A Genome-Wide Association Study for Neonatal Diseases

• ClinicalTrials.gov Identifier: NCT04074824
• Recruitment Status: Recruiting
• First Posted: August 30, 2019
• Last Update Posted: September 3, 2019
• Sponsor: Chinese University of Hong Kong
• Information provided by (Responsible Party): Kathy Chan, Chinese University of Hong Kong

Study Description

Brief Summary:

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.

Condition or disease
Neonatal Disease; Necrotizing Enterocolitis

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 310 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Genome-Wide Association Study on Chinese Preterm Neonates and Identification of Functional Variants for Susceptibility to Necrotising Enterocolitis
• Actual Study Start Date: September 1, 2018
• Estimated Primary Completion Date: October 31, 2021
• Estimated Study Completion Date: October 31, 2022

Groups and Cohorts

Group/Cohort
Non-NEC; Those without NEC
NEC; Those with NEC

Outcome Measures

Primary Outcome Measures :

1. NEC [ Time Frame: First year ]
   Neonatal Disease

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Chinese infants

Criteria

Inclusion Criteria:

Chinese infants admitted in the neonatal unit (NNU)

Exclusion Criteria:

Refuse consent for study

Contacts and Locations

Contacts

Contact: Kathy Chan, Ph. D.; 852 3505 2858; kathyyychan@cuhk.edu.hk

Locations

Hong Kong

Prince of Wales Hospital; Recruiting

Hong Kong, Hong Kong

Contact: Kathy Chan, Ph. D. 852 3505 2858 kathyyychan@cuhk.edu.hk

Sponsors and Collaborators

Chinese University of Hong Kong

Investigators

• Principal Investigator: Kathy Chan, Ph. D.; CUHK

More Information

Publications:

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.

• Responsible Party: Kathy Chan, Scientific Officer, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT04074824
• Other Study ID Numbers: 2017.493
• First Posted: August 30, 2019
• Last Update Posted: September 3, 2019
• Last Verified: August 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Enterocolitis; Enterocolitis, Necrotizing; Infant, Newborn, Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases