EAL

CD: Villous Atrophy (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate nutritional indices, bone mineralization, pregnancy outcome and psychological status of adults with childhood diagnosis of celiac disease who were re-exposed to gluten after a few years and now on a gluten-containing diet, compared with adults with recent diagnosis of celiac disease, and adults who remained on gluten-free diet after childhood diagnosis.

Inclusion Criteria:

Adults with a biopsy suggestive of celiac disease in childhood or adulthood and gluten-free diet for at least 1 year after diagnosis.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Consecutive examination of patients with celiac disease.

Design

Cohort study.

Blinding used (if applicable)

Not used.

Intervention (if applicable)

Consecutive subjects had medical check-ups and consultations.

Statistical Analysis

Student's t test for unpaired observations, ANOVA and post hoc Bonferroni test, univariate and multivariate regression analyses, and analysis of 95% confidence intervals were used.

Data Collection Summary:

Timing of Measurements

Subjects had medical check-ups, dietetic consultation, and psychological consultation.

Dependent Variables

Anthropometrics
Physical examination
Laboratory tests, including antiendomysium and anti-tissue transglutaminase antibodies
Abdominal ultrasound
Upper endoscopy
Duodenal and jejunal biopsies
Bone densitometry measured by DEXA
Dermatology and gynecology consultation
Psychological consultation with single psychologist
Zung Self-rating Depression Scale

Independent Variables

Gluten free diet - compliance was self-reported and checked through Knowledge Rating Scale and Dietetic Restriction Compliance

Control Variables

Description of Actual Data Sample:

Initial N: 215 adult patients with diagnosis of celiac disease in childhood, 165 newly diagnosed adults.

Attrition (final N): 195 adults diagnosed in childhood; 110 adhered to gluten-free diet, 85 followed gluten-free diet for at least 1 year and now are noncompliant. 165 newly diagnosed adults. 20 dropouts - in 11, CD not confirmed, 9 refused to participate.

Age: GFD subjects: 21.9 +/- 3.7 years, transient GF: 23.7 +/- 4.3 years, never GF: 23.1 +/- 3.2 years

Ethnicity: Not mentioned

Other relevant demographics: GFD subjects on gluten-free diet for 15.7 +/- 6.0 years, transient GF subjects on gluten-free diet for 2.2 +/- 0.9 years

Anthropometrics: Newly diagnosed subjects were age and sex matched.

Location: Italy

Summary of Results:

	GFD (n=73)	Transient GF (n=57)	Never GF (n=78)	P-value
Age at menarche (yrs)	12.6 +/- 1.4	13.1 +/- 1.7	12.5 +/- 1.4	0.091
Pregnancies (n)	0.22 +/- 0.7 (11)	0.47 +/- 0.8 (16)	0.5 +/- 1.0 (32)	0.074
Offspring (n)	0.11 +/- 0.4 (6)	0.35 +/- 0.7 (13)	0.44 +/- 0.8 (27)	0.006
Abortion (n)	0.11 +/- 0.3 (3)	0.10 +/- 0.5 (4)	0.09 +/- 0.4 (6)	0.956
Abortion-to-pregnancy ratio	0.34 +/- 0.4	0.22 +/- 0.4	0.13 +/- 0.3	0.360
Threatened abortion (n)	0.0 +/- 0.0 (0)	0.9 +/- 0.3 (5)	0.0 +/- 0.0 (0)	0.020
Preterm delivery (n)	0.03 +/- 0.27 (1)	0.04 +/- 0.20 (1)	0.09 +/- 0.4	0.870
Offspring birth weight (g)	3290.2 +/- 220.2	2892.3 +/- 169.8	2478.0 +/- 517.2	0.001
Months of breast feeding	4.50 +/- 2.1	2.56 +/- 1.3	1.77 +/- 0.5	0.001

Other Findings

Of 110 subjects on gluten-free diet, only 65 were strictly compliant.

BMI and main laboratory indices were statistically different among groups (lowest in never on gluten-free diet, highest in gluten-free diet).

The lowest average levels of bone mineral density were found among never on gluten-free diet patients. The BMD at femur was not significantly different among GFD and transient GF patients.

Prevalence of autoimmune disorders was increased in never on gluten-free diet when compared with the transient gluten-free diet and gluten-free diet groups.

Histology revealed villous subatrophy in all patients of never on gluten-free diet group, in 39 of 110 patients of gluten-free diet and in 84 of 85 of transient gluten-free diet groups.

Herpetiform dermatitis was found in 3 patients of gluten-free diet, 3 of transient gluten-free diet and 3 of never on gluten-free diet.

Dental enamel defects were found in 15 patients of transient gluten-free diet, 43 of never on gluten-free diet, and in 0 of the gluten-free diet group.

The number of threatened abortions was significantly greater in transient GF women compared with GFD women. Pregnancy outcome was not significantly different between the groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten-free diet group.

More than 20% of celiac patients showed clinical signs of depression. Compliance to GFD was strongly related to depression; the better the compliance, the worse the depression (F = 36.063; P = 0.001; CI: 20.21 +/- -2.543; upper 29.26 +/- -1.279), independent from the duration in years of GFD (F = 0.136, P = NS).

Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten-free diet group when compared with the other 2 groups.

Author Conclusion:

In conclusion, the main result of this study is that a short period of gluten-free diet during childhood or even a low compliance to diet for intentional or unintentional habitual gluten intake might have a long-term protective effect from gluten-related diseases.

Funding Source:

University/Hospital:

University of Napoli (Italy)

Reviewer Comments:

Inclusion/exclusion criteria not well defined. Dietary adherence measured through self-reported Knowledge Rating Scale and Dietetic Restriction Compliance. Only 65/110 GFD subjects were actually compliant.

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?		???
	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?	???
	2.2.	Were criteria applied equally to all study groups?	???
	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?	???
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)	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	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?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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.)	No
	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?		???
	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?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	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)?	Yes
	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