Anti-reflux medications in preterm infants; a whole cornucopia of toxic placebos.

I have written frequently about this on my blog in the past, and even written a book chapter about the subject (in the book titled “Nutrition for the Preterm Neonate” edited by Sanjay Patole). I recently mentioned the subject in my comments on the AAP choosing wisely recommendations.

The reason for posting about this now is a new publication, from a multi-site network of pediatric primary care practitioners that indicates that 37% of the babies born before 36 weeks received medication for reflux in their first year of life, most of which was started after NICU discharge. (D’Agostino JA, et al. Use of Gastroesophageal Reflux Medications in Premature Infants After NICU Discharge. Pediatrics. 2016). 40% of the treated babies received 2 medications, usually simultaneously, very often the 2 medications were both acid blockers, and some poor babies were getting 3 different acid blockers.

If you click on Gastro-oesophageal reflux in the word cloud at the left of this post you will be taken to a series of posts that address the issues.

But I will summarize:

Almost all babies have reflux, and almost all regurgitate occasionally, so we need to define what is GERD (GORD in England and anywhere else they know how to spell properly) or gastro-(o)esophageal reflux disease:
that is actually more difficult than you might expect, but basically that term means disease caused by gastro-oesophageal reflux, and includes changes caused by intestinal contents refluxing into the oesophagus or higher. Many articles about GER have diagnosed reflux by a percentage of time with acid in the oesophagus that is more than the 90th -percentile, which of course would mean that 10% of babies have ‘pathological’ reflux. But does that identify those babies that have reflux disease? Clearly not.

Can we clinically diagnose reflux? Basically no.

In the NICU there are no clinical signs which have been shown to differentiate between babies that have “excessive” reflux and those without, and one study with pH metry and video monitoring found just as many “reflux specific” clinical signs when the infant was not refluxing as when they were. Another study found that there was no correlation in the scores on 2 different supposedly validated scoring schemes for reflux, and another study showed that anti-acid medications had no impact on the symptoms that were attributed to reflux.

There are of course 2 broad categories of agents that are used for reflux, those which are given to reduce the frequency or duration of reflux events, and those which are given to inhibit acid production and hopefully reduce the adverse effects of reflux.

The first category consists of metoclopramide, cisapride, domperidone and erythromycin, (apparently now there are even people using bethanechol). All of these agents are toxic placebos, or toxic and worse than placebo, (that is both metoclopramide and domperidone have been shown to increase reflux) as you will see from the blog posts about each of them. Indeed as these are all prokinetic agents (although cisapride may not be prokinetic in the newborn) it is not too surprising that they may not improve, or may actually worsen reflux; increasing stomach emptying can easily send the contents in both directions!

Suppressing acid production is neither effective nor safe. It does not decrease symptoms that are attributed to reflux, and is associated with multiple complications. This is true whether you use good old ranitidine, or the latest expensive PPI.

I don’t understand why pediatricians would treat so many ex-preterm infants with agents that are ineffective and have secondary effects. Their use in the NICU has I think been decreasing, but much care of former preterm infants may well be delivered by general pediatricians who do not have the same approach as we do.

Time for more education, and perhaps more regulation, of drugs that have not been adequately tested in this population, are of uncertain efficacy, and have important secondary effects.

In the meantime, if you have a baby where you are convinced that their symptoms are caused by acid reflux, and you can’t stop yourself from prescribing an acid-blocking drug, the least worst harm you could do would be perhaps a “therapeutic trial”. Which means that after a few days if there is no improvement, stop the therapy. If there is an improvement, you should also stop the therapy, to see if the change is just due to the baby getting older, and if the symptoms recur, then you have a reasonable indication for continuing the treatment.

About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged . Bookmark the permalink.

1 Response to Anti-reflux medications in preterm infants; a whole cornucopia of toxic placebos.

  1. Otilia B Neo says:

    I would say that the same applies for term baby that are being treated as much as preterm babies due maternal and pediatric anxiety.

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