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Atlas / Disease / Necrotizing enterocolitis

Necrotizing enterocolitis

disease
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Also known as NECnecrotizing enterocolitis in fetus or newbornnecrotizing enterocolitis in foetus or newborn

Summary

Necrotizing enterocolitis (MONDO:0005313) is a disease with 29 GWAS associations across 1 studies and 152 clinical trials. Top therapeutic interventions include melatonin, pentoxifylline, and acetylcysteine. A subtype of intestinal disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

  • Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
  • GWAS associations: 29
  • Phenotypes (HPO): 34
  • Clinical trials: 152

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Point prevalence1-5 / 10 00045WorldwideValidated

Signs & symptoms

Clinical features (HPO)

34 HPO clinical features (Orphanet curated; top 34 by frequency):

HPO IDTermFrequency
HP:0001622Premature birthVery frequent (80-99%)
HP:0000961CyanosisFrequent (30-79%)
HP:0001518Small for gestational ageFrequent (30-79%)
HP:0001875Decreased total neutrophil countFrequent (30-79%)
HP:0001974LeukocytosisFrequent (30-79%)
HP:0002014DiarrheaFrequent (30-79%)
HP:0002902HyponatremiaFrequent (30-79%)
HP:0003270Abdominal distentionFrequent (30-79%)
HP:0004396Poor appetiteFrequent (30-79%)
HP:0012378FatigueFrequent (30-79%)
HP:0012537Food intoleranceFrequent (30-79%)
HP:0025085Bloody diarrheaFrequent (30-79%)
HP:0030144Hypoactive bowel soundsFrequent (30-79%)
HP:0000969EdemaOccasional (5-29%)
HP:0001254LethargyOccasional (5-29%)
HP:0001541AscitesOccasional (5-29%)
HP:0001543GastroschisisOccasional (5-29%)
HP:0001627Abnormal heart morphologyOccasional (5-29%)
HP:0001662BradycardiaOccasional (5-29%)
HP:0001873ThrombocytopeniaOccasional (5-29%)
HP:0001941AcidosisOccasional (5-29%)
HP:0001942Metabolic acidosisOccasional (5-29%)
HP:0002013VomitingOccasional (5-29%)
HP:0002104ApneaOccasional (5-29%)
HP:0002151Increased circulating lactate concentrationOccasional (5-29%)
HP:0002586PeritonitisOccasional (5-29%)
HP:0002615HypotensionOccasional (5-29%)
HP:0003074HyperglycemiaOccasional (5-29%)
HP:0005521Disseminated intravascular coagulationOccasional (5-29%)
HP:0005968Temperature instabilityOccasional (5-29%)
HP:0011014Abnormal glucose homeostasisOccasional (5-29%)
HP:0031273ShockOccasional (5-29%)
HP:0032545Abdominal rigidityOccasional (5-29%)
HP:0040187Neonatal sepsisOccasional (5-29%)

Identifiers

Disease identifiers

FieldValue
Canonical namenecrotizing enterocolitis
Mondo IDMONDO:0005313
EFOEFO:0003928
MeSHD020345
Orphanet391673
ICD-10-CMK55.3
ICD-11141267925
NCITC84915
SNOMED CT2707005
UMLSC0520459
MedGen105440
GARD0009767
Is cancer (heuristic)no

Also known as: NEC · necrotizing enterocolitis · necrotizing enterocolitis in fetus or newborn · necrotizing enterocolitis in foetus or newborn

Data availability: 29 GWAS associations (1 study).

Disease family

This is a subtype of intestinal disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › necrotizing enterocolitis

