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Organophosphate and Pyrethroid Pesticide Exposures Measured before Conception and Associations with Time to Pregnancy in Chinese Couples Enrolled in the Shanghai Birth Cohort.

Background: Pesticides have been associated with reproductive disorders, but there is limited research on pesticide exposures and human fertility. 
Objective: We aimed to investigate the effects of preconception exposure to pesticides on time to pregnancy (TTP) and on infertility in a general population of couples planning to become pregnant in Shanghai, China. 
Methods: A total of 615 women who were planning a pregnancy were enrolled before conception and were prospectively followed for 1 y to observe their TTP. Preconception pesticide exposures were assessed by measuring urinary metabolites of organophosphates (OPs) and pyrethroids (PYRs). Fecundability odds ratios (FORs) and odds ratios (ORs) of infertility were estimated using Cox and logistic regression models, respectively. All analyses were repeated after restricting the sample to nulliparous women (n = 569）. 
Results：After adjusting for age, prepregnancy BMI, current smoking, education, annual household income, age at menarche, and two items from the Perceived Stress Scale (PSS-10), women in the highest quartile of diethylthiophosphate (DETP; an OP metabolite) had significantly longer TTP [adjusted FOR = 0.68 (95% CI: 0.51, 0.92)] and increased infertility [adjusted OR = 2.17 (95% CI: 1.19, 3.93)] compared with women in the lowest quartile. The highest versus lowest quartile of 3-phenoxybenzoic acid (3PBA; a PYR metabolite) was associated with longer TTP and infertility, with significant associations in nulliparous women [adjusted FOR = 0.72 (95% CI: 0.53, 0.98); adjusted OR for infertility = 2.03 (95% CI: 1.10, 3.74)]. 
Conclusion：Our study provides some of the first evidence that preconception OP and PYR exposures are associated with decreased fertility in Chinese couples. Given that OPs and PYRs are rapidly metabolized in humans, more studies are needed to confirm our findings.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances affects leukocyte telomere length in female newborns.

Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasingoxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns (β = −1.42 × 10−4, P = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a “programming” role of PFASs on fetal telomere biology system in females in intrauterine stage.

Fetal vitamin D concentration and growth, adiposity and neurodevelopment during infancy.

Backgroud/Object:To determine the association between cord blood 25-hydroxyvitamin D (25(OH)D) concentration with growth, adiposity and neurodevelopment during infancy. 
Subject/ Methods: Serum 25(OH)D was measured in cord blood by the liquid chromatography tandem mass spectrometry (LC-MS/MS) from the Shanghai's "Allergy and Obesity Cohort study" (n = 1244). Weight, length, head circumference, and body mass index (BMI) z-scores for age were calculated based on World Health Organization Standard (at 6 months, 1 years, and 2 years).Neurodevelopment was measured at 2 years using Ages and Stages Questionnaire. Generalized estimating equation and multivariable logistic regression model were exploited to examine associations between fetal 25(OH)D concentration and offspring outcomes. 
Results: The median of the 25(OH)D concentration in cord blood was 22.4 ng/ml (interquartile range, 27.3-8.6). Infants born in winter had lower 25(OH)D concentration. 25(OH)D deficiency was not associated with weight z-score (mean difference, 0.07; 95% confidence internal (CI), -0.09 to 0.23), length z-score (mean difference, 0.01; 95% CI, -0.19 to 0.21), head circumference z-score (mean difference, -0.06; 95% CI, -0.27 to 0.15) and BMI z-score (mean difference, 0.09; 95% CI, -0.07 to 0.25) or neurodevelopmentduring infancy, adjusting for sex, socio-economic position, pre-pregnancy maternal BMI, and maternal and neonatal characteristics. The associations did not vary by gender. A sensitivity analysis of available case analysis showed virtually the same results. 
Conclusions: Fetal vitamin D concentration was not associated with growth, adiposity or neurodevelopment during infancy. The role of vitamin D concentration and its mechanistic pathway in the early origins of adiposity needs to be clarified.

Maternal urinary triclosan level, gestational diabetes mellitus and birth weight in Chinese women

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

Maternal Urinary Triclosan Concentration in Relation to Maternal and Neonatal Thyroid Hormone Levels: A Prospective Study.

