CONGENITAL HEART DISEASE (CHD): MATERNAL DIABETES AND ASSOCIATED CONTRIBUTING FACTORS
Diabetes Mellitus Diabetes mellitus (DM) is one of the most common maternal conditions complicating pregnancies, affecting ≈3% to 10% of all pregnancices. Of these, 20% (or ≈1% of all pregnant women) have DM before conception and are considered to have pregestational DM (87). Overall, there is nearly a 5-fold (3%–5%) increase in CHD compared with the general population in women with pregestational DM.(6)
A higher relative risk noted for specific cardiac defects includes 6.22 for heterotaxy, 4.72 for truncus arteriosus, 2.85 for transposition of the great arteries (d-TGA), and 18.24 for single-ventricle defects in pregestational diabetes pregnancies. (7)
Several studies indicate that lack of preconceptional glycemic control, as evidenced by elevation in serum hemoglobin A1C (HbA1c) levels >8.5% in the first trimester, is associated with an increase in all congenital malformations,(8) Additional studies, however, have suggested that there is no threshold HbA1c value that increases risk for fetal CHD.(7,89) In a study of 3 different diabetic populations, HbA1c values slightly above the normal range (mean, 6.4%) were associated with a significantly increased risk of cardiac malformation of 2.5% to 6.1% in offsprings.(7) Therefore, it appears that although the risk may be highest in those with HbA1c levels >8.5%, all pregnancies of pregestational diabetic women are at some increased risk.
Given this information, a fetal echocardiogram should be performed in all women with pregestational DM.
Insulin resistance acquired in the third trimester, or gestational DM, does not appear to confer an increased risk of CHD in the fetus.90 For this reason, a fetal echocardiogram is not indicated for these pregnancies. Fetuses may develop ventricular hypertrophy late in gestation in the presence of poorly controlled maternal gestational or pregestational DM, and the degree of hypertrophy has been shown to be related to glycemic control. In women with HbA1c levels <6% in the second half of pregnancy, the effects are mild, so fetal echocardiogram is not recommended.91 If HbA1c levels are >6%, fetal echocardiogram in the third trimester to assess for ventricular hypertrophy may be considered, but its usefulness has not been determined.
Several studies have analysed the impact of Pregestational diabetes on the fetus. Here is a summary of current literature.
In a meta-analysis, Simone et al in 2015 analysed 12 large studies:
The meta-analysis of 12 studies was used to estimate risks and estimate population attributable fractions (PAFs). The authors calculated the annual number of CHDs in the U.S. potentially preventable by establishing glycemic control before pregnancy.
Women with pregestational diabetes mellitus (PGDM), have 2–5 times the risk of having a baby with CHD compared to women without diabetes. (4-7) The major teratogen in diabetic pregnancies is presumed to be hyperglycemia caused by poor glycemic control during organogenesis. (11)
The relative risk (Odds Ratio-OR) for PGDM and all CHDs estimated in the meta-analysis was 3.8. PGDM and AVSD had the largest summary OR (10.6), and PGDM and coarctation of the aorta had the smallest summary OR (3.7).
In the U.S., for all CHDs considered in the analysis, reducing the risk for women with PGDM to that of women without PGDM could potentially reduce the annual number of CHD cases by 2670.
In one of the largest population based studies published in 2013 in Circulation, Liu et al conducted the study in Canada. Their conclusions were as follows:
A population-based study of all mother-infant pairs (n=2,278,838) in Canada (excluding Quebec) from 2002 to 2010 was carried out. There were 26 488 infants diagnosed with CHDs at birth or at rehospitalization in infancy; the overall CHD prevalence was 116.2 per 10,000 live births, of which the severe CHD rate was 22.3 per 10,000. Risk factors for CHD included maternal age ≥40 years, multifetal pregnancy, diabetes mellitus type 1, type 2, hypertension, thyroid disorders, congenital heart disease (aOR, 9.92; 95% CI, 8.36-11.8), systemic connective tissue disorders (aOR, 3.01; 95% CI, 2.23-4.06), and epilepsy and mood disorders (aOR, 1.41; 95% CI, 1.16-1.72).
In another large population based study of Washington state spanning 1992-2007, 14,142 children identified with CHD with 141,420 control. Infants with CHD were more likely to have an obese mother. The association was greatest for left and right ventricular outflow tract defects. A greater risk of CHD among offspring is an important outcome of maternal obesity, and suggests a need for targeted medical management strategies.