Maternal age and risk of stillbirth: a systematic review

Background: The number of women who delay childbirth to their late 30s and beyond has increased significantly over the past several decades. Studies regarding the relation between older maternal age and the risk of stillbirth have yielded inconsistent conclusions. In this systematic review we explored whether older maternal age is associated with an increased risk of stillbirth. Methods: We searched MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews for all relevant articles (original studies and systematic reviews) published up to Dec. 31, 2006. We included all cohort and case-control studies that measured the association between maternal age and risk of stillbirth. Two reviewers independently abstracted data from all included studies using a standardized data abstraction form. Methodologic and statistical heterogeneities were reviewed and tested. Results: We identified 913 unique citations, of which 31 retrospective cohort and 6 case-control studies met our inclusion criteria. In 24 (77%) of the 31 cohort studies and all 6 of the case-control studies, we found that greater maternal age was significantly associated with an increased risk of stillbirth; relative risks varied from 1.20 to 4.53 for older versus younger women. In the 14 studies that presented adjusted relative risk, we found no extensive change in the direction or magnitude of the relative risk after adjustment. We did not calculate a pooled relative risk because of the extreme methodologic heterogeneity among the individual studies. Interpretation: Women with advanced maternal age have an increased risk of stillbirth. However, the magnitude and mechanisms of the increased risk are not clear, and prospective studies are warranted.