Exposure to indoor air pollution and adverse pregnancy outcomes in low and middle-income countries: a systematic review and meta-analysis.

Introduction: Exposure to indoor air pollution such as biomass fuel and particulate matter is a significant cause of adverse pregnancy outcomes. However, there is limited information about the association between indoor air pollution exposure and adverse pregnancy outcomes in low and middle-income countries. Therefore, this meta-analysis aimed to determine the association between indoor air pollution exposure and adverse pregnancy outcomes in low and middle-income countries. Methods: International electronic databases such as PubMed, Science Direct, Global Health, African Journals Online, HINARI, Semantic Scholar, and Google and Google Scholar were used to search for relevant articles. The study was conducted according to the updated Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A random effect model at a 95% confidence interval was used to determine the association between indoor air pollution exposure and adverse pregnancy outcomes using STATA version 14. Funnel plot and Higgs I2 statistics were used to determine the publication bias and heterogeneity of the included studies, respectively. Results: A total of 30 articles with 2,120,228 study participants were included in this meta-analysis. The pooled association between indoor air pollution exposure and at least one adverse pregnancy outcome was 15.5% (95%CI: 12.6-18.5), with significant heterogeneity (I2 = 100%; p < 0.001). Exposure to indoor air pollution increased the risk of small for gestational age by 23.7% (95%CI: 8.2-39.3) followed by low birth weight (17.7%; 95%CI: 12.9-22.5). Exposure to biomass fuel (OR = 1.16; 95%CI: 1.12-1.2), particulate matter (OR = 1.28; 95%CI: 1.25-1.31), and kerosene (OR = 1.38; 95%CI: 1.09-1.66) were factors associated with developing at least one adverse pregnancy outcomes. Conclusions: We found that more than one in seven pregnant women exposed to indoor air pollution had at least one adverse pregnancy outcome. Specifically, exposure to particulate matter, biomass fuel, and kerosene were determinant factors for developing at least one adverse pregnancy outcome. Therefore, urgent comprehensive health intervention should be implemented in the area to reduce adverse pregnancy outcomes.

Investigation of the relationship between air pollution and gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) can have negative effects on both the pregnancy and perinatal outcomes, as well as the long-term health of the mother and the child. It has been suggested that exposure to air pollution may increase the risk of developing GDM. This study investigated the relationship between exposure to air pollutants with gestational diabetes. METHODS: The present study is a retrospective cohort study. We used data from a randomised community trial conducted between September 2016 and January 2019 in Iran. During this period, data on air pollutant levels of five cities investigated in the original study, including 6090 pregnant women, were available. Concentrations of ozone (O3), nitric oxide (NO), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 (PM2.5) or <10 µm (PM10) were obtained from air pollution monitoring stations. Exposure to air pollutants during the three months preceding pregnancy and the first, second and third trimesters of pregnancy for each participant was estimated. The odds ratio was calculated based on logistic regression in three adjusted models considering different confounders. Only results that had a p < .05 were considered statistically significant. RESULTS: None of the logistic regression models showed any statistically significant relationship between the exposure to any of the pollutants and GDM at different time points (before pregnancy, in the first, second and third trimesters of pregnancy and 12 months in total) (p > .05). Also, none of the adjusted logistic regression models showed any significant association between PM10 exposure and GDM risk at all different time points after adjusting for various confounders (p > .05). CONCLUSIONS: This study found no association between GDM risk and exposure to various air pollutants before and during the different trimesters of pregnancy. This result should be interpreted cautiously due to the lack of considering all of the potential confounders.

The health of pregnant women and their children can be impacted by gestational diabetes mellitus (GDM), one of the prevalent pregnancy complications. Some of studies showed that the incidence of gestational diabetes can be influenced by genetic or environmental factors. Air pollution is an environmental stimulus that may predispose pregnant women to GDM. This research explored whether air pollution could increase the risk of developing gestational diabetes. Over 6000 pregnant women in five cities of Iran participated in the study and were screened for gestational diabetes. Their exposure to the various air pollutants during the three months preceding pregnancy and total pregnancy period was measured. In this study, we found no clear association between air pollution and gestational diabetes. However, this finding needs to be interpreted cautiously since all the influential factors were not assessed.

