A Genome-Wide Association Study for Neonatal Diseases


This is an observational study to identify genetic risks for neonatal diseases, necrotizing enterocolitis (NEC) using genome-wide association study (GWAS) and enterotype investigation. We hypothesize that specific genetic factors and microbiome could predispose preterm neonates for the development of NEC.

Full Title of Study: “A Genome-Wide Association Study on Chinese Preterm Neonates and Identification of Functional Variants for Susceptibility to Necrotising Enterocolitis”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: October 31, 2021

Detailed Description

NEC is the most frequently encountered surgical emergencies and a life-threatening disease that predominantly affects preterm neonates. The incidence is estimated to be 7-10% in ver low birth weight (VLBW) neonates (Lin and Stoll, 2006; Neu and Walker, 2011). However, a significant proportion of affected neonates (20-30%) develops severe progressive disease with intestinal necrosis and complications resulting in gut perforation and peritonitis which require urgent surgical intervention (surgical cases) (Sharma et al., 2006). The mortality rate of surgical cases is high (25-50%), and may increase to 100% in patients with pan-necrosis of the bowel. Those neonates who survived often suffer severe morbidity, including short bowel syndrome, parenteral nutrition-associated cholestasis, poor physical growth and neurodevelopmental impairment (Neu and Walker, 2011; Salhab et al., 2004). However, the etiology and pathophysiology of NEC remain incompletely understood. The current knowledge has directed towards multiple predisposing factors which include prematurity, immature gut mucosa and host defense immunity, formula milk feeding and altered microbial colonization in the gut resulting in excessive inflammatory response, leading to irreversible intestinal cell death and gut necrosis (Neu and Walker, 2011; Chan et al., 2013). To date, no genetic risk markers or biomarkers are available for reliable prediction of neonates who are at high risk of developing NEC. Besides host genetic factors, gut bacteria have been reported to predispose neonates to disease risk (Mai et. al., 2011; Neu and Pammi, 2018). In this study, we shall conduct a GWAS on Chinese preterm neonates for identification of genetic risks for NEC and determine gut microbiome structure (enterotype) of NEC.

Arms, Groups and Cohorts

  • Necrotizing enterocolitis
    • Neonates diagnosed with NEC based on the Modified Bell criteria for NEC including clinical, radiological and Laboratory findings.
  • Non-NEC
    • Neonates diagnosed with other conditions including low birthweight, prematurity, infection, metabolic, cardiovascular, CNS, respiratory or gastrointestinal problems.

Clinical Trial Outcome Measures

Primary Measures

  • NEC
    • Time Frame: First year
    • Neonatal Disease

Participating in This Clinical Trial

Inclusion Criteria

Chinese infants admitted in the neonatal unit (NNU) Exclusion Criteria:

Refuse consent for study

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Chinese University of Hong Kong
  • Provider of Information About this Clinical Study
    • Principal Investigator: Kathy Chan, Scientific Officer – Chinese University of Hong Kong
  • Overall Official(s)
    • Kathy Chan, Ph. D., Principal Investigator, CUHK
  • Overall Contact(s)
    • Kathy Chan, Ph. D., 852 3505 2858, kathyyychan@cuhk.edu.hk


Lin PW, Stoll BJ. Necrotising enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83. Review.

Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med. 2011 Jan 20;364(3):255-64. doi: 10.1056/NEJMra1005408. Review.

Sharma R, Hudak ML, Tepas JJ 3rd, Wludyka PS, Marvin WJ, Bradshaw JA, Pieper P. Impact of gestational age on the clinical presentation and surgical outcome of necrotizing enterocolitis. J Perinatol. 2006 Jun;26(6):342-7.

Salhab WA, Perlman JM, Silver L, Sue Broyles R. Necrotizing enterocolitis and neurodevelopmental outcome in extremely low birth weight infants <1000 g. J Perinatol. 2004 Sep;24(9):534-40.

Chan KY, Leung KT, Tam YH, Lam HS, Cheung HM, Ma TP, Lee KH, To KF, Li K, Ng PC. Genome-wide expression profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in human intestinal tissues: dysregulation of functional pathways. Ann Surg. 2014 Dec;260(6):1128-37. doi: 10.1097/SLA.0000000000000374.

Mai V, Young CM, Ukhanova M, Wang X, Sun Y, Casella G, Theriaque D, Li N, Sharma R, Hudak M, Neu J. Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS One. 2011;6(6):e20647. doi: 10.1371/journal.pone.0020647. Epub 2011 Jun 6.

Neu J, Pammi M. Necrotizing enterocolitis: The intestinal microbiome, metabolome and inflammatory mediators. Semin Fetal Neonatal Med. 2018 Dec;23(6):400-405. doi: 10.1016/j.siny.2018.08.001. Epub 2018 Aug 17. Review.

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