The prevalence of childhood obesity in the United States is one in five children. An increase in prevalence continues in most categories of obesity across all age groups, in particular adolescents, with 41.5% of 16- to 19-year-olds affected by obesity (Skinner, Ravanbakht, Skelton, Perrin, & Armstrong, 2018). Obesity is associated with many health problems, with the most recognized being cardiovascular disease and metabolic disorders. Gallbladder disease is an established obesity-related comorbidity in adults. Currently, the association between obesity and gallbladder disease is being studied in children and adolescents in light of the obesity epidemic (Mehta et al., 2012). The purpose of this review is to highlight an increasing cause of right upper quadrant pain in children and adolescents also affected by obesity.
Along with the rise of childhood obesity, the incidence of gallstones is increasing in children and adolescents; therefore, more cholecystectomies are now performed in this population (Balaguer, Price, & Burd, 2006). Obesity increases the risk of gallstones more than fourfold in youth and causes 8%–33% of pediatric gallstones in children (Baker et al., 2005). Biliary dyskinesia is increasingly recognized as the cause of abdominal pain in children and adolescents, which results in the need for cholecystectomy (Vegunta et al., 2005). It is important that clinicians are aware of the increased incidence of biliary disease in children and adolescents with obesity to better enable them to diagnose and manage this condition.
Whereas gallstone disease and cholecystectomy are common in adults, they have been rare in pediatric patients and historically have been associated with hemolytic disease, prematurity, and parental nutrition (Greer, Heywood, Croaker, & Gananadha, 2018; Kim, Kim, & Cho, 2015). The demographics of children who require a cholecystectomy are changing with an increased prevalence of pediatric cholecystectomy because of gallstone disease related to obesity worldwide (Kim et al., 2015).
BILIARY DISEASE AND PEDIATRIC OBESITY
Children and adolescents with obesity now comprise a significant portion of the patients with biliary disease who require cholecystectomy. The association in adults between obesity and gallstone formation is well established; recent research shows a similar association in children and adolescents (Greer et al., 2018; Kim et al., 2015). In a study by Frybova et al. (2018), results suggested that elevated body mass index (BMI) in children was a risk factor for developing choledocholithiasis; patients with cholelithiasis had a significantly higher BMI than the general pediatric population, and patients with choledocholithiais had a significantly higher BMI than patients with cholelithiasis (Frybova et al., 2018).
More recent data also suggest that gallbladder disease related to nonhemolytic risk factors such as obesity, female gender, ethnicity, oral contraceptive use, and pregnancy is rising (Mehta et al., 2012). A study by Khoo, Cartwright, Berry, and Davenport (2014) shows a dramatic increase in pediatric cholecystectomy among White females in England since 1997, but the risk factor of obesity is only inferred because obesity was poorly coded as a secondary diagnosis in the study. There are also certain risk factors in adults that can be assumed in children: female gender and adolescence (older than age 12) (Kim et al., 2015). Changing demographics for gallstone disease in children are seen in several countries within the Organization for Economic Cooperation and Development, with a rise in obesity among children and adolescents of White ethnicity and female patients (Campbell et al., 2016).
With the changing etiology of gallstone disease in children, the risk profile is now similar to adults with a female predominance and a trend toward adolescence. A study by Campbell et al. (2016) showed that pediatric gallstone disease is most common in female adolescents with obesity (Campbell et al., 2016). In the study by Mehta et al. (2012), gallstone disease was associated with hemolytic disease in 23% of patients and 39% in those with obesity. Results in children with obesity indicated older age and Hispanic ethnicity as independent risk factors for nonhemolytic disease (Mehta et al., 2012), particularly with children with severe obesity (over the 99th percentile for age and gender).
In a study by Kiuru et al. (2014), obesity was a risk factor for cholecystectomy, with most cholecystectomies performed on female patients. The female predominance was seen after puberty in adolescence, particularly in the subjects with obesity. The trend toward female predominance is not surprising given the association between female hormonal changes of puberty and their effect on gallbladder motility promoting gallstone formation (Greer et al., 2018; Khoo et al., 2014).
