Infections are a common cause of both morbidity and mortality in premature infants; examples of infections include necrotizing enterocolitis (NEC) and sepsis (infection of the bloodstream). Infections in premature infants result in prolonged ventilation, prolonged hospitalization, and higher medical costs, and can cause neurodevelopment impairment (Manzoni et al., 2009). The use of high-potency antibiotics can lead to resistant strains of bacteria and potentially damage the infant’s liver and/or kidney function. Within the past decade, research has turned from finding treatments to finding methods to reduce infections.
Breastfeeding and human milk has been well supported through research to provide immunity and positive outcomes for preterm and full-term infants. Breastfeeding and human milk provides nutritional, gastrointestinal, immunological, developmental, and psychological benefits to preterm infants and plays an important role on their long-term health and development (Callen & Pinelli, 2005). The components of breastmilk that support immunity include lactoferrin, lysozymes, interferon, and sIgA antibody (Callen & Pinelli, 2005).
Specifically, lactoferrin (LF) is an iron-binding glycoprotein found not only in breastmilk, but also in saliva, tears, and other bodily secretions; LF has biological functions which include immunomodulatory, antimicrobial, and antioxidant effects, and inhibits growth of pathogenic bacteria, fungi, and viruses (Yen et al., 2009). The described functions of LF support the protective role in immunity. The purpose of this investigation is to determine the effects of oral lactoferrin supplementation on reducing infections in preterm infants.
Nature of Problem and Importance to Nursing Practice
A nosocomial infection is described as an infection that is acquired after 48 hours of hospital admission (Rodriguez et al., 2010). In neonates, a late-onset infection is defined as an infection obtained after the perinatal period (Manzoni et al., 2009). Nosocomial infections include infections of the gastrointestinal tract (necrotizing enterocolitis, NEC), blood stream (sepsis), and lung (pneumonia). The effects of an infection in a preterm infant can lead to “poor growth, adverse long-term neurological sequelae, increased length of hospital stay, and a substantial cost to families, hospitals, and society” (Rodriguez et al., 2010, p. 207). The risk of nosocomial infections increases with the decreasing birth weight and gestational age, and roughly 21% of very low birth-weight (VLBW) infants will encounter a late-onset infection (Stoll et al., 2002).
The most common gastrointestinal infection in premature infants is NEC, affecting 2.6% to 28% of VLBW infants (Lin et al., 2005). NEC is widely considered as a multifactorial disease, with no specific pathogenesis; three major factors have been proposed: the presence of a pathogenic organism, the challenge of enteral feeding, and altered enteric mucosa integrity (Lin et al., 2005). NEC is “characterized by necrotizing injury to the intestine that requires antibiotic treatment and, in severe cases, surgical intervention” (Brooks et al., 2006, p. 347). Reduction of infections in preterm infants is of high priority and active research is being performed to find safe preventative measures, improve patient outcomes, and decrease hospital length of stay.
Lactoferrin is an iron-binding protein found in mammalian milk and is important in innate immune host defenses (Manzoni et al., 2009). Partial digestion of LF in the stomach produces peptides called “lactoferricin” that contain more potent antimicrobial activity (Yen et al., 2009). Human colostrum contains more LF than breastmilk, saliva, tears, or other mucosa linings in the body. Studies have been performed to determine bovine or porcine LF effect on prevention of infection in mice and rat pups; conclusions showed a reduction in “the frequency of bacterial infections in the GI tract while promoting the growth of Lactobacillus and Bifidobacteria species, which are generally believed to be beneficial to the host” (Yen et al., 2009, p. 591).
Bovine, porcine, and human LF molecules are similar, and bovine and porcine LF has been reported to show higher antimicrobial activity compared to human LF (King et al., 2007). In 2001, the US Food and Drug Administration declared bovine lactoferrin generally recognized as safe (CFSAN, 2001). Bovine or human LF can be given as a formula additive, breastmilk additive, or given to patients by swabbing of the mouth, either actively feeding or with nil per os (NPO) statuses. Research studies have now been performed on the effects of bovine or porcine LF on prevention of infections in VLBW and preterm infants, and LF shows to be a promising agent of prevention.
Evidence-based Practice Question
Evidence-based practice (EBP) is defined as “a practice that involves clinical decision-making based on the best available evidence, with an emphasis on evidence from disciplined research” (Polit & Beck, 2008, p. 753). Nursing practices are changing in the NICU to include swabbing of the infants mouth with colostrum every six hours to assist in prevention of infection and improve feeding tolerance. The following question is developed to determine the outcomes of infection prevention by LF in preterm infants: Does the supplementation of LF decrease the occurrence of nosocomial infections in preterm infants?
The studies reviewed did not mention a conceptual or theoretical framework pertaining to the relationship of the subjects investigated. A conceptual model of nursing, Levine’s Conservation Model, can be utilized in applying the methods investigated to provide care and prevention of infection in preterm infants. Levine’s Conservation Model is focused in promoting adaptation and maintaining wholeness using the principles of conservation (“Current Nursing,” 2010). The model guides the nurse to focus on the influences and responses at the organismic level and accomplish the goals of the model through the conservation of energy, structure, and personal, and social integrity (“Current Nursing,” 2010).
