therapy can provide surgical opportunities for patients with advanced gastric cancer (GC) and bring survival benefits. However, the results of the current study show that the regimen used in conversion therapy is still controversial. Apatinib, as the standard third-line treatment for GC, has an inconclusive status in conversion therapy. Methods: This study retrospectively analyzed GC patients admitted to Zhejiang Provincial People's Hospital from June 2016 to November 2019. All patients were pathologically diagnosed, had unresectable factors, and received SOX regimen with or without apatinib as conversion therapy. Results: A total of 50 patients were enrolled in the study. Altogether 33 patients (66%) received conversion surgery and 17 patients (34%) received conversion therapy without surgery. The median progression-free survival (PFS) between surgery group and non-surgery group were 21.0 versus 4.0 months (p < 0.0001), and the median overall survival (OS) were 29.0 versus 14.0 months (p < 0.0001). In conversion surgery group, 16 patients (16/33) were treated with SOX plus apatinib, and the R0 resection rate was 81.3%; 17 patients (17/33) were treated with SOX regimen along, and the R0 resection rate was 41.2% (p = 0.032). The PFS in the SOX combined with apatinib group was significantly longer than that of SOX group (25.5 versus 16 months, p = 0.045), and the median OS were 34.0 versus 23.0 months (p = 0.048). The addition of apatinib did not increase the incidence of serious adverse reactions throughout the preoperative therapy period. Conclusions: Patients with advanced inoperable gastric cancer could benefit probably from conversion chemotherapy and subsequence conversion surgery. Apatinib-targeted therapy combined with SOX chemotherapy may be a safe and feasible option for conversion therapy. [ABSTRACT FROM AUTHOR]

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission. [ABSTRACT FROM AUTHOR]

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p <.05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children. [ABSTRACT FROM AUTHOR]

Background: Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal–fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment. Methods: This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24–28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted. Results: In our cohort, 14.0% had an IPI < 12 months. IPI < 12 months increased the failure of the communication domain, fine motor domain, and personal social domain of the ASQ (relative risks (RRs) with 95% confidence interval (CI): 1.73 [1.11,2.70]; 1.73 [1.10,2.72]; 1.51 [1.00,2.29]). Maternal homeostasis model assessment of insulin resistance (HOMA-IR) and cord blood C-peptide was significantly associated with failure in the communication domain [RRs with 95% CI: 1.15 (1.02, 1.31); 2.15 (1.26, 3.67)]. The proportion of the association between IPI and failure of the communication domain risk mediated by maternal HOMA-IR and cord blood C-peptide was 14.4%. Conclusions: IPI < 12 months was associated with failing the communication domain in infants. Maternal–fetal glucose metabolism abnormality may partially explain the risk of neurodevelopmental delay caused by short IPI. [ABSTRACT FROM AUTHOR]

Background: The evidence on the associations of the timing of maternal gestational diabetes mellitus (GDM) with the comprehensive growth trajectory from perinatal to early childhood in offspring is limited. The potential mechanism remains elusive. Our aim is to estimate the associations of the timing of GDM diagnosis and gestational weight gains (GWG) with the growth trajectory of children from perinatal to early childhood. Methods: A total of 7609 participants are included from the Maternal & Infants Health in Hefei cohort study. Primary predictors were the timing of maternal GDM diagnosis and GWG during pregnancy. The main outcomes included fetal ultrasonic measurements, birth size as well as BMI peak indicators during infancy within 48 months. Results: GDM diagnosed before 26 weeks was associated with increased risks of overgrowth for fetal abdominal circumference (OR 1.19, 95% CI 1.04–1.36) and birth weight (OR 1.51, 95% CI 1.19–1.91) when compared with unexposed. GDM diagnosis < 26 weeks was related to the higher BMI peak (β 0.16, 95%CI 0.03–0.28) within 48 months. The significantly additive impacts of maternal early GDM diagnosis and excessive gestational weight gains (EGWG) on offspring overgrowth were observed. Women in GDM < 26 weeks with early EGWG group had higher levels of hsCRP compared with GDM > 26 weeks (P < 0.001). Conclusions: Exposure to maternal GDM diagnosed before 26 weeks with early EGWG could lead to shifts and/or disruptions from the typical growth trajectory from perinatal to early childhood in offspring. [ABSTRACT FROM AUTHOR]