Association of prenatal multiple metal exposures with child neurodevelopment at 3 years of age: A prospective birth cohort study.

Prenatal exposures to toxic metals and trace elements have been linked to childhood neurodevelopment. However, existing evidence remains inconclusive, and further research is needed to investigate the mixture effects of multiple metal exposures on childhood neurodevelopment. We aimed to examine the associations between prenatal exposure to specific metals and metal mixtures and neurodevelopment in children. In this prospective cohort study, we used the multivariable linear regressions and the robust modified Poisson regressions to explore the associations of prenatal exposure to 25 specific metals with neurodevelopment among children at 3 years of age in 854 mother-child pairs from the Jiangsu Birth Cohort (JBC) Study. The Bayesian kernel machine regression (BKMR) was employed to assess the joint effects of multiple metals on neurodevelopment. Prenatal manganese (Mn) exposure was negatively associated with the risk of non-optimal cognition development of children, while vanadium (V), copper (Cu), zinc (Zn), antimony (Sb), cerium (Ce) and uranium (U) exposures were positively associated with the risk of non-optimal gross motor development. BKMR identified an interaction effect between Sb and Ce on non-optimal gross motor development. Additionally, an element risk score (ERS), representing the mixture effect of multiple metal exposures including V, Cu, Zn, Sb, Ce and U was constructed based on weights from a Poisson regression model. Children with ERS in the highest tertile had higher probability of non-optimal gross motor development (RR = 2.37, 95 % CI: 1.15, 4.86) versus those at the lowest tertile. Notably, Sb [conditional-posterior inclusion probabilities (cPIP) = 0.511] and U (cPIP = 0.386) mainly contributed to the increased risk of non-optimal gross motor development. The findings highlight the importance of paying attention to the joint effects of multiple metals on children's neurodevelopment. The ERS score may serve as an indicator of comprehensive metal exposure risk for children's neurodevelopment.

Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy and timing of pubertal onset in a longitudinal mother-child cohort in rural Bangladesh.

BACKGROUND: In experimental studies, several polycyclic aromatic hydrocarbons (PAHs) have shown endocrine disrupting properties, but very few epidemiological studies have examined their impact on pubertal development and results have been heterogenous. OBJECTIVE: To explore if maternal PAH exposure during pregnancy was associated with the offspring's timing of pubertal onset. METHODS: We studied 582 mother-daughter dyads originating from a population-based cohort in a rural setting in Bangladesh. Maternal urinary samples, collected in early pregnancy (on average, gestational week 8), were analyzed for monohydroxylated metabolites of phenanthrene (1-OH-Phe, Σ2-,3-OH-Phe, and 4-OH-Phe), fluorene (Σ2-,3-OH-Flu), and pyrene (1-OH-Pyr) using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The girls were interviewed on two separate occasions concerning date of menarche, as well as breast and pubic hair development according to Tanner. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox proportional hazards regression or ordered logistic regression. RESULTS: In early pregnancy, the mothers' median urinary concentrations of Σ1-,2-,3-,4-OH-Phe, Σ2-,3-OH-Flu, and 1-OH-Pyr were 3.25 ng/mL, 2.0 ng/mL, and 2.3 ng/mL respectively. At the second follow-up, 78 % of the girls had reached menarche, and the median age of menarche was 12.7 ± 0.81 years. Girls whose mothers belonged to the second and third quintiles of ΣOH-Phe metabolites had a higher rate of menarche, indicating a younger menarcheal age (HR 1.39; 95 % CI 1.04, 1.86, and HR 1.41; 95 % CI 1.05, 1.88, respectively), than girls of mothers in the lowest quintile. This trend was not observed in relation to either breast or pubic hair development. None of the other maternal urinary PAH metabolites or the sum of all thereof in early pregnancy were associated with age at menarche or pubertal stage. CONCLUSIONS: Indications of non-monotonic associations of prenatal phenanthrene exposure with the daughters' age of menarche were found, warranting further investigation.

