A Genome-Wide Association Study for Neonatal Diseases

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Neonatal Disease, Necrotizing Enterocolitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese infants admitted in the neonatal unit (NNU) Exclusion Criteria: Refuse consent for study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Necrotizing enterocolitis<br>Neonates diagnosed with NEC based on the Modified Bell criteria for NEC including clinical, radiological and Laboratory findings. | |
| Non-NEC<br>Neonates diagnosed with other conditions including low birthweight, prematurity, infection, metabolic, cardiovascular, CNS, respiratory or gastrointestinal problems. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NEC | Neonatal Disease | First year |