| Objectives To describe the concentration distribution characteristics of umbilical blood inflammatory cytokines in first,second and third trimester,to reveal the exposure tracjectory of inflammatory cytokines throughout pregnancy.To illustrate the relevance and gender difference among pregnancy,umbilical blood inflammatory cytokines concentration and preschool children’s asthma,and to explore whether there was a critical period of pregnancy or in the very early life in which exposure to inflammation affected childhood asthma risk.Methods This study is based on Ma’anshan Birth Cohort Study(MABC),which is aimed to identify the effects of maternal environmental exposure during pregnancy on adverse pregnancy outcomes,the development and health of children.From May 2013 to September 2014,3474 pregnant women in the first trimester who came to the antenatal clinics of Ma’anshan Maternal and Child Health Care Hospital were recruited.They were interviewed by using standardized questionnaire across three trimesters(first trimester: 10.39 ± 2.11 gestational weeks;second trimester: 25.99 ± 1.02 gestational weeks;third trimester: 34.39 ± 1.09 gestational weeks),information of demographics,pregnancy,disease history,and lifestyle factors was collected.Guardian-completed questionnaire for preschool children was performed at age 42 days,once-every-3-months from 3 to 12 months,and once-every-6-months from 1.5 to 6 years.The 5 m L fasting venous blood samples of pregnant women from three trimesters,as well as cord blood,were collected and stored in refrigerator at-80 oC.This cohort study includes dataset of asthma from 2,442 mother-child and five progeny.We collected serum of pregnant women during early,middle,late pregnancy and baby’s umbilical cord blood for inflammatory factor detection.In addition,asthma status of children(Parents’ reports)diagnosed by doctor were collected at 6,12,18,36,48 months’ follow-up.We applied GAM to explore the trajectory of serum levels of inflammatory cytokines during pregnancy.The generalized estimating equations was used to assess the longitudinal association between levels of inflammatory factors during pregnancy or delivery and asthma status of offspring.In the sensitivity analysis,we further adjusted for birth weight,preterm birth,delivery way,father’s education level and job category.Results General characteristics were comparable between those included in the present research(n=2442)and the excluded(n=1032),except for a slight difference in maternal age,monthly family income per capita,parity,and gestational age.Almost all the 8 serum inflammatory cytokines were moderately to highly correlated with each other in each trimester.We observed a linearly increasing trend for IFN-γ and IL-10,a U shaped curve for IL-1β,IL-8,and IL-17 A,and there were a nearly J shaped curve for IL-6,TNF-α,and IL-12p70.IL-17 A had fair-to-good reproducibility across pregnancy(ICC=0.42),IFN-γ,IL-6,IL-10,and IL-12p70 had poor reproducibility.Serum levels of most cytokines in the third trimester was higher than that in the cord blood except IL-8 and TNF-α.Besides,cord serum levels of cytokines had poor correlations with that in the maternal blood.Among all the children,OR for asthma was 2.24(95% CI,1.05-4.74)comparing extreme quartiles of maternal serum IFN-γ level in the second trimester.Elevated maternal serum IL-6 level in the third trimester was also associated with increased offspring asthma risk(OR [95% CI]=2.53 [1.09-5.86] for Q4 vs Q1).When compared with children in the Q1 of maternal serum IL-17 A level in the first trimester and cord blood,children in the Q4 had 3.36-fold(95% CI,1.37-8.26)and 4.15-fold(95% CI,1.01-17.21)risk of asthma.Besides,there was a positive association between cord serum level of TNF-α and children asthma risk(OR [95% CI]=1.81 [1.02-3.19] for Q4 vs Q1).In the sensitivity analysis,the aforementioned results were essentially unchanged.When stratified by sex,the period-specific positive associations of IFN-γ,IL-17 A,and TNF-α with offspring asthma risk were mainly observed in the boys.Interestingly,we observed positive associations of IL-8 in the cord blood,IL-12p70 in the second trimester and cord blood with asthma risk in girls.Conclusions We observed a linearly increasing trend for IFN-γ and IL-10,a U shaped curve for IL-1β,IL-8,and IL-17 A,and there were a nearly J shaped curve for IL-6,TNF-α,and IL-12p70.These findings suggested that the positive associations of maternal or cord serum levels of IFN-γ,IL-17 A,and TNF-α with childhood asthma were mainly observed in boys.Furthermore,our findings add to the body of evidence that the process of asthma development begins in utero and provide potential molecular targets for primary prevention. |
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