Edraki et al. BMC Pediatrics(2024) 24:513
https://doi.org/10.1186/s12887-023-04283-9

BMC Pediatrics

RESEARCH

Open AccessFrequency of seropositive celiac disease
and hypothyroidism among children
and adolescents with congenital heartdisease: A case-control study
Mohammad Reza Edraki1, Ali Jamshidi Kerachi2, Negar Yazdani3, Naser Honar3,4*, Reza Dehghani5, Zhila Afshar2,
Mohsen Dehghani6 and Hamid Amoozgar1
Abstract
Background The prevalence of celiac disease (CD) and hypothyroidism exhibit significant variation in different
studies among patients with congenital heart disease (CHD). This study evaluated the frequency of laboratory test
abnormalities in children and adolescents with CHD in Shiraz, Iran.
Methods This prospective case-control study was conducted on 223 children and adolescents with CHD and healthy
individuals referred to the heart clinic affiliated with Shiraz University of Medical Sciences between February 2019 andDecember 2021. They were classified into case and control groups. Blood tests were performed for total IgA antibody,anti-tissue transglutaminase IgA antibody (anti-TTG Ab), T4, and thyroid stimulating hormone (TSH) and anti-thyroid
peroxidase antibodies in serum, along with transthoracic echocardiography. Likewise, demographic characteristics
of patients, including age, sex, weight, height, and body mass index (BMI), were recorded. Also, anti-TTG Ab levels
were compared among CHD patients according to cyanosis status, gender, age (above and below five years), and BMI(under and over 18.5).
Results Ninety-eight CHD patients and 100 healthy individuals with an average age of 5.32 ± 4.05 years (1–18 years)
were examined. In children with CHD, atrial septal defect (27%), ventricular septal defect (20%), and tetralogy of Fallot(13%) were the most prevalent disorders. Only one CHD patient had an anti-TTG Ab level of 16.6 unit/mL, consideredborderline for seropositive CD diagnosis. There was no difference in anti-TTG Ab levels between age (above andbelow five years), BMI (under and over 18.5), cyanosis status, and gender groups. Seven CHD patients had high TSHlevels, three had cyanotic CHD, and one had Down syndrome. The TSH levels and non-autoimmune hypothyroidism
were significantly higher in CHD patients than in normal subjects (p < 0.05).
Conclusions According to the results of this study, the serum level of TSH and prevalence of non-autoimmune
hypothyroidism were higher in patients with CHD than in normal subjects, but the serum level of anti-TTG Ab was notdifferent between the two groups.

*Correspondence:
Naser Honar
honarn@sums.ac.ir
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use,sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) andthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in thisarticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not includedin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you willneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The
Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available
in this article, unless otherwise stated in a credit line to the data.

Edraki et al. BMC Pediatrics(2024) 24:513

Page 2 of 6

Keywords Child, Congenital heart defects, Hypothyroidism, Adolescence, Celiac Disease

Background
Celiac disease (CD) is an enteropathy linked to theimmune system, defined as a permanent genetic sensitivity to wheat gliadin or other prolamins in oats [1]. Thiscondition occurs through the interaction among gluten,
immune factors, genetics, and environment [2]. The CDprevalence ranges from 0.5 to 3% worldwide [3]. For
instance, its prevalence in Europe and the Asia-Pacificregion is reported as 2.67%, while it is 1% in Iran [4].
Some studies support a possible association between
congenital heart disease (CHD) and CD and thyroid dysfunction [5, 6]. However, a study by Bhargava et al. in
India stated that the relationship between CD and CHD
is rare [7].
The abnormal immunological profiles of the cellularand humoral immune systems in CD and thyroid disease
have a genetic origin. Genetic ailments are also seen in
CHDs [8], which may describe why the higher prevalenceof some chromosomal disorders, such as Down syndrome, exists in CHD [4]. In some studies, CD was associated with several congenital malformations in the face,neck, ear, heart, and digestive system [5].
Furthermore, due to some genetic comparations,patients with CHD have a higher prevalence of thyroid
dysfunction, so in some studies, 5% of infants with congenital hypothyroidism had CHD [9]. Among the origins
of congenital hypothyroidism and CHD, we can mention
the expression of the NKX2.5 genes in the heart and thyroid, its mutation, and the role of the HOXA3 and TBX1
genes in the development of the thyroid, blood vessels,
and heart structures [10]. Also, during embryogenesis,
the thyroid gland shares nuclear transcription factors
with the heart and the great vessels during organogenesis [11]. Mild hypothyroidism has also been observedin about 12% of children with CHD, which is perhaps
related to thyroid autoimmunity or dysgenesis [11]. One
study reported a 10-fold higher risk of non-autoimmune
hypothyroidism in CHD patients than in individuals
without CHD [12]. However, there is still insufficient
information about the prevalence and severity of thyroid
disorders among patients with CHD.
Since the prevalence of CD and hypothyroidism inpatients with CHD varies across different studies, thisstudy aimed to examine the frequency of abnormal laboratory test results for these two conditions in children
and adolescents with CHD in Shiraz, Iran.
Methods
Design and subjects

