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Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic
Gitte Hedermann1, Paula L Hedley1, Ida N Thagaard1,2
1Department for Congenital Disorders, Danish National Biobank and Biomarkers, Statens Serum Institut, Copenhagen, Denmark.
Insights
Maternal metabolic disorders like diabetes and preeclampsia increase offspring congenital heart defect (CHD) risk. Combinations of these conditions may further elevate risks, necessitating further research into their combined effects.
Area of Science:
- Cardiovascular Science
- Maternal-Fetal Medicine
- Endocrinology
Background:
- Congenital heart defects (CHDs) are common birth defects with complex origins.
- Maternal metabolic disorders, including obesity, diabetes, and hypertension, are linked to increased CHD risk.
- These conditions often coexist, suggesting combined effects warrant investigation.
Purpose of the Study:
- To review evidence associating maternal metabolic disorders (obesity, diabetes, hypertension, preeclampsia, dyslipidemia) with offspring CHDs.
- To evaluate the significance of combined maternal metabolic conditions, such as metabolic syndrome, as risk factors for CHDs.
Main Methods:
- Systematic literature search of PubMed and Embase (1990-2021).
- Included English-language case-control and cohort studies assessing maternal metabolic disorders and offspring CHDs.
- Studies were selected based on quality assessment.
Main Results:
- 32 studies qualified for inclusion; most examined individual disorders.
- Obesity, gestational diabetes, and hypertension showed marginal increases in CHD risk.
- Pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs.
- One study indicated a potential additive risk from maternal obesity and gestational diabetes.
Conclusions:
- Further research is needed on glucose-insulin homeostasis in the etiology of metabolic disorders during pregnancy.
- Investigating the combined effects of maternal metabolic disorders, not just individual conditions, is crucial for understanding CHD development.
- Understanding these associations can inform strategies for preventing CHDs.
Background:
Congenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors.
Methods:
A systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score.
Results:
Of the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes.
Conclusions:
Future studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and-particularly-in combination, with CHDs are needed.
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