Syphilis Treatment in Pregnancy

Treatment Regimens

The American College of Obstetricians and Gynecologists recommends treating all pregnant women with syphilis using benzathine penicillin G at doses appropriate for the stage of disease, as this is the only proven therapy to prevent congenital syphilis and maternal-to-fetal transmission 1
For primary, secondary, or early latent syphilis, administer benzathine penicillin G 2.4 million units IM as a single dose, with a second dose of 2.4 million units IM one week after the initial dose, particularly for women in the third trimester or those with secondary syphilis 1
For 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

The Centers for Disease Control and Prevention recommends that pregnant women with penicillin allergy undergo desensitization followed by penicillin treatment, as there are no acceptable alternatives 1
Skin testing should be performed to confirm allergy status, and never use tetracycline, doxycycline, or erythromycin in pregnancy, as they can cause maternal hepatotoxicity and fetal bone/teeth staining, or fail to reliably cure fetal infection 2, 1

Repeat serologic titers in the third trimester and at delivery, and check titers monthly in women at high risk for reinfection or in areas with high syphilis prevalence 1
Perform pretreatment ultrasound in viable pregnancies when feasible, particularly after 20 weeks gestation, and sonographic signs of fetal syphilis include hepatomegaly, placentomegaly, ascites, hydrops, and elevated middle cerebral artery peak systolic velocity 1, 2

Screen all pregnant women for syphilis at the first prenatal visit, and in high-risk populations or areas with high syphilis prevalence, perform additional screening at 28-32 weeks gestation and at delivery 1
Any woman who delivers a stillborn infant after 20 weeks gestation should be tested for syphilis, and no newborn should be discharged without documented maternal syphilis screening at least once during pregnancy 2, 1

Treat sexual partners exposed within 90 days of diagnosis presumptively, even if seronegative, and offer HIV testing to all patients with syphilis 3, 2

Pregnant women treated in the second half of gestation are at increased risk for premature labor and fetal distress if a Jarisch‑Herxheimer reaction occurs after penicillin therapy. CDC recommends close obstetric monitoring because the reaction can precipitate these adverse outcomes. [4][5]

Sonographic findings that suggest fetal syphilis include hepatomegaly, placentomegaly, ascites, hydrops fetalis, and an elevated middle‑cerebral‑artery peak systolic velocity. Detection of any of these signs warrants immediate specialist consultation. CDC emphasizes that these imaging markers identify fetuses at higher risk for treatment failure. [4][5]6
Ultrasound abnormalities should not postpone maternal penicillin treatment; therapy must be initiated promptly regardless of imaging results. CDC states that delaying therapy for imaging compromises fetal outcomes. [5][6]

When the mother has received adequate penicillin therapy (≥ 4 weeks before delivery) and shows no evidence of reinfection, the newborn requires only a single intramuscular dose of benzathine penicillin G 50,000 U/kg. CDC recommends this limited regimen for infants at low risk of congenital infection. [7][8]
If maternal treatment was inadequate (≤ 4 weeks before delivery), if the infant exhibits clinical signs of congenital syphilis, or if the mother’s therapy status is uncertain, the infant must undergo a full evaluation—including cerebrospinal‑fluid analysis, long‑bone radiographs, and a complete blood count with platelet count—and receive a 10‑day course of parenteral penicillin. CDC specifies this comprehensive approach for high‑risk neonates. [7][8]
Infants born to mothers with untreated primary syphilis at delivery should be treated with a 10‑day regimen of parenteral penicillin, irrespective of clinical findings. CDC mandates this therapy to prevent progression of congenital disease. [7][8]

Do not delay maternal syphilis treatment while awaiting ultrasound results; imaging should inform prognosis but never postpone therapy. This recommendation is reinforced by the CDC to ensure timely eradication of treponemes. [5][6]