Celiac disease (CD) is a multifactorial, immune-mediated enteropathic disorder that may occur at any age with heterogeneous clinical presentation. In the last years, unusual manifestations have become very frequent, and currently, it is not so uncommon to diagnose CD in subjects with overweight or obesity, especially in adults; however, little is known in the pediatric population. This systematic review aims to evaluate the literature regarding the association between CD and overweight/obesity in school-age children.
Methods:
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. An electronic database search of articles published in the last 20 years in English was carried out in Web of Sciences, PubMed, and Medline. The quality of the included studies was assessed by using the STrengthening the Reporting of OBservational studies in Epidemiology statement.
Results:
Of the 1396 articles identified, 9 articles, investigating overweight/obesity in children/adolescents affected by CD or screening CD in children/adolescents with overweight/obesity, met the inclusion criteria. Overall, the results showed that the prevalence of overweight or obesity in school-age children (6–17 years) affected by CD ranged between 3.5% and 20%, highlighting that the coexistence of CD with overweight/obesity in children is not uncommon as previously thought.
Conclusion:
Although CD has been historically correlated with being underweight due to malabsorption, it should be evaluated also in children with overweight and obesity, especially those who have a familiar predisposition to other autoimmune diseases and/or manifest unusual symptoms of CD.
KagnoffMK.Overview and pathogenesis of celiac disease. Gastroenterology, 2005; 128:S10–S18.
3.
ElliL, FerrettiF, OrlandoS, et al.Management of celiac disease in daily clinical practice. Eur J Intern Med, 2019; 61:15–24.
4.
FasanoA, CatassiC. Celiac disease. N Engl J Med, 2012; 367:2419–2426.
5.
KangJY, KangAHY, GreenA, et al.Systematic review: Worldwide variation in the frequency of coeliac disease and changes over time. Aliment Pharmacol Ther, 2013; 38(3):226–245.
6.
SinghP, AroraA, StrandTA, et al.Global prevalence of celiac disease: Systematic review and meta-analysis. Clin Gastroenterol Hepatol, 2018; 16(6):823–836.e2.
7.
LionettiE, CatassiC. New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment. Int Rev Immunol, 2011; 30(4):219–231.
8.
GuandaliniS, AssiriA. Celiac disease: A review. JAMA Pediatr, 2014; 168(3):272–278.
ReillyNR, FasanoA, GreenPHR. Presentation of celiac disease. Gastrointest Endosc Clin N Am, 2012; 22(4):613–621.
11.
VillanuevaM, OyarzúnA, LeytonB, et al.Changes in age at diagnosis and nutritional course of celiac disease in the last two decades. Nutrients, 2020; 12(1):156.
12.
TelegaG, BennetTR, WerlinS. Emerging new clinical patterns in the presentation of celiac disease. Arch Pediatr Adolesc Med, 2008; 162(2):164–168.
13.
NardecchiaS, AuricchioR, DiscepoloV, et al.Extra-intestinal manifestations of coeliac disease in children: Clinical features and mechanisms. Front Pediatr, 2019; 7:56.
CiccocioppoR, KruzliakP, CangemiGC, et al.The spectrum of differences between childhood and adulthood celiac disease. Nutrients, 2015; 7(10):8733–8751.
16.
GhiselliA, BizzarriB, GaianiF, et al.Growth changes after gluteen free diet in pediatric celiac patients: A literature-review. Acta Biomed, 2018; 89(9-S):5–10.
17.
DickeyW, KearneyN. Overweight in celiac disease: Prevalence, clinical characteristics, and effect of a gluten-free diet. Am J Gastroenterol, 2006; 101(10):2356–2359.
18.
TuckerE, RostamiK, PrabhakaranS, et al.Patients with coeliac disease are increasingly overweight or obese on presentation. J Gastrointestin Liver Dis, 2012; 21(1):11–15.
19.
CardTR, WestJ, HolmesGKT. Risk of malignancy in diagnosed coeliac disease: A 24-year prospective, population-based, cohort study. Aliment Pharmacol Ther, 2004; 20(7):769–775.
20.
SinghI, AgnihotriA, SharmaA, et al.Patients with celiac disease may have normal weight or may even be overweight. Indian J Gastroenterol, 2016; 35(1):20–24.
21.
