DOnor Milk to REpair the Full-term Infant MIcrobiome in Infants Born Via Cesarean Section.
- Conditions
- Microbial Colonization
- Interventions
- Other: Donor Human Milk - Nutritional Replacement
- Registration Number
- NCT06177184
- Lead Sponsor
- University of Calgary
- 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.
- 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 delivered via caesarean section. 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 caesarean section born, full-term infants whose mothers are planning on breastfeeding.
Recruitment: Mothers greater than 37 weeks' gestation in the labour and delivery or postpartum unit who deliver via caesarean section will be screened for participation in the study by nurses on the postpartum and labour and delivery units. Upon recruitment and completion of informed consent, infants requiring supplementation of MOM will be randomized to the control or intervention group. Investigators will randomize 90 mother-infant dyads, providing adequate power to detect overall microbiome differences (\~45 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 week, 3 months and 6 months postpartum.
Secondary outcomes include infant growth, sleep, and breastfeeding outcomes that will be collected at one week, 3 months and 6 months postpartum.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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.
- Diagnosed with clinically significant major congenital malformation that will interfere with breastfeeding or growth
- No intention to breastfeed
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Donor Human Milk Donor Human Milk - Nutritional Replacement Infants randomized to the intervention group will receive DHM each time supplementation is required for the first 7 days of life.
- Primary Outcome Measures
Name Time Method Infant gut microbiome - shallow shotgun metagenomics (RA) six months postpartum Relative abundance
Infant gut microbiome - shallow shotgun metagenomics (beta diversity) six months postpartum beta diversity of microbiome
Infant gut microbiome - shallow shotgun metagenomics (alpha diversity) six months postpartum alpha diversity of microbiome
- Secondary Outcome Measures
Name Time Method Infant Growth - length six months postpartum Length - in centimeters; weight and height will be combined to report BMI in kg/m\^2
Infant Growth - BMI six months postpartum Body mass index - weight and height will be combined to report BMI in kg/m\^2
Infant feeding six months postpartum breastfeeding exclusively - measured by 7-day maternal recall. Number of participants who consume only breastmilk.
Maternal Depression six months postpartum Edinburgh Postnatal Depression Screen - Range in score from 0 to 30; higher scores indicate worse outcomes
Infant Growth - head six months postpartum Head circumference - in centimeters
Infant Growth - weight six months postpartum Weight - in grams; weight and height will be combined to report BMI in kg/m\^2
Infant Sleep six months postpartum Brief Infant Sleep Questionnaire - Scores on each subscale and the total score are scaled from 0 to 100, with higher scores denoting better sleep quality, more positive perception of infant sleep, and parent behaviors that promote healthy and independent sleep.
Maternal Anxiety six months postpartum State-trait Anxiety inventory: Total scores range from 20 to 80 (each for state and trait), with higher scores indicating worse outcomes (higher anxiety).
Maternal Anger six months postpartum LEVEL 2 - ANGER - Adult (PROMIS Emotional Distress - Anger - Short Form): Range in score from 5 to 25 with higher scores indicating greater severity of anger.
Maternal Breastfeeding Self-efficacy six months postpartum Breastfeeding self-efficacy scale - short form: Total scores range from 14 to 70, with higher scores reflecting more significant levels of breastfeeding self-efficacy.
Trial Locations
- Locations (1)
Rockeyview General Hospital
🇨🇦Calgary, Alberta, Canada