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Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c
R He1, L K Hornberger1, A Kaur1
1Fetal & Neonatal Cardiology Program, Division of Cardiology, Department of Pediatrics, Women & Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada.
Insights
Pregestational diabetes mellitus (PDM) increases congenital heart disease (CHD) risk by 2.8 times. Poor glycemic control (HbA1c > 8.0%) further elevates this risk to 8.5 times, highlighting the need for careful pregnancy screening.
Area of Science:
- Obstetrics and Gynecology
- Maternal-Fetal Medicine
- Cardiology
Background:
- Pregestational diabetes mellitus (PDM) is a known risk factor for congenital heart disease (CHD).
- The impact of glycemic control during pregnancy on CHD risk requires further clarification.
Purpose of the Study:
- To determine the relative risk (RR) of major congenital heart disease (mCHD) in offspring of pregnancies with PDM.
- To assess the influence of first-trimester glycemic control on mCHD risk.
Main Methods:
- Retrospective cohort study using Alberta Perinatal Health Program registry data.
- Linked diabetes status and first-trimester hemoglobin A1c (HbA1c) levels for 594,773 births.
- Log-binomial modeling used to calculate adjusted relative risks (aRR).
Main Results:
- PDM was associated with a 2.8-fold increased risk of mCHD (RR, 2.8; 95% CI, 2.1-3.7).
- Elevated first-trimester HbA1c levels significantly increased mCHD risk in PDM pregnancies.
- HbA1c > 8.0% in PDM pregnancies showed an 8.5-fold increased risk of mCHD (aRR, 8.5; 95% CI, 5.0-14.4).
Conclusions:
- PDM significantly elevates the risk of mCHD in offspring.
- First-trimester glycemic control is critical; higher HbA1c levels markedly increase mCHD risk.
- Findings support refining screening protocols for high-risk pregnancies.
Objectives:
The association between pregestational diabetes mellitus (PDM) 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 (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk.
Methods:
We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling.
Results:
Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%).
Conclusions:
PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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