Prenatal Perfluoroalkyl Substances Research Articles

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies

BackgroundWomen with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. ObjectiveTo estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. MethodsOur study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. ResultsUsing quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. ConclusionsThe first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

Prenatal Exposure to Poly- and Perfluoroalkyl Substances (2009-2014) and Vaccine Antibody Titers of Measles, Mumps, Rubella, and Varicella in Children Four to Eight Years Old from the Healthy Start Cohort.

Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations. We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization. We measured serum antibody titers of 145 children (4-8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009-2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in of mothers and continuous or non-high-censored ("low") antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture. Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%-100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males. Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. https://doi.org/10.1289/EHP12863.

Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense Child Cohort

IntroductionExposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. ObjectivesTo determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. MethodsIn the Odense Child Cohort, Denmark, pregnant women were recruited in 2010–2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid(PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 881) and/or at age 18 months (n = 668) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. ResultsHigher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of 18-month exposure to PFNA or PFOS, BMD Z-scores were lowered by −0.10 (95 % CI −0.19;-0.00) and −0.08 (-0.17;-0.00), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. DiscussionBone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Association between prenatal exposure to perfluoroalkyl substance mixtures and intrauterine growth restriction risk: A large, nested case–control study in Guangxi, China

Intrauterine growth restriction (IUGR) is an abnormal fetal growth pattern that can lead to neonatal morbidity and mortality. IUGR may be affected by prenatal exposure to environmental pollutants, including perfluoroalkyl substances (PFASs). However, research linking PFAS exposure to IUGR is limited, with inconsistent results. We aimed to investigate the association between PFAS exposure and IUGR by using nested casecontrol study based on Guangxi Zhuang Birth Cohort (GZBC), in Guangxi, China. A total of 200 IUGR cases and 600 controls were enrolled in this study. The maternal serum concentrations of nine PFASs were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLCMS). The associations single and mixed effects of prenatal PFAS exposure on IUGR risk were assessed using conditional logistic regression (single-exposure), Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models. In the conditional logistic regression models, the log10-transformed concentrations of perfluoroheptanoic acid (PFHpA, adjusted OR: 4.41, 95% CI: 3.03–6.41), perfluorododecanoic acid (PFDoA, adjusted OR: 1.94, 95% CI: 1.14–3.32), and perfluorohexanesulfonate (PFHxS, adjusted OR: 1.83, 95% CI: 1.15–2.91) were positively associated with risk of IUGR. In the BKMR models, the combined effect of PFASs was positively associated with IUGR risk. In the qgcomp models, we also found an increased IUGR risk (OR=5.92, 95% CI: 2.33–15.06) when all nine PFASs increased by one tertile as a whole, and PFHpA (43.9%) contributed the largest positive weights. These findings suggested prenatal exposure to single and mixtures of PFASs may increase IUGR risk, with the effect being largely driven by the PFHpA concentration.

In utero exposure to poly- and perfluoroalkyl substances and children respiratory health in the three first years of life

BackgroundPoly- and perfluoroalkyl substances (PFAS) are used in a wide range of products. Experimental studies suggested impaired lung development and pro-inflammatory response following exposure to some PFAS. We aimed to assess the associations between prenatal exposure to PFAS and children respiratory health. MethodsThe study is based on 433 mother-child pairs. 26 PFAS were measured in maternal serum collected during pregnancy. Lung function parameters were measured at 2 months using tidal breathing flow-volume loops and multiple-breath nitrogen washout and at 36 months using oscillometry. Incidence of respiratory health diseases (asthma, wheeze, bronchitis, bronchiolitis) in the first 36 months of life was assessed by repeated questionnaires. A cluster-based analysis was applied to identify prenatal PFAS exposure patterns. Adjusted linear and logistic regressions were performed to assess the associations between PFAS exposure patterns as well as individual PFAS, and each respiratory health parameter. ResultsWe excluded 13 PFAS due to low quantification (<5%). Relying on the 13 remaining PFAS, we identified three exposure clusters, characterized by low (N = 163), medium (N = 236) and high (N = 51) pregnancy PFAS concentrations. Compared to children belonging to the low exposure group, children in the moderate exposure group had higher reactance at 7 Hz (X7) and lower frequency dependence of resistance between 7 Hz and 19 Hz (R7-19) at 36 months, suggesting better lung function. No association of any exposure metric was detected with respiratory diseases in the first 3 years of life. ConclusionsOur study relying on both mixture and uni-pollutant analyses, does not provide evidence for a deleterious effect of prenatal PFAS exposure on respiratory health at an early age.

