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

Abstract

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. Key Points

Gestational and pregestational diabetes in pregnant women with cystic fibrosis

“…One study of 691 pregnancies in women with type 1 diabetes compared to pregnancies without diabetes demonstrated a 3 times increased risk for malformation with first trimester A1c 5.6–6.8%, with risk rising to ∼5 times for A1c 9.4% or higher, which correlated to absolute malformation risk of 4.1% versus 6.6%, respectively; interestingly, the highest relative risk (6.0) was associated with mothers who went without A1c testing in early pregnancy [47] . Another study of 1649 pregnancies affected by pregestational diabetes (type 2 and type 1 diabetes) similarly documented a linear risk for most congenital malformations with higher risk beginning with A1c of 6% or higher, and with fetal malformation incidence progressively reaching 15% in the highest A1c categories [50] . Like GDM, pregestational diabetes carries elevated risk for perinatal mortality, but the risk is even higher [41] , [52] .…”

“…The extent of malformation risk is directly related to the degree of maternal hyperglycemia. HbA1c in the first trimester portends risk of fetal malformation and neonatal and perinatal mortality, and risk elevations begin even with minor elevations in HbA1c [47] , [50] , [51] . One study of 691 pregnancies in women with type 1 diabetes compared to pregnancies without diabetes demonstrated a 3 times increased risk for malformation with first trimester A1c 5.6–6.8%, with risk rising to ∼5 times for A1c 9.4% or higher, which correlated to absolute malformation risk of 4.1% versus 6.6%, respectively; interestingly, the highest relative risk (6.0) was associated with mothers who went without A1c testing in early pregnancy [47] .…”

Prenatal monitoring of pregnancies complicated by diabetes mellitus

“…Congenital malformations (CM) are the leading cause of perinatal mortality in diabetes, accounting for 50%, compared to 20% to 30% in the general population. Children whose mothers are preconception diabetics (type I and type II) have an increased risk for congenital anomalies (18). Some authors indicate that elevated HbA1c values in the first trimester are associated with a higher risk for CM.…”

“…Some authors indicate that elevated HbA1c values in the first trimester are associated with a higher risk for CM. Diabetic vasculopathy has also been linked to an increased risk of CM in some studies (18).…”

Unmasking Barriers in the Delivery of Preconception Counseling and Contraception Provision for Patients With Type 1 or Type 2 Diabetes

“…Suboptimal glycemic control among women with type 1 or type 2 diabetes before conception and during the early part of pregnancy is a powerful risk factor for fetal anomalies, macrosomia, and stillbirth. Major congenital anomalies occur in up to 25–30% of infants of women with type 1 or type 2 diabetes ( 1 ). Hyperglycemia during fetal organogenesis (5–8 weeks after the last menstrual period) is a considerable teratogen, and, consequentially, the risk of fetal anomalies related to preexisting maternal diabetes can be reduced to background risk when glycemic control is at goal.…”