Maternal occupational noise exposure during pregnancy and children's early language acquisition.

INTRODUCTION: Noise exposure during pregnancy may affect a child's auditory system, which may disturb fetal learning and language development. We examined the impact of occupational noise exposure during pregnancy on children's language acquisition at the age of one. METHODS: A cohort study was conducted among women working in the food industry, as kindergarten teachers, musicians, dental nurses, or pharmacists who had a child aged <1 year. The analyses covered 408 mother-child pairs. Language acquisition was measured using the Infant-Toddler Checklist. An occupational hygienist assessed noise exposure individually as no (N = 180), low (70-78 dB; N = 108) or moderate/high exposure (>79 dB; N = 120). RESULTS: Among the boys, the adjusted mean differences in language acquisition scores were -0.4 (95% CI -2.5, 1.8) for low, and -0.7 (95% CI -2.9, 1.4) for moderate/high exposure compared to no exposure. Among the girls the respective scores were +0.1 (95% CI -2.2, 2.5) and -0.1 (95% CI -2.3, 2.2). Among the children of kindergarten teachers, who were mainly exposed to human noise, low or moderate exposure was associated with lower language acquisition scores. The adjusted mean differences were -3.8 (95% CI -7.2, -0.4) for low and -4.9 (95% CI -8.6, -1.2) for moderate exposure. CONCLUSIONS: In general, we did not detect an association between maternal noise exposure and children's language acquisition among one-year-old children. However, the children of kindergarten teachers exposed to human noise had lower language acquisition scores than the children of the non-exposed participants. These suggestive findings merit further investigation by level and type of exposure.

Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Wildfire particulate exposure and risks of preterm birth and low birth weight in the Southwestern United States.

OBJECTIVES: Wildfire air pollution is a growing concern on human health. The study aims to assess the associations between wildfire air pollution and pregnancy outcomes in the Southwestern United States. STUDY DESIGN: This was a retrospective cohort study. METHODS: Birth records of 627,404 singleton deliveries in 2018 were obtained in eight states of the Southwestern United States and were linked to wildfire-sourced fine particulate matter (PM2.5) and their constituents (black carbon [BC] and organic carbon [OC]) during the entire gestational period. A double-robust logistic regression model was used to assess the associations of wildfire-sourced PM2.5 exposures and preterm birth and term low birth weight, adjusting for non-fire-sourced PM2.5 exposure and individual- and area-level confounder variables. RESULTS: Wildfire-sourced PM2.5 contributed on average 15% of the ambient total PM2.5 concentrations. For preterm birth, the strongest association was observed in the second trimester (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.05-1.07 for PM2.5; 1.06, 95% CI: 1.05-1.07 for BC; 1.04, 95% CI: 1.03-1.05 for OC, per interquartile range increment of exposure), with higher risks identified among non-smokers or those with low socio-economic status. For term low birth weight, the associations with wildfire-sourced PM2.5 exposures were consistently elevated for all trimesters except for the exposure averaged over the entire gestational period. Overall, the associations between wildfire-sourced PM2.5 and pregnancy outcomes were stronger than those with total PM2.5. CONCLUSIONS: Wildfire-sourced PM2.5 and its constituents are linked to higher risks of preterm birth and term low birth weight among a significant US population than the effects of ambient total PM2.5.

Prenatal phthalate exposure and sex steroid hormones in newborns: Taiwan Maternal and Infant Cohort Study.

