| ObjectivesTo investigate the association between the concentration of 7 inflammatory cytokines in the first,second,and third trimester,and cord blood serum and the level of intelligence development of preschool children,and to reveal the sensitive period and gender differences of the association,so as to provide theoretical basis for the prevention of children’s intellectual development injury and developmental origin diseases.MethodsBased on the Ma’anshan Birth Cohort（MABC）,our study finally included 1 641mother-child pairs for analysis.Fasting peripheral venous blood was collected from mothers during the first,second,and third trimester examinations,and cord blood was collected during delivery.Luminex liquid suspension protein technique was used to detect the concentrations of 7 inflammatory cytokines in the serum,including interferon-γ（IFN-γ）,interleukin（IL）-1β,IL-6,IL-8,IL-10,IL-12p70,tumor necrosis factor-α（TNF-α）;The preschool children’s intelligence were tested by the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition-Chinese [(WPPSI-IV（CN）].Linear mixed models（LMMs）were used to analyze the association between the concentrations of inflammatory cytokines throughout pregnancy and the level of intellectual development in preschool children.Multiple linear regression models were used to investigate the sensitive period of the association after stratifying the sampling time,and then the above results were stratified by gender to investigate gender differences in the association.ResultsAfter adjusting for confounders,LMMs results showed that serum IL-10 concentration throughout pregnancy was positively associated with visual spatial index（VSI）and fluid reasoning index（FRI）;this association was significant in girls after gender stratification,but not in girls IFN-γ concentration was also found to be positively associated with FRI,TNF-α concentration was positively associated with verbal comprehension index（VCI）and FRI;in boys,IL-10 concentration was positively associated with working memory index（WMI）.Single point analysis showed that IFN-γ and IL-1β concentrations were negatively associated with WMI,IL-6 concentration was negatively associated with WMI and processing speed index（PSI）,and IL-8 concentration was negatively associated with full scale IQ（FSIQ）,VSI,WMI and PSI in the first trimester.In the second trimester,IL-10 concentration was positively associated with FSIQ,VSI and FRI.In the third trimester,IL-8 concentration was positively associated with FSIQ and VCI.In cord blood,IL-6 concentration was negatively associated with FRI,while IL-10 concentration was positively associated with WMI.After gender stratification,the results showed that in boys,IFN-γ and IL-6concentrations were negatively associated with WMI,while IL-8 concentration was negatively associated with FSIQ,VSI,WMI and PSI in the first trimester.There was a positive association between IL-10 concentration and WMI in the second trimester.IL-8concentration in third trimester was positively associated with VCI.The concentrations of IFN-γ,IL-1β and IL-8 in cord blood were negatively associated with FRI,while IL-10 was positively associated with WMI.For girls,IL-1β concentration was positively associated with FRI in the first trimester.IL-10 concentration was positively associated with VSI and FRI in the second trimester.TNF-α concentration in the third trimester was positively associated with FSIQ and VCI.The concentrations of IFN-γand IL-6 in cord blood were negatively associated with PSI,while the concentrations of IL-10 were positively associated with WMI.Sensitivity analysis further adjusted delivery mode,paternal age and paternal smoking during pregnancy,and the model results were basically robust.ConclusionsThere was a association between the concentration of inflammatory cytokines in pregnancy and cord blood and the level of intelligence development of preschool children.The increased concentration of pro-inflammatory cytokines in first trimester（negative association）and anti-inflammatory cytokines in second trimester（positive association）had a more significant impact on the intelligence development of preschool children.The former is mainly reflected in boys,while the latter is mainly reflected in girls.The increased association of inflammatory cytokines in cord blood has an effect on the intellectual development of both boys and girls（pro-inflammatory cytokines have a negative association,anti-inflammatory cytokines have a positive association）,but the specific impact area is different. |
