Risk of Recurrent Stillbirth: Systematic Review and Meta-Analysis

Despite being one of the most common adverse obstetric outcomes, 9.5% to 50.2% of stillbirths are classified as unexplained. Although this may be due in part to the many complex interacting factors that contribute to fetal death, there is also still great uncertainty surrounding stillbirth recurrence risks, with studies reporting inconsistent rates, from 2- to 10-fold. In this systematic review and meta-analysis, authors examine possible associations between stillbirth in an initial pregnancy and risk of stillbirth in subsequent pregnancies, in attempts to clarify some of these concerns. This study was a meta-analysis and systematic review of recurrent stillbirth; stillbirth was defined as fetal death occurring at more than 20 weeks' gestation or a birth weight of at least 400 g. To prevent distortion of findings from variations in clinical practice and health care accessibility, only studies from high-income countries were used. A total of 16 studies, published between 2001 and 2014, were included in this analysis (13 cohort studies and 3 case-control studies). A total of 3,412,079 women were included in these 16 studies; 99.3% had a live birth, and 0.7% had a stillbirth in the initial pregnancy. Of the women with initial live births, 0.4% experienced a subsequent stillbirth, whereas of the women with initial stillbirths, 2.5% experienced a subsequent stillbirth. Pooled adjusted and unadjusted odds ratios (3.38 and 4.44, respectively) both indicated increased risk of subsequent stillbirth in women with previous history of stillbirth. When analysis was restricted to the 12 studies that specifically examined risk of stillbirth recurrence in women with first and second subsequent pregnancies, the risk was still 4.77-fold. Four of the studies addressed risk of recurrence of unexplained stillbirth, although methodological differences in the study prevented subgroup analysis. Nevertheless, the odds ratios in each of these studies ranged from 1.00 to 4.18, indicating increased recurrence risk. This trend was also true in the sensitivity analyses, which adjusted for confounding factors. Risk was slightly attenuated when adjusting for maternal characteristics only. However, this is not of clinical significance as previous studies have shown that much of recurrence risk cannot be explained by modifiable maternal factors. Overall, this comprehensive review and meta-analysis supports previous findings that women who experience stillbirth in their initial pregnancy are at higher risk of stillbirth in a subsequent pregnancy. Some limitations of the review are high heterogeneity of studies and possible publication bias, where smaller studies with large effects may be underrepresented.