Syphilis Screening in Pregnancy

Syphilis is a bacterial infection that is primarily spread sexually by direct contact with lesions during oral, vaginal, and anal sex. It also can be spread in the bloodstream (hematogenously) from mother-to-child. Many people with syphilis do not seek care as they may not notice the early signs and symptoms, and these can go away without treatment even though the infection remains. Untreated syphilis can have long-term sequelae, including permanent vision or hearing loss, cardiovascular problems, and even death.

Untreated or inadequately treated syphilis infections during pregnancy can cause miscarriages or be passed to the fetus, causing congenital syphilis. Congenital syphilis is associated with premature birth, low birth weight, stillbirth, neonatal death, and significant abnormalities in the infant such as deformed bones, enlarged liver and spleen, jaundice, brain and nerve problems (eg, permanent vision or hearing loss), and meningitis.¹

Some communities are disproportionately affected by syphilis. There are significant racial, ethnic, and geographic disparities in syphilis infections. American Indian/Alaskan native and Black/African American individuals have higher rates of syphilis. Geographically in the Unites States, the Midwest and South have higher rates of syphilis. Factors such as systemic racism, social determinants of health, substance use, and lack of access to health care cause inequities that lead to these disparities. Significant historical events contribute, such as the Tuskegee study in 1932, which followed Black men with syphilis without allowing treatment once it became available. You can learn more about the rates of syphilis in your community by viewing data from the Centers for Disease Control and Prevention. It is necessary to approach our response to today’s syphilis public health crisis with cultural awareness, humility, and sensitivity to build trust.² 

The American College of Obstetricians and Gynecologists (ACOG) endorses the Centers for Disease Control and Prevention (CDC) Sexually Transmitted Infections Treatment Guidelines 2021.³ In the context of the rapidly increasing rates of congenital syphilis, ACOG also recommends that obstetrician–gynecologists and other obstetric care professionals should screen all pregnant individuals serologically for syphilis at the first prenatal care visit, followed by universal rescreening during the third trimester and at birth, rather than use a risk-based approach to testing (see ACOG’s Practice Advisory, Screening for Syphilis in Pregnancy). Where access to prenatal care is not optimal, screening and treatment (if indicated) should be performed as soon as pregnancy is identified, and treatment needs to be initiated as soon as possible. It is also important to make any health care encounter during pregnancy—including those in urgent care, emergency departments, jails, substance use treatment programs, syringe service programs, and maternal and child health programs—an opportunity to screen for syphilis and treat as indicated.⁴

There are serological and point-of-care tests available to screen for syphilis. The serological tests include treponemal and non-treponemal tests. For more information, refer to ACOG’s Syphilis Screening Algorithm.

Clinicians should be aware of whether their lab uses the traditional syphilis algorithm (nontreponemal screening) or the reverse algorithm (treponemal screening). Clinicians should correlate the patient’s symptoms, previous treatment history and risk factors for reinfection to make an accurate diagnosis. In addition, the decision to use serologic testing versus point-of-care testing may depend on prior treatment history and ability to return quickly for treatment if needed.⁵ Partnering with your local health department can be an important way to know a patient’s syphilis testing and treatment history (See How should the patient with a positive treponemal specific test, and low titer RPR and no symptoms be managed?).

This scenario represents either previously adequately treated syphilis OR latent syphilis. The only way to distinguish between these two scenarios include a detailed history, including the dates and type of previous treatment. Calling your local health department for verification of previous treatment dates, adequacy and RPR titers is essential to determine if a pregnant patient should be retreated during pregnancy. If previous treatment history is inadequate or not documented, retreatment should occur during the index pregnancy (See What is the recommended adequate treatment of syphilis during pregnancy?).

Syphilis is treatable and curable. Clinicians should refer to the CDC’s Sexually Transmitted Infections Treatment Guidelines for the most up-to-date treatment guidance.

Benzathine penicillin G is the only known effective treatment for syphilis during pregnancy as it can treat fetal infection and prevent congenital syphilis.³ During pregnancy, it is imperative that clinicians treat people as soon as possible and do not wait for the next scheduled prenatal visit.

Timely initiation and completion of treatment are imperative and often complicated by stigma, multiple injections, treatment shortages, reporting and follow-up requirements, and mistrust of the medical system.⁶ By ensuring that all pregnant people receive timely syphilis screening during their pregnancy and appropriate treatment if they are diagnosed with syphilis, the rising numbers of congenital syphilis can be turned around. 