Prenatal exposure to legacy PFAS and neurodevelopment in preschool-aged Canadian children: The MIREC cohort

BackgroundExposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. ObjectiveTo quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. MethodsWe measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. ResultsGeometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10–2.50), 4.97 (3.20–6.20) and 1.09 (0.67–1.60) μg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p < .01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = −2.80, 95% CI: −4.92, −0.68; PFOS: B = −2.64, 95% CI: −4.77, −0.52; PFHxS: B = −2.92, 95% CI: −4.72, −1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = −3.16, 95% CI: −4.90, −1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: −0.99, 2.26). No significant associations were found for EF in either males or females. ConclusionsHigher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.

Association between prenatal and early postnatal exposure to perfluoroalkyl substances (PFAS) and IQ score in 7-year-old children from the Odense Child Cohort.

Perfluoroalkyl substances (PFAS) are persistent chemicals capable of crossing the placenta and passing into breastmilk. Evidence suggests that PFAS exposure may affect brain development. We investigated whether prenatal or early postnatal PFAS exposure was associated with IQ-scores in schoolchildren from the Odense Child Cohort, Denmark 2010 to 2020. We assessed perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) concentrations in maternal serum collected in the 1st trimester of pregnancy and in child serum at age 18 months. At 7 years of age children completed an abbreviated version of Wechsler Intelligence Scale for Children version-V (WISC-V) from which Full Scale Intelligence Quotient (FSIQ) and Verbal Comprehension Index (VCI) were estimated. In multiple linear regressions among 967 mother-child pairs a doubling in maternal PFOS and PFNA concentrations was associated with lower FSIQ, while no significant associations were observed for PFOA, PFHxS or PFDA. PFAS concentrations at 18 months and duration of breastfeeding were strongly correlated and even in structural equation models it was not possible to differentiate the opposite effects of PFAS exposure and duration of breastfeeding on FSIQ. As PFAS exposure is ubiquitous association with even a small reduction in IQ is of public health concern.

In utero exposure to perfluoroalkyl substances and early childhood BMI trajectories: A mediation analysis with neonatal metabolic profiles

BackgroundIn utero perfluoroalkyl substances (PFAS) exposure has been associated with childhood adiposity, but the mechanisms are poorly known. ObjectiveTo investigate the potential mediating role of neonatal metabolites in the relationship between prenatal PFAS exposure and childhood adiposity trajectories in the first four years of life. MethodsWe analyzed the data for 1671 mother-child pairs from the Shanghai Birth Cohort study. We included those with PFAS exposure information in early pregnancy, neonatal metabolites data and at least three child anthropometric measurements at 6, 12, 24 and/or 48 months. Body mass index (BMI) z-score trajectories were identified using latent class growth mixture modeling. The associations between PFAS concentrations and trajectory classes were assessed using multinomial logistic regression. Screening and penalization-based selection was used to identify neonatal amino acids and acylcarnitines with significant mediation effects. ResultsThree BMI z-score trajectories in early childhood were identified: a persistent increase trajectory (Class 1, 2.2 %), a stable trajectory (Class 2, 66 %), and a transient increase trajectory (Class 3, 32 %). Increased odds of being in Class 1 were observed in association with one log-unit increase in concentrations of perfluorooctane sulfonate (odds ratio [OR], 1.76 [95 % CI, 0.96–3.23], Class 2 as reference; OR, 2.36 [95 % CI, 1.27–4.40], Class 3 as reference), perfluorononanoic acid (OR, 1.90 [95 % CI, 0.97–3.72], Class 2 as reference; OR, 2.23 [95 % CI, 1.12–4.42], Class 3 as reference) and perfluorodecanoic acid (OR, 1.95 [95 % CI, 1.12–3.38], Class 2 as reference; OR, 2.14 [95 % CI, 1.22–3.76], Class 3 as reference). The effect of prenatal PFAS exposure on being in Class 1 was significantly but partly mediated by octanoylcarnitine (2.64 % for perfluorononanoic acid and 3.70 % for sum of 10 PFAS). ConclusionsIn utero PFAS exposure is a risk factor for persistent growth in BMI z-score in early childhood. The alteration of neonatal acylcarnitines suggests a potential molecular pathway.