Conservation of energy in preterm infants is necessary for appropriate growth, and is achieved by adequate rest and nutrition; fighting an infection in preterm infants results in NPO status and irritability, thus expending energy. The conservation of structural integrity means to prevent physical breakdown and promote healing, and is the consequence of an effective immune system (“Current Nursing,” 2010). The technique of LF supplementation and its potential preventative outcome on infection helps the patient conserve energy and structural integrity.
Variables and Findings
Manzoni et al. (2009) performed a prospective, multicenter, double-blind, placebo-controlled, randomized trial examining whether oral supplementation with bovine LF alone or in combination with Lactobacillus rhamnosus GG (LGG) reduces late-onset sepsis in 472 VLBW infants. The independent variable of this study is the supplementation of bovine LF or LGG and the dependent variable is the occurrence of infections in VLBW infants. The study randomly allocated infants into three groups; groups consisted of a control group (n = 168, infants supplemented with a placebo) and an experimental group (n = 153, infants given bovine LF alone and n = 151, infants given bovine LF with LGG). The main outcome measured the first episode of late-onset sepsis (sepsis occurring after 72 hours of birth); all tests were two-tailed, and P < .05 was considered statistically significant (Manzoni et al., 2009).
When stratifying for birth weight, Manzoni et al. (2009) noted a significant decrease in late-onset sepsis in extremely low birth-weight (ELBW, birth-weight < 1000g) infants (P = .002 for bovine LF v. control and P = .002 for bovine LF plus LGG v. control) whereas it was not significant in infants weighing 1001 to 1500 g (P = .34 for bovine LF v. control and P = .07 in bovine LF plus LGG v. control). Overall, the results showed a significant decrease in the occurrence of infection in VLBW infants in the experimental groups versus the control group (P = .002 for bovine LF v. control and P < .001for bovine LF plus LGG v. control) (Manzoni et al., 2010).
A double-blind, placebo-controlled pilot study examined the impact of bovine LF supplementation to bottle-fed infants (King et al., 2006). The participants included 52 infants between the age of 0-4 weeks of age, ≥34 weeks of gestational age, and ≥2000 g, and who were strictly bottle-fed. The infants were randomized in a double-blind fashion; the control group received a small dose of bovine LF and the experimental group received a higher dose of bovine LF (King et al., 2006). The independent variable is the supplementation of the higher dose of bovine LF and the dependent variable is the impacts observed in the first year of life.
The outcomes measured included diarrhea, upper respiratory infection (URI), acute otitis media (AOM), and lower respiratory tract infection (LRTI). The infants were examined six times throughout the year on the measured outcomes. The results showed a significant decrease in the occurrence of LRTIs in the experimental group than in the control group (P < 0.05) (King et al., 2006). Even though this study did not include preterm infants < 34 weeks, the effects of bovine LF are still apparent in the protection against infection.
Yen et al. (2009) performed a study to examine the effects of porcine LF as a selective decontamination of the digestive tract (SDD) regimen in neonatal mice. Transgenic mice were generated to express porcine LF; the neonatal mice fed from the transgenic mice and were then challenged with pathogens to evaluate in vivo antimicrobial activity of porcine LF (Yen et al., 2009). The control group contained mice that were fed normal milk and the experimental group contained mice that were fed the porcine LF (Yen et al., 2009). The independent variable is the transgenic mice with porcine LF supplementation and the dependent variable is the antimicrobial activity observed.
The outcome measures included the growth rate of the mice pups, the state of the intestinal tract mucosa, and the circulating cytokines (Yen et al., 2009). Yen et al. (2009) concluded that the experimental group of neonatal mice showed a significant reduction of severity of illness (P < .01), a significant inhibition of microbial survival in the intestinal tract (P < .01), and a significant decrease in the number of bacteria cultured (P < .05) than in the control group. The authors proposed that porcine LF is an ideal natural SDD regimen for the prevention of nosocomial infections in critically ill patients (Yen et al., 2009).
Research has proven the high incidence of a nosocomial infection and its adverse outcomes in a preterm infant. The efforts of research have changed to finding a method to reduce or prevent nosocomial infections in preterm infants. Human colostrum is best in supplying the infant with LF to fight infection, but other methods of supplying LF are being studied. Research has recently proven that the supplementation of bovine LF has decreased the occurrence of infections in VLBW and preterm infants.
Future research should include a larger, neonatal population specifically targeting VLBW and/or ELBW infants and the effect of LF supplementation on prevention of NEC. Further studies are needed to determine the dosing, duration, and type of LF (bovine, porcine, or human) that will be most effective in the prevention of infection in preterm infants without causing adverse effects or intolerance (Venkatesh & Abrams, 2010).
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