International Health Faculty Investigate the Role of Probiotics in Child Growth and Survival

Department of International Health faculty are collaborating with the WHO and colleagues in sub-Saharan Africa and Asia on two new projects investigating probiotic use in newborns and children in low- and middle-income settings. The projects will help advance our understanding of how probiotics can improve newborn health and how they can be used safely and efficiently at scale to treat children in LMIC settings.    

The first project­—the Probiotics in Preterm and Small for Gestational Age Infants, or PROPS, trial—is a five-country, three-year randomized controlled trial testing whether a newly developed probiotic supplement can reduce mortality and improve growth among premature and low-birthweight newborns in low- and middle-income countries. WHO’s Department of Maternal, Newborn, Child and Adolescent Health and Ageing is coordinating the trial. Kayur Mehta, MD, MSc, an assistant scientist in International Health, is leading pre-trial activities, including the development of study protocols and ensuring all regulatory requirements are met before the study begins

Estimates for premature and low-birth weight in LMIC range from 15% to 50%. While there has been some evidence that probiotics can improve growth and survival rates among this population, most studies have been small and focused on high-income countries. 

“Preterm and small for gestational age, or SGA, infants have a 2- to 10-fold higher risk of mortality than infants born at term and with normal birth weight, and are particularly vulnerable to infection, malabsorption, necrotizing enterocolitis, difficulty feeding, and growth failure,” says Mehta. “While numerous trials conducted in the last decade have reported that probiotics can improve short- and long-term mortality, necrotizing enterocolitis and sepsis rates, and growth and neurodevelopment in these at-risk infants, most trials were small with a high to moderate risk of bias,” he adds. 

This trial will enroll 14,000 preterm and SGA newborns in urban, peri-urban, and rural areas of Bangladesh, Ethiopia, Kenya, Nigeria, and Pakistan. Enrollment in the study will begin in late 2025. It will be one of the largest studies of its kind and one of the few set in low- and middle-income countries.

With IH faculty senior research associate Melissa Higdon, MPH, and research associate Sheri Morgan, MPH, Mehta will develop all study materials and protocols for each of the sites. His team will also ensure that the new probiotic supplement is ready for regulatory approval and complies with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use—Good Clinical Practice.

The new probiotic supplement is a combination of two live bacteria—Bifidobacterium longum subsp. Infantis DSM33361 (B. Infantis) and and Lactobacillus rhamnosus GG DSM33156 (L. rhamnosus GG). Each bacteria has been shown individually to help prevent harmful bacteria from developing through the gut. Researchers hypothesize that the combination will provide additional protection to preterm and SGA newborns. 

Many Department collaborating institutions will be involved in conducting the study, including St Paul’s Hospital Millennium Medical College, Addis Ababa; University of Ibadan and University College Hospital, and Aga Khan University, Pakistan.

Abullah Baqui, MBBS, DrPH ’90, MPH ’85, a professor in the Department, will be a site PI in Bangladesh. He and Department associate scientist Rasheda Khanam, MBBS, DrPH, MPH, will work with the Projahnmo Research Foundation, a long-term collaborating institution, to enroll over 3,000 children from the peri-urban region of Sylhet. 

Judd Walson, MD, MPH, the Robert E. Black Chair in International Health, will be a co-investigator with the team in Kenya. He will work with site lead, Benson Singa, MBChB, MPH, from the Kenya Medical Research Institute. The Kenya site will enroll close to 3,000 participants from a mostly rural area of the country.  

Safety and systems assessment for probiotic use among children in LMICs
In a separate but related project, Walson, in collaboration with colleagues Kirk Tickell, MBBS, MPH, and Arianna Means, PhD, MPH, at the University of Washington, will lead the development of the first safety and monitoring framework for probiotic treatment among children. The team, which includes Higdon and Mehta, will also conduct a health systems assessment to determine what will be needed to scale up probiotic use for children in LMICs. The project is funded by the Gates Foundation and includes other researchers from University of Washington’s Department of Global Health and the Brighton Collaboration, and aims to include researchers from Kenya, Pakistan, Ethiopia, Rwanda, Bangladesh and other LMIC settings. 

In a recent review of probiotic trials that included infants and children, Walson’s team found that few included any approach to assessing adverse events. Developing a monitoring and warning system is especially important given that infants with severe conditions could be more at risk from such interventions that are safe and effective for children less critically ill. Even in the few studies with some safety assessments, probiotic-associated adverse events could have been obscured by the overall reduction in mortality. This safety framework will help public health experts and government officials evaluate and make evidence-based decisions about new probiotics, as well as other treatments, in clinical settings. 

Researchers will conduct key informant interviews with officials at bilateral and multilateral agencies, including WHO. The findings will contribute to blueprints for a global standard of probiotic regulation. The team will also assess the capacity and readiness of current national healthcare systems to incorporate probiotic interventions.  

“Our work will fill crucial research gaps and provide standardized criteria for safety assessment, monitoring, and reporting in studies evaluating live bacterial products as interventions in LMIC settings,” says Walson. “Our findings will also characterize the policy, regulatory, and implementation context across various settings to identify factors that could influence the feasibility of introducing probiotic interventions into routine health facility activities in LMIC settings,” he adds.