Clinical trial NCT05815433: Comparing Impacts of Donor Human Milk to Formula Supplementation on the Gut Microbiome of Full-term Infants
Official title: Comparing Impacts of Donor Human Milk to Formula Supplementation on the Gut Microbiome of Full-term Infants Exposed to Antibiotics in Labour: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Microbial Colonization
Keywords: Sleep
Microbiome
Growth
Postpartum depression
Maternal anger
Breastfeeding
Self-efficacy
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: University of British Columbia
name: University of Victoria
name: NorthernStar Mothers Milk Bank
First posted: 2023-04-18
Enrollment: 105
Sex: ALL
Minimum age (years): 37
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An experimental study design in which each participants will be randomized to one of two groups (intervention \[DHM\] or standard care/control \[formula\])
Primary purpose: TREATMENT

Brief summary: The goal of this pilot randomized controlled trial (RCT) is to examine donor human milk (DHM) as a clinical intervention targeted at achieving beneficial microbiome signatures in full-term infants who are exposed to intrapartum antibiotic prophylaxis (IAP) therapy during labour. 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 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 high breastfeeding self-efficacy and exclusive breastfeeding rates compared to mothers whose infants receive formula.

Detailed description: Investigators propose to conduct a pilot clinical RCT in the postpartum hospital setting examining DHM as an intervention provided to full-term infants who are exposed to Group B Streptococcus (GBS) antibiotic prophylaxis during labour. Randomization of participant infants is currently an ethical practice because DHM supplementation is not standard practice in this population; infants receive formula if supplementation of mother's own milk (MOM) is required. Additionally, randomization will allow investigators to determine causal relationships between DHM supplementation compared to formula supplementation on the infant gut microbiome. Finally, conducting research in the clinical setting will allow for pragmatic assessment of DHM as an intervention, enhancing external validity and increasing the likelihood of its implementation into healthcare systems to improve healthcare quality.

Population: The population of interest is vaginally born, full-term infants who are exposed to antibiotics in labour through IAP and whose mothers are planning on breastfeeding.

Recruitment: Mothers greater than 37 weeks' gestation admitted to the postpartum unit who test positive for GBS and deliver vaginally will be screened for participation in the study by nurses on the postpartum unit. Approximately 20% of all pregnant mothers will test positive for GBS and Alberta Health Services protocol indicates that GBS-positive mothers are given intravenous antibiotics during labour. Only mothers who receive the complete Alberta Health Services protocol will qualify for the study. Upon recruitment and completion of informed consent, infants requiring supplementation of MOM will be randomized to the control or intervention group. Investigators will randomize 60 mother-infant dyads, providing adequate power to detect overall microbiome differences (\~30 in each group).

Intervention - Donor Human Milk (DHM): Infants randomized to the intervention group will receive DHM each time supplementation is required for the first 7 days of life. The exposure time of 7 days was selected due to feasibility of DHM cost, and this is the period when breastfeeding is being established and most formula supplementation occurs. Infants in the control group will receive formula when supplementation is required (standard care). All DHM in North America is pasteurized and provided through certified milk banks regulated by the Human Milk Banking Association of North America and DHM for this study will be obtained from the NorthernStar Mothers Milk Bank (NMMB).

Data Collection, Analysis, and Outcomes: The primary outcome for this pilot study will result from comparisons of DHM to formula supplementation groups for differences in microbiome signatures, such as diversity, proportions of Bifidobacteria, and proportions of pathogenic organisms. Infant stool samples will be collected from soiled diapers at one, six and 12 weeks postpartum.

Secondary outcomes include infant growth, sleep, and breastfeeding outcomes that will be collected at one, six and 12 weeks postpartum.

Eligibility criteria: Inclusion Criteria:

* Gestation greater than 37 weeks (full-term)
* Completion of antibiotic protocol for GBS during labour
* Vaginal delivery
* Intending on breastfeeding
* Consent for infant to receive DHM
* Working understanding (proficient in reading and understanding) 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.

Exclusion Criteria:

* Diagnosed with clinically significant major congenital malformation that will interfere with breastfeeding or growth
* No intention to breastfeed
* Receiving extended courses of antibiotics (beyond that of the IAP in labour)

Primary outcomes:
measure: Infant gut microbiome - shallow shotgun metagenomics (RA)
timeFrame: one week postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (RA)
timeFrame: six weeks postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (RA)
timeFrame: twelve weeks postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)
timeFrame: one week postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)
timeFrame: six weeks postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)
timeFrame: twelve weeks postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (beta diversity)
timeFrame: one week postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (beta diversity)
timeFrame: six weeks postpartum
measure: Infant gut microbiome - shallow shotgun metagenomics (beta diversity)
timeFrame: twelve weeks postpartum
Secondary outcomes:
measure: Infant Sleep
timeFrame: Six weeks postpartum
measure: Infant Sleep
timeFrame: Twelve weeks postpartum
measure: Infant Growth - weight
timeFrame: one week postpartum
measure: Infant Growth - length
timeFrame: one week postpartum
measure: Infant Growth - BMI
timeFrame: one week postpartum
measure: Infant Growth - BMI
timeFrame: six weeks postpartum
measure: Infant Growth - BMI
timeFrame: twelve weeks postpartum
measure: Infant Growth - head
timeFrame: one week postpartum
measure: Infant Growth - weight
timeFrame: six weeks postpartum
measure: Infant Growth- length
timeFrame: six weeks postpartum
measure: Infant Growth - head
timeFrame: six weeks postpartum
measure: Infant Growth - weight
timeFrame: Twelve weeks postpartum
measure: Infant Growth- length
timeFrame: Twelve weeks postpartum
measure: Infant Growth - head
timeFrame: Twelve weeks postpartum
measure: Infant feeding
timeFrame: one week postpartum
measure: Infant feeding
timeFrame: six weeks postpartum
measure: Infant feeding
timeFrame: twelve weeks postpartum
measure: Maternal Depression
timeFrame: one week postpartum
measure: Maternal Depression
timeFrame: six weeks postpartum
measure: Maternal Depression
timeFrame: twelve weeks postpartum
measure: Maternal Anger
timeFrame: one week postpartum
measure: Maternal Anger
timeFrame: six weeks postpartum
measure: Maternal Anger
timeFrame: twelve weeks postpartum
measure: Maternal Breastfeeding Self-efficacy
timeFrame: one week postpartum
measure: Maternal Breastfeeding Self-efficacy
timeFrame: six weeks postpartum
measure: Maternal Breastfeeding Self-efficacy
timeFrame: twelve weeks postpartum
measure: Maternal Anxiety
timeFrame: Baseline - (birth/enrolment)
measure: Maternal Anxiety
timeFrame: six weeks postpartum
measure: Maternal Anxiety
timeFrame: twelve weeks postpartum
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Rockyview General Hospital
state: Alberta
Study officials:
affiliation: University of Calgary
name: Meredith Brockway, PhD RN
role: PRINCIPAL_INVESTIGATOR
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