Congenital Syphilis

Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted from a pregnant woman to her fetus. The Centers for Disease Control and Prevention (CDC) case definition for congenital syphilis includes:

• The child has physical, laboratory, or radiographic signs of congenital syphilis (confirmed/highly probable congenital syphilis), or
• The child was born to a mother with untreated, inadequately, or suboptimally treated syphilis (presumed congenital syphilis)

Maternal risk factors for syphilis during pregnancy include sex with multiple partners, sex in conjunction with drug use, transactional sex, lack of prenatal care, methamphetamine or heroin use, incarceration of the woman or her partner, and unstable housing. 

Transplacental transmission of T. pallidum can occur at any time during gestation but occurs with increasing frequency as gestation advances. Women with untreated primary or secondary syphilis are more likely to transmit syphilis to their fetuses than women with latent disease (60-90% risk in primary or secondary versus 40% in early latent and <10 percent in late latent syphilis). Untreated syphilis during pregnancy can cause spontaneous abortion, stillbirth, and early infant death.

Congenital syphilis cases have more than tripled in recent years. More than 4,000 cases were reported in the United States in 2024 alone. This is the highest number of cases reported in one year since 1994.

To prevent congenital syphilis, the 2009 U.S. Preventive Services Task Force (USPSTF) Recommendation Statement and 2015 CDC Sexually Transmitted Disease Treatment Guidelines recommend serologic syphilis screening for all women at first prenatal care visit. They recommend additional testing at 28 to 32 weeks' gestation and at delivery for women at high risk.

The diagnosis of congenital syphilis can be difficult, as maternal nontreponemal and treponemal IgG antibodies can be transferred through the placenta to the fetus, complicating the interpretation of reactive serologic tests for syphilis in neonates. Therefore, 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 neonate; and 4) comparison of maternal (at delivery) and neonatal nontreponemal serologic titers using the same test, preferably conducted by the same laboratory. Any neonate at risk for congenital syphilis should receive a full evaluation and testing for HIV infection.

All neonates born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test (RPR or VDRL) performed on the neonate’s serum, because umbilical cord blood can become contaminated with maternal blood and yield a false-positive result, and Wharton’s jelly within the umbilical cord can yield a false-negative result. Conducting a treponemal test (i.e., TP-PA, FTA-ABS, EIA, or CIA) on neonatal serum is not recommended because it is difficult to interpret. No commercially available immunoglobulin (IgM) test can be recommended.

All neonates 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 pseudoparalysis of an extremity). Pathologic examination of the placenta or umbilical cord using specific staining (e.g., silver) or a T. pallidum PCR test using a CLIA-validated test should be considered; DFA-TP reagents are not available. Darkfield microscopic examination or PCR testing of suspicious lesions or body fluids (e.g., bullous rash and nasal discharge) also should be performed. In addition to these tests, for stillborn infants, skeletal survey demonstrating typical osseous lesions might aid in the diagnosis of congenital syphilis.

Neurosyphilis in neonates and infants is usually asymptomatic. However, up to 60% of neonates born with symptoms of congenital syphilis will also have neurosyphilis. Cerebrospinal fluid should be analyzed for cell count, protein concentration and VDRL testing. In neurosyphilis, CSF cell count is >25 cells/uL and CSF protein is >150 mg/dL. VDRL is positive.

CSF VDRL results are highly specific (>90%) but sensitivity is only 50%. Therefore, a reactive CSF VDRL is diagnostic of neurosyphilis, but a non-reactive result does not rule it out. 

References

https://www.cdc.gov/std/treatment-guidelines/congenital-syphilis.htm#

Arnold SR, Ford-Jones EL. Congenital syphilis: A guide to diagnosis and management. Paediatr Child Health. 2000;5(8):463-469.

The Lancet Congenital syphilis in the USA. Lancet. 2018;392(10154):1168.

Papp JR,et al. CDC Laboratory Recommendations for Syphilis Testing, United States, 2024. MMWR Recomm Rep. 2024;73(1):1-32.

Marks M, et al. Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review. Sex Transm Infect. 2018;94(8):585-588.