DOnor Milk to REpair the Full-term Infant MIcrobiome in Infants Born Via Caesarean Section
概览
- 阶段
- 不适用
- 干预措施
- Donor Human Milk - Nutritional Replacement
- 疾病 / 适应症
- Microbial Colonization
- 发起方
- University of Calgary
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Infant gut microbiome - shallow shotgun metagenomics (RA)
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
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.
详细描述
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.
研究者
Meredith Brockway
Assistant Professor
University of Calgary
入排标准
入选标准
- •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.
排除标准
- •Diagnosed with clinically significant major congenital malformation that will interfere with breastfeeding or growth
- •No intention to breastfeed
研究组 & 干预措施
Donor Human Milk
Infants randomized to the intervention group will receive DHM each time supplementation is required for the first 7 days of life.
干预措施: Donor Human Milk - Nutritional Replacement
Standard Care (Infant Formula)
Infants randomized to the standard care group will receive formula each time supplementation is required for the first 7 days of life.
结局指标
主要结局
Infant gut microbiome - shallow shotgun metagenomics (RA)
时间窗: six months postpartum
Relative abundance
Infant gut microbiome - shallow shotgun metagenomics (beta diversity)
时间窗: six months postpartum
beta diversity of microbiome
Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)
时间窗: six months postpartum
alpha diversity of microbiome
Infant gut microbiome - shallow shotgun metagenomics (RA)
时间窗: one week postpartum
Relative abundance
Infant gut microbiome - shallow shotgun metagenomics (RA)
时间窗: three months postpartum
Relative abundance
Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)
时间窗: one week postpartum
alpha diversity of microbiome
Infant gut microbiome - shallow shotgun metagenomics (alpha diversity)
时间窗: 3 months postpartum
alpha diversity of microbiome
Infant gut microbiome - shallow shotgun metagenomics (beta diversity)
时间窗: one week postpartum
beta diversity of microbiome
Infant gut microbiome - shallow shotgun metagenomics (beta diversity)
时间窗: three months postpartum
beta diversity of microbiome
次要结局
- Infant Sleep(six months postpartum)
- Infant Growth - weight(six months postpartum)
- Infant Growth - head(six months postpartum)
- Maternal Anxiety(six months postpartum)
- Infant Growth - length(six months postpartum)
- Infant Growth - BMI(six months postpartum)
- Infant feeding(six months postpartum)
- Maternal Anger(six months postpartum)
- Maternal Breastfeeding Self-efficacy(six months postpartum)
- Maternal Depression(six months postpartum)
- Infant Sleep(three months postpartum)
- Infant Growth - weight(one week postpartum)
- Infant Growth - length(one week postpartum)
- Infant Growth - BMI(one week postpartum)
- Infant Growth - BMI(three months postpartum)
- Infant Growth - head(one week postpartum)
- Infant Growth - weight(three months postpartum)
- Infant Growth - length(three months postpartum)
- Infant Growth - head(three months postpartum)
- Infant feeding(one week postpartum)
- Infant feeding(three months postpartum)
- Maternal Depression(one week postpartum)
- Maternal Depression(three months postpartum)
- Maternal Anger(one week postpartum)
- Maternal Anger(three months postpartum)
- Maternal Breastfeeding Self-efficacy(one week postpartum)
- Maternal Breastfeeding Self-efficacy(three months postpartum)
- Maternal Anxiety(Baseline - (birth/enrolment))
- Maternal Anxiety(three months postpartum)