CD: Pregnancy Outcomes (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To investigate the incidence of fertility, abortions and perinatal mortality, age at menarche and menopause in celiac disease.
Inclusion Criteria:
All female patients with celiac disease between ages of 16 and 65.  Diagnosis was only accepted after histological confirmation.  Patients with all clinical grades of severity of the disease were included.  All women who were allive and still resident in the area were approached.
Exclusion Criteria:

Women who had moved out of the area and women with established disease who had moved into the area were excluded.  Women of ethnic origin were also excluded because of lack of response and their small number.

Description of Study Protocol:

Recruitment

Patients identified from thorough review of various sources.  Matched controls identified through friends of patients and normal healthy people from age/sex registers kept in general practice.

Design

Case-control.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Patients and matched controls were sent questionnaires.

Statistical Analysis

Paired t tests, McNemar's matched pairs analysis, Yates continuity corrected chi-square tests, Mann Whitney U tests, Fisher's exact tests.

Data Collection Summary:

Timing of Measurements

Patients and controls sent questionnaires about fertility profile and other obstetric and gynecological problems.

Dependent Variables

  • Details of any miscarriages, stillbirths, or complications of pregnancy
  • Menarche and menopause
  • History of hysterectomy or difficulties in conception
  • Children born before and after diagnosis

Independent Variables

  • Current age
  • Marital status and age at marriage
  • Age at diagnosis
  • Children's dates of birth

Control Variables

 

Description of Actual Data Sample:

 

Initial N: 80 patients, 79 age- and sex-matched controls

Attrition (final N):  Only 68 pairs were matched for study.  Dropouts not discussed.

Age:  Actual age not mentioned. 

Ethnicity:  Ethnic groups were excluded. 

Other relevant demographics:

Anthropometrics:  Control group matched for age within 2 years and sex

Location:  Leicestershire, UK 

 

Summary of Results:

 

  Number of Children

t-test

Paired p
Before dx: patients 1.4 +/- 1.1   <0.02
Before dx:  controls 1.8 +/- 1.4 1.8 NS
After dx:  patients

0.5 +/- 0.9

 

NS

Before dx: controls

0.7 +/- 1.1

-1.7

NS

Other Findings

The mean age of menarche in patients was significantly older than in controls (13.6 +/- 1.9 vs 12.7 +/- 1.4 years, t = 3.6, p < 0.001).

Mean ages at menopause in patients and controls were 47.6 and 50.1 years, respectively.

The mean number of children born to patients was significantly less at 1.9 +/- 0.9 compared to 2.5 +/- 1.2 in controls (t = 3.2, p < 0.001).

Before diagnosis, the mean number of children born to patients was 1.4 +/- 1.1 and 1.8 +/- 1.4 in controls (t = 1.8, p < 0.02).

After diagnosis and treatment, patients had 0.5 +/- 0.9 children compared to 0.7 +/- 1.2 in controls (NS).  It seems likely that the overall difference in fertility is due to relative infertility prior to diagnosis and its correction by a gluten-free diet.

Significantly more conceptions among women with celiac disease (15%) ended in miscarriage prior to diagnosis than among controls (6%).  After diagnosis and treatment, the rate of miscarriage was similar. 

There were 120 live babies and 7 stillbirths to patients compared with 161 live babies and 1 stillbirth to controls.  The incidence of stillbirth among patients was significantly higher (p < 0.03).

Author Conclusion:
Previous reports have suggested patients with untreated celiac disease to be subfertile and that pregnancy may be associated with various obstetric and gynaecological abnormalities.  The causes of infertility are not yet known, but malnutrition and folic acid deficiency may be important.  Treatment of celiac disease with a gluten-free diet does not completely rectify these problems and in the future, patients with this condition will need counseling.  Joint management with obstetricians may have somew benefit during pregnancy and in view of reduced fertility, preconceptual referrals should be considered.  Screening with antigliadin antibodies may be used as a diagnostic tool for celiac disease in infertility clinics.
Funding Source:
University/Hospital: Leicester General Hospital (UK)
Reviewer Comments:
No definition of gluten-free diet or compliance mentioned.  Ethnic groups excluded entirely.  Dropouts not discussed.  Questionnaire reliability and validity not mentioned.
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? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? No
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.) N/A
  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? Yes
  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.) Yes
  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? ???
  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? No
  4.4. Were reasons for withdrawals similar across groups? ???
  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? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  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? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  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? 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? ???
  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? ???
  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? ???
  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