Maternal Reproductive History and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis

Epidemiological studies have reported conflicting results on the association of congenital heart defect (CHD) risk in offspring with a maternal history of prior pregnancies and abortions, but no meta-analysis has been reported. We searched MEDLINE and EMBASE from their inception to April 14, 2014, for relevant studies that assessed the association between maternal reproductive history and CHD risk. Two authors independently assessed eligibility and extracted data. Fixed-effects or random-effects models were used to calculate the pooled odds ratios (ORs). Among 1,599 references, 17 case–control studies and one nested case–control study were included in this meta-analysis. The summary OR for the ever versus nulligravidity was 1.18 (95 % CI 1.03–1.34). A dose–response analysis also indicated a positive effect of maternal gravidity on CHD risk, and the summary OR for each increment in number of pregnancies was 1.13 (95 % CI 1.08–1.18). A history of abortion was associated with a 24 % higher risk of CHD, OR = 1.24 (95 % CI 1.11–1.38). When stratified by abortion category, CHD risk increased by 18 and 58 % with a history of spontaneous abortion and induced abortion, respectively. The summary OR for each increment of one abortion was 1.28 (95 % CI 1.18–1.40). In summary, this study provides evidence that increased maternal gravidity was positively associated with a risk of CHDs in offspring. Meanwhile, our results demonstrate a positive association of any history of abortion with an increased risk of CHDs.