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Background: Studies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters. Objective: We identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort. Methods: This population-based retrospective cohort study included 294,937 mother–child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)], nitrogen dioxide (NO2), and ozone (O3) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season. Results: There were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive PM2.5 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1–27 wk of gestation, cumulative hazard ratio (HR)=1.14 [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) (7.4-μg/m3) increase]. O3 exposure during 34–37 wk of gestation was associated with increased risk [HR=1.06 (95% CI: 1.01, 1.11) per IQR (17.4 ppb) increase] but with reduced risk during 20–28 wk of gestation [HR=0.93 (95% CI: 0.89, 0.98)]. No associations were observed with NO2. Sex-stratified early gestational PM2.5 associations were stronger among boys [boys HR=1.16 (95% CI: 1.08, 1.26); girls HR=1.06 (95% CI: 0.89, 1.26)]. O3 associations in later gestation were observed only in boys [boys HR=1.10 (95% CI: 1.04, 1.16); girls HR=0.94 (95% CI: 0.84, 1.05)]. Conclusions: Exposures to PM2.5 in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of O3 exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509

Background: Prenatal exposure to perfluoroalkyl substances (PFAS) has been previously associated with preeclampsia, although findings are mixed with respect to the direction and magnitude of effect. To our knowledge, no studies have examined associations between PFAS and preeclampsia subtypes, which may have distinct etiologies. Objective: We examined associations between PFAS, any preeclampsia diagnosis, and early- and late-onset preeclampsia. In addition, we estimated associations between PFAS and the angiogenic biomarkers soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF), which provide an estimate of pro- and anti-angiogenic activity within the placenta. Methods: This case–control study (n=75 cases, n=75 controls) was sampled from the LIFECODES birth cohort. Nine legacy PFAS were quantified in maternal plasma from early pregnancy (median= 10 wk) and angiogenic biomarkers were quantified in maternal plasma from four study visits (median= 10, 18, 26, and 35 wk). Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the association between an interquartile range (IQR)-increase in PFAS and preeclampsia outcomes. Linear regression was used to estimate associations between an IQR-increase in PFAS and concentrations of angiogenic biomarkers. Results: Both perfluorodecanoic acid (OR= 1.64, 95% CI: 1.08, 2.47) and perfluorooctanesulfonic acid (OR= 1.60, 95% CI: 1.06, 2.43) were associated with higher odds of late-onset preeclampsia. Associations tended to be below the null for early-onset preeclampsia, although findings were imprecise. Few associations were noted between PFAS and angiogenic biomarkers. Discussion: Maternal PFAS concentrations were associated with higher odds of late-onset preeclampsia. Heterogeneity of preeclampsia should be considered in future studies because populations may have different distributions of disease subtypes. https://doi.org/10.1289/EHP9091

BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood. OBJECTIVES: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case-control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico. METHODS: GLY and AMPA in urine samples collected at 18±2 (Visit 1) and 26±2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery

BACKGROUND: High levels of nitrate ( NO 3 - ) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent.OBJECTIVES: We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term ( ≥ 37 wk gestation) live-born singletons.METHODS: We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991-2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable.RESULTS: There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of - 9.71 g (95% confidence interval: - 14.60 , - 4.81 ) was predicted at 25 mg / L (half the value of the European Union drinking water standard) compared with 0 mg / L NO 3 - . Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO 3 - and head circumference or LBW.DISCUSSION: Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings. https://doi.org/10.1289/EHP7331.

Background: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. Objectives: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. Methods: Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR)

Background: Environmental factors may contribute to the development of Kawasaki disease in children, but prenatal environmental exposures are understudied. Objective: We used a population-based cohort to investigate whether prenatal exposure to outdoor air pollution is associated with the incidence of Kawasaki disease in childhood. Methods: We performed a longitudinal cohort study of all children born in Quebec, Canada, between 2006 and 2012. Children were followed for Kawasaki disease from birth until 31 March 2018. We assigned prenatal air pollutant exposure according to the residential postal code at birth. The main exposure was annual average concentration of ambient fine particulate matter [PM ≤2.5μm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2) from satellite-based estimates and land-use regression models. As secondary exposures, we considered industrial PM2.5, NO2, and sulfur dioxide (SO2) emissions estimated from dispersion models. We estimated hazard ratios (HRs) using Cox proportional hazards models, adjusted for maternal age, parity, sex, multiple birth, maternal smoking during pregnancy, socioeconomic status, birth year, and rural residence. We considered single and multipollutant models. We performed several sensitivity analyses, including assessing modifying effects of maternal comorbidities (e.g., diabetes, preeclampsia). Results: The cohort comprised 505,336 children, including 539 with Kawasaki disease. HRs for each interquartile range increase in ambient air pollution were 1.16 (95% CI: 0.96, 1.39) for PM2.5 and 1.12 (95% CI: 0.96, 1.31) for NO2. For industrial air pollution, HRs were 1.07 (95% CI: 1.01, 1.13) for SO2, 1.09 (95% CI: 0.99, 1.20) for NO2, and 1.01 (95% CI: 0.97, 1.05) for PM2.5. In multipollutant models, associations for ambient PM2.5 and NO2 (i.e., from all sources) were robust to adjustment for industrial pollution, and vice versa. Discussion: In this population-based cohort study, both prenatal exposure to ambient and industrial air pollution were associated with the incidence of Kawasaki disease in childhood. Further studies are needed to consolidate the observed associations. https://doi.org/10.1289/EHP6920