This prospective case-control study was conducted onchildren and adolescents diagnosed with CHD. They

were referred to the heart clinic affiliated with Shiraz
University of Medical Sciences between February 2019and December 2021. A consecutive sampling method
was followed. The study included children and adolescents aged 1 to 18 with cyanotic and non-cyanotic CHD,
operated or not operated, and with or without Down syndrome. Among the heart diseases that can be classified
according to the disease severity, patients with a moderate degree or more were included in this study. Patientswith mild CHD grades, a deficiency of total serum IgAlevels, a history of amiodarone prescription, previous
multiple imaging procedures, or those who were ill orsick were excluded from the study. It should be notedthat amiodarone and multiple X-ray imaging could interfere with the results of thyroid function tests.
Measurements

In this study, CHD patients aged 1 to 18 years as the casegroup were compared with the corresponding healthy
subjects as the control group. Based on valid echocardiography guidelines, CHD was diagnosed via transthoracic echocardiography using 2D, M-mode, doppler, andcolor doppler methods, and CHD patients were classified
into two groups, cyanotic and non-cyanotic [13, 14].
We performed CD laboratory tests by measuringserum anti-tissue transglutaminase IgA antibody (antiTTG Ab) and total IgA antibody. Five milliliters of blood
were taken from the participants and stored at -20 °C for
evaluation. The IgA level was measured by the indirect
immunofluorescence method. The AESKU kit (number
3504) made in Germany was used to measure anti-TTG
Ab, and the Pishtaz kit made in Iran was used to measure thyroid stimulating hormone (TSH) and T4. Bothtests were performed on serum, and the sample was centrifuged at 60,000 rpm for 10 min. Anti-TTG Ab levelsof more than 18 units/mL were categorized as positive,
fewer than 16 units/mL as normal, and between these
two as borderline.
Regarding the thyroid tests, the cut-off points for TSH,
T4, and anti-thyroid peroxidase antibodies in our study
were determined based on Table 1. The selection criterion for high TSH level was the level of our requested
test or the patients’ previous tests (and of course only forthree of them who were already taking levothyroxine)[15–17].
Also, demographic characteristics of the participants,
including age, sex, weight, height, and body mass index(BMI), were recorded in the relevant form.
For measuring over two-year-old children’s weight,a digital scale made in Iran with a precision of 50 g wasused, and for children under two years, a Beurer scale

Edraki et al. BMC Pediatrics(2024) 24:513

Page 3 of 6

Table 1 Reference values for normal serum TSH, T4, and antithyroid peroxidase antibodies at selected ages
Variable
TSH, 97.5 percentile (mU/L)

T4, -2 SD (nmol/liter)

Serum level of anti-TPO Ab

Age (years)
1–5
6–10
11–14
15–18
1–5
6–10
11–14
15–18
< 35 IU/ml

Normal level
6.25
5.40
4.61
4.33
92.10
73.56
65.40
62.27

Anti−TPO Ab: Anti−thyroid peroxidase antibodies, SD: Standard deviation, TSH: Thyroid−stimulating hormone

Table 2 Descriptive characteristics of the study population
Characteristics
Age (year)
Height (cm)Weight (kg)Minimum
1.00
61.00
7.50

Maximum
18.00
179.0084.00

Mean ± SD
5.32 ± 4.05
107.22 ± 25.81
13.78 ± 18.38

Table 3 Classifications of congenital heart disease patients
Characteristics
Type of CHD
Cyanotic
Non-cyanotic
Down syndrome
Yes
No
Age (years)

N (%)

≤5
>5

66 (67.35)

