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Research Article | Volume 10 Issue 2 (July-December, 2024) | Pages 146 - 151
A Study to Evaluate the Proportions of Children with Moderate to Severe Iron Deficiency Anemia Associated with Celiac Disease
 ,
 ,
 ,
1
Resident, dept of Pediatrics, Sardar Patel Medical college, Bikaner, India
2
Assistant professor, dept of Pediatrics, GMC, Karauli, India
3
Senior Resident, dept of Pediatrics, Sardar Patel Medical college, Bikaner, India
4
Senior professor, dept of Pediatrics, Sardar Patel Medical college, Bikaner, India
Under a Creative Commons license
Open Access
Received
Oct. 15, 2024
Revised
Oct. 30, 2024
Accepted
Nov. 20, 2024
Published
Dec. 4, 2024
Abstract

Introduction: Iron deficiency is ‘perhaps           the most frequent nutritional deficiency in the world. Aim: To evaluate the proportions of children with moderate to severe iron deficiency anemia associated with celiac disease. Methods: This was a prospective observational study on 60 cases(group A) and 60 healthy controls (group B) aged up to 14 yrs by Simple random sampling over a period of one year in a tertiary care hospital. Moderate-to-severe anemia was diagnosed according to the WHO criteria. Serum IgA tTG antibody levels measured using indirect solid-phase enzyme immunosorbent assay (ELISA) kits. Esophagogastrodudenoscopy is only to be done in patients diagnosed with celiac disease. Four biopsies were taken from the first/second part of duodenum for histopathological examination. Results: Mean age in group A was 9.25 ± 3.26 yr, whereas 9.14 ± 3.4 yr in group B. 12% cases in group A were positive for IgA TTG, whereas 1.33% in group B were IgA TTG positive (p<0.0001*). Among IgATTG positive cases 66.67% in group A had subtotal villous atrophy, 27.77% had partial villous atrophy whereas in group B, 50% had partial or subtotal villous atrophy (p<0.05). Mean serum ferritin level were 10.2 ± 4.6 ng/ml and 58.4 ± 20.96 ng/ml in group A and group B respectively. (p<0.05). Mean transferrin saturation were 17.65 ± 1.65 % and 39.5 ± 10.5 % in group A and group B respectively. (p<0.05). Conclusion: Anemic children, especially those presenting with severe anemia have significantly higher likelihood of having Celiac disease. Physicians treating children with severe anemia may consider screening them for celiac disease. We recommend for community-based studies to confirm these findings.

Keywords
INTRODUCTION

Iron deficiency is ‘perhaps the most frequent nutritional deficiency in the world’. Globally upto 1.62 billion individuals are affected with iron deficiency anemia.1  

Iron deficiency is the most widespread nutritional disorder in the world along with being the most common problem among micronutrients deficiency. Anemia affects productivity of the entire nation. Thus, anemia constitutes a public health epidemic. Over 30% of the world's population is anemic, mainly due to iron deficiency. The reported prevalence in south Asia is more than 66%.2 In India anemia has been a big public health issue. The prevalence of anemia among children less than 5 years of age has been shown to be around 70% as per the data collected by National Family Health Survey (NFHS) III, with Bihar topping the list. The prevalence of anemia increases to 79% among children aged less than 3 years, with the highest prevalence among 6 to 23 months age group. Iron deficiency affects the activity of numerous enzymes adversely.2,3Infants, whose organs are still developing, including the brain, are affected significantly by anemia resulting in growth retardation and impairment of intellectual development.

 

Celiac disease (CD) is a unique autoimmune disease, with a known environmental predisposition factor in the form of gluten, in genetically predisposed individuals.4 It is the most common cause of malabsorption syndrome.5 Over the past two decades, CD has emerged as a common health-care problem in Asian countries, with current seroprevalence of  1.6% and prevalence of 0.5%.6

 

Anemia is one of the most common extraintestinal manifestations of CD, reported to occur in 5–40% of patients in the West and in more than 80% patients in developing countries, with a higher prevalence in Asian countries.7 Studies have shown that anemia in CD is actually multifactorial and can have varied etiologies, including mixed nutritional deficiency, anemia of chronic disease (ACD), and aplastic anemia.8 With increasing prevalence of CD in developing countries, it is important to know the contributing factors of anemia in different populations.

