EAL

CD: Pregnancy Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the risk of adverse outcomes in women with celiac disease diagnosed prior to pregnancy and in women who did not receive a diagnosis of celiac disease until after the delivery.

Inclusion Criteria:

Women with a hospital-based discharge diagnosis of celiac disease between 1964 - 2001 were identified through the Swedish national inpatient registry. The subjects of this study consisted of all live-born singleton infants who were born in Sweden during the period 1973 - 2001 to mothers aged 15 - 44 years.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Swedish national inpatient register obtained from the Swedish National Board of Health and Welfare, data from 1964 - 2001.

Design

Population-based cohort.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Data from Swedish national register was analyzed.

Statistical Analysis

Frequency data. Categorical independent variables were tested against outcome measures using Pearson chi-square test (with Yates correction or Fisher exact test when expected value of any cells was less than 5). Logistic regression was used to calculate ORs and 95% confidence intervals for each fetal outcome in relation to presence of celiac disease in the mother. 95% CIs not including 1.00 were considered statistically significant. In multivariate model I, the risk of adverse fetal outcome in relation to celiac disease was analyzed adjusting simultaneously for infant sex, parity, maternal age at delivery, nationality, and calendar period. Multivariate model II (births from 1983 and onward), was adjusted for smoking. Comparisons between groups were made with the Student t test and multiple linear regression.

Data Collection Summary:

Timing of Measurements

Data retrospectively reviewed.

Dependent Variables

Intrauterine growth retardation
Low birth weight (<2500 g)
Very low birth weight (<1500 g)
Preterm birth (<37 gestational weeks)
Very preterm birth (<30 gestational weeks)
Cesarean section
Low Apgar score at 5 minutes

Independent Variables

Diagnosis of celiac disease prior to or after birth

Control Variables

Smoking
Diagnosis of diabetes

Description of Actual Data Sample:

Initial N: There were a total of 2,822,805 women without celiac disease. 2078 offspring to women who had received diagnosis of celiac disease. 1149 offspring to women diagnosed prior to birth and 929 offspring to women diagnosed after birth.

Attrition (final N): See above

Age: Most women were 20 -34 years of age when giving birth

Ethnicity: Over 93% were of Nordic ancestry

Other relevant demographics: Few women reported smoking during pregnancy

Anthropometrics:

Location: Sweden

Summary of Results:

Variable	Adjusted OR, 95% CI	P-value
IUGR - Undiagnosed CD	1.62, 1.22-2.15	0.001
IUGR - Diagnosed CD	1.29, 0.94-1.78	0.115
LBW - Undiagnosed CD	2.13, 1.66-2.75	<0.001
LBW - Diagnosed CD	1.25, 0.93-1.67	0.137
VLBW - Undiagnosed CD	2.45, 1.35-4.43	0.003
VLBW - Diagnosed CD	0.98, 0.44-2.18	0.956
Preterm Birth - Undiagnosed CD	1.71, 1.35-2.17	<0.001
Preterm Birth - Diagnosed CD	1.25, 0.98-1.59	0.066
Very Preterm Birth - Undiagnosed CD	2.06, 0.92-4.60	0.078
Very Preterm Birth - Diagnosed CD	0.99, 0.37-2.64	0.981
Low Apgar Score - Undiagnosed CD	1.18, 0.68-2.04	0.563
Low Apgar Score - Diagnosed CD	0.86, 0.47-1.56	0.615
Cesarean Section - Undiagnosed CD	1.82, 1.27-2.60	0.001
Cesarean Section - Diagnosed CD	0.87, 0.53-1.41	0.563

Other Findings

Undiagnosed celiac disease was associated with an increased risk of intrauterine growth retardation (OR = 1.62, 95% CI: 1.22 - 2.15), low birth weight (OR = 2.13, 95% CI: 1.66 - 2.75), very low birth weight (OR = 2.45, 95% CI: 1.35 - 4.43), preterm birth (OR = 1.71, 95% CI: 1.35 - 2.17), and caesarean section (OR = 1.82, 95% CI: 1.27 - 2.60).

In contrast, a diagnosis of celiac disease made before the birth was not associated with these adverse fetal outcomes.

Smoking did not appear to modify the effect on birth outcomes of undiagnosed celiac disease, and results were only marginally affected when presence of diabetes was included in the models.

Author Conclusion:

This study found that women with celiac disease that was undiagnosed at the time of delivery were more likely to have a preterm birth, cesarean section, or have an offspring with IUGR, LBW or VLBW. In contrast, maternal celiac disease diagnosed before birth was not associated with adverse fetal outcomes. Undiagnosed maternal celiac disease is a risk factor for unfavorable fetal outcomes, but the risks are reduced when celiac disease has been diagnosed. Celiac disease diagnosed prior to pregnancy does not constitute a great a risk as undiagnosed celiac disease.

Funding Source:

Government:

Swedish Research Council

University/Hospital:

Orebro University Hospital, Karolinska Institute

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Data adjusted for smoking and diabetes. Compliance with gluten-free diet assumed after diagnosis. Subjects had been identified through symptoms and not through screening. Patients may have been diagnosed prior to hospitalization.

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?	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)	N/A
	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?	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.)	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%.)	N/A
	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?		???
	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?	???
	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?	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?		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