Background: Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity. Objective: We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood. Methods: We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex. Results: Median (25–75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1–7.7), 24.8 (18.4–33.9), 2.4 (1.6–3.8), and 0.6 (0.5–0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m 2 (95% CI: –0.05, 0.48) higher body mass index, 0.76 mm (95% CI: –0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m 2 (95% CI: –0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures. Conclusions: In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Antecedentes: pocos estudios han examinado si la exposición prenatal a sustancias perfluoroalquilo (PFAS) está asociada con la adiposidad infantil. Objetivo: Examinamos las asociaciones de la exposición prenatal a los PFAS con la adiposidad en la niñez temprana y media. Métodos: medimos las concentraciones plasmáticas de PFAS en 1.645 mujeres embarazadas (mediana, 9,6 semanas de gestación) inscritas en Project Viva, un estudio prospectivo de cohortes prenatal en Massachusetts (EE. UU.), Entre 1999 y 2002. Evaluamos la adiposidad general y central en 1.006 niños en la primera infancia (mediana, 3,2 años) y 876 en la infancia media (mediana, 7,7 años) mediante mediciones antropométricas y de absorciometría de rayos X duales (DXA). Ajustamos modelos de regresión lineal multivariable para estimar las asociaciones exposición-resultado y evaluamos la modificación del efecto por sexo del niño. Resultados: La mediana (percentiles 25-75) de perfluorooctanoato plasmático prenatal (PFOA), sulfonato de perfluorooctano (PFOS), sulfonato de perfluorohexano (PFHxS) y perfluorononanoato (PFNA) en niños evaluados en la primera infancia fue de 5,6 (4,1-7,7), 24,8 ( 18,4 a 33,9), 2,4 (1,6 a 3,8) y 0,6 (0,5 a 0,9) ng / ml, respectivamente. Entre las niñas, cada incremento del rango intercuartílico de las concentraciones prenatales de PFOA se asoció con 0,21 kg / m 2 (IC del 95%: –0,05, 0,48) mayor índice de masa corporal, 0,76 mm (IC del 95%: –0,17, 1,70) mayor suma de subescapular y espesor del pliegue cutáneo del tríceps, y 0,17 kg / m 2 (IC del 95%: –0,02, 0,36) índice de masa grasa total DXA más alto en la infancia media. Se observaron asociaciones similares para PFOS, PFHxS y PFNA. Observamos asociaciones nulas para los niños y las medidas de adiposidad en la primera infancia. Conclusiones: En esta cohorte, la exposición prenatal a los PFAS se asoció con pequeños aumentos en las mediciones de adiposidad en la infancia media, pero solo entre las niñas. Antecedentes: Poucos estudos examinaram se a exposição pré-natal a substâncias perfluoroalquil (PFASs) está associada à adiposidade infantil. Objetivo: Nós examinamos associações de exposição pré-natal a PFASs com adiposidade na primeira e na metade da infância. Métodos: Medimos as concentrações plasmáticas de PFAS em 1.645 mulheres grávidas (mediana, 9,6 semanas de gestação) inscritas no Projeto Viva, um estudo de coorte prospectivo pré-nascimento em Massachusetts (EUA), entre 1999 e 2002. Avaliamos a adiposidade geral e central em 1.006 crianças na primeira infância (mediana, 3,2 anos) e 876 na meia-infância (mediana, 7,7 anos) usando medidas antropométricas e absortometria de raio-X duplo (DXA). Ajustamos modelos de regressão linear multivariável para estimar as associações de exposição-desfecho e avaliamos a modificação do efeito por sexo da criança. Resultados: As concentrações de perfluorooctanoato plasmático pré-natal (PFOA), perfluorooctano sulfonato (PFOS), perfluorohexano sulfonato (PFHxS) e perfluorononanoato (PFNA) em crianças avaliadas na primeira infância foram 5,6 (4,1-7,7), 24,8 ( 18,4–33,9), 2,4 (1,6–3,8) e 0,6 (0,5–0,9) ng / mL, respectivamente. Entre as meninas, cada incremento do intervalo interquartil das concentrações pré-natais de PFOA foi associado a 0,21 kg / m 2 (IC 95%: -0,05, 0,48) índice de massa corporal mais alto, 0,76 mm (IC 95%: -0,17, 1,70) maior soma do subescapular e espessura da dobra cutânea tricipital, e 0,17 kg / m 2 (IC 95%: –0,02, 0,36) índice de massa gorda total DXA mais alto no meio da infância. Associações semelhantes foram observadas para PFOS, PFHxS e PFNA. Observamos associações nulas para meninos e medidas de adiposidade na primeira infância. Conclusões: Nesta coorte, a exposição pré-natal a PFASs foi associada a pequenos aumentos nas medidas de adiposidade no meio da infância, mas apenas entre as meninas. Boston University School of Public Health, United States Universidad Nacional, Costa Rica Harvard Medical School and Harvard Pilgrim Health Care Institute, United States Harvard T.H. Chan School of Public Health, United States National Center for Environmental Health, United States University of California, United States Instituto Regional de Estudios en Sustancias Tóxicas

Background: The autonomic nervous system plays a key role in maintaining homeostasis and responding to external stimuli. In adults, exposure to fine particulate matter (PM2.5) has been associated w...

