Association between fluid trajectories in the first postnatal week and moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a retrospective cohort study

Abstract Background To characterize the longitudinal trajectories of fluid output, fluid balance, and related indicators during the first postnatal week in very preterm infants and examine their associations with moderate-to-severe bronchopulmonary dysplasia (BPD) at 36 weeks of postmenstrual age. Methods This single-center retrospective cohort study included 211 very preterm infants with a gestational age (GA) < 32 weeks who survived for 36 weeks. The primary outcome was moderate to severe BPD (NICHD, 2018). Generalized linear mixed models compared the daily trajectories over days 1–7. Cum_Output3-7 was the primary exposure. To isolate its effect from fluid intake, a joint model including both Cum_Output3-7 and Cum_Intake3-7 was constructed. A reference model using Cum_Balance3-7 alone was performed. Results Of 211 infants, 77 (36.5%) developed moderate-to-severe BPD. A significant BPD-by-time interaction was found for daily fluid balance ( P = 0.031) but not for output, intake, intake-to-output ratio, or weight loss (all P > 0.05). After adjustment, each 10 mL/kg increase in Cum_Output3-7 remained independently associated with BPD (aOR 1.073; 95% CI 1.031–1.115; P < 0.001), whereas Cum_Intake3-7 was not significant (aOR 0.961; 95% CI 0.924–0.999; P = 0.063). A reference model using Cum_Balance3-7 alone showed a reciprocal trend (aOR 0.942; 95% CI 0.923–0.960; P < 0.001). Conclusions Higher fluid output, independent of intake, was unexpectedly associated with moderate-to-severe BPD. These findings call into question the conventional emphasis on cumulative net balance and highlight the potential importance of fluid output dynamics. Given the observational design, they are hypothesis generating and require prospective validation. Trial registration ChiCTR2500095712 (Retrospectively registered on 10 January 2025).