How to manage a newborn with positive Venereal Disease Research Laboratory (VDRL) and Treponema Pallidum Haemagglutination Assay (TPHA) results?

Management of a Newborn with Positive VDRL and TPHA Results

A newborn with positive VDRL and TPHA results should be fully evaluated for congenital syphilis and treated with aqueous crystalline penicillin G 100,000-150,000 units/kg/day IV for 10 days, regardless of maternal treatment status. 1

Initial Evaluation

The evaluation of a newborn with positive serologic tests for syphilis should include:

• Complete physical examination for evidence of congenital syphilis (nonimmune hydrops, jaundice, hepatosplenomegaly, rhinitis, skin rash, pseudoparalysis of extremity) 1
• CSF analysis for VDRL, cell count, and protein 1
• Complete blood count with differential and platelet count 1
• Long-bone radiographs 1
• Other tests as clinically indicated:
  • Chest radiograph 1
  • Liver function tests 1
  • Cranial ultrasound 1
  • Ophthalmologic examination 1
  • Auditory brainstem response 1
• Pathologic examination of the placenta or umbilical cord using specific fluorescent antitreponemal antibody staining 1
• Darkfield microscopy or direct fluorescent antibody staining of suspicious lesions or body fluids (e.g., nasal discharge) 1

Treatment Algorithm

Scenario 1: Newborn with abnormal physical examination OR serum quantitative nontreponemal titer fourfold greater than mother's titer OR positive darkfield/fluorescent antibody test

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 the first 7 days of life and every 8 hours thereafter for a total of 10 days 1
• OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days 1

Scenario 2: Newborn with normal physical examination and serum quantitative nontreponemal titer same or less than fourfold the maternal titer AND mother was inadequately treated or treatment status unknown

Recommended Treatment:

• Full evaluation as above 1
• Aqueous crystalline penicillin G or procaine penicillin G for 10 days as in Scenario 1 1

Scenario 3: Newborn with normal physical examination and serum quantitative nontreponemal titer same or less than fourfold the maternal titer AND mother was adequately treated during pregnancy >4 weeks before delivery with no evidence of reinfection/relapse

Recommended Treatment:

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

Scenario 4: Newborn with normal physical examination and serum quantitative nontreponemal titer same or less than fourfold the maternal titer AND mother was adequately treated before pregnancy with stable low titers

Recommended Treatment:

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

Follow-Up Management

• Serologic testing (nontreponemal test) every 2-3 months until the test becomes nonreactive or the titer decreases fourfold 1
• Nontreponemal antibody titers should decline by 3 months of age and become nonreactive by 6 months of age if:
  • The infant was not infected (positive result due to passive transfer of maternal IgG antibody) 1
  • The infant was infected but adequately treated 1
• If titers are stable or increasing after 6-12 months of age:
  • Re-evaluate the child, including CSF examination 1
  • Treat with a 10-day course of parenteral penicillin G 1
• For infants with abnormal initial CSF evaluation:
  • Repeat lumbar puncture approximately every 6 months until results normalize 1
  • A persistently reactive CSF VDRL or abnormal CSF indices requires re-treatment for possible neurosyphilis 1

Special Considerations

Treponemal Test Interpretation

• Do not use treponemal tests (like TPHA) to evaluate treatment response 1
• Passively transferred maternal treponemal antibodies can persist in an infant until 15 months of age 1
• A reactive treponemal test after 18 months of age is diagnostic of congenital syphilis 1
  • If nontreponemal test is nonreactive at this time, no further evaluation or treatment is necessary 1
  • If nontreponemal test is reactive at 18 months, fully re-evaluate and treat for congenital syphilis 1

Penicillin Allergy

• Infants with history of penicillin allergy or who develop allergic reaction should be desensitized and then treated with penicillin 1
• No proven alternatives to penicillin exist for treating congenital syphilis 1
• If a non-penicillin agent must be used, close serologic and CSF follow-up is essential 1

HIV Co-infection

• Data are insufficient regarding whether infants with congenital syphilis born to HIV-coinfected mothers require different evaluation, therapy, or follow-up 1
• All children at risk for congenital syphilis should receive HIV testing 1

Common Pitfalls and Caveats

• Umbilical cord blood should not be used for serologic testing as it can be contaminated with maternal blood and yield false-positive results 1
• Interpretation of CSF results in neonates can be challenging - normal values differ by gestational age and are higher in preterm infants 1
• If more than 1 day of therapy is missed, the entire course should be restarted 1
• The VDRL test alone has high rates of biological false positives (26% in one large study), emphasizing the importance of confirmatory treponemal testing 2
• Serologic response may be slower for infants treated after the neonatal period 1