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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
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Raiten, Daniel J
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University of Texas Health Science Center Houston
Internal Medicine/Medicine
Schools of Public Health
United States
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Rueda, Maria S; Calderon-Anyosa, Renzo; Gonzales, Jorge et al. (2018) Antibiotic Overuse in Premature Low-Birth-Weight Infants in a Developing Country. Pediatr Infect Dis J :
Ochoa, Theresa J; Sizonenko, Stéphane V (2017) Lactoferrin and prematurity: a promising milk protein? Biochem Cell Biol 95:22-30
Zambruni, Mara; Villalobos, Alex; Somasunderam, Anoma et al. (2017) Maternal and pregnancy-related factors affecting human milk cytokines among Peruvian mothers bearing low-birth-weight neonates. J Reprod Immunol 120:20-26
Turin, C G; Zea-Vera, A; Rueda, M S et al. (2017) Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns. J Perinatol 37:507-512
Villavicencio, Aasith; Rueda, Maria S; Turin, Christie G et al. (2017) Factors affecting lactoferrin concentration in human milk: how much do we know? Biochem Cell Biol 95:12-21
Zea-Vera, Alonso; Turín, Christie Gloria; Rueda, María Susana et al. (2016) [Use of lumbar puncture in the evaluation of late-onset sepsis in low birth weight neonates]. Rev Peru Med Exp Salud Publica 33:278-82
Zea-Vera, Alonso; Ochoa, Theresa J (2015) Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr 61:1-13
Ochoa, Theresa J; Zegarra, Jaime; Cam, Luis et al. (2015) Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g. Pediatr Infect Dis J 34:571-6
Ochoa, Theresa J; Zea-Vera, Alonso; Bautista, Rossana et al. (2015) Vaccine schedule compliance among very low birth weight infants in Lima, Peru. Vaccine 33:354-8
Zea-Vera, Alonso; Turin, Christie G; Ochoa, Theresa J (2014) [Unifying criteria for late neonatal sepsis: proposal for an algorithm of diagnostic surveillance]. Rev Peru Med Exp Salud Publica 31:358-63

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