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Original Investigation |

Risk Factors Associated With Pediatric Acute Recurrent and Chronic Pancreatitis Lessons From INSPPIRE

Soma Kumar, MD1; Chee Y. Ooi, MBBS, PhD2; Steven Werlin, MD3; Maisam Abu-El-Haija, MD4; Bradley Barth, MD5; Melena D. Bellin, MD6; Peter R. Durie, MD7; Douglas S. Fishman, MD8; Steven D. Freedman, MD, PhD9; Cheryl Gariepy, MD1; Matthew J. Giefer, MD10; Tanja Gonska, MD7; Melvin B. Heyman, MD, MPH11; Ryan Himes, MD8; Sohail Z. Husain, MD12; Tom K. Lin, MD4; Mark E. Lowe, MD, PhD12; Veronique Morinville, MD13; Joseph J. Palermo, MD, PhD4; John F. Pohl, MD14; Sarah Jane Schwarzenberg, MD6; David Troendle, MD5; Michael Wilschanski, MD15; M. Bridget Zimmerman, PhD16; Aliye Uc, MD16
[+] Author Affiliations
1Nationwide Children’s Hospital, Columbus, Ohio
2University of New South Wales, Sydney Children’s Hospital Randwick, Sydney, Australia
3Medical College of Wisconsin, Milwaukee
4Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
5University of Texas Southwestern Medical School, Dallas
6University of Minnesota Masonic Children’s Hospital, Minneapolis
7Hospital for Sick Children, Toronto, Ontario, Canada
8Baylor College of Medicine, Houston, Texas
9Harvard Medical School, Boston, Massachusetts
10Seattle Children’s Hospital, Seattle, Washington
11University of California, San Francisco
12Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
13Montreal Children’s Hospital, McGill University, Montreal, Quebec, Canada
14University of Utah, Salt Lake City
15Hadassah Hebrew University Hospital, Jerusalem, Israel
16University of Iowa Children’s Hospital, Iowa City
JAMA Pediatr. 2016;170(6):562-569. doi:10.1001/jamapediatrics.2015.4955.
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Importance  Pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood.

Objective  To characterize and identify risk factors associated with ARP and CP in childhood.

Design, Setting, and Participants  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.

Main Outcomes and Measures  Demographic characteristics, risk factors, abdominal pain, and disease burden.

Results  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).

Conclusions and Relevance  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.

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