The mother-offspring transfer of chlorothalonil through human breast milk: A multi-city cross-sectional study.

4-Hydroxychlorothalonil (4-OH CHT), the main metabolite of chlorothalonil and the most widely used fungicide, has been frequently detected in human samples during monitoring. 4-OH CHT may exhibit higher toxicity and persistence in the environment compared to its prototype. In this study, a total of 540 paired serum and breast milk samples from pregnant women in three provinces in China were monitored for contaminant residues. 4-OH CHT was analyzed in the samples using ultra high-performance liquid chromatography - high-resolution mass spectrometry with a detection limit of 20 ng/L. The study investigated the effects of demographic factors, such as BMI, region of residence, and education level, on the levels of 4-OH CHT residues in serum and breast milk. Among the three provinces, the highest median concentration of 4-OH CHT in serum samples was observed in Hebei (1.04 × 103 ng/L), while the highest median concentration of 4-OH CHT in breast milk samples was observed in Hubei and Guangdong (491 ng/L). Multiple linear regression was used to investigate the significant positive correlation between 4-OH CHT in serum and breast milk (p = 0.000) after adjusting for personal characteristics. Based on this, the study further explored the influencing factors of transfer efficiencies (TEs) in conjunction with the individual TEs and the personal characteristics of the participants. Our results demonstrated that the age of the volunteers and their exercise habits had an effect on TEs, but further studies are needed to determine whether exercise leads to an increase in TEs.

The relationship between air pollutants and preterm birth and blood routine changes in typical river valley city.

OBJECTIVE: To collect maternal maternity information on preterm births in two tertiary hospitals in the urban area of Baota District, Yan'an City, from January 2018 to December 2020, to explore the long-term and short-term effects of air pollutants (PM2.5, PM10, SO2, NO2, CO and O3) and preterm births, and to explore changes in blood cell counts due to air pollutants. METHODS: Daily average mass concentration data of six air pollutants in the urban area of Yan'an City from January 1, 2017 to December 31, 2020 were collected from the monitoring station in Baota District, Yan'an City. Meteorological information was obtained from the Meteorological Bureau of Yan'an City, including temperature,relative humidity and wind speed for the time period. The mass concentration of air pollutants in each exposure window of pregnant women was assessed by the nearest monitoring station method, and conditional logistic regression was used to analyze the relationship between air pollutants and preterm births, as well as the lagged and cumulative effects of air pollutants. Multiple linear regression was used to explore the relationship between air pollutants and blood tests after stepwise linear regression was used to determine confounders for each blood test. RESULTS: The long-term effects of pollutants showed that PM2.5, PM10, SO2, NO2and CO were risk factors for preterm birth. In the two-pollutant model, PM2.5, PM10, SO2 and NO2 mixed with other pollutants were associated with preterm birth. The lagged effect showed that PM2.5, PM10, SO2, NO, and CO were associated with preterm birth; the cumulative effect showed that other air pollutants except O3 were associated with preterm birth. The correlation study between air pollutants and blood indicators showed that air pollutants were correlated with leukocytes, monocytes, basophils, erythrocytes, hs-CRPand not with CRP. CONCLUSION: Exposure to air pollutants is a risk factor for preterm birth. Exposure to air pollutants was associated with changes in leukocytes, monocytes, basophils and erythrocytes and hs-CRP.

Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring.

BACKGROUND: Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. METHODS: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. RESULTS: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. CONCLUSIONS: Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

Metal exposure and blood lipid biomarkers in early pregnancy: A cross-sectional study.

