Dataset Information

Prenatal Exposure to Perfluoroalkyl Substances and Birth Outcomes; An Updated Analysis from the Danish National Birth Cohort.

ABSTRACT: Perfluoroalkyl substances (PFASs) are widespread industrial pollutants that are extremely persistent in the environment. A previous study in the Danish National Birth Cohort (DNBC) found prenatal perfluorooctanoate (PFOA) exposure was associated with decreased birth weight, but had insufficient statistical power to evaluate adverse birth outcomes. Here, we conducted additional analyses in three samples originating from the DNBC for 3535 mothers and infant pairs to evaluate associations between prenatal PFASs exposures and low birth weight and preterm birth. Maternal plasma concentrations were measured for six types of PFASs in early pregnancy. Several PFASs were associated with a reduction in birth weight and gestational age. We estimated a nearly 2-fold increase in risks of preterm birth for the higher quartiles of PFOA and perflourooctanesulfonate (PFOS) exposure. In spline models, risk of preterm birth was increased for perfluorononanoic acid (PFNA), perfluoroheptane sulfonate (PFHpS) and perfluorodecanoic acid (PFDA) in higher exposure ranges. We also observed some elevated risks for low birth weight but these estimates were less precise. Our findings strengthen the evidence that in-utero PFASs exposures affect fetal growth. Future studies are needed to evaluate whether these associations persist with the decline of PFOA and PFOS in populations and should also investigate newer types of fluorinated compounds introduced more recently.

SUBMITTER: Meng Q

PROVIDER: S-EPMC6164159 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Prenatal Exposure to Perfluoroalkyl Substances and Birth Outcomes; An Updated Analysis from the Danish National Birth Cohort.

Meng Qi Q Inoue Kosuke K Ritz Beate B Olsen Jørn J Liew Zeyan Z

International journal of environmental research and public health 20180824 9

Perfluoroalkyl substances (PFASs) are widespread industrial pollutants that are extremely persistent in the environment. A previous study in the Danish National Birth Cohort (DNBC) found prenatal perfluorooctanoate (PFOA) exposure was associated with decreased birth weight, but had insufficient statistical power to evaluate adverse birth outcomes. Here, we conducted additional analyses in three samples originating from the DNBC for 3535 mothers and infant pairs to evaluate associations between p ...[more]

PMID: 30149566

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Project description:BackgroundIt remains unsettled whether prenatal exposure to perfluoroalkyl substances (PFASs) affects human reproductive health through potential endocrine disruption.ObjectivesWe aimed to explore the associations between prenatal exposure to several PFASs and various aspects of pubertal development in boys and girls.MethodsWe studied two samples ([Formula: see text] and 445) from the Puberty Cohort, nested within the Danish National Birth Cohort (DNBC), measuring PFAS in maternal plasma from early gestation. Data on pubertal development were collected biannually from the age of 11 y until full maturation, using web-based questionnaires. Outcomes were age at menarche, voice break, first ejaculation, and Tanner stages 2 to 5 for pubic hair, breast, genital development, and a combined puberty indicator. A regression model for censored data was used to estimate mean difference (months) in age at achieving the pubertal outcomes across tertiles of PFAS concentrations and with a doubling of PFAS concentrations (continuous). For perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), a meta-analysis was used to provide a weighted average of the point estimates from samples 1 and 2.ResultsOverall, prenatal exposure to PFOS, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PDFA) (girls) and PFHxS and PFHpS (boys) was associated with lower mean age at puberty marker onset. PFDA and PFNA exposure was associated with higher mean age at onset of puberty in boys. Nonmonotonic associations in girls (PFOS, PFHpS, PFDA) and boys (PFDA, PFNA) were observed, showing larger mean age differences for the combined puberty indicator in the middle tertile [girls: PFOS: [Formula: see text] mo, 95% confidence interval (CI): [Formula: see text], [Formula: see text]; PFHpS: [Formula: see text] mo, 95% CI: [Formula: see text], 1.85; PFDA: [Formula: see text] mo, 95% CI: [Formula: see text], 1.83; and boys: PFNA: 4.45 mo, 95% CI: [Formula: see text], 10.21; PFDA: 4.59 mo, 95% CI: [Formula: see text], 10.11] than in the highest tertile with the lowest as reference.ConclusionsOur population-based cohort study suggests sex-specific associations of altered pubertal development with prenatal exposure to PFASs. These findings are novel, and replication is needed. https://doi.org/10.1289/EHP3567.