 

Recently, more and more emphasis has been placed on micronutrient deficiency as a diagnostic clue to occult celiac disease, particularly for iron, and iron deficiency anemia. In children, iron deficiency anemia in celiac disease is common and further screening with tissue transglutaminase antibodies has been strongly recommended. Interestingly, pica may be the presenting clinical symptom of celiac disease coupled with iron deficiency anemia in children.

 

AIM: To evaluate the proportions of children with moderate to severe iron deficiency anemia associated with celiac disease.

METHODS

This was a prospective observational study on 60 cases(group A) and 60 healthy controls (group B) aged up to 14 yrs by Simple random sampling over a period of one year from july 2021 to august 2022 in tertiary care teaching hospital in Northwestern Rajasthan. A written informed consent was obtained from either of the parents or guardian,a verbal assent was taken from older children. The study was initiated after obtaining a prior formal ethical approval from the Institutional Ethics Committee. All patients with visible pallor as detected on physical examination having moderate-to-severe iron deficiency anaemia (IDA) according to the WHO criteria7 were included as cases and healthy children or siblings visiting pediatrics out patient  department were taken as controls.

 

Patients /guardians not giving consent, or child not giving verbal  assent, child with coexistent diseases, overt gastrointestinal bleed or hematological disorders and history of intake of chemotherapy or radiotherapy in the last 6 weeks were ruled out of study.

 

A thorough clinical history with emphasis on current or past gastrointestinal symptoms was taken from patients. Nutritional status of all the children was assessed at the time of recruitment. All the eligible children from ‘cases’ group with anaemia were undergo a complete clinical assessment, duration of symptoms, hemogram, peripheral blood film, serum ferritin, total iron binding capacity, transferrin saturation, serum IgA transglutaminase level, esophagogastrodudenoscopy and stool examination on two consecutive days to assess parasitic infestation. Moderate-to-severe anemia was diagnosed according to the World Health Organization criteria. Serum IgA tTG antibody levels measured using indirect solid-phase enzyme immunosorbent assay (ELISA) kits (Celikey, Phadia GmbH, Freiburg, Germany).

 

IgA tTG level >18 U/mL was considered as positive for celiac disease, 12-14 U/mL as equivocal, and <12 U/mL as negative.

Esophagogastrodudenoscopy is only to be done in patients diagnosed with celiac disease. Four biopsies were taken from the first/second part of duodenum for histopathological examination.

 

All statistical analyses were performed using SPSS version 23. The continuous variables were compared using student’s t-test, whereas the categorical variables were compared using the Chi-squared test. A P-value of <0.05 was considered significant

RESULTS

In our study, in group A maximum 50% cases were in 5 – 12 yr, whereas 46.67% were in group B with mean age in group A was 9.25 ± 3.26 yr, whereas 9.14 ± 3.4 yr in group B(p>0.05).

In both group maximum were male.

Mean weight in group A was 15.27 ± 7.5kg, whereas 17.5 ± 5.9 kg in group B and mean height in group A was 109.5 ± 15.6 cm, whereas 113.6 ± 12.65 cm in group B both groups were comparable in basic features. Maximum 55% cases were rural in group A, whereas 56.67% were in group B. Maximum 55% cases were Hindu, In group B 56.67% were Hindu.

In our study, 23.3% cases in group A, whereas 26.67% in group B had history of celiac disease in their family.

 

Table 1: Sociodemography

Age (Years)

Group A (60)

Group B (60)

P value

No.

%

No.

