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