See “Repeated Screening Can Be Restricted to At-Genetic-Risk Birth Cohorts” by Björck et al on page 271.
In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Sara Björck and coauthors publish their article “Repeated Screening Can Be Restricted to At-Genetic-Risk Birth Cohorts” (1). Basically, the authors prospectively performed celiac disease (CD) screening in HLA DQ2 and/or DQ8-positive (n = 2550) and -negative (n = 2904) children from a big Swedish birth cohort. CD screening was performed at both the ages 3 (n = 1620 and n = 1815, HLA-positive and -negative, respectively) and 9 years (n = 1910 and n = 2167, HLA-positive and -negative, respectively). Among 3-year-old HLA-positive children, 4.5% had tissue-transglutaminase antibodies (tTGA) and 3.5% developed CD, as confirmed by intestinal biopsy. At the age of 9 years, 4.1% of the children were tTGA-positive and CD was confirmed in 3.8%. Of the original cohort of children screened at age 3 years, 30 new patients with CD (3.1%) were identified by age 9 years. No patients with CD were diagnosed among the HLA-negative group. The authors conclude that the screening for CD can be restricted to children carrying HLA-DQ2 and/or DQ8 and repeated screening using tTGA is necessary to identify new patients by 9 years of age.
This article is interesting for 2 major reasons. First, it reopens the discussion on the indications for CD mass screening in the general population. Second, this study offers useful data on the diagnostic methods and patient ages during which CD screening must be performed.
CD mass screening has long been controversial mainly because of incomplete adherence to Wilson and Jungner's 10 classic screening principles (2). Literature shows that CD screening complies with the first 5 principles, that is, CD may be considered an important health problem, it has an accepted treatment, there are available diagnostic and treatment facilities, it has recognizable latent or early symptomatic stages, and there is a suitable test for disease detection. Until recently, information has been scarce to support the remaining principles, 6 to 10 (3). Current prospective evidence now, however, supports the idea that screening is well accepted (principle 6) (4). Moreover, the natural history of CD has been increasingly understood (principle 7) (5). CD develops frequently at a young age, and most children with affected first-degree relatives, as well as many from the general population, already have the disease by age 3 years (5,6). There is good compliance to a gluten-free diet in patients with CD detected by screening, thereby resulting in health improvement (principle 8) (7,8). Mass screening is also found to be cost-effective in young adults, assuming a standardized mortality ratio ≥ 1.5 in untreated patients, with a cost-efficiency of 48,960 USD/QALY (principle 9) (9). With the introduction of the rapid point of contact testing to determine tTGA, the cost of screening decreases as its effectiveness increases. Finally, CD mass screening may prove to be a continuous process (principle 10). Health economic evaluations for different age groups, using diverse strategies, will, however, be necessary to determine the specific age and method to use in mass screening. A screening, if done too early in life, risks missing CD that may develop later on, as shown by Björck et al (1). Doing so may, however, prevent the clinical manifestations of CD in the youngest of children (10), the ones mostly afflicted by severe forms of the disease. Moreover, CD screening 6 years thereafter may be considered too late because children detected by screening at this age already present with short stature and diminished bone mineral density (11). In addition, gluten-free dietary adherence is more easily learned at a younger age than later on in life. The ideal age for screening may also be country dependent because respective health care organizations may offer various “windows of opportunity” to perform this task. The convenience of disease screening through initial HLA-typing should also be the subject of health economic analyses in various settings. In novel pediatric screening, ethical implications must also be considered. These include promotion of informed choice by parents, an awareness for parental and staff acceptability, and regard for the psychological impact and parental anxiety that a child with a possible health condition or false-positive results may bring.
1. Björck S, Lynch K, Brundin C, et al. Repeated screening can be restricted to at-genetic-risk birth cohorts. J Pediatr Gastroenterol Nutr
2. Wilson JM, Jungner G. Principles and Practice of Screening for Disease. Geneva, Switzerland: World Health Organisation; 1968.
3. Mearin ML. The prevention of coeliac disease. Best Pract Res Clin Gastroenterol
4. Rosén A, Emmelin M, Carlsson A, et al. Mass screening for celiac disease from the perspective of newly diagnosed adolescents and their parents: a mixed-method study. BMC Public Health
5. Vriezinga SL, Auricchio R, Bravi E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med
6. Csizmadia CG, Mearin ML, von Blomberg BM, et al. An iceberg of childhood coeliac disease in the Netherlands. Lancet
7. Webb C, Myléus A, Norström F, et al. High adherence to a gluten-free diet in adolescents with screening-detected celiac disease. Pediatr Gastroenterol Nutr
8. Kurppa K, Paavola A, Collin P, et al. Benefits of a gluten-free diet for asymptomatic patients with serologic markers of celiac disease. Gastroenterology
9. Hershcovici T, Leshno M, Goldin E, et al. Cost effectiveness of mass screening for coeliac disease is determined by time-delay to diagnosis and quality of life on a gluten-free diet. Aliment Pharmacol Ther
10. Vriezinga SL, Schweizer JJ, Koning F, et al. Coeliac disease and gluten-related disorders in childhood. Nat Rev Gastroenterol Hepatol
11. Jansen MA, Kiefte-de Jong JC, Gaillard R, et al. Growth trajectories and bone mineral density in anti-tissue transglutaminase antibody-positive children: the Generation R Study. Clin Gastroenterol Hepatol