BACKGROUND: Triclosan (TCS) is a synthetic antibacterial chemical widely used in personal care products. TCS exposure has been associated with decreased thyroid hormone levels in animals, but human studies are scarce and controversial. 
OBJECTIVE: We evaluated the association between maternal TCS exposure and thyroid hormone levels of mothers and newborns. 
METHODS: TCS was measured by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) in urine samples collected during gestational weeks 38.8 ± 1.1 from 398 pregnant women in a prospective birth cohort enrolled in 2012–2013 in Shanghai, China. Maternal serum levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were obtained from medical records. Cord blood levels of free triiodothyronine (FT3), FT4, TSH, and TPOAb were measured. Multiple linear and logistic regression models were used to examine the relationship between maternal urinary TCS and thyroid hormone levels. 
RESULTS: TCS was detectable (≥0:1 ng=mL) in 98.24% of maternal urine samples with tertile of urinary TCS levels: low (<0:1–2:75 lg=g:Cr), medium (2:75–9:78 lg=g:Cr), and high (9:78–427:38 lg=g:Cr). With adjustment for potential confounders, cord blood log(FT3)pmol/L concentration was 0.11 lower in newborns of mothers with medium and high urinary TCS levels compared with those with low levels. At third trimester, the high TCS concentration was associated with 0.03 [95% confidence interval (CI) −0:08, −0:02] lower maternal serum log(FT4)pmol/L, whereas the medium TCS concentration was associated with 0.15 (95% CI: −0:28, −0:03) lower serum log(TSH)mIU/L with adjustment for covariates. 
CONCLUSIONS: Our results suggest significant inverse associations between maternal urinary TCS and cord blood FT3 as well as maternal blood FT4 concentrations at third trimester.

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood atopic dermatitis: a prospective birth cohort study

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been reported to suppress immune function. However, previous studies on prenatal exposure to PFASs and allergic disorders in offspring provided inconsistent results. We aimed to examine the association between prenatal exposure to PFASs and childhood atopic dermatitis (AD) in offspring up to 24 months of age. 
Methods: A prospective birth cohort study involving 1056 pregnant women was conducted in two hospitals in Shanghai from 2012 to 2015. Prenatal information was collected by an interview with the women and from medical records. Fetal umbilical cord blood was collected at birth. Cord blood plasma PFASs were measured. Children were followed at 6, 12 and 24 months and information on the development of AD was recorded. AD was diagnosed by 2 dermatologists independently based on the questionnaires. Multiple logistic regression was used to compute odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between AD and each PFASs, adjusting for potential confouders. 
Results: A total of 687 children completed a 2-year follow-up visit and had PFASs measurement. AD was diagnosed in 173 (25.2%) children during the first 24 months. In female children, a log-unit increase in perfluorooctanoic acid (PFOA) was associated with a 2.1-fold increase in AD risk (AOR 2.07, 95% CI 1.13–3.80) after adjusting for potential confounders. The corresponding risk was 2.22 (1.07–4.58) for perfluorononanoic acid (PFNA). The highest PFOA quartile was significantly associated with AD (2.52, 1.12–5.68) compared with the lowest quartile. The highest quartile of PFNA, perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS) were associated with AD with AOR (95% CI) being 2.14 (0.97–4.74), 2.14 (1.00–4.57), and 2.30 (1.03–5.15), respectively. Additionally, the second quartile of perfluorododecanoic acid (PFDoA) was associated with a 3.2-fold increase in AD risk (3.24, 1.44–7.27). However, no significant associations were found in male children. 
Conclusions: Prenatal exposure to PFOA, PFDA, PFDoA and PFHxS significantly increased the risk of childhood AD in female children during the first 24 months of life. In addition, the associations between AD with prenatal exposure to PFNA were close to statistical significance. 

Plasma Perfluoroalkyl and Polyfluoroalkyl Substances Concentration and Menstrual Cycle Characteristics in Preconception Women

Background: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent synthetic chemicals that are widely used in industrial applications and often detectable in humans. In rats, PFASs can interfere with the estrous cycle. In humans, menstruation has been viewed as a proxy of female fecundity, and periodic menstruation plays a critical role in endometrial sloughing in the absence of pregnancy and in preparing for embryo implantation. 
Objectives:We investigated the association between PFAS exposure and menstrual cycle characteristics in women who plan to become pregnant.
Results: Pre-pregnant women with higher levels of log-transformed perfluorooctanate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonate (PFHxS) had increased odds of self-reported history of irregular menstrual cycle [PFOA - adjusted odds ratio (OR) = 1.52 (95% CI: 1.08, 2.15); PFOS OR = 1.29 (95% CI: 0.98, 1.70); PFNA OR = 1.50 (95% CI: 1.03, 2.07); PFHxS OR = 1.80 (95% CI: 1.17, 2.77)] and long menstrual cycle [PFOA OR = 1.50 (95% CI: 1.06, 2.10); PFOS OR = 1.34 (95% CI: 1.02, 1.75); PFNA OR = 1.49 (95% CI: 1.05, 2.11); PFHxS OR = 1.73 (95% CI: 1.13, 2.65)]. Log-transformed PFOA, PFOS, PFNA. and PFHxS levels were negatively associated with self-reported history of menorrhagia [PFOA OR = 0.37 (95% CI: 0.21, 0.65); PFOS OR = 0.57 (95% CI: 0.37, 0.90); PFNA OR = 0.47 (95% CI: 0.26, 0.86); PFHxS OR = 0.14 (95% CI: 0.06, 0.36)]. 
Conclusions: Certain PFASs are associated with abnormal menstruation in humans. 

Sleep disorders and allergic diseases in Chinese toddlers

Objective Optimal sleep is important for child growth, development, and immune function. We aimed to explore whether sleep disorders were associated with the risk of allergic diseases in Chinese toddlers. 
Methods This study included 566 children (aged 23.9 ± 0.7 months; 51.1% boys) in Shanghai, China. Sleep parameters (total sleep time, sleep onset latency, nocturnal awaking and snoring) were assessed by an expanded version of the Brief Infant Sleep Questionnaire (BISQ-expanded). Information on four allergic diseases (wheeze, eczema, food allergy, and allergic rhinitis) in the past year was collected via standard questionnaire and judged bypediatricians. We used logistic regression to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for having any/and each of the four allergic diseases, based on sleep parameters, adjusting for children's age and gender, mode of delivery, any breastfeeding duration, children's body mass index (BMI), children's exposure to passive smoking, maternal education, family income, family allergic history, and children's antibiotic use. 
Results There were 23.3% of children with at least one of the four allergic diseases. Snoring was significantly associated with increased odds of having any allergy (adjusted OR = 1.95; 95% CI: 1.17, 3.26), eczema (OR = 1.83, 95% CI: 1.03, 3.23) and food allergy (OR = 4.31, 95% CI: 1.23, 15.14), after adjustment for potential confounders. Nocturnal awaking ≥2 times per night was associated with higher risk of food allergy (OR = 3.92, 95% CI: 1.00, 15.35) and wheeze (OR = 6.16, 95% CI: 1.28, 29.74). 
Conclusion In this study, presence of certain sleep disorders was associated with higher risk of having allergic diseases in Chinese toddlers. 

Urinary Bisphenol A Concentration and Gestational Diabetes Mellitus in Chinese Women

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

Impact of Dehydroepiandrosterone Sulfate on Newborn Leukocyte Telomere Length

The newborn setting of leukocyte telomere length (LTL) likely has important implications for telomere dynamics over the lifespan. However, its determinants are poorly understood. Hormones play an important role during pregnancy and delivery. We hypothesized that exposure to hormones may impact the fetal telomere biology system. To test this hypothesis, cortisol, estradiol, dehydroepiandrosterone sulfate (DHEAS) and reactive oxygen species (ROS) were measured in cord blood of 821 newborns from a prospective study. After accounting for the effects of potential determinants of newborn LTL, a 10-fold increase in DHEAS concentration was associated with a 0.021 increase in T/S ratio of newborn LTL (95% confidence interval: 0.009–0.034, P = 0.0008). For newborns who fell in the lowest quartile of DHEAS level, the mean newborn LTL was estimated to be approximately 2.0% shorter than the newborns in the highest DHEAS concentration quartile (P = 0.0014). However, no association was found between newborn LTL and cortisol or estradiol. As expected, newborns with higher ROS level (ROS > 260 mol/L) had lower LTL compared to that with lower ROS level (ROS ≤ 260 mol/L) (P = 0.007). There was also an inverse relationship between DHEAS and ROS (P < 1×10−4). Our findings suggest that exposure to DHEAS may exert a “programming” effect on the newborn telomere biology system.

