Chlorothiazide is associated with a weaker diuretic response than furosemide in infants with bronchopulmonary dysplasia (BPD)

Objective: To compare the acute diuretic effect of furosemide versus chlorothiazide in preterm infants with high-grade bronchopulmonary dysplasia (BPD). Study Design: We conducted a retrospective cohort study of infants with grade 2 or 3 BPD admitted to a level IV NICU between 36 and 60 weeks’ postmenstrual age. Novel diuretic exposures were defined as administration of furosemide or chlorothiazide without prior exposure to the same agent in the preceding 7 days. The primary outcome was the within-subject change in net fluid balance (mL/kg) in the 24 hours before and after diuretic initiation. Multivariable linear regression adjusted for diuretic dosing, route, frequency, and clinical covariates. Results: Among 300 infants contributing 136 furosemide and 215 chlorothiazide exposures, furosemide was most often dosed every 24 hours (73%) and chlorothiazide every 12 hours (90%). After covariate adjustment, furosemide was associated with a threefold greater reduction in net fluid balance compared to chlorothiazide (-32.0 mL/kg vs. -10.5 mL/kg; p < 0.001). More frequent dosing (every 12 hours) was associated with greater diuretic effect than every 24-hour dosing for both agents (-22.4 vs. -11.3 mL/kg; p = 0.032). Concomitant use of both agents was common, yet the order of administration did not significantly influence fluid balance. No other clinical or biochemical characteristics were significantly associated with diuretic response. Conclusion: Furosemide has a significantly greater acute diuretic effect than chlorothiazide in infants with high-grade BPD. These findings may inform short-term fluid management strategies and support further investigation into optimal diuretic selection and dosing in this population.