Target Fortification of Breast Milk: How Often Breast Milk Needs to be Measured?

Study Overview
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Brief Summary
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It has been observed that target fortification on different schedules leads to meal to meal variation. It changes the ratio of protein to energy and the percentage of carbohydrate to non-protein energy which may, affect growth. In the past, the investigators have analyzed the outcomes of breast milk composition when target fortification is done with different analysis schedules. The investigators were able to measure the macronutrient intake for different milk analysis schedules via a theoretical model and show that the more frequent schedules reduce the variation of fortified-breast milk, whereas a reduced schedule leads to a high variation of macronutrients. It was observed that, in all the breast milk samples measured twice per week, infants achieved on average the recommended macronutrients in line with current recommendations. Nonetheless, the model only looks at the macronutrient intake and does not investigates the relationship between macronutrient variation and its effect on growth. The aim of the current study is to compare a frequent schedule of measurement of macronutrient analysis with a reduced schedule of measurement and to study its affect on growth, protein accretion and metabolic parameter.

Official Title
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Target Fortification of Breast Milk: The Effect of Different Schedules for Milk Analysis on the Growth and Development of Preterm Infants.

Conditions
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Postnatal Growth Disorder

Intervention / Treatment
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* Dietary Supplement: Fortification with modular protein
* Dietary Supplement: Fortification with modular carbohydrate
* Dietary Supplement: Fortification with modular fat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age < 30 weeks (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; Written informed consent has been obtained from the infant's legal representative. Multiple births: Each infant will be included in the study if he/she meets the study criteria, and siblings will be individually randomized to one or other of the treatment arms. Discussion with Most Responsible Physician (MRP) and the staff in order to discuss any potential transfer during the next 7 days. Exclusion Criteria: Gastrointestinal malformation, major congenital anomalies and chromosomal abnormalities; Babies with enterostoma or short gut syndrome; Infants fed more than 25% of mean caloric intake for a consecutive week with formula milk; Fluid restriction <140 mL/kg/d for ≥ 3 consecutive days; Sepsis - all infants with gram-negative sepsis will be removed from the study; 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/L and creatinine of 130mmol/L Participation in another clinical trial that may provide an alternative nutritional intervention, which might affect the outcomes of this study. outcomes of this study; Probability of transfer to another neonatal intensive care unit or level II nursery outside the McMaster Children's Hospital, as discussed with the most responsible physician (MRP)

Ages Eligible for Study
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Maximum Age: 29 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: 5 milk analysis<br>Macronutrient content (for protein, carbohydrate and fat content) will be analyzed five times per week, of native breast milk batches which had been prepared for 24 hours 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: Fortification with modular protein<br>* Modular product supplementation is based on most recent breast analysis done for the participant.<br>Dietary Supplement: Fortification with modular carbohydrate<br>* Modular product supplementation is based on most recent breast analysis done for the participant.<br>Dietary Supplement: Fortification with modular fat<br>* Modular product supplementation is based on most recent breast analysis done for the participant.<br>|
| Experimental: 1 milk analysis<br>Macronutrient content (for protein, carbohydrate and fat content) will be analyzed once per week of native breast milk batches which had been prepared for 24 hours 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: Fortification with modular protein<br>* Modular product supplementation is based on most recent breast analysis done for the participant.<br>Dietary Supplement: Fortification with modular carbohydrate<br>* Modular product supplementation is based on most recent breast analysis done for the participant.<br>Dietary Supplement: Fortification with modular fat<br>* Modular product supplementation is based on most recent breast analysis done for the participant.<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 |  | first three weeks during intervention before 36 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Nutrient intake (kcal, lactose, protein, fat) measured with conventional milk analysis |  | from inclusion at postmenstrual age <30 weeks until 36 weeks of gestation | 
| Weight Gain |  | from inclusion at postmenstrual age <30 weeks until 36 weeks of gestation or discharge | 
| Oxidative stress by 8-Oxo-2'-deoxyguanosine metabolites in urine | Measured by mass spectroscopy | from inclusion at postmenstrual age <30 weeks until discharge | 
| Protein synthesis analyzed by nitrogen excretion in urine [µmol/mL] |  | first three weeks during intervention before 36 weeks of gestation | 
| Feeding intolerance questionaire | volume of gastric residuals, color of gastric residuals, vomiting, abdominal girth, abdominal distention | from inclusion at postmenstrual age <30 weeks until discharge | 
| Fat mass [g] | Measured with bioelectrical impedance analysis | from inclusion at postmenstrual age <30 weeks until discharge | 
| Lean mass [g] | Measured with bioelectrical impedance analysis | from inclusion at postmenstrual age <30 weeks until discharge | 
| Head circumference [cm] | Measured by tape | from inclusion at postmenstrual age <30 weeks until discharge | 
| Body length [cm] | Measured by length board | from inclusion at postmenstrual age <30 weeks until discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Target Fortification, Breast milk analysis, Nutrition, Macronutrient intake, Protein accretion