In addition, women who use oral contraceptives are at a higher risk of developing gallstones than their peers irrespective of weight (Khoo et al., 2014). Other studies suggest that pregnancy also increases the risk of gallstones and the need for cholecystectomy in the adolescent population (Constantinescu et al., 2012). In regard to parity, an early study by Honoré (1980) showed a strong association between cholesterol cholelithiasis, obesity, and parity. In addition, patients with gallstone disease had a higher rate of contraceptive use (Honoré, 1980).
PRESENTATION AND TREATMENT
The patient with cholelithiasis or acute cholecystitis often presents with right upper quadrant pain, typically worse after eating. Patients may experience nausea or vomiting with a possible history of gallstones. A physical examination may elicit pain when the patient breathes deeply while the examiner palpates the abdomen in the region of the gallbladder (known as Murphy's sign). Emergency room evaluation includes laboratory tests (complete blood count, basic metabolic panel, urinalysis, liver function tests, amylase, lipase, and beta human chorionic gonadotropin (hCG) in female patients who have reached menarche) as well as abdominal ultrasound to rule out the presence of gallstones, thickened gallbladder wall, and pericholecystic fluid (Stoops & Slusher, 2013).
A child or adolescent diagnosed with gallstones will require a cholecystectomy, but the procedure is not urgent and can be scheduled as an elective outpatient procedure. A delayed diagnosis of cholelithiasis may lead to more serious disease states, most often acute cholecystitis. A patient with acute cholecystitis often presents with fever, vomiting, and right upper quadrant pain with potentially elevated liver function tests, serum amylase, and white blood count. This patient requires hospital admission, intravenous antibiotics, and emergent surgery (Hebra & Lesher, 2011). Complicated obstructive disease and gallstone pancreatitis are two further complications of a delayed diagnosis of gallstones. Patients with choledocholithiasis often need hospitalization, requiring an endoscopic retrograde cholangiopancreatography before cholecystectomy once their liver enzymes and amylase levels decrease or normalize (Frybova et al., 2018).
In the infant population, gallstones sometimes spontaneously resolve without intervention (Jacir, Anderson, Eichelberger, & Guzzetta, 1986). However, in children older than 2 years old, the resolution of gallstones is low, so cholecystectomy is the treatment of choice (Stringer, 2005). Laparoscopic cholecystectomy rather than open cholecystectomy is the standard operative approach irrespective of obesity (Mehta et al., 2012; Rothstein & Harmon, 2016). Obesity is not found to affect perioperative parameters or surgical approach (Kiuru et al., 2014) but may increase operative time in children in laparoscopic cholecystectomy (Pandian, Ubl, Habermann, Moir, & Ishitani, 2017).
One limitation of the studies presented here is interpreting whether the increasing incidence of cholecystectomy represents a true rise in gallstone disease or a result of better detection of gallstones with the widespread use of ultrasonography (Greer et al., 2018; Khoo et al., 2014; Rothstein & Harmon, 2016). However, most asymptomatic gallstones do not require cholecystectomies, which limits the role of ultrasonography in the increasing rates of cholecystectomy (Greer et al., 2018).
Children and adolescents with a BMI over the 85th percentile, who present with right upper quadrant or epigastric pain, need to be assessed for gallbladder disease. Studies clearly show a marked increase in the incidence of gallstones and cholecystectomy in children and adolescents worldwide. The main reason for the increased incidence appears to be early-onset overweight and obesity (Khoo et al., 2014). Within this vulnerable population, there is a female predominance with White and Hispanic ethnicity majority. Clinicians need to be aware of the comorbidity of gallbladder disease and the subsequent need for cholecystectomy in children and adolescents with obesity to allow for early detection and treatment for this patient population.
Baker S., Barlow S., Cochran W., Fuchs G., Klish W., Krebs N., … Udall J. (2005). Overweight children and adolescents: A clinical report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of Pediatric Gastroenterology and Nutrition
, 40(5), 533–543.
Balaguer E. J., Price M. R., & Burd R. S. (2006). National trends in the utilization of cholecystectomy in children. The Journal of Surgical Research
, 134(1), 68–73.
