title: Risk Factors Associated With Pediatric Acute Recurrent and Chronic Pancreatitis: Lessons From INSPPIRE.
abstract: Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood.
  
  
  
  To characterize and identify risk factors associated with ARP and CP in childhood.
  
  
  
  A multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged ≤19 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson χ2 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test.
  
  
  
  Demographic characteristics, risk factors, abdominal pain, and disease burden.
  
  
  
  A total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR] = 0.51; 95% CI, 0.29-0.92; P = .02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP (P < .001). Children with PRSS1 or SPINK1 mutations were more likely to present with CP compared with ARP (PRSS1: OR = 4.20; 95% CI, 2.14-8.22; P < .001; and SPINK1: OR = 2.30; 95% CI, 1.03-5.13; P = .04). Obstructive risk factors did not differ between children with ARP or CP (33% in both the ARP and CP groups), but toxic/metabolic risk factors were more common in children with ARP (21% overall; 26% in the ARP group and 15% in the CP group; OR = 0.55; 95% CI, 0.31-0.99; P = .046). Pancreatitis-related abdominal pain was a major symptom in 81% of children with ARP or CP within the last year. The disease burden was greater in the CP group compared with the ARP group (more emergency department visits, hospitalizations, and medical, endoscopic, and surgical interventions).
  
  
  
  Genetic mutations are common in both ARP and CP. Ethnicity and mutations in PRSS1 or SPINK1 may influence the development of CP. The high disease burden in pediatric CP underscores the importance of identifying predisposing factors for progression of ARP to CP in children.
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Soma
authors.initials: S
authors.lastname: Kumar
authors.affiliation: University of New South Wales, Sydney Children's Hospital Randwick, Sydney, Australia.
authors.forename: Chee Y
authors.initials: CY
authors.lastname: Ooi
authors.affiliation: Medical College of Wisconsin, Milwaukee.
authors.forename: Steven
authors.initials: S
authors.lastname: Werlin
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Maisam
authors.initials: M
authors.lastname: Abu-El-Haija
authors.affiliation: University of Texas Southwestern Medical School, Dallas.
authors.forename: Bradley
authors.initials: B
authors.lastname: Barth
authors.affiliation: University of Minnesota Masonic Children's Hospital, Minneapolis.
authors.forename: Melena D
authors.initials: MD
authors.lastname: Bellin
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Durie
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Fishman
authors.affiliation: Harvard Medical School, Boston, Massachusetts.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
authors.affiliation: Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Gariepy
authors.affiliation: Seattle Children's Hospital, Seattle, Washington.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Giefer
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Tanja
authors.initials: T
authors.lastname: Gonska
authors.affiliation: University of California, San Francisco.
authors.forename: Melvin B
authors.initials: MB
authors.lastname: Heyman
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Ryan
authors.initials: R
authors.lastname: Himes
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Sohail Z
authors.initials: SZ
authors.lastname: Husain
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Tom K
authors.initials: TK
authors.lastname: Lin
authors.affiliation: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lowe
authors.affiliation: Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Veronique
authors.initials: V
authors.lastname: Morinville
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Palermo
authors.affiliation: University of Utah, Salt Lake City.
authors.forename: John F
authors.initials: JF
authors.lastname: Pohl
authors.affiliation: University of Minnesota Masonic Children's Hospital, Minneapolis.
authors.forename: Sarah Jane
authors.initials: SJ
authors.lastname: Schwarzenberg
authors.affiliation: University of Texas Southwestern Medical School, Dallas.
authors.forename: David
authors.initials: D
authors.lastname: Troendle
authors.affiliation: Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilschanski
authors.affiliation: University of Iowa Children's Hospital, Iowa City.
authors.forename: M Bridget
authors.initials: MB
authors.lastname: Zimmerman
authors.affiliation: University of Iowa Children's Hospital, Iowa City.
authors.forename: Aliye
authors.initials: A
authors.lastname: Uc
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000208:Acute Disease; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002918:Chymotrypsin / Q000235:genetics; D017281:Cost of Illness; D003430:Cross-Sectional Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018450:Disease Progression; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010195:Pancreatitis / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D050500:Pancreatitis, Chronic / Q000453:epidemiology / Q000209:etiology / Q000628:therapy; D012008:Recurrence; D012307:Risk Factors; D014357:Trypsin / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D002918:Chymotrypsin; C117569:chymotrypsin C; C489303:PRSS1 protein, human; D014357:Trypsin