Related subtypes (57): intestinal atresia, steatorrhea, angiodysplasia of intestine, endometriosis of intestine, hypertrophic pyloric stenosis, mucocele of appendix, gastroenteritis, diverticulitis, intestinal obstruction, postgastrectomy syndrome, chronic intestinal vascular insufficiency, bowel dysfunction, irritable bowel syndrome, Whipple disease, inflammatory bowel disease, intestinal polyp, intestinal perforation, neurogenic bowel, pneumatosis cystoides intestinalis, volvulus of midgut, abetalipoproteinemia, aplasia cutis congenita-intestinal lymphangiectasia syndrome, trichohepatoenteric syndrome, protein-losing enteropathy, chronic diarrhea with villous atrophy, Satoyoshi syndrome, glucose-galactose malabsorption, congenital diarrhea 7 with exudative enteropathy, chronic atrial and intestinal dysrhythmia, congenital enterocyte heparan sulfate deficiency, short bowel syndrome, intractable diarrhea-choanal atresia-eye anomalies syndrome, solitary rectal ulcer syndrome, NK-cell enteropathy, chronic intestinal failure, intestinal lymphangiectasia, refractory celiac disease, eosinophilic gastrointestinal disease, cryptogenic multifocal ulcerous stenosing enteritis, chronic enteropathy associated with SLCO2A1 gene, cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder, malakoplakia, malabsorption syndrome, ischemic bowel disorder, intestinal neoplasm, intestinal motility disease, 4-hydroxyphenylacetic aciduria, parasitic intestinal disorder, Aeromonas hydrophila intestinal disease, large intestine disorder, small intestine disorder, primary desmosis coli, isolated mesenteric vein thrombosis, collagenous sprue, visceral leiomyopathy, African degenerative, intestinal dysmotility syndrome, intestinal fistula

Subtypes (1): perinatal necrotizing enterocolitis

Genetics & variants

GWAS landscape

29 GWAS associations across 1 studies. Top hits map to 13 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs105052327e-09CARS1P2 - TRPS1?
rs31813821e-07ADCY4?
rs99277323e-07BANP?
chr11:1247440054e-07?
chr18:391300321e-06?
rs351987252e-06Y_RNA - SRSF6?
rs20170272e-06KIAA1328?
rs69396013e-06TIAM2?
rs176948393e-06MACROD2?
chr10:237023853e-06?
chr2:48383944e-06?
chr3:88013914e-06?
rs585785624e-06ADAM7-AS1, ADAM28?
rs29558854e-06IDO2?
chr10:151273664e-06?
rs48221125e-06TCF20?
rs622787385e-06OTOL1 - TOMM22P6?
chr13:826875645e-06?
rs564024486e-06SLC37A3?
chr16:603940556e-06?
rs613297467e-06RNF144A - RN7SKP112?
rs117194097e-06GPATCH11P1 - RNU6-1270P?
rs1860497e-06MCTP1?
chr13:283656647e-06?
rs621762848e-06TESHL?
rs96486348e-06NXPH1 - GAPDHP68?
rs93103989e-06SYN2?
chr8:154366299e-06?
rs601402899e-06RPS19P6 - RPS20P25?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST005800Jilling T2018200Surgical necrotizing enterocolitis in extremely premature neonates is associated with genetic variations in an intergenic region of chromosome eight.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR1
Tier 3: regulatory0
Tier 4: intronic/intergenic28

