EXPRESS-Nutrium

Long-term health effects of neonatal nutrition for extremely premature babies

BACKGROUND

Medical advances have improved survival rates for premature babies, and today, neonatal intensive care can save the lives of even extremely premature babies. Even if most of these children avoid serious disability, there is a significant risk of long-term sight impairment and poorer cognitive development. In Sweden, survival among the least developed children, born at 23–26 weeks’ gestation, is among the best in the world, so the scope to further reduce mortality is limited and the major challenge is rather to improve the long-term health of these children at high risk.

An increasing number of studies indicate that many chronic diseases in children and adults are caused by disturbed growth and development of organ systems in the womb or in early infancy. Nutritional factors could ‘programme’ the metabolism using epigenetic mechanisms and influence the risk of conditions including diabetes and cardiovascular disease in adulthood.

Giving optimal nutrition to extremely premature babies is a very difficult task because of the babies’ fragile state of health and very high nutritional needs. The smallest babies need to increase their weight by a multiple of five over 3–4 months. Malnutrition is unfortunately a major problem among these children and they often demonstrate serious delayed growth that can continue up to school age. It is not known what role this early malnutrition plays for the development of the central nervous system, but the brain should normally grow and develop very rapidly during this period. Protein, energy, calcium, phosphorus, iron, zinc, sodium, vitamin D and polyunsaturated fatty acids are some of the nutrients that are essential to the development of the brain, and premature babies often have insufficient intake of these. It must also be borne in mind that excessive intake of some nutrients can have a negative impact on babies.

There is a major lack of evidence-based data on the nutritional needs of extremely premature babies and this has led to major variation in local practice.

RESEARCH QUESTION

In the Nutrium Express study, we will study the links between nutritional intake during care in a neonatal unit (the first three months of the baby’s life) and the child’s early growth, early illness (e.g. retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), early brain development (MRI at full term in a sub-group) and later health (cognitive development, heart and lung function and growth) up to at least six years of age.

METHOD

Population: All extremely premature babies (< 27 weeks’ gestation) born between 1 April 2004 and 31 March 2007 in Sweden (707 live births) are included in a cohort as part of the national EXPRESS study.

Nutrition and growth data

In the present study, we have gathered detailed nutrition and growth data for all the children in the EXPRESS cohort using a web-based IT system that we have developed (Nutrium, www.nutrium.se).

The following patient records data has been gathered:

1)      Daily intake of all food products: a) Enteral nutrition (mother’s or donated breast milk, formula) b) Nutritional analysis of the macronutrient content of the breast milk c) Enteral enrichment powder and nutritional supplements d) Parenteral nutrition e) Blood products and other parenteral fluid. This is registered on a daily basis for the first four weeks of life and then once a week (day 35, 42, etc.) during the period of care.

2)      Growth data: The readings taken are weight, height and head circumference during the period of care.

3)      Biomarkers: All readings taken for the following nutrition-related biomarkers: glucose, s-urea, s-albumin, s-ferritin, Hb, reticulocytes, s-Ca, s-phosphate, s-Na, s-K, s-Cl, pH, base excess and folic acid.

This unique, detailed data collection, in combination with detailed background data from the EXPRESS study, will offer unique opportunities to study the role of early nutrition and growth in later illness, independent of other risk factors.

Ethical approval: An application for the project has been approved by the Regional Ethical Review Board, Lund. Reg. No 138/2008. 

PRELIMINARY RESULTS

We have recently presented preliminary results of the study at a number of national and international meetings, showing that Swedish extremely premature babies have a low intake of macronutrients during the first 28 days of life compared with their estimated needs, especially of protein and energy, and that they demonstrate marked postnatal delayed growth. Our observation of significant positive links between macronutrient intake and weight change imply that increased early nutrient intake could prevent delayed postnatal growth in this risk group.

Participants: Reader Magnus Domellöf (principal investigator), Elisabeth Stoltz Sjöström (doctoral student) and Inger Öhlund (PhD), Umeå University. Dr Fredrik Ahlsson (MD, PhD) and Professor Fredrik Serenius, Uppsala University. Professor Mikael Norman, Karolinska Institutet. Professor Vineta Fellman, Professor Karel Marsal and Reader Karin Källén, Lund University. Eva Engström (MD, PhD) and Professor Ann Hellström, University of Gothenburg. Elisabeth Olhager (MD, PhD), Linköping University.

SIGNIFICANCE

The results will have direct clinical significance as data to support new, improved nutrition regimes for extremely premature babies and it is hoped that it will thus lead to improved growth, development and later health of this new generation of survivors.