DOnor Milk to REpair the Full-term Infant MIcrobiome in Infants Born Via Cesarean Section.

NCT06177184 | Recruiting

• 1 other identifier: REB23-1356
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this novel study is to establish proof of concept using a pilot randomized controlled trial to determine the effect of DHM compared to formula supplementation on the microbiome in full-term infants who are born via caesarean section and require supplementation. Secondarily, this study aims to compare the infant health outcomes of sleep and growth between groups to assess if these outcomes are mediated by infant feeding type or potential differences in microbial signatures. Finally, this study will compare maternal outcomes of depression, anger, breastfeeding self-efficacy and breastfeeding rates between groups. The infant gut microbiome plays a critical role in the developing immune, neurologic, and endocrine systems. Yet, most infants experience early life disruptions (ELDs) to their microbiome that have potential long-term health and development impacts. A major source of disruption is caesarean section (c-section) delivery because the infant is born surgically and is not exposed to important commensal bacteria required to establish the infant microbiome. Currently in Canada, over 28% of infants are born via c-section. Exclusive breastfeeding can improve gut microbiota composition in infants who are born via c-section. However, approximately 60% of infants born via c-section require formula supplementation in their first week of life. Evidence indicates that even one bottle of formula can further disrupt the gut microbiome. Donor human milk (DHM) is a superior alternative to formula when supplementation is required as its biotic properties minimize perturbations to the infant gut microbiome and may help to repair the microbiome in infants who experience ELDs. Yet, while DHM is well researched in preterm populations, evidence on the impact of DHM as a therapeutic intervention on the full-term infant gut microbiome is lacking. The hypothesis of this study is: that replacing formula with DHM supplementation will minimize gut microbiome dysbiosis and foster homeostasis following supplementation. In addition, it is hypothesized that improved homeostasis will promote improved sleep and growth outcomes in participant infants. Finally, mothers whose infants receive DHM will have lower depression and anger scores and higher breastfeeding self-efficacy and exclusive breastfeeding rates compared to mothers whose infants receive formula.

Conditions

Microbial Colonization

Outcome Measures

Primary Outcomes (9)

• Infant gut microbiome - shallow shotgun metagenomics (RA)

  Relative abundance

  one week postpartum

• Infant gut microbiome - shallow shotgun metagenomics (RA)

  Relative abundance

  three months postpartum

• Infant gut microbiome - shallow shotgun metagenomics (RA)

  Relative abundance

  six months postpartum

• Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)

  alpha diversity of microbiome

  one week postpartum

• Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)

  alpha diversity of microbiome

  3 months postpartum

• Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)

  alpha diversity of microbiome

  six months postpartum

• Infant gut microbiome - shallow shotgun metagenomics (beta diversity)

  beta diversity of microbiome

  one week postpartum

• Infant gut microbiome - shallow shotgun metagenomics (beta diversity)

  beta diversity of microbiome

  three months postpartum

• Infant gut microbiome - shallow shotgun metagenomics (beta diversity)

  beta diversity of microbiome

  six months postpartum

Secondary Outcomes (29)

• Infant Sleep

  three months postpartum

• Infant Sleep

  six months postpartum

• Infant Growth - weight

  one week postpartum

• Infant Growth - length

  one week postpartum

• Infant Growth - BMI

  one week postpartum

Study Arms (2)

Donor Human Milk

EXPERIMENTAL

Infants randomized to the intervention group will receive DHM each time supplementation is required for the first 7 days of life.

Other: Donor Human Milk - Nutritional Replacement

Standard Care (Infant Formula)

NO INTERVENTION

Infants randomized to the standard care group will receive formula each time supplementation is required for the first 7 days of life.

Interventions

Donor Human Milk - Nutritional Replacement OTHER

All DHM in North America is pasteurized and provided through certified milk banks regulated by the Human Milk Banking Association of North America. DHM for this study will be obtained from the NorthernStar Mothers Milk Bank (NMMB). The milk is pasteurized and rigorously tested according to Human Milk Banking Association of North America guidelines. In Canada, DHM is categorized as food or nutritional therapy and the milk bank is monitored and certified by the Canadian Food Inspection Agency. The product used for this study will be the same product that is provided to other hospital units (mainly the neonatal intensive care units) in Alberta and around Canada. The product will not be modified or tampered with in any way.

