The Association Of Maternal Urinary Environmental Phenols Levels With Birth Outcomes

Environmental phenols are widely applied to the manufacture of numerous daily products which relate closely to the human life.Bisphenol A(BPA)?bisphenol S(BPS)and triclosan(TCS)belong to the most used environmental phenols.BPA is a common plasticizer with a history of over fifty years.BPS is widely used as an emerging alternative of BPA since the 20th century.And TCS is taken as a broad-spectrum antimicrobial chemical for more than forty years.These chemicals can be detected frequently in the environment,such as water,food,dust,soil,sludge,and so on.Due to their long time and direct exposure through ingestion,dermal route and inhalation,they have posed the unneglectable threat to the general population.Besides,studies have demonstrated that bisphenols and TCS can cross the placenta barrier and be secreted through milk causing the general exposure for the fetuses and newborns.Both of bisphenols and TCS belong to the endocrine disrupter chemicals(EDCs).They have abilities to interrupt the homeostasis of sex hormones and thyroid hormones,which will lead to adverse effects on the growth and development,reproduction,nervous system,and so forth.Basing on the "Development origins of health and disease(DOHaD)" hypothesis proposed by prof.Baker,fetal and neonatal periods are critical for development and also vulnerable to the environmental exposures.Exposure to the environmental pollutants in early life can cause fetal developmental adaptations,and result in alternations of the function,structure of organs and systems.These alternations are related with intrauterine growth restriction,adverse birth outcomes,even stillbirth,and abortion in short term,as well as long term health risk persisting over the whole life,such as the growth retardation in childhood,cardiovascular disease,and metabolic syndrome in adulthood.Therefore,prenatal exposure to the bisphenols and TCS which may cause adverse effects on health over the life-course deserves especial concern.However,to date,the findings from epidemiological studies about associations between prenatal BPA exposure and birth outcomes are inconsistent,and previous studies suggested that there may be sex-based differences which have not been well studied.And studies about the associations of maternal BPS and TCS exposure with birth outcomes are limited.To better understand the potential risk of these chemicals,we took advantage of the Health Baby Cohort(HBC),a large-scale prospective birth cohort,randomly selected mother-infant pairs recruited in Wuhan,assessed maternal urinary BPA,BPS,and TCS levels during pregnancy,and investigated their associations with birth outcomes,respectively.Part 1:Maternal urinary bisphenol A levels and infant low birth weight:a nested case-control studyObjectives:We investigated whether maternal exposure to BPA during pregnancy is associated with an increased risk of infant low birth weight(LBW).Methods:A total 452 mother-infant pairs(113 LBW cases and 339 matched controls)were selected from the participants enrolled in the prospective HBC in Wuhan city,China,during 2012-2014.Maternal urinary samples were collected at delivery,urinary BPA concentrations were measured by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),and the information of birth outcomes was retrieved from the medical records.A conditional logistic regression was used to evaluate the relationship between urinary BPA levels and LBW.Results:Mothers with LBW infants had significantly higher urinary BPA levels(median:4.70 ?g/L)than the control mothers(median:2.25 ?g/L)(P<0.05).Increased risk of LBW was associated with higher maternal urinary levels of BPA[adjusted odds ratio(OR)= 3.13 for the medium tertile,95%confidence interval(CI):1.21,8,08;adjusted OR = 2,49 for the highest tertile,95%CI:0.98,6.36].The association was more pronounced among female infants than among male infants,with a statistical evidence of heterogeneity in risk(P = 0.03).Conclusions:Prenatal exposure to higher levels of BPA may potentially increase the risk of delivering LBW infants,especially for female infants.This is the first case-control study to examine this association in China mainland.Part 2:Relationship of maternal urinary bisphenol A and bisphenol S levels with birth outcomesObjectives:The present study was designed to evaluate the associations of maternal urinary BPS and BPA concentrations with birth outcomes.Methods:BPS and BPA concentrations were detected in urine samples collected before delivery from 985 pregnant women in the HBC in China.We applied linear regression models and logistic regression models to evaluate the associations between maternal bisphenol exposures and birth outcomes with adjustment for potential confounders.Results:BPA and BPS were found in more than 90%samples,with the specific gravity adjusted geometric mean(GM)concentration of 2.09 pg/L and 0.17 ?g/L,respectively.Each.In-unit increase in maternal urinary BPA was significantly related with shortened gestational age(adjusted ? =-0.65,95%CI:-0.97,-0.34]and increased odds of preterm delivery(adjusted OR = 1.58,95%CI:1.28,1.95)for all newborns.In contrast,each In-unit increase in BPS was significantly related with increased gestational age(adjusted ? ? 1.06,95%Cl:0.50,1.61)and increased odds of late term birth(adjusted OR = 1.29,95%Cl:1.00,1.67)only for girls.Further analyses including maternal urinary BPA and BPS in one model almost did not change the results.None obvious associations of BPA and BPS with birth weight and birth length were observed.Conclusions:Our findings showed that maternal urinary BPA level was related with shortened gestational age and increased odds of preterm birth.Also,we provided the first evidence suggesting that higher maternal BPS exposure may interfere with gestational duration in girls.Our results need further confirmation.Part 3:Urinary levels of triclosan in a population of Chinese pregnant women and its association with birth outcomesObjectives:Aiming to determine maternal urinary TCS level and investigate its association with birth outcomes.Methods:Pregnant women(n = 1006)were randomly selected from the prospective HBC enrolled in 2014,and we measured TCS concentrations in their urine samples collected at delivery and recorded birth outcomes from the medical records.Multiple linear regression models were applied to assess relationships of maternal urinary TCS levels with birth outcomes including birth weight,birth length,and gestational age,and logistic regressions were used to evaluate associations with preterm birth,late term birth,low birth weight,and small for gestational age.Results:The median and GM concentrations for TCS in maternal urine were 0.60,0.73 ng/mL,respectively.Compared with pregnant women from many other countries,our population was exposed to a relatively low level of TCS.No significant associations of maternal TCS levels with birth weight(P =-6.41,95%CI:-18.92,6.10),and birth length(?=0.00,95%Cl:-0.05,0.05)were observed among all the infants.Maternal urinary TCS levels tended to be positive with gestational age at birth(? = 0.28,95%Cl:0.00,0.57,P ?0.05),however,this relationship attenuated after stratified by infant sex.Maternal TCS levels were not related with preterm birth,late term birth,low birth weight,and small for gestational age(all/P>0.10).Conclusions:Our findings firstly reported the relatively low level of TCS among Chinese pregnant women.With such exposure level,we did not find strong evidence for associations between maternal TCS exposure and birth outcomes.Longitudinal studies concerning about different potential effects of TCS on perinatal health are necessary.