The Effects Of Perinatal Factors On Childhood Allergic Disorders

Recent years,the incidence of allergic diseases,especially asthma and atopic dermatitis,has increased dramaticly.Based on DOHaD(developmental origins of health and disease)theory,it is believed that early life may be a critical period of allergic disease.In this study,a prospective cohort study in Shanghai was used to explore the perinatal risk factors for childhood allergic disorders from three dimensions.1.This part aimed to explore the effect of prenatal factors on childhood allergic diseases.Analyzed the association of prenatal factors,including prenatal stress,prenatal active and passive smoke,prenatal alcohol intake,drug use during pregnancy,obstetric complications and parental allergic diseases,with childhood allergic disorders.We found that maternal allergic disease was a potential risk factor for children with eczema during the first two years,adjusted OR was 2.04(95%CI,1.33-3.12).2.This part aimed to explore the effects of prenatal perfluorniated compounds(PFCs)exposure on stress hormones and childhood allergic disorders.Analyzed the effect of cord blood plasma PFCs concentrations on hormones levels of cord blood serum and childhood allergic diseases.The results showed that ln-cortisol was positive correlated with ln-PFOA(?=0.14,standard error [SE]=0.04),and ln-PFHxS(?=0.21,SE=0.06).Ln-estradiol was positive correlated with ln-PFOS(?=0.07,SE=0.03),and ln-PFNA(?=0.11,SE=0.04).ln-DHEAS(dehydroepiandrosterone sulfate)was positive correlated with ln-PFOA(?=0.14,SE=0.07),and ln-PFBS(?=0.12,SE=0.06).When PFCs were divided into quartiles,the highest PFOA quartile was significantly associated with eczema in comparison to the lowest quartile after adjusting for potential confounders,aOR was 1.79(95% CI,1.06-3.02).A stratified analysis by gender further revealed that this association mainly existed in female children,aOR=2.64(95% CI,1.19-5.86).Similarly,the highest quartile of PFHxS was also significantly associated with eczema in female children,aOR= 2.60(95% CI,1.18-5.69).Additionally the second quartile of PFDoA level were also associated with eczema in female children,aOR=2.47(95% CI,1.10-5.51).3.This part aimed to explore the effects of delivery mode on stress hormones and childhood allergic disorders.The effects of delivery mode on cord blood serum hormone levels,cord blood cells DNA methylation states,intestinal flora at 1 years and childhood allergic disorders were analyzed.The results showed cord blood serum cortisol concentration of cesarean deliveries on maternal request(CDMR)group was 31.97 g/dl,lower than that of vaginal delivery group(69.30 g/dl).The cord blood serum estradiol concentration of CDMR group was 7854.39 pg/ml,lower than that of vaginal delivery group(10387.32 pg/ml).After DNA methylation analysis,168 differentially methylated positions(DMPs)were found between CDMR group and vaginal delivery group.61.3%(103 of 168)of the DMPs were found to be hypermethylated in the CDMR as compared to vaginal deliveries.After GO and KEGG enrichment analysis,the DMPs were potentially associated with the immune system.Cord blood serum cortisol levels were negatively associated with eczema during the first two years,OR 0.62(95% CI,0.37-1.03)per ln-unit.In summary,we found that childhood allergic disorders are influenced by genetic factors.Perinatal exposure to environmental pollutants can alter fetal hormone levels,and increase the risk of allergic disorders in girls.Meanwhile,cesarean section can change the fetal hormone levels compared with vaginal delivery.The reduction of the fetus cortisol level in cesarean section may be one of the mechanisms of childhood allergic disorders.