Background
Of the ~ 11% of babies born preterm each year, > 80% are born moderate- to late-preterm (MLPT) between 32
+ 0 and 36 completed weeks’ gestation [
1]. Although survival of MLPT babies is excellent, these babies constitute a much larger proportion of the health care burden related to prematurity than do extremely preterm babies [
1,
2]. Compared to children born at term, MLPT babies have a 36% increased risk for developmental delay or disability at pre-school ages and a 50% increased risk of special education needs at school [
3] and account for almost ten times as many children with neurodisability than do extremely preterm babies [
4]. MLPT birth also carries an increased risk of adverse long-term health outcomes, including obesity, hypertension and diabetes, even by the 3rd and 4th decades of life [
5,
6]. This metabolic risk is substantially related to increased adiposity. Late preterm babies demonstrate an 182% increase in fat mass between birth and term-corrected age, by which time they have ~ 50% greater percentage body fat than term-born controls [
7]. This appears to be due to preserved development of fat mass, but impaired accretion of lean mass, indicative of inadequate protein intake between birth and term corrected age [
7].
Nutritional practices in early life may impact on later metabolic health through different pathways. A period of relative undernutrition whilst enteral feeds are established may be accompanied by faltering growth which is followed by accelerated growth when nutrition is restored. The postnatal period also represents a critical window for establishing the infant microbiome, which also is associated with later adiposity [
8]. More rapid growth in infancy may protect the infant from cognitive impairment but is linked to childhood adiposity, persisting through adulthood [
9], suggesting that there may be a trade-off in preterm babies whereby providing enhanced nutrition to prevent postnatal growth faltering results in better brain growth and cognitive outcomes, but accelerates weight gain thus increasing the risk of later metabolic and cardiovascular disease [
9].
MLPT babies inevitably experience a delay between birth and the establishment of full enteral feeds due to immature suck/swallow/breathe coordination, immature gut motility, and delayed supply of sufficient breastmilk. Practices around nutritional support for MLPT babies during this period vary widely as there is little high-quality evidence to guide clinical decision making. The usual practice is to provide intravenous fluids while gradually increasing the volumes of milk given by gastric tube until full enteral feeds are tolerated, and then transitioning to sucking feeds as suck/swallow/breathe coordination matures. However, there are many variations within this general approach. There are no data on whether it is better to start supplemental milk early, either donor milk or formula, or to wait until the mother’s breastmilk is available. Whilst waiting for full milk feeds to be tolerated, there are no data on whether the provision of dextrose alone is sufficient, despite the inevitable catabolism and accumulating nitrogen deficit [
10], or whether babies should receive parenteral nutrition containing protein. All of these approaches are in use around the world. A study of nutritional support of 33–35 week gestation late-preterm infants in 10 California and Massachusetts hospitals found the rate of intravenous nutrition use varied from 5 to 66% and the rate of discharge with an enriched formula varied from 5 to 71% [
11].
Taste and smell also may be important in food tolerance. Even before ingestion of food, taste and smell initiate metabolic processes through secretion of hormones such as insulin and ghrelin [
12]. However, the role that these senses play is not usually considered in the care of preterm infants, despite preterm infants having functional taste receptors from 18 weeks’ gestation and flavour perception from around 24 weeks’ gestation [
13]. Taste receptors in the mouth relay signals to the brainstem and higher centres, leading to activation of the cephalic phase response and the release of appetite hormones in saliva [
14]. These salivary hormones are postulated to play a role in metabolism [
14]; indeed, impaired oral nutrient sensing is associated with increased energy intake and a greater body mass index [
15]. A pilot trial exposing very preterm infants to the taste and smell of milk before each tube-feed found that infants in the intervention group reached full enteral feeds and tended to have the nasogastric tube removed at an earlier gestational age [
16]. These data suggest that the simple intervention of providing taste and smell stimuli before gastric tube feeds may enhance feed tolerance.
Thus, we hypothesise that:
1.
Early nutrition supplementation including protein will prevent a protein deficit leading to
a.
Body composition at 4 months’ corrected age similar to that of term-born children, and
b.
Improved neurodevelopmental outcomes
2.
Exposure of MLPT babies to taste and smell before each feed before establishment of full breastfeeds will decrease time to full enteral feeds and full sucking feeds.
Aims
To investigate the impact of different feeding strategies currently in use on feed tolerance, body composition, and on developmental outcome in MLPT babies.
Acknowledgements
The authors would like to thank all those in the DIAMOND study group: Tanith Alexander1, 2, Jane M. Alsweiler3, 4, Sharin Asadi1, Friederike Beker5, 6 Frank H. Bloomfield1, 3, David Cameron-Smith1, 7, 8, Clara Y.L. Chong1, Caroline A. Crowther1, Laura Galante1, Jane E. Harding1, Yannan Jiang9, Michael P. Meyer2, 4, Amber Milan1, Mariana Muelbert1, Justin M. O’Sullivan1, Jutta M. van den Boom10, Clare R. Wall11.
1.Liggins Institute, University of Auckland, Auckland, New Zealand, 2. Neonatal Unit, Kidz First, Middlemore Hospital, Auckland, New Zealand, 3. Newborn Services, Auckland City Hospital, Auckland, New Zealand, 4. Department of Paediatrics: Child and Youth Health, 5. Department of Newborn Services, Mater Mothers’ Hospital, Brisbane, QLD, Australia, 6. Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia, 7. Food and Bio-based Products, AgResearch Grasslands, Palmerston North, New Zealand, 8. The Riddet Institute, Massey University, Palmerston North, New Zealand, 9. Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand, 10. Newborn Services, Waitemata District Health Board, Auckland, New Zealand, 11. Department of Nutrition, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.