Prenatal exposure to per- and polyfluoroalkyl substances and cognitive development in infancy and toddlerhood

https://doi.org/10.1016/j.envres.2021.110939Get rights and content

Highlights

  • We investigated prenatal exposure to PFAS in association with cognitive development.

  • Prenatal PFOA was inversely associated with MSEL scores at 24 and 36 months of age.

  • Longitudinally, PFOA was inversely associated with MSEL scores from 6 to 36 months.

  • In trajectory analysis, PFOA and PFNA were associated with risk of cognitive deficit.

Abstract

Background/Objective

Per- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal serum PFAS concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood.

Methods

We included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson regression models to estimate associations expressed as relative risks (RR).

Results

Among six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (β = −5.22, 95% CI: −8.27, −2.17) and 36 months of age (β = −5.18, 95% CI: −9.46, −0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03).

Conclusions

Prenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.

Section snippets

Background

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic fluorine-containing compounds that have been widely used in consumer and industrial applications, including non-stick cookware, food packaging materials, and stain- and water-repellent fabrics (ATSDR 2018). The widespread applications of PFAS in consumer products resulted in ubiquitous detection of several PFAS in serum of the general U.S. population (CDC 2019; Kato et al., 2011a; Olsen et al., 2017). PFAS have also been

Study population

The present study included participants from MARBLES (Markers of Autism Risk in Babies – Learning Early Signs) (Hertz-Picciotto et al., 2018). Launched in 2006, the MARBLES study is an ongoing cohort that follows pregnant women who previously had a child diagnosed with autism spectrum disorder (ASD) and are thus at high risk (~28%) of having a child with delays or deficits in areas of development or behavior (Ozonoff et al., 2014). Participants are mostly recruited from the lists of families

Participant characteristics and MSEL scores

Of the 140 mother-child pairs included in the current study, 59% of children were males and 91% were full-term birth children (Table 1). Approximately 20% of mothers were obese before pregnancy, 19% had gestational diabetes, and 54% were multiparous at study enrollment. The majority of mothers were non-Hispanic white (51%) and were high school graduate or had some college credit without a degree in higher education (45%). There was no difference in population characteristics between this study

Discussion

To better understand the potential effect of prenatal maternal exposure to PFAS on child's cognitive development, we used prenatal maternal serum PFAS concentrations and child's MSEL scores repeatedly evaluated at four time points (i.e., 6, 12, 24, 36 months of age) in the MARBLES cohort study and examined both cross-sectional associations at each time point and longitudinal associations over four assessment time points. To our knowledge, this is the first study that reported cross-sectional

Conclusions

In this prospective birth cohort study, prenatal maternal serum PFOA was associated with decreased scores of cognitive functions throughout infancy and toddlerhood among children who had an older sibling diagnosed with ASD. Further, we observed modified associations of PFOA, PFHxS, and PFNA with cognitive development at 12 months of age by breastfeeding duration. Because the current study included a large fraction of children with developmental delays or cognitive deficits, population-based

Ethics approval and consent to participate

The MARBLES study protocol and this study were approved by the institutional review boards for the State of California, the University of California-Davis (UC-Davis), and the University of Texas-Arlington (UT-Arlington). Participants provided written informed consent before collection of any data. The analysis of coded specimens at the Centers for Disease Control and Prevention (CDC) laboratory was determined by CDC not to constitute engagement in human subject research.

Consent for publication

Not applicable.

Availability of data and material

Portions of the datasets generated and analyzed during this study are publicly available in the National Institute of Mental Health (NIMH) Data Archive. The entire non-identifiable dataset is available from the authors upon reasonable request and with permission from the IRBs at UT-Arlington and UC-Davis.

Funding

This research was supported by grants from the National Institute of Environmental Health Sciences (R21-ES028131, R01-ES020392) and was supported in part by the UC Davis MIND Institute Intellectual and Developmental Disabilities Research Center (U54 HD079125); and the U.S. Environmental Protection Agency STAR #R829388, R833292, and RD83543201.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.

Author's contributions

JO and HS conceived the study and IH oversaw its coordination. JO conducted data analyses and drafted the initial manuscript. HS, RS and IH helped oversee the study. AC quantified PFAS in maternal serum samples. DT advised on data analysis, interpretation, and reporting. DR oversaw cognitive assessment of children. All authors read and approved the final manuscript.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RJ has received lodging for the Baby Siblings Research Consortium Meeting; travel and lodging for invited talks at the University of Sherbrooke, Sherbrooke, Québec, Canada; the University of California Santa Cruz. Santa Cruz, California (Lodging); Epigenomics 2016, Puerto Rico (Lodging); Neurotoxicity Society & International Neurotoxicology Association,

Acknowledgements

Authors would like to acknowledge the MARBLES participants for helping make this research possible. The authors also wish to thank Kayoko Kato for the quantification of the serum PFAS concentrations.

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