BACKGROUND:Pregnant women in the Shanghai Birth Cohort (SBC) of China faced dual threats of per- and polyfluoroalkyl substances (PFAS) exposure and vitamin D (VD) insufficiency, potentially impacting offspring neurodevelopment. However, little is known about whether maternal VD status modifies PFAS-related neurodevelopment effect. OBJECTIVES:To explore the modifying role of maternal VD status in the effect of prenatal PFAS exposure on childhood neurodevelopment. METHODS:We included 746 mother-child pairs from the SBC. Ten PFAS congeners and VD levels were measured in maternal blood samples collected during the first and second trimester respectively. At 2 years of age, toddlers underwent neurodevelopment assessments using Bayley-III Scales. Multivariate linear, logistic regression, and weighted quantile sum approach were used to estimate associations of Bayley-III scores with individual and mixture PFAS. We stratified participants into VD sufficient and insufficient groups and further balanced PFAS differences between these groups by matching all PFAS levels. We fitted the same statistical models in each VD group before and after matching. RESULTS:Nearly half (46.5 %) of pregnant women were VD insufficient (<30 ng/mL). In the overall population, PFAS exposure was associated with lower language scores and an increased risk for neurodevelopmental delay, but higher cognitive scores. However, adverse associations with PFAS were mainly observed in the VD sufficient group, while the VD insufficient group showed positive cognitive score associations. Higher PFAS concentrations were found in the VD sufficient group compared to the VD insufficient group. Post-matching, adverse associations in the VD sufficient group were nullified, whereas in the VD insufficient group, positive associations disappeared and adverse associations becoming more pronounced. CONCLUSION:In this Chinese birth cohort, high prenatal PFAS exposure and low maternal VD levels collectively heighten the risk of adverse childhood neurodevelopment. However, disentangling PFAS and VD interrelationships is crucial to avoid paradoxical findings.

Background and aim: Epidemiological evidence on the association between prenatal exposure to Perfluoroalkyl substances (PFAS) and child cognition remains unclear. Thus, we aimed to investigate whether prenatal exposure to PFAS is associated with intelligence quotient (IQ) in offspring.Method: This study population included 2031 mother-child pairs in the Shanghai Birth Cohort (SBC) enrolled during 2013-2016. Ten PFAS were measured by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in maternal plasma samples collected in early gestation between 9 and 16 weeks of gestation. Child IQ was assessed using the Wechsler Preschool and Primary Scales of Intelligence-Fourth Edition (WPPSI-IV) at 4 years of age. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into tertiles) and child IQ. A quantile g-computation approach was used to evaluate the joint and independent effects of PFAS on IQ. We also examined whether the associations varied by child sex.Results: We found no significant associations between ln-transformed nine individual PFAS and child full scale IQ (FSIQ) or subscale IQ after adjusting for potential confounders. The observed associations were not modified by child sex. PFAS in tertiles showed the same pattern. Results from quantile g-computation showed that PFAS mixture was not associated with child IQ; perfluorobutane sulfonate was negatively associated with FSIQ (beta, -0.81; 95 % CI: -1.55, -0.07), and perfluorooctane sulfonate was also associated with lower fluid reasoning index scores (beta, -1.61; 95 % CI: -3.07, -0.16) while adjusting for the other PFAS.Conclusion: PFAS mixture during early pregnancy was not associated with child IQ. For certain individual PFAS, there were inverse associations with FSIQ or subscale IQ. Considering the evidence is still inconsistent, further research is needed to confirm or refute these results in other populations and to elucidate the potential neurotoxicology of PFAS.

Bisphenol A (BPA) substitutes, such as bisphenol S (BPS) and bisphenol AF (BPAF), are increasingly used due to restrictions on BPA usage, a known endocrine disrupting chemical and putative obesogen. However, little is known about the obesogenic effects of exposure to BPA substitutes in children. A total of 426 children aged 7 years old originally recruited from Laizhou Wan Birth Cohort in Shandong, China, during 2010–2013 participated in the 2019–2020 survey. Urinary BPA and its substitutes including BPS, BPAF, bisphenol B (BPB), bisphenol AP (BPAP), bisphenol Z (BPZ), and bisphenol P (BPP) were determined. Anthropometric measures including height, weight, waist circumference, and body fat percentage were assessed, and overweight/obesity was defined as BMI z-score ≥ 85th percentile. Linear and logistic regressions were used on continuous and binary obesity measures, respectively, and weighted quantile sum (WQS) regression was further used to estimate the mixture effects of exposure to diverse bisphenols, and sex-stratified analysis was performed. BPA substitutes were widely detected (> 75