IRET Background: Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence. Objective: We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. Methods: We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort (n = 334). We used age-specific linear regression models and generalized estimating equation mpdels to assess longitudinal effects and examined differences by sex. Results: Phthalate metabolites were detected in 88%-100% of samples, depending on the metabolite. Associations of phthalates with neurodevelop- mental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates (ΣLMW) were associated with more self-reported hyperactivity [ß = 0.8, 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in ΣLMW phtha- lates], attention problems (ß= 1.5, 95% CI: 0.7, 2.2), and anxiety (ß = 0.9, 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., ß for Full-Scale IQ for boys= —1.9, 95% CI: —4.1, 0.3 and -1.7,95% CI: -3.8, 0.3, respectively; ß for girls = 1.8, 95% CI: 0.1,3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; p-int= 0.01 for both). Conclusion: We found predominantly null associations of prenatal phthalates with neurodevelopment in CHAMACOS, and weak associations of SLMW phthalates with internalizing and externalizing behaviors in adolescence. No previous studies have examined associations of prenatal phthal- ate exposure with neurodevelopment into adolescence, an important time for manifestations of effects. © 2019, Public Health Services, US Dept of Health and Human Services. All rights reserved. Estudios previos sugieren que la exposición prenatal a ftalatos, sustancias químicas sintéticas ubicuas, puede afectar negativamente el desarrollo neurológico. Sin embargo, los datos sobre cómo los ftalatos afectan la cognición, la función ejecutiva y la función conductual en la adolescencia son limitados. Objetivo: Nuestro objetivo fue investigar las asociaciones de la exposición prenatal a ftalatos con el neurodesarrollo en la niñez y la adolescencia en el estudio del Centro de Evaluación de la Salud de Madres e Hijos de Salinas (CHAMACOS). Métodos: Examinamos las asociaciones entre las concentraciones de metabolitos de ftalato urinario materno medidas dos veces durante el embarazo y una variedad de resultados del desarrollo neurológico desde los 7 hasta los 16 años en la cohorte de nacimiento CHAMACOS (n = 334). Usamos modelos de regresión lineal específicos por edad y modelos de ecuaciones de estimación generalizadas para evaluar los efectos longitudinales y examinamos las diferencias por sexo. Resultados: Se detectaron metabolitos de ftalato en 88% -100% de las muestras, dependiendo del metabolito. Las asociaciones de ftalatos con resultados del neurodesarrollo fueron en gran parte nulas con algunos patrones notables. Las concentraciones prenatales más altas de metabolitos de ftalatos de bajo peso molecular (ΣLMW) se asociaron con más hiperactividad autoinformada [ß = 0,8, intervalo de confianza (IC) del 95%: 0,1, 1,4 por aumento de 2 veces en ΣLMW ftalatos], problemas de atención (ß = 1,5, IC del 95%: 0,7, 2,2) y ansiedad (ß = 0,9, IC del 95%: 0,0, 1,8) a los 16 años. Observamos diferencias específicas por sexo para las sumas de peso molecular alto y di (2-etilhexil) metabolitos y resultados cognitivos (p. ej., ß para el coeficiente intelectual de escala completa para niños = —1,9; IC del 95%: —4,1, 0,3 y -1,7; IC del 95%: -3,8, 0,3, respectivamente; ß para niñas = 1.8, IC del 95%: 0.1,3.4 y 1.6, IC del 95%: 0.0, 3.2, respectivamente; p-int = 0.01 para ambos). Conclusión: Encontramos asociaciones predominantemente nulas de ftalatos prenatales con neurodesarrollo en CHAMACOS, y asociaciones débiles de ftalatos SLMW con conductas internalizantes y externalizantes en la adolescencia. Ningún estudio previo ha examinado las asociaciones de la exposición prenatal a los ftalatos con el desarrollo neurológico en la adolescencia, un momento importante para las manifestaciones de los efectos. © 2019, Servicios de salud pública, Departamento de Salud y Servicios Humanos de EE. UU. Reservados todos los derechos. University of California at Berkeley, USA Universidad Nacional, Costa Rica Centers for Disease Control and Prevention, USA Instituto Regional de Estudios en Sustancias Tóxicas

Background: Telomere length (TL) is a marker of biological aging and is inversely related to aging-related diseases. The setting of TL at birth may have important implications for lifelong telomere dynamics; however, its determinants remain poorly understood. Objectives: The purpose of our study was to explore the relationships between prenatal exposure to phthalates and umbilical cord blood TL. Methods: A total of 762 mother–newborn pairs were recruited from a birth cohort study performed between November 2013 and March 2015 in Wuhan, China. Relative cord blood TL was measured using quantitative real-time polymerase chain reaction. Six phthalate metabolites were measured in urine samples acquired from pregnant women during the three trimesters. Multiple informant models were applied to estimate the associations between prenatal exposure to phthalates and cord blood TL and to evaluate potential windows of vulnerability. Results: Exposure to mono-ethyl phthalate (MEP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-butyl phthalate (MBP), and di(2-ethylhexyl) phthalate (ΣDEHP) during the first trimester were inversely related to cord blood TL. In addition, we observed a female-specific association between maternal exposure to MEP during the first trimester and cord blood TL (psex‐int=0.03). The associations between maternal exposure to MECPP, MEHHP, MEOHP, and ΣDEHP during the first trimester and cord blood TL were consistent between males and females (all psex‐int>0.10). Conclusion: This prospective study demonstrated that prenatal exposure to some phthalate metabolites were associated with shorter cord blood TL. Our results, if confirmed in other populations, may provide more evidence of adverse health outcomes of phthalate exposure and support the hypothesis that the intrauterine environment may be one of the major determinants for newborn TL. https://doi.org/10.1289/EHP4492

Background: Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans. Objectives: We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones. Methods: We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother–infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way. Results: We found a dose–response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were –23.98-ng/mL (95% CI: –0.47.12, –11.99; p for trend = 0.006) and –63.21-ng/mL (95% CI: –132.56, –26.72; p for trend < 0.001) lower, respectively, in infants with prenatal PFOS exposure in the fourth quartile compared with those in the first quartile. The highest quartile of prenatal PFOS exposure was positively associated with a 1.33-ng/mL higher DHEA level compared with the lowest quartile (95% CI: 0.17, 1.82; p for trend = 0.017), whereas PFOA showed a negative association with DHEA levels (quartile 4 vs. quartile 1: –1.23 ng/mL, 95% CI: –1.72, –0.25; p for trend = 0.004). We observed no significant association between PFCs and androstenedione levels. Conclusions: Our results indicate that prenatal exposure to PFCs is significantly associated with glucocorticoid and DHEA levels in cord blood. Citation: Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, Nakazawa H, Nonomura K, Kishi R. 2017. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido Study. Environ Health Perspect 125:111–118; http://dx.doi.org/10.1289/EHP142

Background: Perfluorocarboxylic acids (PFCAs) are environmentally and biologically persistent synthetic chemicals. PFCAs include perfluorooctanoic acid (PFOA; C8) and long-chain PFCAs (C9–C20). Studies examining long-chain PFCAs and fetal and postnatal growth are limited. Objectives: We investigated the associations of prenatal exposure to long-chain PFCAs with fetal and postnatal growth. Methods: For 223 Taiwanese mothers and their term infants, we measured PFOA and four long-chain PFCAs (ng/mL) in third-trimester maternal serum; infant weight (kg), length and head circumference (cm) at birth; and childhood weight and height at approximately 2, 5, 8, and 11 years of age. For each sex, we used multivariable linear regression to examine associations between ln-transformed prenatal PFCAs and continuous infant measures, and logistic regression to examine small for gestational age (SGA). Linear mixed models were applied to prenatal PFCAs and childhood weight and height z-scores. Results: In girls, prenatal perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) concentrations were inversely associated with birth weight [e.g., βbirth weight (kg) = –0.06, 95% CI: –0.11, –0.01 per 1 ln-unit PFUnDA increase]; prenatal PFDeA and PFUnDA were associated with elevated odds of SGA; and PFDeA, PFUnDA, and PFDoDA were associated with lower average childhood height z-score. In boys, prenatal PFNA, and PFDoDA were associated with reductions in height at certain ages in childhood, but not with size at birth. Conclusions: Prenatal exposure to long-chain PFCAs may interfere with fetal and childhood growth in girls, and childhood growth in boys. Citation: Wang Y, Adgent M, Su PH, Chen HY, Chen PC, Hsiung CA, Wang SL. 2016. Prenatal exposure to perfluorocarboxylic acids (PFCAs) and fetal and postnatal growth in the Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 124:1794–1800; http://dx.doi.org/10.1289/ehp.1509998

Background: Prenatal exposure to organophosphorous (OP) pesticides has been found to be associated with adverse effects on child neurodevelopment, but evidence on potential effects induced by both prenatal and postnatal OP exposure in infants is limited. Objectives: Our aim was to investigate the associations of both prenatal and postnatal OP exposure with birth outcomes and infant neurodevelopment. Methods: Exposure to OP in 310 mother–infant pairs was assessed by measuring dimethylphosphate (DM), diethylphosphate (DE), and total dialkylphosphate (DAP) metabolites in urines from pregnant women and their children at 2 years of age. The Gesell Developmental Schedules was administered to examine neurodevelopment of 2-year-old children. Results: Based on the Gesell Developmental Schedules, the proportions of children with developmental delays were < 6%. Adverse associations between head circumference at birth and prenatal OP exposure were demonstrated. Both prenatal and postnatal OP exposure was significantly associated with increased risk of being developmentally delayed. Specifically, odds ratio (OR) value for prenatal DEs was 9.75 (95% CI: 1.28, 73.98, p = 0.028) in the adaptive area, whereas in the social area, OR values for postnatal DEs and DAPs were 9.56 (95% CI: 1.59, 57.57, p = 0.014) and 12.00 (95% CI: 1.23, 117.37, p = 0.033), respectively. Adverse associations were observed only in boys, not in girls. Conclusions: Both prenatal and postnatal OP exposure may adversely affect the neurodevelopment of infants living in the agricultural area. The present study adds to the accumulating evidence on associations of prenatal and postnatal OP exposure with infant neurodevelopment. Citation: Liu P, Wu C, Chang X, Qi X, Zheng M, Zhou Z. 2016. Adverse associations of both prenatal and postnatal exposure to organophosphorous pesticides with infant neurodevelopment in an agricultural area of Jiangsu Province, China. Environ Health Perspect 124:1637–1643; http://dx.doi.org/10.1289/EHP196

