Unexplained Recurrent Maternal Fever Leading To Fetal Demise: Role of Empirical Therapy For Successful Outcome

Background: Pyrexia of unknown origin (PUO) during pregnancy is uncommon and poses significant diagnostic and management challenges. It may reflect underlying immune dysregulation, contributing to adverse fetal outcomes. Case Presentation: We report a 26-year-old woman with recurrent mid-trimester high-grade fevers during two consecutive pregnancies, both ending in intrauterine fetal demise (IUFD). Extensive investigations failed to identify an infectious, malignant, or inflammatory cause. Placental histopathology revealed inflammatory changes. Lupus anticoagulant was later found to be positive. In her third pregnancy, early initiation of empirical immunosuppressive therapy—azathioprine, low-dose steroids, low-molecular-weight heparin, and aspirin—resulted in a successful outcome with delivery of a healthy infant. Conclusion: PUO in pregnancy may be a manifestation of immune dysregulation or fetal allograft rejection. In select cases, empirical immunomodulatory therapy instituted preconceptionally or early in pregnancy may improve outcomes. A high index of suspicion and multidisciplinary management are crucial in such scenarios.