Note from the National Guideline Clearinghouse: This guideline references a drug(s) for which important revised regulatory and/or warning information has been released.

Note from the National Guideline Clearinghouse (NGC) and the Centers for Disease Control and Prevention (CDC): When more than one therapeutic regimen is recommended, the sequence is alphabetized unless the choices for therapy are prioritized based on efficacy, convenience, or cost. For sexually transmitted diseases (STDs) with more than one recommended regimen, almost all regimens have similar efficacy and similar rates of intolerance or toxicity unless otherwise specified.

Effective prevention and detection of congenital syphilis depends on the identification of syphilis in pregnant women and, therefore, on the routine serologic screening of pregnant women during the first prenatal visit. In communities and populations in which the risk for congenital syphilis is high, serologic testing and a sexual history also should be obtained at 28 weeks' gestation and at delivery. Moreover, as part of the management of pregnant women who have syphilis, information concerning treatment of sex partners should be obtained to assess the risk for reinfection. All pregnant women who have syphilis should be tested for human immunodeficiency virus (HIV) infection. Routine screening of newborn sera or umbilical cord blood is not recommended. Serologic testing of the mother's serum is preferred rather than testing of the infant's serum because the serologic tests performed on infant serum can be nonreactive if the mother's serologic test result is of low titer or if the mother was infected late in pregnancy (see Diagnostic Considerations and Use of Serologic Tests above). No infant or mother should leave the hospital unless the maternal serologic status has been documented at least once during pregnancy and at delivery in communities and populations in which the risk for congenital syphilis is high.

Evaluation and Treatment of Infants in the First Month of Life

The diagnosis of congenital syphilis is complicated by the transplacental transfer of maternal nontreponemal and treponemal immunoglobulin G (IgG) antibodies to the fetus. This transfer of antibodies makes the interpretation of reactive serologic tests for syphilis in infants difficult. Treatment decisions frequently must be made on the basis of 1) identification of syphilis in the mother; 2) adequacy of maternal treatment; 3) presence of clinical, laboratory, or radiographic evidence of syphilis in the infant; and 4) comparison of maternal (at delivery) and infant nontreponemal serologic titers using the same test and preferably the same laboratory.

All infants born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test (rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]) performed on infant serum, because umbilical cord blood can become contaminated with maternal blood and could yield a false-positive result. Conducting a treponemal test (i.e., Treponema pallidum particle agglutination [TP-PA] or fluorescent treponemal antibody absorbed [FTA-ABS]) on a newborn's serum is not necessary. No commercially available immunoglobulin M (IgM) test can be recommended.

All infants born to women who have reactive serologic tests for syphilis should be examined thoroughly for evidence of congenital syphilis (e.g., nonimmune hydrops, jaundice, hepatosplenomegaly, rhinitis, skin rash, and/or pseudoparalysis of an extremity). Pathologic examination of the placenta or umbilical cord using specific fluorescent antitreponemal antibody staining is suggested. Darkfield microscopic examination or direct fluorescent antibody (DFA) staining of suspicious lesions or body fluids (e.g., nasal discharge) also should be performed.

The following scenarios describe the evaluation and treatment of infants for congenital syphilis.

Scenario 1. Infants with proven or highly probable disease

1. an abnormal physical examination that is consistent with congenital syphilis
2. a serum quantitative nontreponemal serologic titer that is fourfold greater than the mother's titer (Note: The absence of a fourfold or greater titer for an infant does not exclude congenital syphilis); or
3. a positive darkfield or fluorescent antibody test of body fluid(s)

Recommended Evaluation

• Cerebrospinal fluid (CSF) analysis for VDRL, cell count, and protein. (Note: CSF test results obtained during the neonatal period can be difficult to interpret; normal values differ by gestational age and are higher in preterm infants. Values as high as 25 white blood cells (WBCs)/mm³ and/or protein of 150 mg/dL might occur among normal neonates; some specialists, however, recommend that lower values (i.e., 5 WBCs/mm³ and protein of 40 mg/dL) be considered the upper limits of normal. Other causes of elevated values also should be considered when an infant is being evaluated for congenital syphilis.)
• Complete blood count (CBC) and differential and platelet count.
• Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver-function tests, cranial ultrasound, ophthalmologic examination, and auditory brainstem response).

Recommended Regimens

Aqueous crystalline penicillin G 100,000-150,000 units/kg/day, administered as 50,000 units/kg/dose intravenously (IV) every 12 hours during the 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 intramuscularly (IM) in a single daily dose for 10 days.

If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.

Scenario 2. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the

1. mother was not treated, inadequately treated, or has no documentation of having received treatment
2. mother was treated with erythromycin or other nonpenicillin regimen (Note: A woman treated with a regimen other than those recommended in the guidelines for treatment should be considered untreated)
3. mother received treatment <4 weeks before delivery; or

Recommended Evaluation

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

A complete evaluation is not necessary if 10 days of parenteral therapy is administered. However, such evaluation might be useful; a lumbar puncture might document CSF abnormalities that would prompt close follow-up. Other tests (e.g., CBC, platelet count, and bone radiographs) may be performed to further support a diagnosis of congenital syphilis. If a single dose of benzathine penicillin G is used, then the infant must be fully evaluated (i.e., through CSF examination, long-bone radiographs, and CBC with platelets), the full evaluation must be normal, and follow-up must be certain. If any part of the infant's evaluation is abnormal or not performed, or if the CSF fluid analysis is rendered uninterpretable because of contamination with blood, then a 10-day course of penicillin is required. (Note: If the infant's nontreponemal test is nonreactive and the likelihood of the infant being infected is low, certain specialists recommend no evaluation but treatment of the infant with a single intramuscular (IM) dose of benzathine penicillin G 50,000 units/kg for possible incubating syphilis, after which the infant should receive close serologic follow-up.)

Recommended Regimens

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

OR

Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days

OR

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

Some specialists prefer the 10 days of parenteral therapy if the mother has untreated early syphilis at delivery.

Scenario 3. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the

1. mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery; and
2. mother has no evidence of reinfection or relapse

Recommended Evaluation

No evaluation is required.

Recommended Regimen

Benzathine penicillin G 50,000 units/kg/dose IM in single dose. (Note: Some specialists would not treat the infant but would provide close serologic follow-up in those whose mother's nontreponemal titers decreased fourfold after appropriate therapy for early syphilis or remained stable or low for late syphilis.)

Scenario 4. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the

1. mother's treatment was adequate before pregnancy and
2. mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4)

Recommended Evaluation

No evaluation is required.

Recommended Regimen

No treatment is required; however, some specialists would treat with benzathine penicillin G 50,000 units/kg as a single IM injection, particularly if follow-up is uncertain.

Evaluation and Treatment of Older Infants and Children

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