Individualized Fortification of Breast Milk

Study Overview
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Brief Summary
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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.

Official Title
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Individualized Fortification of Breast Milk With Fat, Carbohydrate and Protein for Preterm Infants

Conditions
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Postnatal Growth Disorder, Neurodevelopment

Intervention / Treatment
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* Dietary Supplement: Individualized fortification of breast milk
* Dietary Supplement: Routine fortification of breast milk


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Gestational age < 32weeks (maternal dates or early fetal ultrasound); Tolerating an enteral intake of ≥ 100 ml/kg/d for ≥ 24h; Subject is anticipated to receive the intervention for ≥ 3 consecutive weeks after full enteral feeding (≥ 150 mL/kg/d) has been achieved; and Written informed consent has been obtained from the infant's legal representative. Exclusion criteria: 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 Gastrointestinal malformation, major congenital anomalies and chromosomal abnormalities; Babies with enterostoma or short gut syndrome; 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); 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; 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); Participation in another clinical trial that may affect outcomes of this study; or 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: Infants fed more than 25% of mean caloric intake for a consecutive week with formula milk; Fluid restriction < 140mL/kg/d for ≥ 3 consecutive days; Sepsis - all infants with gram-negative sepsis will be removed from the study.

Ages Eligible for Study
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Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualized fortification of breast milk<br>Macronutrient content (for protein, carbohydrate and fat content) will be analyzed of native breast milk batches which had been prepared for 24 hr feeding. Routine fortifier will be added to breast milk batches. Modular products for individual adjustment of protein and/or carbohydrate and/or fat will be given in order to achieve target macronutrient level. | Dietary Supplement: Individualized fortification of breast milk<br>* Lactose, fat and protein content will be measured prior to breast milk fortification. Subsequently, breast milk for preterm infants will individually fortified adjusted by using data from milk analysis.<br>|
| Active Comparator: Routine fortification of breast milk<br>Macronutrient content (for protein, carbohydrate and fat content) will be analyzed of native breast milk batches which had been prepared for 24 hr feeding. Routine fortifier will be added to breast milk batches. | Dietary Supplement: Routine fortification of breast milk<br>* Infants will be fed routine fortified breast milk.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| growth during first three weeks of intervention | change in body weight gain will be accessed daily. | first three weeks during intervention before 36 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| enteral energy intake | fat, carbohydrate, protein, and caloric intake by enteral feeding will be assesed daily | from inclusion at postmentrual age <32 weeks until 36 weeks | 
| neurodevelopment | Bayley Scales of Infant Development III | at 18 month corrected age | 
| weight gain | change in body weight [g] | from inclusion at postmentrual age <32 weeks until 18 month corrected age | 
| body length | change in body length [cm] | from inclusion at postmentrual age <32 weeks until 18 month corrected age | 
| head circumference | change in head circumference [cm] | from inclusion at postmentrual age <32 weeks until 18 month corrected age | 
| body composition | change in body composition measured with air displacement plethysmography (body weight, body volume, calculated fat and lean mass) | from inclusion at postmentrual age <32 weeks until 3 month corrected age | 
| body composition (bio-electrical impedance analysis) | change in body composition measured with bio-electrical impedance analysis (impedance at 5, 50, 100 and 200 kHz, resistance at 50 kHz, reactance at 50 kHz, phase angle at 50 kHz) | from inclusion at postmentrual age <32 weeks until 18 month corrected age | 
| skin fold thickness | change in skin fold thickness [cm] | from inclusion at postmentrual age <32 weeks until 18 month corrected age | 
| feeding intolerance | occurence of feeding intolerance defined by vomitting, bloody gastric residuals, or abnormal abdomen (tender, discolored, absent bowel sounds) | during intervention (postmentrual age <32 weeks until 36 weeks) | 
| morbidity |  | during intervention (postmentrual age <32 weeks until 36 weeks) | 
| nutrient's blood parameter | triglycerides, glucose, blood urea nitrogen, blood gases, electrolytes, pH | during intervention (postmentrual age <32 weeks until 36 weeks) | 
| breast milk analysis | using near-infrared analysis breast milk's macronutrients (fat, lactose and protein) will be measured daily | during intervention (postmentrual age <32 weeks until 36 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postnatal development, Breast milk fortification, Composition of breast milk