in progress

Draft Research Plan

Syphilis Infection in Pregnant Persons: Screening

December 01, 2022

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.

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The analytic framework depicts the key questions within the context of the eligible populations, screenings, treatments, comparisons, outcomes, settings, and study designs. On the left, the population of interest is asymptomatic pregnant persons. Moving from left to right, the figure illustrates the overarching key question (KQ): Does screening for syphilis in pregnant persons reduce the incidence of congenital syphilis in newborns? (KQ 1). Screening may result in harms (KQ 2). After detection of syphilis infection in pregnant persons, the figure illustrates the following question: What are the harms of treatment of syphilis with penicillin during pregnancy to pregnant persons or newborns? (KQ 3).

  1. Does screening for syphilis in pregnant persons reduce the incidence of congenital syphilis in newborns?
  2. What are the harms of screening for syphilis in pregnant persons?
  3. 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.

  1. How frequently do pregnant persons who initially test negative for syphilis with 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 proposed 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 who are 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: Treatment of syphilis 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; maternal or infant morbidity and mortality

KQ 2: Harms of screening (e.g., false-positive and false-negative results, stigma, psychosocial harms)

KQ 3: Harms of treatment of syphilis with penicillin during pregnancy (e.g., allergic reaction, premature labor, Jarish-Herxheimer reaction, fetal harms, other maternal harms)

 Cost-effectiveness or cost-related outcomes
Setting Primary care 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)  
Country Studies conducted in countries categorized as "high" or "very high" on the Human Development Index (as defined by the United Nations Development Programme)  
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; 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; systematic reviews and meta-analyses (of included study designs)

 Narrative reviews, editorials, and case reports
Publication Language English Non-English studies
Study Quality Good- or fair-quality studies Poor-quality studies

Abbreviation: KQ = key question.