• This study is the first large-sample prospective cohort study to examine the association between placental inflammatory cytokines mRNA expression and preschoolers' behavioral problems. • In preschool boys, a positive association between placental pro-inflammatory chemokines IL-8 mRNA levels and CBCL scores on anxious/depressed problems, aggressive behaviors, externalizing problems and total problems is observed. • In preschool girls, medium levels of pro-inflammatory cytokines (CRP, IL-6, IL-1β) seems to be associated with a decreased risk of some behavioral problems (emotionally reactive problems, externalizing problems, withdrawal) compared to high or low levels. • For anti-inflammatory cytokines, medium levels of IL-4 are found to be associated with a low risk of externalizing problems in preschool girls and medium levels of IL-10 were related to a low risk of internalizing problems in preschool boys, compared to low levels. Placental inflammation may contribute to brain abnormalities and childhood neuropsychiatric disorders, but limited knowledge is available on the association of placental inflammatory cytokine levels and offspring's behavioral development. This study aimed to examine the sex-specific association between placental inflammatory cytokine mRNA expression and preschoolers' behavioral development. 3474 pregnant women were recruited as the initial study population in the Ma'anshan birth cohort (MABC) study. Placentas (n = 2519) were collected during childbirth, and the mRNA expression of IL-8, IL-1β, CRP, TNF-α, IL-6, IL-10, and IL-4 was assessed. The Child Behavior Checklist 1.5–5 (CBCL 1.5–5) was used to assess children's behavioral development at 4 years old. A T-score ≥ 60 on summary scales or a score ≥ 65 on syndrome scales was regarded as the borderline clinical range. Multiple linear regression models and binary logistic regression models were applied to explore the sex-specific associations between placental inflammatory cytokines mRNA transcript levels and preschoolers' behavioral development. Sex-specific associations between placental inflammatory cytokines mRNA expression and preschoolers' behavioral development were observed. There was a positive association between IL-8 and CBCL scores for boys on anxious/depressed problems, aggressive behaviors, externalizing problems and total problems. Logistic regression models showed that high levels of IL-8 were associated with a higher risk of girls' emotionally reactive problems and sleep problems compared to low/medium levels. High TNF-α was correlated with increased sleep problem scores in boys, and medium TNF-α (vs. low levels) was associated with an increased risk of girls' externalizing problems. Medium levels of CRP, IL-1β, and IL-6 were found to be associated with a decreased risk of girls' behavioral problems compared to low/high levels. For anti-inflammatory cytokines, medium IL-10 and IL-4 (vs. low levels) were observed to be associated with a lower risk of internalizing problems in boys and externalizing problems in girls, respectively. High IL-10 was correlated with decreased attention problem scores in boys. This study indicates that placental inflammatory cytokine mRNA expression of IL-8, CRP, TNF-α, IL-1β, IL-4 and IL-10 may be associated with preschoolers' behavioral development in a sex-specific manner. [ABSTRACT FROM AUTHOR]

Introduction: Biomonitoring of bisphenol A (BPA) in human blood is still scarce, although already noticeable. We aimed to examine the associations between prenatal serum BPA concentrations and behavior and cognitive function in preschool children. Methods: A total of 1,782 mother-child pairs with complete demographic information, blood samples, and psychological measurements were included from the China-Anhui Birth Cohort (C-ABCS). We detected serum BPA concentrations and assessed children's neurodevelopment using a set of psychometric scales. Results: The median prenatal maternal serum BPA concentration was 0.23 (P25, P75: 0.07, 0.52) ng/mL, with a detection frequency of 85.19%. Compared with the girls with the lowest concentrations, those with highest BPA concentrations had increased risks of inhibitory self-control impairment [relative risk (RR) = 3.66, 95% confidence interval (CI): 1.53, 7.58], emergent metacognition impairment (RR = 1.70, 95% CI: 1.07, 2.78), conduct problem (RR = 1.68, 95% CI: 1.12, 2.39), peer relationship problem (RR = 2.57, 95% CI: 1.33, 4.47), higher total difficulties score (RR = 1.76, 95% CI: 1.12, 2.67), and higher impact factor score (RR = 1.52, 95% CI: 1.11, 2.05), while the boys with the highest prenatal BPA concentrations had an increased risk of conduct problem compared with those with the lowest concentrations (RR = 1.59, 95% CI: 1.09, 2.24) (P-interaction = 0.011). After stratification by age, high prenatal BPA concentrations were associated with increased ADHD (RR = 4.44, 95% CI: 1.54, 10.85) among children aged 3 years, not among children aged 4 years. Conclusion: Our study revealed the sex-specific and age-specific impacts of prenatal BPA exposure on preschool children's cognitive and behavioral development. [ABSTRACT FROM AUTHOR]

