Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study.
Level 3 - non-randomized controlled study
Prospective observational cohort study with follow-up
PubMed 39486680 · doi:10.1016/j.envres.2024.120253
What was done
In the PEACE cohort of 195 children born to parents recruited from a Boston fertility clinic between 2004 and 2017, investigators measured 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers preconception (n = 179), fathers preconception (n = 121), and mothers during pregnancy (n = 177). When children were 6 to 15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire. Linear mixed-effects models estimated covariate-adjusted associations between log e-transformed biomarker concentrations and age- and gender-standardized SRS T-scores. Quantile g-computation models evaluated chemical mixtures, and effect modification by maternal preconception folate and iron intake was examined in a subset.
What was found
The mean offspring SRS T-score was 47.7 (±7.4). Most individual biomarker and mixture associations were negative and imprecise. Higher mono-isobutyl phthalate (MiBP) concentrations were associated with lower SRS T-scores per log e unit increase during maternal preconception (β = -1.6, 95% CI -2.7 to -0.4) and paternal preconception (β = -2.9, 95% CI -4.6 to -1.2). Stronger inverse associations were observed in subsets with higher maternal preconception folate and iron intake, especially for folate and MiBP. Urinary phthalates and BPA across preconception and pregnancy periods were not associated with adverse autistic behaviors.
Why it matters
This study adds prospective human data assessing both maternal and paternal preconception exposures alongside pregnancy exposures, finding no evidence that urinary phthalates or BPA increased parent-reported autistic behaviors in this cohort.
Limits
The sample size was modest (n = 195 overall; n = 121 for paternal preconception), yielding imprecise estimates. Participants were recruited from a single fertility clinic, limiting generalizability to the general population. Autistic behaviors were evaluated using parent-completed SRS screening questionnaires rather than formal clinical diagnostic evaluations. Unmeasured confounding or multiple testing may explain the counterintuitive inverse associations observed with MiBP.