Syphilis Infection in Pregnant Persons: Screening

The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms to improve the health of people nationwide.

It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.

The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision-making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.

The USPSTF is committed to mitigating the health inequities that prevent many people from fully benefiting from preventive services. Systemic or structural racism results in policies and practices, including healthcare delivery, that can lead to inequities in health. The USPSTF recognizes that race, ethnicity, and gender are all social rather than biological constructs. However, they are also often important predictors of health risk. The USPSTF is committed to helping reverse the negative impacts of systemic and structural racism, gender-based discrimination, bias, and other sources of health inequities, and their effects on health, throughout its work.

Syphilis is an infection that is primarily sexually transmitted. Untreated syphilis infection in pregnant persons can 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, anemia, enlarged liver and spleen, jaundice, brain and nerve problems (e.g., permanent vision or hearing loss), and meningitis.¹ In 2022, there were 3,761 cases of congenital syphilis in the United States, including 231 stillbirths and 51 infant deaths, the highest number reported in over 30 years.²

Rates of new syphilis cases have continued to rise over the past three decades, especially in women. Although men account for the majority of syphilis cases, the change in incidence rate among women ranged from 2 to 4 times higher than that of men between 2017 and 2021.³ Consequently, cases of congenital syphilis have also increased. Congenital syphilis increased more than tenfold over a decade, from 334 cases in 2012 to 3,700 cases in 2022.² Certain racial and ethnic groups in the United States are disproportionately affected by syphilis; babies born to Black, Hispanic, or Native American/Alaska Native mothers in 2021 were up to 8 times more likely to have congenital syphilis compared with babies born to White mothers.⁴ These disparities likely reflect social and structural factors influencing health behaviors and inequitable access to sexual healthcare.^2,5,6 It is estimated that almost 90% of new congenital syphilis cases could have been prevented with timely testing and treatment.²

In 2018, the USPSTF reviewed the evidence for screening for syphilis infection in asymptomatic pregnant women and issued an A recommendation.⁷ The USPSTF has decided to use a reaffirmation deliberation process to update this recommendation. The USPSTF uses the reaffirmation process for well-established, evidence-based standards of practice in current primary care practice for which only a very high level of evidence would justify a change in the grade of the recommendation.⁸ In its deliberation of the evidence, the USPSTF considers whether the new evidence is of sufficient strength and quality to change its previous conclusions about the evidence.

Using a reaffirmation process, the USPSTF concludes with high certainty that screening for syphilis infection in asymptomatic pregnant persons has a substantial net benefit.

See Table 1 for more information on the USPSTF recommendation rationale and assessment. For more details on the methods the USPSTF uses to determine the net benefit, see the USPSTF Procedure Manual.⁸

Patient Population Under Consideration

This recommendation applies to all pregnant persons.

Screening Tests

Screening for syphilis involves a blood test that detects antibodies to the organism that causes syphilis, Treponema pallidum. Treponemal tests, such as the T. pallidum particle agglutination (TP-PA) test, detect an antibody response to antigens specific to T. pallidum.⁹ Nontreponemal tests, such as the Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) test, detect antibodies that may reflect tissue damage from T. pallidum infection, or tissue damage from other conditions that can cause the release of lipoidal antigens. Because of high false-positive rates associated with nontreponemal tests alone, especially in pregnancy, a two-step process is used to improve diagnostic accuracy. A traditional screening algorithm is a two-step process that begins with a nontreponemal test (e.g., VDRL or RPR) followed by a confirmatory treponemal test (e.g., TP-PA) for persons with positive nontreponemal test results. A reverse sequence algorithm uses an automated treponemal test (e.g., enzyme-linked or chemiluminescence immunoassay) for the initial screening, followed by a nontreponemal test for reactive samples. Discordant results in the reverse sequence are resolved with a second confirmatory treponemal test (TP-PA preferred). The automated processes used in reverse sequence may be appropriate for high-volume laboratories.^1,9

Point-of-care tests for antibodies to T. pallidum can be performed in a clinical setting using fingerstick blood samples that do not require laboratory processing. A new rapid home test has also been recently approved by the U.S. Food and Drug Administration.¹⁰ Having the ability to get rapid, on-site results could potentially speed diagnosis and initiate early treatment with reduced loss to followup. It is unclear how results from point-of-care testing alone, without additional confirmatory testing, should guide treatment decisions.

