What is the appropriate management and treatment for a neonate born to a mother with syphilis?

Management of Neonate Born to Mother with Syphilis

All neonates born to mothers with syphilis require immediate risk stratification based on maternal treatment history, infant examination findings, and serologic titers, with treatment ranging from a single dose of benzathine penicillin to 10-14 days of IV aqueous crystalline penicillin G depending on the clinical scenario. 1, 2

Initial Assessment and Risk Stratification

Every neonate requires:

• Physical examination looking specifically for hepatosplenomegaly, jaundice, rash, rhinitis ("snuffles"), skeletal abnormalities, or neurologic signs 1
• Quantitative nontreponemal serologic testing (RPR or VDRL) to compare with maternal titers 1
• Review of maternal treatment records including timing, adequacy, and type of therapy 1

Scenario 1: Proven or Highly Probable Congenital Syphilis

Treat immediately with 10-14 days of IV penicillin if the infant has ANY of the following 1, 2:

• Abnormal physical examination consistent with congenital syphilis
• Infant's nontreponemal titer is ≥4-fold higher than mother's titer
• Positive darkfield or fluorescent antibody test of body fluids

Required Evaluation Before Treatment:

• CSF analysis for VDRL, cell count, and protein 1, 2
• Complete blood count with differential and platelet count 1, 2
• Long-bone radiographs 1
• Additional tests as indicated: chest radiograph, liver function tests, ophthalmologic examination, auditory brainstem response 1

Treatment Regimen:

Aqueous crystalline penicillin G 100,000-150,000 units/kg/day IV, divided as 1, 2, 3:

• 50,000 units/kg/dose every 12 hours during first 7 days of life
• Then every 8 hours thereafter for total of 10 days

Alternative: Procaine penicillin G 50,000 units/kg/dose IM once daily for 10 days 1

Critical caveat: If >1 day of therapy is missed, restart the entire 10-day course 1

Scenario 2: Normal Exam, Titer ≤4-fold Maternal, BUT Inadequate Maternal Treatment

Treat with 10 days of parenteral penicillin if mother had 1:

• No treatment or undocumented treatment
• Non-penicillin regimen (considered untreated) 1
• Treatment <4 weeks before delivery
• Inadequate serologic response (titers did not decrease 4-fold for early syphilis)
• Suspected reinfection or relapse (4-fold increase in maternal titer)

Two Treatment Options:

Option A (Preferred if mother has untreated early syphilis): 1

• Aqueous crystalline penicillin G 100,000-150,000 units/kg/day IV for 10 days (dosing as above)
• OR Procaine penicillin G 50,000 units/kg/dose IM daily for 10 days
• Complete evaluation unnecessary if full 10-day course given, but lumbar puncture may be useful to document CSF abnormalities 1

Option B (Only if full evaluation is normal and follow-up certain): 1

• Single dose benzathine penicillin G 50,000 units/kg IM
• Requires: Normal CSF examination, normal long-bone radiographs, normal CBC with platelets 1
• If any part of evaluation is abnormal, not done, or CSF contaminated with blood, must use 10-day parenteral regimen 1

Scenario 3: Normal Exam, Titer ≤4-fold Maternal, Adequate Maternal Treatment

Single dose benzathine penicillin G 50,000 units/kg IM if mother 1:

• Was treated during pregnancy with appropriate penicillin regimen for stage of infection
• Treatment was >4 weeks before delivery
• For early syphilis: nontreponemal titers decreased 4-fold after therapy
• For late latent: titers remained stable and low
• No evidence of reinfection or relapse

Alternative approach: Some experts recommend close serologic follow-up without treatment if maternal titers appropriately decreased for early syphilis or remained stable/low for late syphilis 1

Additional consideration: If infant's nontreponemal test is nonreactive in this scenario, no treatment is necessary 1

Scenario 4: Maternal Treatment Before Pregnancy

No treatment required if 1:

• Mother treated before pregnancy
• Multiple evaluations documented
• Nontreponemal titers remained low and stable throughout pregnancy and at delivery (VDRL ≤1:2; RPR ≤1:4)

However: Consider single dose benzathine penicillin G 50,000 units/kg IM if follow-up is uncertain 1

Follow-Up Protocol for All Treated or At-Risk Infants

Mandatory serologic monitoring 1, 2:

• Quantitative nontreponemal testing every 2-3 months until nonreactive or decreased 4-fold
• Titers should decline by 3 months and become nonreactive by 6 months if infant was uninfected or adequately treated 1, 2
• If titers stable or increase after 6-12 months: Full re-evaluation including CSF examination and re-treatment with 10-day IV penicillin 1

For infants with abnormal initial CSF: Repeat lumbar puncture every 6 months until normal 1

Treponemal tests should NOT be used to evaluate treatment response, as they remain positive despite effective therapy 1

Special Considerations

Penicillin Allergy:

Desensitization is mandatory - there are no proven alternatives to penicillin for congenital syphilis 1, 2. If non-penicillin agents are used, close serologic and CSF follow-up are essential 1

Older Infants (>1 month):

Aqueous crystalline penicillin G 200,000-300,000 units/kg/day IV for 10-14 days, administered as 50,000 units/kg every 4-6 hours 1, 2, 3

Common Pitfalls:

• Do not assume absence of 4-fold higher titer excludes congenital syphilis 1
• CSF values in neonates are difficult to interpret - normal values differ by gestational age (up to 25 WBCs/mm³ and protein 150 mg/dL may be normal, though some experts use lower cutoffs of 5 WBCs/mm³ and 40 mg/dL) 1
• Women treated with non-penicillin regimens must be considered untreated 1
• Never use ampicillin or other alternatives - data are insufficient and close follow-up required 1