We’ve known for a while now that suppressing gastric acid production in preterm infants increases Necrotising Enterocolitis and also systemic sepsis. Presumably this is because the intestinal microbiome is deranged by allowing the survival of pathogens as they pass through the stomach. There is direct evidence of this effect.

In older children we also know from a large multicenter RCT that PPI (proton pump inhibitor) use increases pulmonary infections in children with poorly controlled asthma, without any benefit.

There are also data about the adverse impacts of PPI use on iron and calcium absorption, mostly from adults, and that this increases the chance of having low bone density and more fractures. They also cause hypomagnesaemia and reduce B12 absorption.

Now observational data from a huge database (Malchodi L, et al. Early Acid Suppression Therapy Exposure and Fracture in Young Children. Pediatrics. 2019:e20182625)
show the same association in young children. There were nearly a million children in the database of the US Military HealthCare System, and, amazingly, more than 10% of them had acid suppression therapy in the first year of life. 0.9% of the children had a PPI, 8% a H₂Receptor Antagonist, and 2% had both.

Exposed infants were more likely to have fractures,  the longer they received acid suppressants and the earlier they started, the greater the risk.

Although there is some doubt about the precise mechanism, the data are very consistent, and our very preterm babies, who are already at risk of poor bone mineralisation, should not be placed on acid suppression therapy unless there is reliable evidence that they have a clinical condition caused by gastric acid.

For most of the 10% of the infant population who received the therapy in this study, I can wager that there was no such evidence apart from, perhaps, a tiny minority. For nearly all of the NICU patients who receive such therapies, I can make the same wager, and be quite sure that my stake will be safe.

Even among infants who are thought to have clinical events related to reflux (a thought which is almost always shown to be erroneous when tested objectively) there is little or no reason to block acid production.

The latest in a large number of studies attempting to elucidate the relationship, if any, between reflux and cardio-respiratory events, presents recordings of multi-channel impedance, ph-metry and cardiorespiratory recordings in 52 preterm infants who had symptoms thought to be due to reflux (regurgitation, rumination or irritability) and on-going cardiorespiratory events. (Nobile S, et al. Correlation between cardiorespiratory events and gastro-esophageal reflux in preterm and term infants: Analysis of predisposing factors. Early Hum Dev. 2019;134:14-8.) Babies were on average about 1kg birth weight and between 1 and 2 months old when studied. Five of the 52 babies perhaps had a temporal association between reflux and events, as calculated by the “symptom association probability” of more than 95%, and in only 3 of those did the events follow the reflux, within 2 minutes. Of those events which followed reflux episodes, many were non-acid or very weakly acidic.

So even among the small proportion of events which occur within a couple of minutes of a proven reflux event, which may be a random association or possibly causative, there is no good reason to suppose that blocking gastric acid production will make any difference.

In the absence of multiple intraluminal impedance studies, the only clinical sign which strongly suggests reflux is a vomit stain somewhere. (As we are just past father’s day, I can testify to the diagnosis of reflux from the puke-stained shoulders of my shirts). If the baby is found with regurgitated milk in their bed, then they have had a reflux episode, no other clinical sign is reliable.

In a recent review article from an expert in the field, Sudarshan Jadcherla, the highlight of the conclusion regarding therapy of reflux disease was “No single pharmaceutical or non-pharmacological target exists to treat infant GERD”. Not only that but commonly used therapies are toxic, and may affect your patients’ bones.