Association Between Maximal Weight Loss and Fluid Administration in the First 7 Days After Birth and In-hospital Outcomes in Extremely Preterm Neonates

Background: Physiologic weight loss is important in the newborn transition, but the threshold at which physiologic weight loss becomes pathologic, if any, remains uncertain. While studies have evaluated the impact of fluid administration or weight loss on adverse outcomes, there is a paucity of literature assessing both factors on outcomes, noting one may influence the other. This study assesses effects of total fluid administration and weight loss patterns on in-hospital neonatal morbidities and mortality among a contemporary cohort of extremely preterm (EP) neonates.

Methods: We implemented a retrospective analysis of the Preterm Epo Neuroprotection Trial (PENUT) evaluating maximal weight loss (MWL) in the first week after birth, total administered fluids, and their association with neonatal mortality and in-hospital morbidities. We evaluated all EP neonates enrolled in PENUT, a multicenter trial across 30 NICUs in the United States, who had daily weight information over the first 7 days after birth. Outcome analyses were based upon 3 separate MWL categories: high (>15%), intermediate (5-15%), and low ( <5%, including weight gain) MWL; and three averaged fluid administration categories: low ( <120 mL/kg birthweight/day), intermediate (120-150 mL/kg birthweight/day), and high (>150 mL/kg birthweight/day). Outcomes included bronchopulmonary dysplasia, grade 2b or 3 necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA) requiring surgical intervention, intracranial hemorrhage at days 7-9 after birth, and mortality prior to discharge.

Results: Eight hundred eighty-three infants were included. MWL between 5-15% from birthweight was associated with decreased adjusted odds of NEC compared to MWL >15% (OR 0.48, 95% CI 0.25-0.95, p=0.03) (Table 1). Average fluid administration >150 mL/kg birthweight/day over the first 7 days after birth was associated with increased adjusted odds of NEC (OR 1.21, 95% CI 1.07-1.36, p=0.002) and PDA requiring surgery (OR 1.19, 95% CI 1.07-1.33, p=0.002) (Table 1). Neonates born at 24 weeks’ gestation had a mean (SD) MWL of 11.2% (7.8%) compared to 9.4% (5.7%) in those born at 27 weeks’ gestation (Figure 1). The median day of MWL for all included neonates was day 3 (Figure 1). Increasing total fluids and higher maximal weight loss was not associated with BPD in our adjusted analysis. Similarly, mortality was similar in all groups.

Conclusion: Physiologic weight loss is common. As MWL <5% or >15% was associated with higher rates of NEC, this finding suggests a potential optimal window of MWL of 5-15%. In this cohort, increasing average fluid administration in the first week (mL/kg/day) was also associated with poorer neonatal outcomes, especially NEC and PDA requiring surgery.