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Likelihood of congenital syphilis infection in newborn infants whose birthing parent tested positive for syphilis during pregnancy

Likelihood of congenital syphilis infection in newborn infants whose birthing parent tested positive for syphilis during pregnancy
Category Definition Additional evaluation to perform Treatment Follow-up testing
(applies to all categories)
Proven or highly probable congenital syphilis (scenario 1)
  • Birthing parent tested positive for syphilis during pregnancy or at delivery, regardless of treatment received

    • Plus

  • Newborn has any of the following:
    • Clinical findings consistent with congenital syphilis*
    • Infant serum VDRL or RPR titer ≥4-fold birthing parent's titer
    • Positive darkfield microscopy or PCR of skin lesions, body fluid(s), placenta, or umbilical cordΔ
  • LP for CSF cell count, protein, and CSF VDRL
  • CBC with differential and platelet count
  • Comprehensive metabolic panel (LFTs, electrolytes, kidney function tests)
  • Skeletal survey
  • ABR
  • Eye examination
  • Other tests as clinically indicated:
    • Chest radiograph if there are pulmonary findings
    • Neuroimaging if there are concerning neurologic findings
    • Abdominal imaging if there is significant organomegaly
 10 days of IV penicillin G
  • Monitor clinical examination for development of new concerning findings
  • Perform follow-up serologic testing:
    • For infants with reactive nontreponemal serologies: Perform serial serologic testing with VDRL or RPR (use same test as for initial testing) at 1, 2, 4, 6, and 12 months or until nonreactive. If nontreponemal tests are still positive at 6-12 months, the infant should be re-evaluated (including LP) and treated with an extended course of parenteral penicillin
    • For infants with nonreactive nontreponemal serologies: Recheck VDRL or RPR (use same test as for initial testing) at age 3 months to confirm infant remains seronegative
Possible congenital syphilis (scenario 2) All of the following:
  • Birthing parent tested positive for syphilis during pregnancy or at delivery
  • Birthing parent did not receive treatment, or received inadequate/suboptimal treatment, or had evidence of relapse or reinfection◊
  • Infant physical examination is normal
  • Infant serum VDRL or RPR titer <4-fold birthing parent's titer
 We further classify newborns in the "possible" category as higher or lower risk:
  • Higher risk: Neonate's VDRL or RPR is reactive or birthing parent' risk of untreated syphilis is high
  • Lower risk: Neonate's VDRL or RPR is nonreactive and birthing parent's risk of untreated syphilis is low
Higher risk:
  • Perform same evaluation as for the "proven or highly probable" category (refer above)§
 Higher risk:
  • If any part of the additional evaluation is abnormal, not performed, or uninterpretable (eg, traumatic LP) or if follow-up is uncertain: 10 days of IV penicillin G
  • If all tests in the additional evaluation are performed and are normal: Single dose of IM penicillin benzathine
Lower risk:
  • Additional evaluation is not necessary
 Lower risk:
  • Single dose of IM benzathine penicillin
Less likely congenital syphilis (scenario 3) All of the following:
  • Birthing parent tested positive for syphilis during pregnancy or at delivery
  • Birthing parent received appropriate treatment during pregnancy (at least 4 weeks before delivery)◊
  • Birthing parent has no evidence of reinfection or relapse◊
  • Infant physical examination is normal
  • Infant serum VDRL or RPR titer <4-fold birthing parent's titer
 Not required Single dose of IM penicillin benzathine¥
Unlikely congenital syphilis (scenario 4) All of the following:
  • Birthing parent tested positive for syphilis during pregnancy or at delivery
  • Birthing parent received appropriate treatment before pregnancy◊
  • Birthing parent's titers had cleared or declined by >4-fold and remained low (VDRL <1:2; RPR <1:4) and stable before and during pregnancy and at delivery
  • Infant physical examination is normal
  • Infant serum VDRL or RPR titer <4-fold birthing parent's titer
 Not required Not required‡
This table summarizes the likelihood of congenital syphilis infection based upon VDRL or RPR titers (in both the infant and birthing parent), the infant's physical examination, the birthing parent's treatment history, and other findings. Evaluation for congenital syphilis in the newborn is warranted if the birthing parent tested positive for syphilis during pregnancy or at delivery. This generally requires that the birthing parent had both a positive nontreponemal test (VDRL or RPR) and treponemal test. However, in some cases it may be appropriate to test the newborn if the birthing parent underwent reverse sequence testing yielding discordant results (ie, positive treponemal test with negative VDRL or RPR). Refer to UpToDate's topics on syphilis during pregnancy and congenital syphilis for additional details.

ABR: auditory brainstem response; CBC: complete blood count; CDC: Centers for Disease Control and Prevention; CSF: cerebrospinal fluid; DFA: direct fluorescent antibody; IM: intramuscular; IV: intravenous; LFTs: liver function tests; LP: lumbar puncture; PCR: polymerase chain reaction; RPR: rapid plasma regain; VDRL: venereal disease research laboratory.

* Findings of congenital syphilis may include hepatosplenomegaly, rash, condyloma lata, snuffles, jaundice (nonviral hepatitis), pseudoparalysis, pallor (anemia), or edema (nephrotic syndrome and/or malnutrition). Refer to UpToDate topic on congenital syphilis for additional details.

¶ A 4-fold titer is equivalent to two dilutions (eg, newborn's titer 1:32 when birthing parent's titer is 1:8).

Δ These tests are not available in many clinical settings.

◊ Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with CDC treatment guidelines, appropriate for stage of infection and initiated ≥4 weeks before delivery. Relapse or reinfection after treatment is suggested by a 4-fold increase of the birthing parent's VDRL or RPR titers after treatment. Inadequate/suboptimal therapy includes any of the following:

  • Treatment with a nonpenicillin antibiotic
  • Treatment given <4 weeks before delivery
  • Inappropriate dose for stage of disease
  • Inadequate documentation of treatment in the birthing parent
  • Inadequate response to therapy (ie, birthing parent's VDRL or RPR titers did not decline at least 4-fold after treatment)

§ The CDC guidelines include a caveat that additional evaluation may not be necessary for neonates in the "possible" category if a 10-day treatment course is planned. Nevertheless, we suggest performing the evaluation in higher-risk neonates (as defined above) since the evaluation may inform decisions regarding treatment and follow-up.

¥ Some specialists opt not to treat infants in this category if the birthing parent was treated adequately and close follow-up of the infant is certain. If this approach is chosen, close serologic follow-up (ie, monthly) is necessary, and treatment should be provided if the infant's titers do not decline as expected over the first few months after birth.

‡ If follow-up is uncertain, some specialists would provide a single dose of IM benzathine penicillin to protect the infant in the unlikely event that the birthing parent was reinfected.

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