Introduction

Celiac disease (CD) is a chronic autoimmune condition, which affects mainly the small intesti ne in genetically susceptible individuals¹. The CD is an increasingly common disorder in both childhood and adulthood with a prevalence of 1% to 3% in the Western population, and it is considered that for each diagnosed patient there are other five non-diagnosed patients with CD².

Its etiopathogenesis is the result of gluten intake, which is a group of proteins that are present in cereals, such as wheat (gliadin), rye (secalin), barley (orcein), triticale, kamut, and spelt. In the CD, a severe decrea se in the nutrients absorption occurs, this deficiency would appear as a involvement of multiple tissues and systems, therefore, it becomes relevant in the child po pulation due to its fast development and growth^2,3.

In childhood, the CD classic presentation is cha racterized by intestinal disorders, such as chronic diarrhea, abdominal distention, chronic vomiting, recurrent abdominal pain, rectal prolapse, and constipation. However, the non-classic presentation with extraintestinal manifestations is becoming more fre quent, including stomatitis, endocrine, hepatic, neu rological, dermatological, hematological, and dental alterations, and short stature^4,5.

In the classic CD presentation, it is common to find malabsorption syndromes, which causes a deficiency of certain micronutrients⁶. Iron deficiency anemia is one of the most common hematological disorders due to the iron deficiency^2,4. However, the prolonged defi ciency of vitamin D (vitD) has been less studied, which causes bone mineralization alterations, leading to ric kets in children, osteopenia in adults and children, os teomalacia and osteoporosis mainly in adults⁷. In the last decade, the extra-bone roles of this vitamin have been discussed, since the characterization of the vit D metabolic pathway has demonstrated that its active form regulates the transcription of genes involved in adipogenesis, inflammation, and adipose tissue insulin resistance. The vit D has also been related to a potential role in autoimmune processes¹.

In the study conducted in Spain and Israel with children and adults with CD, Lerent et al. found that plasma 25-hydroxyvitamin D [25(OH)D] concen trations negatively correlated with age but not with intestinal damage, the older, the lower the 25(OH)D concentrations. According to this finding, there was no evidence of vit D deficiency in the pediatric popula tion with CD¹. A possible explanation is that the vit D deficiency in children and adults with CD would not depend exclusively on its gastrointestinal absorption, but also on the endogenous production of it, specia lly vitamin D3, which is formed from the exposure of 7-dehydrocholesterol in the skin through the solar ultraviolet-B rays transforming it into previtamin D3⁸.

So far, there is only one Chilean report published in 2003, where 25 celiac children were studied (aged from 5 to 15 years), who had low plasma concentra tions of vit D⁹. Since there is a lack of bibliographic information found in the Chilean children population, the objective of this study was to determine plasma concentration of 25(OH)D in Chilean children and adolescents with CD.

Patients and Method

Results

Out of the 16 pediatric patients, three were male and 13 were female, one preschooler, nine scholars and seven adolescents, with an average age of 11.04 ± 4 years (Table 1). According to the BMI, 11 children and adolescents had a normal nutritional status, four had overweight, and one had obesity. The height diagno sis showed seven cases of short stature and low normal height (Table 2). The fat and muscle compartments were mostly normal and only one patient had an increased FM% (Table 3).

Table 1 Baseline characteristics of patients. Data expressed as mean (DS) and median (Q1-Q3), percentage or current number. 

Table 2 Status Nutritional and concentrations of 25OHD D. 

Table 3 Indicators of Body Composition of patients. 

(Table 2) shows that four out of 16 patients had suffi cient plasma 25(OH)D concentrations, eight had insufficient and four had deficient concentrations.

Regarding hematocrit, the values ranged from 34% to 43%, presenting only one case under normal values according to his/her age. With regard to SGO-T and SGP-T, only one patient in the sample had higher- than-normal values (SGO-T: 69 U/l and SGP-T: 73 U/I). IgA results were normal for all patients. Fina lly, the ATA of two patents were higher-than-normal values (62.7 ng/ml and 63.5 UI/m) (Table 1). One of them with a recent CD diagnosis and the second one was in recovery from an infectious condition.

When associating the plasma 25(OH)D concentra tions with the nutritional status of the patients, insufficient and deficient parameters were found in nine ce liac patients with a normal nutritional status, two with overweight and one with obesity, representing 75% of the studied children and adolescents (Figure 1). The higher deficit was found in the normal nutritional sta tus. These results had no statistical significance.

Figure 1 25 OHD plasma concen trations according to nutritional status. 

Associations were made between the plasma 25(OH)D concentrations with the BMI classification, gender, height classification, FM%, AMC, AFA, AMA, and tricipital skinfold classification, where no statisti cally significant difference was found as well as in the associations between plasma 25(OH)D concentration with age, age of diagnosis, evolution time, height and BMI z-score, SGP-T, hemoglobin, hematocrit, IgA, ATA, FM%, and tricipital skinfold.

Discussion

Most of the studied group had an adequate con trol of the CD management, which was reflected in the ATA levels and the normal nutritional status, except for five patients with malnutrition by excess, four with overweight, and one with obesity. When comparing this with national data, we can observe that our sample showed lower figures of malnutrition by excess than the rest of the healthy Chilean child population¹⁹.

