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.

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.

Lactoferrin Levels in Human Milk after Preterm and Term Delivery.

Background Lactoferrin (LF) is a highly represented, functional glycoprotein in human milk, exerting a wide range of anti-infective, immunomodulatory, and prebiotic actions in the neonate. Limited data are available assessing the concentrations and levels of LF in maternal milk over time during lactation in mothers who delivered infants at different GAs. Our aim with the present study was to determine the levels of LF in human milk from mothers of preterm and term infants and to evaluate the variations at a different time from delivery, in colostrum and mature milk. Methods Mothers of preterm and term infants from the Neonatology Unit in Foggia, Italy, were approached and enrolled in this study. From each mother, milk samples were collected within the first 3 days after birth (group A, 0-72 hours), between the 5th and 7th day after delivery (group B, 120-168 hours), and after the 10th day (group C, > 240 hours). All milk samples were divided into five groups, according to the GA of the infants: 24 to 27.6 weeks of GA (I), 28 to 31.6 weeks of GA (II), 32 to 34.6 weeks of GA (III), 35 to 37.6 weeks of GA (IV), and > 38 weeks of GA (V). Milk samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the content of LF. Results A total of 84 milk samples were collected from 28 mothers. We found that infant's GA, as well as the time of sampling, affected the levels of LF in milk. On one hand, LF showed higher content in human milk from group I (GA: 24-27.6 weeks) compared with the other groups (p < 0.01), and the levels of LF in colostrum were significantly correlated with GA (r = -0.31; p < 0.05). On the other hand, the LF content of milk had a significant decreasing trend over time. Overall, the highest values of LF were detected in preterm infants' maternal milk with a baby birth weight, lower than 1,400 g. Approximately 350 µg/mL was identified as the mean, physiological LF content in human mature milk in our population. Conclusions Levels of LF in human milk vary significantly over time during lactation and according to GA. This variability in the LF content of human milk may reflect the different needs of different infants during the early days and weeks of life. These data might help to inform models to design tailored supplementation strategies of LF in the nurseries and after home discharge.

A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.

BACKGROUND: Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates. METHODS: During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing. RESULTS: Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect. CONCLUSIONS: Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).