Infantile Hypertrophic Pyloric Stenosis: A Multidimensional Systems‑Biology Perspective Integrating Early‑Life Determinants, PNEI Interactions, and Functional Gastrointestinal Mechanisms

Abstract

Objectives: To re‑examine infantile hypertrophic pyloric stenosis (IHPS) through a contemporary, multidimensional framework that integrates structural, functional, and psycho‑neuro‑endocrine‑immune (PNEI) mechanisms. This review synthesises current evidence on IHPS epidemiology, pathophysiology, and clinical presentation, and evaluates minimally invasive diagnostic and therapeutic approaches. It further explores how emerging insights into gut–brain and neuroimmune regulation position IHPS within the broader spectrum of functional gastrointestinal disorders.

Design: Narrative review.

Data Sources: Peer‑reviewed literature from paediatric surgery, gastroenterology, neurogastroenterology, developmental physiology, and PNEI‑axis research. Sources include systematic reviews, cohort studies, mechanistic studies, and foundational texts relevant to IHPS, functional gastrointestinal disorders, and early‑life neuroendocrine‑immune development.

Eligibility Criteria: Studies addressing: 1. IHPS epidemiology, diagnosis, or management; 2. Neuromuscular, neurohormonal, or neuroimmune mechanisms relevant to gastric motility; 3. Gut–brain axis or PNEI‑axis physiology in early life; 4. Minimally invasive diagnostic or therapeutic innovations. No date restrictions were applied; emphasis was placed on high‑quality and conceptually relevant evidence.

Results: IHPS remains a common cause of gastric outlet obstruction in early infancy, with well‑defined structural features including pyloric muscle hypertrophy and impaired gastric emptying. However, converging evidence from neurobiology and developmental physiology suggests that aberrant innervation, altered nitric oxide signalling, and neurohormonal influences contribute to functional dysregulation of pyloric motility. These findings align IHPS with mechanistic domains shared by functional gastrointestinal disorders, including impaired enteric neuromuscular coordination and disrupted gut–brain communication. The PNEI axis provides a unifying framework linking early‑life stressors, neuroendocrine maturation, immune signalling, and gastrointestinal motor function. Diagnostic pathways increasingly rely on high‑resolution ultrasonography and dynamic assessment, while laparoscopic pyloromyotomy remains the therapeutic gold standard, offering excellent outcomes with minimal morbidity. Emerging non‑surgical and endoscopic approaches reflect a shift toward precision and minimally invasive intervention.

Conclusions: Reframing IHPS as a disorder with both structural and functional dimensions enriches understanding of its pathogenesis and highlights the relevance of neurogenic and PNEI‑mediated mechanisms. This integrative perspective supports continued refinement of diagnostic strategies and encourages exploration of targeted, minimally invasive therapies. Future research should investigate neuroimmune and neuroendocrine pathways in IHPS to clarify its position within the spectrum of disorders of gut–brain interaction.

Keywords: Infantile Hypertrophic Pyloric Stenosis; Functional Gastrointestinal Disorders; Gut–Brain Axis; Psycho‑Neuro‑Endocrine‑Immune (PNEI) Axis; Neurogastroenterology; Early‑Life Physiology; Minimally Invasive Surgery; Laparoscopic Pyloromyotomy; Paediatric Motility Disorders; Enteric Nervous System

Citation

Zaparackaite I, Govani ND, Singh H, Singh SJ, Mehta AR, Midha PK, et al. Infantile Hypertrophic Pyloric Stenosis: A Multidimensional Systems-Biology Perspective Integrating Early-Life Determinants, PNEI Interactions, and Functional Gastrointestinal Mechanisms. WebLog J Gastroenterol. wjg.2026.a1303. https://doi.org/10.5281/zenodo.18307787