Title: Amylin peptide: An association with feed intolerance in preterm neonates and infants of diabetic mothers Introduction: Delayed enteral nutrition due to feed intolerance is common in preterm infants and infants of mothers whose pregnancy was complicated by diabetes mellitus (IMDM). Amylin, a 37 amino-acid polypeptide hormone, is a potent inhibitor of gastric emptying that may play a role in the patho-physiology of feed intolerance in these infants. Aims and Objectives: To determine serum amylin levels (i) at birth (umbilical cord) and postnatal day 5 (Guthrie) in healthy preterm and term infants-Study A, (ii) at birth (umbilical cord) and postnatal day 5 (Guthrie) in preterm and term IMDM-Study B, and (iii) in preterm infants experiencing feed-intolerance (nTOL) and feed-tolerance (TOL)-Study C. Hypothesis: Serum amylin levels are raised in (i) IMDM and (ii) preterm infants with increased gastric residual volumes (GRV); which may explain their feed intolerance. Methods and Material: Blood samples were analysed for total amylin immunoreactivity using monoclonal antibody based sandwich immunoassay. Results: Serum amylin concentrations (median (interquartile range)) in healthy term infants at birth (n=138) and postnatal day 5 (n=14) were 6.10 (3.30-9.70) pmol/L and 5.65 (3.10-8.20) pmol/L respectively. Similarly, the amylin concentrations in healthy preterm infants at birth (n=43) and postnatal day 5 (n=25) were 4.60 (1.90–8.30) pmol/L and 6.9 (2.75–9.50) pmol/L respectively. The amylin concentrations were significantly raised in both term IMDM at birth [n=17, 34.30 (28.35-50.00) pmol/L, p<0.0001] and postnatal day 5 [n=4, 25.20 (22.20-48.75) pmol/L, p<0.0001] and preterm IMDM at birth [n=14, 32.0 (18.65-44.27) pmol/L, p<0.0001] and postnatal day 5 [n=9, 23.4 (15.37-46.57) pmol/L, p<0.0001]. The amylin concentration was significantly elevated in nTOL group [n=30, 47.9 (21.4-79.8) pmol/L, p<0.0001)] compared to TOL group [n=30, 8.7 (5.7-16) pmol/L]. Conclusions: Amylin by virtue of its inhibitory effect on gastric emptying may be responsible in delaying establishment of enteral nutrition in preterm infants and infants of mothers whose pregnancy was complicated by diabetes mellitus.