Interpregnancy Interval and Risk of Perinatal Death: A Systematic Review and Meta-Analysis

Background: Interpregnancy interval (IPI) is a potentially modifiable risk factor for reducing risk of adverse perinatal health outcomes. This review aims to evaluate the international literature on perinatal death associated with IPI. Methods: We performed a systematic review and meta-analysis of observational studies evaluating the association between IPI and measures of perinatal death, including stillbirth and neonatal death (Prospero Registration# CRD42018092792). Two independent reviewers reviewed articles identified in MEDLINE, EMBASE, and Scopus from inception to 4 April 2019. Data were extracted from selected articles and a random-effects meta-analysis was conducted to compare reported risks of perinatal death associated with IPI <6 months and IPI ≥6 months. Findings: Of the 624 unique articles identified, 26 met inclusion criteria. The pooled unadjusted odds ratio of perinatal death for an IPI <6 months was 1.34 (95% CI 1.17-1.53) following a previous live birth, 0.85 (95% CI 0.73-0.99) following a previous spontaneous abortion, and 1.07 (95% CI 0.84, 1.36) following a previous stillbirth compared to IPI ≥6 months. Although adjusted estimates reported by low and middle-income country (LMIC) studies suggested an increased risk of perinatal death associated with IPI <6 months after live birth, few high-income country (HIC) studies reported an association after adjustment. Interpretation: Differences in variable definitions made comprehensive comparisons of IPI and perinatal death difficult, and further high-quality investigations across HICs and LMICs are needed to inform recommendations for optimal birth spacing. Funding Statement: This work was supported by funding from the National Health and Medical Research Council (GNT1099655). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Prospero Registration# CRD42018092792.