False-Positive Syphilis Serology in a Neonate Due to Maternal Immunoglobulin Treatment

To the Editors: We wish to report a newborn with false-positive syphilis serology due to maternal immunoglobulin treatment during pregnancy. A 25-year-old woman whose first pregnancy was affected by neonatal alloimmune thrombocytopenia was transferred to tertiary care during her third pregnancy. She was treated with weekly intravenous immunoglobulin Octagam (IVIG), at a dose of 1 g/kg from 28 weeks of gestation. Maternal blood taken at 34 weeks of gestation (6 weeks following initiation of IVIG therapy) tested positive for syphilis antibodies (see Table 1); though her pregnancy booking bloods had been negative. Laboratory advice to repeat the test was not actioned before delivery.TABLE 1.: Blood Test Results for Mother and BabyAt birth, the infant was clinically well with a normal platelet count (see Table 1). At 2 weeks, the infant was reviewed to re-check the platelet count and the positive syphilis serology was discussed with the mother. It was advised that this could be consistent with her having contracted syphilis during pregnancy which caused significant distress for the parents. Blood taken from mother and baby at this time showed positive screening tests for syphilis but negative non-treponemal tests. No treatment was given to mother or baby as it was suspected these were false-positive results due to antenatal IVIG treatment. At the genitourinary medicine clinic four weeks after delivery, both parents had negative syphilis tests. Parents therefore declined further testing for baby when reviewed in the pediatric infectious diseases clinic as baby was clinically well. IVIG is manufactured from the pooled plasma of up to 60,000 blood donors. False-positive syphilis serology due to immunoglobulin treatment has been described previously,1–3 and specifically in pregnancy,4 but this is the first case to our knowledge where false-positive syphilis serology has been detected in an infant due to maternal immunoglobulin treatment. The key to differentiating between true syphilis infection and passive antibody transfer is an understanding of the tests involved.5 Non-treponemal tests, such as the rapid plasma reagin test, are used for screening low-risk populations (eg, blood donors). These are positive in acute syphilis and usually become negative within 2 years of adequate treatment. However, these are non-specific and can be falsely positive in other conditions such as autoimmune disease. Positive non-treponemal tests should be confirmed with a specific treponemal test such as Treponema pallidum particle agglutination assay, which is much more specific but can remain positive for life and are therefore not useful for monitoring treatment effectiveness. Blood donors need a negative non-treponemal test for their blood to be accepted. However, if they had been successfully treated for syphilis in the past, their plasma could contain syphilis antibodies which could lead to false-positive treponemal tests. In pregnancy, the situation becomes more complicated because transfer of IgG antibodies across the placenta means syphilis antibodies from IVIG can be transferred to the fetus. It is important for clinicians to be aware of the potential for false-positive antibody results in patients who have been given immunoglobulin and to be aware that these false-positive antibodies can cross the placenta and be detected in infants. Violet Swain, MBChBAndrew Riordan, MDDepartment of Paediatric Infectious Diseases and Immunology, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom