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INTRODUCTION: To date, the evidence for an association between perfluoroalkyl substances (PFAS) exposure and attention deficit and hyperactivity disorder (ADHD) is inconclusive. OBJECTIVE: We investigated the association between early life exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and ADHD in a collaborative study including nine European population-based studies, encompassing 4,826 mother-child pairs. METHODS: Concentrations of PFOS and PFOA were measured in maternal serum/plasma during pregnancy, or in breast milk, with different timing of sample collection in each cohort. We used a validated pharmacokinetic model of pregnancy and lactation to estimate concentrations of PFOS and PFOA in children at birth and at 3, 6, 12, and 24 months of age. We classified ADHD using recommended cutoff points for each instrument used to derive symptoms scores. We used multiple imputation for missing covariates, logistic regression to model the association between PFAS exposure and ADHD in each study, and combined all adjusted study-specific effect estimates using random-effects meta-analysis. RESULTS: A total of 399 children were classified as having ADHD, with a prevalence ranging from 2.3% to 7.3% in the studies. Early life exposure to PFOS or PFOA was not associated with ADHD during childhood [odds ratios (ORs) ranging from 0.96 (95% CI: 0.87, 1.06) to 1.02 (95% CI: 0.93, 1.11)]. Results from stratified models suggest potential differential effects of PFAS related to child sex and maternal education. CONCLUSION: We did not identify an increased prevalence of ADHD in association with early life exposure to PFOS and PFOA. However, stratified analyses suggest that there may be an increased prevalence of ADHD in association with PFAS exposure in girls, in children from nulliparous women, and in children from low-educated mothers, all of which warrant further exploration. https://doi.org/10.1289/EHP5444, Introduction Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder during childhood. The global prevalence of ADHD in the population younger than 18 years of age has been [...]

Background: Higher concentrations of single perfluorinated alkyl acids (PFAAs) have been associated with lower birth weight (BW), but few studies have examined the combined effects of PFAA mixtures. PFAAs have been reported to induce estrogen receptor (ER) transactivity, and estrogens may influence human fetal growth. We hypothesize that mixtures of PFAAs may affect human fetal growth by disrupting the ER. Objectives: We aimed to study the associations between the combined xenoestrogenic activity of PFAAs in pregnant women's serum and offspring BW, length, and head circumference. Methods: We extracted the actual mixture of PFAAs from the serum of 702 Danish pregnant women (gestational wk 11-13) enrolled in the Aarhus Birth Cohort (ABC) using solid phase extraction, high-performance liquid chromatography (HPLC), and weak anion exchange. PFAA-induced xenoestrogenic receptor transactivation (XER) was determined using the stable transfected MVLN cell line. Associations between XER and measures of fetal growth were estimated using multivariable linear regression with primary adjustment for maternal age, body mass index (BMI), educational level, smoking, and alcohol intake, and sensitivity analyses with additional adjustment for gestational age (GA) (linear and quadratic). Results: On average, an interquartile range (IQR) increase in XER was associated with a 48 g [95% confidence interval (CI): -90, -6] decrease in BW and a 0.3 cm (95% CI: 0.1, 0.5) decrease in birth length. Upon additional adjustment for GA, the estimated mean differences were -28 g (95% CI: -60, 4) and -0.2 cm (95% CI: -0.4, 0.0), respectively. Conclusion: Higher-serum PFAA-induced xenoestrogenic activities were associated with lower BW and length in offspring, suggesting that PFAA mixtures may affect fetal growth by disrupting ER function. https://doi.org/10.1289/EHP1884, Introduction Perfluorinated alkyl acids (PFAAs) are synthetic surfactants used in food packaging, impregnation of, e.g., shoes and textiles and other products. PFAAs are persistent in the environment and bioaccumulate in [...]

Background: Previous studies have investigated the associations between perfluoroalkyl acids (PFAAs) in women and time to pregnancy (TTP). Inconsistent results may be explained by differences in conditioning on parity. OBJECTIVES: We used causal directed acyclic graphs to illustrate potential confounding related to previous pregnancies and exposure measurement error due to differences in the interpregnancy interval in pregnancy-based studies that include parous women. We exemplified the potential importance of these issues using data from the Danish National Birth Cohort. Methods: We used discrete time survival models to estimate associations between maternal plasma PFAAs in early pregnancy and TTP in 638 nulliparous and 613 parous women. Results: PFAA quartiles were not associated with the TTP in nulliparous women. In parous women, higher PFAA quartiles were associated with longer TTP. The strongest associations were estimated for perfluorohexane sulfonate and perfluorooctane sulfonate. PFAA concentrations were higher in women with longer interpregnancy intervals. Accounting for the interpregnancy interval attenuated the estimated associations. Conclusions: Associations between PFAAs and TTP in parous women may be biased by confounders related to previous pregnancies and exposure measurement error. To avoid these biases, studies that include parous women may need to condition on a) common causes of PFAAs and the TTP in the index pregnancy, b) previous births (a descendant of a collider), c) PFAA levels or common causes of PFAA levels and the TTP in the previous pregnancy (to alleviate collider stratification bias caused by conditioning on previous births), and d) the interpregnancy interval (in pregnancy-based studies). Alternatives would be to restrict studies to nulliparous women or to use toxicokinetic modeling to correct exposure estimates in parous women. These recommendations may be extended to studies of other chemicals with similar toxicokinetic properties. https://doi.org/10.1289/EHP1493, Introduction Since 2009, a number of studies have investigated associations between perfluoroalkyl acids (PFAAs) in women and fecundability, indicated by the time to pregnancy (TTP), with inconsistent results (Bach et [...]

BACKGROUND: Perfluoroalkyl substances (PFASs) are widespread persistent organic compounds that have been suggested to affect neurodevelopment. Objective: We aimed to evaluate whether prenatal exposure to PFASs is associated with IQ in children. METHODS: We studied 1,592 pregnancies enrolled in the Danish National Birth Cohort (DNBC) during 1996-2002. Sixteen PFASs were measured in maternal plasma collected in early gestation. Child IQ was assessed at 5 y of age using the Wechsler Primary and Preschool Scales of Intelligence-Revised (WPPSI-R) administered by trained psychologists. Using multivariable linear regression models, we estimated the differences in child IQ scores according to PFAS concentration [per natural-log (ng/mL) unit increase or values categorized in quartiles]. RESULTS: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples, and five additional PFASs were quantified in >80% of the samples. Overall, we found no strong associations between a natural-log unit increase in each of the seven PFASs we evaluated and child IQ scores. A few positive and negative associations were found in the sex-stratified PFAS quartile analyses, but the patterns were inconsistent. CONCLUSION: Overall, we did not find consistent evidence to suggest prenatal exposure to PFASs to be associated with child IQ scores at 5 y of age in the DNBC. Some of the sex-specific observations warrant further investigation. Additional studies should examine offspring IQ at older ages and assess other functional cognitive and neuropsychiatric measures in addition to intelligence. Postnatal exposures to PFASs and mixture effects for PFASs and PFASs with other environmental pollutants should also be considered in future research. https://doi.org/10.1289/EHP2754, Introduction Perfluoroalkyl substances (PFASs) are a group of synthetic fluorine-containing compounds that have been widely used in commercial and manufacturing products since the 1950s for the treatment of paper, clothing, [...]