Association Between Maternal Chronic Conditions and Congenital Heart Defects: a Population-based Cohort Study

Background: This study quantifies the association between maternal medical conditions/illnesses and congenital heart defects (CHDs) among infants.

Methods And Results: We carried out a population-based study of all mother-infant pairs (n=2,278,838) in Canada (excluding Quebec) from 2002 to 2010 using data from the Canadian Institute for Health Information. CHDs among infants were classified phenotypically through a hierarchical grouping of International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada codes. Maternal conditions such as multifetal pregnancy, diabetes mellitus, hypertension, and congenital heart disease were defined by use of diagnosis codes. The association between maternal conditions and CHDs and its subtypes was modeled using logistic regression with adjustment for maternal age, parity, residence, and other factors. 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 (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.39-1.58), multifetal pregnancy (aOR, 4.53; 95% CI, 4.28-4.80), diabetes mellitus (type 1: aOR, 4.65; 95% CI, 4.13-5.24; type 2: aOR, 4.12; 95% CI, 3.69-4.60), hypertension (aOR, 1.81; 95% CI, 1.61-2.03), thyroid disorders (aOR, 1.45; 95% CI, 1.26-1.67), 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). Specific CHD subtypes were associated with different maternal risk factors.

Conclusions: Several chronic maternal medical conditions, including diabetes mellitus, hypertension, connective tissue disorders, and congenital heart disease, confer an increased risk of CHD in the offspring.