BACKGROUND: Newborn anogenital distance (AGD) has been associated with prenatal exposure of phthalates. The association between prenatal phthalate exposure and sex steroid hormones in newborns is unclear. OBJECT: This study aimed to examine whether cord-blood sex hormone levels were associated with prenatal phthalate exposure and newborn anogenital distance (AGD). METHODS: In the Taiwan Maternal and Infant Cohort Study, we recruited 1,676 pregnant women in their third trimester in 2012-2015 in Taiwan. We determined 11 urinary phthalate metabolites in pregnant women, three maternal and five cord-blood steroid sex-hormone concentrations. Five hundred and sixty-five mother-infant pairs with sufficient data were included. Trained neonatologists measured 263 newborns' AGD. We examined the associations of prenatal phthalate metabolite levels with AGD and hormones using linear regression models and evaluated correlations between maternal and cord-blood sex hormone levels and AGD. RESULTS: Compared with the male newborns exposed to maternal phthalate metabolites at the first tertile, AGD was -3.75, -3.43, and -3.53 mm shorter among those exposed at the median tertile of di-2-ethylhexyl phthalate (DEHP) metabolites, monobenzyl phthalate (MBzP), and monomethyl phthalate (MMP), respectively. Compared with those who had exposed at the first tertile, cord-blood follicle-stimulating hormone (FSH) decreased among male newborns exposed at higher levels of MMP, mono-n-butyl phthalate (MnBP), MBzP and DEHP, and among female newborns exposed at higher levels of MMP, MBzP and mono(2-ethyl-5-hydroxyhexyl) phthalate. However, we did not observe significant correlations of maternal or cord-blood sex steroid hormones with newborns' AGDs. CONCLUSIONS: Alterations in cord-blood sex steroid hormone levels were associated with prenatal phthalate exposures, particularly in male newborns. Women aspiring to be pregnant should be alerted of the need of reducing phthalate exposure.

Evidence of reduced gestational age in response to in utero arsenic exposure and implications for aging trajectories of the newborn.

Arsenic exposure is associated with a plethora of age-related health outcomes of disparate etiology. However, evidence of the impact of arsenic on aging remains limited. Here, we investigated the utility of epigenetic clocks in two different populations and the impact of maternal arsenic exposure during pregnancy on epigenetic gestational age at birth. To do this, we examined publicly available DNA methylation data and estimated gestational age across five gestational clocks in two unrelated human populations. These populations also differ in the extent of arsenic exposure and the targeted tissue of analysis (cord blood and placental tissue). Our results indicate that same-tissue clocks produce gestational age estimates that are more highly correlated with clinical gestational age. Interestingly, our results also indicate that arsenic exposure is associated with gestational age, with higher arsenic exposures associated with decreased gestational age. We also applied two pediatric clocks to evaluate infant biological age in the same samples. The data is suggestive of higher pediatric age in infants exposed to higher arsenic levels during gestation. Taken altogether, our findings are consistent with past work indicating that that in utero arsenic exposure is associated with decreased gestational maturity as characterized by infant outcomes such as low birthweight and lung underdevelopment and dysfunction in arsenic exposed infants. The findings are also consistent with arsenic exposure setting infants on a trajectory of accelerated epigenetic aging that starts at birth.

Maternal exposure to deltamethrin during pregnancy and lactation impairs neurodevelopment of male offspring.

Deltamethrin (DM) is a highly effective and widely used pyrethroid pesticide. It is an environmental factor affecting public and occupational health and exerts direct toxic effects on the central nervous system. As the major target organs for neurotoxicity of DM, the hippocampus and the cerebellum are critical to the learning and motor function. Pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PN) 21. The PC12 cells were selected to further verify the regulatory mechanisms of DM on the neurodevelopmental injury. We found that maternal exposure to DM caused learning, memory and motor dysfunction in male offspring. Maternal exposure to DM induced the decrease in the density of hippocampal dendritic spines in male offspring through the reduced expression of M1 mAchRs, which in turn reduced the mediated AKT/mTOR signaling pathway, contributing to the inhibition of dynamic changes of GluA1. Meanwhile, DM exposure inhibited the BDNF/TrkB signaling pathway, thereby reducing phosphorylation of stathmin and impairing cerebellar purkinje cell dendrite growth and development. Taken together, maternal exposure to DM during pregnancy and lactation could impair neurodevelopment of male offspring.

Maternal exposure to ZIF-8 derails placental function by inducing trophoblast pyroptosis through neutrophils activation in mice.

