What is the recommended management of syphilis in pregnancy?

Management of Syphilis in Pregnancy

Treat all pregnant women with syphilis using benzathine penicillin G according to disease stage, as it is the only proven therapy to prevent maternal-to-fetal transmission and cure fetal infection. 1, 2

Treatment Regimens by Stage

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

• Administer benzathine penicillin G 2.4 million units IM as a single dose 1, 2
• Consider a second dose of 2.4 million units IM one week after the initial injection, particularly for women in the third trimester or those with secondary syphilis, as treatment failures have been reported with single-dose regimens 1, 2, 3
• For HIV-infected pregnant women, a second injection one week later should be strongly considered due to additional concerns about treatment efficacy 1

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

Screening Requirements

• Screen all pregnant women at the first prenatal visit 1, 2
• In high-risk populations or high-prevalence areas, repeat screening at 28-32 weeks gestation and again at delivery 1, 2
• No infant should be discharged without documented maternal syphilis screening at least once during pregnancy 1

Management of Penicillin Allergy

Pregnant women with penicillin allergy must undergo skin testing and desensitization, then be treated with penicillin—there are no acceptable alternatives. 1, 2

• Erythromycin does not reliably cure fetal infection and should not be used 1
• Tetracyclines and doxycycline are contraindicated due to maternal hepatotoxicity and fetal bone/teeth staining 1
• Azithromycin and ceftriaxone have insufficient data for routine use in pregnancy 1

Critical Monitoring and Precautions

Jarisch-Herxheimer Reaction Management

• Counsel women to seek immediate obstetric attention if they experience contractions or decreased fetal movements within 24 hours of treatment, as the Jarisch-Herxheimer reaction can precipitate preterm labor or fetal distress 1, 2
• For viable pregnancies after 20 weeks gestation, consider administering the first dose in a labor and delivery unit with continuous fetal monitoring for 24 hours 4
• Do not delay necessary treatment due to concerns about stillbirth risk—untreated syphilis causes far greater fetal harm 1, 2

Ultrasound Evaluation

• Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation 1, 2, 4
• Sonographic signs of fetal syphilis (hepatomegaly, placentomegaly, ascites, hydrops, elevated middle cerebral artery peak systolic velocity) indicate higher risk for fetal treatment failure 1, 4
• Pregnancies with ultrasound abnormalities require consultation with obstetric specialists, though imaging should not delay therapy 1, 2
• After 20 weeks gestation with sonographic evidence of fetal infection, consider fetal and contraction monitoring for 24 hours after treatment initiation 1

Follow-Up Protocol

• Repeat serologic titers in the third trimester and at delivery 1, 2
• Check titers monthly in women at high risk for reinfection or in high-prevalence geographic areas 1, 2
• Most women will deliver before serologic response can be definitively assessed 1
• Maternal treatment is likely inadequate if delivery occurs within 30 days of therapy, clinical signs persist at delivery, or maternal titer is fourfold higher than pretreatment 1

Special Populations and Considerations

HIV-Infected Pregnant Women

• Use the same stage-appropriate penicillin regimen as for HIV-uninfected women 1
• Strongly consider a second dose one week after initial treatment for early syphilis due to concerns about treatment efficacy 1
• Test all pregnant women with syphilis for HIV infection 1

Secondary Syphilis

• This stage carries the highest risk of fetal treatment failure (94.7% success rate vs. 98-100% for other stages) 5
• Consider the second dose of benzathine penicillin G one week after initial treatment, especially in the third trimester 2, 5

Common Pitfalls to Avoid

• Never discharge a newborn without documented maternal syphilis screening 1, 2
• Do not use non-penicillin regimens (erythromycin, tetracyclines, doxycycline) as they do not prevent congenital syphilis 1, 2
• Do not delay treatment for ultrasound evaluation—imaging facilitates management but should never postpone therapy 1
• Ensure adequate treatment duration: treponemicidal coverage of 3 weeks or less results in significantly worse outcomes (increased prematurity, perinatal mortality, and congenital syphilis rates comparable to no treatment) 3
• For women presenting before 28 weeks gestation or with RPR titers >1:16, single-dose therapy is particularly inadequate 3