Health-related quality of life is not impaired in children with undetected as well as diagnosed celiac disease: a large population based cross-sectional study

Celiac disease is one of the most common chronic diseases in childhood, affecting around 1% of the population [1]. In some genetically predisposed individuals, dietary intake of gluten, found in wheat, ray, and barley, results in an immune-mediated small intestinal enteropathy [1‐3]. Although the classical symptoms are related to the enteropathy (diarrhea, malnutrition, and failure to thrive), it has become evident that celiac disease can develop at any age with varying clinical presentations [4, 5]. Especially when untreated, the disease has been associated with an increased risk of morbidity and mortality [3, 6, 7]. Serological markers indicative of untreated disease are in general use, but demonstration of small intestinal enteropathy remains the gold standard for diagnosis [8]. With treatment, a strict gluten-free diet, the serological markers normalize, the small intestinal mucosa recovers, and symptoms alleviate [3, 9]. However, adhering to a strict gluten-free diet poses difficulties in everyday life including increased costs, social restrictions and stigmatisation, which may impact negatively on the health-related quality of life (HRQoL) [10‐14].

Screening studies have shown that the majority of children with celiac disease are undiagnosed [4, 15, 16], and mass screening might be an option for finding these cases [17]. The high rate of under-diagnosis has been attributed to the varying clinical presentation, where the classical gastrointestinal symptoms most commonly are either mild or lacking [9, 18]. Children with undiagnosed celiac disease do not experience enough symptoms to receive correct diagnosis; however, it remains poorly understood whether these children are completely unaffected or if undiagnosed celiac disease affects the HRQoL.

HRQoL assessments have become increasingly important in health care and research as it offers a more comprehensive understanding of the disease impact for the individual compared to that of laboratory analyses and disease related symptoms alone [19]. HRQoL is defined as a multidimensional construct encompassing several areas of life; physical, emotional, mental, social and behavioural components of functioning and wellbeing, as perceived by the individual and/or others [20, 21]. Several HRQoL instruments have been developed during the last decades, including a European cross-country instrument called Kidscreen [21, 22].

In previous studies among adults, undetected celiac disease has been associated with reduced HRQoL, mostly with a subsequent improvement after initiation of treatment [14, 23]. Such an improvement has also been seen among screening-detected cases [24, 25], although the findings are inconsistent [14, 23, 24, 26, 27]. Most previous studies of HRQoL and celiac disease have been performed among adults and studies of HRQoL in children with celiac disease are limited and inconclusive [23, 28‐31].

In this study we investigated and compared the HRQoL assessed by the generic Kidscreen instrument in three groups of 12-year-olds with: i) undetected celiac disease at the data collection, who thereafter received the diagnosis through screening, ii) clinically diagnosed celiac disease, and iii) children without celiac disease.

In this large population based study in Sweden, children with undetected celiac disease reported similar HRQoL as children with diagnosed celiac disease. These children also reported HRQoL comparable to Swedish children without celiac disease. Accordingly, children with undetected or diagnosed celiac disease were not at increased odds for having low HRQoL. To the best of our knowledge, this is the first large population based study capturing the HRQoL of children with both undetected and diagnosed celiac disease by use of a comprehensive standardized HRQoL measure.

A previous population based study from our group, found no HRQoL difference between 153 school aged children with undetected celiac disease and children without celiac disease, when investigating self-reported HRQoL by the shorter six item EQ-5D-Y HRQoL instrument [29]. In the current study we confirmed these results in an extended study group (238 12-year old children with undetected celiac disease) and by use of a more comprehensive assessment of HRQoL (full-form 52 item Kidscreen instrument). These findings thus suggest that HRQoL is not impaired in school aged children with undetected celiac disease.

One study in younger children is however partly contradictive. This study found lower parent-reported HRQoL in children diagnosed through screening at age 2–4 years, but only among the children with gastrointestinal symptoms; children without symptoms had similar HRQoL as a population based reference group [36]. In our study, stratifying for gastrointestinal symptoms did not affect the results. The issue of gastrointestinal symptoms in children with celiac disease is however complicated. In a qualitative study from our group it was shown that school aged children diagnosed with celiac disease through screening in retrospect realized that they had experienced a varying degree of symptoms associated with the undetected disease, which they were not aware of prior to treatment [13]. Similarly, among children who were diagnosed with celiac disease through screening in at-risk groups, 50% of those with no symptoms at diagnosis reported alleviation of symptoms after one year of treatment [28], further indicating that unawareness of celiac disease related symptoms prior to treatment is common among children. This adaption to symptoms related to celiac disease in childhood may partly explain the lack of HRQoL impairment in children with undetected celiac disease when they report prior to knowledge of the disease.

