Clinical trial NCT01609894: Individualized Fortification of Breast Milk
Official title: Individualized Fortification of Breast Milk With Fat, Carbohydrate and Protein for Preterm Infants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postnatal Growth Disorder
Neurodevelopment
Keywords: Postnatal development
Breast milk fortification
Composition of breast milk
Lead sponsor: McMaster Children's Hospital
Sponsor class: OTHER
First posted: 2012-06-01
Enrollment: 112
Sex: ALL
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The proposed research will investigate individualized fortification of breast milk based on daily milk analysis of carbohydrate, protein, and fat content in a randomized double blind controlled trial. The combination of additional fat, carbohydrate and protein and commercial fortifier will be added to ensure that the milk contains the target amounts of nutrient. Growth and development of these infants will be compared with that of infants fed mother's milk that has been supplemented with the current standard amounts. The postnatal growth of the infants will be assessed by measuring weight, length and head circumference and fat and lean mass using highly accurate, non-invasive methods throughout the intervention period and at the first follow-up visit after discharge at 3 months. Neurological development will be analyzed at the age of 18 months.

The investigators hypothesize that individualized fortification of breast milk improves the nutritional intake of preterm infants, optimizing growth, and thus this will positively impact neurodevelopment and health.


Eligibility criteria: Inclusion criteria:

1. Gestational age \< 32weeks (maternal dates or early fetal ultrasound);
2. Tolerating an enteral intake of ≥ 100 ml/kg/d for ≥ 24h;
3. Subject is anticipated to receive the intervention for ≥ 3 consecutive weeks after full enteral feeding (≥ 150 mL/kg/d) has been achieved; and
4. Written informed consent has been obtained from the infant's legal representative.

Exclusion criteria:

1. Infants with intrauterine growth restriction, small for gestational age defined by a weight less than 3rd percentile using sex specific reference data for birth weight
2. Gastrointestinal malformation, major congenital anomalies and chromosomal abnormalities;
3. Babies with enterostoma or short gut syndrome;
4. Necrotizing enterocolitis, defined by feeding intolerance associated with positive x-ray findings (pneumatosis intestinalis - Bell Stage 2; air in the biliary tract or free air in the peritoneum - Bell Stage 3);
5. Renal disease, defined by symptoms (oliguria, anuria, proteinuria, hematuria) associated with an increased blood urea nitrogen 10 mmol/L79 and creatinine of 130 mmol/L80;
6. Hepatic dysfunction, defined by jaundice (direct bilirubin \>1.0 mg/dl) that is associated with one or more abnormal liver function tests (AST, ALT or GGT);
7. Participation in another clinical trial that may affect outcomes of this study; or
8. Probability of transfer to another NICU or level II nursery outside the McMaster Children's Hospital before the minimum period of three weeks is completed.

Post-randomisation exclusion criteria:

1. Infants fed more than 25% of mean caloric intake for a consecutive week with formula milk;
2. Fluid restriction \< 140mL/kg/d for ≥ 3 consecutive days;
3. Sepsis - all infants with gram-negative sepsis will be removed from the study.

Primary outcomes:
measure: growth during first three weeks of intervention
timeFrame: first three weeks during intervention before 36 weeks of gestation
Secondary outcomes:
measure: enteral energy intake
timeFrame: from inclusion at postmentrual age <32 weeks until 36 weeks
measure: neurodevelopment
timeFrame: at 18 month corrected age
measure: weight gain
timeFrame: from inclusion at postmentrual age <32 weeks until 18 month corrected age
measure: body length
timeFrame: from inclusion at postmentrual age <32 weeks until 18 month corrected age
measure: head circumference
timeFrame: from inclusion at postmentrual age <32 weeks until 18 month corrected age
measure: body composition
timeFrame: from inclusion at postmentrual age <32 weeks until 3 month corrected age
measure: body composition (bio-electrical impedance analysis)
timeFrame: from inclusion at postmentrual age <32 weeks until 18 month corrected age
measure: skin fold thickness
timeFrame: from inclusion at postmentrual age <32 weeks until 18 month corrected age
measure: feeding intolerance
timeFrame: during intervention (postmentrual age <32 weeks until 36 weeks)
measure: morbidity
timeFrame: during intervention (postmentrual age <32 weeks until 36 weeks)
measure: nutrient's blood parameter
timeFrame: during intervention (postmentrual age <32 weeks until 36 weeks)
measure: breast milk analysis
timeFrame: during intervention (postmentrual age <32 weeks until 36 weeks)
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Faculty of Health Science, McMaster Children's Hospital
state: Ontario
Study officials:
affiliation: McMaster Children's Hospital
name: Christph Fusch, MD, PhD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fabrizio V, Trzaski JM, Brownell EA, Esposito P, Lainwala S, Lussier MM, Hagadorn JI. Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk. Cochrane Database Syst Rev. 2020 Nov 23;11(11):CD013465. doi: 10.1002/14651858.CD013465.pub2.
citation: Rochow N, Fusch G, Ali A, Bhatia A, So HY, Iskander R, Chessell L, El Helou S, Fusch C. Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial. Clin Nutr. 2021 Jan;40(1):54-63. doi: 10.1016/j.clnu.2020.04.031. Epub 2020 May 6.