MAF distribution

BucketVariants
common (>=0.05)19
low_freq (0.01-0.05)0
rare (<0.01)0
unknown10

Functional consequences

ConsequenceCount
intron_variant11
unknown10
intergenic_variant7
3_prime_UTR_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs105052328114878275A>C,T0.05intergenic_variantCARS1P2 - TRPS17e-09Tier 4: intronic/intergenic
rs31813821424320104G>C,T0.05intron_variantADCY41e-07Tier 4: intronic/intergenic
rs99277321688043118C>A,G,T0.05intron_variantBANP3e-07Tier 4: intronic/intergenic
chr11:1247440054e-07Tier 4: intronic/intergenic
chr18:391300321e-06Tier 4: intronic/intergenic
rs351987252043455408C>A,G,T0.05intergenic_variantY_RNA - SRSF62e-06Tier 4: intronic/intergenic
rs20170271837225231C>G,T0.053_prime_UTR_variantKIAA13282e-06Tier 2: splice/UTR
rs69396016155222857G>C0.05intron_variantTIAM23e-06Tier 4: intronic/intergenic
rs176948392015609842C>T0.05intron_variantMACROD23e-06Tier 4: intronic/intergenic
chr10:237023853e-06Tier 4: intronic/intergenic
chr2:48383944e-06Tier 4: intronic/intergenic
chr3:88013914e-06Tier 4: intronic/intergenic
rs58578562824323415C>A0.05intron_variantADAM7-AS1, ADAM284e-06Tier 4: intronic/intergenic
rs2955885840008298A>G,T0.05intron_variantIDO24e-06Tier 4: intronic/intergenic
chr10:151273664e-06Tier 4: intronic/intergenic
rs48221122242335534G>A,C,T0.05intergenic_variantTCF205e-06Tier 4: intronic/intergenic
rs622787383161954571C>T0.05intergenic_variantOTOL1 - TOMM22P65e-06Tier 4: intronic/intergenic
chr13:826875645e-06Tier 4: intronic/intergenic
rs564024487140387149G>A0.05intron_variantSLC37A36e-06Tier 4: intronic/intergenic
chr16:603940556e-06Tier 4: intronic/intergenic
rs6132974627089647G>A,C0.05intergenic_variantRNF144A - RN7SKP1127e-06Tier 4: intronic/intergenic
rs11719409373189542A>G0.05intergenic_variantGPATCH11P1 - RNU6-1270P7e-06Tier 4: intronic/intergenic
rs186049594937747C>G0.05intron_variantMCTP17e-06Tier 4: intronic/intergenic
chr13:283656647e-06Tier 4: intronic/intergenic
rs621762842217064297A>C,G0.05intron_variantTESHL8e-06Tier 4: intronic/intergenic
rs964863479545334A>G0.05intergenic_variantNXPH1 - GAPDHP688e-06Tier 4: intronic/intergenic
rs9310398312015255A>G0.05intron_variantSYN29e-06Tier 4: intronic/intergenic
chr8:154366299e-06Tier 4: intronic/intergenic
rs60140289981314691G>A0.05intron_variantRPS19P6 - RPS20P259e-06Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
PentoxifyllinePhase 3 (in late-stage trials)

Clinical trials & evidence

Clinical trials

Clinical trials: 152.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified107
PHASE311
PHASE211
PHASE18
PHASE1/PHASE25
EARLY_PHASE14
PHASE43
PHASE2/PHASE33

