Associations Of Normal Range Glycated Hemoglobin A1c During Pregnancy With Adverse Birth Outcomes

Objective:To explore the association between the HbA1c level which was below 6.5%within 24 weeks of pregnancy and adverse birth outcomes,such as preterm birth,low birth weight(LBW),macrosomia,small for gestational age(SGA)and large for gestational age(LGA).and to put forward the suitable range of the HbA1c level in Chinese pregnant women,so as to provide scientific basis for reducing adverse neonatal outcomes and monitoring the glucose metabolism of pregnant women.Methods:After excluding the pregnant women with gestational diabetes mellitus(GDM)and the pregnant women whose HbA1c level were higher than 6.5%,4 861pregnant women and their newborns who gave birth in Guangdong Maternal and Child Health Hospital from September 2014 to May 2018 were included.Generalized linear regression model was used to analyze the influencing factors of the HbA1c level within 24 weeks of pregnancy.According to the quartile of HbA1c level,the subjects were divided into four groups(Q1,Q2,Q3,Q4 from low to high).Logistic regression model was used to explore the relationship between the HbA1c level and adverse birth outcomes.The suitable range of the HbA1c level in Chinese population within 24 weeks of pregnancy was put forward based on the pregnant women without adverse birth outcomes and verified by restricted cubic spline(RCS).Results:(a)In this study,the average age of pregnant women was 31.2±4.4years old,and the average pre-pregnancy BMI was 20.6±2.7 kg/m~2.Among the newborns,there were 2550(52.5%)boys,with an average gestational age of 39.0±1.5weeks and an average birth weight of 3.2±0.4kg.The incidence rates of premature birth,LBW,macrosomia,SGA and LGA were 4.4%,4.0%,4.3%,10.1%and 6.2%,respectively.(b)The median of the HbA1c level within 24 weeks of pregnancy were 4.8%.The HbA1c level was correlated with pregnant women’s age,pre-pregnancy BMI,parity and blood glucose concentration at 0 h,1h and 2h of OGTT.The distribution of the HbA1c level in pregnant women with or without preterm birth,LBW,macrosomia and LGA was different.(c)According to the quartile of HbA1c level,the HbA1c levels in Q1,Q2,Q3and Q4 groups were 3.0-4.6%,4.7-4.8%,4.9-5.1%and 5.2-6.0%,respectively.After adjusting for potential confounding factors,the results of Logistic regression model showed that the risks of macrosomia,SGA and LGA in Q4 group were 1.73 folds(95%CI:1.11-2.70),1.51 folds(95%CI:1.10-2.07)and 1.57 folds(95%CI:1.08-2.27)than those in Q1 group.The HbA1c level was not associated with preterm birth and LBW.In the sensitivity analysis of excluding special population,these associations were still steady.(d)The results of stratified analysis showed that the positive correlation between the HbA1c level during pregnancy with LBW and SGA were more significant in male infants,the positive correlation between the HbA1c level with LGA during pregnancy was more significant in female infants,and the positive correlation between HbA1c level during pregnancy with macrosomia,SGA and LGA were more significant in older and higher BMI pregnant women.(e)In this study,healthy pregnant women without adverse neonatal outcomes were taken as the reference population,and the suitable range of the HbA1c level within 24 weeks of pregnancy was 4.6-5.0%.The risk of various adverse birth outcomes was low when the HbA1c level is within this range according to the results of RCS.Conclusions:Even if the HbA1c level of pregnant women was lower than 6.5%within 24 weeks of pregnancy,the higher level of HbA1c would increase the risk of macrosomia,SGA and LGA.The HbA1c level maintained within the range of 4.6-5.0%was beneficial for decrease the adverse birth outcomes.In the future,more large sample prospective studies are needed to verify our research results,especially those based on Chinese population.