Association between Abnormal Glucose Regulation at Different Time Point and Fetal Congenital Heart Diseases during Pregnancy: a Cohort Study of 72236 Births

BACKGROUND: GDM or prepregnancy diabetes mellitus during pregnancy will lead to an increased risk of fetal congenital malformations 16-18 . However, the influence of different time periods on blood glucose level is not clear, the object of this study was to explore the association between abnormal glucose regulation at different time point and congenital heart diseases during pregnancy METHODS: This retrospective and consecutive cohort study were conducted on singleton pregnancies carried to 20 completed weeks of gestation or beyond, from the Fujian Provincial Maternity and Children’s Hospital, China, between January 1, 2014 and December 31, 2020. A diagnosis of gestational diabetes was defined according to Fasting blood glucose level and 75-g OGTT. Maternal and infant characteristics and outcomes were compared between neonates born to mothers with and without Abnormal blood glucose at different time of OGTT. Descriptive statistics are shown as mean ± standard deviation or median (range interquartile) for continuous variables and tested with ANOVA or Kruskal-Wallis rank-sum test, whereas frequency (percentage) and χ2 test were used for categorical variables. All analyses were conducted using R version 4.1.0. RESULTS: A total of 71703 normal subjects and 533 subjects with fetal cardiovascular malformations were included in this study. Pregnant women who deliver a normal fetus tend to older and have higher rate of gestational hypertension and abnormal glucose during pregnancy than those who deliver a newborn with CHD (P < 0.05). Compared to the corresponding normal group, GDM, OGTT 0 hour≥5.1mmol/L, OGTT 1 hour≥10mmol/L, and OGTT 2 hour≥8.5mmol/L confer to 55%, 48%, 54%, and 59% increase in risk of CHD, respectively. Compared to group 1 (OGTT 0h and OGTT 1h and 2h are both normal), group 3 (OGTT 0h is normal, while OGTT 1h or 2h is abnormal) and group 4 (OGTT 0h and OGTT 1h or 2h are both abnormal) exhibit higher risk of CHD (OR= 1.53 and 2.21, respectively, all P<0.05 ). However, group 2 (OGTT 0h is abnormal, while OGTT 1h and 2h is normal) did not demonstrate a statistically significant elevated risk. CONCLUSION: Gestational diabetes is an identified hazard factor for neonatal CHD. The effect of GDM on CHD is more reflected in impaired tolerance of glucose regulation than in elevated fasting blood glucose levels. Pregnant women with normal fasting glucose but abnormal OGTT 1 hour or 2 hour may be overlooked as an implicit risk population, and should be given adequate attention.