Recognizing the risk factors for dyslipidemia during pregnancy is crucial for safeguarding the health of both the mothers and the offspring. Growing evidence emerged and suggested links between environmental factors, including metals, and alteration in lipid levels or dyslipidemia in general populations. However, knowledge of the associations during pregnancy remains extremely lacking. Herein, we aimed to explore whether elevated metal exposure constitutes a risk factor for dyslipidemia in pregnant women. Based on the Tongji-Shuangliu Birth Cohort (TSBC), a total of 663 pregnant women were recruited and their urinary levels of 17 metals and blood lipid biomarkers in early pregnancy were measured, namely triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The multivariable linear regression models revealed that exposure to selected metals during early pregnancy was significantly associated with some important biomarkers. In particular, after natural log-transformed for the levels of lipid biomarkers and metals, copper (Cu) exposure was positively associated with HDL-C (ß = 0.024, 95% CI: 0.001, 0.046), while zinc (Zn) was associated with TG (ß = 0.062, 95% CI: 0.013, 0.110) and selenium with TC (ß = 0.028, 95% CI: 0.004, 0.054). Exposure to rubidium (Rb) was positively associated with multiple lipid biomarkers, including HDL-C (ß = 0.020, 95% CI: 0.002, 0.037) and LDL-C (ß = 0.022, 95% CI: 0.001, 0.042). Mixture exposure analysis further identified significant associations between Cu and HDL-C, Zn and TG, Rb and HDL-C, when multiple metal exposures were considered in the Bayesian kernel machine regression model simultaneously. Our findings showed that exposure to several metals during early pregnancy was associated with an increased prevalence of blood lipid abnormalities in pregnant women. These findings underscore the potential impact of metal combinations on lipid metabolism and increase our understanding of the risk factors associated with abnormal lipid metabolism during pregnancy.

Prenatal per- and polyfluoroalkyl substances (PFAS) and maternal oxidative stress: Evidence from the LIFECODES study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully understood, evidence suggests PFAS may disrupt endocrine functions and contribute to oxidative stress (OS) and inflammation. OBJECTIVE: We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race. METHODS: We used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models. RESULTS: We observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: -17.68%, -0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed. CONCLUSIONS: This study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations.

Fetal and Infancy Exposure to Phenols, Parabens, and Phthalates and Anthropometric Measurements up to 36 Months, in the Longitudinal SEPAGES Cohort.

BACKGROUND: Endocrine-disrupting chemicals may play a role in adiposity development during childhood. Until now literature in this scope suffers from methodologic limitations in exposure assessment using one or few urine samples and missing assessment during the infancy period. OBJECTIVES: We investigated the associations between early-life exposure to quickly metabolized chemicals and post-natal growth, relying on repeated within-subject urine collections over pregnancy and infancy. METHODS: We studied the associations of four phenols, four parabens, seven phthalates, and one nonphthalate plasticizer from weekly pooled urine samples collected from the mother during second and third trimesters (median 18 and 34 gestational weeks, respectively) and infant at 2 and 12 months of age, and child growth until 36 months. We relied on repeated measures of height, weight and head circumference from study visits and the child health booklet to predict growth outcomes at 3 and 36 months using the Jenss-Bayley nonlinear mixed model. We assessed associations with individual chemicals using adjusted linear regression and mixtures of chemicals using a Bayesian kernel machine regression model. RESULTS: The unipollutant analysis revealed few associations. Bisphenol S (BPS) at second trimester was positively associated with all infant growth parameters at 3 and 36 months, with similar patterns between exposure at third trimester and all infant growth parameters at 3 months. Mono-n-butyl phthalate (MnBP) at 12 months was positively associated with body mass index (BMI), weight, and head circumference at 36 months. Mixture analysis revealed positive associations between exposure at 12 months and BMI and weight at 36 months, with MnBP showing the highest effect size within the mixture. CONCLUSIONS: This study suggests that exposure in early infancy may be associated with increased weight and BMI in early childhood, which are risk factors of obesity in later life. Furthermore, this study highlighted the impact of BPS, a compound replacing bisphenol A, which has never been studied in this context. https://doi.org/10.1289/EHP13644.

