Association Of Prenatal Exposure To Perfluoroalkyl And Polyfluoroalkyl Substances With Telomere Length In Newborns

Perfluoroalkyl and polyfluoroalkyl substances（PFASs）are a type of persistent organic pollutants（POPs）that have been widely used in industrial and consumer products for decades.In many parts of the world,PFASs have been detected in human,wild animals,plants samples.Telomere is a small piece of DNA-protein complex that exists at the end of linear chromosomes in eukaryotic cells,and has a tandem TTAGGG repeat structure at the end of the chromosome.Telomere length（TL）is considered to be a marker of biological aging,and is related to diseases such as tumors.TL of newborns is affected by environment in the uterus.Although some studies have shown that exposure to environmental pollutants affects human telomere length,the effect of exposure to PFASs during pregnancy with TL of newborns is still unclear.The present study was aimed to explore the association of exposure to PFASs during pregnancy with TL in newborns.Part 1:Exposure Levels of Perfluoroalkyl and Polyfluoroalkyl Substances during pregnancy and their influencing factorsObjective:This part of the study was aimed to assess the exposure levels of PFASs during pregnancy and analyze the exposure influencing factors.Methods:In this part of the study,1047 mother-infant pairs recruited in Wuhan Maternal and Child Health Center from 2013 to 2014 were selected as the research objects.Basic information of the pregnant women and their babies was obtained from electronic medical records,and social demographic information of pregnant women was obtained by questionnaires.To reveal the exposure level of PFASs during pregnancy,the concentration of 12 PFASs in cord blood serum were deteced,including plsfluorooctanoic acid（PFOA）,perfluorononanoic acid（PFNA）,perfluorodecanoic acid（PFDA）,perfluoroundecanoic acid（PFUn DA）,perfluorododecanoic acid（PFDo DA）,perfluorotridecanoic acid（PFTri DA）,perfluorotetradecanoic acid（PFTe DA）,perfluorobutane sulfonic acid（PFBS）,perfluorohexane sulfonate（PFHx S）,perfluorooctane sulfonate（PFOS）,6:2 chlorinated polyfluorinated ether sulfonate（6:2 Cl-PFESA）,8:2 chlorinated polyfluoninated ether sulfonate（8:2 Cl-PFESA）.The generalized linear lodel（GENMOD）was used to evaluate the influencing factors of PFASs exposure during pregnancy.False Discovery Rate（FDR）was used to correct the P value.Results:1.A total of 12 PFASs were detected in this study,of which 9 types were detected with a detection rate of>90%.The detection rate of PFOA,PFNA,PFUn DA,PFHx S,PFOS,6:2 Cl-PFESA were 100%.Among the 12 PFASs,PFOS and PFOA had the highest concentration.The median concentration from high to low is:PFOS（4.03ng/m L）>PFOA（1.59ng/m L）>6:2 Cl-PFESA（0.76ng/m L）>PFHx S（0.40ng/m L）>PFNA（0.27ng/m L）>PFUn DA（0.19ng/m L）>PFDA（0.15ng/m L）>PFTri DA（0.11ng/m L）>PFBS（0.05ng/m L）>8:2Cl-PFESA（0.03ng/m L）>PFDo DA（0.02ng/m L）>PFTe DA（0.01ng/m L）.2.Mothers aged<28 years old at delivery,cord blood concentrations of PFNA,PFDA,PFHx S,PFOS,6:2 Cl-PFESA,8:2 Cl-PFESA concentrations were lower than those of pregnant women aged≥28 years old at delivery.Mothers received education≤12years had higher cord blood concentrations of PFDA,PFOS,6:2 Cl-PFESA,8:2Cl-PFESA than mothers received education>12 years.Mothers with pre-pregnancy body mass index（BMI）（kg/m²）<18.5 and 18.5-24 had higher exposure concentrations of PFUn DA,PFDo DA,PFTri DA,PFTe DA,6:2 Cl-PFESA,8:2 Cl-PFESA than the mothers with pre-pregnancy BMI≥24.Compared with the postpartum,the concentrations of PFDA,PFUn DA,PFDo DA,PFTri DA and PFTe DA in the primipara were lower.Mothers with hypertension in pregnancy had higher exposure concentrations of PFNA,PFDA,PFDo DA,PFHx S,PFOS,8:2 Cl-PFESA but lower PFBS concentration.The concentration of PFTe DA in pregnant women who gave birth to boys were lower than those of pregnant women who gave birth to girls.Conclusions:1.PFASs exposures were widely detected in pregnant women,the highest concentrations of the detected PFASs was PFOS and PFOA.2.Maternal age,educational level,pre-pregnancy BMI,parity,hypertension in pregnancy,and infant gender may affect the exposure levels of PFASs during pregnancy.Part 2:Association of Prenatal Exposure to Perfluoroalkyl and Polyfluoroalkyl Substances with Telomere Length in NewbornsObjectives:This part of the study was aimed to analyze the impact of PFASs exposure levels on TL of newborns,and explore the modification of maternal age,pre-pregnancy BMI,and infant gender.Methods:This part of the study population was a subgroup of the first part.The 169mother-infant pairs who had complete covariate information and data about telomere length in cord blood were included for this study.Fluorescence quantitative PCR was used to detect telomere length in cord blood.GENMOD was used to analyze the relationship of the exposure levels of 12 PFASs during pregnancy with TL in newborns.Stratified analysis by maternal age,pre-pregnancy BMI,and infant gender were performed.FDR was used to correct the P value.Result:1.After adjusting for confounding factors,in the 169 mother-infant pairs,the concentrations of PFUn DA,PFDo DA,PFTri DA,and PFTe DA during pregnancy are positively assocaited with TL in newborns.（PFUn DAβ=0.088,95%CI:0.010,0.166;PFUn DAβ=0.070,95%CI:0.004,0.135;PFTri DAβ=0.121,95%CI:0.051,0.191;PFTe DAβ=0.129,95%CI:0.048,0.210）.2.In the analysis stratified by infant gender stratification,the concentrations of PFASs in cord blood were not associated to the TL in female infants,while PFNA,PFDA,PFUn DA,PFDo DA,PFTri DA,PFTe DA,6:2 Cl-PFESA,8:2 Cl-PFESA were positively associated with the TL in male infants.In the analysis stratified by maternal age stratification,the concentrations of PFASs in cord blood were not associated to the TL in mothers aged≥28 years old at delivery,while PFNA,PFDA,PFUn DA,PFDo DA,PFTri DA,PFTe DA,6:2 Cl-PFESA,8:2 Cl-PFESA were positively associated with the TL in mothers aged<28 years old at delivery.The interaction items between the above two stratification factors and PFASs are statistically significant(P_interaction<0.05).In the analysis stratified by pre-pregnancy BMI stratification,the concentrations of PFUn DA,PFTri DA,PFTe DA,8:2 Cl-PFESA in cord blood were associated to the TL in mothers with pre-pregnancy BMI<24kg/m²,while PFDA,PFUn DA,PFDo DA,PFTri DA,PFTe DA,6:2 Cl-PFESA,8:2 Cl-PFESA were positively associated with the TL in mothers with pre-pregnancy BMI≥24kg/m².The interaction items between pre-pregnancy BMI and PFASs were not statistically significant(P_interaction>0.05).Conclusion:PFNA,PFDA,PFUn DA,PFDo DA,PFTri DA,PFTe DA,6:2 Cl-PFESA,8:2 Cl-PFESA exposures were associated with telomere length of newborns,and the associations were modified by infant gender,maternal age.The associations between PFASs exposures and telomere length were more significant in male infants.