Comparing Impacts of Donor Human Milk to Formula Supplementation on the Gut Microbiome of Full-Term Infants Born Via Cesarean Section: Protocol for a Pilot Randomized Controlled Trial

J Hum Lact. 2025 Nov;41(4):575-586. doi: 10.1177/08903344251369442. Epub 2025 Sep 30.

Abstract

Background: A disrupted gut microbiome during an infant's first 1000 days of life can lead to long-lasting negative effects on child health. Cesarean delivery and formula feeding are two factors that can detrimentally impact infant microbiome development as well as maternal mental health. Donor human milk may be a superior supplementation alternative to formula.

Research aim: To examine donor human milk supplementation compared to formula supplementation in full-term infants born via Cesarean section and the impact on the infant gut microbiome, infant health outcomes, breastfeeding outcomes, and maternal mental health.Methods and Planned Analyses:We are conducting a pilot clinical randomized controlled trial, comparing donor human milk to formula supplementation for 187 full-term infants born via Cesarean section who are breastfeeding and require supplementation in the first postnatal week of life. Infant stool samples, breastfeeding outcomes, maternal mental health, and child health outcomes will be measured at 1-week, 3-, 6-, and 12-months postpartum. Additionally, child health and maternal mental health are being assessed at 18- and 36-months postpartum.

Discussion: This study will generate essential data on the association between supplementation types and the full-term infant microbiome, breastfeeding exclusivity and duration, and infant health. It will also provide preliminary data to inform a multi-site, longitudinal mixed-methods randomized controlled trial that will assess longer term child health outcomes. This evidence may be used to inform guidelines and policies that will increase accessibility to and raise awareness of donor human milk as a supplementation option in this population.

Keywords: Caesarean section; breastfeeding; donor human milk; exclusive breastfeeding; formula feeding; full-term Infant; gastrointestinal microbiome; maternal mental health; randomized controlled trials.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Breast Feeding / methods
  • Cesarean Section* / adverse effects
  • Cesarean Section* / methods
  • Dietary Supplements / standards
  • Female
  • Gastrointestinal Microbiome* / drug effects
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Infant
  • Infant Formula* / standards
  • Infant, Newborn
  • Milk, Human* / microbiology
  • Pilot Projects
  • Randomized Controlled Trials as Topic