CD: Pregnancy Outcomes (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To estimate fertility, to establish an account of the reproductive experience and to determine the true magnitude of the associated risks in women with celiac disease compared with the general female population.
Inclusion Criteria:
All people with a recorded diagnosis of celiac disease in their record between June 1987 and April 2002 were identified for the cohort.  Up to 5 comparison subjects without celiac disease were obtained and matched based on age, sex, general practice, and follow-up time of general practice record.
Exclusion Criteria:
None specifically mentioned.
Description of Study Protocol:

Recruitment

 Data obtained from the General Practice Research Database, a source of longitudinal records of routine primary care visits for more than 8 million people registered at general practices in the UK.

Design

 Population-based cohort.

Blinding used (if applicable)

 Not applicable.

Intervention (if applicable)

 Primary care data for women with celiac disease matched to women without celiac disease.  Population-based rates of fertility and adverse pregnancy outcomes were estimated.

Statistical Analysis

 Using Poisson regression, fertility rates were estimated as the number of live births per 1000-person years women contributed to the up-to-standard fertile period.  To account for variation in age, fertility rates were stratified by 5 year age bands.  Proportion of birth events for each mode of delivery and pregnancy complications were calculated as rates per 1000 live births.  Confounding variables were assessed using multivariate analyses. 

Data Collection Summary:

Timing of Measurements

 Data was retrospectively reviewed.

Dependent Variables

  • Mode of delivery (assisted delivery, cesarean section, or breech delivery)
  • Pregnancy complications (preeclampsia, postpartum hemorrhage, ectopic pregnancy)
  • Stillbirths
  • Miscarriages
  • Terminations
  • Occurrence of babies born to women in cohort with neural tube defects

Independent Variables

  •  Gluten-free diet - compliance assumed based on fact that >90% had at least 1 gluten-free prescription in their general practice record

Control Variables

  •  Potential confounders:  maternal age at first birth, total number of births, weight, height, smoking habits, diagnosed diabetes, diagnosed thyroid abnormality, diagnosed infertility, and infertility drug treatment
Description of Actual Data Sample:

 Initial N: Of 4732 people with celiac disease and 23,620 comparison subjects, 1521 women with celiac disease, 7732 age- and practice-matched women without celiac disease were potentially fertile

Attrition (final N):  Same as above

Age:  Subjects categorized based on age at first birth, there were no differences between groups regarding age at first birth 

Ethnicity:  Not mentioned 

Other relevant demographics:  There were no differences between groups in total number of births 

Anthropometrics:  Subjects were age-matched.  Women with celiac disease were more likely to have never smoked (P < 0.01) and to have a lower BMI (P < 0.01) compared with women without celiac disease.

Location:  United Kingdom 

 

Summary of Results:

 

Variable Celiac Cohort (n=1521) Comparison Cohort (n=7723) Odds Ratio / Rate Ratio (95% CI)
Cesarean section 93 (10.6%) 368 (8.2%) 1.33 (1.03-1.70)

Assisted birth

85 (9.7%)

 354 (7.9%)

 1.25 (0.97-1.61)

Breech birth

15 (1.7%)

 71 (1.6%)

 1.08 (0.57-1.92)

Preeclampsia 11 (12.5/1000) 38 (8.4/1000) 1.48 (0.76-2.90)
Postpartum hemorrhage 9 (10.2/1000) 44 (9.8/1000) 1.05 (0.51-2.15)
Ectopic pregnancy 19 (21.6/1000) 61 (13.5/1000) 1.60 (0.95-2.67)
Stillbirth 10 (11.2/1000) 40 (8.8/1000) 1.28 (0.64-2.55)
Termination 264 (230.8/1000) 1321 (226.6/1000) 1.02 (0.89-1.16)
Miscarriage 111 (112.0/1000) 422 (85.6/1000) 1.31 (1.06-1.61)

 Other Findings

 Crude fertility rates were 48.2 and 47.7 live births per 1000 person-years for women with and without celiac disease, respectively (rate ratio, 1.01, 95% confidence interval, 0.90 - 1.14).

Age-specific fertility rates showed that women with celiac disease had lower fertility when younger but higher fertility when older compared with women without celiac disease.  This increase in relative fertility with increasing age held whether women had treated or untreated celiac disease.

Risks of cesarean section (OR, 1.33, 95% CI, 1.03 - 1.70) and miscarriage (rate ratio, 1.31, 95% CI, 1.06 - 1.61) were moderately higher in women with celiac disease, but risks of assisted birth, breech birth, preeclampsia, postpartum hemorrhage, ectopic pregnancy, stillbirth and termination were similar. 

None of the women with celiac disease gave birth to babies with neural tube defects.

 

Author Conclusion:
Overall, women with celiac disease have fertility similar to that of the general female population, but they have their babies at an older age.  Women with celiac disease also had pregnancy experiences similar to those of women in the general population, although they had moderately increased risks of cesarean section and miscarriage.  Although our findings may reflect a disease effect, the age shift in fertility rates and the increase in cesarean section risk is consistent with socioeconomic or educational advantages of women with celiac disease.
Funding Source:
University/Hospital: University of Nottingham, Nottingham City Hospital (UK)
Reviewer Comments:
Interesting to look at all potentially fertile subjects.  Authors note that underreporting in the medical record was possible.
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? Yes
  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) 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? Yes
  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? Yes
  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? ???
  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