22 (22.45)
76 (77.55)
7 (7.14)91 (92.86)

32 (32.65)

BMI≤ 18.5> 18.578 (79.59)
20 (20.41)

CHD: Congenital heart disease, BMI: Body mass index

made in Germany with a precision of 5 g was used. They
were prepared to sit on the scale with minimal clothing.
Furthermore, the height of children under two years wasmeasured while lying down, and the height of children
over two years was measured using a vertical meter. The
BMI was calculated using the formula BMI = weight (kg)/height (m2). Also, CHD patients were divided according
to gender, cyanosis, age, and BMI, and then anti-TTG
Ab levels were compared among them. Those ≤ 5 years
were compared with those > 5 years only for anti-TTG Ab
level, and those with a BMI ≤ 18.5 kg/m2 were comparedwith those with a BMI > 18.5 kg/m2.
Statistical analysis

Data were analyzed using SPSS version 26 software.
The data were described in tables and graphs using frequency, percentage, mean, and standard deviation. An
independent t-test was used to compare the mean serumanti-TTG Ab values between age groups (≤ 5 years and> 5 years), BMI groups (≤ 18.5 and > 18.5), and cyanotic/
non-cyanotic groups. The prevalence was reported as
frequency and percentage. A p-value of less than 0.05 wasconsidered significant.

Results
In this study, 123 CHD patients were evaluated. According to the inclusion criteria, the final analysis was doneon 98 patients, of whom 51 (52.04%) were female and 47(47.96%) were male, with a mean age of 5.32 ± 4.05 years(1–18).
Table 2 shows the demographic characteristics of CHD
patients, along with other variables.
Table 3 shows the classification of patients based on
cyanosis and Down syndrome, and the classification ofpatients according to the age of five years and BMI of
18.5 was demonstrated.
Figure 1 indicates that Atrial Septal Defect (ASD)(27%), Ventricular Septal Defect (VSD) (20%), and Tetralogy of Fallot (TOF) (13%) were the most prevalent CHDs,
in sequence.
None of the patients had an anti-TTG Ab serum level
above 18 units/mL (Mean ± SD: 3.24 ± 2.69 units/mL,
ranging from 0.3 to 16.6 units/mL), and only one girlwith VSD-type CHD and BMI of 15.9 had an anti-TTG
Ab level of 16.6 units/mL, which was considered asborderline.
In our study, the mean serum anti-TTG Ab did nothave a statistically significant difference between boys
and girls (p = 0.26). The mean serum anti-TTG Ab was
not significantly different between the cyanotic and noncyanotic groups (p = 0.19). Also, other study variables did
not show a statistically significant difference between
these two groups (Table 4).
In the present study, 100 healthy subjects were examined as the control group for CD. The anti-TTG Ab levelin two of them (2%) was between 16 and 18 units/mL,
considered borderline.
Also, our study assessed thyroid function among CHD
patients. Seven patients had high TSH levels; three wereusing levothyroxine since early infancy with the diagnosisof congenital hypothyroidism, and parents of the otherfour were unaware of this issue. Moreover, T4 in thesefour patients was more than the cut-off points of hypothyroidism, and they had subclinical hypothyroidism.
Three of these seven patients had a surgically correctedcyanotic heart disease and were free from cyanosis at thetime of the study. One person had Down syndrome witha non-cyanotic CHD. No patients were in critical or ill
condition (Table 5). Anti-thyroid peroxidase antibodies
were normal in all these seven cases.
Among the 100 people in the control group, two had
TSH of more than normal for their age, and their T4

Edraki et al. BMC Pediatrics(2024) 24:513

Page 4 of 6

Fig. 1 Frequency of different types of cardiac abnormalities

Table 4 Serum anti-TTG IgA Ab among patients
VariablesType of CHD
Non- cyanotic patients
Cyanotic patients
GenderFemaleMale
Age categories≤ 5 years old> 5 years old
BMI categories
BMI ≤ 18.5
BMI > 18.5

NumberMean ± SD

P value76
22

3.39 ± 2.34
2.44 ± 1.98

0.192

52
46

3.25
2.92

0.265

66
32

2.87 ± 2.11
4.01 ± 3.52

0.460

78
20

3.16 ± 4.34
3.01 ± 5.12

3.879

and anti-thyroid peroxidase antibodies levels werealso normal, suggesting subclinical non-autoimmune
hypothyroidism.
The TSH level of CHD patients and healthy subjects
differed significantly (p = 0.01), while the T4 level did not
differ significantly between these two groups (p = 0.16).

