No single aetiology is causative of pyloric stenosis. Hyperacidity as a result of antral distention with feeding and hypertrophy of the pylorus from repeated contraction is believed to be a cause.[25]Rogers IM. The true cause of pyloric stenosis is hyperacidity. Acta Paediatr. 2006 Feb;95(2):132-6.
http://www.ncbi.nlm.nih.gov/pubmed/16449017?tool=bestpractice.com
Additionally, poor pyloric muscle neuronal innervation is believed to play a role.[26]Vanderwinden JM, Liu H, Menu R, et al. The pathology of infantile hypertrophic pyloric stenosis after healing. J Pediatr Surg. 1996 Nov;31(11):1530-4.
http://www.ncbi.nlm.nih.gov/pubmed/8943116?tool=bestpractice.com
[27]Okazaki T, Yamataka A, Fujiwara T, et al. Abnormal distribution of nerve terminals in infantile hypertrophic pyloric stenosis. J Pediatr Surg. 1994 May;29(5):655-8.
http://www.ncbi.nlm.nih.gov/pubmed/8035277?tool=bestpractice.com
The lack of intestinal-pacemaker cells of Cajal is postulated to be another mechanism leading to pyloric stenosis.[28]Vanderwinden JM, Liu H, De Laet MH, et al. Study of the interstitial cells of Cajal in infantile hypertrophic pyloric stenosis. Gastroenterology. 1996 Aug;111(2):279-88.
http://www.ncbi.nlm.nih.gov/pubmed/8690192?tool=bestpractice.com
Nitric oxide synthase deficiency is also implicated as a biochemical cause, by decreasing smooth muscle relaxation.[29]Vanderwinden JM, Mailleux P, Schiffmann SN, et al. Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis. N Engl J Med. 1992 Aug 20;327(8):511-5 (erratum in: N Engl J Med. 1992 Oct 22;327(17):1252).
http://www.ncbi.nlm.nih.gov/pubmed/1378938?tool=bestpractice.com
[30]Subramaniam R, Doig CM, Moore L. Nitric oxide synthase is absent in only a subset of cases of pyloric stenosis. J Pediatr Surg. 2001 Apr;36(4):616-9.
http://www.ncbi.nlm.nih.gov/pubmed/11283889?tool=bestpractice.com
[31]Kusafuka T, Puri P. Altered messenger RNA expression of the neuronal nitric oxide synthase gene in infantile hypertrophic pyloric stenosis. Pediatr Surg Int. 1997;12(8):576-9.
http://www.ncbi.nlm.nih.gov/pubmed/9354728?tool=bestpractice.com
However, none of these aetiologies have been definitively confirmed.
Several risk factors have been associated with an increased incidence of disease. For example, the incidence of pyloric stenosis has been noted to vary depending on geography and ethnic background. Specifically the incidence of pyloric stenosis is reported to be almost four times less in Chinese and Southeast Asian populations than in those with Western heritage.[32]Pandya S, Heiss K. Pyloric stenosis in pediatric surgery: an evidence-based review. Surg Clin North Am. 2012 Jun;92(3):527-39, vii-viii.
http://www.ncbi.nlm.nih.gov/pubmed/22595707?tool=bestpractice.com
Although there is no clear genetic basis for pyloric stenosis, it has been noted to run in some families and there are several genetic syndromes, including Cornelia de Lange, that have been associated with it.[17]Schechter R, Torfs CP, Bateson TF. The epidemiology of infantile hypertrophic pyloric stenosis. Paediatr Perinat Epidemiol. 1997 Oct;11(4):407-27.
http://www.ncbi.nlm.nih.gov/pubmed/9373863?tool=bestpractice.com
[19]Rasmussen L, Green A, Hansen LP. The epidemiology of infantile hypertrophic pyloric stenosis in a Danish population, 1950-84. Int J Epidemiol. 1989 Jun;18(2):413-7.
http://www.ncbi.nlm.nih.gov/pubmed/2767855?tool=bestpractice.com
[33]MacMahon B. The continuing enigma of pyloric stenosis of infancy: a review. Epidemiology. 2006 Mar;17(2):195-201.
