Cumulative risk assessment of phthalates associated with birth outcomes in pregnant Chinese women: A prospective cohort study

A prospective cohort study of a Chinese population of mother-neonate pairs (n = 3103) was conducted to investigate the relationship between the cumulative hazard index (HI) of combined diethyl phthalate (DEP), dibutyl phthalate (DBP), dibenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) exposure and birth outcomes. The estimated HI for phthalates was based on phthalate metabolite concentrations in urine collected between 5th and 14th gestational weeks. The median HI values according to the European Food Safety Authority tolerable daily intake (HITDI) and U.S. Environmental Protection Agency reference dose (HIRfD) were 0.358 and 0.187, respectively. A total of 16.3% and 1.9% of the women exhibited HITDI and HIRfD exceeding the value of one, respectively. In unadjusted models, the categories (low < P25, median P25-P50, high > P75) of HITDI were associated with decreased birth weight (β = -26.34 g, p = 0.021) and head circumference (β = -0.09 cm, p = 0.029), whereas those for HIRfD were negatively associated with birth weight (β = -31.74 g, p = 0.005), birth length (β = -0.11 cm, p = 0.032), head circumference (β = -0.13 cm, p = 0.003) and chest circumference (β = -0.10 cm, p = 0.021) in all neonates. Adjustment for potential confounders revealed that HIRfD was inversely associated with head circumference (β = -0.10 cm, p = 0.020). Stratification by gender indicated that HIRfD was associated with decreased birth length (β = -0.17 cm, p = 0.041) in infant boys and HITDI was associated with decreased birth weight (β = -33.12 g, p = 0.036) and head circumference (β = -0.13 cm, p = 0.027) in girls. This is the first study on the cumulative risk assessment of phthalate exposures in pregnant Chinese women. We found that the HI values of multiple phthalate co-exposure were sex-specifically related to birth outcomes.