What is the most significant risk for a pregnant woman diagnosed with syphilis if left untreated?

Congenital Syphilis is the Most Significant Risk

If left untreated, a pregnant woman with syphilis is most at risk for congenital syphilis, which results in stillbirth in up to 40% of cases, with additional risks of neonatal death, severe fetal infection, and permanent sequelae in surviving infants. 1, 2

Understanding the Magnitude of Risk

The consequences of untreated maternal syphilis are devastating and directly impact fetal morbidity and mortality:

• Stillbirth occurs in approximately 40% of pregnancies with untreated maternal syphilis, making it the most catastrophic outcome 2
• Among pregnancies that continue beyond 20 weeks gestation with untreated syphilis, up to 40% of fetuses are either stillborn or die from infection during infancy 2
• Congenital syphilis develops when maternal infection transmits to the fetus through the placenta, and this can occur at any stage of maternal disease and in any trimester 3

Specific Fetal and Neonatal Complications

Beyond stillbirth, untreated maternal syphilis causes severe fetal pathology:

• Sonographic findings of fetal syphilis include hepatomegaly, placentomegaly, ascites, hydrops fetalis, fetal anemia (detected by elevated middle cerebral artery peak systolic velocity), and thickened placenta 1, 3
• Neonatal manifestations include nonimmune hydrops, jaundice, hepatosplenomegaly, rhinitis, skin rash, and pseudoparalysis of extremities 1
• Pregnancies with ultrasound abnormalities carry higher risk for fetal treatment failure even when maternal treatment is administered 1, 3

Stage-Specific Maternal Risk

The risk of fetal treatment failure varies by maternal disease stage:

• Secondary syphilis carries the highest risk of fetal treatment failure compared to other stages, with a success rate of only 94.7% (71 of 75 cases) versus 98.2% overall 4
• Two of six fetal treatment failures in one study resulted in preterm stillborns, both occurring in mothers with secondary syphilis 4

Critical Treatment Window

The effectiveness of preventing congenital syphilis depends entirely on timing:

• Maternal treatment with penicillin is 98% effective at preventing congenital syphilis when administered appropriately during pregnancy and at least 28 days before delivery 5, 6
• Inadequate maternal treatment is the strongest predictor of congenital syphilis, with an adjusted odds ratio of 86.1 (95% CI: 15.9-466.5) 6
• Screening in the third trimester (AOR 8.4,95% CI: 2.9-24.6) or fewer than 28 days before delivery (AOR 8.1,95% CI: 1.4-47.8) significantly increases risk of congenital syphilis compared to first or second trimester screening 6

Additional Maternal Complications

While congenital syphilis is the primary concern, untreated maternal syphilis also poses direct maternal risks:

• Placental inflammation from congenital infection may increase the risk of perinatal HIV transmission in co-infected women 1
• Premature labor and fetal distress can occur if treatment precipitates the Jarisch-Herxheimer reaction, particularly when treatment occurs in the second half of pregnancy 1

Common Pitfall to Avoid

Never delay treatment due to concerns about Jarisch-Herxheimer reaction causing stillbirth—while stillbirth is a rare complication of treatment itself, untreated syphilis causes far greater fetal harm with stillbirth rates up to 40% 1, 7, 2