Background: Prenatal exposure to ambient PM2.5, (i.e., fine particulate matter, aerodynamic diameter ≤ 2.5 μm) has been associated with preterm birth and low birth weight. The association between prenatal PM2.5 exposure and intrauterine inflammation (IUI), an important risk factor for preterm birth and neurodevelopmental outcomes, has not been evaluated. Objectives: We aimed to investigate the association between maternal exposure to PM2.5 and IUI in the Boston Birth Cohort, a predominantly urban low-income minority population. Methods: This analysis included 5,059 mother–infant pairs in the Boston Birth Cohort. IUI was assessed based on intrapartum fever and placenta pathology. PM2.5 exposure was assigned using data from the U.S. EPA’s Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) quantified the association of maternal PM2.5 exposure during preconception and various periods of pregnancy with IUI. Results: Comparing the highest with the lowest PM2.5 exposure quartiles, the multi-adjusted association with IUI was significant for all exposure periods considered, including 3 months before conception (OR = 1.52; 95% CI: 1.22, 1.89), first trimester (OR = 1.93; 95% CI: 1.55, 2.40), second trimester (OR = 1.67; 95% CI: 1.35, 2.08), third trimester (OR = 1.53; 95% CI: 1.24, 1.90), and whole pregnancy (OR = 1.92; 95% CI: 1.55, 2.37). Conclusions: Despite relatively low exposures, our results suggest a monotonic positive relationship between PM2.5 exposure during preconception and pregnancy and IUI. IUI may be a sensitive biomarker for assessing early biological effect of PM2.5 exposure on the developing fetus. Citation: Nachman RM, Mao G, Zhang X, Hong X, Chen Z, Soria CS, He H, Wang G, Caruso D, Pearson C, Biswal S, Zuckerman B, Wills-Karp M, Wang X. 2016. Intrauterine inflammation and maternal exposure to ambient PM2.5 during preconception and specific periods of pregnancy: the Boston Birth Cohort. Environ Health Perspect 124:1608–1615; http://dx.doi.org/10.1289/EHP243

Background: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties, and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD)—the distance from the anus to the genitals in male offspring. Few human studies have been conducted, but associations between the anti-androgenic phthalates and male AGD have been reported. Objective: We aimed to study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010–2012 and AGD in their male infants at 3 months of age (n = 273). Methods: In the Odense child cohort study, urinary concentrations of 12 phthalate metabolites of diethyl, di-n-butyl, diisobutyl, di(2-ethylhexyl), butylbenzyl, and diisononyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP, and DiNP, respectively) were measured among 245 mothers of boys at approximately gestational week 28 (range, 20.4–30.4) and adjusted for osmolality. AGD, penile width, and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. Results: Phthalate levels were lower in this population than in a recent Swedish study in which phthalates were measured in the first trimester. No consistent associations were seen between any prenatal phthalate and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose–response patterns, and associations were not statistically significant (p > 0.05). Conclusion: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population. Citation: Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM. 2016. Prenatal exposure to phthalates and anogenital distance in male infants from a low-exposed Danish cohort (2010–2012). Environ Health Perspect 124:1107–1113; http://dx.doi.org/10.1289/ehp.1509870

Background: Prenatal exposures to endocrine-disrupting chemicals (EDCs) during critical developmental windows have been implicated in the etiologies of a wide array of adverse perinatal and pediatric outcomes. Epidemiological studies have concentrated on the health effects of individual chemicals, despite the understanding that EDCs act together via common mechanisms, that pregnant women are exposed to multiple EDCs simultaneously, and that substantial toxicological evidence of adverse developmental effects has been documented. There is a move toward multipollutant models in environmental epidemiology; however, there is no current consensus on appropriate statistical methods. Objectives: We aimed to review the statistical methods used in these studies, to identify additional applicable methods, and to determine the strengths and weaknesses of each method for addressing the salient statistical and epidemiological challenges. Methods: We searched Embase, MEDLINE, and Web of Science for epidemiological studies of endocrine-sensitive outcomes in the children of mothers exposed to EDC mixtures during pregnancy and identified alternative statistical methods from the wider literature. Discussion: We identified 74 studies and analyzed the methods used to estimate mixture health effects, identify important mixture components, account for nonmonotonicity in exposure–response relationships, assess interactions, and identify windows of exposure susceptibility. We identified both frequentist and Bayesian methods that are robust to multicollinearity, performing shrinkage, variable selection, dimension reduction, statistical learning, or smoothing, including methods that were not used by the studies included in our review. Conclusions: Compelling motivation exists for analyzing EDCs as mixtures, yet many studies make simplifying assumptions about EDC additivity, relative potency, and linearity, or overlook the potential for bias due to asymmetries in chemical persistence. We discuss the potential impacts of these choices and suggest alternative methods to improve analyses of prenatal exposure to EDC mixtures. https://doi.org/10.1289/EHP2207

