The Moderating Role Of Cord Blood Vitamin D In The Association Between Gestational Cardiovascular Health And Offspring Neurodevelopment

ObjectiveGestational cardiovascular health(CVH)may be a key factor influencing fetal glucolipid metabolism disorders and optimizing infant neurodevelopment.It is unknown whether the association between gestational CVH and infant neurodevelopment differs by cord blood vitamin D levels.Therefore,this study aimed to assess the association of gestational CVH with infant neurodevelopment,and whether such relation was modified by cord blood 25-hydroxyvitamin D [25(OH)D] concentrations.MethodsBased on a prospective birth cohort,from March 2018 to June 2021,pregnant women were recruited from three hospitals in Hefei and were followed up from baseline(16-23 weeks)to 12 months postpartum.The enrolled participants were interviewed faceto-face and completed a questionnaire including demographic and lifestyle characteristics.At 24-28 gestational weeks,pregnant women underwent a 75 g oral glucose tolerance test and routine prenatal examination.Health data were extracted from the medical record to assess gestational CVH.At the time of delivery,cord blood was collected,and basic information on neonatal birth outcomes was obtained from the medical record.At 12 months postpartum,infants were tested with the Ages and Stages Questionnaire Edition3(ASQ-3)to assess infant neurodevelopmental outcomes.Cord blood samples collected in this study were used to measure 25(OH)D,C-peptide,a glucose metabolism indicator,total cholesterol(TC),triacylglycerol(triacylglycerol),high density lipoproteincholesterol(HDL-C),and low density lipoprotein-cholesterol(LDL-C).This study’s final sample for analysis was 1714 mother-infant pairs with complete gestational CVH data,cord blood sample results,and infant ASQ-3 test results at 12 months of age.Statistical analyses were performed with SPSS 25.0(IBM Corp)and R studio(4.0.3)software.Multiple Logistic regression models were used to examine the association between gestational CVH exposure and infant neurodevelopmental outcomes at 12 months of age.Linear regression models were used to investigate the association between gestational CVH and cord blood glycolipid metabolism parameters.The mediating effect was used to explore the role of cord blood C-peptide in the relationship between gestational CVH and infant neurodevelopment.To explore the relationship between cord blood 25(OH)D level and cord blood C-peptide metabolism as well as infant neurodevelopment using a restricted cubic spline regression model.Further stratified analysis was performed according to cord blood vitamin D status to explore the association between gestational CVH exposure and cord blood glucose metabolism as well as infant neurodevelopmental outcomes.ResultsAmong 1714 mother-infant pairs included in the analysis,26.3% of pregnant women had poor CVH at 24-28 weeks of gestation,30.5% had intermediate CVH,and 43.2% had ideal CVH.At the age of 12 months,the abnormal rates of ASQ-3 communication domain in ideal,intermediate,and poor CVH groups were 4.6%,4.8%,and 9.6%,respectively.After adjusting for potential confounding factors,compared with the ideal level group,the poor level group of gestational CVH was significantly associated with infant communication domain failure(RR=2.06,95%CI: 1.24,3.42).However,no significant association was found between gestational CVH and other domains of ASQ-3(gross motor,fine motor,problem-solving,personal social).Compared with the ideal CVH group,the umbilical cord blood glucose metabolism index C-peptide concentration changed by 9.0%(β=0.09,95%CI: 0.06,0.13)in the poor CVH group.There were no correlation in cord blood lipid metabolism indexes(TC,TG,HDL-C,LDL-C)among the three groups.For each unit increase in cord blood C-peptide concentration,infant communication domain failure risk increased(RR=3.31,95%CI:2.06,5.32).Mediation analysis showed that cord blood C-peptide partially mediated the association between gestational CVH and infant communication domain failure.The results of the restricted cubic spline regression model showed that when the cord25(OH)D concentration <50 nmol/L,the association of cord 25(OH)D with the risk of hyperinsulinemia and the risk of infant communication domain failure decreased(p<0.001).Further stratified analysis according to cord blood vitamin D status showed that only in cord blood vitamin D deficiency(25(OH)D<50 nmol/L).Compared with the ideal CVH level group,the poor CVH level group was significantly associated with the increased risk of hyperinsulinemia and the risk of infant communication domain failure(RR=1.99,95%CI: 1.30,3.05;RR=2.44,95%CI: 1.41,4.21).ConclusionsGestational poor CVH was associated with an increased risk of infant neurodevelopment at ASQ-3 failure in the communication domain.Adequate cord blood25(OH)D levels might attenuate this association.