Likelihood of congenital syphilis infection in newborn infants born to mothers with reactive nontreponemal and treponemal tests during pregnancy

Category	Definition	Additional evaluation to perform	Treatment	Follow-up testing (applies to all categories)
Proven or highly probable	Mother diagnosed with syphilis during pregnancy (reactive nontreponemal and treponemal tests), 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 maternal titer^¶ Positive darkfield microscopy, DFA, or PCR of skin lesions, body fluid(s), placenta, or umbilical cord^Δ	LP for CSF cell count, protein, and CSF VDRL CBC with differential and platelet count LFTs Long-bone radiographs 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	ALL of the following: Mother diagnosed with syphilis during pregnancy (reactive nontreponemal and treponemal tests) Mother 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 maternal titer^¶	We further classify newborns in the "possible" category as higher or lower risk: Higher risk: Neonate's VDRL or RPR is reactive or maternal risk of untreated syphilis is high Lower risk: Neonate's VDRL or RPR is nonreactive and maternal risk of untreated syphilis is low
		Higher risk: Perform same evaluation as for the "proven or highly probable" category (see 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	ALL of the following: Mother diagnosed with syphilis during pregnancy (reactive nontreponemal and treponemal tests) Mother received appropriate treatment during pregnancy (at least 4 weeks before delivery)^◊ Mother has no evidence of reinfection or relapse^◊ Infant physical examination is normal Infant serum VDRL or RPR titer <4-fold maternal titer^¶	Not required	Single dose of IM penicillin benzathine^¥
Unlikely	ALL of the following: Mother had reactive nontreponemal and treponemal tests during pregnancy Mother received appropriate treatment before pregnancy^◊ Mother's titers 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 maternal titer^¶	Not required	Not required^‡

This table summarizes the likelihood of congenital syphilis infection based upon maternal and newborn serologies, adequacy of maternal treatment, clinical findings in the infant, and other findings. Evaluation for congenital syphilis is warranted in all newborns born to mothers who have reactive nontreponemal and treponemal tests for syphilis during pregnancy. For mothers screened with the traditional approach, the treponemal test is necessary to exclude a false-positive nontreponemal result. When reverse sequencing is used, the nontreponemal test is still necessary for comparison with the mother's result and for monitoring of treatment success (two nontreponemal tests are needed when there is discordance between syphilis antibody and nontreponemal test during reverse sequencing). Refer to UpToDate's topics on syphilis during pregnancy and congenital syphilis for additional details.

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

* 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 if maternal 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 maternal 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 maternal treatment
Inadequate response to therapy (ie, maternal 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 and instead provide close (ie, monthly) serologic follow-up. If this approach is chosen, 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 mother was reinfected.

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Likelihood of congenital syphilis infection in newborn infants born to mothers with reactive nontreponemal and treponemal tests during pregnancy