Acute pancreatitis is a rare disease in pediatric patients. However, there has been a considerable increase in the number of cases in recent years, with an incidence of 1 to 13 cases/100,000 pediatric patients. The mean age at presentation is 9.2 ± 2.4 years with a 1:2 male-to-female ratio.1

Contrasting with etiology in adults (where alcohol and biliary stones account for more than 60% of cases), etiology in pediatrics is more diverse. Causes include biliary disorders, systemic conditions, infections, trauma, medications, structural abnormalities, metabolic diseases, autoimmune diseases, and idiopathic diseases.2

In Mexico, epidemiologic information is still limited, although a greater frequency of biliary and idiopathic pancreatitis has been reported, with a predominance in school-age girls.1

The diagnosis of acute pancreatitis in pediatric patients is made with at least two of the following criteria (INSPPIRE):3

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  Characteristic abdominal pain

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  Serum amylase/lipase determination, at least 3 or more times the upper limit of normal (ULN)

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  Imaging study findings (transabdominal ultrasound, computed tomography, or magnetic resonance imaging)

One of the primary challenges of this condition is classifying its severity, and numerous studies have been carried out for resolving the problem. In 2002, DeBanto et al. were the first to define acute pancreatitis severity in the pediatric patient, utilizing the 1991 Atlanta Classification applied to adults.4 But there are significant differences in that classification, from clinical presentation to etiology, making it inappropriate for defining severity in pediatric patients.

In 2017, according to the NASPGHAN Pancreas Committee,5 the disease can be classified as:

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  Mild: acute pancreatitis that is not associated with systemic failure or local or systemic complications, and usually resolves a week after presentation

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  Moderate: acute pancreatitis with the development of transient organ failure (not more than 48 hours) or the development of local or systemic complications

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  Severe: acute pancreatitis with the development of organ dysfunction, which lasts more than 48 hours

Organ failure may be single or multiple and develop within the first 48 hours of presentation.5

The treatment of acute pancreatitis focuses on fluid management, pain management, and nutritional support.

Most cases of acute pancreatitis are mild and resolve without complications, but up to 30% of patients may present with local and/or systemic complications. Some of the risk factors associated with the development of complications are malnutrition, obesity, traumatic etiology, medications, hypoalbuminemia, and elevated C-reactive protein.6 Complications can be classified as early (<4 weeks) and late (>4 weeks), and include:

Systemic complications: The acute phase of acute pancreatitis is characterized by a marked inflammatory state, which lasts approximately one week. In some cases, acinar injury can result in an increase in the inflammatory cascade, resulting in systemic inflammatory response syndrome. Such patients present with the risk of developing systemic complications, such as sepsis, shock, and multiple organ failure, with cardiac, respiratory, and renal involvement, among others.7

Local complications: These are suspected when abdominal pain persists or is exacerbated, with an increase in pancreatic enzyme levels and/or systemic inflammatory response data. They are8:

• 1

  Acute peripancreatic fluid collection (appearance < 4 weeks), characterized by a homogeneous, non-encapsulated fluid content and confined to the peripancreatic fascia.

• 2

  Pancreatic necrosis (appearance < 4 weeks). In the initial phases, the collection is a mixture of solid tissue, which then liquifies and becomes encapsulated. It can be sterile or infected but tends to be infected after two weeks. Most cases are monomicrobial and due to Gram-negative bacteria.

• 3

  Pancreatic pseudocyst (appearance > 4 weeks). It is an extrapancreatic collection encapsulated by granulation tissue and a well-defined fibrous wall.

• 4

  Pancreatic abscess (appearance > 4 weeks). It is a heterogeneous collection and encapsulated within the parenchyma. Most deaths from acute pancreatitis are attributed to it, within the context of pancreatic necrosis.

The latest study conducted in Mexico on the epidemiology and association of risk factors for developing complications in acute pancreatitis was carried out in 2009 by García Dávila et al. They reported that the development of complications was associated with overweight and obesity.9

In 2020, Thavamani et al., in studies conducted in Cleveland, Ohio, found that malnutrition and obesity were associated with greater severity of acute pancreatitis, as well as with longer hospital stay and higher costs.10,11

In 2013, Coffey et al. reported that lipase levels seven times the ULN within 24 hours of presentation, could be a severity predictor of acute pancreatitis in pediatric patients.12 In 2021, Al Hindi et al. found a significant association between an elevated leukocyte count and admission to the intensive care unit.13

Recent studies, such as the one by Bhanot et al. in 2022, reported that the most frequent complications at hospital admission were pancreatic necrosis, multiple organ failure, and hyperglycemia requiring management with insulin.14 Also in 2022, a 10-year retrospective study by Wang et al.15 conducted in China, that conflicted with data reported by Bhanot et al.,14 found that the most frequent local or systemic complications were acute kidney injury and acute respiratory distress syndrome.15

In more recent studies (2024), the mortality rate of acute pancreatitis in pediatric patients has been reported at 1.6 to 3.6%.16 Approximately 15–35% will present with recurrent pancreatitis, associated with overweight/obesity, male sex, and necrotic pancreatitis.17

The present study aimed to determine whether sex, age group, etiology, nutritional status, lipase level, albumin level, and leukocyte count were associated with the development of early complications in pediatric patients diagnosed with acute pancreatitis.

