Syphilis during pregnancy: a preventable threat to maternal-fetal health

Am J Obstet Gynecol. 2017 Apr;216(4):352-363. doi: 10.1016/j.ajog.2016.11.1052. Epub 2016 Dec 9.


Syphilis remains the most common congenital infection worldwide and has tremendous consequences for the mother and her developing fetus if left untreated. Recently, there has been an increase in the number of congenital syphilis cases in the United States. Thus, recognition and appropriate treatment of reproductive-age women must be a priority. Testing should be performed at initiation of prenatal care and twice during the third trimester in high-risk patients. There are 2 diagnostic algorithms available and physicians should be aware of which algorithm is utilized by their testing laboratory. Women testing positive for syphilis should undergo a history and physical exam as well as testing for other sexually transmitted infections, including HIV. Serofast syphilis can occur in patients with previous adequate treatment but persistent low nontreponemal titers (<1:8). Syphilis can infect the fetus in all stages of the disease regardless of trimester and can sometimes be detected with ultrasound >20 weeks. The most common findings include hepatomegaly and placentomegaly, but also elevated peak systolic velocity in the middle cerebral artery (indicative of fetal anemia), ascites, and hydrops fetalis. Pregnancies with ultrasound abnormalities are at higher risk of compromise during syphilotherapy as well as fetal treatment failure. Thus, we recommend a pretreatment ultrasound in viable pregnancies when feasible. The only recommended treatment during pregnancy is benzathine penicillin G and it should be administered according to maternal stage of infection per Centers for Disease Control and Prevention guidelines. Women with a penicillin allergy should be desensitized and then treated with penicillin appropriate for their stage of syphilis. The Jarisch-Herxheimer reaction occurs in up to 44% of gravidas and can cause contractions, fetal heart rate abnormalities, and even stillbirth in the most severely affected pregnancies. We recommend all viable pregnancies receive the first dose of benzathine penicillin G in a labor and delivery department under continuous fetal monitoring for at least 24 hours. Thereafter, the remaining benzathine penicillin G doses can be given in an outpatient setting. The rate of maternal titer decline is not tied to pregnancy outcomes. Therefore, after adequate syphilotherapy, maternal titers should be checked monthly to ensure they are not increasing four-fold, as this may indicate reinfection or treatment failure.

Keywords: congenital syphilis; fetal syphilis; syphilis during pregnancy.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Anemia / etiology
  • Anti-Bacterial Agents / therapeutic use
  • Ascites / diagnostic imaging
  • Female
  • Hepatomegaly / diagnostic imaging
  • Humans
  • Hydrops Fetalis / diagnostic imaging
  • Penicillin G Benzathine / therapeutic use
  • Placenta Diseases / diagnostic imaging
  • Polyhydramnios / diagnostic imaging
  • Pregnancy
  • Pregnancy Complications, Infectious / diagnosis*
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / epidemiology
  • Syphilis / diagnosis*
  • Syphilis / drug therapy
  • Syphilis / epidemiology
  • Syphilis, Congenital / diagnostic imaging
  • Syphilis, Congenital / prevention & control*
  • Ultrasonography, Prenatal


  • Anti-Bacterial Agents
  • Penicillin G Benzathine