Adequate treatment for patients with primary, secondary, or early latent syphilis includes at least one dose of benzathine penicillin G 2.4 million units intramuscularly, at least 30 days prior to pregnancy conclusion. The CDC STI treatment guidelines note that “certain evidence indicates that additional therapy is beneficial for pregnant women to prevent congenital syphilis. For women who have primary, secondary, or early latent syphilis, a second dose of benzathine penicillin G 2.4 million units IM can be administered 1 week after the initial dose.³ " Adequate treatment for patients with late latent or unknown duration should receive 3 doses of benzathine penicillin G 2.4 million units intramuscularly weekly, at least 30 days prior to pregnancy conclusion. Missed doses >9 days between doses are not acceptable for pregnant women receiving therapy for late latent syphilis. An optimal interval between doses is 7 days for pregnant women. Pregnant women who miss a dose of therapy > 9 days should repeat the full course of therapy. If a pregnant patient had previous inadequate treatment prior to the index pregnancy, they should be retreated during the index pregnancy.

The criteria for possible and confirmed and highly likely congenital syphilis can be found in the CDC Sexually Transmitted Infections Treatment Guidelines, 2021.  This document also includes the recommended neonatal evaluation and treatment in these scenarios.

In patients with a known severe allergy to penicillin, desensitization followed by penicillin treatment is recommended (see ACOG’s Practice Advisory, Screening for Syphilis in Pregnancy, Sexually Transmitted Infections Treatment Guidelines, 2021).

A penicillin (PCN) allergy evaluation in pregnancy is beneficial for pregnant individuals with a low or moderate risk history of allergy, based on previous symptoms. Individuals with a history of severe reactions like anaphylaxis should not undergo allergy testing in pregnancy, and the current standard of care is to desensitize them for treatment of syphilis.^7,8

For more information on penicillin protocols and the importance of delabeling people who report penicillin allergies during pregnancy and outside of pregnancy, visit the Penicillin Allergy Center of the American Academy of Allergy, Asthma & Immunology.

We recommend serologic follow-up in appropriately treated patients 8 weeks after treatment completion and again at delivery. Treatment failure or reinfection in the context of pregnancy should be defined as a fourfold (two-dilution) rise in titer.³

The benefits of treating syphilis for the pregnant patient and to prevent congenital syphilis outweigh the risks. The main risks include allergic reaction or the Jarish-Herxheimer (JH) reaction, which is an acute systemic reaction caused by release of inflammatory products from rapid killing of spirochetes during treatment. Symptoms during the JH reaction include worsening skin lesions, fever, chills, tachycardia, arthralgias, headache, leukocytosis, and pharyngitis. It occurs most often with early syphilis and may be more common during pregnancy. Notably, the JH reaction during pregnancy may result in preterm contractions and fetal heart rate changes. Treatment is supportive, including intrauterine resuscitation and obstetric management based on gestational age.

Obstetrician–gynecologists and other women’s health care practitioners can support efforts to improve health care for incarcerated pregnant, postpartum, and nonpregnant individuals. Reproductive health care for incarcerated individuals should be provided in accordance with the same guidelines and recommendations as for those who are not incarcerated, with attention to the increased risk of infectious diseases common to incarcerated populations. Jail and prison health care services can serve as potential intervention points for syphilis testing and treatment, as a significant proportion of people with syphilis either have a history of incarceration or are linked to a partner with such a history. With the introduction of syphilis testing at intake within jails, syphilis cases can be quickly identified, and individuals can be linked to treatment. Consider implementing rapid syphilis point-of-care testing to prevent incomplete or missed treatment for people who are justice-involved and may be lost to follow-up.^9,10

Fetal infection can occur with maternal infection and is most common in early syphilis. The most common ultrasound findings include placentomegaly, polyhydramnios, hydrops, ascites, hepatomegaly and fetal anemia. After maternal treatment, the findings of fetal syphilis improve over time. Pregnant patients with signs of fetal syphilis may be at increased risk of the JH reaction.¹¹

In addition to ensuring that all pregnant people diagnosed with syphilis are effectively treated, it is important that their sexual partners are also reached for testing and treatment. It is essential that sexual partners of infected people are treated to prevent further reinfection. Contact your local health department for partner notification and additional guidance.