Targeted Fortification of Donor Breast Milk in Preterm Infants

NCT ID: NCT04294368

Last Updated: 2025-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-09

Study Completion Date

2026-03-31

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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Control group to receive standard fortification of donor breast milk. Experimental group to receive targeted fortification of donor breast milk.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Control

Standard fortification of breast milk

Group Type OTHER

Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid

Intervention Type DIETARY_SUPPLEMENT

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.

Similac Liquid Protein Fortifier

Intervention Type DIETARY_SUPPLEMENT

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.

Nestle Microlipid

Intervention Type DIETARY_SUPPLEMENT

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.

Medica Nutrition SolCarb

Intervention Type DIETARY_SUPPLEMENT

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.

Analysis with Miris (AB) Human Milk Analyzer

Intervention Type OTHER

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.

Experimental

Targeted fortification of breast milk

Group Type EXPERIMENTAL

Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid (Targeted Fortification)

Intervention Type DIETARY_SUPPLEMENT

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.

Similac Liquid Protein Fortifier (Targeted Fortification)

Intervention Type DIETARY_SUPPLEMENT

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.

Nestle Microlipid (Targeted Fortification)

Intervention Type DIETARY_SUPPLEMENT

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

Medica Nutrition SolCarb (Targeted Fortification)

Intervention Type DIETARY_SUPPLEMENT

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

Analysis with Miris (AB) Human Milk Analyzer

Intervention Type OTHER

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.

Interventions

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Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid

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.

Intervention Type DIETARY_SUPPLEMENT

Similac Liquid Protein Fortifier

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.

Intervention Type DIETARY_SUPPLEMENT

Nestle Microlipid

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.

Intervention Type DIETARY_SUPPLEMENT

Medica Nutrition SolCarb

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.

Intervention Type DIETARY_SUPPLEMENT

Similac Human Milk Fortifier Extensively Hydrolyzed Protein Concentrated Liquid (Targeted Fortification)

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.

Intervention Type DIETARY_SUPPLEMENT

Similac Liquid Protein Fortifier (Targeted Fortification)

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.

Intervention Type DIETARY_SUPPLEMENT

Nestle Microlipid (Targeted Fortification)

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

Intervention Type DIETARY_SUPPLEMENT

Medica Nutrition SolCarb (Targeted Fortification)

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

Intervention Type DIETARY_SUPPLEMENT

Analysis with Miris (AB) Human Milk Analyzer

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.

Intervention Type OTHER

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
Minimum Eligible Age

1 Day

Maximum Eligible Age

21 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marianne Garland, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Columbia University Medical Center/ New York - Presbyterian

New York, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Marianne Garland, MD

Role: CONTACT

212 305 0952

Facility Contacts

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Marianne Garland, MD

Role: primary

References

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Arslanoglu S, Boquien CY, King C, Lamireau D, Tonetto P, Barnett D, Bertino E, Gaya A, Gebauer C, Grovslien A, Moro GE, Weaver G, Wesolowska AM, Picaud JC. Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification. Front Pediatr. 2019 Mar 22;7:76. doi: 10.3389/fped.2019.00076. eCollection 2019.

Reference Type BACKGROUND
PMID: 30968003 (View on PubMed)

Billard H, Simon L, Desnots E, Sochard A, Boscher C, Riaublanc A, Alexandre-Gouabau MC, Boquien CY. Calibration Adjustment of the Mid-infrared Analyzer for an Accurate Determination of the Macronutrient Composition of Human Milk. J Hum Lact. 2016 Aug;32(3):NP19-27. doi: 10.1177/0890334415588513. Epub 2015 Jun 2.

Reference Type BACKGROUND
PMID: 26037506 (View on PubMed)

Fusch C. Avoiding Postnatal Growth Retardation by Individualized Fortification of Breast Milk: Implications for Somatic and Neurodevelopmental Outcomes. Breastfeed Med. 2019 Apr;14(S1):S15-S17. doi: 10.1089/bfm.2019.0031. No abstract available.

