In which trimester should syphilis screening be performed?

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Syphilis Screening in Pregnancy: Timing and Frequency

All pregnant women must be screened for syphilis at the first prenatal visit (first trimester), with high-risk women requiring additional screening at 28-32 weeks gestation (early third trimester) and again at delivery. 1

Universal First Trimester Screening

  • Every pregnant woman should undergo serologic syphilis testing at the initial prenatal visit, regardless of risk factors. 1, 2 This represents a universal screening recommendation endorsed by the USPSTF, CDC, American College of Obstetricians and Gynecologists, American Academy of Pediatrics, and American Academy of Family Physicians.

  • The screening should use nontreponemal tests (RPR or VDRL) initially, followed by confirmatory treponemal antibody testing if reactive. 1

  • No infant should leave the hospital without maternal serologic status documented at least once during pregnancy. 1, 2

Third Trimester Rescreening for High-Risk Women

Women at high risk for syphilis acquisition require repeat screening at 28-32 weeks gestation (early third trimester) AND at delivery. 1, 2

High-risk criteria include:

  • Living in areas with high syphilis prevalence 1
  • Previous positive serologic test during first trimester 1
  • Not previously tested during pregnancy 1
  • Multiple or new sex partners 1
  • History of other sexually transmitted infections 1
  • Illicit drug use 1
  • Commercial sex work 1
  • Inconsistent condom use 1

Delivery Screening

  • All high-risk women must be screened at delivery in addition to earlier screening. 1 Many states mandate universal screening at delivery for all women. 1

  • Any woman who delivers a stillborn infant after 20 weeks gestation should be tested for syphilis. 1

Rationale for Multiple Screening Points

The evidence supporting third trimester rescreening is compelling: among pregnant women who accessed timely prenatal care but still delivered infants with congenital syphilis, 46.8% acquired syphilis after an initial nonreactive test. 3 This demonstrates that a single first-trimester screen misses nearly half of infections in high-risk populations.

Syphilis can be transmitted to the fetus at any stage of maternal infection and in any trimester, with transmission rates approaching 100% during primary and secondary syphilis. 4, 3 Early detection through repeated screening allows for treatment at least 30 days before delivery, which is associated with the best neonatal outcomes. 5

Common Pitfalls to Avoid

  • Do not rely solely on first trimester screening in high-risk populations. Recent data show that 46.8% of congenital syphilis cases occurred in women who acquired infection after an initial negative test. 3

  • Do not delay screening until later in pregnancy. Among congenital syphilis cases, 30.9% of mothers did not receive timely prenatal care (≥45 days before delivery), and 8.5% of those with timely care did not receive initial testing until <45 days before delivery. 3

  • Do not assume low-risk status persists throughout pregnancy. Risk factors can change, and screening at 28-32 weeks captures new infections in the critical window before delivery. 1, 6

Monthly Monitoring for Highest-Risk Women

In geographic areas with very high syphilis prevalence or for women at exceptionally high risk for reinfection, serologic titers may be checked monthly after the initial screen. 1 This intensive monitoring ensures rapid detection of new infections or treatment failures.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Syphilis Treatment in Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Factors Contributing to Congenital Syphilis Cases - New York City, 2010-2016.

MMWR. Morbidity and mortality weekly report, 2018

Research

Syphilis during pregnancy: a preventable threat to maternal-fetal health.

American journal of obstetrics and gynecology, 2017

Research

Syphilis: A Review.

JAMA, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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