This retrospective cohort study with 236 subjects (55% received acid blockers) provides a compelling argument that acid suppression is unlikely to be beneficial in infants with laryngomalacia and to consider the possibility of aspiration in them as well. Among all subjects, 27% received H2RA, 11% received PPI, and 17% received both.
Subjects treated with acid suppression had a greater risk of supraglottoplasty (hazard ratio 3.36, 95% CI 1.36-8.29, P = .009), shorter time to supraglottoplasty (5.64 ± 0.92 vs 7.98 ± 1.92 months, P = .006), and increased respiratory hospitalization risk (relative risk 1.97, 95% CI 1.01-3.85, 0.047), even after adjustment for covariates
Subjects receiving thickening had fewer respiratory hospitalization nights and longer time to supraglottoplasty (9.3 ± 1.7 vs 4.56 ± 0.73 months, P = .004), even after adjustment.
Subjects with moderate-to-severe laryngomalacia were more likely to have aspiration on a video fluoroscopic swallow study (VFSS)
Of the 40 patients who had a supraglottoplasty, only 4 (10%) had a VFSS before and afterwards. All repeat VFSS showed improvement at a mean of 4.7 months after supraglottoplasty
It is noted that 36% of subjects underwent a VFSS and 40% had a clinical feeding evaluation. The authors note that other studies have found “a high rate of silent aspiration in laryngomalacia.”
Acid blockers are unlikely to be beneficial in infants with laryngomalacia and are potentially detrimental (findings limited by retrospective design in a tertiary care setting)
Symptoms in children with laryngomalacia may be due to aspiration and evaluation is needed in those with significant symptoms
A recent study (P Manzoni et al. J Pediatr 2018; 193: 62-7) provide more data on the detrimental effects of gastric acid inhibitors (eg. proton pump inhibitors, histamine-2 receptor antagonists). This study was a secondary analysis using prospectively collected data from 235 preterm very low birth weight infants. Key findings:
“After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS [late-onset sepsis] (OR 1.03); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS.”
Acid suppression therapy was associated with gram-negative (P<.001) and fungal pathogens (P=.001)
The study showed an association between acid blockers and with necrotizing enterocolitis, which was mitigated in those who received bovine lactoferrin
My take (borrowed, in part, from authors): This data “confirm, strengthen, and expand on previous reports describing an association between inhibitors of gastric acidity and infections.” Thus, the risks of these medications is likely greater than the benefits in the majority of preterm infants.
J Jimenez et al. (JPGN 2015; 61: 208-11) provide more data that gastric acid suppression is associated with an increase risk of Clostridium difficile infection (CDI). This was a retrospective case-control study with 138 children with CDI and 276 controls. After adjustment, acid-suppression therapy had a 1.8 Odds Ratio association with CDI.
S Harel et al. (JPGN 2015; 61: 190-3) in this retrospective ‘pilot’ study of patients receiving topical budesonide for eosinophilic esophagitis, 6 of 14 (43%) had mild biochemical evidence of adrenal suppression, as measured by ACTH testing. Bottomline: a prospective study is likely needed to confirm or refute these findings. In the meanwhile, stress steroid coverage could be considered in patients on prolonged budesonide.
Previously, this blog has noted an association between ranitidine usage and necrotizing enterocolitis (NEC) (see below). Now, another study provides insight into a potential mechanism (JPGN 2013; 56: 397-400).
This study examined the fecal microbiota in 76 premature infants who were enrolled in a case-controlled, cross-sectional study. 25 infants receiving H2-blockers were compared with 51 matched controls.
Results: microbial diversity was lower, relative abundance of Proteobacteria was increased, and Firmicutes was decreased in the stools of infants receiving H2-blockers.
While this study did not specifically examine the effect of H-2 blockers on NEC (no infants in this study had NEC), there are multiple reasons why the findings should be a cause for concern.
Gastric acidity acts as a natural defense against bacterial growth and H-2 blockers (as well as proton pump inhibitors) inhibit this defense
Previous studies have shown an association between NEC and with diminished microbial diversity/increased Proteobacteria. Proteobacteria include well-known pathogens like Klebsiella, Shigella, Escherichia coli, and Citrobacter.