Drugs for reflux disease in infants may come with unintended consequences

When my girls were newborns, I spent a lot of time damp. Fluids were everywhere, some worse than others. One of the main contributors was milk, which, in various stages of digestion, came back to haunt me in a sloppy trail down my back.

I was sometimes alarmed at the volume of fluid that came flying out of my tiny babies. And I remember asking our pediatrician if it was a problem. We were lucky in that the amount and frequency of the regurgitations didn’t seem to signal trouble.

But some babies spit up a lot more, and seem to be in distress while doing so. That’s led doctors to prescribe antacids to treat reflux disease in these infants. A U.S.-based survey found that from 2000 to 2003, infant use of a type of antacid called proton-pump inhibitors quadrupled.

Those numbers point to worried doctors and parents who want to help babies feel better. The problem, though, is that antacids come with side effects. Mucking with acid levels can affect the body beyond the stomach, and these unintended effects may be even more meddlesome in babies.

“What we found in adults and what we’re starting to see more in children is that [the drugs] are not as benign as we used to think,” says U.S. Air Force Captain Laura Malchodi, a pediatrician at Walter Reed National Military Medical Center in Bethesda, Md.

Infants who took proton-pump inhibitors, a class of drugs that includes Prilosec and Nexium, in their first six months of life broke more bones over the next several years than children who didn’t receive the drugs. That example comes from research Malchodi presented May 7 at the 2017 Pediatric Academic Societies Meeting in San Francisco.

Malchodi and her colleagues examined medical records of nearly 900,000 healthy children. Of those, about 7,000 were prescribed proton-pump inhibitors by the time they were 6 months old. About 67,000 were prescribed histamine H2-blocking drugs, such as Zantac or Pepcid, and about 11,000 babies were prescribed both types of drugs.
Children who had received proton-pump inhibitors, either alone or in combination with a histamine H2-blocker, had more fractures over the next five years than children who weren’t prescribed that type of drug. The researchers tried to rule out other differences between the groups of babies that might explain the higher number of fractures. When those differences were removed from the analysis, proton-pump inhibitor prescriptions were still linked to fractures.

The study can’t say whether proton-pump inhibitors definitely caused weaker bones. But that’s not an unreasonable hypothesis given what’s seen in adults, for whom the link between long-term use of proton-pump inhibitors and broken bones is stronger.

If proton-pump inhibitors do interfere with bones, it’s still a mystery exactly how. One idea was that the drugs hinder calcium absorption, leading to weaker bones. That idea has fallen out of favor, Malchodi says. Another proposal centers on cells called osteoclasts. To do their job, these cells rely on proton pumps to create acidic pockets around bones. But if osteoclasts aren’t working properly, “in the end, what you get is disorganized bone,” Malchodi says.

Reflux disease is not the same thing as reflux, which babies are nearly guaranteed to experience. For one thing, the amount of liquid they’re slurping down relative to their body weight is huge. And that liquid is held down by an esophageal sphincter that’s often underdeveloped in babies. (One technical term for reflux is “poor gastric compliance,” but I bet you’ve got more colorful descriptions.)

Antacids won’t stop babies from spitting up, says Malchodi. “We definitely counsel parents all the time that this is not going to stop the reflux,” she says. Instead, the drugs are thought to change the pH of the liquid coming back up in an attempt to make it less irritating.

Some babies may need that pharmaceutical help. But many may not. If babies are growing well and don’t seem to be in long-lasting distress, then it’s possible that they may need the “tincture of time” to outgrow the reflux. (Malchodi points out that so-called “happy spitters” are probably not smiling while they’re barfing, because obviously, throwing up is not fun. It’s just that these babies don’t seem to be bothered long after the spitting.)

She hopes that her research and other studies like it will prompt more careful discussions between parents and doctors before antacids are prescribed. And if they are deemed necessary, “have a stop point in mind,” she says.