Background: Prenatal fine particulate matter (PM2.5) exposure has been linked to infant cognitive and motor functions, but the effects of PM2.5 chemical composition remain unclear. Objectives: We aimed to explore the associations of prenatal PM2.5 and its composition exposure with infant cognitive and motor functions. Methods: We studied 2,435 mother-infant pairs in the Shanghai Birth Cohort Study. PM2.5 and its seven compositions [primary particles (black carbon, mineral dust and sea salts) and secondary particles (NH4+, NO3-, SO42- and organic matter)] during the three trimesters of pregnancy were retrieved from the V4.CH.03 product developed by using a combined geoscience-statistical method. At the 12-month-old follow-up, infant cognitive and motor functions in five domains were assessed using the Ages and Stages Questionnaire (ASQ). We used multivariable linear regressions to estimate the effects of PM2.5 and its composition on the ASQ scores, for all infants and stratifying by sex and breastfeeding duration. Results: PM2.5 exposure was negatively associated with gross motor, problem-solving and personal-social scores for all infants. PM2.5 compositions were inversely associated with ASQ scores in all five domains, and the effects of different compositions varied across domains. Specifically, all compositions except organic matter were correlated with lower problem-solving scores [e.g., = (beta(SO42-)= - 10.79, 95 % CI: -17.40, -4.18) - (beta(NO3-) = 4.68, 95 % CI: -7.84, -1.53); for each 10 mu g/m(3) increase in PM2.5 compositions during the third trimester]. Primary and some secondary particles (organic matter, NO3-) were related to lower gross motor scores. Secondary particles were also inversely associated with communication (organic matter and NO3-), fine motor (NH4+, NO3-, SO42-) and personal-social (NH4+) scores. Additionally, boys and infants breastfed for < 6 months appeared to be more susceptible. Conclusions: We found negative associations of PM2.5 and its compositions with infant cognitive and motor functions over a range of domains, especially the problem-solving domain.

Background: An increasing number of studies have reported that prenatal per-and polyfluoroalkyl substances (PFAS) exposure may increase childhood adiposity. However, limited data is available in China, and the overall effects of PFAS mixture remain unclear. Objective: To examine the association of prenatal exposure to individual PFAS and their mixture with childhood adiposity at 7 years of age.Methods: A total of 206 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China between 2010 and 2013. Ten PFAS were measured in maternal serum. The measurements of fat mass, body fat percentage, body mass index, waist circumference, waist-to-height ratio and overweight/obesity were used to assess adiposity in children aged 7. We fitted logistic regression, linear regression and weighted quantile sum (WQS) regression models to estimate the association of prenatal exposure to individual PFAS and their mixture with childhood adiposity.Results: We found negative associations of perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (PFOSA) exposure with adiposity measurements in all children. The result from the WQS model consistently revealed that the PFAS mixture was inversely related to adiposity measurements. Each quartile increase of the PFAS mixture was associated with a 1.14 kg decrease (95% CI:-2.27,-0.02) in fat mass and a 2.32% decrease (95% CI:-4.51,-0.14) in body fat. Moreover, significant sex differences were found. PFAS mixture was negatively associated with five adiposity measurements in boys, but positively associated with all adiposity measurements except body fat percentage in girls. PFOSA, PFHpA and perfluorobutanesulfonate (PFBS) with weights >0.300 were the main contributors to the overall effects observed among all children, boys and girls, respectively.Conclusion: This study suggests potential sex-specific associations of prenatal exposure to individual PFAS and their mixture with childhood adiposity, with the observed relationship being negative for boys but positive for girls.

BACKGROUND AND AIM: Perfluorononanoic Acid (PFNA), a kind of fluorinated aliphatic molecules, had been extensively used in industrial applications as a surface protectant and known to accumulate in humans and wildlife. Although PFNA had been adversely associated with the growth and development of wild-type mice, much less is known about the impact of short-term exposure to PFNA during gestation on neurobehavioral development in rat offspring. The purpose of this study was to investigate the effects of PFNA on the physical and neurobehavioral development in sprague-dawley rat offspring. METHODS: Dams were dosed daily via oral gavage during gestation days 1-19 with control, 0.02, 0.2, 1.0, and 5.0 mg/kg of PFNA. During postnatal day (PND) 1-21, a series of developmental test battery were conducted, including body weight, maturational milestones (pinnae unfolding, incisor eruption, hair growth and eye opening) and neurobehavioral reflex (surface righting reflex, negative geotaxis, and cliff avoidance tests). Morris water maze tests were performed to study the learning and memory ability of the rat offspring on PND 28. RESULTS:PFNA exposure during gestation resulted in lower weight (≥1.0 mg/kg), later eye opening and worse performance in negative geotaxis (5.0 mg/kg), but no associations were observed between PFNA exposure and other maturational milestones or neurobehavioral reflex. Further, morris water maze tests indicated damaged spatial learning and memory ability of offspring (≥0.2 mg/kg). CONCLUSIONS:Our study reveals that PFNA exposure during gestation produce multiple adverse effects on neuro-development in rat, research is needed to examine the potential mechanisms linked to the adverse effects of PFNA. KEYWORDS: perfluorononanoic acid, neurobehavioral development, rat offspring, prenatal exposure

全氟与多氟烷基物质(PFAS)是一类用于工业生产并广泛存在于环境中的氟代有机化合物,是一类环境内分泌干扰物,对人体具有多种毒性作用.近年来,PFAS所产生的生殖毒性受到越来越多的关注.在男性中,PFAS与精子质量下降、睾酮水平降低有关;在女性中,PFAS与女性体内异常的性激素水平、不孕风险增加有关,还与女性不正常的生理周期有关.机制研究表明,PFAS可能通过影响下丘脑-垂体-性腺轴,干扰性激素生成,诱导生殖细胞氧化应激等途径产生生殖毒性.本文主要从人群流行病学、动物研究及其机制方面概述PFAS的生殖毒性,有助于进一步了解其毒性效应及机制.