Background: Continued efforts to phase out bisphenol A (BPA) from consumer products have been met with the challenges of finding safer alternatives. Objectives: This study aimed to determine whether early-life exposure to BPA and its related analogues, bisphenol AF (BPAF) and bisphenol S (BPS), could affect female pubertal mammary gland development and long-term mammary health in mice. Methods: Timed pregnant CD-1 mice were exposed to vehicle, BPA (0.5, 5, 50mg/kg), BPAF (0.05, 0.5, 5mg/kg), or BPS (0.05, 0.5, 5mg/kg) via oral gavage between gestation days 10–17. Mammary glands were collected from resulting female offspring at postnatal day (PND) 20, 28, 35, and 56, and at 3, 8, and 14 months for whole mount, histopathological evaluation, and quantitative real-time polymerase chain reaction (qPCR); serum steroid concentrations were also measured at these time points. Results: In the bisphenol-exposed mice, accelerated mammary gland development was evident during early puberty and persisted into adulthood. By late adulthood, mammary glands from bisphenol-exposed female offspring exhibited adverse morphology in comparison with controls; most prominent were undifferentiated duct ends, significantly more lobuloalveolar hyperplasia and perivascular inflammation, and various tumors, including adenocarcinomas. Effects were especially prominent in the BPAF 5mg/kg and BPS 0.5mg/kg groups. Serum steroid concentrations and mammary mRNA levels of Esr1, Pgr, Ar, and Gper1 were similar to controls. Conclusions: These data demonstrate that prenatal exposure of mice to BPAF or BPS induced precocious development of the mammary gland, and that siblings were significantly more susceptible to spontaneous preneoplastic epithelial lesions and inflammation, with an incidence greater than that observed in vehicle- and BPA-exposed animals. https://doi.org/10.1289/EHP3189

BackgroundAlthough indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) and pyrethroids effectively controls malaria, it potentially increases human exposure to these insecticides. Previous studies suggest that prenatal exposure to these insecticides may impact human neurodevelopment.ObjectivesWe aimed to estimate the effects of maternal insecticide exposure and neurodevelopment of toddlers living in a malaria-endemic region currently using IRS.MethodsThe Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort of 752 mother-child pairs in Limpopo, South Africa. We measured maternal exposure to DDT and its breakdown product, dichlorodiphenyldichloroethylene (DDE), in maternal serum, and measured pyrethroid metabolites in maternal urine. We assessed children's neurodevelopment at 1 and 2 y of age using the Bayley Scales of Infant Development, third edition (BSID-III), and examined associations with maternal exposure.ResultsDDT and DDE were not associated with significantly lower scores for any BSID-III scale. In contrast, each 10-fold increase in cis-DCCA, trans-DCCA, and 3-phenoxybenzoic acid were associated, respectively, with a -0.63 (95% CI: -1.14, -0.12), -0.48 (95% CI: -0.92, -0.05), and -0.58 (-1.11, -0.06) decrement in Social-Emotional scores at 1 y of age. In addition, each 10-fold increase in maternal cis-DBCA levels was associated with significant decrements at 2 y of age in Language Composite scores and Expressive Communication scores [β=-1.74 (95% CI: -3.34, -0.13) and β=-0.40 (95% CI: -0.77, -0.04), respectively, for a 10-fold increase]. Significant differences by sex were estimated for pyrethroid metabolites and motor function scores at 2 y of age, with higher scores for boys and lower scores for girls.ConclusionsPrenatal exposure to pyrethroids may be associated at 1 y of age with poorer social-emotional development. At 2 y of age, poorer language development was observed with higher prenatal pyrethroid levels. Considering the widespread use of pyrethroids, these findings deserve further investigation. https://doi.org/10.1289/EHP2129.

Background Fatty acids (FAs) are essential for fetal growth. Exposure to perfluorinated chemicals (PFCs) may disrupt FA homeostasis, but there are no epidemiological data regarding associations of PFCs and FA concentrations. Objectives We estimated associations between perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) concentrations and maternal levels of FAs and triglyceride (TG) and birth size of the offspring. Methods We analyzed 306 mother–child pairs in this birth cohort between 2002 and 2005 in Japan. The prenatal PFOS and PFOA levels were measured in maternal serum samples by liquid chromatography–tandem mass spectrometry. Maternal blood levels of nine FAs and TG were measured by gas chromatography–mass spectrometry and TG E-Test Wako kits, respectively. Information on infants’ birth size was obtained from participant medical records. Results The median PFOS and PFOA levels were 5.6 and 1.4 ng/mL, respectively. In the fully adjusted model, including maternal age, parity, annual household income, blood sampling period, alcohol consumption, and smoking during pregnancy, PFOS but not PFOA had a negative association with the levels of palmitic, palmitoleic, oleic, linoleic, α-linolenic, and arachidonic acids (p < 0.005) and TG (p-value = 0.016). Female infants weighed 186.6 g less with mothers whose PFOS levels were in the fourth quartile compared with the first quartile (95% CI: –363.4, –9.8). We observed no significant association between maternal levels of PFOS and birth weight of male infants. Conclusions Our data suggest an inverse association between PFOS exposure and polyunsaturated FA levels in pregnant women. We also found a negative association between maternal PFOS levels and female birth weight. Citation Kishi R, Nakajima T, Goudarzi H, Kobayashi S, Sasaki S, Okada E, Miyashita C, Itoh S, Araki A, Ikeno T, Iwasaki Y, Nakazawa H. 2015. The association of prenatal exposure to perfluorinated chemicals with maternal essential and long-chain polyunsaturated fatty acids during pregnancy and the birth weight of their offspring: the Hokkaido Study. Environ Health Perspect 123:1038–1045; http://dx.doi.org/10.1289/ehp.1408834