Adverse environmental factors during maternal gestation pose a threat to pregnancy. Environmental factors, particularly nanoparticles, can impact pregnancy by causing damage to the placenta. Compared to early gestation, foetuses in late gestation are more robustly developed and at lower risk of adverse effects from environmental factors. Delivery systems for targeted therapy during pregnancy is predominantly focused on their application in late gestation. Zeolitic imidazolate framework-8 (ZIF-8) holds great potential for targeted drug therapy. To evaluate the value of ZIF-8 in targeted treatment of disorders associated with late gestation, it is crucial to investigate the biological effects of ZIF-8 exposure during late gestation. Here, a mouse model exposed to ZIF-8 particles at different doses (5, 10, and 15 mg/kg) during late gestation was constructed. We found that ZIF-8 particles were deposited in the uterus of pregnant mice. ZIF-8 could trigger placental neutrophil aggregation and induce inflammation, which led to trophoblast pyroptosis and impair placental function, adversely affecting the foetus. Neutrophil depletion alleviated placental and foetal damage induced by ZIF-8. This study provides a novel mechanistic view of the reproductive toxicity induced by ZIF-8 and may offer clues to reduce the latent harm of adverse environmental factors to pregnancy.

Windows of sensitivity for risk of adverse birth outcomes related to gestational PM2.5 exposure: Evidence from a natural experiment.

While numerous studies have associated maternal exposure to PM2.5 with adverse birth outcomes, findings remain inconsistent and difficult to generalize. We aimed to investigate the causal relationship and window of sensitivity between gestational exposure to PM2.5 and birth outcomes. We leveraged high-resolution satellite data to quantify gestational PM2.5 exposure at the individual level, along with a combined model to determine daily relative risks (RRs) of birth outcomes in COVID-19 prelockdown and lockdown groups. RRs between the two groups were further compared using a longitudinal pre-post non-experimental design to identify sensitivity windows of adverse birth outcomes. A total of 73,781 pregnant women from the COVID-19 prelockdown group and 6267 pregnant women from the lockdown group were included for analysis. The daily mean PM2.5 concentrations in the lockdown group decreased by 21.7% compared to the prelockdown group. During the first trimester, every 10 µg/m3 increase in PM2.5 significantly increased the risk of congenital abnormalities of major organs such as the cardiovascular system, gastrointestinal tract, nervous system, urinary system, and respiratory system. Moreover, gestational exposure to PM2.5 during the first trimester was associated with higher risks of premature delivery and term low birth weight. While PM2.5 exposure during the second trimester was positively correlated with macrosomia. Gestational exposure to PM2.5 is associated with increased risks of various adverse birth outcomes with specific sensitive windows. We demonstrated that gestational exposure to PM2.5 increased risks of various adverse birth outcomes with specific window of sensitivity through the natural experiment design. Our findings underscore the urgent need for policies and initiatives targeting PM2.5 reduction, especially during critical periods of pregnancy.

Infantile allergic diseases: a cohort study prenatal fish intake and mercury exposure context.

BACKGROUND: Allergic diseases (ADs) have been increasingly reported in infants and children over the last decade. Diet, especially the inclusion of fish intake, may help to lower the risk of ADs. However, fish also, can bioaccumulate environmental contaminants such as mercury. Hence, our study aims to determine what effects the type and frequency of fish intake have on ADs in six-month-old infants, independently and jointly with mercury exposure. METHODS: This study is part of the prospective birth cohort: Mothers and Children's Environmental Health (MOCEH) study in South Korea. Data was collected on prenatal fish intake, prenatal mercury concentration and ADs for infants aged six months for 590 eligible mother-infant pairs. Logistic regression analysis was conducted to evaluate the risk of prenatal fish intake and mercury concentration on ADs in infants. Finally, interaction between fish intake and mercury concentration affecting ADs in infants was evaluated. Hazard ratios of prenatal fish intake on ADs in 6 month old infants were calculated by prenatal mercury exposure. RESULTS: Logistic regression analysis showed that white fish (OR: 0.53; 95% CI 0.30-0.94; P < 0.05) intake frequency, once a week significantly decreased the risk of ADs in infants. Stratification analysis showed that consuming white fish once a week significantly reduced the hazard of ADs (HR: 0.44; 95% CI 0.21-0.92; P < 0.05) in infants in the high-mercury (≥ 50th percentile) exposure group. CONCLUSION: The result indicates that prenatal white fish intake at least once a week reduces the risk of ADs in infants, especially in the group with high prenatal mercury exposure.

Maternal exposure to polystyrene nanoplastics causes defective retinal development and function in progeny mice by disturbing metabolic profiles.

