Early amino acid administration in very preterm infants: Too little, too late or too much, too soon?

https://doi.org/10.1016/j.siny.2013.02.002Get rights and content

Summary

Early postnatal growth failure is well described in very preterm infants. It reflects the nutritional deficits in protein and energy intake that accumulate in the first few weeks after birth. This coincides with the period of maximum parenteral nutrition (PN) dependency, so that protein intake is largely determined by intravenous amino acid (AA) administration. The contribution of PN manufacture, supply, formulation, prescribing and administration to the early postnatal nutritional deficit is discussed, focusing on total AA intake. The implications of postnatal deficits in AA and energy intake for growth are reviewed, with particular emphasis on early head/brain growth and long-term neurodevelopmental outcome. The rationale for maximising AA acid intake as soon as possible after birth is explained. This includes the benefits for very early postnatal nutritional intake and metabolic adaptation after birth. These benefits relate to total AA intake and so have to be interpreted with some caution, given the very limited evidence base surrounding the balance of individual AAs in neonatal PN formulations. This work mostly predates current nutritional recommendations and therefore may not provide a true reflection of individual AA utilisation in current clinical practice.

Introduction

Early postnatal growth failure or extrauterine growth restriction coincides with the severe nutritional deficit that develops in very preterm infants (VPIs) in the first few weeks of life.1, 2, 3 The deficit refers to the gap between the energy and protein actually provided and that required to mimic fetal growth rates.4 Based on the latter, the recommended calorie intake is 110–135 kcal/kg/day (110–120 kcal/kg/day parenteral) and protein intake is 3–4.5 g/kg/day (2.5–4 g/kg/day parenteral).5, 6 These estimates do not take into account co-morbidities that may increase individual infant requirements (such as chronic respiratory disease) and therefore increase the risk of postnatal growth failure.7 Indeed, postnatal malnutrition may be inevitable based on current recommendations.8

This postnatal growth failure was described in detail by Ehrenkranz et al.9 who produced growth curves based on gestation and birth weight for infants <30 weeks of gestation. These showed that the majority of appropriate for gestational age (AGA) very low birth weight (VLBW) infant weights are below the 10th centile by 36 weeks of corrected gestational age (CGA). Much of the growth failure occurs in the first few weeks after birth, with infants born <1000 g taking a mean of 14.4–17.2 days to regain birth weight. VLBW infants born small for gestational age (SGA) are even more vulnerable to postnatal nutritional deficits because of the antenatal growth failure. The interpretation of early weight loss is complicated by physiological fluid loss in the first few days of life.10 Nevertheless, early nutritional interventions have been shown to improve weight gain in VPIs in both observational studies11, 12, 13, 14, 15 and randomised controlled trials.16, 17 This suggests that there is a reversible nutritional deficit.

Section snippets

Why is there an early nutritional deficit?

Very preterm infants have a gut that is too immature to digest milk in sufficient quantity to meet nutritional requirements. Virtually all preterm infants <29 weeks of gestation and <1200 g require parenteral nutrition (PN) for a period that depends on gestational birth weight and other morbidities. The mean duration of PN (>75% all nutrition) in these infants (survivors) is 15.6 days.9, 17 The data indicate that early protein intake in these infants is mainly derived from intravenous amino

Early AA administration: practical difficulties

The limitations of PN policy/guidelines (i.e. factors that affect all PN-dependent infants) have to be distinguished from those factors that affect actual nutrient delivery. These factors involve PN prescription, formulation and administration and vary between infants. Conventional neonatal PN strategy has been based on individualised prescription and formulation to address the rapidly changing and variable fluid and electrolyte needs characteristic of the VPI. Unfortunately this process

Nutrition, head growth and neurodevelopmental outcome

In humans, the fastest brain growth takes place during the last trimester and the first 3 months of postnatal life with high growth rates persisting until the end of the second year. There is growing evidence that malnutrition during this critical period of central nervous system development results in irreversible long-term neurological deficits.55 VPIs have to navigate this period of critical brain growth entirely ex utero, exposed to all the risks of neonatal intensive care including

Early postnatal protein, head growth and neurodevelopmental outcome

Given that nadir in weight and head circumference occurs at about 4 weeks of postnatal age, it is logical to focus on early postnatal nutrition in order to prevent the increased deficit occurring in the first place, thus reducing the need for catch-up growth. Changing early nutritional policy can improve growth in large preterm cohorts18 including discharge head circumference.12 Using multivariate analysis, Berry et al.7 showed that energy intake correlated positively with weight gain in the

Early protein and the regulation of early postnatal growth

Protein plays an important part in modulating the endocrine controls on growth as well as providing the substrate for protein synthesis. Growth is a complex process governed by the interactions between several hormone axes and adequate nutrition.75 Insulin-like growth factor-1 (IGF-1), IGF-2 and their binding proteins and receptors play an essential role in fetal growth together with insulin.76 In postnatal life, nutrition, insulin and IGF-1 still dominate growth regulation.77 Whereas growth

Amino acids and early metabolic adaptation

The fetus receives large quantities of AAs across the placenta to meet intrauterine growth rates. One of the arguments against early, aggressive AA administration is that VPIs are in a catabolic state in the first few days after birth and are therefore unable to utilise protein for growth. However, several studies26, 27, 28 clearly indicate that positive nitrogen balance may be achieved by starting AA immediately after birth, even in the first 48 h. Extreme prematurity used to be frequently

Amino acid formulations in neonatal PN

Early protein intake in VPIs comprises total intravenous AAs (parenteral) and enteral protein. Although there has been much debate about the individual AA constituents in neonatal PN, there has been little change in neonatal parenteral AA formulations for more than two decades. Therefore current AA formulations predate recent recommended protein intakes and the evidence supporting AA administration immediately after birth. There have been relatively few studies of individual AA levels28, 34, 88

Conflict of interest statement

None declared.

