Association of prenatal exposure to phthalates with measures of cognition in 4.5-month-old infants

Abstract

Background: Phthalates are endocrine disrupting chemicals found in consumer products. Previous studies reported associations of prenatal phthalate exposure with adverse child neurodevelopment, but few assessed the impact on cognitive development in early infancy. Methods: As part of a prospective cohort study, physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants. Phthalate metabolites were quantified in urine collected at 16-18 weeks of pregnancy and a pool of five urines collected across pregnancy. Infants’ looking times to a physically impossible and a possible event were recorded via infrared eye-tracking. At 4.5 months, females recognize this impossible event, as indicated by longer looking at the impossible versus possible event. Males demonstrate this knowledge 4-6 weeks later. Associations of phthalate biomarkers with looking time differences (impossible - possible) were adjusted for infant age, household income, maternal age, education, and order of event presentation and assessed with multivariable general linear models stratified by sex. Results: Mothers were mostly white and college educated with household incomes >$60,000. Each interquartile range (IQR) increase of the sum of di(2-ethylhexyl) phthalate metabolites at 16-18 weeks (0.054 µmol/L) was associated with females’ 1.7 seconds (95%CI=0.2, 3.1) increased looking to the impossible event. For males, an IQR increase in the sum of di(isononyl) phthalate metabolites at 16-18 weeks and the pooled sample (β=-1.1; 95%CI=-1.9,-0.4 and β=-1.2; 95%CI=-2.3,-0.05 seconds per 0.035-0.036 µmol/L, respectively), the sum of Anti-Androgenic phthalate metabolites in the pooled sample (β=-3.8; 95%CI=-6.4, -1.2 seconds per 0.17 µmol/L), and the sum of metabolites at 16-18 weeks (β=-3.1; 95%CI=-5.3, -0.9 seconds per 0.37 µmol/L) were associated with increased looking to the possible event— typical behavior of early learning stages about a physical event. Conclusion: Results need corroboration in a larger sample, but suggest that higher prenatal phthalate exposure may be associated with delays in males’ physical reasoning. ES007326;ES022848;RD83543401;OD023272.