Interaction Between Elective Cesarean Section And CRHR1 Gene Polymorphism On Preschool Children’s Cognitive Development

ObjectiveTo clarify the interaction between elective cesarean section（ECS）and corticotropin-releasing hormone receptor 1（CRHR1）gene polymorphism on preschool children’s cognitive development.MethodsBased on Ma’anshan Birth Cohort（MABC）,pregnant women living in Ma’anshan for more than 6 months and coming to Ma’anshan Maternal and Child Care Center for first antenatal checkup within 14 gestational weeks were recruited from May 2013 to September 2014.A total of 3 474 women were recruited after informed consents.Participants with pregnancy termination,twin pregnancy,assisted delivery,unclear delivery mode,pregnancy complications,childbirth complications,preterm birth,low birth weight,incomplete cognitive developmental assessment and lack of venous blood were excluded.After then,propensity score matching were performed according to maternal age,infant sex,date of birth,delivery mode（vaginal delivery and cesarean section）by 1:1.After further excluding participants with emergency cesarean section（n=77）,totally 957 mother and infant pairs entered the final analysis.Information of maternal basic demographic characteristics,previous adverse pregnancy outcomes,pregnancy life style and pregnancy-related diseases were collected by questionnaire survey.Delivery modes and infant characteristics were abstracted from medical records.The Wechsler Preschool and Primary Scale of intelligence-4th Edition（WPPSI-IV）was used to assess children’s verbal comprehension index（VCI）,visual space index（VSI）,fluid reasoning index（FRI）,working memory index（WMI）,processing speed index（PSI）and full-scale intelligent quotient（FSIQ）.DNA were extracted from the venous blood collected when children were 5 years old,and the CRHR1 rs242924 and rs110402 gene polymorphism were analyzed by fluorescence quantitative polymerase chain reaction.CRHR1 genotypes were divided into G allele carrier（high risk type）and AA homozygote.Chi-square tests and independent t tests were used to compare demographic characteristics and children’s cognitive development in various delivery modes.For further analysis,the cognitive development of preschool children was divided into two groups: subnormal group（not higher than 90 scores）;normal and above normal group（higher than 90 scores）.Chi-square tests and logistic regression were respectively used to compare children’s cognitive development in various delivery modes and CRHR1 genotypes.Binary logistic regression models were used to analyze the association between ECS and children’s cognitive development in different CRHR1 genotypes.Results The overall prevalence of cesarean section was 48.9%（1 537/3 146）,and the rate of ECS was 46.4%（1 459/3 146）.In final sample of 957 pregnant women,the average age was（26.5±3.4）years old at delivery,the mean education years was（13.4±3.2）years,and the mean weight gain during pregnancy was（17.7±5.0）kg.Compared with those who gave birth by vaginal deliveries,women that had childbirth by ECS had more weight gain during pregnancy（P < 0.001）.Compared with women living in urban areas,women living in rural areas were more likely to give birth by ECS（P =0.001）.Infants’ birth weights were higher with ECS than in those with vaginal delivery（P < 0.001）.There were 786 and 171 children who were respectively identified as AA homozygotes and G allele carriers.There were no statistically significant differences in the score of VCI,VSI,FRI,WMI,PSI and FSIQ（P > 0.05）in different modes of delivery.After adjusting for paternal age,education level,family income,place of residence,parity,maternal intelligence quotient,pregnancy anxiety and pre-pregnancy BMI,children with G allele had more possibilities of lower proportion of normal/above normal working memory（OR=0.554,95%CI: 0.313 ～ 0.981）.In AA homozygotes,there were no statistically significant differences in the score of VCI,VSI,FRI,WMI,PSI or FSIQ（P >0.05）between ECS and vaginal delivery.In G allele carriers,after adjusting parents’ education level,family income,place of residence,parity,maternal intelligence quotient,pregnancy anxiety and weight gain during pregnancy,it showed that ECS was associated with children’s low proportion of normal/above normal fluid reasoning（OR = 0.056,95%CI: 0.004 ～ 0.720）.Compared with ECS* AA homozygote,it showed that ECS*G allele was associated with children’s low proportion of normal/above normal fluid reasoning（OR=0.373,95%CI:0.143～0.976）after adjusting for relevant confounding.ConclusionThe G allele of the CRHR1 rs110402 and rs242924 may be a high-risk genotype that is associated with preschool children’s working memory.In children with CRHR1 G allele carriers,ECS affected children’s fluid reasoning.ECS and CRHR1 high-risk genotype may have an interaction on preschool children’s cognitive development.