title: Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study.
abstract: Fortifying human milk contributes to the prevention of postnatal growth failure in preterm infants. Because of the natural variability of human milk, targeted fortification of human milk has been advocated. However, data regarding the efficacy and safety of prolonged targeted fortification are scarce. We aimed to assess the safety of targeted fortification of human milk in preterm infants compared with standard fortification, as well as the effects on infant growth.
  
  
  
  We conducted an interventional study during hospital stay in healthy very low birth weight preterm infants who were exclusively fed human milk. Pools of human milk collected for 24 h were analysed using mid-infrared transmission spectroscopy. Targeted fortification of human milk was performed by adding macronutrients to native human milk to obtain optimal ratios of fat (4.4 g), carbohydrates (8.8 g), and protein (3 g) per 100 ml. The intervention period lasted 4-7 weeks. Weekly weight and daily growth rates were compared with those of a standardized fortification group of very low birth weight preterm infants who received standard fortified human milk (n = 10). The osmolality as well as the metabolic and gastrointestinal tolerance were monitored. Intergroup differences were evaluated using the Mann-Whitney U-test.
  
  
  
  A total of 10 preterm infants (birth weight 1223 ± 195 g; gestational age 29.1 ± 1.03 weeks) were enrolled and 118 samples of pooled milk were analysed. On average, 1.4 ± 0.1 g of protein, 2.3 ± 0.5 g of carbohydrate, and 0.3 ± 0.1 g of fat per 100 ml were added to the milk. Osmolality values after target fortification were within recommended limits (376 ± 66 mOsml/kg). Weekly weight gain (205.5 g; 95 % CI 177-233 vs 155 g; 95 % CI 132-178; p = 0.025) and daily growth rates (15.7 g/kg/day; 95 % CI 14.5-16.9 vs 12.3 g/kg/day; 95 % CI 10.7-13.9; p = 0.005) were higher in infants receiving target fortification than in infants receiving standardized fortification. The infants receiving targeted fortified milk consumed similar volumes as infants in the standardized fortification group (148 ± 4.5 vs 146 ± 4 ml/kg/day). No signs of either gastrointestinal or metabolic intolerance were observed.
  
  
  
  Target fortification appears to promote growth in very low birth weight preterm infants without any detrimental effects. Trial registration NCT02716337.
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy. laura.morlacchi@mangiagalli.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Morlacchi
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Mallardi
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Maria Lorella
authors.initials: ML
authors.lastname: Giannì
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Roggero
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Orsola
authors.initials: O
authors.lastname: Amato
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Pasqua
authors.initials: P
authors.lastname: Piemontese
authors.affiliation: Epidemiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.affiliation: Neonatal Intensive Care Unit, Department of Clinical Science and Community Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Via Commenda 12, 20122, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
mesh_terms: D002241:Carbohydrates / Q000032:analysis; D005260:Female; D005527:Food, Fortified / Q000032:analysis*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D008055:Lipids / Q000032:analysis; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D009752:Nutritional Status
chemical_list: D002241:Carbohydrates; D008055:Lipids
keywords: Growth rate; Human milk target fortification; Osmolality; Preterm infants