Associations Of Prenatal Exposure To Bisphenols With Childhood Growth Trajectories In The First 2 Years

Bisphenols are the main materials used in the production of plastic water bottles,food packaging and plastic lunch boxes.The representative bisphenols include Bisphenol A(BPA),Bisphenol S(BPS)and Bisphenol F(BPF),etc.Since BPA has been proved to have environmental endocrine disruption effects and developmental toxicity,as a result,BPF and BPS are widely produced to replace the application of BPA in many consumer products marketed as "BPA-free".However,a growing number of studies have shown that these BPA substitutes also have endocrine disrupting effects and other toxic effects,which may endanger the health of people.Pregnant women and fetuses are more susceptible to the harmful effects of endocrine disruptors like bisphenols than general population.This study is based on a large prospective birth cohort to collect urine samples from pregnant women in the 1st,2nd,and 3rd trimesters to assess the exposure levels of BPA,BPS,and BPF,and then the exposure to BPA,BPS,and BPF during pregnancy on the growth trajectory of children were further explored.Furthermore,we detected estrogen levels in neonatal cord blood samples,and then explored the mediating effect of fetal estrogen levels on the association between exposure to BPA,BPS,BPF and the growth trajectory of children.This study will provide new epidemiological evidence for the mechanism of adverse health effects caused by bisphenols.Part 1:Pattern and predictors of childhood growth trajectories in the first 2 years.Objective:We analyzed the growth trajectories pattern of weight,length and BMI z-scores of children aged 0-2 years,and explored the predictors as social factors,children’feeding,parental characteristics and maternal diseases during pregnancy on growth trajectories.Methods:Based on a prospective birth cohort study,4121 pregnant women were recruited who were resident in Wuhan and delivered in Wuhan Children’s Hospital from 2013 to 2016.Anthropometric data for children were followed up at birth,1,3,6,8,12,18 and 24 months of age,respectively.Feeding,the time of sleep and outdoor activities of children were followed up at meanwhile.Weight,length and BMI z-scores were computed with reference to the WHO standards.Group-based trajectory modeling was used to estimate BMI growth trajectory.A multiple logistic regression was used to estimate the relationship between predictors and the growth trajectories of children.Results:(1)The growth trajectory patterns of weight,length and BMI z-scores were classified into three categories,which were slow trajectory,normal trajectory and fast trajectory respectively.Among them,three types of weight trajectories accounted for 27.7%,52.4%and 19.9%,respectively.Three types of length trajectories accounted for 27.0%,51.9%and 21.1%,respectively.Three types of trajectories of the BMI accounted for 22.0%,57.2%and 20.9%,respectively.(2)Compared with normal trajectory of weight,inadequate gestational weight gain and pre-pregnancy underweight were positively related to slow growth trajectory,OR(95%CI)was 1.06(1.04,1.08),1.48(1.20,1.82),respectively.While multiparous,excessive gestational weight gain,pre-pregnancy overweight or obesity,paternal overweight or obesity predicted fast trajectory,OR(95%CI)was 1.05(1.02,1.09)、1.62(1.24,2.11),1.35(1.11,1.63),respectively.(3)Compared with normal growth trajectory of length,inadequate gestational weight gain and parents are short significantly associated with slow trajectory,OR(95%CI)was 1.04(1.02,1.07),1.04(1.02,1.07),1.06(1.03,1.09),respectively.While excessive gestational weight gain,parents are tall,pre-pregnancy overweight or obesity,breasteeding for more than 6 months were associated with fast trajectory,OR(95%CI)was 1.03(1.01,1.05),1.08(1.06,1.11),1.07(1.05,1.10),1.25(1.01,1.56),respectively.