EAL

CD: Pregnancy Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the prevalence of untreated celiac disease among women attending the obstetrics-gynecology department, in an attempt to improve the mothers' reproductive status by diagnosing the condition and prescribing treatment.

Inclusion Criteria:

Only pregnant women or women in labor were considered.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

All women admitted to the obstetrics-gynecology department of the medical school.

Design

Case-Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Evaluation of endomysial antibodies.

Statistical Analysis

Percentages were compared by rates and proportion; odds ratio with 95% confidence intervals are reported. We also used the corrected chi-square test or Fisher's exact test to compare percentages, and the unpaired Student's t test to compare the means of normally distributed variables.

Data Collection Summary:

Timing of Measurements

Endomysial antibodies evaluated in routine blood tests for all women attending the obstetrics-gynecology department of a large city hospital over a 90 day period. Patients with positive results were offered a complete gastrointestinal exam to confirm diagnosis.

Dependent Variables

Endomysial antibodies determined as described by Ladinser et al and Volta et al on human umbilical cord sections. 221 of the blood samples were retested to verify the procedure and concordance reached in 220 of 221 samples due to readers unaware of the first result. Retested sample for concordance.
Small intestinal biopsies to confirm diagnosis

Independent Variables

Gluten-free diet not defined or monitored.

Control Variables

Description of Actual Data Sample:

Initial N: 1037 admitted to hospital, 39 admitted twice but tested once, 23 declined, 150 had no sample available at time of admission so 20 had a blood sample taken at home within 10 days of admission. Control group formed by random number selection method from 206 pregnant women without celiac disease.

Attrition (final N): Eligible population of 998, 845 pregnant women screened (84.7%), 12 identified as having celiac disease

Age: Ages were similar between groups (28 vs 29 years).

Ethnicity: Not mentioned

Other relevant demographics: Menarche occurred later in the patients with celiac disease: mean age 13.03 +/- 1.5 vs 12.0 +/- 1.3 years (t = -2.99, p < 0.05).

Anthropometrics: Ages similar among groups.

Location: Naples, Italy

Summary of Results:

Other Findings

Of 845 pregnant women screened, 12 were identified as having celiac disease.

3 had been previously diagnosed but were not following a gluten free diet. Remaining 9 underwent a small intestinal biopsy, which confirmed the diagnosis. Severe to total villous atrophy, crypt hyperplasia, and lymphocyte infiltration were found in all cases.

The outcome of pregnancy was unfavourable in 7 of the 12 women: 5 small for gestational age newborns (41%) and 3 preterm deliveries (25%). Among the multiparae, 4 out of 5 had experienced at least 1 miscarriage, and 2 had a history of two or more miscarriages.

4 of the 12 women had a hemoglobin concentration below 100 g/l on admission, at 24, 36, 37 and 39 weeks of pregnancy.

A history of previous miscarriage was more common in women with celiac disease than in controls; 8/12 (67%) reported no previous abortion compared with 161/206 (78.2%) of controls; 2 had 1 abortion (compared with 39 controls) and 2 had 2 or more abortions (compared with 6 controls) (chi-square test 6.06, p = 0.04).

2/206 controls had stillbirth, 2 suffered from perinatal disease, but no babies died after birth. 3 of 13 babies born to women with celiac disease died in the first week of life.

All 12 pregnant women with celiac disease reached delivery.

Mean gestation at delivery was 36.75 weeks, similar to controls (36.77 weeks), but 4/12 (33%) terminated before the 37th week of gestation compared with 24/206 (11.6%) controls (odds ratio 3.79; 95% CI 0.8 to 15).

Breech presentation occurred in 3/12 (25%) patients with celiac disease and 3/206 controls (1.4%), (OR 22.5, 95% CI 3 to 170).

Mean birth weight was lower for the patients with celiac disease than controls (2601 vs 3164 g, t = 2.05; p = 0.064) at the border of a 5% significance.

The Apgar score at 1 minute was below 7 in 3 cases (21%) compared to 11 controls (5.8%), (OR 5.91, 95% CI 1.1 to 29). Similarly, the score at 5 minutes was below 7 in 2 cases (17%) compared with 1 control (0.5%), (OR 41, 95% CI 4.8 to 340, Fisher's exact test, p = 0.0081).

Author Conclusion:

Overall, 1 in 70 women was affected by celiac disease, either not diagnosed (9 cases) or not treated (3 cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for celiac disease should be included in the battery of tests prescribed for pregnant women. Celiac disease is considerably more common than most of the diseases for which pregnant women are screened. Unfavourable events associated with celiac disease may be prevented by a gluten-free diet.

Funding Source:

Government:

Regione Campania (Naples Italy), Istituto Superiore di Sanita (Rome)

Reviewer Comments:

Author reports results of healthy baby delivery after gluten-free diet, however, this finding is not supported by the research in the paper.

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?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		???
	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?	???
	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.)	???
	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?	???
	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?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	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?	???
	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