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. 2024 Jan 2;7(1):e2350579.
doi: 10.1001/jamanetworkopen.2023.50579.

Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring

Riitta Turunen  1   2 , Anna Pulakka  2   3 , Johanna Metsälä  2 , Tero Vahlberg  4 , Tiina Ojala  1 , Mika Gissler  5   6   7 , Eero Kajantie  2   8   9 , Emmi Helle  1   2   10   11
Affiliations

Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring

Riitta Turunen et al. JAMA Netw Open. .

Abstract

Importance: Maternal diabetes and overweight or obesity are known to be associated with increased risk of congenital heart defects (CHDs) in offspring, but there are no large studies analyzing outcomes associated with these factors in 1 model.

Objective: To investigate the association of maternal diabetes and overweight or obesity with CHDs among offspring in 1 model.

Design, setting, and participants: This nationwide, population-based register study was conducted in a birth cohort from Finland consisting of all children born between 2006 and 2016 (620 751 individuals) and their mothers. Data were analyzed from January 2022 until November 2023.

Exposures: Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obesity (≥30), was assessed. Maternal diabetes status, classified as no diabetes, type 1 diabetes (T1D), type 2 or other diabetes, and gestational diabetes, was assessed.

Main outcomes and measures: Odds ratios (ORs) of isolated CHDs in children were found. In addition, 9 anatomical CHD subgroups were studied.

Results: Of 620 751 children (316 802 males [51.0%]; 573 259 mothers aged 20-40 years [92.3%]) born in Finland during the study period, 10 254 children (1.7%) had an isolated CHD. Maternal T1D was associated with increased odds of having a child with any CHD (OR, 3.77 [95% CI, 3.26-4.36]) and 6 of 9 CHD subgroups (OR range, 3.28 [95% CI, 1.55-6.95] for other septal defects to 7.39 [95% CI, 3.00-18.21] for transposition of great arteries) compared with no maternal diabetes. Maternal overweight was associated with left ventricular outflow tract obstruction (OR, 1.28 [95% CI, 1.10-1.49]) and ventricular septal defects (OR, 0.92 [95% CI, 0.86-0.98]), and obesity was associated with complex defects (OR, 2.70 [95% CI, 1.14-6.43]) and right outflow tract obstruction (OR, 1.31 [95% CI, 1.09-1.58]) compared with normal maternal BMI.

Conclusions and relevance: This study found that maternal T1D was associated with increased risk for most types of CHD in offspring, while obesity and overweight were associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. These different risk profiles of T1D and overweight and obesity may suggest distinct underlying teratogenic mechanisms.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Pulakka reported receiving grants from the European Commission outside the submitted work. Dr Metsälä reported receiving grants from the Finnish Cultural Foundation outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Maternal Factors and Isolated Congenital Heart Defects (CHDs)
The association of maternal body mas index (BMI; calculated as weight in kilograms divided by height in meters squared) and diabetes with CHDs was investigated using child birth year–adjusted (A) and multivariable (B) logistic regression analysis. Multivariable analysis was adjusted to maternal smoking, maternal age, child birth year, first parity, and highest parental education level. Normal BMI (18.5-24.9) and no diabetes were used as reference groups in logistic regression analysis. Statistical significance was reached with P < .05. GD indicates gestational diabetes; OR, odds ratio; T1D, type 1 diabetes; T2D, type 2 diabetes.
Figure 2.
Figure 2.. Association Between Maternal Factors and Congenital Heart Defect (CHD) Subgroups
The analysis of the association of maternal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and diabetes with offspring CHD subgroup was adjusted by birth year of the child. Normal BMI (18.5-24.9) and no diabetes were used as reference groups. Statistical significance was reached with P <. 05. Factors with NA could not be analyzed owing to low population numbers. ASD indicates atrium septal defect; GD, gestational diabetes; LVOTO, left ventricle outflow tract obstruction; NA, not applicable; OR, odds ratio; RVOTO, right ventricle outflow tract obstruction; T1D, type 1 diabetes; T2D, type 2 diabetes or other diabetes; TGA, transposition of great arteries; VSD, ventricular septal defect.
Figure 3.
Figure 3.. Association Between Maternal Factors and Congenital Heart Disease (CHD) Subgroups in Multivariable Analysis
The multivariable logistic regression analysis of the association of maternal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and diabetes with CHD subgroups was adjusted to maternal smoking, maternal age, birth year of the child, first parity, and highest parental education level. Normal BMI (18.5-24.9) and no diabetes were used as reference groups. Statistical significance was reached with P < .05. Factors with NA could not be analyzed owing to low population numbers. ASD indicates atrium septal defect; GD, gestational diabetes; LVOTO, left ventricle outflow tract obstruction; NA, not applicable; OR, odds ratio; RVOTO, right ventricle outflow tract obstruction; T1D, type 1 diabetes; T2D, type 2 diabetes or other diabetes; TGA, transposition of great arteries; VSD, ventricular septal defect.
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