http://www.ncbi.nlm.nih.gov/pubmed/16477261?tool=bestpractice.com
[34]Panteli C. New insights into the pathogenesis of infantile pyloric stenosis. Pediatr Surg Int. 2009 Dec;25(12):1043-52.
http://www.ncbi.nlm.nih.gov/pubmed/19760199?tool=bestpractice.com
Male sex, prematurity and birth order (first born) have also been described as risk factors.[17]Schechter R, Torfs CP, Bateson TF. The epidemiology of infantile hypertrophic pyloric stenosis. Paediatr Perinat Epidemiol. 1997 Oct;11(4):407-27.
http://www.ncbi.nlm.nih.gov/pubmed/9373863?tool=bestpractice.com
[19]Rasmussen L, Green A, Hansen LP. The epidemiology of infantile hypertrophic pyloric stenosis in a Danish population, 1950-84. Int J Epidemiol. 1989 Jun;18(2):413-7.
http://www.ncbi.nlm.nih.gov/pubmed/2767855?tool=bestpractice.com
[22]Still G. Place in family as a factor in disease. Lancet. 1927;ii:795-853.[24]Stark CM, Rogers PL, Eberly MD, et al. Association of prematurity with the development of infantile hypertrophic pyloric stenosis. Pediatr Res. 2015 Aug;78(2):218-22.
http://www.ncbi.nlm.nih.gov/pubmed/25950452?tool=bestpractice.com
[33]MacMahon B. The continuing enigma of pyloric stenosis of infancy: a review. Epidemiology. 2006 Mar;17(2):195-201.
http://www.ncbi.nlm.nih.gov/pubmed/16477261?tool=bestpractice.com
[35]Krogh C, Gørtz S, Wohlfahrt J, et al. Pre- and perinatal risk factors for pyloric stenosis and their influence on the male predominance. Am J Epidemiol. 2012 Jul 1;176(1):24-31.
http://aje.oxfordjournals.org/content/176/1/24.long
http://www.ncbi.nlm.nih.gov/pubmed/22553083?tool=bestpractice.com
Certain medications have been associated with pyloric stenosis, including erythromycin.[36]Murchison L, De Coppi P, Eaton S. Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis. Pediatr Surg Int. 2016 Dec;32(12):1147-52.
https://www.doi.org/10.1007/s00383-016-3971-5
http://www.ncbi.nlm.nih.gov/pubmed/27655365?tool=bestpractice.com
[37]Almaramhy HH, Al-Zalabani AH. The association of prenatal and postnatal macrolide exposure with subsequent development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis. Ital J Pediatr. 2019 Feb 4;45(1):20.
https://www.doi.org/10.1186/s13052-019-0613-2
http://www.ncbi.nlm.nih.gov/pubmed/30717812?tool=bestpractice.com
However, there are limited data in the literature as to the strength of this association. Similarly, some data exist for the role of prostaglandins or maternal macrolides as a cause of pyloric stenosis, however, these associations remain conflicted and ill defined.[37]Almaramhy HH, Al-Zalabani AH. The association of prenatal and postnatal macrolide exposure with subsequent development of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis. Ital J Pediatr. 2019 Feb 4;45(1):20.
https://www.doi.org/10.1186/s13052-019-0613-2
http://www.ncbi.nlm.nih.gov/pubmed/30717812?tool=bestpractice.com
[38]Cooper WO, Ray WA, Griffin MR. Prenatal prescription of macrolide antibiotics and infantile hypertrophic pyloric stenosis. Obstet Gynecol. 2002 Jul;100(1):101-6.
http://www.ncbi.nlm.nih.gov/pubmed/12100810?tool=bestpractice.com
[39]Mahon BE, Rosenman MB, Kleiman MB. Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis. J Pediatr. 2001 Sep;139(3):380-4.
http://www.ncbi.nlm.nih.gov/pubmed/11562617?tool=bestpractice.com
[40]Shinohara K, Shimizu T, Igarashi J, et al. Correlation of prostaglandin E2 production and gastric acid secretion in infants with hypertrophic pyloric stenosis. J Pediatr Surg. 1998 Oct;33(10):1483-5.
http://www.ncbi.nlm.nih.gov/pubmed/9802796?tool=bestpractice.com