Targeted Fortification of Donor Breast Milk in Preterm Infants

Study Overview
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Brief Summary
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This study is a randomized controlled trial comparing standard fortification of donor breast milk to targeted fortification of donor breast milk in preterm infants. The purpose of the study is to determine if there is a benefit to target fortifying donor breast milk in the preterm population. The investigators hypothesize that infants receiving targeted fortification of donor breast milk will have improved growth compared to infants receiving standard fortification of donor breast milk.

Detailed Description
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Breast milk is the best food for premature infants due to its ability to protect infants from necrotizing enterocolitis (NEC) and late onset sepsis. When a premature infant's mother's own milk supply is not enough to provide all the milk that her premature infant needs, donated breast milk is the next best option. One of the downsides of donor breast milk is that it often does not contain as much nutrition for the developing infant compared to the milk of a mother of a premature infant. This means a higher likelihood for poor growth in infant receiving mostly donor breast milk compared to mom's own milk. Due to an inability to easily measure the nutritional content of donor breast milk, standard practice has been to assume that the milk has a certain amount of fat, carbohydrates, and protein. Based on these assumptions, a set amount of additional nutritional fortifier is added to both donor and mom's own breast milk prior to it being given to the infant. Studies show that there is often less nutrition in the donor breast milk to start with than assumed. Technology is now available which uses a small volume sample to measure fat, protein, and carbohydrates in human milk, and hence, calculate the calories in the milk. Using this technology, in this study, the investigators will customize the fortification of donor breast milk by first measuring what is in the milk and then adding any additional fortification that is needed to reach the recommended goals for fat, protein, and carbohydrates. The investigators hypothesize that infants receiving this customized milk, so-called target fortified donor breast milk, will have better growth than infants receiving the standard amount of fortification added to their donor breast milk. The study design involves measurement of macronutrient and calorie content of donor breast milk using a point-of-care human milk analyzer (Miris, AB). The individual macronutrient (protein, fat, and carbohydrate) concentrations will be targeted in the intervention group such that the infant will receive protein of 4 g/kg/day, fat of 6.6 g/kg/day, and carbohydrates of 11.6-13.2 g/kg/day. Fortification will be added in a step-wise fashion daily over a 3-4 day period starting when the infant reaches about 80 ml/kg/day in feeding volume. Fortifiers that may be used in this study include: Abbott Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid, Abbott Liquid Protein, Nestle Microlipid, and Medica Nutrition SolCarb. Participants in the control arm will receive donor milk that is fortified in the standard fashion at this institution; that is, 4 packets of Human Milk Fortifier will be added to 100 ml of donor breast milk. Additional fortification such as liquid protein or microlipid may be added to the donor milk and mom's own milk in response to poor growth for participants in both groups, as is standard of care in this Neonatal Intensive Care Unit (NICU). Patients in both experimental and control groups will always receive mom's own milk first when it is available. Mom's own milk will not be analyzed and will always be fortified in the standard fashion for both groups. The participants will be studied until they reach 34 weeks corrected gestational age.

Official Title
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Targeted Fortification of Donor Breast Milk in Preterm Infants

Conditions
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Prematurity; Extreme, Failure to Thrive in Newborn, Growth Retardation, Growth Failure, Infant Nutrition Disorders

Intervention / Treatment
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* Dietary Supplement: Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid
* Dietary Supplement: Similac Liquid Protein Fortifier
* Dietary Supplement: Nestle Microlipid
* Dietary Supplement: Medica Nutrition SolCarb
* Dietary Supplement: Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid (Targeted Fortification)
* Dietary Supplement: Similac Liquid Protein Fortifier (Targeted Fortification)
* Dietary Supplement: Nestle Microlipid (Targeted Fortification)
* Dietary Supplement: Medica Nutrition SolCarb (Targeted Fortification)
* Other: Analysis with Miris (AB) Human Milk Analyzer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premature infants born </= 30 weeks gestational age Birth Weight </= 1500 grams Exclusion Criteria: Parents do no consent to donor milk Confounders for poor growth such as congenital heart disease, GI diagnoses such as gastroschisis and omphalocele, and or major congenital anomalies Grade III or IV intraventricular hemorrhage diagnoses prior to randomization Small for gestational age (<3% on Fenton Growth Curve) Failure to initiate fortified feeds prior to 3 weeks of life Diagnosis of necrotizing entercolitis prior to randomization Diagnosis of early onset sepsis confirmed with positive culture

