Preterm birth after recurrent pregnancy loss: a systematic review and meta-analysis

Objective: To evaluate the impact of recurrent pregnancy loss (RPL) on the risk of preterm birth (PTB) in subsequent pregnancies.

Design: Systematic review and meta-analysis.

Setting: Not applicable.

Patient(s): Pregnant women with and without a history of RPL.

Intervention(s): PubMed, Embase, Google Scholar and Cochrane trial registry were used to identify relevant studies.

Main outcome measure(s): The odds ratios (ORs) for the association between RPL and PTB across included studies were evaluated. Effect estimates were pooled using a DerSimonian and Laird random-effects meta-analysis model.

Result(s): Eighteen studies met the inclusion criteria. A total of 58,766 women with a history of RPL and 2,949,222 women without a history of RPL were included. A pooled OR of 1.60 (95% confidence interval [CI], 1.45-1.78; 18 observational studies; I² = 85.6%) was observed in our random-effects meta-analysis. A trend toward higher odds of PTB is observed with the increasing number of pregnancy losses: 2 RPLs (pooled OR, 1.31; 95% CI, 1.09-1.57; I² = 88.9%); ≥2 RPLs (pooled OR, 1.58; 95% CI, 1.27-1.96; I² = 71.7%); and ≥3 RPLs (pooled OR, 1.81; 95% CI, 1.58-2.07; I² = 73.6%). The analysis of the risk of PTB for patients with unexplained RPL demonstrated a significantly heightened risk of PTB in this subgroup (pooled OR, 2.05; 95% CI, 1.46-2.89; I² = 21.0%). Inconsistent adjustment for confounders and significant between-study heterogeneity were noted in this study.

Conclusion(s): Despite significant heterogeneity among studies, we found that women with a history of RPL had significantly higher odds of delivering preterm infants in subsequent pregnancies.

Clinical trial registration number: CRD 224763.