Epidermal Growth Factor in Neonatal Saliva

Abstract

Aims of Study: Epidermal growth factor (EGF) is an amino acid polypeptide that has been shown to promote mucosal healing and intestinal growth in experimental models and has a potential role in the aetiology and treatment of NEC. The aim of this study was to determine the normal levels of salivary EGF in a cohort of healthy neonatal infants. Material and Methods: With appropriate ethical approval and informed consent, saliva was collected using a suction catheter from all normal neonatal infants admitted to our unit over a 9-month period. The samples were immediately frozen at − 20 °C and analysed using an ELISA assay (R & D Systems, Oxford, UK). Samples taken a week prior to and two weeks following a septic episode (as diagnosed by clinical or biochemical evidence) were excluded. Patients with congenital malformations and chromosomal anomalies were excluded. Results: A total of 65 samples were collected and analysed from 27 babies. The mean gestation and weight of the patients was 32.2 (± 5.50) weeks and 1954.44 (± 1045.7) grams, respectively. Five samples from 2 infants were discarded. None of the patients in whom the samples were analysed had clinical or serum markers of sepsis or NEC. All infants were given maternal breast milk starting at the mean age of 5 (± 3.47) days. The mean EGF values were 676.95 (± 168.47) pg/ml. There was a significant rise in serial salivary EGF values in patients (p = 0.0019). There was no correlation between the EGF values and gestation (R = 0.35, p = 0.08). The birth weight, sex or timing of initiating enteral feeds did not correlate with EGF values. Conclusion: In conclusion, our study shows a rise in salivary EGF values in serial samples in a clearly defined group of healthy infants.

Key words

necrotising enterocolitis - epidermal growth factor - newborn

References

• 1 Dvorak B, Fituch C C, Williams C S, Hurst N M, Schanler R J. Increased epidermal growth factor levels in human milk of mothers with extremely premature infants.  Pediatr Res. 2003;  54 15-19
• 2 Dvorak B, Halpern M D, Holubec H, Dvorakova K, Dominguez J A, Williams C S. et al . Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL‐10 in a neonatal rat model.  Pediatr Res. 2003;  53 426-433
• 3 Dvorak B, Halpern M D, Holubec H, Williams C S, McWilliam D L, Dominguez J A. et al . Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model.  Am J Physiol Gastrointest Liver Physiol. 2002;  282 G156-G164
• 4 Goodlad R A, Wilson T J, Lenton W, Gregory H, McCullagh K G, Wright N A. Proliferative effects of urogastrone-EGF on intestinal epithelium.  Gut. 1987;  28 (Suppl) 37-43
• 5 Helmrath M A, Shin C E, Fox J W, Erwin C R, Warner B W. Epidermal growth factor in saliva and serum of infants with necrotising enterocolitis.  Lancet. 1998;  351 266-267
• 6 Holman R C, Stoll B J, Clarke M J, Glass R I. The epidemiology of necrotizing enterocolitis infant mortality in the United States.  Am J Public Health. 1997;  87 2026-2031
• 7 Kaufman E, Lamster I B. The diagnostic applications of saliva – a review.  Crit Rev Oral Biol Med. 2002;  13 197-212
• 8 Miettinen P J, Berger J E, Meneses J, Phung Y, Pedersen R A, Werb Z. et al . Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor.  Nature. 1995;  376 337-341
• 9 Olsen P S, Poulsen S S, Kirkegaard P, Nexo E. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection.  Gastroenterology. 1984;  87 103-108
• 10 Playford R J, Hanby A M, Gschmeissner S, Peiffer L P, Wright N A, McGarrity T. The epidermal growth factor receptor (EGF‐R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract.  Gut. 1996;  39 262-266
• 11 Rao R K, Thomas D W, Pepperl S, Porreca F. Salivary epidermal growth factor plays a role in protection of ileal mucosal integrity.  Dig Dis Sci. 1997;  42 2175-2181
• 12 Scott S M, Guardian C M, Angelus P, Backstrom C. Developmental pattern of urinary epidermal growth factor in the premature infant and the influence of gender.  J Clin Endocrinol Metab. 1991;  72 588-593
• 13 Scott S M, Rogers C, Angelus P, Backstrom C. Effect of necrotizing enterocolitis on urinary epidermal growth factor levels.  Am J Dis Child. 1991;  145 804-807
• 14 Shin C E, Falcone Jr R A, Stuart L, Erwin C R, Warner B W. Diminished epidermal growth factor levels in infants with necrotizing enterocolitis.  J Pediatr Surg. 2000;  35 173-176
• 15 Streckfus C F, Bigler L R. Saliva as a diagnostic fluid.  Oral Dis. 2002;  8 69-76
• 16 Sullivan P B, Brueton M J, Tabara Z B, Goodlad R A, Lee C Y, Wright N A. Epidermal growth factor in necrotising enteritis.  Lancet. 1991;  338 53-54
• 17 Walker-Smith J A, Phillips A D, Walford N, Gregory H, Fitzgerald J D, MacCullagh K. et al . Intravenous epidermal growth factor/urogastrone increases small-intestinal cell proliferation in congenital microvillous atrophy.  Lancet. 1985;  2 1239-1240
• 18 Warner B B, Ryan A L, Seeger K, Leonard A C, Erwin C R, Warner B W. Ontogeny of salivary epidermal growth factor and necrotizing enterocolitis.  J Pediatr. 2007;  150 358-363
• 19 Warner B W. NEC, EGF, milk, and spit.  Gastroenterology. 2002;  123 383-384
• 20 Warner B W, Warner B B. Role of epidermal growth factor in the pathogenesis of neonatal necrotizing enterocolitis.  Semin Pediatr Surg. 2005;  14 175-180
• 21 Wong D T. Towards a simple, saliva-based test for the detection of oral cancer ‘oral fluid (saliva), which is the mirror of the body, is a perfect medium to be explored for health and disease surveillance’.  Expert Rev Mol Diagn. 2006;  6 267-272