Optimizing the Prebiotic Profile of Donor Human Milk for Preterm Infants: Feasibility of a New Donor Milk Matching Strategy Based on Maternal Secretor Status
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Fecal microbiome composition
研究概览
简要总结
This study will evaluate the impact of matching donor human milk to the maternal secretor status of very preterm infants (<34 weeks gestation) on the gut microbiome. Half of enrolled infants will receive donor human milk which is matched their mother's secretor status and half will receive standard (unmatched) donor human milk, which is standard care in the neonatal intensive care unit.
详细描述
Background: The gut microbiome is established early in life and plays an important role in developing the immune system and metabolism. Infants born prematurely (before 37-weeks gestation) account for 1 in 10 births worldwide and are especially vulnerable to serious microbiome-mediated illnesses such as necrotizing enterocolitis and metabolic diseases. Breastfeeding is the most important factor shaping the infant gut microbiome, providing human milk oligosaccharides (HMOs) that serve as prebiotics for beneficial gut bacteria. Donor human milk (DHM) is considered the best alternative when mothers own milk (MOM) is not available. HMO profiles are highly variable between mothers and there is currently no "matching" process to optimize pairing of DHM and recipient infants. The strongest factor influencing HMO composition is maternal secretor status, determined by the expression of a specific gene (α-1, 2-fucosyltransferase-2). About 20% of Caucasians are non-secretors and researchers do not know the impact of feeding DHM from secretor donors to infants of non-secretor mothers. In this study, investigators aim to explore if matching DHM based on maternal secretor status impacts the development of the gut microbiome in preterm infants.
Method: Investigators will use a pilot, randomized, controlled trial to compare three groups of preterm infants (<34 weeks gestation): 1) infants receiving DHM matched to their mother's secretor status, 2) infants receiving standard issue (i.e. unmatched) DHM, and 3) infants who do not require DHM because they are exclusively receiving MOM. Mothers <34 weeks gestation admitted to antenatal units and the labour and delivery units will be screened for eligibility. Enrolled mothers will be randomized to either the intervention (n=30; matched DHM) or control group (n=30; standard unmatched DHM). Infants of mothers assigned to the intervention group will receive "matched" DHM based on maternal secretor status, determined after randomization. Infant fecal samples will be collected weekly from soiled diapers until discontinuation of DHM or discharge/transfer from the unit. Samples of MOM and DHM will also be collected to analyze milk for HMO and nutrient content. Microbial DNA will be analyzed using 16S sequencing. Additionally, for a subset of samples selected based on 16S results, investigators will perform shotgun metagenomics to identify microbial population structures and functional capacity. Microbial composition from intervention (matched DHM), control (unmatched DHM) and reference (exclusive MOM) groups will be compared to determine differences in microbial diversity and taxonomy.
Impact on healthcare: If promising, investigators would like to examine this phenomenon in a much larger cohort of preterm infants from NICUs across Canada. This research could revolutionize how milk banks and neonatal intensive care units provide DHM to preterm infants. Finally, this research will expand on understanding of the prebiotic effects of HMOs on infant microbiome and may inform future prebiotic/probiotic supplementation regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Outcome assessor (lab technician/research assistant) will not be aware of the group allocation or nutritional intake of the infant while completing data analysis.
We cannot blind participants or care providers as provision of matched donor human milk will require preparation which deviates from standard protocol, and the bedside nurse will need to conduct this preparation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestation up to 33 6/7 weeks at hospital admission (to guarantee at least 14 days intervention, since DHM fortification typically ends at 34+0 weeks adjusted gestational age).
- •Provision of consent for infant to receive DHM.
- •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 is able to 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
- •Intestinal perforation or stage 2 necrotizing enterocolitis (NEC)
- •Unlikely to survive the study period
- •Receiving extended courses of antibiotics (most infants are expected to receive up to 48hr antibiotic prophylaxis at birth according to standard NICU protocol; this criterion will only exclude infants receiving prolonged courses of antibiotics)
- •Presence prior to enrollment of intestinal perforation or stage 2 necrotizing enterocolitis (NEC) prior to tolerating fortified feeds
研究组 & 干预措施
Matched donor human milk
Infants randomized to the matched donor human milk arm, will receive donor human milk which is matched to their mother's secretor status.
干预措施: Matched donor human milk (Other)
Standard issue donor human milk
Infants randomized to the standard issue donor human milk arm, will receive donor human milk which is prepared without consideration of secretor status as per standard practice.
结局指标
主要结局
Fecal microbiome composition
时间窗: sampled weekly until infant transferred from level III NICU, they are no longer receiving donor human milk or up to 60 days, whichever comes first.
16S RNA sequencing of fecal bacteria
次要结局
未报告次要终点
研究者
Meghan Azad
Assistant Professor
University of Manitoba