Trimester-specific and sex-specific effects of prenatal exposure to di(2-ethylhexyl) phthalate on fetal growth, birth size, and early-childhood growth: A longitudinal prospective cohort study.

Prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) may cause adverse health outcomes. However, trimester-specific impacts of DEHP exposure on offspring growth from fetal to early childhood stage have not been thoroughly evaluated. In this study, participants who provided a full series of urine specimens at three trimesters were selected from a birth cohort conducted at Wuhan, China from 2014 to 2015. 814 mother-offspring pairs were included in the study. Urinary concentrations of DEHP metabolites were determined using liquid chromatography-tandem mass spectrometry. Z-scores for ultrasound-measured fetal growth parameters at 14.0-18.9, 22.6-27.0, and 29.0-33.9 weeks of gestation, were calculated. Weight, height, and body mass index (BMI) at 6, 12, and 24 months were standardized to z-scores using sex-specific and age-specific WHO child growth standards. Linear regressions with generalized estimating equations were used to assess the relationships of DEHP levels per trimester to fetal growth, birth size, and growth at 6, 12, and 24 months to explore the trimester-specific impacts of DEHP exposure on offspring development. Among males, the1st-trimester DEHP was negatively related to fetal growth (β < 0, p < 0.05), but positively related to 24-month BMI. The 2nd-trimester DEHP was negatively related to birth weight and birth length, but positively related to weight gain rates from birth to 24 months old. The 3rd-trimester DEHP was positively (β > 0, p < 0.05) associated with birth weight and BMI at 6 and 12 months. Among females, the 1st-trimester DEHP was associated with increased birth length, while the 2nd-trimester DEHP was negatively associated with BMI at 6 and 12 months. A negative association between DEHP and weight gain rates at 6 months was noted among females. This prospective cohort revealed the sex-specific and trimester-specific relationships of DEHP exposure to offspring growth from fetal to early-childhood stage.