Discussion
The prevalence of CD and hypothyroidism varies significantly in different studies among children and adolescents with CHD. The present study examined thefrequency of laboratory test abnormalities in children
and adolescents with CHD for these two conditions.

As known, CD and hypothyroidism have an essential impact on CHD, and knowing their coexistence canaffect the patient’s outcomes.
According to the results of the present study, approximately 1% of the healthy population had borderline antiTTG Ab levels between 16 and 18 units/mL, and thesame percentage was observed in CHD patients. Also,
the probability of hypothyroidism was 2% in the healthy
population and 7% in CHD patients.
Studies have shown a diverse association between CD
and some genetic diseases or chromosomal abnormalities
such as CHD, type 1 diabetes mellitus, hypothyroidism,
trisomy 21, and Turner syndrome, etc. In some articles,
there was no relationship between CD and CHD, or thestrength of this relationship was insignificant [18]. However, some studies, including the study of Wingren et al.,Mcneish and Anderson, and Kumhar et al., confirmed
this relationship [5, 18, 19].
Nevertheless, in our study, no person with CHD had
a serum level higher than 18; thus, the CD risk was nothigher in patients with CHD than in the general population. According to a study the prevalence of CD seropositivity in Iran was 0.6% [20]. In a review study, theprevalence of CD was higher in Iran than in Westerncountries (0.6%) [21]. In another study in Iran, the prevalence of CD was 2% in healthy children and adolescents[22].
However, in another Iranian study, the rate of positive celiac serology tests was very high among Down

Edraki et al. BMC Pediatrics(2024) 24:513

Page 5 of 6

Table 5 Individual characteristics, heart disorders, and thyroid test results of seven patients with hypothyroidism
Patient
1
2
3
4
5
6
7

Age/ weight
gender
4.5/ 16.5
F
14.5/ 49M
14.0/ 37.50
M
2.42/ 10.55
F
2.00/ 10.50
F
1.5/ 9.12
F
3.50/ 12.13
F

C/ A

T4
nmole/L
7.80

TSH
µU/L
7.40

Anti-TPO
IU/ml
4.70

Aware of disease

On medication

C

Trisomy
21
No

No

No

C

No

10.70

7.11

3.52

Yes

Yes

C

No

7.52

25.40

2.3

No

No

A

No

0.3

12.35

2.64

No

No

A

Yes

8.35

6.99

3.11

No

No

A

No

8.43

7.23

2,10

Yes

Yes

A

No

8.78

7.76

3.64

Yes

Yes

Anti TPO: anti−thyroid peroxidase antibodies, A: acyanotic congenital heart disease, C: cyanotic congenital heart disease, F: female, M: male, TSH: thyroid stimulating hormone (in the present or past tense)

syndrome patients. More than 30% of Down syndrome
children with or without CHD had a positive serology
test for CD, and the positive rate of the test in individuals
with CHD was about 50% [23]. In the other study from
Iran, the prevalence of CD was 11% in CHD patients and3.50% in healthy individuals. This difference was significant and greatly different from global statistics [4].
However, in our study, this prevalence was reported
as 1%, and there was no significant difference between
the patient and healthy groups. The prevalence of CD in
our study is consistent with the global prevalence of thisdisease in CHD patients. Also, in the present study, no
significant difference was observed in the serum level ofanti-TTG Ab between cyanotic and non-cyanotic CHD
patients. In line with this, one study showed no significant difference between the cyanotic and non-cyanotic
groups [4]. According to the present study, there was no
significant difference in anti-TTG Ab levels in different
age groups (less than and more than five years) and also
in two different BMI groups (less than and more than
18.5). In this regard, Taheri et al.‘s study showed that theprevalence of CD in children with failure to thrive was
8.8%, and the mean anti-TTG Ab levels of children did
not show a significant difference between age and gendergroups [24].
In our study, the prevalence of non-autoimmune hypothyroidism in healthy individuals was 2%, almost equal tothat of acquired hypothyroidism in children (3%). However, the prevalence of non-autoimmune hypothyroidism in CHD patients was 7%, three times more than in
healthy individuals, and mostly mild and subclinical. People in the control group with high TSH underwent subclinical hypothyroidism, and their T4 level was within thenormal range. Parents of four out of seven CHD patients
had subclinical hypothyroidism and were unaware of
their disease, and three patients were treated with levothyroxine due to previous tests. A study by E. Passeri etal. conducted in Italy also reported an increased risk ofabout 10 times for congenital hypothyroidism and threetimes for mild acquired non-immune hypothyroidism
among CHD cases [12], which agreed with our study.
Also, other studies reported a higher prevalence of subclinical hypothyroidism in CHD patients, like our study[25]. Notably, tissue-specific thyroid hormone bioactivity is reduced during chronic hypoxia, leading to low T3
syndrome in critically ill patients [9], while our patientswere not ill or cyanotic.
Limitations