Microplastics (MPs) and nanoplastics (NPs) are widely spreading in our living environment, accumulating in the human body and potentially threating human health. The retina, which is a terminally differentiated extension of the central nervous system, is essential for the visual system. However, the effects and molecular mechanisms of MPs/NPs on retina development and function are still unclear. Here, we investigated the effects and modes of action of polystyrene NPs (PS-NPs) on the retina using mice as a mammalian model species. Maternal PS-NP exposure (100 nm) at an environmentally realistic concentration of 10 mg L-1 (or 2.07 *1010 particles mL-1) via drinking water from the first day of pregnancy till the end of lactation (21 days after birth) caused defective neural retinal development in the neonatal mice, by depositing in the retinal tissue and reducing the number of retinal ganglion cells and bipolar cells. Exposure to PS-NPs retarded retinal vascular development, while abnormal electroretinogram (ERG) responses and an increased level of oxidative stress were also observed in the retina of the progeny mice after maternal PS-NP exposure. Metabolomics showed significant dysregulation of amino acids that are pivotal to neuron retinal function, such as glutamate, aspartate, alanine, glycine, serine, threonine, taurine, and serotonin. Transcriptomics identified significantly dysregulated genes, which were enriched in processes of angiogenesis, visual system development and lens development. Regulatory analysis showed that Fos gene mediated pathways could be a potential key target for PS-NP exposure in retinal development and function. Our study revealed that maternal exposure to PS-NPs generated detrimental effects on retinal development and function in progeny mice, offering new insights into the visual toxicity of PS-NPs.

Similar toxicity potential of glyphosate and glyphosate-based herbicide on cerebellar development after maternal exposure in rats.

Studies on the effects of glyphosate (GlyP) and glyphosate-based herbicides (GBHs) on cerebellar development are extremely limited. This study examined the effects of maternal exposure to GlyP and GBH on rat cerebellar development in male offspring. From day 6 of gestation until day 21 postpartum at weaning, dams were given GlyP at 1.5% or 3.0% in diet or GBH at 1.0% in drinking water (corresponding to 0.36% GlyP). At weaning, GBH exposure was linked to increased numbers of DCX+ migrating granule cells in the cortex and TUNEL+ apoptotic cells in the internal granular layer (IGL), suggesting the disappearance of mismigrated granule cells via apoptosis. GBH also upregulated Nr4a3 and downregulated Cdk5 in the cerebellar vermis, suggesting a causal relation with the impaired granule cell development at this time. GlyP (3.0%) tended to increase in the number of DCX+ migrating granule cells in the IGL and upregulated Nr4a3 at weaning. Both compounds also upregulated genes related to granule cell migration (Astn1, Astn2, Nfia, and/or Nfix) at weaning and in adulthood, which might be an ameliorative response to delayed granule cell migration. Moreover, GBH induced Purkinje cell misalignment at weaning, which could be the result of delayed granule cell migration. In adulthood, GBH was associated with upregulation of the reelin signaling-related genes Reln, Dab1, and Efnb1, suggesting a compensatory response to Purkinje cell misalignment. GlyP induced the same gene expression changes. These results suggest that GBH reversibly disrupts cerebellar development, primarily by targeting granule cell migration and differentiation, whereas GlyP exhibited similar toxic potential as GBH.

Maternal exposure to glyphosate-based herbicide causes vascular dysfunction in offspring female rats.

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based herbicide (O-GBH) and controls (O-CON) rats at six months of age. Relaxation to acetylcholine was reduced in O-GBH than in O-CON. Acute Indomethacin and Apocynin increased relaxation to acetylcholine in O-GBH. The aorta from O-GBH was hyperactive to phenylephrine; the preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GBH. TEMPOL similarly reduced phenylephrine response, and L-NAME prevented this effect. The TBARS and GSH levels were increased in O-GBH than in O-CON. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that oxidative stress parameters altered, and the current levels considered safe for exposure to Glyphosate deserve further investigation, especially in the female gender.

Maternal exposure to particulate matter from duck houses restricts fetal growth due to inflammatory damage and oxidative stress.

