Late and Insufficient Phosphorus Supplementation is Associated with Early Severe Hypophosphatemia in Extremely Low Birth Weight Infants with Early Amino Acid Administration

Abstract

Objective: To investigate the incidence of early severe hypophosphatemia, and examine the associated clinical factors and outcomes, in extremely low birth weight infants (ELBWI) who received early amino acid administration. Methods: Medical records of 82 ELBWI were retrospectively reviewed. Severe hypophosphatemia was defined as a serum phosphate level <2 mg/dL during the first week after birth. Results: Nineteen ELBWI (23.2%) experienced severe hypophosphatemia. The supplementation of phosphorus was started significantly later in the hypophosphatemia group compared to that in the control group (P=0.036). Small for gestational age infants (SGAI) (P=0.006) and bronchopulmonary dysplasia (P=0.016) were more prevalent in the hypophosphatemia group compared to that in the control group. Conclusion: Early severe hypophosphatemia is common in ELBWI. Late and insufficient supplemen tation of phosphorus and SGAI were associated with severe hypophosphatemia.

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 .…”

“…Although the potential role of coagulopathy in the development of IVH is unclear, a recent study in 122 preterm babies reported that concentrations of factor V (a coenzyme needed for coagulation) at birth correlated with IVH and were lower in hypophosphatemic babies 47 . In ELBW babies, 1 small study found twice the rate of severe IVH in those with severe hypophosphatemia (<0.7 mmol.L −1 ) compared with those without (37% vs 18%; P = .48, n = 82), although this was not significant 24 . In the same study, there was also a trend towards higher mortality in the babies with severe hypophosphatemia compared with those without severe hypophosphatemia (42% vs 18%; P = .06, n = 82).…”

“…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. 45 We found that severe hypophosphatemia was associated with a 5-fold increased rate of severe IVH.…”

“…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.…”

“…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.…”