Maternal Parity and the Risk of Congenital Heart Defects in Offspring: A Dose-Response Meta-Analysis of Epidemiological Observational Studies

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.

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.

Conclusion

In summary, this meta-analysis provided a robust estimate of the positive association between maternal parity and risk of CHD.