Increased maternal Body Mass Index is associated with congenital heart defects: An updated meta-analysis of observational studies

Purpose: To review and summarize the epidemiologic evidence on the association of maternal Body Mass Index (BMI) with risk of congenital heart defects (CHDs) and to assess the possible dose-response patterns. Methods: Six electronic databases were searched for eligible studies up to April 2018. The summary risk estimates were calculated using either the fixed-effect models or random-effect models. A dose-response meta-analysis was also performed to capture the shape of the observed association. Subgroup and sensitivity analysis were conducted to explore the potential heterogeneity moderators. Results: Twenty nine studies involving 99.205 CHDs cases among 6,467,422 participants were included in the meta-analysis. Mothers who were overweight (odds ratio [OR] = 1.07; 95% confidence intervals [CI]: 1.00-1.13) and obese (OR = 1.32; 95% Q: 1.21-1.43) had a significantly higher risk of total CHDs in their offspring when compared with those with normal weight. When obesity was further divided into class I (OR = 1.15; 95% CI: 1.11-1.20), class II (OR = 1.26; 95% CI: 1.18-1.34) and class III (OR = 1.42; 95% CI: 1.33-1.51) obesity, a significantly increased risk of total CHDs persisted. Different risks for specific CHD phenotypes were also found in different BMI categories. Furthermore, a nonlinear dose-response relationship between maternal BMI and risk of total CHDs was observed. Subgroup and sensitivity analyses identified the most relevant heterogeneity moderators. Conclusion: The increased maternal BMI is associated with the risk of developing CHDs in offspring. Severe obesity can play an independent role in the observed association, but the effect may be mediated by diabetes mellitus. Preventing obesity or excessive weight gain is a priority for CHDs prevention. (C) 2018 Published by Elsevier B.V.