The EXTrauterine Environment for Neonatal Development Supports Normal Intestinal Maturation and Development

Area of Science:

• Neonatal Physiology
• Gastrointestinal Development
• Immunology

Background:

• Premature birth leads to complications like necrotizing enterocolitis (NEC).
• The Extra-Uterine Environment for Neonatal Development (EXTEND) is a novel system designed to support preterm infants.
• Evaluating bowel development in EXTEND-supported lambs is crucial to assess its efficacy in preventing NEC.

Purpose of the Study:

• To determine if bowel development is normal in lambs supported by the EXTEND system.
• To assess specific markers of immaturity associated with NEC in EXTEND-supported lambs.
• To compare ileal development in EXTEND-supported lambs with in utero fetal lambs.

Main Methods:

• Comparison of terminal ileum from 17 EXTEND-supported preterm lambs (2-4 weeks) with age-matched fetal lambs.
• Evaluation of morphology, epithelial integrity, maturation markers (I-FABP, caspase-3, EGFR), enteric nervous system structure, and bowel motility.
• Assessment of transmural resistance using Ussing chambers and ex vivo organ bath studies.

Main Results:

• EXTEND-supported lamb ileum exhibited normal villus height, crypt depth, goblet cell density, and enteric neuron density.
• Epithelial markers (I-FABP, caspase-3, EGFR), transmural resistance, and bowel motility were all within normal ranges.
• Abnormal Peyer's patch organization was observed in EXTEND ileum, leading to reduced circulating B cells.

Conclusions:

• The EXTEND system supports normal ileal epithelial and enteric nervous system maturation in preterm lambs.
• Classic morphologic and cellular changes associated with NEC were not observed in EXTEND-supported lambs.
• Immune development, specifically Peyer's patch organization and B cell levels, requires further investigation and potential optimization within the EXTEND system.