Maternal syphilis, preventable stillbirth, and treatment protection: a global systematic meta-analysis

Maternal syphilis remains a major cause of adverse pregnancy outcomes, with stillbirth among the most severe. We aimed to estimate the global prevalence of stillbirth among pregnancies complicated by syphilis and to evaluate associated determinants.

This systematic review and meta-analysis searched four databases for studies reporting stillbirth among pregnant women with confirmed maternal syphilis. Random-effects meta-analysis was performed on logit-transformed prevalence estimates. Heterogeneity was assessed using I² and τ² statistics. Subgroup analyses explored geographic region and treatment adequacy; treatment-stratified estimates were prioritized because treatment exposure differed substantially across studies. Risk of bias was also assessed.

Eleven studies met the inclusion criteria. The pooled prevalence of stillbirth was 5.02% (95% confidence interval 2.44-10.06%) with substantial heterogeneity (I² = 90.67%). Stillbirth prevalence was highest in sub-Saharan Africa (10.93%) and lowest in Asia (1.57%; P < .001), although regional estimates were potentially confounded by differences in treatment coverage. Treatment-stratified prevalence was 11.69% in studies with low or absent treatment coverage and 2.81% in studies with moderate-to-high coverage (Q = 22.1, P < .001). In one included study, adequate treatment was associated with 84% lower adjusted odds of stillbirth (adjusted odds ratio = 0.16); this relative effect should not be interpreted as a 16% breakthrough rate. No significant publication bias was detected.

Maternal syphilis remains a significant but preventable cause of stillbirth. Treatment adequacy, rather than geography alone, was the most clinically important source of variation. Early diagnosis and timely, stage-appropriate therapy substantially reduce stillbirth. Strengthening antenatal screening and ensuring prompt treatment are critical to achieving global elimination of congenital syphilis-related mortality.