As well as avoiding putting anything untested in the intestinal tracts of preterm babies, we should also leave alone their intestinal function. My good friend Sanjay Patole has published, with his group of systematic reviewers in Perth, a review of the effects of gastric acid secretion blockers on the incidence of NEC. There were only 2 informative studies found, both focusing on histamine receptor blockers, and the analysis showed a substantial association between the use of this class of agent in the preterm and the occurrence of necrotising enterocolitis. Both the studies were observational, one case control, one a prospective cohort. The size of the effect differed greatly between the 2 studies, which is not surprising for 2 observational studies especially with a different structure, but the effect size was substantial in each of the studies. More K, Athalye-Jape G, Rao S, Patole S: Association of inhibitors of gastric acid secretion and higher incidence of necrotizing enterocolitis in preterm very low-birth-weight infants. American journal of perinatology 2013(EFirst).
Gastric acid is there for a reason, as well as aiding in digestion it kills a lot of ingested organisms, so blocking it increases infection risk, and, as for NEC, presumably permits colonization with more pathogenic bacteria involved in the pathophysiology of NEC, but it is possible that other adverse effects of histamine receptor blockade are involved also.
A reminder that other adverse effects of acid blockade are systemic infections, (also see here) and increased mortality. They also seem to interfere with absorption of calcium, iron and vitamin B12. In older infants histamine blockers cause agitation and headache, PPI agents increase chest infections in asthmatic children, and they do not improve apnea or bradycardia in preterm infants, nor improve symptoms of GER in older infants.
So before blocking acid production we should really think of what clinical benefits we expect to counterbalance these known adverse effects… which sounds a lot like just good basic medical principles to me.
Dear Prof Barrington,
thank you very much for your blog.
You remind us that acid blockade leads to increased mortality.
Could you please point me in the direction of evidence for the increased mortality? In preterm infants? I can not find it.
Thank you also for the talks at Cool Topics!!
The reference for that is ‘Terrin G, Passariello A, De Curtis M, Manguso F, Salvia G, Lega L, Messina F, Paludetto R, Canani RB: Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics 2012, 129(1):e40-45.’ It is an observational study as I said, this one was a prospective cohort, there were 91 VLBW infants who received ranitidine and 183 who did not; the mortality in the ranitidine group was 9.9% against 1.6% in the non-ranitidine treated.
They also showed as possible mechanisms that 37.4% of the ranitidine infants and 9.8% of the non-exposed had a nosocomial infection and that NEC 6.6-fold higher in