Screening Intervals

All pregnant persons should be tested for syphilis when they first present to care, as early in pregnancy as possible. If a person has not received prenatal care, testing should occur at the first opportunity, which may be at admission for delivery. A recent analysis of national data from 2022 found that 5% of congenital syphilis cases (197 out of 3,761 cases) occurred in late pregnancy after having had a negative syphilis screening result earlier in pregnancy.² Similar to the disparities seen in the burden of syphilis, 40.6% of these cases occurred in Black women, 28.4% occurred in Hispanic or Latina women, and 19.8% occurred in White women.² Some retrospective studies estimate that 25% to 50% of congenital syphilis cases could be prevented by repeat screening in the third trimester of pregnancy.^11-13 The Centers for Disease Control and Prevention (CDC),⁵ Women’s Preventive Services Initiative (WPSI),¹⁴ American Academy of Pediatrics (AAP),¹⁵ and American College of Obstetricians and Gynecologists (ACOG)¹⁶ recommend repeat screening in the early third trimester (approximately 28 weeks of gestation) and again at delivery; however, these organizations differ in whether they recommend repeat screening for all pregnant persons¹⁶ or for pregnant persons at high risk for syphilis, including those who live in high-prevalence areas; have a history of HIV, incarceration, or multiple sexual partners; engage in sex in combination with drug use or commercial sex work; or are experiencing homelessness.^5,15 Clinicians should be aware of the prevalence of syphilis infection in the communities they serve and state mandates for syphilis screening. Most states mandate screening for syphilis in all pregnant women at the first prenatal visit, and some mandate repeat screening early in the third trimester and at delivery.¹⁷ 

Treatment

The CDC recommends parenteral penicillin G as the only treatment with documented efficacy during pregnancy. Treatment protocols are specific to the stage of syphilis infection, with later-stage infection requiring longer duration of treatment. When syphilis is diagnosed during the second half of pregnancy, management should include a sonographic fetal evaluation for signs of congenital syphilis. Pregnant persons with a penicillin allergy should be desensitized and then treated with penicillin. It is estimated that perhaps 10% of the general population may be allergic to penicillin.⁵ Clinicians are encouraged to refer to the CDC’s “Sexually Transmitted Infection Treatment Guidelines” for the most up-to-date treatment guidance.⁵

Additional Tools and Resources

A list of state prenatal syphilis screening laws and regulations (https://www.cdc.gov/syphilis/hcp/prenatal-screening-laws/index.html) and county-level data on syphilis infection rates (https://www.cdc.gov/nchhstp/syphilis-county-level/) are available from the CDC. The CDC also provides multilingual materials for patients on syphilis prenatal screening (https://www.cdc.gov/sti/php/communication-resources/syphilis-prenatal-screening-protect-your-baby.html). 

Other Related USPSTF Recommendations

The USPSTF has issued recommendations on screening for syphilis in nonpregnant persons,¹⁸ as well as screening for other sexually transmitted infections, including chlamydia and gonorrhea,¹⁹ hepatitis B virus,^20,21 genital herpes,²² and HIV.²³ The USPSTF has also issued a recommendation on counseling to prevent sexually transmitted infections.²⁴ Current versions of these and other related USPSTF recommendations are available at https://www.uspreventiveservicestaskforce.org/uspstf/.

This recommendation is a reaffirmation of the USPSTF 2018 reaffirmation recommendation statement. In 2018, the USPSTF reviewed the evidence for screening for syphilis infection in asymptomatic pregnant persons and found that the benefits of screening substantially outweighed the harms.⁷ The USPSTF found no new substantial evidence that could change its recommendation and, therefore, reaffirms its recommendation to screen for syphilis infection in pregnant persons.

Scope of Review

To reaffirm its recommendation, the USPSTF commissioned a reaffirmation evidence update. The aim of the evidence update that supports the reaffirmation process is to identify “new and substantial evidence sufficient enough to justify a change in the grade of the recommendation.”⁸ The reaffirmation update focused on key questions on the benefits and harms of screening for syphilis infection in asymptomatic pregnant persons.

