What is the recommended treatment for syphilis in pregnancy?

Treatment of Syphilis in Pregnancy

Benzathine penicillin G is the only proven effective treatment for syphilis during pregnancy and must be used at stage-appropriate dosing to prevent maternal-to-fetal transmission and congenital syphilis. 1, 2, 3

Treatment Regimens by Stage

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

• Benzathine penicillin G 2.4 million units IM as a single dose 1, 4
• Consider a second dose of 2.4 million units IM one week after the initial dose, particularly for:
  • Women in the third trimester 5, 1
  • Women with secondary syphilis (highest risk of fetal treatment failure at 94.7% success vs 98.2% overall) 4
  • HIV-infected pregnant women 5

Late Latent or Latent Syphilis of Unknown Duration

• Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at weekly intervals 1, 4

Neurosyphilis During Pregnancy

• Aqueous crystalline penicillin G 12-24 million units/day IV (administered as 2-4 million units every 4 hours) for 10-14 days 6
• Many experts recommend additional therapy with benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion of IV therapy 6

Management of Penicillin Allergy

There are no proven alternatives to penicillin for treating syphilis in pregnancy or preventing fetal infection. 5, 1

• Pregnant women with penicillin allergy must undergo skin testing and desensitization, then be treated with penicillin 5, 1, 2
• Contraindicated alternatives:
  • Tetracyclines and doxycycline: hepatotoxic to mother, cause fetal bone/teeth staining 5, 7
  • Erythromycin: does not reliably cure fetal infection 5, 7
  • Azithromycin and ceftriaxone: insufficient safety/efficacy data in pregnancy 5

Critical Monitoring and Precautions

Jarisch-Herxheimer Reaction

• Occurs in up to 44% of pregnant women treated for syphilis 2
• Can precipitate preterm labor, fetal distress, contractions, fetal heart rate abnormalities, and rarely stillbirth 5, 2
• For viable pregnancies, administer the first dose of benzathine penicillin G in a labor and delivery unit with continuous fetal monitoring for at least 24 hours 2
• Advise women to seek immediate obstetric attention if they notice contractions or decreased fetal movements within 24 hours of treatment 5

Ultrasound Evaluation

• Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation 2
• Sonographic signs of fetal syphilis indicate higher risk of treatment failure and include: 5, 2
  • Hepatomegaly and placentomegaly (most common)
  • Elevated middle cerebral artery peak systolic velocity (fetal anemia)
  • Ascites and hydrops fetalis
• Pregnancies with ultrasound abnormalities require consultation with obstetric specialists 5
• Do not delay treatment to obtain ultrasound 5

Screening Requirements

All pregnant women must be screened for syphilis at the first prenatal visit 5, 1

High-Risk Populations Require Additional Screening:

• Repeat testing at 28-32 weeks gestation AND at delivery for: 5, 1
  • Women in high-prevalence areas
  • Uninsured women
  • Women living in poverty
  • Commercial sex workers
  • Injection drug users
  • Women with HIV

No infant should leave the hospital without documented maternal syphilis serology status during pregnancy 5, 1

Follow-Up Protocol

• Check serologic titers monthly until delivery to ensure adequate treatment response 5, 1
• Repeat titers in the third trimester and at delivery 5, 1
• Most women will deliver before serologic response can be definitively assessed 5
• A fourfold increase in titers may indicate reinfection or treatment failure and requires retreatment 2
• The rate of maternal titer decline is not tied to pregnancy outcomes after adequate treatment 2

Partner Management

• Sexual partners exposed within 90 days of diagnosis should be treated presumptively, even if seronegative 1, 8
• Long-term partners of women with late syphilis should be clinically and serologically evaluated 1

Common Pitfalls to Avoid

• Never use oral penicillin preparations—they are ineffective 8
• Never delay treatment due to concerns about stillbirth risk from Jarisch-Herxheimer reaction; untreated syphilis causes far greater fetal harm 5
• Never treat with erythromycin, tetracyclines, or other non-penicillin regimens—these do not prevent congenital syphilis 5, 7
• Never discharge a newborn without documented maternal syphilis screening 5
• Maternal treatment is considered inadequate if delivery occurs within 30 days of therapy, if clinical signs of infection are present at delivery, or if maternal titer is fourfold higher than pretreatment 5