%

<5

5

8.33

7

11.67

0.864

5 – 12

30

50.00

28

46.67

12 – 14

25

41.67

25

41.66

Mean

9.25 ± 3.6

9.14 ± 3.4

SEX

 

Male

35

58.33

33

55.00

0.854

Female

25

41.67

27

45.00

Area

Rural

33

55.00

34

56.67

0.875

Urban

27

45.00

26

43.33

Religion

Hindu

45

55.00

43

56.67

0.836

Muslim

15

45.00

17

43.33

             

43.33% cases in group A had 18.5 – 24.9 BMI, whereas minimum 5% had ≥30 BMI. In group B maximum 50% had 18.5 – 24.9 BMI, whereas minimum 8.33% had≥30 BMI. Mean BMI in group A was 20.3 ± 4.56 kg/cm2, whereas 21.5 ± 4.39 kg/cm2 in group B. (p>0.05)

Fig. 1 BMI

Mean Hb level were 7.91 ± 1.96 gm/dl and 12.20 ± 2.96gm/dl in group A and group B respectively (p<0.05).

Mean TLC level were 7.6 ± 2.55 gm/ml and 7.5 ± 2.3 gm/ml in group A and group B respectively (p<0.05).

Mean platelet count were 2.5 ± 0.9 lac/ml and 2.6 ± 0.99 lac/ml in group A and group B respectively (p<0.05).

Mean MCV level were 74.1 ± 4.65 fl/red cell and 82.5 ± 3.28 fl/red cell in group A and group B respectively (p<0.05).

 

Mean MCH level were 21.56 ± 3.98 pg/cell and 28.95 ± 2.15 pg/cell in group A and group B respectively (p<0.05).

Mean RDW were 20.9 ± 3.11 % and 13.1 ± 2.95 % in group A and group B respectively (p<0.05).

 

Table 2: Haemogram

Haemogram

Group A

Group B

P value

Hb (gm/dl)

7.91 ± 1.96

12.20 ± 2.96

0.0001*

TLC (gm/ml)

7.6 ± 2.55

7.5 ± 2.3

0.956

Plateletcount(lac/ml)

2.5 ± 0.9

2.6 ± 0.99

0.987

MCV(fl/red cell)

74.1 ± 4.65

82.5 ± 3.28

0.001*

MCH (pg/cell)

21.56 ± 3.98

28.95 ± 2.15

0.001*

RDW (%)

20.9 ± 3.11

13.1 ± 2.95

0.001*

 

12% cases in group A were positive for IgA TTG, whereas in group B 1.33% were IgA TTG positive. (p<0.0001*)

Table 3. IgA TTG

 

IgA TTG

Group A

Group B

No.

%

No.

%

Yes Positive

18

12.00

2

1.33

No Negative

42

88.00

58

98.67

Total

60

100

60

100

P

0.0001*

In our study, among IgATTG positive cases 66.67% in group A had subtotal VA, 27.77% had partial VA and 5.56% had total VA whereas in group B 50% had partial and subtotal VA. (p<0.05)

 

Fig. 2 Oesophagogastroduodenoscopy

Mean serum ferritin level were 10.2 ± 4.6 ng/ml and 58.4 ± 20.96 ng/ml     in group A and group B respectively.(p<0.05)

Mean transferrin saturation were 17.65 ± 1.65 % and 39.5 ± 10.5 % in group A and group B respectively (p<0.05)

 

Table 3: Distribution of Groups according to serum iron profile

Serum    Iron  profile

Group A

Group B

P value

Serum ferretin (ng/ml)

10.2 ± 4.6

58.4 ± 20.96

0.0001*

Transferrin saturation

17.65 ± 1.65

39.5 ± 10.5

0.001*

 

DISCUSSION

In our study, Mean age in group A was 9.25 ± 3.26 yr, whereas 9.14 ± 3.4 yr in group B, Similarly reported by Bansal D et al (2011).9

In our study, maximum 58.33% cases were male in group A, whereas minimum 41.67% were female. In group B, maximum 55% were male, whereas minimum 45% were female, Similarly seen by Zahra Setavand et al. (2021).10

In our study, mean BMI in group A was 20.3 ± 4.56 kg/cm2, whereas 21.5 ± 4.39 kg/cm2 in group B, Similar to Zahra Setavand et al. (2021).10

In our study, mean Hb level were 7.91 ± 1.96 gm/dl and 12.20 ± 2.96gm/dl in group A and group B respectively (p<0.05), Similarly reported by Narang M et al (2018).11

In our study, 12% cases in group A were positive for IgA TTG, whereas in group B 1.33% were IgA TTG positive, similarly reported by Srihari Mahadev et al. (2018)12 and Narang, M et al (2018).11

In our study, among IgATTG positive cases, 66.67% in group A had subtotal VA, 27.77% had partial VA and 5.56% had total VA whereas in group B 50% had partial and subtotal VA, similarly reported by Markku Mäki et al. (2003)13.

