Severe, late-onset neutropenia associated with prolonged furosemide administration in an extremely preterm infant: a case report and literature review

Abstract

Furosemide is commonly used off-label in the neonatal intensive care unit to promote diuresis and improve pulmonary mechanics in preterm infants, but prolonged exposure carries known renal and ototoxic risks and—rarely—hematologic toxicity. Drug-induced neutropenia is uncommon in neonates and sparsely reported with loop diuretics. We describe an extremely preterm infant who developed profound, late-onset neutropenia temporally associated with extended furosemide therapy. A male infant born at 25+3 weeks’ gestation (birth weight 720 g) received intravenous then enteral furosemide beginning on day of life (DOL) 28 for evolving bronchopulmonary dysplasia and fluid overload (1 mg/kg every 12 hours). On DOL 68 a routine complete blood count revealed isolated severe neutropenia (ANC 220/µL). The infant remained afebrile and clinically stable; blood and urine cultures and an extensive viral PCR panel were negative. After hematology consultation, furosemide was discontinued on DOL 68 (Naranjo score 7, “probable” ADR). Serial CBCs showed a prompt rebound in neutrophils beginning 48 hours after drug cessation, normalization by DOL 72, and full recovery by DOL 75. Chlorothiazide was substituted for ongoing diuresis without recurrence of hematologic abnormality. This case suggests a probable, reversible association between prolonged furosemide exposure and late-onset severe neutropenia in an extremely preterm infant. Clinicians should consider periodic CBC monitoring during extended furosemide therapy and promptly discontinue the agent if unexplained neutropenia occurs.