A retrospective, analytic study, comparing subgroups (with and without complications) from the same diagnosed cohort, was carried out. The STROBE case-control checklist was utilized. Patients under 18 years of age (up to 17 years and 11 months), diagnosed with acute pancreatitis and treated at the Hospital para el Niño Poblano, in Puebla, Mexico, between July 2014 and July 2024, were included.

The inclusion criteria were pediatric patients younger than 17 years and 11 months of age, who met the INSPPIRE criteria for the diagnosis of acute pancreatitis. Patients with chronic and recurrent pancreatitis were excluded, and patients whose clinical records were incomplete were eliminated from the study. For calculating sample size, a population of 186 patients was considered, with a 5% margin of error and a 95% confidence interval, resulting in a sample of 143 patients.

The variables considered potential risk factors were: a) sex (male and female), b) age group (infants, preschoolers, school-age children, and adolescents), c) nutritional status (malnutrition, normal weight, overweight, and obesity); body mass index (BMI) was calculated in children above two years of age, and anthropometric indicators of weight-for-age, height-for-age, and weight-for-height were used in children under two years of age, according to the Centers for Disease Control and Prevention tables,18 d) etiology (trauma, medications, systemic disease, idiopathy, biliary lithiasis, congenital abnormalities/periampullary obstruction, metabolic disorder, alcohol use, and infection), e) lipase level seven times the ULN,16 f) leukocyte count (neutropenia and leukocytosis), and g) albumin level.

Early complications were divided into local complications (pancreatic necrosis and acute peripancreatic fluid collection) and systemic complications (pulmonary, cardiac, metabolic, and renal). Risk factors were compared between patients who presented with complications and those who did not.

A total of 186 pediatric patients diagnosed with acute pancreatitis, who were admitted to the Hospital para el Niño Poblano within the time frame of July 2014 and July 2024, were identified. Forty-three of them were excluded because they did not meet the inclusion criteria, leaving a total of 143 patients, with a slight predominance of females (51%, n = 73) over males (49%, n = 70).

The mean age of the study patients was 10 years ± 4.6. The most frequent age group of the patients with acute pancreatitis was adolescents, at 45% (n = 64), followed by school-age children, at 34% (n = 48), and preschoolers, at 15% (n = 22). Infants were the least affected age group, at 6% (n = 9).

The most frequent nutritional status was normal weight (54%, n = 77), followed by overweight (18%, n = 25), obesity (15%, n = 22), and malnutrition (13%, n = 19).

Trauma was the main etiology, present in 22.4% (n = 32) of the patients, followed by medication-induced etiology in 16.9% (n = 28), systemic disease in 18.2% (n = 26), idiopathic disease in 14.7% (n = 21), biliary lithiasis in 11.9% (n = 17), and congenital abnormality/periampullary obstruction in 7.7% (n = 11). The least frequent causes were metabolic (2.8%, n = 4), alcohol-induced (1.4%, n = 2) and infectious (1.4%, n = 2).

Regarding medication-induced etiology, the most frequent drug was l-asparaginase in 19 of the 28 cases. Other hematology/oncology medications that caused acute pancreatitis were cisplatin (n = 1), mercaptopurine (n = 1), and steroids (n = 1). Regarding etiology secondary to systemic disease, sepsis was the most frequent specific cause (46.2%, n = 12). Other causes were hypoxia (23.1%, n = 6), systemic lupus erythematosus (19.2%, n = 5), hemophagocytic syndrome (7.7%, n = 2), and hypovolemic shock (3.8%, n = 1).

In stratification by severity grade, the most frequent level was severe, at 37% (n = 53), followed by mild, at 34% (n = 48), and moderate, at 29% (n = 42).

Of the patients with severe disease, the etiologies with greatest severity were trauma, at 36% (n = 19), systemic disease, at 32% (n = 17), and medication-induced, at 13% (n = 7) (Table 1).

Table 2 shows the values of the biochemical tests carried out on the study patients. Albumin values were outside of normal ranges (hypoalbuminemia) in 102 patients, 71 patients presented with leukocytosis, and 26 with leukopenia.

Local and systemic complications were evaluated. Regarding the former, the presence of pancreatic necrosis and acute peripancreatic fluid collection was studied. Only 16% (n = 23) of the patients had pancreatic necrosis, 12.6% (n = 18) had acute peripancreatic fluid collection, and 4.2% (n = 6) underwent surgical treatment.

The systemic complications observed in the patients were pulmonary in 18.18% (n = 26), cardiac in 51.75% (n = 74), metabolic in 16.08% (n = 23), and renal in 31.47% (n = 45) (Table 3).