A genetic variant in the placenta-derived MHC class I chain-related gene A increases the risk of preterm birth in a Chinese population.

Preterm birth (PTB) is a predominant contributor to neonatal mortality and morbidity worldwide. However, the pathophysiology of PTB is not well-understood. We tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the placenta-derived MHC class I chain-related gene A (MICA) could disrupt placental development and hence result in PTB. Nineteen selected SNPs in MICA were genotyped in a case–control study of 127 premature infants and 634 term controls in a Chinese Han population. We found that significantly increased PTB risk was associated with homozygosity for the A variant of rs2256318 (adjusted odds ratio = 6.97 and 95% confidence interval = 2.34–20.74 for A/A, compared with G/G genotype, P = 0.001). In addition, the A/A genotype of rs2256318 was associated with decreased placental weight of neonates (β = −25.331; P = 0.033). Furthermore, stratified analysis demonstrated that the A/A genotype of rs2256318 was associated with increased PTB risk in female group. In addition, we observed statistical interaction between the polymorphism rs2516448 and sex (P = 0.04). No significant differences in the distribution of haplotypes between cases and controls were detected. Our results indicate that the polymorphism of rs2256318 in MICA may contribute to the etiology of PTB through interfering with placental development. These findings need to be further validated in larger and multi-ethnic populations.

Perfluoroalkyl and polyfluoroalkyl substances in cord blood of newborns in Shanghai, China: Implications for risk assessment.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are commonly used in industrial applications and consumer products, and their potential health impacts are of concern, especially for vulnerable population like fetuses. However, in utero exposure to PFASs and health implications are far from fully characterized in China. To fill in the gap, we analyzed 10 PFASs in cord plasma samples (N = 687) collected in Shanghai between 2011 and 2012, one of the regions widely polluted with PFASs in China. A questionnaire survey on maternal and diet-related factors was conducted. Except for perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (PFOSA), all other PFASs were detected in ˃90% of the samples. Perfluorooctanoic acid (PFOA) was the most predominant PFAS (median value: 6.96 ng/mL), followed by perfluorooctane sulfonate (PFOS) (2.48 ng/mL). PFOA and PFOS combined contributed to 80% of the total PFASs. The final multiple regression models showed that maternal factors including maternal age, body mass index, gestational age, economic status and educational level as well as consumption of fish and wheat were significantly related with concentrations of PFASs in cord blood. The risk assessment using the hazard quotients (HQs) approach on the basis of plasma PFAS levels indicated no potential concern for developmental toxicity in the local newborns. The results demonstrate the unique profiles of local prenatal exposure to PFASs, suggesting that PFOA has been the primary human exposure due to its widespread use and pollution. Special attention to high PFOA exposure and confirmation of potential determinants should be taken as a priority in the future plan for risk management and actions in this area.

Vitamin D Status and Related Factors in Newborns in Shanghai, China

With the increasing recognition of the importance of the non-skeletal effects of vitamin D (VitD), more and more attention has been drawn to VitD status in early life. However, the VitD status of newborns and factors that influence VitD levels in Shanghai, China, remain unclear. A total of 1030 pregnant women were selected from two hospitals in Shanghai, one of the largest cities in China located at 31 degrees north latitude. Umbilical cord serum concentrations of 25-hydroxy vitamin D [25(OH)D] were measured by LC-MS-MS, and questionnaires were used to collect information. The median cord serum 25(OH)D concentration was 22.4 ng/mL; the concentration lower than 20 ng/mL accounted for 36.3% of the participants, and the concentration lower than 30 ng/mL for 84.1%. A multivariable logistic regression model showed that the determinants of low 25(OH)D status were being born during autumn or winter months and a lack of VitD-related multivitamin supplementation. The relative risk was 1.7 for both autumn (95% CI, 1.1–2.6) and winter (95% CI, 1.1–2.5) births (p < 0.05). VitD-related multivitamin supplementation more than once a day during pregnancy reduced the risk of VitD deficiency [adjusted OR (aOR) = 0.6, 95% CI (0.45–1.0) for VitD supplementation] (p < 0.05). VitD deficiency and insufficiency are common in newborns in Shanghai, China, and are independently associated with season and VitD supplementation. Our findings may assist future efforts to correct low levels of 25(OH)D in Shanghai mothers and their newborn children.