EAL

CD: Pregnancy Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the true prevalence of gynecologic and obstetric disturbances in celiac disease, the correlation between these data and the nutritional status of the patients, the influence of a gluten-free diet on gynecologic and obstetric events in adult women after the treatment, and the influence of a gluten-free diet on gynecologic and obstetric events in patients diagnosed as having celiac disease in early infancy, childhood and adolescence.

Inclusion Criteria:

Diagnosis of IBS based on Roma Criteria II and intestinal biopsy/antiendomysium antibodies performed to exclude celiac disease. Diagnosis of celiac disease based on clinical, laboratory and histologic findings. All 76 adults and 22 adolescents had intestinal biopsies and all patients responded to gluten-free diet.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Consecutive women with GI complaints studied retro and prospectively on the basis of a protocol with clinical, laboratory and histologic data.

Design

Case control study.

Blinding used (if applicable)

Not used.

Intervention (if applicable)

Gynecologic and obstetric history obtained by interviews with same physician.

Statistical Analysis

ANOVA and Student t test. Mann-Whitney U test used to compare proportions.

Data Collection Summary:

Timing of Measurements

Subjects gynecological and obstetrical histories compared to controls with IBS.

Dependent Variables

Degree of malnutrition (without, mild, moderate or severe), based on anthropometric data (weight, height, BMI), hypoproteinemia and percentage of weight loss
Biopsy specimens taken during upper GI endoscopy from descending part of duodenum and classified according to villous architecture as normal, partial or total villous atrophy
Routine testing for ferritin, total proteins and albumin determinations
IgA levels determined by turbidimetry
IgA EmA detected by indirect immunofluorescence

Independent Variables

Gluten-free diet: adherence determined through physician interview. Patients ingesting 3 - 10 g gluten/day considered non-adherent.

Control Variables

Description of Actual Data Sample:

Initial N: 200 consecutive patients. 76 adult female celiac patients and 18 children/adolescents; 84 adult and 22 adolescent controls with irritable bowel syndrome.

Attrition (final N): See above.

Age: Celiac women mean age: 38.8 years, Controls: mean age 45.2 years.

Ethnicity: All white women born in Southern Brazil

Other relevant demographics:

Anthropometrics: Controls were age-matched

Location: Brazil

Summary of Results:

	IBS (n=84)	Celiacs (n=76)	P value
Secondary amenorrhea	0	28.0%	P < 0.0001
Number of pregnancies	76.2%	76.3%	P = 0.864
Spontaneous abortion	17.9%	35.5%	P = 0.019
Age at menopause	48.6 +/- 4.1 years	49.0 +/- 3.7 years	P = 0.684
Reproductive period	35.9 +/- 3.9 years	35.0 +/- 3.7 years	P = 0.347
Anemia	0	84.2%	P < 0.0001
Hypoalbuminemia	0	48.7%	P < 0.0001

Other Findings

Adult celiac patients, irrespective of nutritional status, were younger than controls, presented delayed menarche (13.7 +/- 1.5 years vs 12.8 +/- 1.6 years, P < 0.0001), secondary amenorrhea (detected in 28% of celiac women and none of the controls, P < 0.0001), a higher percentage of spontaneous abortions (35.5% vs 17.9%, P = 0.019), anemia and hypoalbuminemia.

No differences were observed regarding the number of pregnancies, age at menopause and duration of the reproductive period.

When celiacs divided into subgroups according to degree of malnutrition, delayed menarche appeared in all subgroups.

Based on 12 subjects, after treatment with gluten-free diet, patients presented with normal pregnancies and 1 patient presented spontaneous abortion.

The adolescents who were not adherent to gluten-free diet presented delayed menarche (P = 0.003) and secondary amenorrhea (P = 0.041).

Author Conclusion:

On the basis of the present data, we conclude that untreated celiac women did not present infertility but had difficulty in maintaining their pregnancy, therefore we recommend screening with EmA in women with recurrent miscarriage or infertility. In conclusion, gluten per se could explain the disturbances and malnutrition would worden the disease in a consequent vicious cycle. Therefore, celiac disease should be included in the screening of reproductive disorders.

Funding Source:

University/Hospital:

Pontifical Catholic University of Paraná; Federal University of Paraná; Curitiba, Paraná, Brazil

Reviewer Comments:

Inclusion/exclusion criteria not well defined. Effect of gluten-free diet only compared in 12 subjects.

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)	Yes
	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?	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?		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?		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?	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	???
	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