Prenatal perfluoroalkyl substances exposure and maternal sex steroid hormones across pregnancy

BackgroundPoly- and perfluoroalkyl substances (PFAS) are ubiquitous and persistent environmental contaminants that may act as endocrine disruptors in utero, but the specific endocrine pathways are unknown. ObjectiveWe examined associations between maternal serum PFAS and sex steroid hormones at three time points during pregnancy. MethodsPregnant women participating in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaire, and medical record data in each trimester (n = 285). PFAS (including perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA)) were analyzed in second-trimester serum samples by high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Total testosterone [TT], free testosterone [fT], estrone [E1], estradiol [E2], and estriol [E3]) were measured by LC-MS/MS in serum samples from each trimester. Linear mixed models with random intercepts were used to examine associations between log-transformed PFAS concentrations and hormone levels, adjusting for covariates, and stratifying by fetal sex. Results are presented as the mean percentage difference (Δ%) in hormone levels per ln-unit increase in PFAS concentration. ResultsIn adjusted models, PFHxS was associated with higher TT (%Δ = 20.0, 95%CI: 1.7, 41.6), particularly among women carrying male fetuses (%Δ = 15.3, 95%CI: 1.2, 30.7); this association strengthened as the pregnancy progressed. PFNA (%Δ = 7.9, 95%CI: 3.4, 12.5) and PFDA (%Δ = 7.2, 95%CI: 4.9, 9.7) were associated with higher fT, with associations again observed only in women carrying male fetuses. PFHxS was associated with higher levels of E2 and E3 in women carrying female fetuses (%Δ = 13.2, 95%CI: 0.5, 29.1; %Δ = 17.9, 95%CI: 3.2, 34.8, respectively). No associations were observed for PFOS and PFOA. ConclusionPFHxS, PFNA, and PFDA may disrupt androgenic and estrogenic pathways in pregnancy in a sex-dependent manner.

Prenatal perfluoroalkyl substances exposure and neurodevelopment in toddlers: Findings from SMBCS

BackgroundPrenatal perfluoroalkyl substances (PFAS) exposure has been reported to affect offspring neurodevelopment, while epidemiological evidences were limited and inconsistent. ObjectivesWe aimed to evaluate the associations between cord serum PFAS concentrations and neurodevelopment in toddlers from 1 to 3 years of age. MethodsA total of 716 children from Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. 12 PFAS concentrations were quantified in cord serum. Neurodevelopment was assessed using the Developmental Screen Test for Children Aged 0–6 Years at 1 year and the Gesell Developmental Schedules (GDS) at 2 and 3 years, respectively. Development quotient (DQ) z-score was standardized from DQ to eliminate the difference caused by two methods. We used generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) to explore the associations of single or mixture PFAS exposure with neurodevelopment measurements at each time point. Associations between PFAS exposure and longitudinal changes in DQ z-score were investigated through generalized estimating equation (GEE) and trajectory analysis. ResultsIn general, prenatal PFAS concentrations showed negative associations with neurodevelopment measurements at specific age. When accounting for longitudinal changes from 1 to 3 years of age, PFOA was negatively associated with DQ z-score (β = −0.212, 95% CI: −0.422, −0.003), the association was only found significant in boys after stratified by gender (β = −0.327, 95% CI: −0.616, −0.038). Meanwhile, increased PFBS (OR = 2.159, 95% CI: 1.177, 3.959) and PFHpA (OR = 1.700, 95% CI: 1.016, 2.846) exposure was associated with elevated odds for the low-score trajectory group. The results of mixture of PFAS further confirmed above findings. ConclusionsOur findings suggested that prenatal PFAS exposure may be associated with adverse neurodevelopment effects in the first 3 years of life. Further studies are warranted to confirm our findings.

Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense child cohort.

Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7years. In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010-2012, and their children were invited for subsequent health examinations. At 12weeks of gestation the pregnant women delivered a serum sample, and at age 18months serum was obtained from the child to measure perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n=924) and/or at age 18months (n=511) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7years, all estimates were negative although not all significant. For each doubling of prenatal or 18-month exposure to PFDA, BMD Z-scores were lowered by -0.07 (95% CI -0.10; -0.03) and -0.14 (-0.25; -0.03), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Associations between prenatal exposure to perfluoroalkyl substances and neurobehavioral development in early childhood: A prospective cohort study

Findings from epidemiological studies on the associations between prenatal perfluoroalkyl substances (PFASs) exposure and children's neurodevelopment were inconclusive, and most studies did not account for the co-exposure to multiple PFASs with strong inter-correlations. The present study aimed to assess the effects of prenatal multiple PFAS exposure on children’s neurobehavioral development based on 614 mother-infant pairs in the Shanghai-Minhang Birth Cohort Study. Eight PFAS concentrations were measured in maternal plasma at 12–16 weeks of gestation. Children’s neurobehavioral development at 2 and 4 years of age was assessed by the Child Behavior Checklist for Ages 1.5–5. In Bayesian kernel machine regression (BKMR) analyses that could address the inter-correlations between multiple PFASs, PFAS mixture appeared to be associated with fewer Somatic Complaints and more Externalizing Problems in boys, but more Somatic Complaints and Sleep Problems in girls. There were suggestive associations of PFNA and PFOS with decreased risk of Somatic Complaints and of PFUdA and PFTrDA with increased risk of Externalizing Problems in boys; trends of increased risk in girls were observed between PFUdA and Somatic Complaints and between PFTrDA and Sleep Problems. Overall, we found no clear evidence that prenatal exposure to PFASs had negative effects on neurobehavioral development in children. However, the modest associations still suggested the potential developmental neurotoxicity of prenatal PFAS exposure.

Associations between prenatal exposure to perfluoroalkyl substances, hypomethylation of MEST imprinted gene and birth outcomes

Prenatal perfluoroalkyl substance (PFAS) exposure has been linked to adverse birth outcomes, but the underlying mechanism has yet to be elucidated. DNA methylation changes in mesoderm-specific transcript (MEST) imprinted gene may be a mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim was to investigate the prenatal PFASs exposure effects on DNA methylation changes in MEST imprinted gene involved in fetal growth. Among 486 mother-infant pairs from the Taiwan Birth Panel Study, PFASs and DNA methylation levels at 5 CpG sites of MEST promoter region were measured in cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFAS exposure, MEST DNA methylation levels, and child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation between PFASs and birth outcomes. We found that higher prenatal perfluorooctyl sulfonate (PFOS) exposure was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region (an adjusted β range: −1.56, −2.22). Significant negative associations were also found between MEST methylation levels and child birth weight. Furthermore, the associations between PFOS and perfluorooctanoic acid (PFOA) exposure and MEST methylation levels were more profound in girls than in boys. The mediated effect of average MEST methylation level between PFOS exposure and birth weight was 18.3 (95% CI = 2.1, 40.2; p = 0.014). The direct effect of PFOS exposure to birth weight independent to average MEST methylation level was −93.2 (95% CI = −170.5, −17.8; p = 0.018).In conclusion, our results suggest that prenatal PFAS exposure, especially PFOS, is associated with lower methylation levels at MEST promoter region, which not only leverages the role of imprinted gene in ensuring the integrity of fetal growth but also provides a potential mechanism for evaluating the prenatal exposure effect.

Association of exposure to prenatal perfluoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children: The Hokkaido study

Per- and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.

The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study.

Disruption of thyroid hormone (TH) levels during pregnancy contributes to attention deficit hyperactivity disorder (ADHD). Exposure to perfluoroalkyl substances (PFAS) during gestation may affect levels of maternal and neonatal TH; however, little is known about the effect of PFAS on ADHD mediated by TH. We investigated the impact of maternal PFAS exposure on children's ADHD symptoms with the mediating effect of TH. In a prospective birth cohort (the Hokkaido study), we included 770 mother-child pairs recruited between 2002 and 2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFAS were measured in maternal serum obtained at 28-32weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. TH and thyroid antibody, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks) and in cord blood at birth. ADHD symptoms in the children at 8years of age were rated by their parents using the ADHD-Rating Scale (ADHD-RS). The cut-off value was set at the 80th percentile for each sex. Significant inverse associations were found between some PFAS in maternal serum and ADHD symptoms among first-born children. Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity-impulsivity among first-born children. Higher PFAS levels in maternal serum during pregnancy were associated with lower risks of ADHD symptoms at 8years of age. The association was stronger among first-born children in relation to hyperactivity-impulsivity than with regard to inattention. There was little mediating role of TH during pregnancy in the association between maternal exposure to PFAS and reduced ADHD symptoms at 8years of age.