ShahrakiT, ShahrakiM, HillID. Frequency of overweight/obesity among a group of children with celiac disease in Iran. Prz Gastroenterol, 2018; 13(2):127–131.
22.
GrandoneA, MarzuilloP, CirilloG, et al.FTO polymorphism rs9939609 contributes to weight changes in children with celiac disease on gluten-free diet. J Pediatr Gastroenterol Nutr, 2015; 61(2):220–223.
23.
NennaR, MoscaA, MenniniM, et al.Coeliac disease screening among a large cohort of overweight/obese children. J Pediatr Gastroenterol Nutr, 2015; 60(3):405–407.
24.
VallettaE, FornaroM, CipolliM, et al.Celiac disease and obesity: Need for nutritional follow-up after diagnosis. Eur J Clin Nutr, 2010; 64(11):1371–1372.
ReillyNR, AguilarK, HassidBG, et al.Celiac disease in normal-weight and overweight children: Clinical features and growth outcomes following a gluten-free diet. J Pediatr Gastroenterol Nutr, 2011; 53(5):528–531.
27.
NorsaL, ShamirR, ZevitN, et al.Cardiovascular disease risk factor profiles in children with celiac disease on gluten-free diets. World J Gastroenterol, 2013; 19(34):5658–5664.
28.
BrambillaP, PiccaM, DililloD, et al.Changes of body mass index in celiac children on a gluten-free diet. Nutr Metab Cardiovasc Dis, 2013; 23(3):177–1782.
29.
van der PalsM, MyléusA, NorströmF, et al.Body mass index is not a reliable tool in predicting celiac disease in children. BMC Pediatr, 2014; 14:165.
30.
CalcaterraV, RegalbutoC, ManuelliM, et al.Screening for celiac disease among children with overweight and obesity: Toward exploring celiac iceberg. J Pediatr Endocrinol Metab, 2020; 33(8):995–1002.
31.
LiberatiA, AltmanDG, TetzlaffJ, et al.The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration. PLoS Med, 2009; 6(7):e1000100.
ColeTJ, BellizziMC, FlegalKM, et al.Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ, 2000; 320(7244):1240–1243.
34.
ColeTJ, FlegalKM, NichollsD, et al.Body mass index cut offs to define thinness in children and adolescents: International survey. BMJ, 2007; 335(7612):194.
35.
de OnisM, OnyangoAW, BorghiE, et al.Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ, 2007; 85(9):660–667.
36.
CacciariE, MilaniS, BalsamoA, et al.Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest, 2006; 29(7):581–593.
37.
KuczmarskiRJ, OgdenCL, Grummer-StrawnLM, et al.CDC growth charts: United States. Adv Data, 2000;(314):1–27.
38.
De OnisM. World Health Organization reference curves. In: The ECOG's eBook on Child and Adolescent Obesity (FrelutM.L. ed.). 2015. Available from: ebook.ecog-obesity.eu [Last accessed: December 2, 2021].
39.
Revised criteria for diagnosis of coeliac disease. Report of working group of European Society of paediatric gastroenterology and nutrition. Arch Dis Child, 1990; 65:909–911.
40.
HusbyS, KoletzkoS, Korponay-SzabóIR, et al.European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr, 2012; 54(1):136–160.
41.
HusbyS, KoletzkoS, Korponay-SzabóIR, et al.European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr, 2020; 70(1):141–156.
42.
HillID, DirksMH, LiptakGS, et al.Guideline for the diagnosis and treatment of celiac disease in children: Recommendations of the North American Society for pediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr, 2005; 40:1–19.
43.
MurchS, JenkinsH, AuthM, et al.Joint BSPGHAN and Coeliac UK guidelines for the diagnosis and management of coeliac disease in children. Arch Dis Child, 2013; 98(10):806–811.
44.
von ElmE, AltmanDG, EggerM, et al.The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies. PLoS Med, 2007:16; 4(10):e296.
45.
VandenbrouckeJP, von ElmE, AltmanDG, et al.Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration. Ann Intern Med, 2007; 147(8):W163–W194.
46.
AssaA, Frenkel-NirY, TzurD, et al.Cardiovascular risk factors in adolescents with celiac disease: A cross-sectional population-based study. J Pediatr Gastroenterol Nutr, 2017; 65(2):190–194.
47.