In a recently published paper using space-time satellite data to determine air temperature (Ta), Kloog et al. concluded that Ta during pregnancy was associated with lower birth weight and shorter gestational age in the study population. The results obtained pointed to associations between Ta and birth weight during the last trimester, and between Ta and preterm delivery and low birth weight during the entire pregnancy. These results agree with those obtained by Dadvand et al. (2014), indicating Ta has a stressful role influencing low birth weight. There are many epidemiological studies reporting a nonlinear J- or U-shaped relationship between Ta and health indicators such as mortality (Basu and Samet 2002) and morbidity (Ye et al. 2012), with different response times for heat and cold waves (Gasparrini et al. 2015). When Kloog et al. performed linear and logistic models, Ta was introduced with a linear component in multiple time windows before birth. Models also were adjusted for different environmental and sociodemographic factors. However, the authors did not control for heat and cold episodes during pregnancy. From our point of view, a similar nonlinear behavior could be expected or would at least be worth analyzing in the case of adverse birth variables. As a susceptible population group, pregnant women may be more sensitive to changes in temperature and may be at a greater risk of heat stress, because during pregnancy the increase in fat deposition and associated decrease in the ratio of body surface area to body mass result in less capacity for heat loss to the environment (Wells and Cole 2002). A study conducted in Rome with time-series analysis methodology (Schifano et al. 2013) showed that heat, as measured by the maximum temperature during warmer periods, was associated in the short term with preterm birth. This association with temperature was not observed in the cold periods. Similar results were obtained in Madrid (Linares et al. in press). This study considered daily maximum temperatures during heat waves (defined in Madrid during 2001–2009 as daily maximum temperatures above 34°C) and during cold waves (defined in Madrid during 2001–2009 as daily maximum temperatures below –2°C). The results for the influence of high temperatures on low birth weight were similar to those found in Rome, with the same short-term association between temperature rise and increased cases of premature birth and, consequently, low birth weight. This suggests heat waves are an acute stressor on pregnant women, not the chronic stressor described by Kloog et al. The mechanism is unclear by which high temperatures may increase the risk of preterm birth, but there is evidence in the literature that supports a relationship (Carolan-Olah and Frankowska 2014). This short-term effect of Ta on adverse birth outcomes is similar to that already described for traffic noise as a factor in adverse birth outcomes in Madrid (Diaz and Linares in press). Although Kloog et al. introduced Ta values with linear components, from our point of view introducing Ta as a linear component and not taking into account the effects of heat and cold separately minimizes the authors’ ability to draw conclusions about potential impacts. The effects of high temperatures may be offset by cold temperatures. Therefore, it would be interesting to improve the analysis of Kloog et al. by taking into account the effect of Ta, but separating its effect by warm and cold seasons, especially for days within heat and cold waves.

Background Studies on the association between prenatal exposure to fine particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) and term low birth weight (LBW) have resulted in inconsistent findings. Most studies were conducted in snapshots of small geographic areas and no national study exists. Objectives We investigated geographic variation in the associations between ambient PM2.5 during pregnancy and term LBW in the contiguous United States. Methods A total of 3,389,450 term singleton births in 2002 (37–44 weeks gestational age and birth weight of 1,000–5,500 g) were linked to daily PM2.5 via imputed birth days. We generated average daily PM2.5 during the entire pregnancy and each trimester. Multi-level logistic regression models with county-level random effects were used to evaluate the associations between term LBW and PM2.5 during pregnancy. Results Without adjusting for covariates, the odds of term LBW increased 2% [odds ratio (OR) = 1.02; 95% CI: 1.00, 1.03] for every 5-μg/m3 increase in PM2.5 exposure during the second trimester only, which remained unchanged after adjusting for county-level poverty (OR = 1.02; 95% CI: 1.01, 1.04). The odds did change to null after adjusting for individual-level predictors (OR = 1.00; 95% CI: 0.99, 1.02). Multi-level analyses, stratified by census division, revealed significant positive associations of term LBW and PM2.5 exposure (during the entire pregnancy or a specific trimester) in three census divisions of the United States: Middle Atlantic, East North Central, and West North Central, and significant negative association in the Mountain division. Conclusions Our study provided additional evidence on the associations between PM2.5 exposure during pregnancy and term LBW from a national perspective. The magnitude and direction of the estimated associations between PM2.5 exposure and term LBW varied by geographic locations in the United States. Citation Hao Y, Strosnider H, Balluz L, Qualters JR. 2016. Geographic variation in the association between ambient fine particulate matter (PM2.5) and term low birth weight in the United States. Environ Health Perspect 124:250–255; http://dx.doi.org/10.1289/ehp.1408798

Background: Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. Objectives: We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. Methods: Among 83,389 mother–child pairs enrolled in the Danish National Birth Cohort during 1996–2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child’s sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. Results: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother’s PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. Conclusions: In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children. Citation: Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei CY, Bossi R, Henriksen TB, Bonefeld-Jørgensen EC, Olsen J. 2015. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case–control study in the Danish National Birth Cohort. Environ Health Perspect 123:367–373; http://dx.doi.org/10.1289/ehp.1408412

