Gestational syphilis and stillbirth in the Americas: a systematic review and meta-analysis.

Objective: To perform a systematic review and meta-analysis of reported estimates of the association between gestational syphilis (GS) and stillbirth in the Americas region.
Methods: Cochrane Library, Embase, LILACS, MEDLINE/PubMed, PLOS, and ScienceDirect were searched for original research studies quantifying the relationship between GS and stillbirth in the region. A final sample of eight studies was selected. A cumulative meta-analysis plus four subgroup meta-analyses of study data on the association between maternal syphilis during pregnancy and stillbirth were conducted. The four meta-analyses were based on 1) definition of cases and the control; 2) syphilis treatment (presence or absence, effective or ineffective); 3) definition of stillbirth as "showing no signs of life at birth"; and 4) definition of stillbirth based on low birth weight and gestational age. Random-effects metaanalyses were used to calculate pooled estimates of stillbirth with exposure to GS, and each subgroup analysis was tested for heterogeneity.
Results: Women with GS had increased odds of stillbirth (pooled odds ratio (OR): 6.87; 95% confidence interval: 2.93, 16.08). There was considerable heterogeneity across the eight studies (percentage of variance (I²) = 95). The funnel plot was not statistically significant, pointing to a lack of publication bias. Increased odds of stillbirth among pregnant women with syphilis were also seen in all four subgroup meta-analyses.
Conclusions: GS is a major contributing factor for stillbirths in the Americas. Interventions targeting GS are highly cost-effective and, along with high-quality point-of-care testing, should be implemented across the region to help reach the goal of eliminating congenital syphilis.