Al-HussainiA, TronconeR, KhormiM, et al.Mass screening for celiac disease among school-aged children: Toward exploring celiac iceberg in Saudi Arabia. J Pediatr Gastroenterol Nutr, 2017; 65(6):646–651.
48.
SansottaN, GuandaliniS, RomanoS, et al.The gluten free diet's impact on growth in children with celiac disease in two different countries. Nutrients, 2020; 12(6):1547.
49.
Al-RaeeMB, El-SakkaMA, Al-WahaidiAA. In depth analysis of risk factors for coeliac disease amongst children under 18 years old in the Gaza strip. A cross sectional study. Nutr J, 2012; 11:97.
50.
AurangzebB, LeachST, LembergDA, et al.Nutritional status of children with coeliac disease. Acta Paediatr, 2010; 99(7):1020–1025.
51.
CapriatiT, FrancavillaR, FerrettiF, et al.The overweight: A rare presentation of celiac disease. Eur J Clin Nutr, 2016; 70(2):282–284.
52.
GokceS, ArslantasE. Changing face and clinical features of celiac disease in children. Pediatr Int, 2015; 57(1):107–112.
53.
TsiountsiouraM, WongJE, UptonJ, et al.Detailed assessment of nutritional status and eating patterns in children with gastrointestinal diseases attending an outpatients clinic and contemporary healthy controls. Eur J Clin Nutr, 2014; 68(6):700–706.
54.
NennaR, TibertiC, PetrarcaL, et al.The celiac iceberg: Characterization of the disease in primary schoolchildren. J Pediatr Gastroenterol Nutr, 2013; 56(4):416–421.
55.
MyléusA, IvarssonA, WebbC, et al.Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic. J Pediatr Gastroenterol Nutr, 2009; 49(2):170–176.
56.
GemmeG, VignoloM, NaselliA, et al.Linear growth and skeletal maturation in subjects with treated celiac disease. J Pediatr Gastroenterol Nutr, 1999; 29(3):339–342.
57.
FasanoA, CatassiC. Current approaches to diagnosis and treatment of celiac disease: An evolving spectrum. Gastroenterology, 2001; 120:636–651.
58.
NCD Risk Factor Collaboration (NCD-RisC).Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: A pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet, 2017; 390(10113):2627–2642.
59.
KlingelhöferD, BraunM, QuarcooD, et al.Epidemiological influences and requirements of global childhood obesity research. Obes Facts, 2021; 14(4):382–396.
60.
DiamantiA, CapriatiT, BassoMS, et al.Celiac disease and overweight in children: An update. Nutrients, 2014; 6:207–220.
61.
AzzopardiPS, HearpsSJC, FrancisKL, et al.Progress in adolescent health and wellbeing: Tracking 12 headline indicators for 195 countries and territories, 1990–2016. Lancet, 2019; 393:1101–1118.
62.
PattonGC, SawyerSM, SantelliJS, et al.Our future: A Lancet commission on adolescent health and wellbeing. Lancet, 2016; 387:2423–2478.
63.
WilletW, RockströmJ, LokenB, et al.Food in the anthropocene: The EAT–Lancet Commission on healthy diets from sustainable food systems. Lancet, 2019; 393:447–492.
64.
SukkarG, AlshareefAM, AljahaniM, et al.The prevalence of growth variations among pediatric celiac disease patients at the time of diagnosis. Cureus, 2020; 12(11):e11706.
65.
MurrayJA, WatsonT, ClearmanB, et al.Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr, 2004; 79(4):669–673.
66.
BankaitisEC, HaA, KuoCJ, et al.Reserve stem cells in intestinal homeostasis and injury. Gastroenterology, 2018; 155(5):1348–1361.
LevranN, WilschanskiM, LivovskJ, et al.Obesogenic habits among children and their families in response to initiation of gluten-free diet. Eur J Pediatr, 2018; 177(6):859–866.
69.
PetersenC, RoundJL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol, 2014; 16(7):1024–1033.
70.
SinghP, RawatA, Al-JarrahB, et al.Distinctive microbial signatures and gut-brain crosstalk in pediatric patients with coeliac disease and type 1 diabetes mellitus. Int J Mol Sci, 2021; 22(4):1511.
71.
PetraroliM, CastelloneE, PatiannaV, et al.Gut microbiota and obesity in adults and children: The state of the art. Front Pediatr, 2021; 9:657020.
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