The Individual And Combined Effect Of Prenatal Exposure To Harmful Metals On Adverse Maternal And Infants Outcomes

ObjectivesTo describe 7 harmful metal elements serum concentrations and risk factors of exposure during first trimester,second trimester and delivery,preliminary identify patterns of metal mixtures and clarify individual and combined effects of prenatal exposure to harmful metals on pregnancy complications and infant behavior development,therefore to provide scientific evidence for euthenics.MethodsThe study sample comprised 3 474 mother-child pairs in the Chinese Ma’anshan Birth Cohort（MABC）,all participants were obtained written consent forms.General maternal information and demographic characteristics were investigated from questionnaires during each trimester of pregnancy,which were used for exploring the influence factors for serum metals exposure.Blood pressure,blood glucose and urine protein were measured in each trimester of pregnancy,and the glucose tolerance test was performed in the second trimester of pregnancy.Maternal venous blood（first and second trimester）and umbilical cord blood（delivery period）were collected to measure serum metals concentration of Al²⁷、As⁷⁵、Cd¹¹¹、Ba¹³⁷、Tl²⁰⁵、Pb²0808 and Hg²⁰².Children’s behavior development at 6 months old was evaluated by the Ages and Stages Questionnaire-Chinese（ASQ-C）.Geometric mean,mean,minimum value,maximum value and percentiles(P_25,P₅₀、P₇₅5 and P₉₀)were presented for all study subjects.Chi-square test and t test were employed to describe the demographics characteristics in included and excluded subjects,as well as risk factors of metal exposure.Cluster analysis and principal component analysis（PCA）were used for Ln conversion data of serum metal concentration,and to probe category for 7 metals.By the technique of PCA,principal components are created.Then an overall measure of metal exposure that was derived by summing the quartile category score（1–4,with 1 representing the lowest quartile）for each metal to create an overall score with values.We developed separate and summing-up evaluation approach,to test for individual and combined associations of 7metals and outcome variables.Univariate Logistic regression model（model 1）was used to analyze the relation between 7 individual and combined metals and the risk of gestational diabetes mellitus（GDM）,hypertensive disorder complicating pregnancy（HDCP）,preterm birth and child’s behavior development performance.Thereafter,6 other metals were controlled in model 2,meanwhile the relation between 7 individual metals and the risk of the above mentioned adverse outcomes was analyzed.At last,based on model 2,demographic characteristics variables and other confounding factors were controlled,then the relation between 7 individual and combined metals and the risk of the above mentioned adverse outcomes was analyzed（model 3）.ResultsCompared with developed countries,our research results showed that maternal and cord serum metal Al and As concentration were significant higher,while Cd,Pb and Hg concentration were lower.Maternal adverse environment factors,dieting and lifestyle were contributed to various metals exposure which increased the intake and absorption that cause increased metal concentration in pregnant women.Cluster analysis and PCA（C1,C2 and C3）had both divided 7 heavy metal elements into 3 categories,and each category presented stable in different pregnancy trimesters.According to relations between 7 metals and GDM,As and Hg exposure in first trimester and Hg exposure in second trimester could increase the risk of GDM;while the relations were not found in other metals during other trimesters.The summing-up evaluation results showed that the combined exposure of 7 metals in first trimester could increase the risk of GDM;similarly,PCA score analysis showed that C1 component scores in first trimester were significantly associated with GDM risk,which suggested that metal exposure during first trimester maybe the sensitive period for GDM.According to relations between 7 metals and HDCP,Pb exposure in first and second trimester could significantly increase the risk of HDCP,Tl exposure in delivery could significantly increase the risk of HDCP;while the relations were not found in other metals during other trimesters.The summing-up evaluation results showed that the combined exposure of 7 metals during delivery could increase the risk of HDCP;similarly,PCA score analysis showed that C3 component scores during delivery were significantly associated with HDCP risk,which suggested that metal exposure during delivery maybe the sensitive period for HDCP.According to relations between 7 metals and preterm birth,Hg exposure in second trimester could increase the risk the preterm birth;while the relations were not found in other metals during other trimesters.The summing-up evaluation results showed that the combined exposure of 7 metals in each trimester has no obvious relation with preterm birth;while PCA scores analysis shows that C3 component score in second trimesters was significantly associated with preterm birth.According to relations between 7 metals and infant development,Cd exposure in cord blood could increase the dysplasia risk of ASQ-C communication area and problem-solving area;Ba exposure in first and second trimesters could both increase dysplasia risk of ASQ-C gross motor,fine motor,problem-solving and individual-social areas;while Ba exposure in cord blood has no obvious correlation with each ASQ-C area development.Pb exposure in second trimester could increase dysplasia risk of ASQ-C gross motor and individual-social areas;A1 exposure in first trimester and cord blood could increase dysplasia risk of ASQ-C fine motor and individual-social areas.As exposure in first trimester and cord blood could increase dysplasia risk of ASQ-C individual-social area.The summing-up evaluation results showed that,based on the total score calculated by quartile of 7 metals,of the dysplasia risk of communication area,on the high-score metal exposure in cord blood was higher that the low-score exposure group;while the significant correlation between other periods and ASQ-C areas were not found yet.According to the result of PCA score and infant development performance analysis,C1 score in first trimester was statistically associated with individual-social area development;C1 score in second trimester was statistically associated with gross motor,fine motor,problem-solving and individual-social areas development;meanwhile C1 score in cord blood was statistically associated with fine motor,problem-solving and individual-social areas development.ConclusionsThe research has provided large-scale epidemiological baseline data for preliminary investigation on harmful metals exposure levels in different pregnancy period and cord blood;the exploration of harmful metal exposure risk factors in different trimesters could provide evidence for future measures taken to reduce harmful metal pollution in environment.In addition,as to GDM,HDCP,preterm birth and infant development performance,the individual and combined effects of 7 harmful metals exposure are different,as well as the corresponding sensitive periods.The current research has provided basic data for the relation between harmful metal exposure among pregnant women and maternal-child health,as well as the scientific evidence for environmental harmful metal exposure and pollution abatement.