Maternal parity and the risk of congenital heart defects in offspring: A dose-response meta-analysis of epidemiological observational studies

Abstract

Background: Epidemiological studies have reported conflicting results regarding maternal parity and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal parity and CHDs in offspring has not been conducted. Methods: We searched MEDLINE and EMBASE for articles catalogued between their inception and March 8, 2014; we identified relevant published studies that assessed the association between maternal parity and CHD risk. Two authors independently assessed the eligibility of the retrieved articles and extracted data from them. Study-specific relative risk estimates were pooled by random-effects or fixed-effects models. From the 11272 references, a total of 16 case-control studies and 3 cohort studies were enrolled in this meta-analysis. Conclusion: In summary, this meta-analysis provided a robust estimate of the positive association between maternal parity and risk of CHD. Results: The overall relative risk of CHD in parous versus nulliparous women was 1.01 (95% CI, 0.97-1.06; Q = 32.34; P = 0.006; I2 = 53.6%). Furthermore, we observed a significant association between the highest versus lowest parity number, with an overall RR = 1.20 (95% CI, 1.10-1.31; (Q= 74.61, P<0.001, I2 = 82.6%). A dose-response analysis also indicated a positive effect of maternal parity on CHD risk, and the overall increase in relative risk per one live birth was 1.06 (95% CI, 1.02-1.09); Q = 68.09; P<0.001; I2 = 80.9%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among studies. A Galbraith plot was created to graphically assess the sources of heterogeneity.