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RESEARCH PRODUCT

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect

Paolo ManzoniRuben García SánchezMichael MeyerIlaria StolfiLorenza PugniHubert MessnerSilvia CattaniPasqua Maria BettaLuigi MemoLidia DecembrinoLina BollaniMatteo RinaldiMaria FiorettiMichele QuerciaMilena MauleElena TavellaAlessandro MussaChryssoula TziallaNicola LaforgiaFabio MoscaRosario MagaldiMichael MostertDaniele FarinaAmelia Di ComiteAlessandro BorghesiChryssoula TziallaGiovanni AgriestiRiccardo ArisioCaterina FrancoRoberta GuardioneElena BoanoAlessia CatarinellaCristina RomanoCesare MonettiUgo SalaCaterina CarbonaraEmmanuele MastrettaPaola Del SordoClaudio PrioloPaolo GallettoFrancesca CampagnoliMauro VivaldaGiuseppina BonfanteGiovanna GomiratoDavide MontinRoberta CamillaAlessandro MessinaMarta PierettoDomenico CipollaMario GiuffrèGiovanni CorselloFabio NataleGennaro VetranoElisabetta TridapalliGiacomo FaldellaMaria Grazia CaprettiPiermichele PaolilloSimonetta PiconeSerafina LacerenzaGiancarlo GarganoCristiana MagnaniOnofrio Sergio SaiaElena Della Casa

subject

ColonizationProton Pump InhibitorNeonatal intensive care unitAdministration OralHistamine H2 AntagonistProbioticGastroenterologyPediatricsH2 blocker0302 clinical medicineRisk FactorsInfant Very Low Birth Weight030212 general & internal medicineCandidaVLBW neonateLacticaseibacillus rhamnosusGestational agePerinatology and Child HealthHistamine H2 AntagonistsItalyNecrotizing enterocolitismedicine.symptomInfectionInfant PrematureHumanmedicine.medical_specialtyBirth weightGastric AcidSepsis03 medical and health sciencesEnterocolitis NecrotizingIntensive Care Units NeonatalSepsis030225 pediatricsInternal medicinemedicineH2 blockersHumansDietary Supplementbusiness.industryRisk FactorProbioticsInfant NewbornProton Pump Inhibitorsmedicine.diseaseLow birth weightLactoferrinConcomitantDietary SupplementsPediatrics Perinatology and Child HealthVLBW neonatesCandida; Colonization; H2 blockers; Infection; Lactoferrin; VLBW neonates; Pediatrics Perinatology and Child HealthGastric acidLactobacillus rhamnosubusinessNew Zealand

description

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700.

10.1016/j.jpeds.2017.09.080http://hdl.handle.net/2318/1680977