Congenital Malformation Risk According to Hemoglobin A1c Values in a Contemporary Cohort with Pregestational Diabetes

Objective The study aimed to evaluate the association between hemoglobin A1c values and likelihood of fetal anomalies in women with pregestational diabetes. Study Design Women with pregestational diabetes who delivered at a single institution that serves a nonreferred population from May 1, 2009 to December 31, 2018 were ascertained. Hemoglobin A1c values were obtained at the first prenatal visit. Women who delivered a singleton live- or stillborn infant with a major malformation as defined by European Surveillance of Congenital Anomalies criteria were identified. In infants with multiple system anomalies, each malformation was considered separately. Hemoglobin A1c values were analyzed categorically by using Mantel-Haenszel method and continuously with linear regression for trend for fetal anomalies. Results A total of 1,676 deliveries to women with pregestational diabetes were delivered at our institution, and hemoglobin A1c was assessed in 1,573 deliveries (94%). There were 129 deliveries of an infant with at least one major malformation, an overall anomaly rate of approximately 8%. Mean hemoglobin A1c concentration was significantly higher in pregnancies with anomalous infants, 9.3 ± 2.1% versus 8.0 ± 2.1%, and p <0.001. There was no difference in gestational age at the time hemoglobin A1c was obtained, 13 ± 8.3 versus 14 ± 8.7 weeks. Hemoglobin A1c was associated with increased probability of a congenital malformation. This reached 10% with a hemoglobin A1c concentration of 10%, and 20% with a hemoglobin A1c of 13%. Similar trends were seen when examining risk of anomalies by organ system with increasing hemoglobin A1c levels, with the greatest increase in probability for both cardiac and genitourinary anomalies. Conclusion In women with pregestational diabetes, hemoglobin A1c is strongly associated with fetal anomaly risk. Data from a contemporary cohort may facilitate counseling and also highlight the need for preconceptual care and glycemic optimization prior to entry to obstetric care.