Association between maternal serum concentration of perfluoroalkyl substances (PFASs) at delivery and acute infectious diseases in infancy

BackgroundPerfluoroalkyl substances (PFASs) are persistent and bio-accumulative compounds that have been recognized as important immune hazards by animal studies. However, epidemiological studies regarding the impact on infant infections were inconsistent. ObjectivesWe investigated the associations between prenatal exposure to PFASs and acute infectious diseases including common cold, bronchitis/pneumonia, and diarrhea in early childhood. MethodsParticipating 235 mother–infant pairs were recruited from the Laizhou Wan (Bay) birth cohort (LWBC), a prospective study in Shandong, China between September 2010 and 2013. Ten selected PFASs congeners including PFOA, PFOS, PFNA, PFDA, PFUA, PFDoA, PFHxS, PFBS, PFHpA, and PFOSA were measured from maternal serum by HPLC-MS/MS. Detailed information on parent-reported frequency of acute infectious diseases was collected from questionnaires at 1-year follow-up, which was confirmed by the medical records. Logistic and Poisson regression models were used on binary health outcomes (yes/no) and the number of episodes of outcomes, which were reported as odds ratio (OR) and incidence rate-ratio (IRR), respectively. ResultsThe risk of diarrhea increased by 4.99 (95% CI = 1.86, 13.39) per log-unit increase in PFOA. The frequencies of diarrhea increased by 97%–116% for each 10-fold increase in PFOA, PFNA, and PFDA. Moreover, when stratified by exclusively breastfeeding duration (at least 4 months or not), the adverse effects of PFASs exposures on diarrhea were more pronounced among the breastfed infants. There were no associations between prenatal PFASs exposure and common cold or bronchitis/pneumonia. ConclusionsExposure to PFASs was associated with increased risks of diarrhea during the first year of life, and these effects were stronger among the breastfed infants. Due to the small sample size, our results should be interpreted with caution and additional studies on larger populations are needed to confirm our findings.

Prenatal exposure to poly-/per-fluoroalkyl substances is associated with alteration of lipid profiles in cord-blood

IntroductionPoly-/per-fluoroalkyl substances (PFAS) are widespread environmental pollutants that may induce metabolic perturbations in humans, including particularly alterations in lipid profiles. Prenatal exposure to PFAS can cause lasting effects on offspring metabolic health, however, the underlying mechanisms are still unknown.ObjectivesThe goal of the study was to investigate the impact of prenatal PFAS exposure on the lipid profiles in cord blood.MethodsHerein, we combined determination of bile acids (BAs) and molecular lipids by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified cord blood concentrations of sixteen PFAS in a cohort of Chinese infants (104 subjects) in a cross-sectional study. We then evaluated associations between PFAS concentration and lipidome using partial correlation network analysis, debiased sparse partial correlation, linear regression analysis and correlation analysis.ResultsPFAS levels showed significant associations with the lipid profiles; specifically, PFAS exposure was positively correlated with triacylgycerols (TG) and several bile acids. Importantly, exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were associated with increased levels of TGs with saturated fatty acids while multiple classes of phospholipids were decreased. In addition, several free fatty acids showed significant positive correlations with PFOS.ConclusionsOur results indicated that prenatal exposure to PFAS mediated metabolic changes, which may explain the associations reported between PFAS exposure and metabolic health later in life.

Umbilical cord serum concentrations of perfluorooctane sulfonate, perfluorooctanoic acid, and the body mass index changes from birth to 5 1/2\xa0years of age

Prenatal exposure to perfluoroalkyl substances (PFAS) has been reported to affect body weight from birth to childhood, but the results remain inconclusive. We investigated whether umbilical cord blood concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are associated with children’s risk trajectory for obesity. 600 children were randomly selected from the Hamamatsu Birth Cohort for Mothers and Children (HBC study) and their umbilical cord serum PFAS concentrations were quantified. Participants underwent BMI measurements at ages 1, 4, 10, 18, 24, 32, 40, 50, and 66 months. Growth curve modeling with random intercept was performed with standardized BMI as outcome variable. PFOS was negatively associated with standardized BMI (β = − 0.34; p = 0.01), with a marginally significant interaction with the child’s age (β = 0.0038; p = 0.08). PFOA was negatively associated with standardized BMI (β = − 0.26, 95% CI − 0.51, 0; p = 0.05), with a significant interaction with the child’s age (β = 0.005; p = 0.01). Stratified analysis by sex revealed that these effects were significant only among girls. Prenatal exposure to PFAS initially was associated with lower standardized BMI during infancy, but this effect dissipated over time and reversed in direction during later childhood. The effects of prenatal PFAS on higher standardized BMI is stronger in girls.