The composition of particulate matter (PM) in poultry farms differs significantly from that of atmospheric PM as there is a higher concentration of microbes on farms. To assess the health effects of PM from poultry farms on pregnant animals, we collected PM from duck houses using a particulate sampler, processed it via centrifugation and vacuum concentration, and subsequently exposed the mice to airborne PM at 0.48 mg/m3 (i.e., low concentration group) and 1.92 mg/m3 (i.e., high concentration group) on the fifth day of pregnancy. After exposure until the twentieth day of pregnancy or spontaneous delivery, mice were euthanized for sampling. The effects of PM from duck houses on the pregnancy toxicity of mice were analyzed using histopathological analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction (qPCR). The results showed that exposure to PM had adverse effects on pregnant mice that reduced their feed intake in both groups. Microscopic lesions were observed in the lungs and placentas of pregnant mice, and the lesions worsened with increased PM concentrations, as shown by alveolar wall thickening, the infiltration of inflammatory cells in pulmonary interstitium, congestion, edema, and cellular degeneration of placenta. In pregnant mice in the high concentration group, exposure to PM significantly increased the expression of inflammatory cytokines in the lungs and placentas, caused oxidative stress, and decreased estrogen level in the blood. Exposure to PM also resulted in the reduced litter sizes of pregnant mice and shorter body and tail lengths in the fetuses delivered. Beyond that, exposure to PM significantly downregulated the levels of antioxidant factor superoxide dismutase and neurotrophic factor Ngf in the brains of fetuses. Collectively, exposure to a high concentration of PM by inhalation among pregnant mice caused significant pregnancy toxicity that led to abnormal fetal development due to inflammatory damage and oxidative stress. These findings established a foundation for future studies on the underlying mechanisms of pregnancy toxicity induced by exposure to PM.

Maternal nicotine exposure promotes hippocampal CeRNA-mediated excitotoxicity and social barriers in adolescent offspring mice.

Nicotine, an addictive component of cigarettes, causes cognitive defects, particularly when exposure occurs early in life. However, the exact mechanism through which nicotine causes toxicity and alters synaptic plasticity is still not fully understood. The aim of the current study is to examine how non-coding developmental regulatory RNA impacts the hippocampus of mice offspring whose mothers were exposed to nicotine. Female C57BL/6J mice were given nicotine water from one week before pregnancy until end of lactation. Hippocampal tissue from offspring at 20 days post-birth was used for LncRNA and mRNA microarray analysis. Differential expression of LncRNAs and mRNAs associated with neuronal development were screened and validated, and the CeRNA pathway mediating neuronal synaptic plasticity GM13530/miR-7119-3p/mef2c was predicted using LncBase Predicted v.2. Using protein immunoblotting, Golgi staining and behavioral tests, our findings revealed that nicotine exposure in offspring mice increased hippocampal NMDAR receptor, activated receptor-dependent calcium channels, enhanced the formation of NMDAR/nNOS/PSD95 ternary complexes, increased NO synthesis, mediated p38 activation, induced neuronal excitability toxicity. Furthermore, an epigenetic CeRNA regulatory mechanism was identified, which suppresses Mef2c-mediated synaptic plasticity and leads to modifications in the learning and social behavior of the offspring during adolescence. This study uncovers the way in which maternal nicotine exposure results in neurotoxicity in offspring.

Association of exposure to mixture of chemicals during pregnancy with cognitive abilities and fine motor function of children.

Chemical exposures often occur in mixtures and exposures during pregnancy may lead to adverse effects on the fetal brain, potentially reducing lower cognitive abilities and fine motor function of the child. We investigated the association of mothers exposure to a mixture of chemicals during pregnancy (i.e., organochlorine compounds, per- and polyfluoroalkyl substances, phenols, phthalates, organophosphate pesticides) with cognitive abilties and fine motor function in their children. We studied 1097 mother-child pairs from five European cohorts participating in the Human Early Life Exposome study (HELIX). Measurement of 26 biomarkers of exposure to chemicals was performed on urine or blood samples of pregnant women (mean age 31 years). Cognitive abilities and fine motor function were assessed in their children (mean age 8 years) with a battery of computerized tests administered in person (Ravens Coloured Progressive Matrices, Attention Network Test, N-back Test, Trail Making Test, Finger Tapping Test). We estimated the joint effect of prenatal exposure to chemicals on cognitive abilities and fine motor function using the quantile-based g-computation method, adjusting for sociodemographic characteristics. A quartile increase in all the chemicals in the overall mixture was associated with worse fine motor function, specifically lower scores in the Finger Tapping Test [-8.5 points, 95 % confidence interval (CI) -13.6 to -3.4; -14.5 points, 95 % CI -22.4 to -6.6, and -18.0 points, 95 % CI -28.6 to -7.4) for the second, third and fourth quartile of the overal mixture, respectively, when compared to the first quartile]. Organochlorine compounds, phthalates, and per- and polyfluoroalkyl substances contributed most to this association. We did not find a relationship with cognitive abilities. We conclude that exposure to chemical mixtures during pregnancy may influence neurodevelopment, impacting fine motor function of the offspring.

