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.Over the past several decades, economic, technologic and social changes in the developed world have significantly increased the number of women who delay childbirth to their late 30s and beyond. Between 1980 and 1993 in the European Union, the mean maternal age at first birth rose by 1.5 years, from 27.1 to 28.6 years.¹ Between 1991 and 2001 in the United States, the percentage of first births for women 35–39 years of age increased by 36% and that for women 40–44 years of age increased by 70%.^2,3 This huge demographic shift has become an important public health issue, since numerous studies have indicated that increased maternal age (35 years of age or older) is associated with an increased risk of maternal morbidity, obstetric interventions and adverse pregnancy outcomes.^4–11The intention to conceive and the timing of conception are complex issues influenced by many factors. Understanding the potential outcomes of pregnancy at an advanced maternal age may constitute one of these factors. Stillbirth, or late fetal death, is one of the adverse pregnancy outcomes of most concern, but studies on the relation between increased maternal age and stillbirth risk have led to inconsistent conclusions. We therefore conducted a systematic review of observational studies to explore the association between advanced maternal age and the risk of stillbirth.