476Associations between prenatal perfluoroalkyl substance exposure and cord thyroid hormones using BKMR model

Abstract Background Perfluoroalkyl substances (PFASs) are a class of synthetic compounds widely detected in humans. We aimed to examine associations between prenatal PFAS exposure and cord thyroid hormones levels. Methods We studied 300 mother-infant pairs in Shanghai-Minhang Birth Cohort Study. We measured eight PFASs in maternal plasma samples collected at 12-16 gestational weeks, and total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. Bayesian kernel machine regression (BKMR) model was used addressing high correlations between PFAS mixture. Results Maternal PFAS mixture was positively associated with cord T3/FT3 concentrations, such that the 75th percentile of PFAS mixture was associated with 0.074 (95%CI: 0.037, 0.146) nmol/l increase in T3 and 0.095 (95%CI: -0.005, 0.195) pmol/l increase in FT3, compared with the 25th percentile. Regarding single-exposure effect, PFOA at 75th percentile was associated with increased T3 (0.0396 nmol/l, 95%CI: 0.007, 0.072), FT3 (0.159 pmol/l, 95%CI: 0.055, 0.264) and TSH (1.50 uIU/ml, 95%CI: 0.379, 2.621), while PFNA was associated with decreased FT3 (-0.148 pmol/l, 95%CI -0.271, -0.0253) and TSH (-1.621 uIU/ml, 95%CI: -2.959, -0.2835). PFDA was associated with increased FT3 (0.112 pmol/l, 95%CI: -0.0311, 0.2559). Conclusions Prenatal FPAS exposure was positively associated with T3/FT3 with predominant compounds of PFOA, PFNA, and PFDA. Key messages Using BKMR addressing highly correlated PFASs, prenatal exposure to eight PFASs was associated with increased cord T3/FT3 levels with PFOA, PFNA, and PFDA being predominant compounds.

Prenatal Exposure to Perfluoroalkyl Substances and Mental Health in Childhood

BACKGROUND AND AIM: Epidemiological studies have evaluated the effect of prenatal exposure to perfluoroalkyl substances (PFAS) on neurobehavioral and cognitive endpoints in childhood, but a research focus on mental health is lacking. We evaluated the associations between prenatal PFAS exposure and mental health including depressive symptoms, physical or emotional stress, and psychosis-like experience in children at age 11. METHODS: Using pooled samples in the Danish National Birth Cohort established between 1996 and 2002 (N=2,250), we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child self-report mental health outcomes using validated questionnaires. Binary classifications (with or without moderate/severe symptoms) for each of the outcomes and continuous outcome variables were analyzed. We used unconditional logistic regressions to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the binary outcomes according to log2-transformed PFAS concentrations and PFAS tertiles. PFAS mixture by using the weighted-quantile-sum index was conducted. Analyses were repeated using negative binomial regressions for continuous count outcome variables. Sex-specific analyses were conducted. RESULTS:The highest exposure tertile for perfluorooctanoic acid (OR=1.34, 95% CI: 1.06, 1.71), perfluorohexane sulfonate (OR=1.43, 95% CI: 1.06, 1.92) and perfluoroheptane sulfonate (OR=1.37, 95% CI: 1.02, 1.84) were associated with elevated physical or emotional stress in childhood. The WQS index for PFAS mixture was also positively associated with stress in childhood (OR=1.21, 95% CI: 1.05, 1.40). There were no consistent associations found for these PFAS compounds and depressive symptoms or psychosis-like experience. Findings from negative binomial regressions were similar. There were also no apparent differences in analyses stratified by sex. CONCLUSIONS:Higher prenatal levels of three PFAS compounds and PFAS mixtures might influence physical and emotional stress in childhood. More research of fetal exposures to environmental pollutants and mental health risk in the offspring would be needed. KEYWORDS: PFAS, Mental health outcomes, Children's environmental health, Environmental epidemiology