Project description:BACKGROUND:Maternal thyroid hormones are essential for fetal brain development in early gestation. Perfluoroalkyl substances (PFASs)-widespread and persistent pollutants-have been suggested to interfere with maternal thyroid hormones in the second or third trimesters, but evidence for an association in the early pregnancy period is sparse. OBJECTIVES:Our goal was to evaluate the gestational-week specific associations of maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels with plasma concentrations of six PFAS chemicals in the first and second pregnancy trimester. METHODS:A cross-sectional analysis was conducted using 1,366 maternal blood samples collected between gestational weeks (GWs) 5 and 19 (median, 8 gestational weeks) in the Danish National Birth Cohort (DNBC) during 1996-2002. We estimated the percentage changes of serum TSH and fT4 levels according to concentrations (in nanograms per milliliter) of six PFAS chemicals modeled as per interquartile range (IQR) increase or by exposure quartiles. Moreover, we contrasted the estimated week-specific TSH or fT4 levels by PFAS quartile and estimated ORs for binary high or low TSH and fT4 status based on the week-specific distribution according to IQR increase of PFAS. RESULTS:TSH levels followed a U-curve trend in early pregnancy with a nadir at GW10, whereas fT4 levels were less fluctuated in the samples. There were no apparent associations between any of the PFASs and changes of average TSH or fT4 levels in total samples. In gestational-week-specific analyses, we found that the estimated TSH values were higher among the highest perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluoroheptane sulfonate (PFHpS) quartiles compared with the lower quartiles from GW5 to GW10, but the difference became null or even reversed after GW10. For binary outcomes, perfluorodecanoic acid (PFDA) was associated with high fT4 status before GW10 [OR=1.46 (95% CI: 1.04, 2.05)]. CONCLUSIONS:We observed some gestational-week-specific associations between high exposure to several PFAS and TSH level in early gestations. Further research of the biology and the potential clinical impact regarding thyroid hormones disruptions in early pregnancy is needed. https://doi.org/10.1289/EHP5482.

Project description:BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied. METHODS:Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted. RESULTS:We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women. CONCLUSION:Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202.

Project description:BACKGROUND:Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been reported to suppress immune function. However, previous studies on prenatal exposure to PFASs and allergic disorders in offspring provided inconsistent results. We aimed to examine the association between prenatal exposure to PFASs and childhood atopic dermatitis (AD) in offspring up to 24 months of age. METHODS:A prospective birth cohort study involving 1056 pregnant women was conducted in two hospitals in Shanghai from 2012 to 2015. Prenatal information was collected by an interview with the women and from medical records. Fetal umbilical cord blood was collected at birth. Cord blood plasma PFASs were measured. Children were followed at 6, 12 and 24 months and information on the development of AD was recorded. AD was diagnosed by 2 dermatologists independently based on the questionnaires. Multiple logistic regression was used to compute odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between AD and each PFASs, adjusting for potential confounders. RESULTS:A total of 687 children completed a 2-year follow-up visit and had PFASs measurement. AD was diagnosed in 173 (25.2%) children during the first 24 months. In female children, a log-unit increase in perfluorooctanoic acid (PFOA) was associated with a 2.1-fold increase in AD risk (AOR 2.07, 95% CI 1.13-3.80) after adjusting for potential confounders. The corresponding risk was 2.22 (1.07-4.58) for perfluorononanoic acid (PFNA). The highest PFOA quartile was significantly associated with AD (2.52, 1.12-5.68) compared with the lowest quartile. The highest quartile of PFNA, perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS) were associated with AD with AOR (95% CI) being 2.14 (0.97-4.74), 2.14 (1.00-4.57), and 2.30 (1.03-5.15), respectively. Additionally, the second quartile of perfluorododecanoic acid (PFDoA) was associated with a 3.2-fold increase in AD risk (3.24, 1.44-7.27). However, no significant associations were found in male children. CONCLUSIONS:Prenatal exposure to PFOA, PFDA, PFDoA and PFHxS significantly increased the risk of childhood AD in female children during the first 24 months of life. In addition, the associations between AD with prenatal exposure to PFNA were close to statistical significance.