Background: Outdoor artificial light at night (ALAN) has been linked to an elevated risk of diabetes, but the available literature on the relationships between ALAN and glucose homeostasis in pregnancy is limited. Methods: A prospective cohort study of 6730 pregnant women was conducted in Hefei, China. Outdoor ALAN exposure was estimated using satellite data with individual addresses at a spatial resolution of approximately 1 km, and the average ALAN intensity was calculated. Gestational diabetes mellitus (GDM) was diagnosed based on a standard 75-g oral glucose tolerance test. Multivariable linear regression and logistic regression were used to estimate the relationships between ALAN and glucose homeostasis. Results: Outdoor ALAN was associated with elevated glucose homeostasis markers in the first trimester, but not GDM risk. An increase in the interquartile range of outdoor ALAN values was related to a 0.02 (95% confidence interval [CI]: 0.00, 0.03) mmol/L higher fasting plasma glucose, a 0.42 (95% CI: 0.30, 0.54) μU/mL increase in insulin and a 0.09 (95% CI: 0.07, 0.12) increase in homeostatic model assessment of insulin resistance (HOMA-IR) during the first trimester. Subgroup analyses showed that the associations between outdoor ALAN exposure and fasting plasma glucose, insulin, and HOMA-IR were more pronounced among pregnant women who conceived in summer and autumn. Conclusions: The results provided evidence that brighter outdoor ALAN in the first trimester was related to elevated glucose intolerance in pregnancy, especially in pregnant women conceived in summer and autumn, and effective strategies are needed to prevent and manage light pollution. [Display omitted] • The first trimester ALAN exposure was associated with elevated glucose intolerance. • Outdoor ALAN exposure was associated with higher FPG, insulin, and HOMA-IR. • Outdoor ALAN exposure was not associated with a higher risk of GDM. [ABSTRACT FROM AUTHOR]

Background: Vitamin D has been demonstrated a "neuroprotective" effect, but it is unclear whether early-life adequate vitamin D protect adverse neurodevelopment. We aimed to examine the role of neonatal vitamin D in the association of maternal depression (MD) symptoms with toddlers ADHD.Methods: Participants included 1 125 mother-infant pairs from the China-Anhui Birth Cohort study. MD was assessed by the Center for Epidemiological Studies Depression Scale (CES-D) at 30-34 gestational weeks. Toddlers ADHD was reported by the Conners' Hyperactivity Index (CHI) at 48-54 months postpartum. Multiple logistic regression models were performed to evaluate the association of maternal depressive score and toddlers ADHD while cord blood 25(OH)D levels were stratified.Results: Toddlers of mothers with higher depression score were at higher risk of ADHD (20.1% vs 11.1%, P = 0.003; adjusted RR=1.75, 95% CI: 1.10-2.81). Among toddlers with neonatal vitamin D deficiency (VDD), ADHD risk was significantly increased with maternal MD (adjusted RR=3.74, 95% CI: 1.49-9.41), but the association was not found in toddlers with neonatal vitamin D adequacy (VDA). Compared to toddlers without MD, toddlers with both MD and neonatal VDD had higher risk of ADHD (adjusted RR=3.10, 95% CI: 1.44-6.63). But the risk did not significantly increase in toddlers with MD and neonatal VDA (adjusted RR=1.53, 95% CI: 0.86-2.72).Limitations: Maternal depressive symptoms in early pregnancy and anxious symptoms were needed to include.Conclusion: This prospective study indicated that the detrimental effect of maternal prenatal depressive symptoms on offspring's ADHD symptoms strengthened in toddlers with neonatal VDD. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-related anxiety plays a major role in shaping offspring's neural development. However, its gender-specific effect on children's emotional and behavioral development is controversial and the knowledge of critical period is limited. This study aims to examine gender-specific effect of pregnancy-related anxiety on preschooler's emotional and behavioral development.Methods: This study was based on the China-Anhui Birth Cohort Study (C-ABCS). A total of 3443 mother-child pairs were included in final data analysis. Pregnancy-related anxiety was assessed by Pregnancy-Related Anxiety Questionnaire respectively in the 1st and 3rd trimester of pregnancy. Strengths and Difficulties Questionnaires (SDQ) were completed by parents to assess preschool emotional and behavioral development in boys and girls. Logistic regression models were used to examine the association between pregnancy-related anxiety and preschoolers' emotional and behavioral problems.Results: The overall prevalence of pregnancy-related anxiety was 31.6%. Compared with those whose mothers without pregnancy-related anxiety in either 1st or 3rd trimester, preschool boys born of mothers with pregnancy-related anxiety in the 1st trimester and in the 3rd trimester had an increased risk of conduct problems. Pregnancy-related anxiety in the 1st, 3rd trimester and in both trimesters all related with preschool boys' hyperactivity and total difficult problems. Pregnancy-related anxiety in the 1st trimester and in both 1st and 3rd trimester increased the risk of preschool girls' emotional problems and total difficult problems.Conclusion: Pregnancy-related anxiety may relate with preschool boys' externalizing problems in early and late of pregnancy and increase the risk of internalizing problems in girls in early pregnancy.Limitations: There was no data on pregnancy-related anxiety in the second trimester. [ABSTRACT FROM AUTHOR]