Mean serum ferritin level were 10.2 ± 4.6 ng/ml and 58.4 ± 20.96 ng/ml in group A and group B respectively, similarly found by Bel'mer SV et al (2014).14

Mean transferrin saturation were 17.65 ± 1.65 % and 39.5 ± 10.5 % in group A and group B respectively, Also reported by Repo M, et al (2017).15

CONCLUSION

We conclude that anemic children, especially those presenting with severe anemia have significantly higher likelihood of having Celiac disease. Physicians treating children with severe anemia may consider screening them for celiac disease. We recommend community-based studies to confirm these findings.

REFERENCES
  1. National Rural Health National Iron plus initiative. Guidelines for Control of Iron Deficiency Anemia. Adolescent Division Ministry of Health and Family Welfare Government of India 2013;5-17.
  2. Kotecha PV. Nutritional Anemia in Young Children with Focus on Asia and India. Indian J of Comm Med 2011;:8-16.
  3. National family health survey of India conducted by Mumbai, India: International institute for population sci;2005-6:15-6.
  4. Green PR, Cellier C. Celiac disease. N. Engl. J. Med. 2007; 357: 1731–43.
  5. Elizabeth M, Poskitt EME. Historical Review of iron deficiency British J of Hemato 2003;122:554–62.
  6. Singh P, Arora S, Singh A, Strand TA, Makharia Prevalence of celiac disease in Asia: a systematic review and meta-analysis: Celiac disease in Asia. J. Gastroenterol. Hepatol. 2016; 31: 1095– 101.
  7. West J, Fleming KM, Tata LJ, Card TR, Crooks CJ. Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study. Am. J. Gastroenterol. 2014; 109: 757–68.
  8. Zamani F, Mohamadnejad M, Shakeri Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin. World J Gastroenterol 2008; 14:7381-5.
  9. Bansal D, Trehan A, Gupta MK, Varma N, Marwaha R Serodiagnosis of celiac disease in children referred for evaluation of anemia: A pediatric hematology unit's experience. Indian J Pathol Microbiol 2011;54:756-60.
  10. Setavand Z, Ekramzadeh M, Honar N. Evaluation of malnutrition status and clinical indications in children with celiac disease: a cross-sectional Setavand et al. BMC Pediatrics 2021; 21:147. https://doi.org/10.1186/s12887-021-02621-3
  11. Narang M, Natarajan R, Shah D. Celiac Disease in Children with Moderate-to-Severe Iron-deficiency Indian Pediatr 2018;55:31–4.
  12. Mahadev S, Laszkowska M, Sundström J, Björkholm M, Lebwohl B, Green PHR, Ludvigsson JF. Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis. 2018 Aug;155(2):374-382.e1. doi: 10.1053/j.gastro.2018.04.016. Epub 2018 Apr 22. PMID: 29689265; PMCID: PMC7057414.
  13. Mäki M, Mustalahti K, Kokkonen J, Kulmala P, Haapalahti M, Karttunen T, Ilonen J, Laurila K, Dahlbom I, Hansson T, Höpfl P, Knip M. Prevalence of Celiac disease among children in Finland. N Engl J 2003 Jun 19;348(25):2517-24. doi: 10.1056/NEJMoa021687. PMID: 12815137.
  14. Bel'mer SV, Mitina EV, Karpina LM, Smetanina [Iron deficiency anemia and anemia in chronic celiac disease in children]. Eksp Klin Gastroenterol. 2014;:23-9.
  15. Repo M, Lindfors K, Mäki M, Huhtala H, Laurila K, Lähdeaho ML, et al. Anemia and Iron Deficiency in Children With Potential Celiac J Pediatr Gastroenterol Nutr. 2017;64:56-62.
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