What are the treatment guidelines for congenital syphilis in newborns if the mother has received treatment versus no treatment?

Treatment Guidelines for Congenital Syphilis Based on Maternal Treatment Status

For newborns whose mothers have received inadequate or no treatment for syphilis, a full 10-day course of parenteral penicillin therapy is strongly recommended, while infants of adequately treated mothers may require only a single dose of benzathine penicillin G or no treatment depending on specific criteria. 1

Evaluation of Newborns for Congenital Syphilis

The diagnosis of congenital syphilis is complicated by the transplacental transfer of maternal antibodies. Evaluation should include:

• Quantitative nontreponemal serologic test (RPR or VDRL) on infant serum (not cord blood, which may be contaminated with maternal blood) 1
• Thorough physical examination for evidence of congenital syphilis (nonimmune hydrops, jaundice, hepatosplenomegaly, rhinitis, skin rash, pseudoparalysis) 1
• Darkfield microscopy or direct fluorescent antibody staining of suspicious lesions or body fluids when present 1

Treatment Scenarios Based on Maternal Treatment Status

Scenario 1: Mother Received No Treatment or Inadequate Treatment

Clinical presentation: Infants with normal physical examination and serum nontreponemal titer ≤ fourfold the maternal titer, but mother was:

• Not treated, inadequately treated, or lacks documentation of treatment
• Treated with erythromycin or another non-penicillin regimen
• Treated less than 4 weeks before delivery 1

Recommended evaluation:

• CSF analysis for VDRL, cell count, and protein
• CBC, differential, and platelet count
• Long-bone radiographs 1

Recommended treatment:

• Aqueous crystalline penicillin G 100,000-150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during first 7 days of life and every 8 hours thereafter for a total of 10 days; OR
• Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days 1, 2

Important note: A complete evaluation is not necessary if 10 days of parenteral therapy is administered, although such evaluations might be useful to guide follow-up 1

Scenario 2: Mother Received Appropriate Treatment During Pregnancy

Clinical presentation: Infants with normal physical examination and serum nontreponemal titer ≤ fourfold the maternal titer, and mother was:

• Treated during pregnancy with appropriate regimen for stage of infection
• Treatment administered >4 weeks before delivery
• No evidence of maternal reinfection or relapse 1

Recommended treatment:

• Benzathine penicillin G 50,000 units/kg/dose IM in a single dose 1

Alternative approach:

• Close serologic follow-up without treatment if mother's nontreponemal titers decreased fourfold after appropriate therapy for early syphilis or remained stable/low for late syphilis 1

Scenario 3: Mother Treated Adequately Before Pregnancy

Clinical presentation: Infants with normal physical examination and serum nontreponemal titer ≤ fourfold the maternal titer, and mother:

• Received adequate treatment before pregnancy
• Has nontreponemal serologic titer that remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4) 1

Recommended treatment:

• No treatment required
• Consider benzathine penicillin G 50,000 units/kg as a single IM injection if follow-up is uncertain 1

Special Considerations

Infants with Proven or Highly Probable Disease

Clinical presentation:

• Abnormal physical examination consistent with congenital syphilis
• Serum quantitative nontreponemal titer fourfold greater than mother's titer
• Positive darkfield or fluorescent antibody test of body fluid(s) 1

Recommended treatment:

• Full 10-day course of parenteral penicillin therapy as outlined in Scenario 1 1

Treatment Failures and Follow-up

• If more than 1 day of therapy is missed, the entire course should be restarted 1
• Data are insufficient regarding the use of antimicrobial agents other than penicillin 1
• When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis 1
• Use of agents other than penicillin requires close serologic follow-up 1

Pitfalls and Caveats

• Umbilical cord blood should not be used for infant serologic testing as it may be contaminated with maternal blood 1
• A woman treated with a regimen other than those recommended in CDC guidelines should be considered untreated 1
• Treatment failures can occur even with appropriate maternal treatment regimens 3
• The Jarisch-Herxheimer reaction occurs in up to 44% of pregnant women during treatment and can cause contractions, fetal heart rate abnormalities, and rarely stillbirth 4
• After adequate treatment, a fourfold decline in maternal nontreponemal titers may not be observed by delivery and does not necessarily correlate with rates of congenital syphilis 5