Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: a systematic review

SummaryCongenital heart defects (CHDs) are the most common congenital malformations and affect neonatal mortality and morbidity. The aetiology of CHDs is complex. Large cohort studies 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 and possibly metabolic syndrome (MetS). The aim of this review is to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia, and MetS, or combinations thereof and CHDs overall as well as by subtype in the offspring. A literature search of PubMed and Embase databases identified 2,076 studies, 30 qualified for inclusion. All but one study investigated the individual metabolic disorders and their association with CHDs. 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. 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 with CHDs as well as subtypes of CHDs are needed.