Benefits of Early Detection and Treatment

The USPSTF found no new evidence that was inconsistent with the previously established benefits of screening for syphilis infection in pregnant persons. No new studies were identified that evaluated the effectiveness of screening to decrease congenital syphilis rates or improve health outcomes of pregnant persons.¹ Evidence from previous reviews²⁵ demonstrates fewer adverse pregnancy outcomes among pregnant persons screened and treated for syphilis infection compared with those who are not treated. Treatment appears to be more beneficial when provided earlier rather than later in pregnancy.²⁵ A 2014 systematic review of 54 observational studies found that the incidence of congenital syphilis, preterm birth, low birth weight, stillbirth, and neonatal death was dramatically reduced in pregnant persons treated for syphilis during pregnancy compared with those who had untreated syphilis.²⁶ The reduction in stillbirth and fetal loss was much smaller in pregnant patients who were not treated until the third trimester. The USPSTF previously reviewed evidence on the effects of implementing a free syphilis screening and treatment program for all pregnant persons living in Shenzhen, China from 2002 to 2012 (n=2,441,237).²⁷ During followup, screening uptake increased from 89.8% to 97.2%, and the congenital syphilis case rate decreased from 109.3 to 9.4 cases per 100,000 live births. During the same time, the incidence of adverse pregnancy outcomes decreased from 42.7% to 19.2%, and the incidence of stillbirth or fetal loss decreased from 19.0% to 3.3%.

Harms of Screening and Treatment

Potential harms of screening for and treatment of syphilis infection include false-positive or discordant results from screening that require clinical evaluation, unnecessary anxiety to the patient, and harms of antibiotic medication use for treatment. The current reaffirmation review identified five studies (51,118 participants) that evaluated the harms of screening and two studies (130 participants) that evaluated the harms of treatment.¹ The five studies^28-32 that evaluated the harms of screening were all conducted in the United States (one study was conducted in the United States and Argentina³²) and reported on false-positive rates of a single screening test. All five of these studies included participants from a variety of racial and ethnic backgrounds; however, only two studies^28,32 reported this information for their full study cohort. Black participants ranged from 18% to 67%, White participants ranged from 5% to 20%, and “Other” participants ranged from 0.2% to 13%. One of the studies additionally reported including 75% Hispanic participants and 3% Asian participants.²⁸ Two studies, conducted in Canada and Brazil, reported on the harms of treatment, which included rates of Jarisch-Herxhemier reactions and immediate hypersensitivity reactions to penicillin.^33,34

The false-positive rate of the RPR test, when confirmed by a TP-PA test in a traditional screening algorithm approach, was reported as 31% in one study.²⁸ The false-positive rate of a multiplex flow immunoassay was also reported by a single study; 65% of results were false positive when confirmed by a RPR test and then a TP-PA test for discordant results, when following a reverse sequence screening algorithm.³⁰ The false-positive rate of various chemiluminescence immunoassay tests, as confirmed by a RPR test and either TP-PA or fluorescent treponemal antibody-absorption test (depending on the study) for discordant results, using a reverse sequence screening algorithm, was reported in three studies and ranged from 7% to 26%.^28-29,31 One additional study evaluated use of a syphilis immunoassay compared with a composite testing algorithm that simultaneously tested all samples with both the immunoassay and a nontreponemal RPR test, and resolved discordant results with a TP-PA test.³² This study reported a 4.8% positive rate with immunoassay and no false positives or false negatives with immunoassay compared with the composite testing algorithm. Together, these reported false-positive rates reflect results after a single step of testing, compared with a two-step testing process, and thus reinforce the need for a two-step testing process, which would provide the result of a confirmatory test at the same time as the first, false-negative test, hence potentially mitigating the effect of this harm. 

For treatment harms, one small study (n=39) reported that 5.1% of patients receiving penicillin therapy experienced Jarisch-Herxheimer reactions.³³ A second small study (n=91) evaluated an algorithm to help guide penicillin desensitization among pregnant patients with syphilis who had a clinical history of immediate hypersensitivity reaction to penicillin.³⁴ Among patients considered high-risk for an immediate hypersensitivity reaction, 27.3% experienced it after oral desensitization and 2.5% experienced it after intravenous desensitization; 2.5% of patients considered at low risk for an immediate hypersensitivity reaction experienced it after penicillin provocation. Overall, the USPSTF found this evidence consistent with the previously known harms of syphilis screening and treatment in pregnant persons.

See Table 2 for research needs and gaps related to screening for syphilis infection in pregnant persons.

This recommendation statement is consistent with those of other professional and public health organizations. The CDC,⁵ WSPI,¹⁴ AAP,¹⁵ and ACOG¹⁶ recommend initial screening for syphilis infection in all pregnant women at their first prenatal visit, even if previously tested. ACOG¹⁶ recommends universal rescreening during the third trimester and at birth and the CDC,⁵ WSPI,¹⁴ and AAP¹⁵ recommend rescreening at 28 weeks of gestation and again at delivery in women at high risk for acquiring syphilis. AAP¹⁵ and ACOG¹⁶ also recommend repeat screening after exposure to an infected partner. The American Academy of Family Physicians supports the 2018 USPSTF recommendation on screening for syphilis infection in pregnant women.³⁵

1. Screening for Syphilis Infection in Pregnant Persons: A Draft Limited Systematic Evidence Review Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 243. AHRQ Publication No. 24-05317-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2024.
2. McDonald R, O’Callaghan K, Torrone E, et al. Vital Signs: missed opportunities for preventing congenital syphilis — United States, 2022. MMWR Morb Mortal Wkly Rep. 2023;72(46);1269-1274.
3. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021: National Overview of STDs, 2021. Accessed October 24, 2024. https://www.cdc.gov/std/statistics/2022/2021-STD-Surveillance-Report-PDF_ARCHIVED-2-16-24.pdf
4. Centers for Disease Control and Prevention. U.S. Syphilis Cases in Newborns Continue to Increase: A 10-Times Increase Over a Decade. Published November 7, 2023. Accessed October 24, 2024. https://www.cdc.gov/media/releases/2023/s1107-newborn-syphilis.html
5. Workowski KA, Bachmann LH, Chan PA, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1-187.
6. Martin EG, Ansari B, Rosenberg ES, et al. Variation in patterns of racial and ethnic disparities in primary and secondary syphilis diagnosis rates among heterosexually active women by region and age group in the United States. Sex Transm Dis. 2022;49(5):330-337.
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8. U.S. Preventive Services Task Force. Procedure Manual. Accessed October 24, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/procedure-manual
9. Papp JR, Park IU, Fakile Y, Pereira L, Pillay A, Bolan GA. CDC laboratory recommendations for syphilis testing, United States, 2024. MMWR Recomm Rep. 2024;73(1):1-32.
10. U.S. Food and Drug Administration. FDA Marketing Authorization Enables Increased Access to First Step of Syphilis Diagnosis. Published August 16, 2024. Accessed October 24, 2024. https://www.fda.gov/news-events/press-announcements/fda-marketing-authorization-enables-increased-access-first-step-syphilis-diagnosis
11. Slutsker JS, Hennessy RR, Schillinger JA. Factors contributing to congenital syphilis cases - New York City, 2010-2016. MMWR Morb Mortal Wkly Rep. 2018;67(39):1088-1093.
12. Sykes KJ, Scranton RA, Villarroel L, Anderson BV, Salek S, Stall J. Using surveillance data to respond to an outbreak of congenital syphilis in Arizona through third-trimester screening policies, 2017-2018. Public Health Rep. 2021;136(1):61-69.
13. Matthias JM, Rahman MM, Newman DR, Peterman TA. Effectiveness of prenatal screening and treatment to prevent congenital syphilis, Louisiana and Florida, 2013-2014. Sex Transm Dis. 2017;44(8):498-502.
14. Women's Preventive Services Initiative. Recommendations for Well-Woman Care: 2024 Clinical Summary Tables. Updated January 2024. Accessed October 24, 2024. https://www.womenspreventivehealth.org/wp-content/uploads/FINAL-WPSI-Clinical-Summary-Tables-2024.pdf  
15. AAP Committee on Fetus and Newborn and ACOG Committee on Obstetric Practice. Guidelines for Perinatal Care. 8th ed. Itasca, IL: American Academy of Pediatrics; 2017.
16. American College of Obstetricians and Gynecologists. Practice Advisory: Screening for Syphilis in Pregnancy. Published April 2024. Accessed October 24, 2024. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2024/04/screening-for-syphilis-in-pregnancy
17. Centers for Disease Control and Prevention. State Statutory and Regulatory Language Regarding Prenatal Syphilis Screenings in the United States. Published July 25, 2024. Accessed October 24, 2024.  https://www.cdc.gov/syphilis/media/pdfs/2024/07/Prenatal-Syphilis-Screening-Laws-Web-Document-25-July-2024-final.pdf
