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CD: Iron Deficiency Anemia (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To evaluate the clinical and nutritional profile of children diagnosed with celiac disease at the time of diagnosis and after at least 6 months of gluten-free diet.
Inclusion Criteria:
Children with celiac disease diagnosed according to modified ESPGAN criteria (demonstration of histological changes on intestinal biopsy while on gluten and unequivocal improvement on GFD) and having satisfactory dietary compliance on GFD who regularly attended the follow up for at least 6 months.  Diagnostic criteria also included evaluation of antigliadin IgG and IgA, antiendomysial antibody IgA and in some cases, antireticulin antibodies.
Exclusion Criteria:
Children with irregular follow up, on GFD for less than 6 months, or doubtful dietary compliance.
Description of Study Protocol:

Recruitment

Children diagnosed and followed in the Pediatric Gastroenterology and Nutrition Clinic.

Design

Case Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten free diet.

Statistical Analysis

Weight for age and height for age were expressed as Z scores relative to NCHS standards.  Statistical analysis not described further.

Data Collection Summary:

Timing of Measurements

At diagnosis, anthropometric measurements and hematological assessments completed.  Participants were followed in the Pediatric Gastroenterology and Nutrition Clinic and these measurements were completed after institution of GFD.

Dependent Variables

  • Anthropometric measurements - weight, height, mid-arm circumference, skin-fold thickness, weight for height, BMI, weight for age and height for age 
  • Hematological assessment
  • All cases thoroughly evaluated for symptoms of diarrheal episodes, weight loss, pallor, vomiting, abdominal pain, and skin changes
  • General behavior and scholastic examination was carried out for assessment of anemia and signs suggestive of any vitamin deficiency 
  • Repeat biopsy by pediatric fiberoptic endoscope

Independent Variables

  • Gluten free diet - compliance ascertained and quality of food intake assessed

Control Variables

 

Description of Actual Data Sample:

 

Initial N: 65 enrolled cases of celiac disease (30 males, 35 females), 7 did not follow strict GFD

Attrition (final N):  41 children (15 males, 26 females), 41 age- and sex-matched controls.  Remaining 24 (36.9%) children with follow up period less than 6 months (n=15), non-compliant / irregular compliance (n=7), and lost to follow up (n=2) were excluded from analysis.

Age:  4.5 - 11 years (mean 6.67 +/- 2.37 years) 

Ethnicity:  Not mentioned 

Other relevant demographics:  Mean age of diagnosis was 8.7 +/- 3.3 years.  Mean duration of follow-up on GFD was 22 months (range 6 - 48 +/- 5.6 months). 

Anthropometrics (e.g., were groups same or different on important measures)

Location:  New Delhi, India 

 

Summary of Results:

Anthropometric and Hematological Parameters in Cases vs Controls

Parameter

 Diagnosis (n=65) P value

Controls (n=65)

GFD Treatment (n=41)

P value
Height for Age (Z score) -3.144 0.00 -1.029 -2.086 <0.0001
Weight for Age (Z score) -2.889 0.00 -1.029 -1.038 0.96 (NS)
Weight for Height (Z score in %) 86.98 0.00 97.7 101.8 0.56 (NS)
BMI 13.7 0.00 15.1 16.4 <0.0001
Triceps skinfold thickness (mm) 8.9 0.00 12.0 13.2 0.89 (NS)
Biceps skinfold thickness (mm) 8.1 0.00 11.2 11.8 0.74 (NS)
Mid Arm Circumference (cm) 12.9 0.00 16.2 16.9 0.51 (NS)
Hemoglobin (g%) 7.7 0.00 10.9 10.7 0.12 (NS)
Platelet Count (per cu mm) 450 x 103 0.00 285.07 x 103 299.96 x 103 0.42 (NS)
MCV (fl) 63.2 0.00 80.3 72.2 <0.0001
MCH (pg) 18.1 0.00 28.1 22.6 <0.0001
MCHC (% Hb/cell) 28.3 0.00 33.8 33.6 0.52 (NS)

Normocytic Normochromic (%)

     100% 81%  

Microcytic Hypochromic (%)

 80%  

 

19%

 

Dimorphic (%)

 20%  

 

 

 

Other Findings

Diarrhea and failure to thrive were most common presenting symptoms.  All children were malnourished at time of diagnosis and the nutritional and hematological indices were significantly lower in patients than in controls.

Mean duration of follow up on GFD was 22 months (range 6 - 48 +/- 5.6 months).

On follow-up, height for age Z score was significantly lower, mean BMI was significantly higher, and weight for age Z score, weight for height Z score (%), mean triceps and biceps skin fold thickness, and mid arm circumference were comparable to controls.  There was no correlation between the duration of symptoms prior to diagnosis and any of the anthropometric parameters evaluated at the time of diagnosis (p > 0.05).

At diagnosis, 80% cases had microcytic hypochromic anemia and 20% had dimorphic anemia.  All hematological parameters improved on GFD.  On GFD for at least a period of more than 6 months, 19% had microcytic anemia and in 81% the hematological picture was normocytic normochromic.  60% cases had thrombocytosis at diganosis in comparison to 2.3% after treatment.

The intestinal biopsy of 21 children who had completed at least 1 year of treatment of GFD remained moderately affected (biopsy score 5 - 9) in 52.5% of the patients and minimally affected (biopsy score 0-5) in 9 patients (42.8%).  Only in 1 case (4.7%) the intestinal biopsy had reverted to normal histological picture. 

Author Conclusion:
Our results suggest that celiac disease is a common entity in countries like India especially in the northern parts where wheat is one of the staple food constituents.  Celiac children are malnourished at diagnosis and institution of GFD leads to rapid improvement in symptoms and in nutritional and hematological parameters.  However, noncompliance of GFD remains a critical issue in the management of these cases, particularly because not many nutritionally suitable options for GFD are available in our country.  Regular follow up and counseling is recommended to ensure dietary compliance.
Funding Source:
Reviewer Comments:
Noncompliant subjects removed from analysis. 
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? Yes
  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? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  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)? ???
  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