Associations Of Prenatal Phthalates Exposure,DNA Methylation Of Cord Blood And Birth Outcomes

Objective: To explore the mediating role of DNA methylation in associations between prenatal phthalates exposure and birth outcomes in a perspective study.Methods: Eight phthalate metabolites in maternal urine before delivery were measured using high performance liquid chromatography-tandem mass spectrometry among 106 mother-infant pairs.DNA methylation of Alu and long interspersed nucleotide elements(LINE-1)in cord blood were determined using high-quantitative bisulphite polymerase chain reaction pyrosequencing.The associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation were assessed by general linear regression models,and the mediating role of DNA methylation in cord blood was evaluated by mediation analysis.Results: Maternal urinary phthalate metabolites were detectable in > 90% of the samples,except for mono-n-octyl phthalate(MOP)(< 40%).We found mono(2-ethyl-5-hydroxyhexyl)phthalate(MEHHP),mono(2-ethyl-5-oxohexyl)phthalate(MEOHP)were inversely associated with birth length(?=-0.16,95%CI:-0.28,-0.04;?=-0.17,95%CI:-0.30,-0.04,respectively);urinary monobenzyl phthalate(MBz P),mono-(2-ethylhexyl)phthalate(MEHP),MEOHP were positively associated with gestational age(?=0.16,95%CI: 0.03,0.29;?=0.12,95%CI: 0.03,0.22;?=0.18,95%CI: 0.01,0.35,respectively);the inverse associations of maternal urinary MBz P and mono-n-butyl phthalate(MBP)with cord blood Alu methylation were also observed(?=-0.14,95%CI:-0.27,-0.01;?=-0.15,95%CI:-0.28,-0.03,respectively).After fetal sex stratification,the inverse association of MEHHP,MEOHP with birth length were observed both in male and female newborns(P<0.05);the positive association of MBz P with gestational age was observed among male newborns only(P<0.05).The associations of urinary MBz P with Alu and LINE-1methylation was found among female newborns whereas the association of urinary MBP with Alu methylation was found among female newborns(P<0.05).Nevertheless,mediation analysis did not find DNA methylation in cord blood to be a direct mediator in the associations between maternal urinary phthalate metabolites and birth outcomes.Conclusions: Prenatal certain phthalates exposure is associated with altered birth birth weight,birth length and gestational age,as well as decreased Alu and LINE-1 methylation of newborns.However,the adverse birth outcomes exerted by prenatal phthalates exposure does not seem to be directly mediated through repetitive elements methylation of cord blood.Further studies are needed to confirm these findings.