Effect of Low versus High Intravenous Amino Acid Intake on Very Low Birth Weight Infants in the Early Neonatal Period

Abstract

Greater protein intakes are required than have been commonly used to achieve fetal in utero protein accretion rates in preterm neonates. To study the efficacy and safety of more aggressive amino acid intake, we performed a prospective randomized study in 28 infants [mean wt, 946 +/- 40 g (SEM)] of 1 (low amino acid intake, LAA) versus 3 g.kg(-1).d(-1) (high amino acid intake, HAA) at 52.0 +/- 3.0 h of life. After a minimum of 12 h of parenteral nutrition, efficacy was determined by protein balance and was significantly lower in the LAA versus HAA groups by both nitrogen balance (-0.26 +/- 0.11 versus 1.16 +/- 0.15 g.kg(-1).d(-1), p < 0.00005) and leucine stable isotope (0.184 +/- 0.17 versus 1.63 +/- 0.20 g.kg(-1).d(-1), p < 0.0005) methods. Leucine flux and oxidation and nonoxidative leucine disposal rates were all significantly higher in the HAA versus LAA groups (249 +/- 13 versus 164 +/- 8, 69 +/- 5 versus 32 +/- 3, and 180 +/- 10 versus 132 +/- 8 micro mol.kg(-1).h(-1), respectively, p < 0.005), but leucine appearance from protein breakdown was not (140 +/- 15 in HAA versus 128 +/- 8 micro mol.kg(-1).h(-1)). In terms of possible toxicity with HAA, there were no significant differences between groups in the amount of sodium bicarbonate administered, degree of acidosis as determined by base deficit, or blood urea nitrogen concentration. Parenteral HAA versus LAA intake resulted in increased protein accretion, primarily by increasing protein synthesis versus suppressing protein breakdown, and appeared to be well tolerated by very preterm infants in the first days of life.

Safety and efficacy of early amino acids in preterm <28 weeks gestation: prospective observational comparison

“…However, the number of patients studied is too small in both studies to detect significant difference in these outcomes. Other studies have reported 'early administration of AA'; 17,[21][22][23][24] however, the intervention group in those studies were similar to the late AA groups in these studies 12,13 and our study. Postnatal malnutrition has been increasingly implicated not only with postnatal growth but also with neurodevelopmental outcomes and certain adult-onset diseases including diabetes mellitus and hypertension.…”

“…7,25 -29 Previous concerns of metabolic acidosis and hyperammonemia 10,11 have been challenged in recent studies of improved AA formulations. 12,21,23,24 However, a word of caution is warranted as our study and the study by Te Braake et al 13 identified clinically unimportant but statistically significant differences in the values for pH, HCO 3 and base deficit indicative of metabolic acidosis. Overall, from a practical standpoint with the preparation of 'stock' solutions of 5, 7.5 and 10% dextrose and 2 g of AA/100 ml we are now able to initiate AA in the resuscitation room.…”

“…The elevated urea levels in the early AA group in our study are similar to previously reported, 13 and reflects higher protein turnover and elevated oxidation of AA rather than toxicity. 21 Ibrahim et al 12 in another randomized trial of 32 neonates administered AA at 3.5 g/kg/day within 2 h of birth and compared to AA started at 2 g/kg/day at 48 h of age. Early AA administration was well tolerated, resulted in positive nitrogen balance without significant impact on common outcomes of preterm infants.…”

“…The number of infants who developed hyperglycemia was lower in the early AA group compared to the late AA group, which may be owing to release of insulin following administration of certain AAs. 21,30 There was a reduction in the incidence of sepsis which we speculate could be owing to improved nutritional status resulting in improved host defenses or probably owing to reduction in the number of days patient required intravenous access. No difference in other neonatal outcomes is encouraging; however, this needs to be monitored in future studies as there was a statistically insignificant increase in the number of infants with chronic lung disease and duration of respiratory support in the early AA group.…”

Improved growth and decreased morbidities in <1000 g neonates after early management changes

“…[12][13][14] Early amino-acid supplementation dramatically improves the nitrogen balance of ELBW infants, shifting these patients from the catabolic state traditional parenteral support induces to a healthier anabolic state. [15][16][17] The ultimate goal of these three interventions is to improve short-and long-term outcomes. Our primary outcome measure was growth, as EUGR is associated with significantly lower Bayley Mental Development Index (MDI) and Psychomotor Index (PDI) scores at 2 years of age, 18 and impaired long-term growth potential.…”