Prenatal phthalate exposure, birth outcomes and DNA methylation of Alu and LINE-1 repetitive elements: A pilot study in China

Background: Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes. Objective: To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort. Methods: Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis. Results: We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood, For example, the molar sum of di-2-(ethylhexyl) phthalate (Sigma DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P < 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P < 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes. Conclusion: Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood. (C) 2018 Elsevier Ltd. All rights reserved.