Early hypophosphatemia in very low birth weight preterm infants

Abstract

Background. Refeeding Syndrome (RFS) is a well-known group of symptoms which occur after the introduction of enteral or parenteral nutrition in undernourished patients. Intrauterine growth restriction (IUGR) is the equivalent of postnatal RFS following the beginning of feeding. The aggressive parenteral nutrition of neonates with very low birth weight (VLBW) resulting from the termination of intrauterine transplacental nutrition is a source of biochemical disorders.

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

“…Mean IV phosphate, calcium, and magnesium intakes in our cohort were significantly lower than 2018 ESPGHAN–recommended intakes at most sites but broadly similar to intakes reported by others, 6,8,11,12 even in more recent studies 16,23 . The IV amino acid intakes in our cohort are higher in the first 2 days than those reported in similar cohorts 6,8,11,12,16,20,40,51 but similar to intakes in more recent reports on this topic 13‐15,17,21,23,24 . We found RS was more likely in babies with IV amino acid intakes close to the ESPGHAN 2018–recommended range of 2.5–3.5 g.kg −1 .d −1 52 but 3 times more likely when mean IV phosphate intake was lower than recommended 27 .…”

“…In our cohort, only 2 sites supplied ≥0.6 mmol.kg −1 .d −1 phosphate on day 1, and these were also the only 2 sites where mean serum phosphate concentrations were >1.6 mmol.L −1 . Our study adds to accumulating evidence that high IV amino acid intake, combined with low electrolyte intake in the first few days after preterm birth, is associated with RS 3,4,6,7,9‐18,22 . Our findings support the ESPGHAN 2018 recommendation of 0.8–2.0 mmol.kg −1 .d −1 IV phosphate on day 1 followed by 1.6–3.5 mmol.kg −1 .d −1 IV phosphate in week 1 and also the routine monitoring of calcium and phosphate in the first 5 days after birth, especially for SGA ELBW babies 27 …”

“…16,23 The IV amino acid intakes in our cohort are higher in the first 2 days than those reported in similar cohorts 6,8,11,12,16,20,40,51 but similar to intakes in more recent reports on this topic. [13][14][15]17,21,23,24 We found RS was more likely in babies with IV amino acid intakes close to the ESPGHAN 2018-recommended range of 2.5-3.5 g.kg −1 .d −1 52 but 3 times more likely when mean IV phosphate intake was lower than recommended. 27 For rapidly growing preterm babies, an estimated 0.33 mmol of phosphate is needed for every 1 g amino acid because phosphate is an essential component of the nucleic acids, ATP, and membrane phospholipids needed for lean tissue accretion.…”

“…The first reports of associations between enhanced IV nutrition, hypophosphatemia, and hypercalcemia in preterm babies emerged in 2012–2013. 4,6,20 A series of cohort studies and case reports followed describing hypophosphatemia and other biochemical disturbances consistent with RS in preterm babies who were small‐for‐gestational‐age (SGA) and/or born following maternal preeclampsia and who were thought to be triggered by early aggressive IV nutrition in the first week after birth, 6,8‐17 including in randomized controlled trials 18,19 . The definition of hypercalcemia in these reports (>2.8 mmol.L −1 ) is reasonably consistent 4,16,17,20 ; however, the definition of hypophosphatemia varies between <1.1 to <1.6 mmol.L −1 4,9,12,14,16,17,21‐23 and severe hypophosphatemia between <0.7 and <1.0 mmol.L −1 4,9,12‐14,16,22,24 .…”

“…18,19 The definition of hypercalcemia in these reports (>2.8 mmol.L −1 ) is reasonably consistent 4,16,17,20 ; however, the definition of hypophosphatemia varies between <1.1 to <1.6 mmol.L − 1 4,9,12,14,16,17,21-23 and severe hypophosphatemia between <0.7 and <1.0 mmol.L −1 . 4,9,[12][13][14]16,22,24 A clear, consistent definition of neonatal RS has not yet been established.…”