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 21 Days

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Control group to receive standard fortification of donor breast milk. Experimental group to receive targeted fortification of donor breast milk.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control<br>Standard fortification of breast milk | Dietary Supplement: Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid<br>* The control group will receive mother's breast milk when it is available. Mother's breast milk will be fortified with 4 packets of Similac Human Milk Fortifier (HMF) per 100 mL. When mother's breast milk is not available, participants will be fed donor breast milk with 4 packets of HMF.<br>Dietary Supplement: Similac Liquid Protein Fortifier<br>* For participants in the control group, additional fortification can be added to the milk for patients in this group in response to poor growth, as is standard of care in the NICU. The standard dose is 1 ml per 30 ml of breast milk.<br>Dietary Supplement: Nestle Microlipid<br>* For participants in the control group, additional fortification can be added to the milk for patients in this group in response to poor growth, as is standard of care in the NICU. The standard dose is 1 ml per 30 ml of breast milk.<br>Dietary Supplement: Medica Nutrition SolCarb<br>* For participants in the control group, additional fortification can be added to the milk for patients in this group in response to poor growth, as is standard of care in the NICU.<br>Other: Analysis with Miris (AB) Human Milk Analyzer<br>* For participants in both the control and the experimental arms, each batch of donor milk will be analyzed using the Miris Human Milk Analyzer. Manufacturer recommendations for milk analysis will be strictly followed.<br>|
| Experimental: Experimental<br>Targeted fortification of breast milk | Dietary Supplement: Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid (Targeted Fortification)<br>* The experimental group will receive mother's breast milk when it is available. Mother's breast milk will be fortified with 4 packets of Similac Human Milk Fortifier (HMF) per 100 mL. When mother's breast milk is not available, participants will be fed donor breast milk with 4 packets of HMF. For participants in the experimental group, the investigators will continue to add fortification. Two packets of HMF per day will be added until goal fortification is reached.<br>Dietary Supplement: Similac Liquid Protein Fortifier (Targeted Fortification)<br>* Participants in the experimental group will receive a dose that will vary depending on the base protein content in the donor breast milk for each particular batch of donor breast milk.<br>Dietary Supplement: Nestle Microlipid (Targeted Fortification)<br>* Participants in the experimental group will receive a dose that will vary depending on the base fat content in the donor breast milk for each particular batch of donor breast milk<br>Dietary Supplement: Medica Nutrition SolCarb (Targeted Fortification)<br>* Participants in the experimental group will receive a dose that will vary depending on the base carbohydrate content in the donor breast milk for each particular batch of donor breast milk<br>Other: Analysis with Miris (AB) Human Milk Analyzer<br>* For participants in both the control and the experimental arms, each batch of donor milk will be analyzed using the Miris Human Milk Analyzer. Manufacturer recommendations for milk analysis will be strictly followed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Weight change in g/kg/day, z-score value, and change in z-score from week-to-week | Up to 11 weeks | 
| Change in length | Length change in cm/kg/day, z-score value, and change in z-score from week-to-week | Up to 11 weeks | 
| Head circumference | Head circumference change in cm/kg/day, z-score value, and change in z-score from week-to-week | Up to 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Days of Length of Stay in NICU | Today number of days in the NICU. | Up to 1 year | 
| Rate of Mortality | Rate of morality during NICU hospitalization. | Up to one year | 
| Number of Feeding Intolerance Events | The number of feeding intolerance events, defined as 1 or more feeds held. | Up to 34 weeks corrected gestational age | 
| Number of Necrotizing Enterocolitis Events | Number of necrotizing enterocolotis events. | Up to 1 year of age | 
| Incidence of Bronchopulmonary dysplasia | Incidence of supplemental oxygen requirement at 36 weeks corrected gestational age. | Up to 1 year of age | 
| Incidence of Retinopathy of prematurity | Incidence of retinopathy of prematurity | Up to 1 year of age | 
| Percentage of Feeds with Donor Milk and Mother's Milk | Percent of feeds that are donor milk and mom's own milk. | Up to 34 weeks corrected gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Milk Analyzer, Miris, Target Fortification, Targeted Fortification, Donor Breast Milk