EAL

CD: Pregnancy Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine birthweight, low birthweight (<2500 g) and intrauterine growth retardation in offspring of women with celiac disease in relation to their first hospitalization for the disease.

Inclusion Criteria:

Individuals enrolled in the study if they had a discharge diagnosis of celiac disease between January 1997 and December 1992, and the first registration of celiac disease in the registry was regarded as the first time of hospitalization for the disease, the time of diagnosis, and the beginning of treatment with a gluten-free diet.

Exclusion Criteria:

None specifically mentioned. If data appeared questionable, it was excluded (if a baby was born at gestational age > 37 weeks, with length > 50 cm and an Apgar score of 10, a birthweight < 1000 g was excluded).

Description of Study Protocol:

Recruitment

Based on The Danish Medical Birth Registry data of celiac women discharged from Danish hospitals from 1977 - 1992.

Design

Historical cohort.

Blinding used (if applicable)

Not used - retrospective analysis.

Intervention (if applicable)

Data from Danish National Registry of Patients and Danish Medical Birth Registry was analyzed.

Statistical Analysis

Odds ratios estimated by logistic regression models and 95% confidence intervals were calculated. In the model, potential confounding variables were adjusted for: mother's age, parity, and gestational age. Logistic regression models were also used to evaluate the influence of the disease on the risk of low birthweight, intrauterine growth retardation, and preterm birth according to the first hospitalization for celiac disease. Multiple linear regression was used to analyze differences in birthweight and Ponderal Index for newborns between groups. The model fit was evaluated by applying the residuals to predicted value of birthweight.

Data Collection Summary:

Timing of Measurements

Historical data was evaluated.

Dependent Variables

Data on offspring's date and place of birth, birthweight, length at birth, marital status, parity and gestational age recorded in the The Danish Medical Birth Registry
Birth outcomes studies were birthweight, low birthweight (<2500 g), preterm birth (before 37th week), intrauterine growth retardation (birthweight < 2500 g and gestational age > 37 weeks of pregnancy), stillbirths, and perinatal mortality (number of stillbirths and deaths in the first week), and Ponderal Index (birthweight in g x 100/birth length in cubic cm)

Independent Variables

Gluten-free diet not discussed, compliance assumed

Control Variables

Mother's age, parity, gestational age, infant gender, marital status, calendar period

Description of Actual Data Sample:

Initial N: 550 women with celiac disease were identified. 211 newborns to 127 mothers with celiac disease and 1260 control deliveries.

Attrition (final N): 2 birthweights were excluded due to questionable data.

Age: Mean age at time of delivery: celiac = 27.5 years, controls = 26.3 years

Ethnicity: Not mentioned

Other relevant demographics: Not mentioned

Anthropometrics: Celiac subjects matched to 6 controls based on age and county of residence

Location: Denmark

Summary of Results:

Variable	Celiac (%)	Controls (%)	OR (95% CI)	Adjusted OR (95% CI)
Birth >5 years before first hospitalization	Mean birthweight = 3113 g	Mean birthweight = 3403 g		-166 (-278, -54)
Birth 0-5 years before first hospitalization	Mean birthweight = 3050 g	Mean birthweight = 3403 g		-337 (-468, -206)
After first hospitalization	Mean birthweight = 3573 g	Mean birthweight = 3403 g		67 (-88, 223)
LBW	22/205 (10.7%)	60/1253 (4.8%)	2.4 (1.4-4.0)	2.2 (1.1-4.5)
LBW before first hospitalization	19/155 (12.3%)	60/1253 (4.8%)	2.8 (1.6-4.8)	2.6 (1.3-5.5)
LBW after first hospitalization	3/50 (6.0%)	60/1253 (4.8%)	1.3 (0.4-4.2)	0.7 (0.1-6.1)
IUGR	11/175 (6.3%)	27/1111 (2.4%)	2.7 (1.3-5.5)	2.8 (1.4-5.9)
IUGR before first hospitalization	11/132 (8.3%)	27/1111 (2.4%)	3.6 (1.8-7.5)	3.4 (1.6-7.2)
IUGR after first hospitalization	0/43 (0%)	27/1111 (2.4%)
Gestational age <37 weeks	14/193 (7.3%)	57/1171 (4.9%)	1.5 (0.8-2.8)	1.5 (0.8-2.8)

Other Findings

At the time of giving birth, the women with celiac disease were older than controls.

Before celiac women were first hospitalized the mean birthweight of their newborns was 238 g (95% CI = 150, 325 g) lower than that of the control women, after adjustment for potential confounders.

After the first hospitalization the mean birthweight for newborns of diseased women was higher than that of controls, by 67 g (95% CI = -88, 223 g) after adjustment for potential confounders.

Before celiac women were first hospitalized, we found an increased risk of low birthweight (OR = 2.6, 95% CI = 1.3 - 5.5) and intrauterine growth retardation (OR = 3.4, 95% CI = 1.6 - 7.2).

After celiac women were first hospitalized, we found no increased risk of low birthweight and no babies with intrauterine growth retardation.

Author Conclusion:

The major finding in our study was an increased risk of LBW and more than a threefold higher risk of IUGR in babies born to women with celiac disease, but only in births that occurred before the first hospitalization of the mother. After the mother's first hospitalization, the birthweight was similar to controls and no increased risk of low birthweight was seen. Our study indicates that treatment of celiac women is important in the prevention of fetal growth retardation.

Funding Source:

Government:

Danish National Research Foundation

University/Hospital:

Danish Epidemiology Science Centre University of Aarhus

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Compliance with gluten-free diet assumed. Authors note that they were unable to control for smoking and other determinants that are associated with reduced fetal growth. Some women may have been diagnosed with celiac disease prior to any 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?		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?	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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.)	Yes
	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?		???
	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?	???
	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?	No
	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