• Universal screening at the first prenatal visit (required by law in most jurisdictions).
• Rescreen at 28 weeks and at delivery for high-risk patients or those in high-prevalence areas.
• Evaluation of any patient presenting with an unexplained maculopapular rash (palms/soles) or painless genital ulcer (chancre).
• Mandatory workup for all cases of fetal hydrops or unexplained stillbirth.

An acute febrile response occurring within 24 hours of starting treatment for syphilis. In pregnancy, this may trigger preterm labor or fetal distress (late decelerations) due to the massive release of treponemal lipopolysaccharides. This is NOT a penicillin allergy.

• Penicillin G is the ONLY effective treatment for preventing congenital syphilis. No alternatives (e.g., Azithromycin, Doxycycline) are acceptable in pregnancy.
• If a pregnant patient is Penicillin-allergic, they MUST be hospitalized for desensitization and then treated with Penicillin.
• Treatment is considered "adequate" only if completed ≥30 days prior to delivery.
• A 4-fold (two-titer) increase in RPR after treatment indicates reinfection or treatment failure.

• Hepatomegaly (most common finding).
• Placentomegaly (placental thickness >4cm).
• Polyhydramnios.
• Fetal Hydrops (ascites, pericardial/pleural effusions).
• Abnormal Doppler (increased Middle Cerebral Artery peak systolic velocity indicating anemia).

• Administer first dose of IM Benzathine Penicillin G immediately upon diagnosis.
• Monitor for Jarisch-Herxheimer reaction (especially if >20 weeks gestation).
• Repeat RPR/VDRL titers monthly to ensure an appropriate response (expect 4-fold decrease in 6–12 months).
• Ensure partner is treated to prevent ping-pong reinfection.
• Notify public health authorities (Mandatory Reportable Disease).

Syphilis is caused by the spirochete Treponema pallidum. While it was nearly eradicated in the late 20th century, the US has seen a catastrophic 200%+ increase in congenital syphilis cases over the last decade, leading to renewed emphasis on triple-screening during pregnancy.

Before the advent of Penicillin in 1943, syphilis was a leading cause of fetal loss and neonatal disability. It is known as the "Great Imitator" because its clinical manifestations (especially in the secondary stage) can mimic almost any other medical condition.