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04304807PHASE4COMPLETEDEffect of Melatonin on Feeding Intolerance and Incidence of Necrotizing Enterocolitis in Preterm Infants
NCT05311228PHASE4COMPLETEDThe Efect of Azithromicyn on Bronchopulmonary Displasia in Extremely Preterm and Very Preterm Infant
NCT06202911PHASE4UNKNOWNEffect of Oral N-Acetyl Cysteine in Prevention of Necrotizing Enterocolitis in Preterm Neonates With Feeding Intolerance
NCT03797157PHASE2/PHASE3ACTIVE_NOT_RECRUITINGHuman Milk Fortification in Extremely Preterm Infants
NCT06810154PHASE3NOT_YET_RECRUITINGMulti-strain Probiotics to Prevent Necrotizing Enterocolitis in Very Preterm Infants
NCT00254176PHASE2/PHASE3UNKNOWNCysteine Supplementation in Critically Ill Neonates
NCT00707785PHASE3COMPLETEDEffect of Vitamin A in the Treatment of Neonatal Sepsis and Necrotizing Enterocolitis
NCT01263041PHASE2/PHASE3COMPLETEDEffect of L-arginine and Glutamine on Preterm
NCT01315821PHASE3UNKNOWNEffect of Saccharomyces Boulardii on Necrotizing Enterocolitis in Very Low Birth Weight Infants
NCT01340469PHASE3COMPLETEDEffect of Oral Probiotic Supplementation on The Rate of Hospital Acquired Infection and Necrotizing Enterocolitis in Preterm Very Low Birth Weight Infants
NCT01531179PHASE3COMPLETEDLactobacillus Reuteri for Prevention of Necrotizing Enterocolitis in Very Low-birth Weight Infants
NCT01868737PHASE3COMPLETEDProbiotics in the Management of Necrotizing Enterocolitis in HIV-exposed Premature Infants
NCT02650869PHASE3COMPLETEDRole of Probiotics for Prevention of NEC in Preterm VLBW Infants
NCT03431558PHASE3UNKNOWNBovine Lactoferrin and Neonatal Survival in Low Birth Weight Babies.
NCT03978000PHASE3UNKNOWNIBP-9414 for the Prevention of Necrotizing Enterocolitis - The Connection Study
NCT04696003PHASE3UNKNOWNTreatment of Classic Mid-trimester PPROM by Means of Continuous Amnioinfusion
NCT06422000PHASE3COMPLETEDEffect of Pentoxifylline Versus Probiotic on Preterm Neonates With Necrotizing Enterocolitis
NCT05279664PHASE2ACTIVE_NOT_RECRUITINGRIC-NEC Randomized Controlled Trial
NCT06315738PHASE1/PHASE2RECRUITINGStudy to Assess the Safety, Tolerability, and Preliminary Efficacy of ST266 in Infants With Necrotizing Enterocolitis (NEC)
NCT00271336PHASE2UNKNOWNPentoxifylline in the Treatment of NEC in Premature Neonates
NCT00437567PHASE2UNKNOWNPrebiotics in the Prevention of Necrotizing Enterocolitis
NCT00616876PHASE2COMPLETEDLactulose Supplementation in Premature Infants
NCT00621192PHASE1/PHASE2COMPLETEDPharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections
NCT01441427PHASE1/PHASE2COMPLETEDEnteral Granulocyte Colony Stimulating Factor and Erythropoietin Early in Life Increases Feeding Tolerance in Preterm Infants: A Randomized Controlled Trial
NCT01603368PHASE2COMPLETEDProphylactic Probiotics to Extremely Low Birth Weight Prematures
NCT01674478PHASE2COMPLETEDEarly Supplementation of Enteral Microlipid With and Without Fish Oil in Premature Infants With Enterostomies
NCT01745510PHASE1/PHASE2COMPLETEDEnteral Administration of Docosahexaenoic Acid to Prevent Necrotizing Enterocolitis in Preterm Neonates
NCT01805206PHASE2WITHDRAWNPrediction of NEC With Urinary iFABP
NCT01958320PHASE2COMPLETEDEarly Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus
NCT02472769PHASE2COMPLETEDIBP-9414 for the Prevention of Necrotizing Enterocolitis
NCT02796703PHASE2UNKNOWNHeat Killed Probiotics in the Prevention of Necrotizing Enterocolitis
NCT04541771PHASE2UNKNOWNThe Role of Lactobacillus Reuteri in Preventing Necrotizing Enterocolitis (NEC) in Pre-term Infants
NCT05033639PHASE1/PHASE2COMPLETEDEfficacy Of Oral Melatonin To Prevent Necrotizing Enterocolitis
NCT07416695PHASE1RECRUITINGA Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HLX3901 in Patients With Advanced SCLC or NEC
NCT00840983PHASE1COMPLETEDEffects of Delayed Cord Clamping in Very Low Birth Weight Infants
NCT01222585PHASE1COMPLETEDMetronidazole Pharmacokinetics (PK) in Premature Infants
NCT01954017PHASE1COMPLETEDSTP206 for the Prevention of Necrotizing Enterocolitis (NEC)
NCT02050971PHASE1UNKNOWNAutologous Cord Blood Infusion for the Prevention and Treatment of Prematurity Complications In Preterm Neonates
NCT02405637PHASE1UNKNOWNSimulated Amniotic Fluid In Preventing Feeding Intolerance and Necrotizing Enterocolitis VLBW Neonates
NCT03302338PHASE1UNKNOWNSimulated Amniotic Fluid Solution in Neonates Recovering From GIT Surgeries

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
MELATONIN42
PENTOXIFYLLINE42
ACETYLCYSTEINE41
AZITHROMYCIN41
CEFAZOLIN41
CITRIC ACID41
DEXTROSE41
FISH OIL41
GLUTAMINE41
INULIN41
LACTULOSE41
MEROPENEM41
NEOMYCIN41
RETINOL41
ARGININE32
L-CITRULLINE32
BIFIDOBACTERIUM SPP.31
CHONDROITIN SULFATE31
CHONDROITIN SULFATE SODIUM31
DOCONEXENT31
FRAMYCETIN31
MALTODEXTRIN31
SENNA31
CHEMBL429938101
CHEMBL42370701
CHEMBL375409301
CHEMBL429924701
CHEMBL443941301
SPERMINE01

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 23

This page pulls from 23 datasets indexed by BioBTree:

chembl_moleculecivic_evidenceclinical_trialsclinvardbsnpefogardgenccgwasgwas_studyhgncicd10cmicd11medgenmeshmimmondomondochildmondoparentncitorphanetsctidumls