Exocrine Pancreatic Insufficiency Treated With Pancreatic Replacement Enzyme in a Premature Neonate: A Case Report

Exocrine pancreatic insufficiency (EPI) in neonates is rare and challenging to diagnose, particularly in extremely preterm infants in whom physiologic pancreatic immaturity may mimic disease. Persistent malabsorption, poor growth, and repeatedly abnormal fecal elastase-1 (FE1) levels can help differentiate true EPI from transient developmental insufficiency. An extremely preterm female born at 25.0 weeks adjusted gestational age (AGA), weighing 775 g, developed feeding intolerance, direct hyperbilirubinemia, and growth failure during her neonatal intensive care unit course. Serial FE1 testing on days of life 47 and 67 showed persistently low values consistent with EPI. Despite nutritional optimization, including the use of medium-chain triglyceride (MCT)-containing formula and immobilized lipase, the patient exhibited inadequate weight gain. Pancreatic enzyme replacement therapy (PERT) with pancrelipase was initiated at 35.5 weeks AGA, leading to significant improvement in weight gain and normalization of direct bilirubin. Genetic testing identified three CFTR variants of uncertain clinical significance; parental studies confirmed carrier status, and rapid exome sequencing did not identify alternative etiologies. FE1 normalized by 40.6 weeks AGA, permitting discontinuation of PERT. The infant was medically stable for discharge at 42.5 weeks AGA following gastrostomy tube placement for feeding support. This case underscores the diagnostic complexity of distinguishing EPI from physiologic enzyme immaturity in extremely preterm infants. FE1 served as a useful biomarker when interpreted in the context of gestational age and feeding status. Nutritional strategies, including MCT supplementation, PERT, and immobilized lipase, support growth; however, their use should be reserved for infants with objective evidence of EPI. The presence of CFTR variants of uncertain significance underscores the importance of cautious interpretation of genetic results and ongoing monitoring for the development of pancreatic dysfunction. EPI should be considered in extremely preterm infants with persistent malabsorption and growth faltering beyond expected physiologic immaturity. Early identification through serial FE1 testing and targeted therapy can optimize nutritional outcomes. Further research is needed to clarify the clinical relevance of CFTR variants of uncertain significance and to refine evidence-based approaches to enzyme supplementation in this population.