Hypophosphatemia is Prevalent among Preterm Infants Less than 1,500 Grams

Abstract

Objective This article identifies the prevalence and associated factors of hypophosphatemia (HP) in very low birth weight (VLBW) infants in the first week of life. Study Design Prospective exploratory cohort study of 106 consecutive VLBW infants admitted to neonatal intensive care at Foothills Hospital, Calgary, Canada. HP was defined as at least one measurement of serum phosphate < 1.5 mmol/L (4.5 mg/dL). Results Seventy-seven percent (82/106) of the VLBW infants had HP, with significantly higher prevalence in infants < 1,000 g (94%) compared to infants ≥ 1,000 g (61%) (p < 0.001). Hypophosphatemic infants had lower birth weight (p < 0.001), gestational age (p < 0.001), and their increase in phosphate intake was slower (p = 0.003). Respiratory distress syndrome (RDS) (p = 0.002), intraventricular hemorrhage (IVH) ≥ grade III (p = 0.020), and hyperglycemia (p = 0.013) were more frequent among hypophosphatemic infants, especially among those < 1,000 g. Mortality, seizures, arrhythmias, and need for transfusion were not different between groups. Birth weight modified the association between RDS, IVH, hyperglycemia, and HP. Conclusion HP was ubiquitous among infants < 1,000 g and highly prevalent among those weighing 1,000 to 1,500 g. While the direction of effect was not clear, RDS, IVH, and hyperglycemia were associated with HP. Prevention of HP in these physiologically immature neonates might improve neonatal outcomes.

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 ESPGHANrecommended 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][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.…”

“…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.…”

“…11 If followed by generous amino acid and energy supply in the absence of adequate electrolyte intake, this may lead to RS (as seen in malnourished children and adults 43 ) because amino acid intake increases endogenous insulin production and the demand for electrolytes because of the transfer of phosphate and potassium into cells for energy production and synthesis of glycogen, fat, and protein. 29 Electrolyte disturbances consistent with RS have been described previously in smaller preterm cohorts and reported to be associated with sepsis, 6 hyperglycemia, 23 chronic lung disease, 23 enhanced nutrition intakes, 6 and lower phosphate intakes. 24,44 Similarly, intrauterine growthrestricted piglets fed an enteral feed containing 50% more protein than standard sow milk without additional electrolytes developed RS symptoms, and 32% died.…”

“…Electrolyte disturbances consistent with RS have been described previously in smaller preterm cohorts and reported to be associated with sepsis, 6 hyperglycemia, 23 chronic lung disease, 23 enhanced nutrition intakes, 6 and lower phosphate intakes 24,44 . Similarly, intrauterine growth–restricted piglets fed an enteral feed containing 50% more protein than standard sow milk without additional electrolytes developed RS symptoms, and 32% died 45 …”

“…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 . A clear, consistent definition of neonatal RS has not yet been established.…”