USPSTF Reaffirms Universal Syphilis Screening in Pregnancy (2025)

— Amid syphilis surge, is it time to expand screening to all three trimesters and delivery?

by Rachael Robertson, Enterprise & Investigative Writer, MedPage Today May 13, 2025 • 4 min read

The U.S. Preventive Services Task Force (USPSTF) renewed its recommendation for early and universal screening for syphilis during pregnancy.

In line with its 2018 guidance, the update, published in JAMA, endorsed early and universal screening for syphilis infection during pregnancy and screening at the first available opportunity if an individual is not screened in early pregnancy.

This recommendation for all pregnant adolescents and adults, regardless of exposure to syphilis risk factors, got an A grade, meaning the task force strongly recommends the intervention. It noted that the screening should involve both a treponemal and non-treponemal test.

"Using a reaffirmation process, the USPSTF concludes with high certainty that screening for syphilis infection in pregnancy has a substantial net benefit," wrote task force chair Michael Silverstein, MD, MPH, of Brown University in Providence, Rhode Island, and colleagues.

An evidence review published in JAMA turned up no new relevant studies pertaining to the effectiveness of screening to reduce congenital syphilis or other adverse pregnancy outcomes.

However, Gary Asher, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues found five new studies looking at the harms of screening, which focused on reports of false-positives. They also found two small studies looking at the harms of treatment: one study found 5.1% of patients receiving penicillin experienced a Jarisch-Herxheimer reaction; the other found that, among patients at high risk for an immediate hypersensitivity reaction to penicillin, 27.3% experienced it after oral desensitization and 2.5% after IV desensitization, whereas only 2.5% of low-risk patients experienced it at all.

"Overall, the USPSTF found this evidence consistent with the previously known harms of syphilis screening and treatment during pregnancy," they wrote.

Congenital syphilis is associated with a slew of adverse neonatal outcomes, including premature birth, low birth weight, stillbirth, neonatal death, congenital abnormalities, and meningitis. It can be transmitted in utero or during birth. In 2023, the U.S. saw the highest number of reported congenital syphilis cases in more than 30 years with 3,882 cases and 279 congenital syphilis-related stillbirths and neonatal or infant deaths.

In an accompanying editorial, Thomas Dobbs, MD, MPH, of the University of Mississippi Medical Center in Jackson, and colleagues wrote that "the newly released reaffirmation statement is not only a testimony to the power of prevention but also a timely reminder of the nationwide spike in congenital syphilis."

"The resurgence of congenital syphilis is eminently preventable with timely diagnosis and treatment of infected mothers," Dobbs noted, adding that "screening for syphilis during pregnancy is a highly effective, safe, and cost-efficient tool to reduce vertical transmission and even eliminate congenital infection."

However, the editorialists challenged the USPSTF to join the CDC and American College of Obstetricians and Gynecologists (ACOG) in recommending additional testing in the third trimester and at delivery for higher-risk mothers; USPSTF has not added this recommendation because of what it deemed a lack of sufficient evidence, instead calling for more research on repeat screening.

Six states have gone the extra step and instituted mandatory syphilis testing during all three trimesters and at delivery, which the editorialists say is an approach "warmly welcomed and urgently needed" as syphilis incidence rises. They also noted that the increase in congenital syphilis has occurred in the past decade "even though the vast majority of states have mandated early and universal screening for years." Another barrier to syphilis care, they pointed out, is the "exorbitant cost of benzathine penicillin" which "disincentivizes clinics to maintain local supplies, limiting timely access to treatment."

Ultimately, the editorialists reminded clinicians that, as critical members of the public health system, those providing prenatal care "must maintain high fidelity to screening guidelines and take responsibility for overcoming the systematic barriers that impede effective syphilis management" amid rising syphilis numbers.

For the evidence report, Asher and colleagues searched Cochrane Library, Ovid MEDLINE, and trial registries from Jan. 1, 2017, through July 25, 2023, with surveillance through March 21, 2025. Eligible studies on screening used looked at asymptomatic pregnant adolescents and adults and used FDA-approved syphilis tests comparing different two-step serologic screening algorithms or single tests with a two-step algorithm.

For these studies, screening benefits would include reduction in congenital syphilis and neonatal and maternal morbidity and mortality. Harms would include false test results and psychosocial harms. Eligible studies on treatment harms only included studies of syphilis treatment during pregnancy using penicillin; harms included allergic reactions, preterm labor, Jarisch-Herxheimer reaction, and maternal and fetal harms.

In terms of limitations of the new evidence, studies on the harms of screening used a variety of screening tests, and the studies on harms of treatment "do not permit causal inference but offer ranges of estimates for bounding of harms," the evidence review noted.