Gastric Acid Inhibitors May Increase Late-Onset Sepsis Risk in Preterm Infants

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Study showed that very low birth weight infants exposed to gastric acid inhibitors have significantly increased odds of developing infections, and that the risk increases with each day of exposure.

Exposure to gastric acid inhibitors was associated with late-onset sepsis (LOS) in very low birth weight (VLBW) preterm infants, according to a study published in The Journal of Pediatrics.

Gastric acidity is a primitive defense mechanism against ingested microorganisms, and exposure to inhibitors is hypothesized to reduce the ability of preterm infants to fight off these infections. 

A secondary analysis of data collected during a multicenter randomized controlled trial conducted in Italy and New Zealand was used to assess risk for LOS and inhibitor exposure. Originally, 743 VLBW infants were enrolled and randomly assigned to receive bovine lactoferrin (BLF) alone (n=247) or in combination with the probiotic Lactobacillus rhamnosus GG (n=238) or placebo (n=258). Of these, 235 infants were also treated with gastric acid inhibitors for at least 1 day and included in the secondary analysis.

Treatment with gastric inhibitors in VLBW infants was significantly and independently associated with LOS (odds ratio 1.03; 95% CI, 1.008-1.067; P =.01). This risk was significant for Gram-negative (P <.001) and fungal (P =.001) pathogens, but not for Gram-positive pathogens (P =.97).

The interaction between treatment with BLF and LOS results showed that for every 1 additional day of exposure to inhibitors, an additional 7.7% risk for LOS (P =.003) was incurred in BLF-untreated infants, but dropped to 1.2% (P =.58) in BLF-treated infants.

One important study limitation is that the results were derived from a post hoc analysis of trial data with a different primary outcome. Therefore, the investigators suggested that an “investigation of the pathogenesis of infections in infants exposed to inhibitors of gastric acidity is warranted.” However, the results suggest “that inhibitors of gastric acidity be administered when only strictly necessary, over the shortest possible course, and with consideration of concomitant administration of BLF.”

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Manzoni P, García Sánchez R, Meyer M, et al; Italian Task Force for the Study, and Prevention of Neonatal Fungal Infections and the Italian Society of Neonatology. 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 [published online November 30, 2017]. J Pediatr. doi: 10.1016/j.jpeds.2017.09.080