Donor Human Milk

Eligibility Criteria

• Age: 37 Weeks+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gestation greater than 37 weeks gestation (full-term)
• Caesarean Section delivery
• Intending to breastfeed
• Consent for infant to receive DHM
• Working understanding (proficient in reading and understanding) of English
• Mother has provided signed and dated informed consent and authorization to use protected health information, as required by national and local regulations.
• In the investigator's opinion, the subject mother understands and can comply with protocol requirements, instructions, and protocol-stated restrictions, and is likely to complete the study as planned.

You may not qualify if:

• Diagnosed with clinically significant major congenital malformation that will interfere with breastfeeding or growth
• No intention to breastfeed

Sponsors & Collaborators

• University of Calgary: lead
• University of British Columbia: collaborator
• University of Victoria: collaborator
• NorthernStar Mothers Milk Bank: collaborator

Study Sites (1)

Rockeyview General Hospital

Calgary, Alberta, T2V1P9, Canada

RECRUITING

Related Publications (21)

• Robertson RC, Manges AR, Finlay BB, Prendergast AJ. The Human Microbiome and Child Growth - First 1000 Days and Beyond. Trends Microbiol. 2019 Feb;27(2):131-147. doi: 10.1016/j.tim.2018.09.008. Epub 2018 Oct 24.

  PMID: 30529020 RESULT

• Matenchuk BA, Mandhane PJ, Kozyrskyj AL. Sleep, circadian rhythm, and gut microbiota. Sleep Med Rev. 2020 Oct;53:101340. doi: 10.1016/j.smrv.2020.101340. Epub 2020 May 13.

  PMID: 32668369 RESULT

• Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016 Jul 7;22(7):713-22. doi: 10.1038/nm.4142.

  PMID: 27387886 RESULT

• Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014 Sep 5;5:427. doi: 10.3389/fimmu.2014.00427. eCollection 2014.

  PMID: 25250028 RESULT

• Korpela K, de Vos WM. Infant gut microbiota restoration: state of the art. Gut Microbes. 2022 Jan-Dec;14(1):2118811. doi: 10.1080/19490976.2022.2118811.

  PMID: 36093611 RESULT

• Persaud RR, Azad MB, Chari RS, Sears MR, Becker AB, Kozyrskyj AL; CHILD Study Investigators. Perinatal antibiotic exposure of neonates in Canada and associated risk factors: a population-based study. J Matern Fetal Neonatal Med. 2015 Jul;28(10):1190-5. doi: 10.3109/14767058.2014.947578. Epub 2014 Aug 14.

  PMID: 25053193 RESULT

• Zimmermann P, Curtis N. Effect of intrapartum antibiotics on the intestinal microbiota of infants: a systematic review. Arch Dis Child Fetal Neonatal Ed. 2020 Mar;105(2):201-208. doi: 10.1136/archdischild-2018-316659. Epub 2019 Jul 11.

  PMID: 31296695 RESULT

• Stuivenberg GA, Burton JP, Bron PA, Reid G. Why Are Bifidobacteria Important for Infants? Microorganisms. 2022 Jan 25;10(2):278. doi: 10.3390/microorganisms10020278.

  PMID: 35208736 RESULT

• Liu Y, Qin S, Song Y, Feng Y, Lv N, Xue Y, Liu F, Wang S, Zhu B, Ma J, Yang H. The Perturbation of Infant Gut Microbiota Caused by Cesarean Delivery Is Partially Restored by Exclusive Breastfeeding. Front Microbiol. 2019 Mar 26;10:598. doi: 10.3389/fmicb.2019.00598. eCollection 2019.

  PMID: 30972048 RESULT

• Korpela K, Salonen A, Virta LJ, Kekkonen RA, de Vos WM. Association of Early-Life Antibiotic Use and Protective Effects of Breastfeeding: Role of the Intestinal Microbiota. JAMA Pediatr. 2016 Aug 1;170(8):750-7. doi: 10.1001/jamapediatrics.2016.0585.

  PMID: 27294842 RESULT

• Dai DLY, Petersen C, Hoskinson C, Del Bel KL, Becker AB, Moraes TJ, Mandhane PJ, Finlay BB, Simons E, Kozyrskyj AL, Patrick DM, Subbarao P, Bode L, Azad MB, Turvey SE. Breastfeeding enrichment of B. longum subsp. infantis mitigates the effect of antibiotics on the microbiota and childhood asthma risk. Med. 2023 Feb 10;4(2):92-112.e5. doi: 10.1016/j.medj.2022.12.002. Epub 2023 Jan 4.

