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Table 2 Cause specific mortality effect and quality grade of the estimate for the effect of at least 2.4MU penicillin treatment for active syphilis in pregnancy

From: Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality

Cause specific mortality to act on:
The proportion of stillbirth mortality that is related to syphilis.
The proportion of preterm mortality that is related to syphilis.
The proportion of neonatal sepsis mortality that is due to congenital syphilis.
Cause specific estimate of effect in affected pregnancies and range:
Reduction in stillbirth of 82% (95% c.i. 67 – 90%)
Reduction in the incidence of preterm delivery of 64% (95% c.i. 53 – 73%)
Reduction in the incidence of clinical congenital syphilis of 97% (95% c.i. 93 – 98%)
Assuming 15% of livebirths from syphilis affected pregnancies result in a neonatal death attributable to congenital syphilis (expert consensus) and that treatment does not affect case fatality, 97% (95%c.i. 93 – 98%) of these deaths could be averted.
Quality of input evidence:
For stillbirth – There is a large and consistent effect size from 8 observational studies. The GRADE quality of evidence is low.
For preterm - There is a large and consistent effect size from 7 observational studies. The GRADE quality of evidence is low.
There is a large and consistent effect size on incidence of clinical congenital syphilis and confounding is unlikely, so GRADE rules result in upgrading the low to moderate quality evidence.
The GRADE recommendation is STRONG, based on large and consistent effect sizes across studies, and biological plausibility.
Proximity of the data to cause specific mortality effect:
For the effect on preterm and neonatal sepsis due to congenital syphilis, the evidence is on incidence and distal to mortality estimate.
Possible adverse effects:
Penicillin allergic symptoms may occur in 2% of individuals [89]; however, severe allergic reactions (e.g. anaphylaxis) are rare events, estimated to occur in 10 to 50 of every 100,000 exposed individuals [90, 91]. Up to 40% of patients with primary or secondary syphilis may experience Jarisch-Herxheimer reactions with antibiotic treatment. These reactions involving malaise, anxiety, fever, headache, sweating, or rigors are believed caused by microbial lysis. If the reaction occurs late pregnancy it could lead to fetal distress, uterine contractions and preterm delivery [92, 93]. There is some evidence of possible increased maternal infection after antepartum treatment [94]