(4)Compared with normal growth trajectory of BMI,pre-pregnancy underweight,inadequate gestational weight gain,paternal underweight and family income below 50,000 significantly associated with slow trajectory,OR(95%CI)was 1.64(1.31,2.04),1.06(1.03,1.08),2.05(1.12,3.76),respectively.Pre-pregnancy overweight or obesity,excessive gestational weight gain,and paternal overweight or obesity significantly related to fast trajectory,OR(95%CI)was 1.64(1.27,2.10),1.04(1.02,1.06),1.32(1.09,1.59),respectively.Conclusion:Factors such as maternal weight gain during pregnancy,pre-pregnancy weight status,paternal weight status,breastfeeding time,parental height,and family income were associated with growth trajectory patterns of children.Part 2.Association between prenatal exposure to bisphenols and childhood growth trajectories in the first 2 years.Objective:We aimed to explore the association of maternal urinary BPA,BPS and BPF with the growth trajectories of children aged 0-2 years.Methods:Based on Part 1,we selected 823 mother-child pairs who had complete urine during the 1st,2nd,and 3rd trimesters of pregnancy and completed the growth and development data of children aged 0-2 years.Maternal urine concentrations of BPA,BPF and BPS were measured using ultra-high performance liquid chromatography coupled with triple.The distribution of urinary bisphenols levels was natural logarithm(In-).Generalized estimated equation(GEE)model was conducted to explore the relationships of urinary BPA,BPS,BPF exposure levels and weight,length,and BMI z-score at birth,1,3,6,8,12,18 and 24-month-old of children.Group-based trajectory modeling was used to estimate BMI growth trajectory.A multiple logistic regression was used to estimate the relationship between BPA,BPS,and BPF exposure and the growth trajectory of children.Results:The detection rate of BPA,BPS and BPF was more than 74.5%,84.3%and 98.2%respectively in all samples.The geometric mean concentrations of BPA,BPS and BPF were 1.24-1.30 ng/mL,0.53-0.54 ng/mL and 0.70-0.76 ng/mL,respectively.Compared to normal trajectory,BPS concentrations in 1st trimester associated with slow trajectory of weight,OR(95%CI)was 2.11(1.17,3.80).BPS concentrations in 2nd trimester was negatively related to fast trajectory of weight z-score,OR(95%CI)was 0.54(0.35,0.81).BPF concentrations in 1st,2nd,3rd trimester of associated with slow trajectory of weight z-score,OR(95%CI)was 0.61(0.41,0.92),0.63(0.42,0.95),0.56(0.37,0.84),and BPF concentrations in 3rd trimester was associated with slow trajectory of BMI z-score,OR(95%CI)was 1.71(1.04,2.81).Conclusion:Prenatal exposure to bisphenols had adverse effects on the growth of children aged 0-2 years,they were positively related to slow trajectory of weight and BMI z-score.Part 3:Potential mediating roles of estrogen in the association between prenatal exposure to bisphenols and childhood growth trajectories.Objective:To explore the association of prenatal exposure to BPA,BPS and BPF with estrogen in umbilical cord blood,and to analyze the mediating role of estrogen in the association of bisphenols with growth trajectories of children.Methods:The liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect estrone,estradiol,and estriol of 601 neonates.GEE model was used to explore the association between BPA,BPS and BPF concentrations and estrone,estradiol,and estriol.A multiple linear regression model was performed to analyze the association between estrone,estradiol,and estriol in cord blood and the growth trajectory of child weight,length and BMI z-score.Mediation analysis was performed to analyze the mediating effect of estrogen between the association of bisphenols and growth trajectory.Results:(1)The median concentrations of estrone,estradiol and estriol in cord blood were 11.12ng/mL,2.79ng/mL and 121.82ng/mL,respectively.Urinary BPF was positively correlated with estrogen.An IQR increase in BPF concentrations in 1st trimester,the level of estrone increased by 10.04%(95%CI:0.55%,19.54%).An IQR increase in BPF concentrations in 1st and 2nd trimester,the level of estradiol increased by 15.60%(95%CI:4.50%,26.70%)and 14.59%(95%CI:3.62%,25.56%),respectively.Urinary BPA and BPS were not significantly associated with estrogen levels.(2)Estrone was associated with slow trajectory of weight and length z-score,OR(95%CI)was 1.99(1.21,3.26)and 2.02(1.37,2.97),and negatively related with fast trajectory of BMI z-score,OR(95%CI)was 0.68(0.48,0.98).Estradiol was associated with slow trajectory of weight and length z-score,OR(95%CI)was 1.63(1.06,2.49)and 1.71(1.22,2.40),and negatively related with fast trajectory of BMI z-score,OR(95%CI)was 0.71(0.52,0.96).Estriol was associated with slow trajectory of length z-score with an OR(95%CI)of 1.61(1.06,2.44).(3)Estradiol mediated the effects of BPF concentrations in 2nd trimester on slow trajectory of weight and length z-score,and on fast trajectory of BMI z-score,with the mediating percentages of 13.09%,19.39%and 6.94%,respectively.Conclusion:There is a mediating effect of estradiol in the association of BPF exposure during pregnancy on the growth trajectory of weight,length and BMI z-score.BPF may slow down the child growth by increasing estrogen levels.