Relationship Of Prenatal Metal Exposure With Allergic Diseases And Immune Response In Preschool Children

Exposure to metal pollutants is one of the most important environmental public health problems.Previous researches showed that gestation was the critical period of embryo development,and metals can cross the placenta barrier from the mother to affect the development of embryo’s immune system,and even affect the risk of children’s allergic diseases such as eczema and asthma.In the studies about relationship of prenatal metal exposure with allergic diseases in children,few kinds of metals were included and most of them focused on the effect of single metal.Studies about the relationship of multiple metals exposure and allergic diseases are scare.In addition,existing studies have confirmed that metal exposure can affect body’s immune function,but the relationship of prenatal metal exposure with children’s immune response is still unclear.Based on a prospective birth cohort study,we selected six metals with high detection rate which may be associated with immune function mentioned in current literatures.The concentrations of metals in maternal urine during pregnancy were used as prenatal metal exposure levels,to analyze the relationship of prenatal metal exposure with allergic diseases.We further analyzed the relationship with T lymphocyte subsets and cytokines in children’s blood to explore the effect of metal exposure on children’s immune response.Part 1 Relationship of prenatal metal exposure with allergic diseases in preschool childrenObjective:To investigate the relationship of prenatal metal exposure with allergic diseases in preschool children.Methods:Based on a prospective birth cohort study,we collected urine samples of mothers in the third trimester and measured the urinary levels of six metals,combined with a follow-up questionnaire for children in kindergarten（N=3355）to obtain their information on allergic diseases and symptoms,including wheezing,allergic rhinitis,and eczema.Single-metal Logistic regression model was used to calculate OR and95%CI,and creatinine-adjusted metal levels（ln-transformed）were used as continuous variables to analyze the relationship of prenatal metal exposure with allergic diseases in preschool children.At the same time,the metal concentrations were divided into four grade variables according to the quartile concentrations（Q1,Q2,Q3,Q4）,and the first quartile concentrations（Q1）were taken as the reference to explore the possible nonlinear relationship.Furthermore,all the metals with statistical significance in the single-metal model were included in the multi-metal Logistic regression model.Results:（1）Single-metal model analyses showed that prenatal urinary exposure levels of manganese and nickel were associated with an increasing risk of wheezing in preschool children;prenatal urinary exposure levels of chromium and nickel were associated with an increasing risk of eczema.（2）Multi-metal model analyses showed that when metal levels（ln-transformed）were used as continuous variables,there were no significant associations with allergic diseases,and when metal levels were used as quartile grade variables,prenatal urinary levels of chromium in the second quintile was associated with 32%（95%CI:1.08,1.63）increasing risk of eczemacompare to the lowest quartile.Conclusions:Prenatal metal exposure may affect the occurrence of allergic diseases in children,and chromium exposure may be a risk factor for eczema in children.Part 2 Relationship of prenatal metal exposure with immune response in preschool childrenObjective:To investigate the relationship of prenatal metal exposure with immune response in preschool children.Methods:Based on a prospective birth cohort study,we measured six metals in mother’s urine samples collected in the third trimester and T lymphocyte subsets（N=394）and immune cytokines（N=326）in 3-year-old children’s blood samples collected during a physical examination when they entered into the kindergarten.Theβvalue and95%CI were calculated by single-metal general linear regression model,and the creatinine-adjusted metal levels（ln-transformed）were incorporated into the model as continuous variables.At the same time,the metal concentrations were divided into four grade variables according to the quartile concentrations（Q1,Q2,Q3,Q4）,and the first quartile concentrations（Q1）were taken as the reference to explore the possible nonlinear relationship.Furthermore,all the metals with statistical significance in the single-metal model were analyzed in the multi-metal general linear regression model.Results:（1）Single-metal model analyses of the relationship of prenatal metal exposure with children’s peripheral blood T lymphocyte subsets showed that prenatal urinary chromium exposure levels was associated with decreased absolute counts of CD3⁺,CD3⁺CD8⁺,and CD3⁺CD4⁺cells;prenatal lead exposure was associated with increasing absolute count of CD3⁺cells.Single-metal model analyses about the relationship of prenatal metal exposure with cytokines in children’s plasma showed that prenatal urine nickel,chromium and zinc exposure were associated with decreased IL-2;prenatal manganese and lead exposure were associated with decreased IL-4;prenatal lead exposure was associated with decreased IL-10;prenatal chromium exposure was associated with decreased TNF-α.（2）The relationship of prenatal metal exposure with immune response was analyzed using multi-metal model.The results showed that when metal levels（ln-transforned）were used as continuous variables,each nature log unit increase of maternal urinary chromium concentration was associated with 3.67%（95%CI:-6.20%,-1.07%）decreased absolute count of CD3⁺cells;there was no significant associations between prenatal urinary metals and cytokines.When metal levels（ln-transforned）were used as quartile grade variables,we also found that maternal urinary chromium exposure was associated with decreased absolute counts of CD3⁺cells in maternal urine were reduced by 10.52%（95%CI:-20.37%,-0.67%）and 14.41%（95%CI:-24.40%,-4.42%）in the third and fourth quantile of maternal urine chromium relative to the lowest quantile,respectively,and a significant trend was observed(P_trend=0.02),urinary lead exsposure was associated with 10.37%（95%CI:1.03%,19.70%）increasing absolute count of CD3⁺cells among the T lymphocyte subsets;compare to the lowest quantile,urinary zinc exposure was associated with the 18.83%（95%CI:-31.77%,-5.89%）decreased IL-2 among the cytokines.Conclusions:Prenatal metal exposure may be related to children’s immune response.Prenatal chromium exposure was associated with decreased absolute count of CD3⁺cells;prenatal lead exposure was associated with incerasing absolute count of CD3⁺cells;prenatal zinc exposure was associated with decreased IL-2.