What is the recommended treatment for syphilis in a pregnant woman?

Treatment of Syphilis in Pregnant Women

Benzathine penicillin G is the only proven effective treatment for syphilis during pregnancy and must be used at doses appropriate for disease stage—there are no acceptable alternatives. 1, 2, 3

Treatment Regimens by Disease Stage

Primary, Secondary, or Early Latent Syphilis (< 1 year duration)

• Administer benzathine penicillin G 2.4 million units IM as a single dose, followed by a second dose of 2.4 million units IM exactly one week later. 1, 2, 3
• The two-dose regimen is particularly critical for women in the third trimester, those with secondary syphilis, or HIV-infected pregnant women, as single-dose therapy has been associated with treatment failure. 2, 4
• Research demonstrates that treponemicidal coverage lasting 3 weeks or less (essentially one injection) results in significantly worse outcomes including lower birth weight, increased prematurity, and higher perinatal mortality compared to longer coverage. 4

Late Latent or Unknown Duration Syphilis (> 1 year or uncertain)

• Administer benzathine penicillin G 7.2 million units total, given as three separate doses of 2.4 million units IM each, with exactly 7-day intervals between injections. 1, 2, 3
• This extended regimen ensures adequate treponemicidal coverage for established infection. 5

Critical Management of Penicillin Allergy

Pregnant women reporting penicillin allergy must undergo skin testing and desensitization, then be treated with penicillin—this is non-negotiable. 6, 1, 2, 3

Contraindicated Alternatives

• Never use tetracycline or doxycycline: These cause maternal hepatotoxicity and fetal tooth/bone staining. 6, 2
• Never use erythromycin: It does not reliably cross the placenta to cure fetal infection, making it ineffective for preventing congenital syphilis. 6, 2
• Never use azithromycin or ceftriaxone: Insufficient data exist to recommend these agents during pregnancy. 6

Desensitization Protocol

• Perform skin testing to confirm true penicillin allergy status. 6, 2
• Use either oral step-wise penicillin dose challenge or a four-hour intravenous desensitization protocol in a critical care setting with appropriate monitoring. 7
• After successful desensitization, immediately proceed with stage-appropriate benzathine penicillin G treatment. 7

Monitoring for Jarisch-Herxheimer Reaction

Women treated during the second half of pregnancy are at risk for Jarisch-Herxheimer reaction, which can precipitate premature labor, fetal distress, or rarely stillbirth. 6

Recommended Monitoring Strategy

• 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, particularly for viable pregnancies after 20 weeks gestation. 8
• Counsel women to seek immediate obstetric attention if they experience fever, contractions, or decreased fetal movements after treatment. 6, 2
• Do not delay necessary treatment due to concerns about Jarisch-Herxheimer reaction—untreated syphilis causes far greater fetal harm than the reaction itself. 6, 2
• Subsequent doses can be administered in an outpatient setting after the first dose is tolerated. 8

Ultrasound Evaluation for Fetal Syphilis

Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation, but do not delay therapy for imaging. 6, 2, 8

Sonographic Signs of Fetal Infection

• Hepatomegaly and placentomegaly are the most common findings. 8
• Elevated middle cerebral artery peak systolic velocity (indicating fetal anemia). 3, 8
• Ascites and hydrops fetalis in severe cases. 6, 8
• Pregnancies with ultrasound abnormalities require consultation with obstetric specialists and are at higher risk for fetal treatment failure despite appropriate therapy. 6, 8

Screening Requirements

All pregnant women must be screened for syphilis at the first prenatal visit—no exceptions. 6, 1, 2, 3

Additional Screening for High-Risk Populations

• Repeat serologic testing at 28-32 weeks gestation and at delivery for women in high-prevalence areas or those at high risk for infection. 6, 1, 2, 3
• High-risk factors include: history of sexually transmitted infections, multiple sexual partners, condomless sex, substance use, incarceration, sex work, or partners with known syphilis. 9
• Any woman who delivers a stillborn infant after 20 weeks gestation must be tested for syphilis. 6, 1, 3
• No newborn should be discharged without documented maternal syphilis screening at least once during pregnancy. 6, 1, 2, 3

Follow-Up Serologic Monitoring

Repeat nontreponemal titers (RPR or VDRL) at 28-32 weeks gestation and at delivery. 6, 1, 2

Monitoring Protocol

• Check titers monthly in women at high risk for reinfection or in geographic areas with high syphilis prevalence. 6, 1, 2
• Use the same nontreponemal test (RPR or VDRL) for all follow-up testing—titers from different tests are not directly comparable. 6, 1
• Most women will deliver before their serologic response to treatment can be definitively assessed, as adequate response typically takes months. 6, 5
• A fourfold increase in titers suggests reinfection or treatment failure and requires retreatment. 8

Defining Adequate Treatment

• Inadequate maternal treatment is likely if delivery occurs within 30 days of therapy, if clinical signs of infection persist at delivery, or if maternal antibody titer at delivery is fourfold higher than pretreatment titer. 6

Management of Sexual Partners

Presumptively treat all sexual partners exposed within 90 days prior to diagnosis, even if they are seronegative. 1, 2, 3

• Long-term sexual partners of patients with late syphilis should undergo clinical and serologic evaluation. 2
• Offer HIV testing to all patients diagnosed with syphilis. 6, 1, 2, 3

Common Pitfalls to Avoid

• Do not use single-dose therapy for pregnant women with early syphilis—the two-dose regimen significantly improves outcomes, particularly when treatment occurs more than 4 weeks before delivery. 1, 4
• Do not compare titers between different nontreponemal tests (RPR vs. VDRL)—they are not interchangeable. 6, 1
• Do not substitute non-penicillin antibiotics—they do not prevent congenital syphilis. 1, 2
• Do not discharge a newborn without documented maternal screening—this is a critical patient safety measure. 1, 2, 3
• Do not delay treatment to obtain ultrasound—imaging should not postpone therapy. 6, 2