Early Nutrition Study.

Rationale:

Lack of enteral nutrition results in intestinal atrophy potentially causing increased bacterial translocation, thereby making VLBW infants more prone to sepsis. According to current feeding protocols in NICU’s, minimal enteral feeding is initiated within 6 hours after birth. After premature delivery the onset of lactation is often delayed and therefore VLBW infants are often being fed with preterm formula during the first few days of life. Feeding VLBW infants with own mother’s milk is to be preferred because it reduces the incidence of sepsis and NEC. When own mother’s milk is not available during this period, donor milk might be of benefit to these infants when compared to formula. We hypothesize that feeding VLBW infants with a diet that is completely based on human milk during the first 10 days of life will result in a decrease in the incidence of serious infections, necrotizing enterocolitis (NEC), and neonatal mortality.



Objective:

To determine whether (supplemental) human donor milk has beneficial effects (in terms of reduction of infectious episodes and mortality) when compared to (supplemental) preterm formula during the first 10 days of life in VLBW infants.



Study design:

Double blind randomized controlled trial.



Study population:

VLBW infants admitted to one of the participating centers.



Intervention:

If own mother’s milk is not available in sufficient amounts, the intervention group (group A) will receive additional donor milk and the control group (group B) will receive additional standard preterm formula. Donor milk and formula therefore serve as ‘add-on’ therapy to own mother’s milk.



Main study parameters/endpoints:

Main endpoint: Combined incidence of serious infections/NEC and death.

Secondary endpoints: Composition of fecal microbiota, time to full enteral feeding, days on TPN, growth rate, bone density. Bayley Scores of Infant Development III (at 2 years of age), growth rate (at 2 years of age).

28-jun-2014: Three amendments were added (MEC approval for all):
1. Early Supplementation study Amendment (applicable in St. Radboud UMC Nijmegen (RUNMC) en VUmc Amsterdam)
- Rationale: Preterm born infants miss out on active fetal mineralization in utero during

2. Adrenocortical function amendment (applicable in VUmc)
- Rationale: There is a male disadvantage in neonatal mortality, and in acute and chronic
conditions after very preterm birth, which could be partially counteracted by nutritional
strategies. We speculate that variation in the adrenocortical function underlie these sex-
specific observations

3. Body Composition amendment (applicable in VUmc and AMC Amsterdam)
- Rationale: It is likely that the pattern of body composition in preterm infants is in part
a consequence of the nutrition they receive during the first period of life. From term
infants it is known that throughout the first year of life, formula fed infants have lower
fat mass compared to breast fed infants with a switch at 12 months of age. It is possible
that this trend continues in later life. We hypothesize that feeding VLBW infants with a
diet that is completely based on human milk during the first period of life will result in a
lower fat percentage in later life.

We hypothesize that feeding VLBW infants with a diet that is completely based on human milk during the first 10 days of life will result in a decrease in the incidence of serious infections, necrotizing enterocolitis (NEC), and neonatal mortality.

N/A

Infants in group A will receive banked donor milk in case their own mother’s milk falls short. Infants in group B will receive preterm formula currently in use if their own mother’s milk falls short. Infants will receive the study diets until they are 10 days of age. After the intervention period infants will receive the standard feeding regimen, that is (if available) milk of the own mother’s + breast milk fortifier or otherwise preterm formula.

1. Early Supplementation study Amendment (applicable in St. Radboud UMC Nijmegen (RUNMC) en VUmc Amsterdam)
- Intervention: Infants born at RUNMC are randomized to either participate in the Early
the third trimester and are therefore at risk of reduced bone mineral content (BMC),
which may lead to disease in later life. Minerals are administered parentally and via
breast milk fortifier. However, fear for nephrocalcinosis and feeding intolerance makes
clinicians prudent to administer breast milk fortifier from birth onwards, which may lead
to osteopenia. It is currently unknown what is the most optimal timing, amount and
route to supply minerals to preterm infants.

Nutrition Study (and therefore receive late mineral supplementation) or to receive early
(day of life 4-5) mineral supplementation according to the standard feeding protocol at
the RUNMC.

2. Adrenocortical function amendment (applicable in VUmc)
- Intervention: original ENS intervention

3. Body Composition amendment (applicable in VUmc and AMC Amsterdam)
- Intervention: original ENS intervention