Pregnancy involves significant physiological changes that can lead to a false-positive result on a syphilis screening test. This occurs because the screening method detects non-specific antibodies that become elevated during pregnancy, rather than those produced exclusively in response to the syphilis bacterium. Since syphilis poses severe risks to both the pregnant person and the fetus, routine prenatal screening is standard practice. A positive screening test, therefore, requires immediate follow-up with more specialized testing to determine if an actual infection is present.
Defining Syphilis Screening Tests
The diagnosis of syphilis relies on a two-step approach using two distinct types of antibody tests, since the causative bacteria, Treponema pallidum, is difficult to culture in a laboratory setting. The first step involves a nontreponemal test, commonly the Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test, used for mass screening due to its simplicity. These tests measure antibodies produced against cardiolipin, a lipid material released from damaged host cells during infection. This makes nontreponemal tests highly sensitive for screening but prone to false-positive results from other conditions.
The second category is the treponemal test, which includes assays like the T. pallidum particle agglutination (TP-PA) or the fluorescent treponemal antibody absorption (FTA-ABS) test. These confirmatory tests are highly specific because they detect antibodies directed only against antigens unique to the Treponema pallidum bacterium itself. A treponemal test is required to confirm a diagnosis after a positive screening result. The Centers for Disease Control and Prevention (CDC) recommends using both types of tests in combination to ensure an accurate diagnosis.
The Biological Basis for False Positives in Pregnancy
The occurrence of a false-positive result during pregnancy is known as a biological false positive, which is limited to the initial nontreponemal screening test. Pregnancy causes a natural, transient shift in the immune system, leading to an increase in various circulating antibodies and immunoglobulins. These antibodies are not specific to the syphilis bacteria but are produced as part of the body’s generalized immune response.
The nontreponemal tests use an antigen composed of cardiolipin, cholesterol, and lecithin to mimic the lipid antigens released during a syphilis infection. The elevated, non-specific antibodies in the pregnant person’s blood can cross-react with this cardiolipin antigen used in the RPR or VDRL test. This cross-reaction causes the test to register as “reactive” or “positive,” even though the Treponema pallidum bacterium is not present.
This type of false positive is temporary and generally resolves after the pregnancy concludes, as the immune system returns to its pre-pregnancy state. A reactive screening test in a pregnant person indicates the presence of these non-specific, cross-reacting antibodies. Since the false positive is not related to the actual bacteria, the more specific treponemal tests will remain nonreactive, ruling out a syphilis diagnosis.
Confirming the Diagnosis: The Testing Algorithm
Given the potential for a biological false positive in pregnancy, a structured testing algorithm is immediately implemented following a reactive nontreponemal screening result. The next step is an automatic follow-up with a specific treponemal confirmatory test, such as the TP-PA or FTA-ABS. The results from both tests are used together to interpret the patient’s true status.
If the initial nontreponemal screen is positive, but the subsequent treponemal confirmatory test is negative, the result is classified as a biological false positive. This discordant pattern means the patient has non-specific antibodies but lacks those specific to the syphilis bacteria. Conversely, if both the nontreponemal screening test and the treponemal confirmatory test are positive, it confirms a true syphilis infection.
Accurate diagnosis is important because syphilis infection during pregnancy can lead to severe outcomes, including miscarriage, stillbirth, or congenital syphilis in the newborn. If the confirmatory test is positive, treatment with penicillin is initiated immediately, as this medication is effective at preventing fetal infection. A positive nontreponemal test in a patient with a history of treated syphilis must also be carefully evaluated to rule out reinfection, often by comparing the current test’s quantitative titer with past results.
Other Conditions That Mimic Syphilis
While pregnancy is a common physiological reason for a biological false positive, a reactive nontreponemal test can be triggered by many conditions unrelated to the syphilis bacterium. These conditions cause the immune system to produce antibodies that cross-react with the cardiolipin antigen used in the RPR and VDRL screening tests.
Conditions that can cause a biological false positive include:
- Autoimmune disorders, particularly systemic lupus erythematosus.
- Acute viral infections, such as mononucleosis, hepatitis, or recent vaccinations.
- Chronic conditions, including HIV infection and some malignancies.
- Intravenous drug use.
The prevalence of biological false positives in the general population is low, but is higher in specific populations like pregnant individuals.