What is the recommended treatment for syphilis in pregnancy?

Treatment of Syphilis in Pregnancy

Pregnant women with syphilis must be treated with benzathine penicillin G according to their disease stage—this is the only proven therapy to prevent maternal-to-fetal transmission and treat established fetal infection. 1

Screening Requirements

All pregnant women require serologic screening for syphilis at specific timepoints 2, 1:

• First prenatal visit (universal screening)
• Third trimester at 28 weeks (high-risk populations or high-prevalence areas)
• At delivery (high-risk populations or high-prevalence areas; some states mandate universal screening)
• Any stillbirth after 20 weeks gestation warrants maternal syphilis testing 2, 3

Women should be considered infected unless adequate treatment history is documented with appropriate serologic titer decline 2

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 later, particularly for women in the third trimester or those with secondary syphilis 2, 1
• This additional dose addresses concerns about treatment failure, which occurs most commonly in secondary syphilis (94.7% success rate vs. 98-100% for other early stages) 4

Late Latent or Latent Syphilis of Unknown Duration

• Benzathine penicillin G 7.2 million units total: three doses of 2.4 million units IM each, given at weekly intervals 2, 1
• CSF examination should be performed to rule out neurosyphilis before using this regimen 2

Critical Management Considerations

Penicillin Allergy

There are no acceptable alternatives to penicillin during pregnancy—women with penicillin allergy must undergo desensitization followed by penicillin treatment 1, 2 This is non-negotiable because:

• Tetracycline and doxycycline are contraindicated in pregnancy 1, 5
• Erythromycin does not reliably cure fetal infection 2

Jarisch-Herxheimer Reaction

Women treated during the second half of pregnancy face risk of premature labor or fetal distress from this reaction 2, 6, 7:

• Administer the first dose of benzathine penicillin G in a labor and delivery unit with continuous fetal monitoring for at least 24 hours (for viable pregnancies) 7
• Subsequent doses can be given outpatient 7
• Advise patients to seek immediate obstetric attention if they experience contractions or decreased fetal movement after treatment 2
• The risk of stillbirth from this reaction should never delay necessary treatment 2

Ultrasound Evaluation

Perform ultrasound assessment when feasible, particularly after 20 weeks gestation and before treatment 7:

• Look for hepatomegaly, placentomegaly, ascites, hydrops fetalis, or elevated middle cerebral artery peak systolic velocity (indicating fetal anemia) 2, 7
• Pregnancies with these findings have higher risk of fetal treatment failure and should involve obstetric specialist consultation 2, 7

Follow-Up Protocol

Serologic titers must be repeated in the third trimester and at delivery 2, 1:

• Check monthly in women at high risk for reinfection or in high-prevalence areas 2, 1
• Four-fold rise in nontreponemal titers at any point indicates reinfection or treatment failure requiring retreatment 2
• The rate of titer decline does not predict pregnancy outcome, so do not delay delivery based on persistent titers alone 7

Common Pitfalls

Inadequate treatment duration: One injection of 2.4 million units provides only 3 weeks of treponemicidal coverage, which is insufficient—this results in increased prematurity, low birth weight, and perinatal mortality comparable to no treatment 8. This is why the second dose recommendation exists for high-risk scenarios.

Late diagnosis: Women diagnosed at delivery (108 of 448 cases in one study) miss the opportunity for fetal treatment 4. Ensure no infant leaves the hospital without documented maternal serologic status 2, 1.

Assuming serofast state means no treatment needed: Women with low persistent titers (<1:8) after previous adequate treatment still require evaluation and may need retreatment if clinical or serologic evidence suggests active infection 7.