Study On Related Factors Of Abnormal Heart Development In Infants Of Diabetic Mothers

Objectives:To know the general condition of heart development in infants of diabetic mothers(IDMs)and the effects of related factors on cardiac development from maternal and infants’ clinical datas and genetic level,and the correlation analysis of cardiac hypertrophy.Methods:The study was performed at the department of neonatology,first affiliated hospital of Kunming Medical University.63 full-term infants of diabetic mothers with no serious illness were collected from September 2018 to March 2019.For all babys,fasting insulin was measured within 3 days after birth, and cardiac ultrasound were completed before discharge,NKX2.5 gene were detected in infants with abnormal cardiac development.The IDMs were divided into following groups:1)according to the mother’s blood glucose levels:the IDMs were divided into well-controlled blood glucose group and pooly-controlled blood glucose group,to analyze the effects of blood glucose on cardiac development;2)according to the mother’s cotrolled ways of blood glucose:the IDMs were divided into insulin controlled group and diet and exercise controlled group,to analyze the effects of insulin therapy on cardiac development;3)according to the insulin level of infnats after birth:the IDMs were divided into non-hyperinsulinemia group and hyperinsulinemia group,to analyze the effects of hyperinsulinemia on cardiac development;4)according to the diagnosis time of maternal diabetes:the IDMs were divided into pre-pregnancy and early pregnancy group and middle-late pregnancygroup,to analyze the effects of duration of diabetes on cardiac development;5)according to materal pre-pregnancy BMI:the IDMs were divided into normal weight group and obesity group,to analyze the effects of mother obesity on fetal heart development;6)according to the results of cardiac ultrasound:the IDMs were divided into the abnormal cardiac development group and the normal cardiac development group,and NKX2.5 gene were detected in abnormal cardiac development group to analyze the relationship between NKX2.5 gene polymorphism and cardiac development.Finally,the study analyzed the correlation between interventricular septum thickness and materal fasting blood glucose,weight gain during pregnancy,neonatal insulin level and birth weight.Statistical analysis of data:single factor analysis using chi-square test,t-test,rank sum test;multi-factors analysis using two-category logistic regression analysis and multiple linear regression analysis;correlation analysis using Spearman rank correlation.Results:1.Among 63 IDMs,56 completed cardiac ultrasound,7 cases had normal heart development,26 cases had patent foramen ovale,23 cases had abnormal cardiac development,and the rate of abnormal cardiac development was 41%.The abnormal cardiac development types include:patent ductus arteriosus(28.6%),atrial septal defect(12.5%),interventricular septal hypertrophy(8.9%),ventricular septal defect(1.8%),thin interventricular septum(5.4%),atrial fissure(3.6%),double lumen right ventricle(1.8%),mild pulmonary hypertension(1.8%).2.1)The proportion of abnormal cardiac development in poorly-controlled blood glucose group(73%)was higher than that in well-controlled blood glucose group(33%),the difference was statistically significant(P=0.041);2)the proportion of abnormal cardiac development in the insulin controlled group(54%)was higher than that in the diet and exercise controlled group(39%),the proportion of abnormal cardiac development in the hyperinsulinemia group(67%)was higher than that in the non-hyperinsulinemia group(36%),the proportion of abnormal cardiac development in the obese group(48%)was higher than that in the normal weight group(37%),the differences were not statistically significant;3)the proportion of abnormal cardiac development in early pregnancy and pre-pregnancy group(40%)is basically the same as that in the second-third trimester(42%),and the difference was not statistically significant(P=0.903).3.1)Maternal fasting blood glucose(5.32±1.00 mmoI/L)in the abnormal cardiac development group was higher than that in the normal cardiac development group(4.85±0.50 mmol/L),the difference was statistically significant(P=0.026);2)The level of insulin(8.4±9.6 mU/L),the pre-pregnancy BMI(25.3±5.3 Kg/m2)were higher than that in the normal cardiac development group(insulin 6.7±4.5 mU/L,BMI 24.2±3.8 Kg/m2),the diagnosis time of maternal diabetes(17.7±8.2w)in the abnormal cardiac development group was earlier than that in the normal heart development group(18.5±9.0w),and the differences were not statistically significant.A two-category logistic regression analysis of the above factors indicated that the poorly-controlled maternal blood glucose was the main factor affecting cardiac development(OR=4.83,95%CI 1.122～20.824,P=0.034),and abnormal cardiac development has no significant correlation with maternal age,controlled ways of blood glucose,pre-pregnancy BMI,the diagnosis time of diabetes and the postnatal insulin level(P>0.05).4.Factors affecting the thickness of the interventricular septum:1)the interventricular septal thickness(3.45±0.52 mm)in the poorly-controlled blood glucose group was thicker than that in the well-controlled blood glucose group(3.27±0.47 mm),but the difference was not statistically significant(P=0.263).2)the thickness of the interventricular septum in the hyperinsulinemia group(3.54±0.47 mm)was thicker than that in non-hyperinsulinemia group(3.26±0.47 mm),but there was no significant difference between the two groups(P=0.059);3)The thickness of ventricular septum was positively correlated with maternal weight gain during pregnancy(y=0.296,P=0.031),and positively correlated with postnatal insulin level(y=0.309,P=0.024).5.The effect of NKX2.5 gene mutation on cardiac development:the study found two polymorphic loci rs2277923(63A>G)and rs703752(66G>T),and one missense mutation(956A>C)on NKX2.5 gene of IDMs.About the rs2277923 locus,the allele frequency of mutated base G was 61.8%,which was higher than the G allele frequency(48.6%)in the Asian population;about the rs703752 locus,the allele frequency of mutated base T was 14.7%,which was higher than the T allele frequency(4.4%)in the the East Asian population.Conclusions:1.The poorly-controlled maternal blood glucose leads to an increase in the rate of abnormal cardiac development in infants of diabetic mothers;2.The thickness of ventricular septum is positively correlated with maternal weight gain and insulin level;3.The polymorphic loci rs2277923 and rs703752 and misspelling mutation sites(956A>C)on NKX2.5 gene may be related to abnormal cardiac development.