This study was limited to the population of Shiraz City.
Future studies with larger sample sizes from other cities
and provinces of the country are recommended.

Conclusion
In the present study, serum levels of TSH and nonimmune hypothyroidism were higher in patients with
CHD than in normal individuals. However, serum antiTTG Ab levels did not differ between the two groups.
Due to the possibility of the negative impact of not diagnosing mild hypothyroidism on the outcome of CHD
in children, frequent examination and more attention
to thyroid problems in CHD patients is recommended.
However, the routine examination of CD tests needs
more research.
Abbreviations
CD	Celiac disease
CHD	Congenital heart disease
TSH	Thyroid stimulating hormone
BMI	Body mass index
ASD	Atrial septal defect
VSD	Ventricular septal defectTOF	Tetralogy of Fallot
Acknowledgements
The authors thank all the participants, coordinators, and administrators fortheir support and help during the research.

Edraki et al. BMC Pediatrics(2024) 24:513

Page 6 of 6

Author contributions
MRE and NH designed the study. MRE led the study, drafted most of the paper,and analyzed the data. AJ, RD, MD, and HA collected data. MRE, NY, and NH
provided technical direction and writing assistance in the preparation of thismanuscript. MRE, NY, and NH guided key elements in the later revision process
to help with data analysis and article writing. All authors critically revised themanuscript and approved the final version for publication.

7.

Funding
There were not any sources of funding for this research.

10.

Data Availability
The datasets analyzed in this study are available from the corresponding
author upon reasonable request.

8.
9.

11.

12.

Declarations
Ethics approval and consent to participate
This study was approved by the Research Ethics Committee of Shiraz
University of Medical Sciences (IR.SUMS.MED.REC.1399.062). Informed consent
was obtained from individuals or their parents. The study is conducted by theprinciples of the Declaration of Helsinki.

13.
14.

Consent for publication
Not applicable.

15.

Competing interests
The authors declare no competing interests.

16.

Author details
1
Cardiovascular Research Center, Shiraz University of Medical Sciences,
Shiraz, Iran
2
School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
3
Community Based Psychiatric Care Research Center, School of Nursing
and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran4
Department of Pediatric Gastroenterology, Neonatal Research Center,
Shiraz University of Medical Sciences, Shiraz, Iran
5
School of Medicine, Bam University of Medical Sciences, Bam, Iran
6
Gastroenterohepatology Research Center, Nemazee Hospital, Shiraz
University of Medical Sciences, Shiraz, Iran
Received: 21 September 2022 / Accepted: 1 September 2023

17.

18.
19.
20.
21.
22.
23.

References
1. Honar N, Yazdani N, Ataollahi M, Imanieh MH, Karamizadeh Z. The frequency
of Serologic Celiac Disease in obese children referring to Endocrine Clinic in
Shiraz. Sadra Med Sci J. 2021;9:145–52.
2. Ciampolini M, Bini S. Serum lipids in Celiac Children. J Pediatr Gastroenterol
Nutr. 1991;12:459–60.
3. Norsa L, Shamir R, Zevit N, Verduci E, Hartman C, Ghisleni D, et al. Cardiovascular disease risk factor profiles in children with celiac disease on gluten-freediets. World J Gastroenterol WJG. 2013;19:5658.
4. Shahramian I, Dehghani SM, Haghighat M, Noori NM, Teymoori AR, Sharafi
E, et al. Serological evaluation of Celiac Disease in children with congenital
heart defect; a Case Control Study. Middle East J Dig Dis. 2015;7:98–103.
5. Wingren CJ, Agardh D, Merlo J. Congenital anomalies and childhood celiac
disease in Sweden. J Pediatr Gastroenterol Nutr. 2012;55:736–9.
6. Polat TB, Urganci N, Yalcin Y, Zeybek C, Akdeniz C, Erdem A, et al. Cardiac functions in children with coeliac disease during follow-up: insights from tissue
doppler imaging. Dig Liver Dis. 2008;40:182–7.

