Neonatal Refeeding Syndrome and Clinical Outcome in Extremely Low-Birth-Weight Babies: Secondary Cohort Analysis From the ProVIDe Trial

Abstract

Background: Refeeding syndrome (RS) following preterm birth has been linked to high intravenous (IV) protein intake in the presence of low electrolyte supply. In extremely low-birth-weight (ELBW) babies, we aimed to determine the incidence of RS and associations with birth characteristics and clinical outcomes.

Method: Prospective cohort study of ELBW ProVIDe Trial participants in 6 New Zealand neonatal intensive care units. RS was defined as serum phosphate < 1.4 mmol.L^-1 and total calcium > 2.8 mmol.L^-1 . Relationships between RS and other factors were explored using 2-sample tests and logistic regression adjusted for sex, gestation, and birth-weight z-score.

Results: Of 338 babies (mean [SD] birth-weight, 780 (134) g, gestational age, 25.9 [1.7] weeks), 68 (20%) had RS. Mortality was greater in babies with RS (32% vs 11%; P < .0001). More small- than appropriate-for-gestational-age babies developed RS (22% vs 8%; P = .001). Growth from birth to 36 weeks' corrected age was not different between babies who did and did not have RS. In logistic regression, the odds of RS decreased by 70% for each 1 mmol per kg^-1 .d^-1 IV phosphate intake (odds ratio [OR], 0.3; CI, 0.1-0.6; P = .002) and increased by 80% for each 1 g.kg^-1 .d^-1 IV protein intake (OR, 1.8; CI, 1.3-2.7; P = .002).

Conclusions: Neonatal RS is common in this cohort of ELBW babies and is associated with increased morbidity and mortality. Optimizing phosphate and calcium intakes in IV nutrition solutions may reduce RS and its consequences.

Keywords: amino acids; fluids-electrolytes/acid-base; hypophosphatemia; intraventricular hemorrhage; mortality; neonates; parenteral nutrition; preterm; proteins; refeeding syndrome.