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (β = 0.111, 95% CI = 0.002–0.221), ABSI (β = 0.145, 95% CI = 0.023–0.268) and BRI (β = 0.046, 95% CI = −0.005–0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502–0.844) and MBP (OR = 0.717, 95% CI = 0.984–1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487–0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210–2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266–5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights. [Display omitted] • The 1st study shows relations of prenatal PAEs with child ABSI and BRI trajectories. • Prenatal MEP exposure is associated with repeated measurements of FMI, ABSI and BRI. • PAE mixture increases the probability of being in higher ABSI and BRI trajectories. • MEP and MBP show largest weights for PAE mixture related to the adiposity trajectory. [ABSTRACT FROM AUTHOR]

Phthalate has been widely used as a type of plasticiser in various consuming products in daily life. Recent studies have suggested that prenatal phthalate exposure may have adverse effects on fetal development. We aimed to identify the effects of in utero phthalate exposure on birth weight (BW). We evaluated a birth cohort comprising 3474 pregnant women and their single infants; 3103, 2975 and 2838 urine samples were collected in the first, second and third trimesters, respectively. Phthalate metabolites included monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEHHP), and mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEOHP), which were analysed in the urine by using high performance liquid chromatography–tandem mass spectrometry. Mixed linear model was used in the statistical analysis. Generally, MMP and MEP exposure during pregnancy was associated with decreased birth weight of infants (MMP, β = − 12.192, p = 0.009; MEP, β = − 11.876, p = 0.014). Hierarchical analysis found that MMP and MEOHP exposure was associated with decreased infants' birth weight only in low birth weight groups (MMP, β = − 42.538, p = 0.005; MEOHP, β = − 63.224, p = 0.008); MEHP and MEHHP exposure was associated with decreased infants' birth weight in both low birth weight group (MEHP, β = − 42.348, p = 0.035; MEHHP, β = − 50.485, p = 0.006) and high birth weight group (MEHP, β = − 16.580, p = 0.034; MEHHP, β = − 18.009, p = 0.040), MBP and MEHP exposure were associated with increased infants' birth weight in male NBW group (MBP, β = 10.438, p = 0.039; MEHP, β = 13.223, p = 0.017). Moreover, the effect has sex difference. The reduction of birth weight associated with MEHP and MEOHP exposure was stronger in male infants, while MMP and MEP exposure was more significant in female infants. [ABSTRACT FROM AUTHOR]

There is currently no consensus about the impact of prenatal phthalate exposure on blood pressure and glycolipids in children. Few studies consider the health effects as an integrated indicator. The combined effect of multiple phthalate exposures is often ignored. Based on the Ma'anshan Birth Cohort, 2298 woman-child pairs were included in this study. Maternal urine was collected in each trimester to analyze 6 phthalate metabolites. The overall cardiometabolic risk (CMR) score was calculated based on serum glycolipids and blood pressure for children aged 4–7 years. A higher score represents a less favorable CMR profile. The restricted cubic spline model was used to explore the relationship between prenatal phthalate exposure and childhood CMR score. In addition, the quantile g-computation and the Bayesian kernel machine regression were used to evaluate the combined effect. The MBP exposure in the 1st trimester (MBP-1st) and the MEP-2nd were non-linearly associated with the CMR score (F nonlinear = 3.28 and 5.60, P nonlinear = 0.0378 and 0.0038, respectively). The MBP-3rd (F linear = 5.31, P linear = 0.0012) and the ∑LMWP-3rd (F linear = 4.37, P linear = 0.0045) were negatively associated with the score in a linear manner. The phthalate mixture in the 2nd trimester increased the score (psil = 0.1747, 95% CI = 0.0077–0.3416), with the MEP being the most common [weights = 0.5290; posterior inclusion probability (PIP) = 0.40]. The phthalate mixture in the 3rd trimester decreased the score (psil = −0.2024, 95% CI = −0.4097－0.0048), with the MEHP (weights = −0.5101; PIP = 0.14) and the MBP (weights = −0.3993, PIP = 1.00) being the greatest contributors. In conclusion, the MBP-1st and the MEP-2nd are non-linearly associated with the cardiometabolic risk in children. The MBP-3rd and the ∑LMWP-3rd decrease the childhood risk. The combined exposure to phthalate mixture in the second and third trimester elevates and decreases the risk of childhood cardiometabolism, respectively. [Display omitted] • Maternal urine was collected and analyzed in each trimester for phthalate metabolites. • Cardiometabolic risk (CMR) was computed based on child glycolipids and blood pressure. • Total phthalates in the 2nd trimester were positively associated with the child CMR. • Combined effect of phthalates in the 3rd trimester on the decreased CMR was revealed. [ABSTRACT FROM AUTHOR]