Project description:BackgroundEvidence of associations between prenatal exposure to perfluoroalkyl substances (PFASs) and fetal thyroid hormones (THs) is controversial, and few studies have estimated the associations, while addressing the high correlations among multiple PFASs. We aimed to examine the associations between prenatal PFAS exposure and thyroid hormone concentrations in cord blood.MethodsA total of 300 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study were included. We measured the concentrations of eight PFASs in maternal plasma samples collected at 12-16 gestational weeks, as well as those of total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. We estimated the associations between maternal PFAS concentrations and TH concentrations using linear regression and Bayesian kernel machine regression (BKMR) models.ResultsIn BKMR models, higher PFAS mixture concentrations were associated with increased T3 concentrations, and there were suggestive associations with increased FT3 concentrations. For single-exposure effects in BKMR models, a change in PFDA, PFUdA, and PFOA concentrations from the 25th to 75th percentile was associated with a 0.04 (95%CrI: - 0.01, 0.09), 0.02 (95%CrI: - 0.03, 0.07), and 0.03 (95%CrI: - 0.001, 0.06) nmol/L increase in T3 concentrations, respectively. PFOA, PFNA, and PFDA were the predominant compounds in PFASs-FT3 associations, and the corresponding estimates were 0.11 (95% CrI: 0.02, 0.19), - 0.17 (95% CrI: - 0.28, - 0.07), and 0.12 (95% CrI: - 0.004, 0.24) pmol/L, respectively. A change in PFNA and PFOA concentrations from the 25th to 75th percentile was associated with a - 1.69 (95% CrI: - 2.98, - 0.41) μIU/mL decrease and a 1.51 (95% CrI: 0.48, 2.55) μIU/mL increase in TSH concentrations. The associations of PFOA and PFNA with T3/FT3 were more pronounced in boys, while those with TSH were more pronounced in girls.ConclusionOur results suggest that prenatal exposure to multiple PFASs was associated with thyroid hormones in cord blood. However, individual PFAS had varied effects-differing in magnitude and direction-on fetal thyroid hormones.

Project description:BackgroundPerfluoroalkyl substances (PFAS) may affect body mass index (BMI) and other components of cardiometabolic (CM) risk during childhood, but evidence is scarce and inconsistent.ObjectivesWe estimated associations between prenatal PFAS exposures and outcomes relevant to cardiometabolic risk, including a composite CM-risk score.MethodsWe measured perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in maternal plasma (first trimester). We assessed weight gain from birth until 6 mo. At 4 and 7 y, we calculated the age- and sex-specific z-scores for BMI, waist circumference (WC), and blood pressure (BP) (n≈1,000). At age 4, we calculated the age-, sex-, and region-specific z-scores for cholesterol, triglycerides (TGs), high-density (HDL-C), and low-density lipoprotein cholesterol (LDL-C) (n=627). At age 4, we calculated a CM-risk score (n=386) as the sum of the individual age-, sex-, and region-specific z-scores for WC, BP, HDL-C, and TGs. We used the average between the negative of HDL-C z-score and TGs z-score to give similar weight to lipids and the other components in the score. A higher score indicates a higher cardiometabolic risk at age 4.ResultsPFOS and PFOA were the most abundant PFAS (geometric mean: 5.80 and 2.32 ng/mL, respectively). In general, prenatal PFAS concentrations were not associated with individual outcomes or the combined CM-risk score. Exceptions were positive associations between prenatal PFHxS and TGs z-score [for a doubling of exposure, β=0.11; 95% confidence interval (CI): 0.01, 0.21], and between PFNA and the CM-risk score (β=0.60; 95% CI: 0.04, 1.16). There was not clear or consistent evidence of modification by sex.ConclusionsWe observed little or no evidence of associations between low prenatal PFAS exposures and outcomes related to cardiometabolic risk in a cohort of Spanish children followed from birth until 7 y. https://doi.org/10.1289/EHP1330.

Project description:BackgroundPer- and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied.ObjectivesWe investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age.MethodsMeasures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial photographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma (median=8 gestational wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log2-PFAS concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential confounders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child's sex were performed.ResultsPrenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluorodecanoic acid (PFDA; per doubling OR=2.02; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures.DiscussionPrenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits. https://doi.org/10.1289/EHP9478.

Dataset Information

Prenatal Exposure to Perfluoroalkyl Substances and Birth Outcomes; An Updated Analysis from the Danish National Birth Cohort.

Publications

Prenatal Exposure to Perfluoroalkyl Substances and Birth Outcomes; An Updated Analysis from the Danish National Birth Cohort.

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