EAL

CD: Iron Deficiency Anemia (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the effect of iron supplementation and gluten-free diet on hematological profile of children with celiac disease.

Inclusion Criteria:

Children of either sex below 12 years of age, diagnosed with celiac disease based on modified ESPGAN criteria with positive serology for Antigliadin A and endomysial antibodies.

Exclusion Criteria:

Chronic infection or history of worm infestation. Children with doubtful compliance to a GFD, having occasional gluten intake or follow-up less than 1 year were also excluded.

Description of Study Protocol:

Recruitment

Not mentioned.

Design

Case Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten free diet and iron supplementation for at least 1 year (mean 1.5 years, range 1 - 2 years). Iron supplementation was based on hematological status (therapeutic dose: 3 mg elemental iron/kg body wt + 250 micrograms folic acid, prophylactic dose: 2 mg elemental iron/kg up to a maximum of 30 mg elemental iron/day + 250 micrograms folic acid).

Statistical Analysis

Results analyzed by paired Student's t test and Pearson coefficient calculated to study correlation between parameters.

Data Collection Summary:

Timing of Measurements

Hematological profile evaluated at study enrollment and after 1 year of gluten free diet and iron supplementation. Repeat intestinal biopsy after at least year of GFD.

Dependent Variables

Hematological profile included hemoglobin estimation, CBC, peripheral blood smear examination, serum iron, TIBC, and serum ferritin estimation through routine blood analysis methods
Repeat intestinal biopsy evaluated for villous pattern, crypt:villous ratio, nature of surface epithelium and inflammatory cell infiltrate in lamina propria
Stool examination for occult blood
Nutritional status assessed by recording weight and height for age, triceps and biceps thickness

Independent Variables

Gluten free diet assessed in dietary analysis by recall method. Compliance measured through detailed dietary inquiry and also parental views on restrictions, both in school and special occasions

Control Variables

Description of Actual Data Sample:

Initial N: 21 children, 16 girls, 5 boys, and 21 age- and sex-matched normal controls

Attrition (final N): 21 children with CD and 21 controls

Age: Mean age 6.67 years (range 4 - 11 years)

Ethnicity: Not mentioned

Other relevant demographics:

Anthropometrics: age- and sex-matched controls

Location: Division of Pediatric Gastroenterology and Nutrition, Kalawati Saran Children's Hospital, New Delhi

Summary of Results:

Parameter	CD Pts at Enrollment	CD Pts on GFD	Control Group	P-value
Hb (g/dl)	8.1 +/- 0.8	11.4 +/- 0.9	11.5 +/- 0.7	> 0.05
MCV (fl)	64.2 +/- 5.8	74.9 +/- 5.6	81.94 +/- 4.01	< 0.05
MCH (pg)	18.6 +/- 2.2	24.8 +/- 2.14	28.1 +/- 2.67	< 0.05
MCHC (% Hb/cell)	28.6 +/- 2.4	33.1 +/- 1.74	33.3 +/- 2.22	> 0.05
Serum iron (ug/dl)	82.45 +/- 25.6	86.93 +/- 23.4	90.89 +/- 23.0	> 0.05
Serum TIBC (ug/dl)	302.6 +/- 51.5	294.8 +/- 42.5	261.9 +/- 27.6	< 0.05
Serum ferritin (ng/ml)	34.6 +/- 15.6	41.9 +/- 13.2	88.3 +/- 36.8	< 0.05

Other Findings

Anemia defined as per the WHO criteria for diagnosis (<11 gm/dl in children 6 months - 6 years and <12 gm/dl in children more than 6 years).

At enrollment, iron supplement was given to all children in therapeutic doses, continued for at least 3 months, and changed to prophylactic dose only after repeat hemoglobin estimation during the follow-up period was within the normal range for age on 2 consecutive visits.

Diets of children with CD on GFD was comparable to the normal diet in caloric content and proteins.

At the time of enrollment, all subjects had hemoglobin level < 11 gm%, 78% had microcytic hypochromic anemia and 22% had dimorphic anemia, with lower mean MCV, MCH and serum ferritin levels (p < 0.001), and a significantly higher mean TIBC than controls (p < 0.001). Stool examination for occult blood was negative in all cases.

After at least 1 year on GFD, mean hemoglobin levels were comparable with controls (11.4 +/- 0.9 g/dl vs 11.5 +/- 0.7 g/dl, p < 0.05) but the subjects continued to have lower mean MCV, MCH and serum ferritin levels (p < 0.05) and higher mean TIBC (p <0.05). 7 children had mild anemia as per the WHO criteria. 9 patients had evidence of iron deficiency with lower levels of serum ferritin.

Serum ferritin levels showed a negative correlation with the grade of villous atrophy and lamina propria infiltrate. There was no correlation between the other hematological parameters and histological changes.

Author Conclusion:

We conclude that an iron deficiency state often exists in children of CD on GFD which could be attributed to continuation of iron losses in the stool, to poor intake due to replacement of wheat by rice or maize, lack of iron rich sources in the diet and lack of iron supplementation. Iron deficiency state in children may lead to retardation of mental and psychomotor functions, growth retardation and impaired physical performance. Apart from offering them a gluten-free diet rich in iron, early detection and treatment of iron deficiency anemia and prophylactic iron folic acid supplementation will go a long way to optimize their mental and psychomotor functions.

Funding Source:

University/Hospital:

Kalawati Saran Children's Hospital (India), Lady Harding Medical College (India)

Reviewer Comments:

Compliance to GFD measured and incompliant subjects excluded.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes