307 - Preventing Refeeding Syndrome in IUGR Preterm Infants Receiving Parenteral Protein

Early high-dose parenteral amino acid supplementation (3.5 g/kg/day after day 1) may prevent catabolism and hyperglycemia, leading to optimal growth and neurodevelopmental outcomes for preterm infants.  However, infants with intrauterine growth restriction (IUGR) due to chronic undernourishment in utero who are receiving high doses of amino acids are at risk for refeeding syndrome (RS).  The main biochemical hallmark of RS is hypophosphatemia, with nadir levels at 3-7 days after birth.  Refeeding syndrome is associated with adverse outcomes because phosphorus (P) plays a vital role in cellular membranes, enzyme systems, and energy conversion. Because of this risk, some national organizations have lowered their recommended early dosing of amino acids to < 3.0 g/kg/d.  Alternatively, active daily adjustment of P and calcium (Ca) intakes may ameliorate the risk of RS for IUGR preterm infants receiving higher doses of amino acids. 

Objective:

Our objective was to assess the incidence of RS and severe hypophosphatemia (< 3 mg/dL) in IUGR preterm infants receiving high-dose amino acid intake accompanied by active daily management of P and Ca intakes.

Design/Methods:

Preterm IUGR infants (< 1500 g BW, n=41) were enrolled retrospectively.  By protocol, infants in our NICU receive early supplementation with amino acids (2.5-3.0 g/kg/day on day 0 and 3.5 g/kg/d on day 1 onward).  Supplementation with P (1.0 – 1.4 mmol/kg) and Ca (1.1-1.5 mmol/kg) start on day 1.  After day 1, P and Ca intake are adjusted each day based on serum concentrations.

Results:

Mean gestational age was 30.7 +/- 3.3 weeks and birth weight 1007 +/- 320 g.  We found that P intake on day 2 was linearly correlated with the sum of protein intake on day 0-2 (r=0.552, p=< 0.001; Fig 1).  The molar ratio of Ca to P intake decreased from day 1-4 (from 1.25 to 0.98) (Fig 2).  Serum concentrations of Ca and P were stable from day 1-7 (10.7 and 4.5 mg/dL, respectively, on day 7: Fig 3).  No infants had severe hypophosphatemia.  On day 30, mean Ca, P, and alkaline phosphatase levels were normal (6.2 mg/dL, 10.3 mg/dL, and 419 IU/L, respectively).

Conclusion(s):

Early parenteral amino acid intake is vital for growth and neurodevelopment but alters P and Ca homeostasis in IUGR preterm infants.  Our findings suggest that early and active management of P and Ca intake leads to decreasing Ca:P intake ratio during the first week and ameliorates the risk for RS and severe hypophosphatemia.  Using this approach, the benefits of high early amino acid supplementation (3.5 g/kg/d) may supersede the risk of RS.