Background
Epidemiology
- Rare, with about 20 per 100,000 live births in the US
- Greatest risk to child is with untreated primary maternal syphilis
Pathophysiology
- Transplacental transmission while bacteremic
- Can be transmitted during delivery, as well
Clinical Manifestations
- Mothers typically have had no prenatal care
- To the fetus, can cause spontaneous abortion (40% in untreated primary syphilis), preterm delivery, polyhydramnios, intra-uterine growth restriction, hydrops fetalis, or intra-uterine fetal demise
- At birth, two thirds of affected neonates are asymptomatic, with disease developing over the following 6 weeks
- Early disease, within the first two years, includes:
- Rhinitis (called snuffles, often bloody and copious), desquamating rash, hepatosplenomegaly, lymphadenopathy, and skeletal abnormalities
- Also: condyloma lata, vesicular rash or bullous rash, periostitis, hydrops, thrombocytopenia, hepatitis, jaundice, or glomerulonephritis
- About 20% involve the CNS
- Late disease, after the first two years, includes:
- Sensorineural hearing loss, intellectual impairment, saddle nose deformity, frontal bossing, jaw, dental, and palatal abnormalities including Hutchison teeth, saber tibia, short stature, and keratitis
Diagnosis
- Darkfield microscopy and/or PCR on body fluids, including nasal discharge or CSF
- Serology
- RPR on infant blood (not cord blood), paired with maternal RPR
- May need CSF analysis
- Also check HIV serology, skeletal survey, chest x-ray, ophthalmology, audiology, and cranial ultrasound
Management
- Treat syphilis in pregnancy with high-dose penicillin to prevent congenital syphilis
- Treat affected infant with penicillin G 50,000 U/kg/day IV q12h for the first 7 days of life, followed by q8h to complete a total of 10 days
- Can treat lower-risk infants with benzathine penicillin G 50,000 U/kg IM once
Canadian guidelines
- Treat infants at birth if:
- Symptomatic
- Infant's RPR at least four-fold higher than mother's
- Maternal treatment inadequate, did not contain penicillin, is unknown or occurred in the last month of pregnancy, or if the maternal serologic response is inadequate
- Adequate follow-up can't be ensured
- Specific scenarios are described in the table below
| Maternal treatment | Neonatal assessment | Recommendations | |||||
|---|---|---|---|---|---|---|---|
| Type | Timing | Outcome | Monthly exam for 3 months | Serology | CBC/CSF/x-rays | Treatment | |
| any | before pregnancy | adequate, with no RPR rise and no risk factors for reinfection | normal exam | no | no | no | none |
| primary, secondary, or early latent | >4 weeks before delivery | adequate | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months | no | none |
| ≤4 weeks before delivery | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | usually | ||
| not penicillin | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | usually | ||
| before or during pregnancy | RPR not decline as expected | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | usually | |
| before pregnancy | inadequate, or reinfection | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | consider | depends on risk and results of assessments | |
| during pregnancy | unknown | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | consider | depends on risk and results of assessments | |
| primary or secondary syphilis | during pregnancy | inadequate | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days |
| late latent | during or after pregnancy | adequate | normal exam, RPR < 4-fold maternal | no | 0, 6, and 18 months | no | none |
| any | during pregnancy | normal exam, RPR < 4-fold maternal | follow-up unlikely | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | consider | depends on risk and results of assessments |
| any | any | treponemes on tissue examination | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |
| infant's RPR four-fold or greater than the mother's at birth | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
| four-fold rise in infant's titre | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
| signs of congenital syphilis at any age | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
| RPR & TT reactive at 6 months | — | — | yes | usually | |||
| reactive RPR & TT at 12 months | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
| reactive TT at 18 months | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
US guidelines
| Initial neonatal assessment | Maternal treatment | Recommendations | |||
|---|---|---|---|---|---|
| RPR/VDRL | Evaluation | Timing | Type | Evaluation | Treatment |
| any | physical exam suggests congenital syphilis | any | any | LP and CBC | 10 days |
| spirochete in a clinical specimen | |||||
| ≥ fourfold maternal titre | any | any | any | LP and CBC | 10 days |
| less than fourfold maternal titre | normal | before pregnancy | adequate | none | none (or one dose) |
| reinfection or relapse (≥4-fold increase in titre) | LP and CBC | one dose (unless exam at all abnormal) | |||
| during pregnancy | adequate | none | one dose (or none) | ||
| inadequate or suboptimal | LP and CBC | one dose (unless exam at all abnormal) | |||
| nonreactive | normal | during pregnancy | adequate | none | none (or one dose) |
| inadequate or suboptimal | none | one dose | |||
- LP should be sent for VDRL, cell count, protein
- CBC with differential for platelet count
