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.

Hypophosphatemia as an Early Metabolic Bone Disease Marker in Extremely Low‐Birth‐Weight Infants After Prolonged Parenteral Nutrition Exposure

“…There were only 4 patients with neonatal refeeding syndrome with hypercalcemia and hypophosphatemia at 1 week of life, and 3 of them resolved after second week of life. The result is comparable to most of the clinical studies in which neonatal refeeding syndrome occurs during the first week of life and no cases are reported after 2 weeks of life until now 23,27,29–33 . The major cause of hypophosphatemia in ELBW infant at 2 weeks of life is inadequate mineral supplement, and it could be in infant with either persistent hypophosphatemia after neonatal refeeding syndrome, or gradually lowering serum P level from normal mineral status at 1 week of life.…”

Early versus later initiation of parenteral nutrition for very preterm infants: a propensity score-matched observational study

“…Indeed, studies of higher intakes of macronutrients in very preterm babies in the early postnatal period are associated with other metabolic derangements, including the refeeding syndrome. 27 The refeeding syndrome was found to be associated with a higher rate of sepsis in a study of enhanced compared with standard feeding. 28 The preterm brain is especially susceptible to injury.…”

“…Indeed, studies of higher intakes of macronutrients in very preterm babies in the early postnatal period are associated with other metabolic derangements, including the refeeding syndrome. 27 The refeeding syndrome was found to be…”

Effects of nutrition therapy on growth, inflammation and metabolism in immature infants: a study protocol of a double-blind randomized controlled trial (ImNuT)

“…Of note, this study was discontinued early due to a high occurrence of a refeeding like syndrome among the intervention infants [11]. The risk of refeeding like syndrome has been confirmed by others [12][13][14][15] and the early need for phosphate and potassium supplementation is highlighted in the revised European guidelines on Pediatric Parenteral Nutrition [16,17]. Moreover, this underlines the importance of conducting well-designed trials on nutritional management in this patient population.…”

“…We have used data from the PRENU-cohort for our determination of sample size. The PRENU study showed decreased regional white matter mean diffusivity (MD), suggestive of improved maturation of cerebral connective tracts in the intervention group [15]. The MD in the superior longitudinal fasciculi was 1.18 × 10-3 (6.18 × 10-2) in the intervention group and 1.25 × 10-3 (5.70 × 10-2) in the control group.…”