Neonatal mortality is an important global public health challenge. Although advances in neonatal intensive care have led to improved survival of premature infants, sepsis continues to be an important cause of morbidity and mortality worldwide. Exposure of the preterm brain to inflammatory mediators during infectious episodes contributes to brain injury and poor developmental outcome. It has been demonstrated that breast milk has a beneficial effect on neurodevelopment outcomes in preterm infants. We hypothesize that lactoferrin, an iron binding protein present in mammalian milk, is the major factor responsible for this effect due to its antimicrobial and immunomodulatory properties. We have found that lactoferrin not only inhibits growth;it impairs virulence of some of the major pathogens by decreasing their ability to adhere to or to invade mammalian cells, and by binding to, or degrading, specific virulence proteins. Lactoferrin may protect infants from sepsis by blocking attachment and invasion of organisms in the gut. We propose a clinical trial in premature infants to determine the effect of lactoferrin on occurrence of sepsis and to determine whether as a result of decreased infections, infants grow and develop better after having been on lactoferrin.
Specific aim 1 : We will test the hypothesis that oral bovine lactoferrin supplementation prevents serious infections in preterm infants. We will conduct a randomized placebo-controlled double blind study in premature infants <2000 gm in Neonatal Units in Lima, Peru to determine whether bovine lactoferrin prevents the first episode of late-onset sepsis.
Specific aim 2 : We will test the hypothesis that bovine lactoferrin supplementation promotes better neurodevelopment and growth outcomes in preterm infants assessed by the Mullen Scales of Early Learning, a standardized neurologic exam and growth measurements at 18 and 24 months corrected age. The use of lactoferrin as a broad-spectrum non-pathogen specific antimicrobial protective protein is an innovative approach. If successful, this study could profoundly affect clinical care of neonates both in the developed and developing world.

Public Health Relevance

Neonatal mortality is an important global public health challenge. The goal of this project is to determine by a randomized double blind placebo controlled trial whether daily oral administration of bovine lactoferrin, a protein present in milk, prevents serious infections in premature infants and to determine whether as a result of decreased infections, infants grow and develop better after having received lactoferrin. If successful, this study could profoundly affect care of neonates both in the developed and developing world.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01HD067694-04
Application #
8652998
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Raiten, Daniel J
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Turin, Christie G; Ochoa, Theresa J (2014) The Role of Maternal Breast Milk in Preventing Infantile Diarrhea in the Developing World. Curr Trop Med Rep 1:97-105
Mosquito, Susan; Zegarra, Gianina; Villanueva, Claudia et al. (2012) Effect of bovine lactoferrin on the minimum inhibitory concentrations of ampicillin and trimethoprim-sulfamethoxazole for clinical Shigella spp. strains. Biochem Cell Biol 90:412-6
Ochoa, Theresa J; Pezo, Alonso; Cruz, Karen et al. (2012) Clinical studies of lactoferrin in children. Biochem Cell Biol 90:457-67