title: Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country.
abstract: BACKGROUND
  Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements.
  
  
  OBJECTIVE
  The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth.
  
  
  METHODS
  This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with ≥ 1 of the following morbidities: late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth.
  
  
  RESULTS
  We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 ± 5.6 g · kg⁻¹ · d⁻¹) and control (17.0 ± 8.7 g · kg⁻¹ · d⁻¹) groups (P = 0.478).
  
  
  CONCLUSIONS
  Oral zinc supplementation given at high doses reduces morbidities and mortality in preterm neonates. This trial was registered in the Australian New Zealand Clinical Trial Register as ACTRN12612000823875.
authors.affiliation: Department of Gynecology-Obstetrics and Perinatal Medicine, University "La Sapienza," Rome, Italy (GT); the Department of Translational Medicine-Pediatric Section and European Laboratory for the Investigation of Food Induced Diseases, University of Naples "Federico II," Naples, Italy (RBC and AS); the Department of Intensive Care, Hospital "Dei Colli," Naples, Italy (AP); the Department of Perinatal Care, Evangelic Hospital "V Betania," Naples, Italy (FM); the Department of Pediatrics, University "La Sapienza," Rome, Italy (MGC, SC, and MDC); and the Department of Pediatrics, University of Turin, Turin, Italy (EB).
authors.forename: Gianluca
authors.initials: G
authors.lastname: Terrin
authors.forename: Roberto
authors.initials: R
authors.lastname: Berni Canani
authors.forename: Annalisa
authors.initials: A
authors.lastname: Passariello
authors.forename: Francesco
authors.initials: F
authors.lastname: Messina
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Conti
authors.forename: Stefano
authors.initials: S
authors.lastname: Caoci
authors.forename: Antonella
authors.initials: A
authors.lastname: Smaldore
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertino
authors.forename: Mario
authors.initials: M
authors.lastname: De Curtis
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000150:complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D002657:Child Development; D019587:Dietary Supplements; D004311:Double-Blind Method; D020345:Enterocolitis, Necrotizing / Q000150:complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal; D057194:Intention to Treat Analysis; D007558:Italy; D007969:Leukomalacia, Periventricular / Q000150:complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D059012:Lost to Follow-Up; D008297:Male; D047928:Premature Birth / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D012178:Retinopathy of Prematurity / Q000150:complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D018805:Sepsis / Q000150:complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D015032:Zinc / Q000008:administration & dosage / Q000627:therapeutic use*; D019287:Zinc Sulfate / Q000008:administration & dosage
chemical_list: D019287:Zinc Sulfate; D015032:Zinc