24.
25.

Bhargava R, Singh A, Aggarwal A, Narang M. Rare association of celiac disease
with congenital heart disease. Indian J Child Health. 2019;6:255–6.
Cheung YF, Tsang HY, Kwok JS. Immunologic profile of patients with proteinlosing enteropathy complicating congenital heart disease. Pediatr Cardiol.
2002;23:587–93.
Lerner RK, Gruber N, Pollak U. Congenital heart disease and thyroid dysfunction: combination, association, and implication. World J Pediatr Congenit
Heart Surg. 2019;10:604–15.
Sinha IP. Nelson textbook of pediatrics. InSeminars in fetal and neonatal
medicine. Elsevier; 2012. p. 380.
Elena P, Marcello F, Rea V, Elena C, Laura F, Patrizia P et al. Mild hypothyroidism in young patients with congenital heart defects: association with 22q11.
2 microdeletions. InEndocrine Abstracts: Bioscientifica. 2010: ea0022p782 |Thyroid | ECE2010.
Passeri E, Frigerio M, De Filippis T, Valaperta R, Capelli P, Costa E, et al.
Increased risk for non-autoimmune hypothyroidism in young patients withcongenital heart defects. J Clin Endocrinol Metab. 2011;96:E1115–9.
Amoozgar H, Salehi M, Borzoee M, Ajami G, Edraki MR, Mehdizadegan N et al.
Balloon valvuloplasty for pulmonary stenosis in children: immediate outcome
and cardiac remodeling during midterm follow-up. Iran J Pediatr. 2017; 27.
Ajami G, Edraki MR, Moarref AR, Amirghofran AA, Borzouee M, Amoozgar
H, et al. Role of speckle tracking echocardiography in the assessment of
post-repair left ventricular function in patients with late presentation of
anomalous origin of the left coronary artery from the pulmonary artery.
Cardiol Young. 2015;25(5):969–75.
Omar MA, Rizk MM, El-Kafoury AA, Kilany D. Screening for thyroid disease
among children and adolescents with type 1 diabetes mellitus. Alexandria J
Med. 2014;50:77–82.
Kapelari K, Kirchlechner C, Högler W, Schweitzer K, Virgolini I, Moncayo R.
Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study. BMC Endocr Disord. 2008;8:1–10.
Lem AJ, de Rijke YB, van Toor H, de Ridder MA, Visser TJ, Hokken-Koelega AC.
Serum thyroid hormone levels in healthy children from birth to adulthoodand in short children born small for gestational age. J Clin Endocrinol Metab.
2012;97:3170–8.
Kumhar M, Kumar AC, Kulkarni D. Celiac disease association with a congenital
heart disease. Inter J Celiac Dis. 2013;1:14–6.
McNeish AS, Anderson CM. The disorder in childhood. Clin Gastroenterol.
1974;3:127–44.
Shahbazkhani B, Malekzadeh R, Sotoudeh M. Eur J Gastroentrol Hepatol.
2003;15:475–8.
Rostami Nejad M, Rostami K, Emami MH, Zali MR, Malekzadeh R. Epidemiology of Celiac disease in Iran; a review. Middle East J Dig Dis. 2011;3:74–7.
Dehghani SM, Haghighat M, Mobayen A, Rezaianzadeh A, Geramizadeh B.
Prevalence of celiac disease in healthy iranian school children. Ann Saudi
Med. 2013;33:159–61.
Noori NM, Teimouri A, Nakhaey Moghaddam M, Shahraki T. The prevalence of
celiac disease in Down syndrome children with and without congenital heart
defects. Int J Pediatr. 2016;4:2143–52.
Taheri M, Sabzali S, Hakim A, Sajadi N, Hakimzade M, Ziaieikajbaf T, et al. The
prevalence of celiac disease in children with unexplained failure to thrive inSouth West of Iran. Int J Pediatr. 2017;5:4663–9.
Martínez-Quintana E, Rodríguez-González F. Follow-up of congenital
heart disease patients with subclinical hypothyroidism. Cardiol Young.
2015;25:1111–8.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.