Risk of major congenital heart disease in maternal diabetes is modified by hemoglobin A1c

The association between pre-gestational maternal diabetes (MD) and risk of congenital heart disease (CHD) is well-recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk of major CHD (mCHD) among offspring in pregnancies complicated by pre-gestational maternal diabetes (MD), and the effect of first trimester glycemic control on mCHD risk.We determined the incidence of mCHD, (requiring an operation at <1 year or resulting in pregnancy termination or fetal demise), among registered births in Alberta. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c ) at <16 weeks gestation and other covariates was performed using the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted risk ratio (aRR) calculated using log-binomial modelling (StataIC14.2).Of 1412 cases of mCHD in 594,755 Alberta births in the study period (2.37/1000), mCHD was present in 48/7449 births with MD (6.4/1000, RR 2.8 (95%CI 2.1, 3.7, p<0.001). In the entire cohort, increased maternal age (aRR 1.03, 95%CI 1.02, 1.04, p<0.0001) and multiple gestations (aRR 1.37 (95%CI 1.3, 2.1, p<0.001) were also associated with mCHD risk, whereas maternal pre-pregnancy weight >91kg was not. The stratified risks for mCHD associated with A1c ≤6.1%, 6.1%-8.0% and ≥8.0% were 4.2/1000, 6.8/1000, 17/1000 births, respectively; the aRR of mCHD associated with MD and an A1c >8.0% was 8.5 (95%CI 5.0, 14.4) compared to no diabetes, and 4.4 (95%CI 2.3, 8.8, p<0.001) compared to MD with a normal HbA1c (<6.1%).MD is associated with a 2.8 risk ratio for mCHD, increasing to 7.3 in those with HbA1c >8%. This data should facilitate refinement of referral indications for high-risk pregnancy screening. This article is protected by copyright. All rights reserved.