Association between early phosphate intake and refeeding syndrome in extremely low-birth-weight infants: A retrospective cohort study.

Background: Preterm infants are at risk of refeeding syndrome, a constellation of biochemical changes associated with nutrition. We aimed to determine whether increased early phosphate intake with routine biochemical monitoring is associated with a reduction in refeeding syndrome.

Methods: Retrospective cohort study in two Auckland neonatal intensive care units comparing infants born <1000 g before (2014-2018, standard phosphate intake) and after (2020-2021, early phosphate intake) changes to intravenous nutrition protocols that increased phosphate intake and introduced biochemical monitoring. The standard phosphate intake cohort comprised the participants who received placebo in a randomized controlled trial of early increased amino acid intake. The early phosphate intake cohort was identified prospectively. Data were retrieved from the trial database or prospectively from electronic medical records. Groups were compared using either the chi-square test or pooled t test and logistic or multiple logistic regression analysis. Refeeding syndrome was defined as concurrent hypophosphatemia (serum phosphate <1.4 mmol L^-1) and hypercalcemia (serum calcium >2.8 mmol L^-1).

Results: The incidence of refeeding syndrome in the first 5 days after birth decreased from 11.9% to 2.9%, hypophosphatemia from 53.5% to 21.2%, and severe hypophosphatemia (<0.9 mmol L^-1) from 11.3% to 1.2%. Probable early- and late-onset sepsis reduced from 51.4% to 28.2% and from 62.5% to 28.0%, respectively.

Conclusions: Increased early phosphate intake with routine biochemical monitoring is associated with a lower incidence of refeeding syndrome, hypophosphatemia, and associated comorbidities. Whether these associations are causal requires further investigation.