Study On The Effect Of Exposure To Polycyclic Aromatic Hydrocarbons And Phthalates During Early Pregnancy On Neonatal Birth Outcomes

Objective:1.To understand the internal exposure level of polycyclic aromatic hydrocarbons and Phthalate metabolites in the urine of pregnant women.2.To explore the influence of polycyclic aromatic hydrocarbons(PAHs)and Phthalate metabolites exposure in early pregnancy on newborn birth outcomes.Methods:In this study,women in the first trimester were enrolled in the First Hospital of Shanxi Medical University and Hubei Maternal and Child Health Hospital from October2020 to August 2021.Pregnant women were instructed to fill in the baseline questionnaire and collect urine samples in the first trimester.Relevant factors were extracted according to the questionnaire,including demographic characteristics,pregnancy-related factors,maternal behavior and lifestyle,and dietary status.Neonatal birth outcome information was collected from the hospital medical record system.10 PAHs metabolites and 10 PAEs metabolites were detected by high-performance gas chromatography mass spectrometry(GC-MS/MS).The 10 metabolites of PAHs were1-OHNap,2-OHNap,2-OHFlu,9-OHFlu,4-OHPhe,9-OHPhe,3-OHPhe,1-OHPhe,2-OHPhe and 1-OHPyr,respectively.The 10 phthalate metabolites are MMP,MEP,MBP,Mi BP,MOP,MBz P,MEHP,MEHHP,MEOHP and MECPP.The effect of creatinine level corrected on urine concentration was determined.In this study,a linear regression Pattern was used to explore the effects of PAHs and phthalate exposure on birth weight,birth length,birth gestational age and Ponderal index,and a stratified analysis of birth outcomes by sex was conducted to explore gender differences.Results:1.Internal exposure levels of polycyclic aromatic hydrocarbons and phthalates in pregnant womenThe highest detection rate of PAHs metabolites in pregnant women urine was9-OHPhe(82.04%).9-OHFlu had the highest concentration,with a median creatinine-adjusted concentration of 0.127(μg/g Cr).The median concentration of1-OHPyr was the lowest among the eight PAHs metabolites(0.005μg/g Cr).The detection rates of MEP,MBP,Mi BP,MEHHP and MECPP in urine PAEs metabolites of pregnant women were more than 98%.MECPP had the highest median creatinine concentration after correction(207.12μg/g Cr),MOP and MBz P had the lowest median creatinine concentration after correction(0.11 and 0.10μg/g Cr,respectively).2.Relationship between exposure to individual PAHs or PAEs metabolites and birth outcomesIn this study,a total of 15 variables were selected as confounding factors,including age,education level,pre-pregnancy BMI,pregnancy weight gain,and pre-pregnancy smoking history,drunkenness in the past year,passive smoking during pregnancy,daily use of skin care products,and staple foods,fish and shrimp,fruits,milk and dairy products,tea,pickled vegetables,smoked or barbecued foods.(1)In the relationship between single PAHs or PAEs metabolites and birth weight,the effects of 9-OHPhe,4-OHPhe,∑OHFlu,2-OHFlu and MMP on birth weight were statistically significant(P<0.05).The effects of 9-OHPhe on the birth weight of both boys and girls were statistically significant(P<0.05).The effects of ∑OHFlu,2-OHFlu and 4-OHPhe on the birth weight of male infants were statistically significant,but had no effect on the birth weight of female infants.MEHP only had a statistically significant effect on birth weight of male infants(P=0.035).(2)In the relationship between single PAHs or PAEs metabolites and birth length,the effects of 9-OHPhe and MMP on birth length were statistically significant(P<0.05).The effects of 9-OHPhe and 4-OHPhe on the birth length of male infants were statistically significant(P<0.05),but had no effect on the birth length of female infants.(3)In the relationship between single PAHs or PAEs metabolites and gestational age,after adjusting for confounding factors,the effects of 9-OHPhe,1-OHPyr,MMP and MBz P on gestational age were statistically significant(P<0.05).MMP had a statistically significant effect on the gestational age of female infants(P=0.025),but had no effect on the gestational age of male infants.MBz P had a statistically significant effect on the gestational age of male infants(P=0.010),but had no effect on the gestational age of female infants.The effects of 9-OHFlu and ∑OHFlu on the gestational age of male infants were statistically significant(P<0.05).(4)In the relationship between individual PAHs or PAEs metabolites and Ponderal index,after adjusting for confounders,The effects of 9-OHPhe,3-OHPhe,1-OHPhe,4-OHPhe,∑OHFlu,2-OHFlu,9-OHFlu,MECPP and ∑DEHP on neonatal Ponderal index were statistically significant(P<0.05).The effects of 9-OHPhe,4-OHPhe,∑OHFlu,2-OHFlu and 9-OHFlu on the Ponderal index of male infants were statistically significant(P<0.05),but had no effect on the Ponderal index of female infants.3.Relationship between mixed exposure to PAHs and PAEs metabolites and birth outcomes(1)Among the relationship between mixed exposure of PAHs and PAEs metabolites and birth weight,Pattern3 is a good model reflecting the influence of mixed exposure of PAHs and PAEs metabolites on birth weight.In Pattern3,controlling for other covariables unchanged,the effects of 9-OHPhe,∑OHFlu and MMP on birth weight were statistically significant(P<0.05).The birth weight increased by 44.268(95%CI: 18.526～70.010)and 24.850(95%CI: 0.769～ 48.931)g for each increase of natural logarithm of9-OHPhe and ∑OHFlu,respectively.Birth weight decreased by 32.467(95%CI:-51.484-13.451)g for each increase in natural logarithm of MMP.(2)The relationship between PAHs and PAEs metabolites mixed exposure and birth length was established.After adjusting for confounding factors,the effects of 9-OHPhe and MMP on birth length were statistically significant(P<0.05).Birth length increased by about 0.158(95%CI: 0.061～ 0.256)cm for every increase in the natural logarithm of9-OHPhe.For each increase in natural logarithm of MMP,birth length decreased by0.104(95%CI:-0.179 ～-0.028)cm.(3)Among the relationship between mixed exposure of PAHs and PAEs metabolites and birth gestational age,Pattern3 was a good model reflecting mixed exposure of PAHs and PAEs metabolites on birth gestational age.The effects of 9-OHPhe,MBz P and MMP on gestational age were statistically significant(P<0.05).(4)Among the relationship between mixed exposure of PAHs and PAEs metabolites and body mass index,Pattern5 was a good model reflecting the influence of mixed exposure of PAHs and PAEs metabolites on newborn body mass index.After adjusting for confounding factors,the effects of 9-OHPhe and MECPP on newborn body mass index were statistically significant(P<0.05).Conclusion:1.In terms of the relationship between single PAHs or PAEs metabolites,combined exposure of PAHs and PAEs metabolites and birth outcomes,the effects of 9-OHPhe on the four birth outcomes were statistically significant,and the effects of MMP on the three birth outcomes(birth weight,length,gestational age)were statistically significant.∑OHFlu may have an effect on birth weight,MBz P may have an effect on gestational age,MECPP may have an effect on body mass index.2.The effects of polycyclic aromatic hydrocarbons(PAHs)and phthalate metabolites on birth outcome were gender different.