A positive syphilis screening result during pregnancy can be intensely stressful, prompting immediate concern about your health and the health of your baby. A reactive result on the initial screening test does not automatically mean you have an active syphilis infection. Routine prenatal screening aims to identify potential risks early, but the test’s nature means a false alarm is a significant possibility. Your healthcare provider will perform additional testing to determine the true meaning of this preliminary result.
Understanding Initial Screening Tests
Routine screening for syphilis is a standard component of prenatal care across the United States. This testing is often required by state laws and is recommended by the Centers for Disease Control and Prevention (CDC) at the first prenatal visit to protect the health of the mother and the fetus. The initial blood test used for this widespread screening is called a non-treponemal test, such as the Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test.
These screening tests do not detect antibodies specific to the syphilis-causing bacterium, Treponema pallidum. Instead, they look for general antibodies the body produces in response to cell damage, specifically those directed against a lipid antigen called cardiolipin. Since the syphilis bacterium contains this cardiolipin-like substance, the test reacts when the body is fighting the infection. However, many other conditions can also trigger the production of these same general antibodies, making the initial screen prone to false-positive results.
Statistical Likelihood of a False Positive Result
False-positive results on initial syphilis screenings are more common than most people realize, especially in low-prevalence populations like routine prenatal screening groups. Studies focused on pregnant individuals have observed that as many as 83% of all initial reactive screening tests ultimately turn out to be false positives upon further investigation. This high rate is a direct consequence of using a non-specific test for broad public health screening.
More broadly, an estimated 11% of all reactive non-treponemal tests are considered false positives, regardless of the patient population. When looking specifically at the pregnant population, the overall rate of a false-positive syphilis test is estimated to be approximately 1% to 2% of all women screened. While this percentage may seem small, it represents thousands of women who experience initial alarm before receiving a confirmed negative diagnosis. The high rate of initial false positives underscores why a two-step testing process is necessary before a syphilis diagnosis is confirmed.
Medical Conditions That Mimic Syphilis
A positive non-treponemal screening result in the absence of syphilis is known as a biologic false positive (BFP). These reactions occur because many conditions cause the immune system to produce non-specific antibodies that cross-react with the cardiolipin antigen in the RPR or VDRL test. Understanding these causes explains why a positive screen is not a definitive diagnosis.
One category of causes involves autoimmune disorders, such as systemic lupus erythematosus (Lupus) or rheumatoid arthritis, where the immune system mistakenly attacks the body’s own tissues. Certain acute or chronic infections, including HIV, mononucleosis, malaria, or Lyme disease, can temporarily stimulate cross-reactive antibodies. Even recent receipt of certain vaccines can occasionally provoke a temporary biologic false positive reaction. Pregnancy itself is a known physiological state that can alter the immune response and lead to a false positive on the initial screening test.
The Path to a Definitive Diagnosis
The resolution of a reactive screening result relies on a second step called confirmatory testing. This subsequent blood test uses a treponemal test, such as the Fluorescent Treponemal Antibody Absorption (FTA-ABS) or the Treponema pallidum Particle Agglutination (TP-PA) assay. These tests are highly specific because they look for antibodies produced only in response to the syphilis bacterium itself.
If the initial non-treponemal test is positive but the confirmatory treponemal test is negative, the result is classified as a biologic false positive, and no treatment for syphilis is required. If the confirmatory test returns a positive result, a true diagnosis of syphilis is made. Immediate treatment with penicillin is necessary to prevent severe complications for the mother and the developing baby. The initial non-treponemal test results are then used to measure the antibody concentration (titer), which is monitored after treatment to ensure the infection has been resolved.