Prenatal and early childhood exposure to phthalates and neurodevelopment in 42 months old children

Increased prevalence of neurodevelopmental syndromes raises concerns regarding risks from environmental exposures. Phthalates are a class of chemicals widely used in daily products. It has been suggested that prenatal and early childhood exposure to phthalates are associated with disruption of developmental outcomes, cognitive and psychomotor functions.

To estimate the association between prenatal and early childhood exposure to phthalates and neurodevelopmental outcomes.

Women were recruited at 11-18 weeks of gestation and provided spot urine samples, analyzed for phthalate metabolites (DEHP, DiNP, MBzBP). Children (n = 102) were examined at 42 months of age, using a broad developmental assessment and standard maternal reports, regarding cognitive, developmental and behavioral problems (WPPSI-III, NIH-toolbox, NEPSY-II, CBCL, ASQ-3 questionnaires), and provided spot urine samples (n = 47). To explore the associations between tertiles or continuous levels of metabolites and developmental outcomes, multivariate general linear models (GLM) were used.

DEHP and DiNP metabolites were above the level of detection (>LOD) in more than 97 % of maternal specimens and MBzBP was detected in 88 % of maternal specimens. Increased DEHP levels were associated with problem solving scores among boys (scores: 53.24 + 2.34, 54.29 + 2.45, and 43.54 + 3.26 for low, medium and high DEHP tertiles, respectively; p = 0.029), and fine motor problems (47.58 + 2.93, 49.75 + 3.07, and 32.01 + 4.07 for low, medium and high DEHP tertiles, respectively; p = 0.003) and attention problems among girls (Flanker scores: 112.53 + 14.28, 110.3 + 12.93, and 98.83 + 12.65 for low, medium and high DEHP tertiles, respectively; p = 0.007). Moreover, in girls, a potential U-shaped association was found between levels of exposure to MBzBP and problem solving (54.55 + 6.87, 44.69 + 14.88, and 54.62 + 6.60 for low, medium and high MBzBP tertiles, respectively; p = 0.015), fine motor problems (56.36 + 5.04, 42.50 + 15.49, and 51.92 + 8.04 for low, medium and high MBzBP tertiles, respectively; p = 0.007), and verbal abilities (Vocabulary scores: 11.46 + 3.01, 8.25 + 3.43, and 11.53 + 2.69 for low, medium and high MBzBP tertiles, respectively; p = 0.007). Early childhood exposure was associated with fine motor scores and DEHP and MBzBP postnatal exposure (DEHP: β = -0.010, Cl: -0.016, -0.004, p = 0.003; MBzBP: β = -0.321, Cl: -0.499, -0.144, p = 0.001). Most associations became nonsignificant after FDR correction for multiple comparisons.

This study suggests associations between prenatal exposure to phthalates and early childhood motor and cognitive abilities, with sex differences, and an association between early childhood exposure with motor abilities. Larger studies are needed to confirm these exploratory findings.