In a retrospective study of 390 Israeli children re cently diagnosed, with an average age of 7.1 years, an 11.8% overweight and 5.6% obesity prevalence was reported²⁰. In line with these results, the CD pediatric population in Western countries shows a malnutrition prevalence between 8% and 40%²¹. The coexistence of CD and obesity has been explained by the compensa tion theory, according to this hypothesis, those nu trients that cannot be absorbed due to the villi atrophy in the proximal small intestine is compensated by the increase in the absorption capacity of the distal small intestine. Therefore, these patients not only do not lose weight but could present overweight or obesity. In addition, it is well documented that the fat absorption coefficient remains static, thus, children with a high- energy intake can develop overweight or obesity^20,22.

In our study, a higher incidence of short stature and low normal height was observed (43.7%), similar to the results reported in the recent study of 530 Finnish children, where 182 (34%) of children with CD had short stature, however, it is important to note that the definition of short stature was different from the one used in our study²³. The most common extra intestinal manifestation in CD children is the short stature, although this association is not yet clear^24,25. Traditionally, it has been attributed to malnutrition, but other authors describe a growth hormone (GH) dysfunction in CD children. Reduced GH levels induce lower IGF-1 concentration, which may contribute to the IGF deregulation in CD children²⁴. Some authors propose that there could be two different physiopathological mechanisms for low height. On one hand, in children with classic symptomatology the cause would be malabsorption, and on the other hand, in those with non-classic presentation would be due to abnormali ties in the IGF-1 GH axis²³. Others describe that a late diagnosis, after the fourth year of age, is the most likely cause of this finding²⁶. In contrast, the recent study of Finnish children showed that short stature in symp tomatic children with CD would be associated with younger age and severe presentation at diagnosis²³.

In this study, the plasma 25(OH)D concentrations in blood were insufficient (20-29 ng/ml) and deficient (< 20 ng/ml) in 75% of the sample, which corresponds to 12 patients. Considering both insufficient and defi cient concentrations, in the Canadian study of 43 chil dren and adolescents (3-17 years), 43% of the sample showed 25(OH)D concentrations lower than 30ng/ ml at the moment of diagnosis²⁷, being lower than our study. In the case of only deficiency, four patients (25%) had it, which was different from the Erdem study⁴, where 50% of 52 pediatric patients from Turkey recently diagnosed with CD, showed 25(OH)D defi ciency, reported as a 25(OH)D deficiency (< 20 mg/ dL). In line with what was reported in the only Chilean study published in 2003, only five (20%) out of the 25 studied celiac children and adolescents had 25(OH)D concentrations lower than 15 ng/ml⁹, emphasizing that the insufficient cut-off point of this study was lower. In the Villanueva study⁸, in a retrospective sample of 24 American children with CD (3-12 years) who, when comparing them with a control group, had no diffe rences in the plasma 25(OH)D concentrations when sorting by BMI. Consistent with these findings, the Lerner et al. study carried out with Spanish and Israe li children and adults, no 25(OH)D deficiencies were found. These authors stated that the possible causes of sufficiency were due to a higher consumption of dairy products and vit D-fortified foods. In addition, they received routinely vit D supplements during the first year of life and had a higher sun exposure and a grea ter adherence to a gluten-free diet¹. It is important to emphasize that the main factors that can increase the vitD deficit risk are the geographic location and higher altitude, in the case of Concepción, which is located at 36° south latitude, which is the recognized limit of higher vit D deficiency risk. Other factors are older age, winter, dark skin, lower sun exposure, the use of sun protection factor, unhealthy eating habits, and low in take of vit D-fortified foods. It is important to note that there are no public policies of vit D food fortification in Chile.

When associating the plasma 25(OH)D concentra tion with the nutritional status in our study, the insufficient and deficient parameter were concentrated in the group with normal nutritional status (nine ca ses, 56.2%). However, no statistically significant diffe rences were found, contrary to what was reported in the Villanueva study, where CD children with obesity showed lower 25(OH)D concentrations, compared with eutrophic children (8). These findings are consis tent with other studies that report that the higher obe sity prevalence, the lower the 25(OH)D concentrations compared to healthy, non-obese children. On the one hand, it is suggested the excess of body fat increases the vit D sequestration and, on the other hand, a lower sun exposure due to sedentism and unhealthy diet in patients with obesity^8,28. It is probable that in the stu died group, most of them eutrophic, the possible use of permanent photoprotection and seasons influenced the 25(OH)D concentrations.

When comparing our results of plasma 25(OH) D concentrations with a recent study of 426 healthy school children that live in Santiago, Chile, we found that 39.7% of the sample had suboptimal 25(OH)D values (< 30 ng/ml), which is much less than the 75% observed in our study²⁹.

One of the limitations of our study is the sample size and the exclusive residence in Concepción. In addition, there was no control group to allow for fur ther analysis.

In conclusion, deficient and insufficient plasma 25(OH)D concentrations are frequent in the group of Chilean children and adolescents with CD, possi bly influenced by the geographic area, malabsorptive diseases, and not having public policies that favor the fortification of food with vit D in the regular diet.

Ethical Responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed according to the Declaration of Helsinki and the World Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regulations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.

Aknowledgments:

The authors wish to thank Project VRID No. 215.073.029-1, from the Universidad de Concepción, the Pro-Paciente Celíaco of Concepción Corporation, parents, caregivers, children participating in the pro ject and the Center for Healthy Life of the Universidad de Concepción.