Short summary

This is a RCT on postdischarge nutrition in 320 very-preterm-born infants with a gestational age of ?32 weeks. Infants breastfed at discharge from the hospital were randomly assigned to receive unfortified or fortified mother's milk, whereas those who were not breastfed received a preterm formula. The intervention lasted until 4 mo of corrected age. 

At 6 years of age a follow-up of 281 VPI was performed. Data on growth including a dual-energy X-ray absorptiometry, blood samples, IQ and allergy was collected. 

Rationale

The type of early nutrition has been proven to affect growth, neurodevelopmental outcome and body composition in childhood among very preterm born infants (VPI). To ensure catch-up growth and optimal brain growth among VPIs, a high protein diet during hospital stay has been adopted in most developed countries; however, early, accelerated catch-up growth may increase the risk of developing metabolic syndrome (MetS) in childhood and adulthood. 

Furthermore, catch-up growth may continue after hospital discharge. It is therefore important also to focus on post discharge nutrition. Human milk appears to be protective against the development of MetS in both in term-born and preterm-born children, but does not meet the caloric requirements of VPIs. Therefore, fortifier is added to the mother's own milk or donor milk during the hospital stay, and preterm formulas are given when human milk is unavailable. It is unknown if fortifier added to mothers own milk post discharge affects growth and neurodevelopmental outcome in childhood. 

The amount and composition of protein, fat, and energy differ in formula compared with human milk, and basic body composition and the risk of developing diseases may therefore vary according to the type of early feeding administered during hospital stay and possibly also post discharge. 

The aim of this study was to evaluate the effect of 3 different types of post discharge nutrition and early rapid growth on different metabolic outcomes and developmental outcome and possible risk of allergy at 6 y of age in children born as VPIs. Small for gestational age (SGA) born children will be evaluated separately according to growth and risk of developing Mets.

Description of the cohort

320 infants born with a gestational age (GA) equal to or below 32+0 weeks.

Data and biological material

Data on growth (weight, length and head circumference), DXA, lungfunction, allergy, blood samples (allergy, growth hormone, blood urea nitrogen).

Collaborating researchers and departments

Neonatal unit at Aarhus University Hosptial, Skejby, Kolding and Holbaek hospitals participated in the original RCT.

Publications associated with the project

1. Factors associated with successful establishment of breastfeeding in very preterm infants.G Zachariassen, J Faerk, C Grytter, B H Esberg, P Juvonen, S Halken. Acta Paediatrica 2010 99, pp.1000-1004.

2. Allergic diseases among very preterm infants according to nutrition after hospital discharge. Zachariassen G, Faerk J, Esberg B, Fenger-Gron J, Mortensen S, Christesen HT, Halken  S. Pediatric Allergy and Immunology. Pediatric Allergy Immunology. 2011 Feb 20. 

3. Nutrient Enrichment of Mother's Milk and Growth of Very Preterm Infants After Hospital Discharge. Zachariassen G, Faerk J, Grytter C, Esberg BH, Hjelmborg J, Mortensen S, Thybo Christesen H, Halken S. Pediatrics. 2011 Mar 14.

4. PhD thesis: Nutrition, Growth, and Allergic Diseases among Very Preterm Infants after Hospital Discharge. Zachariassen G, May 25.th. 2012.

5. The content of macronutrients in milk from mothers of very preterm infants is highly variable. Zachariassen G, Fenger-Gron J, Hviid MV & Halken S. Dan Med J. 2013 Jun;60(6):A4631

6.  Preterm dietary study: meal frequency, regurgitation and the surprisingly high use of laxatives among formula-fed infants following discharge. Zachariassen G, Fenger-Gron J. Acta Paediatr. 2014 Mar;103(3):e116-22. Epub 2013 Dec 23.

7. Early nutrition and signs of metabolic syndrome at 6 years of age in children born very preterm. AJCN May 2018. Toftlund L, Agertoft L, Halken S & Zachariassen G.

8. Catch-up Growth, Rapid Weight Growth and Continuous Growth from birth to 6 years of age in Very Preterm Born Children. Toftlund L, Agertoft L, Halken S & Zachariassen G. Accepted for publication in Neonatology april 2018.