Precision Medicine Brings Clarity to Preterm Infant Reflux

Sudarshan Jadcherla, MD, and team aim to distinguish normal reflux from GERD in preterm infants.

Gastroesophageal reflux (GER) is common in preterm infants regardless of whether they are being fed formula or breast milk, often presenting as irritability, coughing or feeding difficulties. These symptoms often lead clinicians to suspect gastroesophageal reflux disease (GERD), prompting interventions that sometimes include stopping breast milk. But is this always necessary?

Researchers at Nationwide Children’s Hospital, guided by Sudarshan Jadcherla, MD, aim to address a critical gap in diagnosis of GERD in babies in the NICU: distinguishing normal reflux from pathological GERD. “About 45% of babies diagnosed with GERD do not actually have the disease,” says Dr. Jadcherla, principal investigator in the Center for Perinatal Research at Nationwide Children’s. “They have symptoms, but they do not actually have the disease. We need to be able to distinguish between what is abnormal and what is normal. Using precision medicine approaches allows us to do just that.”

The team utilized a type of technology called pH impedance testing, a tool used at Nationwide Children’s that is not widely available and allows clinicians to precisely characterize reflux events. This precision allows physicians to determine whether reflux is abnormal or simply part of normal physiology.

Using pH impedance testing, they measured acidity and whether reflux was liquid, gas or mixed, correlating these findings with real-time symptoms. Abnormal symptoms were associated with missed feeding milestones.

The study, published in Journal of Perinatology, also revealed that breast milk-fed infants exhibited more acid reflux events than formula-fed infants, likely due to breast milk’s natural acidity and lower viscosity. These events sometimes extended higher into the esophagus and lasted longer. However, symptoms and discharge outcomes were similar between groups. Importantly, developmental assessments over two years showed superior receptive and fine motor skills in breast milk-fed infants compared to formula-fed infants.

“Despite its acidic nature and association with reflux episodes, our research upholds the principle that breast milk remains the gold standard for preterm infant nutrition,” says Dr. Jadcherla. “Its unique properties support growth, healing and neurodevelopment — benefits that far outweigh concerns about reflux when managed appropriately.”

Determining whether GER is abnormal or normal allows clinicians to create personalized plans for preterm infants with reflux symptoms. The goal is to maximize the use of breastfeeding for nutrition benefits.

To further improve care, Dr. Jadcherla and his team are conducting the GIFT Trial (GERD Infants in Feeding and Therapeutics), an NIH-funded study evaluating targeted strategies for infants with pathological GERD. Through this clinical study, they hope to identify who needs treated, how to treat them, and for how long.

“Incorporating precision medicine approaches in a carefully tested, randomized, controlled trial manner will lead to better strategies in the future. Without support from health care providers and parents, we can’t advance treatment,” says Dr. Jadcherla.

This article appeared in the 2026 Spring/Summer issue. Download the issue here.

Reference:

Osborn EK, Sultana Z, Bala F, Alshaikh E, Jadcherla SR. Distinct gastroesophageal reflux characteristics in preterm-born infants fed human milk versus formula: insights for clinical practice on outcomes. Journal of Perinatology. 2025;45(12):1765-1771.

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