Systematic review and meta-analysis of birth weight and perfluorohexane sulfonate exposures: examination of sample timing and study confidence.

We examined the association between mean birth weight (BW) differences and perfluorohexane sulfonate (PFHxS) exposure biomarkers.We fit a random effects model to estimate the overall pooled effect and for different strata based on biomarker sample timing and overall study confidence. We also conducted an analysis to examine the impact of a continuous measure of gestational age sample timing on the overall pooled effect.We detected a -7.9 g (95% CI -15.0 to -0.7; pQ=0.85; I2=0%) BW decrease per ln ng/mL PFHxS increase based on 27 studies. The 11 medium confidence studies (ß=-10.0 g; 95% CI -21.1 to 1.1) showed larger deficits than 12 high (ß=-6.8 g; 95% CI -16.3 to 2.8) and 4 low confidence studies (ß=-1.5 g; 95% CI -51.6 to 48.7). 10 studies with mid-pregnancy to late-pregnancy sampling periods showed smaller deficits (ß=-3.9 g; 95% CI -17.7 to 9.9) than 5 post-partum studies (ß=-28.3 g; 95% CI -69.3 to 12.7) and 12 early sampling studies (ß=-7.6 g; 95% CI -16.2 to 1.1). 6 of 12 studies with the earliest sampling timing showed results closer to the null.Overall, we detected a small but statistically significant BW deficit across 27 studies. We saw comparable BW deficit magnitudes in both the medium and high confidence studies as well as the early pregnancy group. Despite no definitive pattern by sample timing, larger deficits were seen in postpartum studies. We also saw results closer to the null for a subset of studies restricted to the earliest biomarker collection times. Serial pregnancy sampling, improved precision in gestational age estimates and more standardised reporting of sample variation and exposure units in future epidemiologic research may offer a greater understanding of the relationship between PFHxS on BW and any potential impact of pregnancy haemodynamics.

The effect of per and polyfluoroalkyl substance (PFAS) exposure on gestational diabetes mellitus and its subclinical risk factors: A systematic review and meta-analysis protocol.

BACKGROUND: Multiple lines of evidence suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may alter glucose homeostasis, particularly during pregnancy, and may affect risk for developing gestational diabetes mellitus (GDM). While previous systematic reviews have been conducted on this topic, they did not assess internal validity of the included studies and their search strategies were narrowly focused. OBJECTIVE: The objective of this study is to assess the effect of higher PFAS exposure (defined by individual compounds or mixtures measured before or during pregnancy) on GDM and subclinical measures of impaired glucose homeostasis (measured during pregnancy) compared to lower PFAS exposure in pregnant. METHODS: We developed our systematic review protocol in accordance with the Navigation Guide. Peer-reviewed journal and grey literature searches were piloted in to identify relevant studies and refine our search terms and strategy. We also piloted the study screening criteria and data extraction form in DistillerSR, and refined our protocol accordingly. The risk of bias assessment protocol was adapted from Navigation Guide guidance and will be piloted and performed in DistillerSR. Pending the identification of comparable studies, quantitative meta-analyses will be performed where possible. Study results that cannot be quantitatively synthesized will be included in a narrative synthesis. The quality and strength of the body of evidence will be evaluated using Navigation Guide methodology, which is informed by guidance from the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation (GRADE). We also made refinements to the quality of evidence considerations based on guidance from the National Institute of Environmental Health Sciences (NIEHS) Office of Health Assessment and Translation (OHAT). FUNDING: This work was supported by the Systematizing Data on Per- and Polyfluoroalkyl Substances and Health Northeastern University TIER 1 Award.

Association of placental weight at birth with maternal whole blood concentration of heavy metals (cadmium, lead, mercury, selenium, and manganese): The Japan Environment and Children's Study (JECS).

