Abstract

BackgroundGlobally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity.ObjectivesThis review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality.MethodsWe conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken.ResultsModerate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 – 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 – 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 – 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 – 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong.ConclusionDetection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

Highlights

  • Syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity

  • The objective of this paper is to provide quantitative estimates of the effect of antenatal syphilis detection based on serological screening in pregnancy combined with treatment with at least 2.4 million units penicillin on syphilis related stillbirths, neonatal mortality and morbidity related to maternal syphilis infection

  • Women not attending antenatal clinics or not adhering to complex penicillin treatment regimes may differ in their risk profiles for stillbirth, preterm delivery and neonatal death from fully compliant infected women

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Summary

Introduction

Syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity. Syphilis classically presents in its primary stage with a painless, spontaneously resolving ulcer (chancre), lasting 3 – 6 weeks, that typically occurs around 21 days, but which may occur up to 3 months post infection. This is followed, 6 – 8 weeks later, by the secondary stage, which consists of a more diffuse inflammatory response characterised by an exanthema which manifests variably and for which healthcare is often not sought even if available. 15 – 40% of infected individuals develop late ‘tertiary’ complications that may occur years after the initial infection: e.g. granulomas, neuropathic joint disease, cardiovascular and neurological complications

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