Few studies have investigated the relationships between gestational phthalate exposure and maternal circulating vitamin D. In the Ma'anshan birth cohort, 3265 pregnant women were included. Each woman provided up to three urine and serum samples for measurement of phthalates and 25(OH)D and calcium, respectively. Linear mixed models were performed to analyse the association between phthalate metabolites and 25(OH)D and calcium. Stratified analyses of the relationship between phthalates and 25(OH)D by urine collection season were conducted. Finally, the post hoc lag effect of phthalate exposure on 25(OH)D was determined if longitudinal associations were significant. Some phthalate metabolites were associated with increased 25(OH)D but with decreased calcium. Furthermore, the relationship of phthalate exposure with 25(OH)D varied with urine collection season. Phthalate metabolites collected in summer and autumn were associated with an increase in 25(OH)D, while monobenzyl phthalate collected in winter and spring was inversely associated with 25(OH)D. Finally, high-molecular-weight phthalates had lag associations with 25(OH)D with a 1-trimester lag period. Low-molecular-weight phthalates exhibited lag associations with 25(OH)D with a 2-trimester lag period. In conclusion, the positive cross-sectional correlation between phthalate metabolites and 25(OH)D was partly affected by urine collection season. This study suggested that gestational phthalate exposure would have a lag association with maternal 25(OH)D levels. [Display omitted] • Phthalate metabolites (PAEs) were measured in multiple urine samples during pregnancy. • Positive cross-sectional relations between PAEs and 25(OH)D were shown. • Relationships between PAEs and 25(OH)D varied by season of urine collection. • High molecular weight PAEs had a lag association with 25(OH)D with a 1-trimester lag period. • Low molecular weight PAEs had a lag association with 25(OH)D with a 2-trimester lag period. [ABSTRACT FROM AUTHOR]

This study enrolled 3266 pregnant women, to explore the relationship of prenatal phthalate exposure with the risk of preterm birth and gestational age. All participants filled questionnaires and provided with up to three urine samples during three trimesters. Seven phthalate metabolites in urines were measured. The incidences of very preterm, late preterm, early-term, late-term and postterm births were 0.58%, 3.52%, 24.22%, 10.53%, and 0.34%, respectively. Non-linear relationships were shown between phthalate metabolites and gestational age. Except for monomethyl phthalate (OR = 1.65, 95%CI = 1.17–2.34), the average concentrations of phthalate metabolites were associated with a slightly and insignificantly increased risk of overall preterm birth (<37+0 gestational weeks). Through a restricted cubic spline regression, phthalate metabolites were found to be related to the risk of overall preterm birth in a linear manner (p -value >0.05) or a non-linear manner (p -value <0.05). All curves indicated the overall preterm birth risk rose with the increase of phthalate metabolite concentrations. Finally, compared with full-term birth (39+0 to 40+6 gestational weeks), phthalate metabolites were associated with the elevated risks of very preterm, late preterm and postterm births, although some relationships were not statistically significant. In conclusion, these findings suggested non-linear associations between phthalate metabolites and gestational age. Exposure to some phthalate metabolites was associated with increased risks of overall preterm birth and postterm birth. • Rates of very preterm, late preterm, early-term and late-term births were 0.58%, 3.52%, 24.22% and 10.53%, respectively. • Non-linear relationship was observed between certain phthalate metabolites and the odds ratio of overall preterm birth. • Some phthalates were associated with increased risks of very preterm, late preterm and postterm births. • Non-linear curves for associations between phthalates and gestational age were revealed. Capsule: Based on a cohort study with large sample size, the levels of phthalate metabolites in urine at 3 time points during pregnancy were analyzed in relation to gestational age and preterm birth, which aimed to confirm the previous findings in this topic. [ABSTRACT FROM AUTHOR]