Reference Type BACKGROUND
PMID: 30985203 (View on PubMed)

Fusch G, Rochow N, Choi A, Fusch S, Poeschl S, Ubah AO, Lee SY, Raja P, Fusch C. Rapid measurement of macronutrients in breast milk: How reliable are infrared milk analyzers? Clin Nutr. 2015 Jun;34(3):465-76. doi: 10.1016/j.clnu.2014.05.005. Epub 2014 May 17.

Reference Type BACKGROUND
PMID: 24912866 (View on PubMed)

Gidrewicz DA, Fenton TR. A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. BMC Pediatr. 2014 Aug 30;14:216. doi: 10.1186/1471-2431-14-216.

Reference Type BACKGROUND
PMID: 25174435 (View on PubMed)

Horbar JD, Ehrenkranz RA, Badger GJ, Edwards EM, Morrow KA, Soll RF, Buzas JS, Bertino E, Gagliardi L, Bellu R. Weight Growth Velocity and Postnatal Growth Failure in Infants 501 to 1500 Grams: 2000-2013. Pediatrics. 2015 Jul;136(1):e84-92. doi: 10.1542/peds.2015-0129.

Reference Type BACKGROUND
PMID: 26101360 (View on PubMed)

John A, Sun R, Maillart L, Schaefer A, Hamilton Spence E, Perrin MT. Macronutrient variability in human milk from donors to a milk bank: Implications for feeding preterm infants. PLoS One. 2019 Jan 25;14(1):e0210610. doi: 10.1371/journal.pone.0210610. eCollection 2019.

Reference Type BACKGROUND
PMID: 30682200 (View on PubMed)

Morlacchi L, Mallardi D, Gianni ML, Roggero P, Amato O, Piemontese P, Consonni D, Mosca F. Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study. J Transl Med. 2016 Jul 1;14(1):195. doi: 10.1186/s12967-016-0957-y.

Reference Type BACKGROUND
PMID: 27370649 (View on PubMed)

Montjaux-Regis N, Cristini C, Arnaud C, Glorieux I, Vanpee M, Casper C. Improved growth of preterm infants receiving mother's own raw milk compared with pasteurized donor milk. Acta Paediatr. 2011 Dec;100(12):1548-54. doi: 10.1111/j.1651-2227.2011.02389.x. Epub 2011 Jul 14.

Reference Type BACKGROUND
PMID: 21707744 (View on PubMed)

O'Connor DL, Ewaschuk JB, Unger S. Human milk pasteurization: benefits and risks. Curr Opin Clin Nutr Metab Care. 2015 May;18(3):269-75. doi: 10.1097/MCO.0000000000000160.

Reference Type BACKGROUND
PMID: 25769062 (View on PubMed)

Quan M, Wang D, Gou L, Sun Z, Ma J, Zhang L, Wang C, Schibler K, Li Z. Individualized Human Milk Fortification to Improve the Growth of Hospitalized Preterm Infants. Nutr Clin Pract. 2020 Aug;35(4):680-688. doi: 10.1002/ncp.10366. Epub 2019 Jul 3.

Reference Type BACKGROUND
PMID: 31268194 (View on PubMed)

Rochow N, Fusch G, Choi A, Chessell L, Elliott L, McDonald K, Kuiper E, Purcha M, Turner S, Chan E, Xia MY, Fusch C. Target fortification of breast milk with fat, protein, and carbohydrates for preterm infants. J Pediatr. 2013 Oct;163(4):1001-7. doi: 10.1016/j.jpeds.2013.04.052. Epub 2013 Jun 12.

Reference Type BACKGROUND
PMID: 23769498 (View on PubMed)

Zhu M, Yang Z, Ren Y, Duan Y, Gao H, Liu B, Ye W, Wang J, Yin S. Comparison of macronutrient contents in human milk measured using mid-infrared human milk analyser in a field study vs. chemical reference methods. Matern Child Nutr. 2017 Jan;13(1):10.1111/mcn.12248. doi: 10.1111/mcn.12248. Epub 2016 Feb 23.

Reference Type BACKGROUND
PMID: 26914990 (View on PubMed)

Other Identifiers

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AAAS6625

Identifier Type: -

Identifier Source: org_study_id

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