Do Symptom Scores and pH Impedance Correlate in Infants Treated for Gastroesophageal Reflux?

Do Symptom Scores and pH Impedance Correlate in Infants Treated for Gastroesophageal Reflux? 1024 683 Lauren Dembeck

Gastroesophageal reflux (GER) — the passage of gastric contents into the esophagus — is a physiologic process that can be considered normal or abnormal depending on whether troublesome symptoms and/or complications also occur. In infants, it is difficult for clinicians to distinguish between GER and pathophysiologic GER disease (GERD).

“Current diagnostic criteria for GERD are based on symptoms, and as a result, diagnosis is largely subjective and provider dependent,” explains Sudarshan Jadcherla, MD, medical director of the Neonatal and Infant Feeding Disorders Program at Nationwide Children’s Hospital. “For example, when a baby spits up, it may be attributable to numerous causes, and when this happens repetitively with other associated symptoms, it becomes a cause of concern for parents, caretakers, bedside nurses and providers. If it is labeled as GERD, that often results in treatment with therapies that are not evidenced based.”

These therapies include off-label use of pharmacologic agents, such as histamine-2 receptor antagonists, proton pump inhibitors and alginates, and empiric non-pharmacologic treatments, such as body positioning, formula thickening, intake volume, feeding frequency and tube feeding.

Dr. Jadcherla and colleagues are challenging the field to establish objective criteria for GERD diagnosis and evidence-based treatment initiation and termination in infants treated for GERD in Nationwide Children’s neonatal intensive care unit (NICU).

“Evidence-based prescription of therapies and evidence-based discontinuation of therapies are needed. Because often times when acid-suppressing medications are initiated nobody subsequently stops them,” says Dr. Jadcherla, who is also professor of Pediatrics at The Ohio State University College of Medicine. “Prolonged use of these medications increases the risk of complications, for example, infections, inadequate digestion and malabsorption of nutrients, iron-, calcium-,  and vitamin deficiencies and osteopenia, especially for babies in the NICU setting who are often nutritionally vulnerable.”

The researchers evaluated if scores from the most commonly used questionnaire for GERD evaluation, the Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R), correlated with data from 24-hour pH-impedance testing, which measures the amount of reflux (both acidic and non-acidic) in the esophagus. They analyzed findings from 94 infants cared for at Nationwide Children’s NICU. The team also acquired longitudinal data from 40 infants that received randomly assigned therapies for GERD, specifically proton pump inhibitor with or without feeding modifications, for 4 weeks and compared the effects of the treatments.

“This questionnaire has been validated in older populations of infants and toddlers, so we wanted to know whether it works for premature babies,” explains first author of the study Zakia Sultana, research associate in the laboratory of Dr. Jadcherla. “Not every hospital or clinic has the capability to provide pH-impedance testing, so this study provides evidence on whether or not doctors can use this tool without pH-impedance testing.”

The study demonstrated that correlations between I-GERQ-R and pH-impedance metrics were weak or non-existent, meaning that physicians cannot depend only on the questionnaire to diagnose and treat GERD in premature infants. The researchers also found that I-GERQ-R sensitivity, specificity and positive predictive values were suboptimal when correlated with pH-impedance metrics. However, the I-GERQ-R negative predictive value was significantly high for acid-symptom-associated-probability (84%) and distal baseline pH-impedance (86%) thresholds, indicating that the questionnaire could accurately identify most babies without problematic acid reflux.

“In babies with symptoms who score as abnormal on the questionnaire, it is still necessary to do pH-impedance testing. Those symptoms may be happening due to other issues, such as esophageal or gastric abnormalities that enable nonacidic reflux (bolus) to come up from the stomach,” says Sultana.

The study also demonstrated that acid-suppressive therapy with feeding modifications had no effect on symptom scores or pH-Impedance metrics, with clearance of refluxate worsening despite proton pump inhibitor therapy. These findings may indicate development of pharyngo-esophageal dysmotility and persistence of symptoms.

“In these high-risk infants, I-GERQ-R can be helpful for excluding acid-GERD diagnosis and minimize unnecessary acid-suppressive treatment, but further testing is needed for diagnosis,” says Dr. Jadcherla. “Future placebo-controlled trials with objective pH-impedance criteria of GERD are needed to develop strategies to diagnose and treat acid- and nonacid GERD.”



Sultana Z, Hasenstab KA, Moore RK, Osborn EK, Yildiz VO, Wei L, Slaughter JL, Jadcherla SR. Symptom Scores and pH-impedance: Secondary Analysis of a Randomized Controlled Trial in Infants Treated for Gastroesophageal Reflux. Gastro Hep Advances. 2022 June 20. [Epub ahead of print]. doi: 10.1016/j.gastha.2022.06.004.

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About the author

Lauren Dembeck, PhD, is a freelance science and medical writer based in New York City. She completed her BS in biology and BA in foreign languages at West Virginia University. Dr. Dembeck studied the genetic basis of natural variation in complex traits for her doctorate in genetics at North Carolina State University. She then conducted postdoctoral research on the formation and regulation of neuronal circuits at the Okinawa Institute of Science and Technology in Japan.