What is the recommended treatment for syphilis in pregnancy?

Treatment of Syphilis in Pregnancy

Treat all pregnant women with syphilis using benzathine penicillin G at doses appropriate for the stage of disease—this is the only proven therapy to prevent congenital syphilis and maternal-to-fetal transmission. 1

Treatment Regimens by Stage

Primary, Secondary, or Early Latent Syphilis

• Administer benzathine penicillin G 2.4 million units IM as a single dose 1
• Consider a second dose of 2.4 million units IM one week after the initial dose, particularly for women in the third trimester or those with secondary syphilis 1
• This additional dose is especially important for women presenting before 28 weeks gestation or with RPR titers >1:16, as single-dose therapy has been associated with increased prematurity, low birth weight, and perinatal mortality in these populations 2

Late Latent or Latent Syphilis of Unknown Duration

• Administer benzathine penicillin G 7.2 million units total: three doses of 2.4 million units IM each, given at weekly intervals 1
• Ensure doses are spaced exactly 7 days apart; if a dose is missed, a 10-14 day interval may be acceptable before restarting the sequence 3

Critical Management of Penicillin Allergy

Pregnant women with penicillin allergy MUST undergo desensitization followed by penicillin treatment—there are no acceptable alternatives. 1

• Skin testing should be performed to confirm allergy status 4
• Never use tetracycline, doxycycline, or erythromycin in pregnancy: tetracyclines cause maternal hepatotoxicity and fetal bone/teeth staining, while erythromycin does not reliably cure fetal infection 4, 1
• Azithromycin and ceftriaxone have insufficient data to recommend their use in pregnancy 4

Monitoring and Follow-Up Protocol

Serologic Monitoring

• Repeat serologic titers in the third trimester and at delivery 1
• Check titers monthly in women at high risk for reinfection or in areas with high syphilis prevalence 1
• A fourfold decline in nontreponemal titers is expected, though most women will deliver before treatment response can be fully assessed 4

Ultrasound Evaluation

• Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation 1, 5
• Sonographic signs of fetal syphilis include hepatomegaly, placentomegaly, ascites, hydrops, and elevated middle cerebral artery peak systolic velocity (indicating fetal anemia) 4, 5
• Pregnancies with ultrasound abnormalities indicate higher risk for fetal treatment failure and should be managed in consultation with obstetric specialists 4, 1

Jarisch-Herxheimer Reaction Management

Women treated in the second half of pregnancy are at risk for premature labor and/or fetal distress from the Jarisch-Herxheimer reaction. 4

• This reaction occurs in up to 44% of pregnant women and can cause contractions, fetal heart rate abnormalities, and rarely stillbirth 5
• Advise women to seek immediate obstetric attention if they notice contractions or decreased fetal movements within 24 hours of treatment 1
• Consider administering the first dose of benzathine penicillin G in a labor and delivery unit under continuous fetal monitoring for at least 24 hours in viable pregnancies 5
• Never delay treatment due to concerns about Jarisch-Herxheimer reaction—untreated syphilis causes far greater fetal harm 1

Screening Requirements

Screen all pregnant women for syphilis at the first prenatal visit 1

• In high-risk populations or areas with high syphilis prevalence, perform additional screening at 28-32 weeks gestation and at delivery 1
• High-risk factors include: history of sexually transmitted infections, multiple sexual partners, substance use, incarceration, sex work, or living in areas with high syphilis rates 6
• Any woman who delivers a stillborn infant after 20 weeks gestation should be tested for syphilis 4
• No newborn should be discharged without documented maternal syphilis screening at least once during pregnancy 1

Treatment Efficacy Evidence

The effectiveness of benzathine penicillin G in pregnancy is well-established:

• Single-dose treatment for high-titer active syphilis (RPR ≥1:8) effectively prevents adverse pregnancy outcomes, with stillbirth/low birth weight rates comparable to uninfected women (2.3%/6.3% vs 2.5%/9.2%) 7
• However, treponemicidal coverage lasting ≤3 weeks results in significantly worse outcomes: decreased birth weight (2,748 vs 3,130 g), increased prematurity (RR 8.5), and increased perinatal mortality (RR 20.5) 2
• Two or more doses ensure treponemicidal activity for >3 weeks, which is critical for optimal fetal outcomes, especially when delivery occurs <4 weeks after treatment 2

Common Pitfalls to Avoid

• Never substitute non-penicillin antibiotics in pregnancy—only penicillin prevents congenital syphilis 1
• Never delay treatment while awaiting partner evaluation or additional testing—immediate treatment is essential 4
• Never use different nontreponemal test methods (RPR vs VDRL) when monitoring serologic response—results cannot be directly compared 3
• Never assume adequate treatment based solely on history—seropositive pregnant women should be considered infected unless adequate treatment is documented with appropriate serologic decline 4

Partner Management

• Treat sexual partners exposed within 90 days of diagnosis presumptively, even if seronegative 3
• Partners exposed >90 days before diagnosis should be treated presumptively if serologic results are not immediately available and follow-up is uncertain 3
• All patients with syphilis should be offered HIV testing 4