ABSTRACT Neonatal IgM antibodies reflect an in utero immune response to Treponema pallidum and may offer added diagnostic value. This study evaluated the test performance of treponemal IgM levels measured by the research-use-only (RUO) Dual Path Platform (DPP) Syphilis TnT point-of-care (POC) assay for congenital syphilis (CS) risk stratification. Conducted from May 2023 to May 2025, this study tested neonatal serum samples from infants born to mothers with syphilis using the DPP Syphilis TnT RUO POC assay, which reports treponemal and nontreponemal IgM levels as relative light units (RLU). Neonates were classified as confirmed proven or highly probable CS , possible CS , or CS less likely per guidelines; 23 neonates without maternal syphilis served as controls. Treponemal IgM levels were compared across categories using nonparametric tests and ordinal logistic regression. Diagnostic performance used prespecified cutoffs, with agreement assessed against neonatal rapid plasma reagin (RPR). Twenty-two maternal-neonatal dyads were included. Mean treponemal IgM levels rose with CS severity, peaking in the high-risk group ( possible or confirmed proven/highly probable CS: 29.9 ± 20.6 RLU) versus CS less likely (17.5 ± 20.8 RLU) and controls (3.5 ± 0.8 RLU; P < 0.05). Higher IgM levels independently linked to elevated CS risk (OR 1.10 per 1 RLU; P = 0.0025). At ≥10 RLU cutoff, treponemal IgM detected 88.9% of high-risk neonates, with 76% agreement to neonatal RPR. The DPP Syphilis TnT RUO POC assay’s treponemal IgM levels discriminated CS risk categories effectively and may supplement current algorithms to improve neonatal CS stratification. IMPORTANCE Congenital syphilis (CS) continues to rise in the United States and globally, yet diagnosis at birth remains difficult because no single laboratory test definitively confirms infection in newborns. Clinical decisions often rely on maternal history and indirect serologic comparisons, which can result in both missed cases and unnecessary treatment of low-risk infants. IgM antibodies are produced by the fetus in response to infection in utero and therefore represent a biologically meaningful marker of congenital infection. This study evaluates the diagnostic potential of the Dual Path Platform Syphilis TnT research-use-only point-of-care assay to detect treponemal IgM in at-risk neonates. We demonstrate that IgM levels increase across CS less likely , possible CS , and confirmed proven or highly probable CS categories and are independently associated with disease risk. These findings provide early evidence that neonatal IgM testing may improve risk stratification and support more precise clinical decision-making in CS management.
Stafford et al. (Mon,) studied this question.