Final Research Plan
Syphilis Infection in Pregnant Persons: Screening
March 02, 2023
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
- Does screening for syphilis in pregnant persons reduce the incidence of congenital syphilis in newborns?
- What are the harms of screening for syphilis in pregnant persons?
- What are the harms of treatment of syphilis with penicillin during pregnancy to pregnant persons or newborns?
Contextual Questions will not be systematically reviewed and are not shown in the Analytic Framework.
- To better understand the need for retesting during pregnancy, the USPSTF will review how frequently do pregnant persons who initially test negative for syphilis by serologic screening either later test positive for syphilis, give birth to a neonate with congenital syphilis, or have a miscarriage or stillbirth attributed to syphilis? Do these associations vary by populations of interest (demographic characteristics or risk factors)?
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the Key Questions.
| Category | Include | Exclude |
|---|---|---|
| Populations | KQs 1, 2: Asymptomatic pregnant adolescent or adults, at any time during pregnancy, who are not known to have syphilis infection
KQ 3: Studies of penicillin treatment in pregnant persons with syphilis infection |
KQs 1, 2: Persons known to have syphilis infection, have symptoms, or are not pregnant; studies conducted exclusively in populations in which syphilis screening may be part of disease management, such as persons living with HIV
KQ 3: Studies of penicillin treatment in nonpregnant persons; studies of penicillin treatment for any condition other than syphilis |
| Interventions | KQs 1, 2: Two-step screening for syphilis with a nontreponemal and treponemal test (traditional or reverse sequence algorithms)
KQ 3: Treatment of syphilis with penicillin started during pregnancy |
KQs 1, 2: Screening tests not currently used in U.S. primary care settings
KQ 3: Syphilis treatment with penicillin outside of pregnancy |
| Comparisons | KQ 1: No screening
KQ 2: No comparator necessary for studies on psychosocial harms; studies on screening test accuracy must define their criteria for false-positive and false-negative results KQ 3: No comparator necessary |
KQ 1: Alternate screening strategy or no comparator |
| Outcomes | KQ 1: Vertical transmission of syphilis (incidence of congenital syphilis); prevalence of congenital syphilis after implementation of a screening program, stillbirth, and maternal or infant morbidity and mortality
KQ 2: Harms of screening (e.g., false-positive and false-negative results, stigma, and psychosocial harms) KQ 3: Harms of treatment of syphilis with penicillin during pregnancy (e.g., allergic reaction, premature labor, Jarish-Herxheimer reaction, fetal harms, and other maternal harms) |
Cost-effectiveness or cost-related outcomes |
| Setting | Primary care–relevant and primary care–referable settings (e.g., obstetrics/gynecology clinics, prenatal clinics, ambulatory care, family planning clinics, health clinics in correctional facilities, sexually transmitted infection clinics) | Nonprimary care or nonprimary care–referable settings |
| Country | Studies conducted in countries categorized as "high" or "very high" on the Human Development Index (as defined by the United Nations Development Programme) | Studies conducted in countries not categorized as “high” or “very high” on the Human Development Index (as defined by the United Nations Development Programme in 2022) |
| Study Designs | KQ 1: Randomized, controlled trials; before-after and ecologic studies reporting effect of implementing a widespread screening program with historical or geographic comparator; and systematic reviews and meta-analyses (of included study designs)
KQs 2, 3: Randomized, controlled trials; cohort studies; case-control studies; diagnostic accuracy studies; large case series; and systematic reviews and meta-analyses (of included study designs) |
Narrative reviews, editorials, and case reports |
| Publication Language | English | Non-English studies |
| Quality | Good- or fair-quality studies | Poor-quality studies |
Abbreviations: HIV=human immunodeficiency virus; KQ=key question.
The draft Research Plan was posted on the USPSTF website for public comment from December 1, 2022, to January 4, 2023. Several comments focused on the outcomes and setting inclusion and exclusion criteria. In response, the USPSTF updated the wording of the Contextual Question to more clearly signify the retesting context. Additionally, the USPSTF updated the description of eligible settings to “Primary care–relevant and primary care–referrable settings…” to indicate the broad inclusion of potentially eligible study recruitment sites. Lastly, the USPSTF updated the Analytic Framework to more clearly specify its interest in morbidity and mortality outcomes in pregnant persons and neonates.