Our findings of an unimpaired self-reported HRQoL in children with undetected celiac disease contributes to an understanding of why most celiac disease cases are not identified in clinical practice. Despite moderate to severe enteropathy [16, 32], they are not presenting an affected overall HRQoL, and children with a low HRQoL do not have higher odds of undetected celiac disease than other children. Thus, mass screening using serological markers might be necessary to identify all cases of celiac disease. However, the issue of mass screening is still controversial and more research is needed before it can be determined whether it is an appropriate public health intervention or not [3, 17].

In our study also children with diagnosed celiac disease reported HRQoL corresponding to that of children without celiac disease. This finding has been seen also in other studies [29, 36, 37], although previous findings are not conclusive. Inconclusive findings could originate from different methods for assessing HRQoL, especially when taking different aspects of HRQoL into account. Domains more linked to feeding and socialization have been shown to be more impaired due to the gluten-free diet [30, 31, 38]. In line with these findings we saw the highest odds for low HRQoL among children with diagnosed celiac disease in the subdomain school environment, although the difference was not statistically significant (Table 2). A celiac disease specific HRQoL instrument focuses in detail on aspects affected by the gluten-free diet and could therefore be more sensitive than a generic instrument [23, 38]. Thus, we cannot exclude that our findings could, at least partly, be explained by a failure of the generic instrument Kidscreen to fully capture if diagnosed celiac disease affects HRQoL.

It has been shown that adherence with the gluten-free diet is important for obtaining similar HRQoL among children with celiac disease as their peers [39]. However, the burden of following a strict gluten-free diet has been associated with reduced HRQoL [40]. In our study, adherence with the gluten-free diet was high (92%) in comparison with other studies [14, 31, 41]. However, occasional gluten intake might not be captured by elevated tTG resulting in overestimation of the adherence. We were also limited by the cross-sectional study design where inference whether non-adherence affected HRQoL, or if children with low HRQoL due to other reasons did not manage to adhere to the gluten-free diet, could not be made. Therefore, we did not further investigate the influence of adherence on HRQoL in our study. Larger longitudinal studies investigating the influence of treatment adherence on HRQoL, and visa verse, are warranted.

A strength of our study was that it was based on an actual population-based screening study. Thus, the children with undetected celiac disease emanated from the general population, and in contrast to several other studies, we were able to assess the HRQoL prior to the diagnosis of screening-detected celiac disease [23, 28]. Moreover, the children with diagnosed celiac disease were also identified from the general population, compared to the more common recruitment through patient societies [23]. As there may be a selection in who joins a patient society, the current strategy is likely to give a more accurate description of HRQoL in children with diagnosed celiac disease. The population-based strategy, however, also constituted a limitation. Albeit a relatively large cohort (n = 12 419 participants) the number of children with celiac disease were limited and we cannot exclude that lack of power affected our findings, especially after stratifications. The participants comprised 69% of all invited children in sixth grade. Their HRQoL were comparable to the that found by the Swedish National Institute of Public Health when they performed a countrywide, all-encompassing survey using the same HRQoL instrument, during the same time period, and in the same age group [42]. This suggests that our HRQoL results are representative for 12-year-old children in Sweden, and due to the homogeneity of the Swedish society, the association between HRQoL and celiac disease likely is the same across the country. The lack of adjustment for socioeconomic status may, however, constitute a potential limitation. Socioeconomic status is negatively associated with HRQoL [43], and might be associated with celiac disease, thereby constituting a potential confounder. However, the relationship between socioeconomic status and celiac disease has contradictory findings also from Sweden [44‐46], with the largest study rejecting an association [47]. To the best of our knowledge, the only previous study which has tested the potential influence of socioeconomic status on HRQoL in celiac disease did not find an association between the two [48].

Children with undetected and thereby untreated celiac disease reported comparable HRQoL as their peers when reporting prior to receiving the celiac disease diagnosis through screening. They also reported similar HRQoL as children with diagnosed celiac disease. Thus, children with diagnosed and treated celiac disease may be able to attain the same HRQoL as their peers without the disease. HRQoL encompasses several areas of functioning and wellbeing, and the current study suggests that children with celiac disease, both undetected and diagnosed, perceive unimpaired functioning and wellbeing within all such areas of HRQoL.