  PMID: 36603585 RESULT

• Forbes JD, Azad MB, Vehling L, Tun HM, Konya TB, Guttman DS, Field CJ, Lefebvre D, Sears MR, Becker AB, Mandhane PJ, Turvey SE, Moraes TJ, Subbarao P, Scott JA, Kozyrskyj AL; Canadian Healthy Infant Longitudinal Development (CHILD) Study Investigators. Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life. JAMA Pediatr. 2018 Jul 2;172(7):e181161. doi: 10.1001/jamapediatrics.2018.1161. Epub 2018 Jul 2.

  PMID: 29868719 RESULT

• Francis J, Mildon A, Stewart S, Underhill B, Ismail S, Di Ruggiero E, Tarasuk V, Sellen DW, O'Connor DL. Breastfeeding rates are high in a prenatal community support program targeting vulnerable women and offering enhanced postnatal lactation support: a prospective cohort study. Int J Equity Health. 2021 Mar 3;20(1):71. doi: 10.1186/s12939-021-01386-6.

  PMID: 33658034 RESULT

• Ho NT, Li F, Lee-Sarwar KA, Tun HM, Brown BP, Pannaraj PS, Bender JM, Azad MB, Thompson AL, Weiss ST, Azcarate-Peril MA, Litonjua AA, Kozyrskyj AL, Jaspan HB, Aldrovandi GM, Kuhn L. Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations. Nat Commun. 2018 Oct 9;9(1):4169. doi: 10.1038/s41467-018-06473-x.

  PMID: 30301893 RESULT

• Chong HY, Tan LT, Law JW, Hong KW, Ratnasingam V, Ab Mutalib NS, Lee LH, Letchumanan V. Exploring the Potential of Human Milk and Formula Milk on Infants' Gut and Health. Nutrients. 2022 Aug 29;14(17):3554. doi: 10.3390/nu14173554.

  PMID: 36079814 RESULT

• Peila C, Moro GE, Bertino E, Cavallarin L, Giribaldi M, Giuliani F, Cresi F, Coscia A. The Effect of Holder Pasteurization on Nutrients and Biologically-Active Components in Donor Human Milk: A Review. Nutrients. 2016 Aug 2;8(8):477. doi: 10.3390/nu8080477.

  PMID: 27490567 RESULT

• Merjaneh N, Williams P, Inman S, Schumacher M, Ciurte A, Smotherman C, Alissa R, Hudak M. The impact on the exclusive breastfeeding rate at 6 months of life of introducing supplementary donor milk into the level 1 newborn nursery. J Perinatol. 2020 Jul;40(7):1109-1114. doi: 10.1038/s41372-020-0657-6. Epub 2020 Mar 30.

  PMID: 32231257 RESULT

• Whipps MDM, Yoshikawa H, Demirci JR, Hill J. Estimating the Impact of In-Hospital Infant Formula Supplementation on Breastfeeding Success. Breastfeed Med. 2021 Jul;16(7):530-538. doi: 10.1089/bfm.2020.0194. Epub 2021 Jun 10.

  PMID: 34115545 RESULT

• Wiggins JB, Trotman R, Perks PH, Swanson JR. Enteral Nutrition: The Intricacies of Human Milk from the Immune System to the Microbiome. Clin Perinatol. 2022 Jun;49(2):427-445. doi: 10.1016/j.clp.2022.02.009.

  PMID: 35659095 RESULT

• McCune S, Perrin MT. Donor Human Milk Use in Populations Other than the Preterm Infant: A Systematic Scoping Review. Breastfeed Med. 2021 Jan;16(1):8-20. doi: 10.1089/bfm.2020.0286. Epub 2020 Nov 25.

  PMID: 33237802 RESULT

• Rao S, Esvaran M, Chen L, Keil AD, Gollow I, Simmer K, Wemheuer B, Conway P, Patole S. Probiotic supplementation in neonates with congenital gastrointestinal surgical conditions: a pilot randomised controlled trial. Pediatr Res. 2022 Oct;92(4):1122-1131. doi: 10.1038/s41390-021-01884-x. Epub 2022 Jan 3.

  PMID: 34980887 RESULT

MeSH Terms

Conditions

Communicable Diseases

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Meredith Brockway, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meredith Brockway, PhD

CONTACT

403-689-0970; mbrockwa@ucalgary.ca

Jannette Festival, BN

CONTACT

403-475-6455; director@northernstarmilkbank.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Assessors who are conducting the microbial analysis and statistical analysis will not be aware of which group is intervention and which is control. These groups will be assigned a number (Group1; Group 2).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: An experimental study design in which each participant will be randomized to one of two groups (intervention \[DHM\] or standard care/control \[formula\]).

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: December 20, 2023
• Study Start: October 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 20, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)