|- candidate number||10848|
|- NTR Number||NTR3225|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||5-jan-2012|
|- Secondary IDs||NL37296.029.11 / 2011/217; CCMO / METc VUmc |
|- Public Title||Early Nutrition Study.|
|- Scientific Title||The Early Nutrition study: Effect Of Donor Human Milk On Severe Infections And Mortality In VLBW Infants.|
|- ACRONYM||ENS (Early Nutrition Study)|
|- hypothesis||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.|
|- Healt Condition(s) or Problem(s) studied||Premature infants, Breastfeeding , Low birth weight, Necrotizing enterocolitis, Late onset sepsis|
|- Inclusion criteria||1. Birth weight < 1500 gram;|
2. Written informed consent.
|- Exclusion criteria||1. Child of mother that abused drugs and/or alcohol during pregnancy;|
2. Major congenital anomalies or birth defects;
3. Congenital infection, defined as: Early Onset Sepsis or suspected TORCHES infection;
4. Perinatal asphyxia with (umbilical or first neonatal) pH < 7.0;
5. Intake of any cowís milk based products prior to randomization.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-feb-2012|
|- planned closingdate||1-feb-2014|
|- Target number of participants||396|
|- Interventions||Infants in group A will receive banked donor milk in case their own motherís milk falls short. Infants in group B will receive preterm formula currently in use if their own motherís 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 motherís + breast milk fortifier or otherwise preterm formula. |
|- Primary outcome||Incidence of the combined outcome of serious late-onset infections (sepsis/ meningitis and NEC) and/ or death occurring between age 72 hours and 60 days.|
|- Secondary outcome||1. Composition of fecalmicrobiota of the first stool and at day 10, 1 month and during regular follow-up at 2 years of age is determined;|
2. Time to full enteral feeding, defined as an enteral intake greater than or equal to 120 mL per kg per day;
3. Days on parenteral nutrition (lipids or amino acids);
4. Growth rate (body weight, length and head circumference) will be recorded weekly during NICU admission as part of routine care. SDS scores will be calculated;
5. Bone density by ultra sound (only in centres where this is recorded as part of routine care) weekly during NICU admission.
At 2 years of age:
1. Bayley Scores of Infant Development III, which are assessed as part of routine care during standard follow-up at 2 years of age;
2. Growth rate (weight, length and head circumference), which are assessed as part of routine care during standard follow-up at 2 years of age.
|- Trial web site||www.moedermelkbank.nl, www.neonatologiestudies.nl (follows)|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. J.B. Goudoever, van|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. J.B. Goudoever, van|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|Mead Johnson Nutrition|
|- Brief summary||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 NICUís, 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 motherís milk is to be preferred because it reduces the incidence of sepsis and NEC. When own motherís 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.
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.
Double blind randomized controlled trial.
VLBW infants admitted to one of the participating centers.
If own motherís 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 Ďadd-oní therapy to own motherís 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).
|- Main changes (audit trail)||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
- 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
- Primary Outcome: bone mineral content (BMC) and body composition measured by DXA
- Secondary Outcomes: ultrasound Ďsound of speedí (SOS) measurements, incidence of
feeding intolerance and nephrocalcinosis, time to full enteral feeding and calcium and
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-
- Intervention: original ENS intervention
- Primary Outcome: Urinary cortisol metabolites at days 10 and 30.
- Secondary Outcome: Urinary cortisol metabolites at 2 years of age.
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.
- Intervention: original ENS intervention
- Primary Outcome: Body composition (body fat%, fat-free mass, lean mass, fat mass, fat-
free mass index, fat mass index) and growth at 1, 2 and 5 years of age.
- Secondary Outcomes: timepoint of introduction en type of complementary feeding and development of allergic diseases.
|- RECORD||5-jan-2012 - 28-jun-2014|