Advances in Neonatal GERD

Sudarshan Jadcherla, MD, principal investigator and director of the Neonatal and Infant Feeding Disorders Program and Nationwide Foundation Endowed Chair in Neonatology at Nationwide Children’s Hospital, says that feeding and airway-digestive problems are common in infants but may not always indicate GERD. Ambiguity lies with the definition of troublesome symptoms in newborns or non-verbal patients in general, making it difficult to demonstrate objectively if and when symptoms are truly due to GERD.

As a result, infants are frequently subjected to a battery of empiric therapies, such as prolonged use of acid suppression medications, feeding modifications and positional changes.

Now, two new papers from Dr. Jadcherla’s lab provide new evidence-based insights into diagnosing, classifying and treating GERD in infants.

In the first study, Dr. Jadcherla and his colleagues used pH-impedance monitoring to differentiate esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms. Symptoms may occur due to esophageal sensitivity to acid, non-acid reflux or other non-GER causes. The researchers documented many symptoms, including vomiting, arching, irritability and cough, and related the frequency of these symptoms to acid reflux.

They found that the majority of symptoms exhibited by babies were not actually related to acid reflux. Only vomiting and cough were found to be caused by acid alone. Other common symptoms, such as irritability and arching, could be related to non-acid reflux.

Dr. Jadcherla and his colleagues differentiated four esophageal sensitivity phenotypes based on pH-impedance monitoring. They hope that by identifying these phenotypes in patients, targeted therapeutic strategies can be developed and unnecessary therapies can be avoided.

“The results highlight that many of the symptoms that doctors and nurses report are not always acid-related and so could be treated without using acid suppression medications,” says Zakia Sultana, a research assistant at Nationwide Children’s and an author of the study.

“You can’t prescribe acid suppressing medication just by looking at a baby,” she says. “You have to do some diagnostic testing, such as pH-impedance with some symptom correlation. Then you can see if this baby’s symptoms might be related to other factors, not necessarily acid in their esophagus or stomach.”

Dr. Jadcherla, who is also a professor of pediatrics at The Ohio State University College of Medicine, says there are risks to prolonged use of acid-suppressing medications in infants.

“These medications can alter the bowel flora, modify bone density, increase the risk of infections to the gut and airway, and cause other long-term consequences,” he says. “I recommend that clinicians investigate before they medicate.”

Sultana emphasizes the need for innovative treatment strategies to address non-acid-related symptoms.

“What is coming up from the stomach to the esophagus? If it’s not acid, what is it and how do we treat it? These are the questions that remain for future studies,” she says.

In the second study, Dr. Jadcherla and his team tested the effectiveness of behavioral modifications for treating GERD in infants in a randomized clinical trial. For decades, nonevidence-based approaches, including restricting feeding volume and changing the baby’s body position, have been thought to modify GERD and its symptoms.

The researchers identified the infants who needed acid suppressant therapy based on objective testing, that is, based on their pH impedance metrics, and then randomized them into two groups. One group received acid-suppressive therapy only, with no restrictions on feeding volume or body positions. In the other group, feeding volume was restricted and body position was regulated, in addition to the acid-suppressive therapy.

“There was no difference between these approaches in short-term or long-term outcomes,” says Dr. Jadcherla. “We found that by the end of four weeks, the infants in both groups were okay and did not need any more interventions.”

The improvement in symptoms and feeding outcomes over time, irrespective of feeding modifications, may suggest that maturation plays a role in resolving symptoms.

In any case, Dr. Jadcherla says this study shows that feeding restrictions and altering body positions have no major influence on GERD or its treatment – and therefore, these factors should no longer be confounding variables in future trials of GERD therapies.

“From this we learned infants can be fed what they can eat without imposing volume restrictions. Variabilities in feeding positions are common and have no effect on GERD,” he says. “And acid-suppressing medication should only be used in those that have evidence of acid-GERD and for only a limited period of time.”

Overall, Dr. Jadcherla says further studies are needed to define true GERD and identify effective therapies to treat its symptoms or complications.

“Reflux often goes away with time and maturation, but when pathological, it requires careful evaluation and therapy,” he says. “One has to be cautious in distinguishing normal from abnormal. That’s where the need for testing comes in, and translation of evidence-based strategies will then be possible.”

Dr. Jadcherla’s research work is supported by R01 awards from the National Institutes of Health (NIDDK).

References:

1. Jadcherla SR, Hasenstab KA, Wei L, Osborn EK, Viswanathan S, Gulati IK, Slaughter JL, Di Lorenzo C. Role of feeding strategy bundle with acid-suppressive therapy in infants with esophageal reflux exposure: a randomized controlled trial. Pediatric Research. 2020 May 7. [Epub ahead of print]
2. Jadcherla SR, Sultana Z, Hasenstab-Kenney KA, Prabhakar V, Gulati IK, Di Lorenzo C. Differentiating esophageal sensitivity phenotypes using pH–impedance in intensive care unit infants referred for gastroesophageal reflux symptoms. Pediatric Research. 2020 May 6. [Epub ahead of print]

Image credit: Nationwide Children’s