Prenatal exposure to polybrominated diphenyl ether (PBDE) and child neurodevelopment: The role of breastfeeding duration.

BACKGROUND: Prenatal and early-life exposure to polybrominated diphenyl ethers (PBDEs) is associated with detrimental and irreversible neurodevelopmental health outcomes during childhood. Breastfeeding may be a child's largest sustained exposure to PBDE- potentially exacerbating their risk for adverse neurodevelopment outcomes. However, breastfeeding has also been associated with positive neurodevelopment. Our study investigates if breastfeeding mitigates or exacerbates the known adverse effects of prenatal exposure to PBDEs and child neurodevelopment. METHODS: Participants included 321 mother-infant dyads from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort in California. PBDE concentrations were measured in maternal serum blood samples collected during pregnancy or at delivery. Using generalized estimated equations (GEE), we estimated associations of PBDE concentrations with children's attention, executive function, and cognitive scores assessed longitudinally between 7 and 12 years of age, stratified by duration of exclusive and complementary breastfeeding. RESULTS: We observed that higher maternal prenatal PBDE concentrations were associated with poorer executive function among children who were complementary breastfed for a shorter duration compared to children breastfed for a longer duration; preservative errors (ß for 10-fold increase in complementary breastfeeding <7 months = -6.6; 95 % Confidence Interval (CI): -11.4, -1.8; ß ≥ 7 months = -5.1; 95 % CI: -10.2, 0.1) and global executive composition (ß for 10-fold increase <7 months = 4.3; 95 % CI: 0.4, 8.2; ß for 10-fold increase ≥7 months = 0.6; 95 % CI: -2.8, 3.9). CONCLUSIONS: Prolonged breastfeeding does not exacerbate but may mitigate some previously observed negative associations of prenatal PBDE exposure and child neurodevelopment.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study.

BACKGROUND: The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. METHODS: A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-phthalates exposure interactions. RESULTS: There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28-2.37; dominant: aOR = 1.86, 95% CI:1.25-2.78; recessive: aOR = 2.50, 95% CI: 1.26-4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54-121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. CONCLUSIONS: The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age.

BACKGROUND: Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors. METHODS: A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children's neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility. RESULTS: Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (ß = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (ß = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins. CONCLUSIONS: Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Maternal exposure to di-(2-ethylhexyl) phthalate impaired the social interaction via activating microglia in male pups.

Di-(2-ethylhexyl) phthalate (DEHP), a common endocrine-disrupting chemical (EDC), is widely used in daily articles, early exposure to DEHP is associated with many behavioral changes in pups. This study aimed to investigate the effects and underlying mechanisms of maternal exposure to DEHP on the impaired social interaction in pups. Pregnant rats were administered 0, 30, 300, or 750 mg/kg/d DEHP daily by oral gavage. Highly aggressive proliferating immortalized (HAPI) cells were treated with mono-(2-ethylhexyl) phthalate (MEHP) and tyrosine phosphorylation inhibitor (AG490). Our results showed that DEHP exposure induced the activation of microglias (MGs) via activating the janus kinase 2 / signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway, and increased the level of pro-inflammatory factors, then impaired the social behavior in male pups, but not female pups. Moreover, MEHP exposure could also activate HAPI via activating this signaling pathway, and AG490 could inhibit the activation of this signaling pathway caused by MEHP. Therefore, we indicated that maternal exposure to DEHP could cause the gender-specific impaired social interaction in pups that might be related to the activation of MGs.