Maternal Exposure To Rare Earth Elements And Their Relation With Birth Outcomes

Objective: Rare earth elements(REEs)are widely applied in industrial,agricultural,medical and high-tech fields,leading to occupational and environmental exposures,thus raising concerns about REEs-associated health effects.Data on the exposure level of REEs across pregnancy and factors that may affect their concentrations have not been established,and there is less research on the effects of pregnancy REEs exposure on birth outcomes.We conducted this study to determine the associations of REEs exposure with neonatal birth outcomes.Methods: We selected 2229 mother-infant pairs as subjects from an ongoing prospective birth cohort in Wuhan city between February 2014 and June 2016.Three maternal urine samples for each pregnant woman from three trimesters(T1: 12.8 ± 1.0 weeks;T2: 23.9±3.3 weeks;T3: 33.9±3.0 weeks)during prenatal examination were collected as internal REEs exposure biomarkers.Thirteen REEs in the urine of pregnant women were measured by inductively coupled plasma mass spectrometry(ICP-MS)method,including La,Ce,Pr,Nd,Sm,Eu,Gd,Dy,Ho,Er,Tm,Yb and Lu,meanwhile urinary creatinine concentrations were examined to normalize the level of REEs in urine.The Mixed Model was used to calculate the intraclass correlation coefficient(ICC)of urinary rare earth elements across pregnancy and determine the predictors of urinary REEs concentrations.We collected characteristics of pregnant women by face-to-face questionnaires and retrieved the information of birth outcomes from the medical records.The generalized estimating equation(GEE)model was performed to assess the associations between maternal urinary creatinine-corrected REEs concentrations at each trimester and birth weight,birth length,ponderal index(PI)and small for gestational age infant(SGA).Results:(1)The detection rates of six REEs in urine samples of 2229 pregnant women in the three trimesters exceeded 90%,and the detection rate of Pr reached 100% in this study.The ICC for urinary creatinine-corrected concentrations of thirteen REEs from three trimester ranged from 0.21(Eu)to 0.32(Gd),showing a higher variability.(2)Passive smoking during pregnancy could increase levels of 11 rare earth elements(La,Ce,Pr,Nd,Eu,Gd,Dy,Ho,Er,Tm and Yb),with their corresponding ?(95% CI)0.36(0.23,0.49),0.39(0.24,0.54),0.30(0.18,0.41),0.20(0.11,0.29),0.27(0.17,0.38),0.19(0.09,0.28),0.24(0.14,0.33),0.32(0.20,0.44),0.27(0.17,0.38),0.33(0.21,0.45)and 0.23(0.13,0.32).Folic acid supplementation during pregnancy was negatively correlated with certain REEs concentrations and the corresponding ?(95% CI)of La?Ce?Pr?Nd?Eu?Ho and Tm were-0.20(-3.31,-0.08),-0.16(-0.29,-0.03),-0.17(-0.27,-0.07),-0.12(-0.20,-0.03),-0.18(-0.27,-0.09),-0.15(-0.26,-0.05)and-0.19(-0.30,-0.08),respectively.(3)The associations between the concentrations of REEs in urine samples of pregnant women and birth weight were as follows: the concentration of REEs(Ce,Pr,Eu,Ho,Er)in the third trimester of pregnancy is negatively correlated with the birth weight of newborns,and their corresponding ?(95% CI)were-10.06g(-20.03,-0.10),-13.49g(-26.13,-0.84),-15.92g(-29.58,-2.26),-12.09g(-23.46,-0.73),and-13.71g(-26.74,-0.69).The concentrations of element Ho and Tm in urine of the third trimester were negatively correlated with the birth weight of male infants,with ? value(95% CI)-15.35g(-30.28,-0.41)and-14.94g(-29.74,-0.15)respectively.The concentration of Pr in urine in the first trimester was negatively correlated with the birth weight of the baby boy,and its effect value ? was-18.04g(95% CI:-33.96,-2.12).(4)The associations between the concentrations of REEs in urine samples of pregnant women and risk of SGA were as follows: each doubling in concentrations of maternal urinary Ce,Pr,Nd,Ho,Tm,Yb in the third trimester increased the risk of SGA by 0.73%,1.09%,1.18%,0.85%,0.85%,and 1.23%,respectively.In the third trimester,with the urinary Gd and Er increased every doubling,the risk of SGA in male infants increased by 1.19%(OR: 1.0119,95% CI: 1.0012,1.0228),1.27%(OR: 1.0127,95% CI: 1.0020,1.0236).The doubling of concentration of Pr in the urine of the first trimester increased the risk of SGA in male infants(OR: 1.0101,95% CI: 1.0014,1.0189).(5)No statistically significant correlation was found between the concentrations of REEs during pregnancy and the birth length and ponderal index of newborns.Conclusion:(1)The higher detection rates of REEs in urine samples of pregnant women indicates that pregnant women are generally exposed to REEs during pregnancy.The low intraclass correlation coefficients(ICC)of REEs in urine samples from different trimesters of pregnancy suggests that the variability of REEs exposure during pregnancy is greater and multiple urine samples can be better represent the exposure during pregnancy.(2)Passive smoking during pregnancy,folic acid supplementation are potential factors that influence urinary REEs concentrations.(3)This study found that exposure to certain REEs during pregnancy may lead to reduce birth weight of total infants and male infants.In addition,REEs exposure during pregnancy may also lead to increase the risk of SGA in total infants and boys.