Assessing the impact of preterm nutrition
Introduction
Nutritional support for extremely preterm infants has always been problematic. The practical and clinical complexities of providing intensive care and delivering enteral and parenteral nutrition have been sufficiently challenging to have justified a focus on short-term goals. But over the last decades illness severity has reduced, physiological stability has improved and the likelihood of survival to adult life has increased. It is time to consider long-term goals.
By the time a preterm infant reaches term equivalent age clear differences in brain and somatic development are apparent in comparison to healthy term-born counterparts. Many of these differences are now known to persist and alter trajectories of normal development for life. The nutritional support of the preterm infant is likely to be a key determinant in establishing this altered phenotype.
How should the success of nutritional support for the preterm infant be assessed? This review will discuss the differences that exist between the preterm infant at term age and beyond in comparison to healthy term-born infants, the evidence demonstrating the impact of early nutrition on trajectories of development, the conundrums faced by neonatologists when considering nutritional support, and the outcomes that might best be used to assess nutritional stratagems.
Section snippets
Somatic growth
Growth, particularly weight gain has traditionally been the favoured means of assessing the adequacy of nutritional support. But what is optimal growth for preterm babies? Preterm birth is the end result of a compromised pregnancy. Thus it is not surprising that an infant born preterm usually weighs less than a fetus remaining in utero at equivalent gestational age, indicating that some degree of deceleration in intrauterine growth has occurred. At 25–26 weeks gestation, newborn weights are
Cardiovascular outcomes
The now landmark epidemiological observations of Barker demonstrating an association between birth size and adult coronary vascular disease [17] have been extended and amplified though data published to date still present an inconsistent picture. It has been suggested that individuals of low birth weight who show rapid weight gain in infancy have the highest risk of adult cardiovascular morbidity though these researchers found no adverse effect on vascular function (measured by flow mediated
Renal function
Aberrant renal development is a further contributor to the adult preterm phenotype. Preterm infants are at risk of exposure to many nephrotoxic insults but reduced nephron number related to poor early nutrition followed by hyperfiltration, exacerbated by a high protein intake has been suggested as an additional determinant of preterm and intrauterine growth restriction associated hypertension [22]. However reduced total renal mass, secondary to congenital unilateral kidney or nephrectomy does
Metabolic outcomes
Reduced insulin sensitivity in infants born preterm (< 32 weeks gestation) has been demonstrated at 4–10 years [55] and 18–27 years of age [23]. In the former study no association was demonstrated between neonatal macronutrient intakes and insulin sensitivity. However there was a significant negative association between rapid growth in infancy and insulin sensitivity. In the latter study preterm adults had higher 2-hour glucose, fasting insulin and 2-hour insulin concentrations. We have found
Body composition
Weight gain is a poor indicator of the success of preterm nutrition as this provides no insight into body composition. Magnetic resonance imaging (MRI) allows direct assessment of adipose tissue (AT) content and it able to quantify individual AT depots [24]. Using whole body MR imaging, we have shown that there is aberrant deposition of AT, with an excess of intra-abdominal AT, in preterm infants by the age of term and reduced lean body mass in comparison to their term-born counterparts [25].
Brain growth and development
The preterm infant is born during a critical period for brain growth. Processes such as cellular migration, cellular differentiation, synaptogenesis, myelination, neurogenesis and development of neurotransmitter pathways may all be susceptible to nutritional deprivation during this period. Studies of perinatal protein undernutrition in rats consistently demonstrate a reduction in brain weight [28], a reduction in dendritic spine density in different neuronal populations [29], [30], [31] and
Preterm nutrition
It has long been argued and is currently widely accepted that adequate nutrition of the preterm infant equates with achieving the equivalent of third trimester intrauterine weight gain (14–18 g/kg/day) and nutrient accretion (1.8–2 g/kg/day of protein and 1.4–1.9 g/kg/day of fat). An obvious limitation of this strategy is that data on human fetal body composition are derived mainly from stillborn fetuses [46]. Ehrenkranz et al. have provided a comprehensive assessment of longitudinal postnatal
Conclusions and future directions
The question for the neonatal clinician is clear: what outcome or outcomes best represent the impact of preterm nutrition? We suggest that it is time for a shift in emphasis when evaluating preterm nutrition, away from short-term growth.
The use of growth as the sole or principal outcome measure to assess preterm nutrition is flawed as we do not know what represents optimal growth. We only know that there are problems at both ends of the spectrum, with poor and rapid early growth associated with
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