Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study

Cecilie Skaarup Uldbjerg; Jordana Leader; Lidia Minguez-Alarcon; Olivia Chagnon; Ramace Dadd; Jennifer Ford; Elvira Fleury; Paige Williams; Anders Juul; David C Bellinger; Antonia M Calafat; Russ Hauser; Joseph M Braun

doi:10.1016/j.envres.2024.120253

Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study

Environ Res. 2024 Oct 30;263(Pt 3):120253. doi: 10.1016/j.envres.2024.120253. Online ahead of print.

Authors

Affiliations

¹ Department of Growth and Reproduction, Copenhagen University Hospitalet - Rigshospitalet, Copenhagen, Denmark; International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMARC), Copenhagen University Hospitalet - Rigshospitalet, Copenhagen, Denmark.
² Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
³ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Harvard Medical School & Brigham and Women's Hospital, Boston, MA, USA.
⁴ Department of Epidemiology, Brown University, Providence, RI, USA.
⁵ Departments of Biostatistics and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁶ Department of Growth and Reproduction, Copenhagen University Hospitalet - Rigshospitalet, Copenhagen, Denmark; International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMARC), Copenhagen University Hospitalet - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁷ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Cardiac Neurodevelopment Program, Boston Children's Hospital, Boston, MA, USA; Department of Neurology and Psychology, Harvard Medical School, Boston, MA, USA.
⁸ National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁹ Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Epidemiology, Brown University, Providence, RI, USA. Electronic address: joseph_braun_1@brown.edu.

PMID: 39486680
DOI: 10.1016/j.envres.2024.120253

Abstract

Background: Environmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures.

Methods: In 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004 and 2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n = 179), paternal preconception (n = 121), and maternal pregnancy (n = 177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors.

Results: The mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (β_{maternal_precon} = -1.6, 95% CI -2.7; -0.4; β_{paternal_precon} = -2.9, 95% CI -4.6; -1.2) for each log_e increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations.

Conclusions: Urinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

Keywords: Autism; Bisphenol A; Endocrine disrupting chemicals; Offspring health; Phthalates; Preconception; Pregnancy.