Funding sources

None.

References (95)

  • R.W. Cooke et al.

    Head circumference as an index of brain weight in the fetus and newborn

    Early Hum Dev

    (1977)
  • A.A. Lindley et al.

    The relationship between clinically measured head circumference and brain volume estimated from head CT scans

    Early Hum Dev

    (1999)
  • M.K. Georgieff et al.

    Effect of neonatal caloric deprivation on head growth and 1-year developmental status in preterm infants

    J Pediatr

    (1985)
  • M.J. Claas et al.

    Postnatal growth of preterm born children ≤750 g at birth

    Early Hum Dev

    (2011)
  • R.I. Holt

    Fetal programming of the growth hormone-insulin-like growth factor axis

    Trends Endocrinol Metab

    (2002)
  • G. Wu et al.

    Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications

    J Nutr Biochem

    (2004)
  • B.B. Poindexter et al.

    Effect of glutamine supplementation on plasma amino acid concentrations in extremely low birthweight infants

    Am J Clin Nutr

    (2003)
  • M.L. Batshaw et al.

    Arginine-responsive asymptomatic hyperammonemia in the premature infant

    J Pediatr

    (1984)
  • S.A. Zamora et al.

    Plasma l-arginine concentrations in premature infants with necrotising enterocolitis

    J Pediatr

    (1997)
  • H. Amin et al.

    Arginine supplementation prevents necrotising enterocolitis in the premature infant

    J Pediatr

    (2002)
  • R.H. Clarke et al.

    Nutrition in the intensive care unit: how do we reduce the incidence of extrauterine growth restriction?

    J Perinatol

    (2003)
  • N.S. Wood et al.

    The EPICure study: growth and associated problems in children born at 25 weeks of gestational age or less

    Arch Dis Child Fetal Neonatal Ed

    (2003)
  • R.J. Cooke

    Postnatal growth in preterm infants

  • C.J. Klein

    Nutrient requirements for preterm formulas. A report from the American Society for Nutritional Sciences, Life Sciences Research Office

    J Nutr

    (2002)
  • B. Koletzko et al.

    Guidelines on paediatric parenteral nutrition

    J Paediatr Gastroentrol Nutr

    (2005)
  • M.A. Berry et al.

    Factors associated with growth of extremely premature infants during initial hospitalisation

    Pediatrics

    (1997)
  • N.E. Embleton et al.

    Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants?

    Pediatrics

    (2001)
  • R.A. Ehrenkranz et al.

    Longitudinal growth of hospitalized very low birthweight infants

    Pediatrics

    (1999)
  • I.E. Olsen et al.

    Intersite differences in weight growth velocity of extremely premature infants

    Pediatrics

    (2002)
  • B.T. Bloom et al.

    Improving growth of very low birth weight infants in the first 28 days

    Pediatrics

    (2003)
  • R. Donovan et al.

    Outcome of early nutrition support in extremely low birth weight infants

    Nutr Clin Pract

    (2006)
  • T. Senterre et al.

    Optimizing early nutritional support based on recent recommendations in VLBW infants and postnatal growth restriction

    J Pediatr Gastroenterol Nutr

    (2011)
  • T. Senterre et al.

    Reduction in postnatal cumulative nutritional deficit and improvement of growth in extremely preterm infants

    Acta Paediatr

    (2012)
  • D.C. Wilson et al.

    Randomised controlled trial of an aggressive nutrition regimen in sick very low birthweight infants

    Arch Dis Child Fetal Neonatal Ed

    (1997)
  • M.J. Tan et al.

    Improving head growth in very preterm infants – a randomized controlled trial. I: neonatal outcomes

    Arch Dis Child Fetal Neonatal Ed

    (2008)
  • C.R. Martin et al.

    Nutritional practices and growth velocity in the first month of life in extremely premature infants

    Pediatrics

    (2009)
  • M. Ahmed et al.

    Education and evidence are needed to improve neonatal parenteral nutrition practice

    J Parenteral Enteral Nutr

    (2004)
  • A. Grover et al.

    Iatrogenic malnutrition in neonatal intensive care units: urgent need to modify practice

    J Parenteral Enteral Nutr

    (2008)
  • D.G. Mason et al.

    Parenteral nutrition for neonates and children: a mixed bag

    Arch Dis Child

    (2010)
  • F. Paize et al.

    Effect of differences in parenteral nutrition policies on preterm early macronutrient intake: telephone survey of UK level 3 neonatal services

    Arch Dis Child Fetal Neonatal Ed

    (2012)
  • N. Murdock et al.

    Low birthweight infants and parenteral nutrition immediately after birth. II. Randomised study of biochemical tolerance of intravenous glucose, amino acids and lipid

    Arch Dis Child Fetal Neonatal Ed

    (1995)
  • P.J. Thureen et al.

    Effect of low versus high intravenous amino acid intake on very low birth weight infants in the early neonatal period

    Pediatr Res

    (2003)
  • H.M. Ibrahim et al.

    Aggressive early total parenteral nutrition in low-birth-weight infants

    J Perinatol

    (2004)
  • K. Kotsopoulos et al.

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

    J Perinatol

    (2006)
  • P. Jadhav et al.

    Parenteral amino acid and metabolic acidosis in premature infants

    J Parenteral Enteral Nutr

    (2007)
  • S. Kashyap et al.

    Energy requirements and protein energy metabolism and balance in preterm and term infants

  • R.H. Clark et al.

    Effects of two different doses of amino acid supplementation on growth and blood amino acid levels in premature infants admitted to the neonatal intensive care unit: a randomized controlled trial

    Pediatrics

    (2007)
  • Cited by (15)

    View all citing articles on Scopus
    View full text