BACKGROUND: Lifelong health is dependent on prenatal growth and development, influenced by the placental intrauterine environment. Charged with dual functions--exchange of oxygen and nutrients as well as a barrier against toxins--the placenta itself is susceptible to environmental exposure to heavy metals. OBJECTIVE: To examine the use of placenta weight as a biomarker for heavy metal exposure using a large Japanese cohort of pregnant women. METHODS: The placenta weight, as a biomarker of exposure to heavy metals (cadmium, lead, and mercury), was investigated using data from the Japan Environment and Children's Study (2011-2014). Selenium and manganese were included as factors directly affecting fetal growth or heavy metal toxicity. Maternal blood samples collected in the second or third trimester were used to measure heavy metal concentrations. The association between maternal blood metal concentrations and placenta weight was explored by applying Z scores and multivariable logistic regression analysis and classifying participants into quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: This study included a total of 73,005 singleton pregnant women who delivered via live births and met the inclusion criteria. The median heavy metal concentrations in the maternal whole blood were 0.662 ng/g cadmium, 5.85 ng/g lead, 3.61 ng/g mercury, 168 ng/g selenium, and 15.3 ng/g manganese. Regression analysis revealed a significant correlation between placenta weight Z scores and maternal blood metal concentrations: cadmium, 0.0660 (standard error = 0.0074, p < 0.001); selenium, -0.3137 (standard error = 0.0276, p < 0.001); and manganese, 0.1483 (standard error = 0.0110, p < 0.001). CONCLUSION: This study provides a robust examination of the association between heavy metal exposure and placenta weight. Cadmium and manganese showed a positive correlation with significant differences, whereas selenium showed a negative correlation. Essential elements notably affect placenta weight differently. No significant association was noted between lead or mercury and placenta weight.

Associations between heat wave during pregnancy and term birth weight outcomes: The PARIS birth cohort.

BACKGROUND: Climate change will make extreme weather events more frequent in the 21st century. Extreme ambient temperatures during the prenatal period have been associated with adverse pregnancy outcomes such as preterm birth. It is unclear, however, whether heat waves during pregnancy impact fetal growth in apparently healthy term newborns. OBJECTIVES: We aimed to investigate associations between heat wave during pregnancy and birth weight outcomes in term newborns from the PARIS birth cohort, and to explore meteorological conditions and air pollution as possible intermediate factors. METHODS: We examined data on 3,359 newborns born between 37 and 42 weeks in Paris, France, between 2003 and 2006. Associations of maternal exposure to heat wave (during whole pregnancy and each trimester) with birth weight and small for gestational age (SGA) at term were studied using linear and logistic regression models adjusted for potential confounders. Maternal characteristics were investigated as possible modifiers. We explored the mediating role of ambient temperature, relative humidity, and air pollution levels in the relationship between heat wave during the first trimester and term SGA. RESULTS: Mothers who were pregnant during the 2003 French heat wave (n = 506, 15 %) were more likely to have a term SGA baby (aOR = 2.70; 95 %CI: 1.38, 5.28) compared to mothers who did not experience heat wave during pregnancy. The association was stronger when heat wave occurred during the first trimester (aOR = 4.18; 95 %CI: 1.69, 10.35). Primiparous women were identified as more vulnerable than multiparous women. Average ambient temperature and air quality index explained about 36 % and 56 % of the association between heat wave during the first trimester and term SGA, respectively. CONCLUSIONS: This study suggests prenatal exposure to heat wave, especially during the first trimester, may adversely affect fetal growth of term newborns, which could be explained by both increasing ambient temperatures and worsening air quality.

Occurrence of rare earth elements in umbilical cord serum and association with thyroid hormones and birth outcomes in newborns.

