#145: The Great Imitator: Unmasking Congenital Syphilis

July 2, 2025 | By Sam Masur

Audio

Summary:

Join us for a great discussion on congenital syphilis with Dr. Ryan Rochat! We’ll shine a light on the darkfield of congenital syphilis and unmask The Great Imitator. We dive into the rationale for screening for syphilis in pregnancy, the testing available, and how the heck to interpret the screening algorithm. We also explore the comprehensive evaluation and follow-up of affected infants.

Congenital Syphilis Pearls

1. Always determine the birthing parent’s serologic syphilis status before discharge from the newborn nursery
2. Pregnant patients with a penicillin allergy should be desensitized to penicillin, then treated with penicillin 
3. All infants who are seropositive require careful follow-up evaluations during well-child care visits at 2, 4, 6, and 12 months of age

Congenital Syphilis Notes 

What is syphilis?

Syphilis is a sexually transmitted infection caused by Treponema pallidum. Often referred to as “The Great Imitator,” syphilis causes a range of clinical presentations. 

In-utero transmission of T. pallidum can occur at any trimester and at any stage of infection, though there is a higher rate during early primary and early secondary infection.

What is the rationale for screening for syphilis in pregnancy?

Screening and treatment are extremely effective at reducing vertical transmission; therefore, screening allows us to identify cases.

Screening frequency varies by guidelines and local legislation. 

• The American College of Obstetrics and Gynecology recommends screening for syphilis at the first prenatal encounter, during the third trimester, and at delivery.
• Only 6 states (Alabama, Arizona, Georgia, Mississippi, North Carolina, and Texas) mandate screening on this timeline; others only require screening if there is increased risk. 

Who is at increased risk of syphilis infection?

CDC data showed that syphilis rates increased year over year across all demographics from 2014-2022.

Congenital syphilis rates correlate with rates of primary and secondary syphilis in women aged 15-44, as vertical transmission is highest in the earlier stages of disease.

Testing for Syphilis

What tests are available for syphilis?

Non-treponemal tests include rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests.

These test for antibodies (anticardiolipin).

RPR is non-specific and can be increased in other disease processes.

Treponemal tests include Treponema pallidum particle agglutination assay (TP-PA),  Fluorescent Treponemal Antibody – Absorbed (FTA-ABS), and Automated T. pallidum Enzyme Immunoassay .

These test for T. pallidum-specific antigens.

TP-PA is generally preferred given better sensitivity and specificity.

The prozone phenomenon refers to a weakly reactive or falsely negative non-treponemal test performed on serum with high antibody concentrations.

Diluting the serum being tested will then result in a positive test result.

40% of people can serorevert, meaning their RPR will be negative.

What about the syphilis screening algorithms?

In general, the algorithms start with evaluating the birthing parent’s history of syphilis:

• Have they had syphilis before and was it treated?
• How long ago was the treatment?
• Did they respond appropriately to treatment?
• Was there concern for re-infection?

Forward screening begins with a non-treponemal test that should be confirmed with a treponemal test.

Reverse screening begins with a treponemal test, confirmed with a non-treponemal test.

What test should we perform in an infant?

Infants should have a thorough physical exam and non-treponemal test (RPR or VDRL) regardless of the birthing parent’s treatment history.

• Treponemal testing may be misleading due to maternal antibody transfer; therefore, they are less reliable for neonatal screening.
• If maternal testing is unavailable, treponemal testing may provide more valuable information.

The Red Book states “no newborn infant should be discharged from the hospital without determination of the mother’s serologic status for syphilis.”

Infants require more comprehensive testing if:

• The infant’s physical exam is abnormal
• The RPR is fourfold or greater than the birthing parent’s
• The birthing parent’s treatment was inadequate or if she was high risk for re-infection

The “full evaluation” for congenital syphilis includes:

• CBC, particularly to evaluate for anemia, thrombocytopenia, leukopenia, or leukocytosis
• CSF studies with cell count, protein, glucose, and VDRL
• Long bone radiography (skeletal abnormalities are pathognomonic)

Other tests (as clinically indicated):

• Chest radiography
• Complete metabolic panel to evaluate for hepatic involvement
• Neuroimaging

• Hearing screen
• Dr. Rochat’s expert opinion is to obtain an ophthalmologic exam, if possible, as ocular findings can occur at any stage of disease
• Histopathologic examination of placenta 
• HIV testing (given risk of co-infection)

An infant who is seroreactive at delivery should have careful follow-up at 2, 4, 6, and 12 months of age, with additional targeted testing around any deficits noted.

What test should we perform in an older person?

Start with a treponemal-specific test if there is a risk they have ever been exposed, then do an RPR.

Treating Syphilis

Penicillin is the mainstay of treatment for syphilis.

• Penicillin is the only reliable treatment in pregnancy due to its ability to cross the placenta adequately to ensure fetal treatment.
• Alternatives (doxycycline, tetracycline, and ceftriaxone) are not reliable during pregnancy as they do not ensure fetal treatment.
• Pregnant patients with a penicillin allergy should be desensitized to penicillin, then treated with penicillin.

Penicillin formulations

Aqueous penicillin G (Intravenous)

• 50,000 units/kg IV every 12 hours (for neonates ≤7 days of age) or every 8 hours (for neonates >7 days of age) for a total of 10 days
• Preferred for congenital syphilis and CNS infection due to its ability to cross the blood-brain barrier
• If more than 1 day of therapy is missed, the entire course should be restarted.

Benzathine penicillin G (Intramuscular)

• 50,000 units/kg given IM as a single dose
• Provides bactericidal activity against T. pallidum for 21-28 days
• Does NOT cross the blood-brain barrier, therefore ineffective in treating neurosyphilis

Procaine penicillin (intramuscular)

• 50,000 units/kg IM as a daily dose for 10 days
• Crosses the blood brain barrier, therefore it is efficacious for treating CNS infection
• No longer being manufactured 

What follow-up is necessary for these infants?

The Red Book states: “All infants who have reactive serologic tests for syphilis or were born to a person who was seroreactive at delivery should receive careful follow-up evaluations during well-child care visits at 2, 4, 6, and 12 months of age.” 

These children may be at risk for developmental deficits, that should be assessed as they arise, rather than recommending therapies generally.

Goal

Listeners will understand the mechanisms of transmission for syphilis, the rationale and frameworks for screenings, treatment of congenital syphilis, and recommendations for follow-up.

Learning Objectives

After listening to this episode listeners will…  

1. Recall the causative agent of syphilis and the modes of transmission.
2. Describe the rationale for screening in pregnancy and how to interpret the screening algorithms and tests.
3. Apply the relevant guidelines to determine the appropriate evaluation for a given patient. 
4. Develop a framework to counsel families on congenital syphilis, treatment, and follow-up. 

Disclosures

Dr. Rochat reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

Rago AR, Rochat, R, Chiu C, Masur S. “#145: The Great Imitator: Unmasking Congenital Syphilis”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com. July 2, 2025.