Effect and safety of lactoferrin for prevention of late-onset sepsis in premature neonates: a systematic review

doi:10.12092/j.issn.1009-2501.2018.06.009

Abstract

Abstract:

AIM: To systematically review the effect and safety of lactoferrin for prevention of late-onset sepsis in premature neonates. METHODS: Cochrane Library databases, Pubmed, EMBase, CNKI, VIP Database, and WHO International Clinical Trial Registry, US Clinical Trial Registration and EU Clinical Trial Register were searched for randomized controlled trials (RCT), in which lactoferrin versus placebo in the prevention of late-onset sepsis in premature infants. After quality evaluation and data extraction，Meta-analysis was performed with Rev Man 5.2 software. RESULTS: A total of 8 RCT (published in ten reports) were included，involving 1 755 patients. Results of Meta analysis indicated that lactoferrin with or without a probiotic decreased late-onset sepsis, fungal sepsis and necrotizing enterocolitis (Bell's stage II or III) in preterm infants with no adverse effects or intolerances, and reduced late-onset sepsis-cause mortality. CONCLUSION: Lactoferrin can effectively prevent the development of late-onset sepsis in premature infants. However, due to the limit of methodological quality and sample size, it remains to be further verified with more large-scale and high-quality RCT. Furthermore, clarification regarding dosing, duration and type of lactoferrin (human or bovine) of prevention of late-onset sepsis for preterm infants is still needed.

Key words: lactoferrin, late-onset sepsis, preterm infants, systematic review

CLC Number:

R722

WEI Liuping, WU Qing, YIN Nange, YANG Bin, MAO Jinxiao. Effect and safety of lactoferrin for prevention of late-onset sepsis in premature neonates: a systematic review[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 653-660.

References

［1］Kaufman D, Fairchild KD. Clinical microbiology of bacterial and fungal sepsis in verylowbirthweight infants［J］. Clin Microbiol Rev, 2004, 17(3):638-680.
［2］Manzoni P, Mostert M, Stronati M. Lactoferrin for prevention of neonatal infections［J］. Curr Opin Infect Dis,2011,24(3):177-182.
［3］Stoll BJ, Hansen N, Fanaroff AA, et al. Lateonset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network［J］. Pediatrics,2002,110(2 Pt 1): 285-291.
［4］Stoll BJ, Hansen NI, Higgins RD, et al. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 20022003［J］. Pediatr Infect Dis J,2005,24(7):635-639.
［5］Speer CP. Inflammatory mechanisms in neonatal chronic lung disease［J］. Eur J Pediatr, 1999, 158(Suppl1):S18- S22.
［6］AdamsChapman I, Stoll BJ. Neonatal infection and longterm neurodevelopmental outcome in the preterm infant［J］. Curr Opin Infect Dis, 2006,19(3):290-297.
［7］Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis: therapeutic decisions based upon clinical staging［J］. Ann Surg, 1978,187(1):1-7.
［8］Manzoni P, Rinaldi M, Cattani S, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial［J］. JAMA, 2009, 302 (13): 1421-1428.
［9］Manzoni P, Stolfi I, Messner H, et al. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial［J］. Pediatrics,2012, 129(1):116-123.
［10］Manzoni P, Meyer M, Stolfi I, et al. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial［J］. Early Hum Dev, 2014, 90 Suppl 1:S60-S65.
［11］Akin IM, Atasay B, Dogu F, et al. Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on Tregulatory cells［J］. Am J Perinatol, 2014, 31(12):1111-1120.
［12］Kaur G, Gathwala G. Efficacy of bovine lactoferrin supplementation in preventing lateonset sepsis in low birth weight neonates: A randomized placebocontrolled clinical trial［J］. J Trop Pediatr, 2015, 61(5):370-376.
［13］Ochoa TJ, Zegarra J, Cam L, et al. Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g［J］. Pediatr Infect Dis J, 2015, 34(6):571-576.
［14］Sherman MP, Adamkin DH, Niklas V, et al. Randomized controlled trial of talactoferrin oral solution in preterm infants［J］. J Pediatr, 2016, 175:68-73.e3.
［15］戴加哲，谢城. 乳铁蛋白结合鼠李糖乳杆菌预防早产儿和低出生体质量儿并发败血症的效果观察［J］. 中国实用医药, 2015, 10(17): 98-100.
［16］刘艳红，关海山，梁桂娟，等. 乳铁蛋白对住院期间低出生体质量儿感染的预防作用观察［J］. 中国妇幼保健, 2016, 31(21): 4464-4465.
［17］唐建平，孙红芹，郑玉辉，等. 牛乳铁蛋白防治早产儿晚发性败血症的随机对照研究［J］. 中国妇幼保健, 2017, 32(32): 1223-1225.
［18］Ronayne de Ferrer PA, Baroni A, Sambucetti ME, et al. Lactoferrin levels in term and preterm milk［J］. J Am Coll Nutr, 2000, 19(3):370-373.
［19］Tsubota A, Yoshikawa T, Nariai K, et al. Bovine lactoferrin potently inhibits liver mitochondrial 8OHdG levels and retrieves hepatic OGG1 activities in LongEvans Cinnamon rats［J］. J Hepatol, 2008,48(3):486-493.
［20］Wakabayashi H, Takakura N, Yamauchi K, et al. Modulation of immunityrelated gene expression in small intestines of mice by oral administration of lactoferrin［J］. Clin Vaccine Immunol, 2006, 13(2):239-245.
［21］Zuccotti GV, Vigano A, Borelli M, et al. Modulation of innate and adaptive immunity by lactoferrin in human immunodeficiency virus (HIV)infected, antiretroviral therapynaive children［J］. Int J Antimicrob Agents, 2007,29(3):353-355.
［22］Venkatesh MP, Pham D, Kong L, et al. Prophylaxis with lactoferrin, a novel antimicrobial agent, in a neonatal rat model of coinfection［J］. Adv Ther, 2007,24(5):941-954.
［23］Vogel HJ. Lactoferrin, a bird's eye view［J］. Biochem Cell Biol, 2012, 90(3):233-244.
［24］Lingappan K, Arunachalam A, Pammi M. Lactoferrin and the newborn: current perspectives［J］. Expert Rev Anti Infect Ther, 2013,11(7):695-707.
［25］Sherman MP, Bennett SH, Hwang FF, et al. Neonatal small bowel epithelia: enhancing antibacterial defense with lactoferrin and lactobacillus GG［J］. Biometals, 2004,17(3):285-289.
［26］Buccigrossi V, de Marco G, Bruzzese E, et al. Lactoferrin induces concentrationdependent functional modulation of intestinal proliferation and differentiation［J］. Pediatr Res, 2007, 61(4): 410-414.

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