Rare earth elements (REEs) are emerging contaminants that are increasingly used in high technology products. However, limited information is available regarding exposure to REEs and associated health effects in neonates. This study aimed to investigate the association between REE concentrations and thyroid hormone levels, as well as birth outcomes in 109 newborns in Beijing, China. We measured the concentrations of 16 REEs and thyroid hormones in umbilical cord serum. To assess the impact of exposure to individual REEs and REE mixtures on thyroid hormone levels and birth outcomes, we employed univariate linear regression, least absolute shrinkage and selection operator (LASSO), and weighted quantile sum (WQS) models. We detected 14 REEs at high rates (92.6%-100%), with yttrium exhibiting the highest median (interquartile range) concentration [43.94 (0.33-172.55) ng/mL], followed by scandium [3.64 (0.46-11.15) ng/mL]. Univariate analyses showed that per logarithmic (ln)-unit change of neodymium (Nd) and samarium (Sm) was associated with 0.039 [95% confidence interval (CI): 0.001, 0.007] and 0.031 (95% CI: 0.003, 0.060) increases in free thyroxine (FT4) levels, respectively. Moreover, 14 REEs exhibited significant associations with triiodothyronine (T3) levels, resulting in increases ranging from 0.066 to 0.307. Elevated concentrations of terbium (Tb) [per ln-unit change: -0.021 (95% CI: -0.041, -0.01)] and lutetium (Lu) [-0.023 (95% CI: -0.043, -0.002)] were inversely correlated with birth length in newborns. A further multiple exposure analysis employing the LASSO model identified Sm, Nd, Y, Sc, and Lu as critical factors influencing FT4 and T3 levels. Additionally, WQS analyses showed positive associations between exposure to a mixture of 14 REEs and FT4 (P = 0.046), T3 (P < 0.001), and birth length (P = 0.049). These findings suggest that in utero exposure to REEs might disrupt thyroid hormone homeostasis and impact intrauterine growth. Further studies are warranted to validate these findings and elucidate the underlying mechanisms.

Maternal concentrations of environmental phenols during early pregnancy and behavioral problems in children aged 4 years from the Shanghai Birth Cohort.

BACKGROUND: Prenatal exposure to environmental phenols such as bisphenol (BPs), paraben (PBs), benzophenone (BzPs), and triclosan (TCS) is ubiquitous and occurs in mixtures. Although some of them have been suspected to impact child behavioral development, evidence is still insufficient, and their mixed effects remain unclear. OBJECTIVES: To explore the association of prenatal exposure to multiple phenols with child behavioral problems. METHOD: In a sample of 600 mother-child pairs from the Shanghai Birth Cohort, we quantified 18 phenols (6 PBs, 7 BPs, 4 BzPs, and TCS) in urine samples collected during early pregnancy. Parent-reported Strengths and Difficulties Questionnaires were utilized to evaluate child behavioral difficulties across four subscales, namely conduct, hyperactivity/inattention, emotion, and peer relationship problems, at 4 years of age. Multivariable linear regression was conducted to estimate the relationships between single phenolic compounds and behavioral problems. Additionally, weighted quantile sum (WQS) regression was employed to examine the overall effects of the phenol mixture. Sex-stratified analyses were also performed. RESULTS: Our population was extensively exposed to 10 phenols (direction rates >50 %), with low median concentrations (1.00 × 10-3-6.89 ng/mL). Among them, single chemical analyses revealed that 2,4-dihydroxy benzophenone (BP1), TCS, and methyl 4-hydroxybenzoate (MeP) were associated with increased behavior problems, including hyperactivity/inattention (BP1: ß = 0.16; 95 % confidence interval [CI]: 0.04, 0.30), emotional problems (BP1: ß = 0.11; 95 % CI: 0.02, 0.20; TCS: ß = 0.08; 95 % CI: 0.02, 0.14), and peer problems (MeP: ß = 0.10; 95 % CI: 0.02, 0.18); however, we did not identify any significant association with conduct problems. Further phenol mixture analyses in the WQS model yielded similar results. Stratification for child sex showed stronger positive associations in boys. CONCLUSION: Our findings indicated that maternal phenol levels during early pregnancy, specifically BP1, TCS, and MeP, are associated with high behavioral problem scores in 4-year-old children.

