Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age

Abstract

Background: Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life.

Objectives: To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age.

Methods: This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level.

Results: No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β=-2.11 [95% CI: -3.73, -0.49]), MEHHP (β=-1.89 [95% CI: -3.64, -0.15]), MEOHP (β=-1.80 [95% CI: -3.58, -0.03]) MECPP (β=-2.52 [95% CI: -4.44, -0.61]), and ΣDEHP (β=-3.41 [95% CI: -5.26, -1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β=1.79 [95% CI: 0.14, 3.45]) and MCPP (β=1.64 [95% CI: 0.15, 3.12]); there was no significant effect on PDI among girls.

Conclusion: This study demonstrates that sex plays a role of an effect modifier in the association between prenatal phthalate exposure and neurodevelopment.

Keywords: BSID II; Biomarkers; CDC; CI; Centers for Disease Control and Prevention; Child development; DEHP; HMWP; LMWP; LOD; Longitudinal study; MBzP; MCPP; MDI; MECPP; MEHHP; MEHP; MEOHP; MEP; Mental Development Index; MiBP; MnBP; Mono-(3-carboxypropyl) phthalate; Mono-ethyl phthalate; Mono-n-butyl phthalate; PDI; Phthalates; Prenatal exposure; Psychomotor Development Index; SG; confidence interval; di-2-ethylhexyl phthalate; high molecular weight phthalates; limit of detection; low molecular weight phthalates; mono-(2-ethyl-5-carboxypentyl) phthalate; mono-(2-ethyl-5-hydroxyhexyl) phthalate; mono-(2-ethyl-5-oxohexyl) phthalate; mono-2-ethylhexyl phthalate; mono-benzyl phthalate; mono-isobutyl phthalate; specific gravity; sum of di-2-ethylhexyl phthalate metabolites; the Bayley Scales of Infant Development II; ΣDEHP.