Background: Prenatal exposure to some per- and polyfluoroalkyl substances (PFASs) may disrupt maternal and neonatal thyroid function, which is critical for normal growth and neurodevelopment. Objectives: We examined associations of PFAS exposure during early pregnancy with maternal and neonatal thyroid hormone levels. Methods: We studied 732 mothers and 480 neonates in Project Viva, a longitudinal prebirth cohort in Boston, Massachusetts. We quantified six PFASs, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), and maternal thyroid hormones [thyroxine (T4), Free T4 Index (FT4I), thyroid stimulating hormone (TSH)] in plasma samples collected at a median 9.6 wk gestation and neonatal T4 levels from postpartum heel sticks. We estimated associations of PFAS concentrations with thyroid hormone levels using covariate-adjusted linear regression models and explored effect measure modification by maternal thyroid peroxidase antibody (TPOAb) status and infant sex. Results: PFAS concentrations were not associated with maternal T4, but PFOA, perfluorohexane sulfonate (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) were inversely associated with maternal FT4I [e.g., −1.87% (95% confidence interval (CI): −3.40, −0.31) per interquartile (IQR) increase in PFOA]. PFAS concentrations [PFOA, PFOS, and perfluorononanoate (PFNA)] were inversely associated with TSH levels in TPOAb-positive women only. Prenatal PFOS, PFOA, and PFHxS concentrations were inversely associated with T4 levels in male [e.g., PFHxS, quartile 4 vs.1: −2.51μg/dL (95% CI: −3.99, −1.04 )], but not female neonates [0.40μg/dL (95% CI: −0.98, 1.79)]. Conclusions: In this study, prenatal exposure to some PFASs during early pregnancy was inversely associated with maternal FT4I and neonatal T4 in male infants. These results support the hypothesis that prenatal exposure to PFASs influences thyroid function in both mothers and infants. https://doi.org/10.1289/EHP2534

Background: Sex-specific associations have been reported between phthalates, bisphenol A (BPA), and child behavior. No data on large study populations are available for other phenols with possible endocrine-disrupting properties. Objectives: We aimed to study associations between prenatal exposure to phthalates and several phenols on behavior among male infants. Methods: We quantified 11 phthalate metabolites and nine phenols (four parabens, benzophenone-3, BPA, two dichlorophenols, triclosan) in spot urine samples collected during pregnancy among EDEN cohort mothers who delivered a boy. Mothers completed the Strength and Difficulties Questionnaire (SDQ) when their children were 3.1 (n=529) and 5.6 (n=464) y old. Results: BPA was positively associated with the relationship problems subscale at 3 y [incidence rate ratio (IRR): 1.11; 95% confidence interval (CI): 1.03, 1.20] and the hyperactivity–inattention subscale scores at 5 y (IRR: 1.08; 95% CI: 1.01, 1.14). Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problem, and emotional symptom scores at 3 y. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 y. After dichotomizing SDQ scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 y. Conclusions: The observed associations between BPA, MnBP, and behavior in boys are consistent with previous findings. Further health impact assessment studies based on dose–response functions corrected for exposure misclassification are required to quantify the public health burden possibly entailed by such associations. https://doi.org/10.1289/EHP1314

BackgroundPrenatal exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment and behaviors related to autism spectrum disorders (ASD) in previous studies, including in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort living in the agricultural Salinas Valley in California.ObjectivesTo investigate the association of prenatal exposure to OP pesticides with traits related to ASD, in childhood and adolescents in CHAMACOS.MethodsWe assessed OP exposure during pregnancy with measurements of dialkyl phosphates (DAP) metabolites in urine, and residential proximity to OP use during pregnancy using California's Pesticide Use Reporting (PUR) data and estimated associations with ASD-related traits using linear regression models. We measured traits reported by parents and teachers as well as the child's performance on tests that evaluate the ability to use facial expressions to recognize the mental state of others at 7, 101/2, and 14 years of age.ResultsPrenatal DAPs were associated with poorer parent and teacher reported social behavior [e.g., a 10-fold DAP increase was associated with a 2.7-point increase (95% confidence interval (CI): 0.9, 4.5) in parent-reported Social Responsiveness Scale, Version 2, T-scores at age 14]. We did not find clear evidence of associations between residential proximity to OP use during pregnancy and ASD-related traits.ConclusionsThese findings contribute mixed evidence linking OP pesticide exposures with traits related to developmental disorders like ASD. Subtle pesticide-related effects on ASD-related traits among a population with ubiquitous exposure could result in a rise in cases of clinically diagnosed disorders like ASD. https://doi.org/10.1289/EHP2580.

Introduction: Evidence from animal models suggests that prenatal exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is associated with adverse reproductive outcomes in females. Exposure during early gestation, a critical period for reproductive development, is of particular concern. Anogenital distance (AGD) is a sensitive biomarker of the fetal hormonal milieu and a measure of reproductive toxicity in animal models. In some studies, the daughters of BPA-exposed dams have shorter AGD than controls. Here, we investigate this relationship in humans. Methods: BPA was assayed in first-trimester urine samples from 385 participants who delivered infant girls in a multicenter pregnancy cohort study. After birth, daughters underwent exams that included two measures of AGD (AGD-AC: distance from center of anus to clitoris; AGD-AF: distance from center of anus to fourchette). We fit linear regression models to examine the association between specific gravity–adjusted (SPG-adj) maternal BPA concentrations and infant AGD, adjusting for covariates. Results: BPA was detectable in 94% of women. In covariate-adjusted models fit on 381 eligible subjects, the natural logarithm of SpG-adj maternal BPA concentration was inversely associated with infant AGD-AC [β=−0.56, 95% confidence interval (CI): −0.97, −0.15]. We observed no association between maternal BPA and infant AGD-AF. Conclusion: BPA may have toxic effects on the female reproductive system in humans, as it does in animal models. Higher first-trimester BPA exposure was associated with significantly shorter AGD in daughters, suggesting that BPA may alter the hormonal environment of the female fetus. https://doi.org/10.1289/EHP875