What is the recommended treatment for syphilis in pregnant women?

Treatment of Syphilis in Pregnancy

Benzathine penicillin G is the only acceptable treatment for syphilis during pregnancy and must be administered at stage-appropriate doses to prevent maternal-to-fetal transmission and congenital syphilis. 1, 2

Treatment Regimens by Stage

Primary, Secondary, or Early Latent Syphilis

• Administer benzathine penicillin G 2.4 million units IM as a single dose 1, 2
• A second dose of 2.4 million units IM should be given one week after the initial dose, particularly for women in the third trimester or those with secondary syphilis 1, 2
• This two-dose approach is critical because single-dose therapy has been associated with increased prematurity, lower birth weight, perinatal mortality, and congenital syphilis when treponemicidal coverage lasts ≤3 weeks 3

Late Latent or Latent Syphilis of Unknown Duration

• Administer benzathine penicillin G 7.2 million units total, given as three doses of 2.4 million units IM each at weekly intervals 1, 2
• Each injection must be spaced exactly 7 days apart 4

Management of Penicillin Allergy

There are no acceptable alternatives to penicillin for treating syphilis in pregnancy—women with penicillin allergy must undergo desensitization followed by penicillin treatment. 1, 2

• Perform skin testing to confirm allergy status before desensitization 5, 2
• Never use tetracycline, doxycycline, or erythromycin during pregnancy: tetracyclines cause maternal hepatotoxicity and fetal bone/teeth staining, while erythromycin does not reliably cure fetal infection 5, 2, 6

Critical Monitoring and Precautions

Jarisch-Herxheimer Reaction Management

• Women treated in the second half of pregnancy are at risk for premature labor and fetal distress from the Jarisch-Herxheimer reaction 5
• Administer the first dose of benzathine penicillin G in a labor and delivery unit under continuous fetal monitoring for at least 24 hours when feasible 7
• Advise women to seek immediate obstetric attention if they notice contractions or decreased fetal movements within 24 hours of treatment 2
• Do not delay treatment due to concerns about stillbirth risk—untreated syphilis causes far greater fetal harm than the Jarisch-Herxheimer reaction 2

Ultrasound Assessment

• Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation 1, 7
• Sonographic signs of fetal syphilis include hepatomegaly, placentomegaly, ascites, hydrops, and elevated middle cerebral artery peak systolic velocity 1, 7
• Pregnancies with ultrasound abnormalities require consultation with obstetric specialists and are at higher risk for fetal treatment failure 5, 7

Screening Requirements

• Screen all pregnant women for syphilis at the first prenatal visit 5, 1, 2
• In high-risk populations or areas with high syphilis prevalence, perform additional screening at 28-32 weeks gestation and at delivery 1, 2
• High-risk groups include women with HIV, those with multiple sexual partners, and those in communities with high syphilis prevalence 5
• No newborn should be discharged without documented maternal syphilis screening at least once during pregnancy 5, 2
• Any woman who delivers a stillborn infant after 20 weeks gestation should be tested for syphilis 1

Follow-Up Protocol

• Repeat serologic titers in the third trimester and at delivery 5, 1, 2
• Check serologic titers monthly in women at high risk for reinfection or in areas with high syphilis prevalence 5, 2
• Use the same nontreponemal test (VDRL or RPR) for follow-up to ensure comparable results 5
• After adequate treatment, monitor titers monthly to ensure they are not increasing fourfold, which may indicate reinfection or treatment failure 7

Partner Management and Additional Testing

• Treat sexual partners exposed within 90 days of diagnosis presumptively, even if seronegative 1, 2
• Offer HIV testing to all patients with syphilis 5, 1
• Long-term sexual partners of patients with late syphilis should be clinically and serologically evaluated 2

Common Pitfalls to Avoid

• Single-dose therapy for early syphilis in pregnancy is inadequate—research demonstrates that treponemicidal coverage ≤3 weeks results in outcomes comparable to no treatment, with relative risks of 8.5 for prematurity and 20.5 for perinatal mortality 3
• Do not use non-penicillin regimens (erythromycin, tetracyclines, azithromycin, ceftriaxone) as they do not prevent congenital syphilis 5, 2
• Do not compare titers between different test types (VDRL vs. RPR) as they are not directly comparable 4
• Ensure treatment is completed at least 4 weeks before delivery when possible, especially for women presenting before 28 weeks gestation or with RPR titers >16 3