Association of diet with per- and polyfluoroalkyl substances in plasma and human milk in the New Hampshire Birth Cohort Study.

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ∼28 gestational weeks and human milk collected at ∼6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ∼28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: -0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring.

Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California.

BACKGROUND: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. METHODS: The present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. RESULTS: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). CONCLUSIONS: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Meta-analysis of fine particulate matter exposure during pregnancy and birth weight: Exploring sources of heterogeneity.

BACKGROUND: Several meta-analyses assessed the relationship between exposure to PM with aerodynamic diameter ≤ 2.5 µm (PM2.5) during pregnancy and birth weight (BW), but results were inconsistent and substantial unexplained heterogeneity was reported. We aimed to investigate the above association and to explore sources of heterogeneity across studies. METHODS: We systematically reviewed the current worldwide evidence examining the association between PM2.5 and BW. The review protocol was registered on the PROSPERO website (CRD42020188996) and followed PRISMA guidelines. We extracted association measures for BW and low birth weight (LBW, BW < 2500 g) from each study to evaluate pooled summary measures and to explore sources of between-study heterogeneity. FINDINGS: Of the 2677 articles identified, 84 met the inclusion criteria (~42 M births). Our random effects meta-analyses revealed substantial heterogeneity among included studies (I2 = 98.4 % and I2 = 77.7 %, for BW and LBW respectively). For LBW, the heterogeneity decreased (I2 = 59.7 %) after excluding four outlying studies, with a pooled odds ratio 1.07 (95 % confidence interval, CI: 1.05, 1.09) per a 10-µg/m3 increase in mean PM2.5 exposure over the entire pregnancy. Further subgroup analysis revealed geographic heterogeneity with higher association in Europe (1.34, (1.16, 1.55)) compared to Asia (1.06, (1.03, 1.10)) and US (1.07, (1.04, 1.10)). CONCLUSION: The association between PM2.5 and birth weight varied depending on several factors. The sources of heterogeneity between studies included modifiers such as study region and period. Hence, it is advisable not to pool summary measures of PM2.5-BW associations and that policy would be informed by local evidence.

Associations among neighborhood walkability, metal exposure, and sex steroid hormone levels: Results from Hangzhou Birth Cohort Study â ¡.

BACKGROUND: Neighborhood walkability may influence maternal-fetal exposure to environmental hazards and maternal-fetal health (e.g., fetal growth restriction, reproductive toxicity). However, few studies have explored the association between neighborhood walkability and hormones in pregnant women. METHODS: We included 533 pregnant women from the Hangzhou Birth Cohort Study II (HBCS-II) with testosterone (TTE) and estradiol (E2) measured for analysis. Neighborhood walkability was evaluated by calculating a walkability index based on geo-coded addresses. Placental metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). TTE and E2 levels in umbilical cord blood were measured using chemiluminescence microparticle immunoassay (CMIA). Linear regression model was used to estimate the relationship between the walkability index, placental metals, and sex steroid hormones. Effect modification was also assessed to estimate the effect of placental metals on the associations of neighborhood walkability with TTE and E2. RESULTS: Neighborhood walkability was significantly linked to increased E2 levels (P trend=0.023). Compared with participants at the first quintile (Q1) of walkability index, those at the third quintiles (Q3) had lower chromium (Cr) levels (ß = -0.212, 95% CI = -0.421 to -0.003). Arsenic (As), cobalt (Co), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and vanadium (V) were linked to decreased TTE levels, and cadmium (Cd) was linked to increased TTE levels. No metal was significantly associated with E2 levels in trend analysis. In the analysis of effect modification, the associations of neighborhood walkability with TTE and E2 were significantly modified by Mn (P = 0.005) and Cu (P = 0.049) respectively. CONCLUSION: Neighborhood walkability could be a favorable factor for E2 production during pregnancy, which may be inhibited by maternal exposure to heavy metals.