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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Donor Human Milk - Nutritional Replacement
  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

Первичные конечные точки

• Infant gut microbiome - shallow shotgun metagenomics (RA) [Срок оценки: one week postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (RA) [Срок оценки: three months postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (RA) [Срок оценки: six months postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (alpha diversity) [Срок оценки: one week postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (alpha diversity) [Срок оценки: 3 months postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (alpha diversity) [Срок оценки: six months postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (beta diversity) [Срок оценки: one week postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (beta diversity) [Срок оценки: three months postpartum]
• Infant gut microbiome - shallow shotgun metagenomics (beta diversity) [Срок оценки: six months postpartum]

Вторичные конечные точки (12)

• Infant Sleep [Срок оценки: three months postpartum]
• Infant Sleep [Срок оценки: six months postpartum]
• Infant Growth - weight [Срок оценки: one week postpartum]
• Infant Growth - length [Срок оценки: one week postpartum]
• Infant Growth - BMI [Срок оценки: one week postpartum]
• Infant Growth - BMI [Срок оценки: three months postpartum]
• Infant Growth - BMI [Срок оценки: six months postpartum]
• Infant Growth - head [Срок оценки: one week postpartum]
• Infant Growth - weight [Срок оценки: three months postpartum]
• Infant Growth - length [Срок оценки: three months postpartum]
• Infant Growth - head [Срок оценки: three months postpartum]
• Infant Growth - weight [Срок оценки: six months postpartum]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Rockeyview General Hospital — Calgary

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06177184 · REB23-1356

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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