18. US Preventive Services Task Force. Screening for syphilis infection in nonpregnant adolescents and adults: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2022;328(12):1243-1249.
19. US Preventive Services Task Force. Screening for chlamydia and gonorrhea: US Preventive Services Task Force recommendation statement. JAMA. 2021;326(10):949-956.
20. US Preventive Services Task Force. Screening for hepatitis B virus infection in pregnant women: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2019;322(4):349-354.
21. US Preventive Services Task Force. Screening for hepatitis B virus infection in adolescents and adults: US Preventive Services Task Force recommendation statement. JAMA. 2020;324(23):2415-2422.
22. US Preventive Services Task Force. Serologic screening for genital herpes infection: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2023;329(6):502-507.
23. US Preventive Services Task Force. Screening for HIV infection: US Preventive Services Task Force recommendation statement. JAMA. 2019;321(23):2326-2336.
24. US Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: US Preventive Services Task Force recommendation statement. JAMA. 2020;324(7):674-681.
25. Lin JS, Eder M, Bean S. Screening for Syphilis Infection in Pregnant Women: A Reaffirmation Evidence Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 167. AHRQ Publication No. 18-05238-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2018.
26. Qin J, Yang T, Xiao S, Tan H, Feng T, Fu H. Reported estimates of adverse pregnancy outcomes among women with and without syphilis: a systematic review and meta-analysis. PLoS One. 2014;9(7):e102203.
27. Qin JB, Feng TJ, Yang TB, et al. Synthesized prevention and control of one decade for mother-to-child transmission of syphilis and determinants associated with congenital syphilis and adverse pregnancy outcomes in Shenzhen, South China. Eur J Clin Microbiol Infect Dis. 2014;33(12):2183-2198.
28. Adhikari EH, Frame IJ, Hill E, et al. Abbott ARCHITECT syphilis TP chemiluminescent immunoassay accurately diagnoses past or current syphilis in pregnancy. Am J Perinatol. 2020;37(1):112-118.
29. Chen MW, Akinboyo IC, Sue PK, et al. Evaluating congenital syphilis in a reverse sequence testing environment. J Perinatol. 2019;39(7):956-963.
30. Williams JEP, Bazan JA, Turner AN, et al. Reverse sequence syphilis screening and discordant results in pregnancy. J Pediatr. 2020;219:263-266.e1.
31.Zofkie AC, Seasely AR, Gaffney D, et al. Syphilis immunoassay signal strength correlates with active infection in pregnant women. Am J Perinatol. 2020;37(7):671-678.
32. Christenson RH, Lessig M, Miles G, Luebcke S, Stillions C, Jones P. Evaluation of the Elecsys syphilis immunoassay for detection of syphilis in populations at risk of disease in the US and Argentina. J Appl Lab Med. 2018;3(1):89-99.
33. Macumber S, Singh AE, Gratrix J, et al. Retrospective cohort study of the incidence and outcomes of Jarisch-Herxheimer reactions after treatment of infectious syphilis in late pregnancy. Sex Transm Dis. 2022;49(10):e107-e109.
34. Garcia JFB, Aun MV, Motta AA, Castells M, Kalil J, Giavina-Bianchi P. Algorithm to guide re-exposure to penicillin in allergic pregnant women with syphilis: efficacy and safety. World Allergy Organ J. 2021;14(6):100549. 
35. American Academy of Family Physicians. Clinical Preventive Service Recommendation: Syphilis. Accessed October 24, 2024. https://www.aafp.org/family-physician/patient-care/clinical-recommendations/all-clinical-recommendations/syphilis.html

Abbreviation: USPSTF=U.S. Preventive Services Task Force.

To fulfill its mission to improve health by making evidence-based recommendations for preventive services, the USPSTF routinely highlights the most critical evidence gaps for making actionable preventive services recommendations. The USPSTF often needs additional evidence to create the strongest recommendations for everyone and especially for persons with the greatest burden of disease. This table summarizes key bodies of evidence needed for the USPSTF to make recommendations for screening for syphilis infection in pregnant persons.