Risk of congenital heart defects in offspring exposed to maternal diabetes mellitus: an updated systematic review and meta-analysis
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A systematic review and meta-analysis was performed to assess the risk of congenital heart defects (CHDs) and its specific phenotypes associated with maternal diabetes mellitus (DM) including pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM).
PubMed, Embase, Medline, Google Scholar, Cochrane Libraries, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Fulltext Database and China Biology Medicine disc were searched from the inception dates to 15 December 2018, to identify case–control or cohort studies assessing the association between maternal DM and risk of CHDs. The exposure of interest was maternal DM; the outcomes of interest were CHDs and its specific phenotypes. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analyses were performed to explore potential heterogeneity moderators.
Total 52 studies, which involved 259,917 patients with CHDs among 16,929,835 participants, were included for analysis. Overall, mothers with DM compared with those without DM had a significantly higher risk of CHDs in offspring [odds ratios (OR) = 2.71, 95% confidence intervals (CI) 2.28–3.23]. When data were restricted to different types of DM, a significantly increased risk of CHDs was observed among mothers with PGDM (OR = 3.18, 95% CI 2.77–3.65) and GDM (OR = 1.98, 95% CI 1.66–2.36). Our study suggested the risk of CHDs was significantly higher among mothers with PGDM than those with GDM. Additionally, this study suggested maternal DM was significantly associated with most phenotypes of CHDs; of these, double outlet of the right ventricle (OR = 10.89; 95% CI 8.77–13.53), atrioventricular septal defect (OR = 5.74; 95% CI 3.20–10.27) and truncus arteriosus (OR = 5.06; 95% CI 2.65–9.65) were identified as the first three of the most common phenotypes of CHDs associated with maternal DM.
The maternal DM including PGDM and GDM are significantly associated with risk of CHDs and its most phenotypes. The PGDM seems to be more likely to cause CHDs in offspring than GDM. Further studies are needed to clarify the underlying mechanisms.
KeywordsMaternal diabetes mellitus Congenital heart defects Pregestational diabetes mellitus Gestational diabetes mellitus Phenotypes Meta-analysis
The authors would like to thank the editors and reviewers for their suggestions.
LTC: literature searching, data collection and manuscript writing. TBY: manuscript writing. LZC: manuscript revision. LSW: data management. TTW: data analysis. LJZ: data collection. ZWY: data interpretation. SMZ: literature searching. LL: data collection. ZZ: data analysis. JBQ: conception, design and revise the manuscript.
This work was supported by the Project Funded by Natural Science Foundation of Hunan Province [Grant numbers 2018JJ2551], National Natural Science Foundation Program of China [Grant numbers 81803313], Hunan Provincial Key Research and Development Program [Grant numbers 2018SK2063; 2018SK2062], and New Teachers’ Scientific Research Driven Foundation of Central South University [Grant numbers 502045001].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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