Associations of prenatal phthalate exposure with neurobehavioral outcomes in 4.5- and 7.5-month-old infants

Authors: SPROWLES, JENNA - University Of Illinois; DZWILEWSKI, KELSEY - University Of Illinois; MERCED-NIEVES, FRANCHESKA - The Icahn School Of Medicine At Mount Sinai; MUSAAD, SALMA - Children'S Nutrition Research Center (CNRC); SCHANTZ, SUSAN - University Of Illinois; GEIGER, SARAH - University Of Illinois

Submitted to: Neurotoxicology and Teratology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/12/2022
Publication Date: 5/16/2022
Citation: Sprowles, J.L., Dzwilewski, K.L., Merced-Nieves, F.M., Musaad, S.M., Schantz, S.L., Geiger, S.D. 2022. Associations of prenatal phthalate exposure with neurobehavioral outcomes in 4.5- and 7.5-month-old infants. Neurotoxicology and Teratology. 92. Article 107102. https://doi.org/10.1016/j.ntt.2022.107102.
DOI: https://doi.org/10.1016/j.ntt.2022.107102

Interpretive Summary: Phthalates are common chemicals that can interfere with the hormone systems in the body. They are found in some foods, toys, plastic bottles, and cosmetics. Some research studies indicate that exposure to phthalates in pregnancy may affect brain development in infants. In this study, phthalates were measured in the urine of pregnant mothers. After birth, we asked the mothers to report on the infant's communication, social, problem solving, and motor activities using a questionnaire. We found that some phthalates delayed these activities. More longitudinal studies are needed to confirm these findings.

Technical Abstract: Phthalates are ubiquitous endocrine-disrupting chemicals, and research indicates that prenatal exposure to some phthalates may affect neurodevelopment. In a prospective birth cohort study, five first-morning urine samples collected across pregnancy were pooled and the following phthalate biomarkers assessed: sum of di-(2-ethylhexyl) phthalate metabolites (sum of DEHP), sum of diisononyl phthalate metabolites (sum of DINP), sum of dibutyl phthalate metabolites (sum of DBP), sum of anti-androgenic metabolites (sum of AA), monoethyl phthalate (MEP), and sum of all phthalate metabolites (sum of All). The Ages & Stages Questionnaires (ASQ), a standardized parent-reported, age-adapted screening tool, measured communication, personal-social, problem solving, and motor domains in infants at 4.5 and 7.5 months (n=123). Adjusting for maternal age, annual household income, gestational age at birth, infant age at assessment, and sex, repeated-measures generalized linear regression models were used to examine associations between prenatal phthalate urine biomarker concentrations and domain scores (assuming a Poisson distribution). Beta estimates were exponentiated back to the domain scale for ease of interpretation. Mothers were mostly white and college-educated, and most reported an annual household income of >=$60,000. Associations of phthalate concentrations with ASQ outcomes are presented as follows: (1) anti-androgenic phthalate metabolites (sum of DEHP, sum of DINP, sum of DBP, and sum of AA), (2) MEP, which is not anti-androgenic, and (3) sum of All. Overall, anti-androgenic phthalates were associated with higher (i.e., better) scores. However, there were exceptions, including the finding that a one-unit increase in SDBP was associated with a 12% increase in problem solving scores in 4.5-month-old females (Beta=1.12; 95% CI: 0.99, 1.28; p=0.067) but a 85% decrease for 7.5-month-old females (Beta=0.54; 95% CI: 0.3, 0.99; p=0.047). In contrast, MEP was associated with poorer scores on several outcomes. Sex- and timepoint-specific estimates demonstrated a one-unit increase in MEP was associated with: a 52% decrease in personal-social scores in 7.5-month-old males (Beta=0.66; 95% CI: 0.46, 0.95; p=0.02), a 39% decrease in fine motor scores in 7.5-month-old males (Beta=0.72; 95% CI: 0.52, 0.98; p=0.035), and a 6% decrease in fine motor scores in 4.5-month-old females (Beta=0.94; 95% CI: 0.88, 0.99; p=0.03). A one-unit increase in SAll was associated with a 4% increase in personal-social scores in 4.5-month-old males (Beta=1.04; 95% CI: 0.99, 1.1; p=0.08) but a 17% decrease in 7.5-month-old males (Beta=0.85; 95% CI: 0.73, 0.99; p=0.03). These data suggest age- and sex-specific associations of prenatal phthalates with infant neurobehavior. The current findings should be confirmed by longitudinal studies with larger sample sizes.