Campbell S., Richardson B., Mishra P., Wong M., Samarakkody U., Beasley S., … Morreau P. (2016). Childhood cholecystectomy in New Zealand: A multicenter national 10year perspective. Journal of Pediatric Surgery
, 51(2), 264–267.
Constantinescu T., Huwood Al Jabouri A. K., Brãtucu E., Olteanu C., Toma M., & Stoiculescu A. (2012). Gallstone disease in young population: Incidence, complications, therapeutic approach. Chirurgia (Bucharest, Romania: 1990)
, 107(5), 579–582.
Frybova B., Drabek J., Lochmannova J., Douda L., Hlava S., Zemkova D., … Keil R. (2018). Cholelithiasis and choledocholithiasis in children; risk factors for development. PLoS One
, 13(5), e0196475.
Greer D., Heywood S., Croaker D., & Gananadha S. (2018). Is 14 the new 40: Trends in gallstone disease and cholecystectomy in Australian Children. Pediatric Surgery International
, 34(8), 845–849.
Hebra A., & Lesher A. (2011). Cholecystitis. In Mattei P. (Ed.), Fundamentals of pediatric surgery
( ed., pp. 579–585). New York, NY: Springer.
Honoré L. H. (1980). Cholesterol cholelithiasis in adolescent females: Its connection with obesity, parity, and oral contraceptive use—A retrospective study of 31 cases. The Archives of Surgery
, 115(1), 62–64.
Jacir N. N., Anderson K. D., Eichelberger M., & Guzzetta P. C. (1986). Cholelithiasis in infancy: Resolution of gallstones in three of four infants. Journal of Pediatric Surgery
, 21(7), 567–569.
Khoo A. K., Cartwright R., Berry S., & Davenport M. (2014). Cholecystectomy in English children: Evidence of an epidemic (1997–2012). Journal of Pediatric Surgery
, 49(2), 284–288.
Kim H. Y., Kim S. H., & Cho Y. H. (2015). Pediatric cholecystectomy: Clinical significance of cases unrelated to hematologic disorders. Pediatric Gastroenterology, Hepatology & Nutrition
, 18(2), 115–120.
Kiuru E., Kokki H., Juvonen P., Lintula H., Paajanen H., Gissler M., & Eskelinen M. (2014). The impact of age and sex adjusted body mass index (ISO-BMI) in obese versus non-obese children and adolescents with cholecystectomy. In Vivo
, 28(4), 615–619.
Mehta S., Lopez M. E., Chumpitazi B. P., Mazziotti M. V., Brandt M. L., & Fishman D. S. (2012). Clinical characteristics and risk factors for symptomatic pediatric gallbladder disease. Pediatrics
, 129(1), e82–e88.
Pandian T. K., Ubl D. S., Habermann E. B., Moir C. R., & Ishitani M. B. (2017). Obesity increases operative time in children undergoing laparoscopic cholecystectomy. Journal of Laparoendoscopic and Advanced Surgical Techniques
, 27(3), 322–327.
Rothstein D. H., & Harmon C. M. (2016). Gallbladder disease in children. Seminars in Pediatric Surgery
, 15(4), 225–231.
Skinner A. C., Ravanbakht S. N., Skelton J. A., Perrin E. M., & Armstrong S. C. (2018). Prevalence of obesity and severe obesity in US children, 1999–2016. Pediatrics
, 141(3), e20173459. doi:
Stoops M. M., & Slusher J. A. (2013). Splenectomy and cholecystectomy. In Browne N. T., Flanigan L. M., McComiskey C. A., & Pieper P. (Eds.), Nursing care of the pediatric surgical patient
(3rd ed., pp. 417–432). Burlington, MA: Jones & Bartlett Learning, LLC.
Stringer M. D. (2005). Disorders of the gallbladder and biliary tract. In Oldham K. T., Columbani P. M., Foglia R. P., & Skinner M. A. (Eds.), Principles and practice of pediatric surgery
( ed., pp. 1495–1510). Philadelphia, PA: Lippincott Williams & Wilkins.
Vegunta R. K., Raso M., Pollock J., Misra S., Wallace L. J., Torres A. Jr., Pearl R. H. (2005). Biliary dyskinesia: The most common indication for cholecystectomy in children. Surgery
, 138(4), 726–731.