Sixteen patients died during the study period, resulting in a mortality rate of 11.18%, signifying that of every nine patients admitted to the hospital during that time, one died.

Acute pancreatitis has not been considered common in the pediatric population, but in recent years, an increase in the number of cases has been seen, as reported by Vázquez Frias et al.1 They described figures from one to 13 cases per 100,000 pediatric patients, with a mean age at presentation of 9.2 ± 2.4 years, a 1:2 male-to-female ratio, and school-age children as the most affected age group. In our study, we also found a slight predominance of females, but the most affected age group was adolescents.

In Mexico, in 2023, the Asociación Mexicana de Gastroenterología1 issued a consensus on the diagnosis and treatment of acute pancreatitis in pediatric patients, stating that there is scant etiologic data in Mexico, with idiopathic and biliary etiologies reported as the most frequent. However, our study placed those two etiologies in fourth and fifth place, respectively, displaced at our institution by the more frequent etiologies of trauma, medications, and systemic disease. In 2014, Suzuki et al.2 commented that etiology may vary importantly between countries and institutions, as occurs in this case. Regarding medication-induced etiology, 19 out of 28 cases in our study were secondary to l-asparaginase, a drug that is known to have the risk of causing acute pancreatitis. Thus, it is extremely important to monitor patients receiving that treatment, especially hematology/oncology patients.

Abu-El-Haija et al.5 reported that most cases of acute pancreatitis were classified as mild. In our study, most of the cases were severe. Because the Hospital para el Niño Poblano is a tertiary care hospital that receives patients with special conditions, including polytraumatized patients, oncology patients, and patients with important organ dysfunction, this could explain why severe cases were the most common, with a higher number of early complication development, both local and systemic.

Mehta et al.6 reported that up to 30% of patients may present with an early complication. In our study, depending on the complication (local or systemic), 12 to 51% of the patients developed an early complication, and the most frequent were cardiac (51%) and renal (31%). Local complications (pancreatic necrosis and acute peripancreatic fluid collection) were less frequent in our study patients. A small number of them (4.2%) required surgical management, indicating that medical management is essential in those patients.

Obesity was confirmed as a risk factor for both systemic (metabolic) and local (peripancreatic collection) complications, coinciding with that reported by Thavamani et al.9 in 2020, who highlighted that both obesity and malnutrition were associated with longer hospital stay, higher costs, and greater disease severity.

Regarding local complications (acute pancreatic necrosis and acute peripancreatic fluid collection), we found a higher frequency in patients with idiopathic and biliary lithiasis etiologies, both with significant association. Of the systemic complications, traumatic etiology was significantly associated with cardiac complications, whereas etiology due to systemic diseases was related to renal complications.

Likewise, we identified that adolescents had a higher risk for developing renal complications. This finding has not been previously described in the literature and warrants more studies.

In our study, hypoalbuminemia was significantly associated with multiple complications (pulmonary and cardiac), but its value as a risk factor was inconsistent (OR < 1). This finding, even though in contrast with that reported by Mehta et al.,6 suggests the importance of monitoring albumin levels in those patients.

In 2013, Coffey et al.12 reported that a lipase level seven times the ULN may be associated with the development of complications, but in our study, it was not a risk factor for the development of early complications in patients with acute pancreatitis.

The mortality rate at our hospital was 11.18%, signifying that one out of every 9 study patients admitted to the hospital died from acute pancreatitis over a 10-year period. This is an alarming datum, given that, in 2019, Uc et al.17 reported a mortality rate below 5%, a concerning figure. Importantly, we found that leukopenia was a mortality risk factor, signifying that we must closely monitor hematology/oncology patients who present with acute pancreatitis.

There are few epidemiologic studies on acute pancreatitis and its risk factors associated with complications in the pediatric population in Mexico. In the present study, we found the clinical variables of obesity and biliary, traumatic, and systemic etiologies were significantly associated with the development of early complications; there was also a significant association between mortality and leukopenia. Those associations allowed us to establish a risk profile at hospital admission, facilitating early evaluation of the severity of the condition and favoring timely therapeutic decisions. We recommend validating our findings in prospective, multicenter studies with larger sample sizes.

The implementation of risk stratification based on the abovementioned factors will enable the development of complications, both local and systemic, to be anticipated and the multidisciplinary management of the pediatric patient with acute pancreatitis to be optimized. This raises the possibility of developing prognostic criteria similar to those utilized in the adult population, such as the Ranson criteria, but adapted to the pediatric population.

Acute pancreatitis is a current problem in the pediatric population that requires timely identification for the early performance of adequate interventions and the prevention of complications that may be fatal.

The present work meets the current bioethical research regulations. Because it contains no information that could identity the patient, ethics committee approval was not required. In addition, informed consent was not requested, given that this article contains no personal data that could identify the patient.

No experiments on humans or animals were conducted in this work. In addition, we declare that no type of generative artificial intelligence was utilized in the writing of this manuscript nor for the creation of figures, graphs, or tables.

This article was financed by the lead author.