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Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies |
Cardwell C R, Stene L C, Joner G, Cinek O, Svensson J, Goldacre M J, Parslow R C, Pozzilli P, Brigis G, Stoyanov D, Urbonaite B, Sipetic S, Schober E, Ionescu-Tirgoviste C, Devoti G, de Beaufort C E, Buschard K, Patterson C C |
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CRD summary The authors concluded that there was a small but significant risk of increased risk of type 1 diabetes following caesarean section. Given the lack of validity assessment and the retrospective nature of the included studies, the reliability of the authors' conclusions was unclear. Authors' objectives To evaluate the evidence for an association between type 1 diabetes and caesarean section, adjusting for potential confounders. Searching MEDLINE, EMBASE and Web of Science were searched to September 2007. Search terms were reported. The reference lists of all relevant articles were handsearched to identify further studies. Study selection Studies that identified a group of 15 or more participants with type 1 diabetes and a group without type 1 diabetes and determined the prevalence of caesarean section in these groups were eligible for inclusion.
Included studies were case-control studies, matched case control studies and cohort studies ascertaining childhood diabetes through regional or national diabetes registers or hospital admission compared to controls identified through birth or population registers, schools records, medical records or matched classmates or colleagues. Ascertainment of caesarean section was achieved either through maternity records or questionnaires. In the majority of studies, the participant was aged 14 or under at the time of diagnosis. The included studies were conducted in 14 different countries.
Two reviewers independently selected the studies for inclusion. Assessment of study quality The authors did not state that they assessed validity. Data extraction The number of caesarean sections in each group was extracted and used to calculate odds ratios (OR) and standard errors (SE), with conditional logistic regression analyses used for matched case control studies. For cohort studies, rate ratios and their SEs were calculated and the Poisson regression was used to adjust for differences in the year of birth between cases and controls. The authors of included studies were contacted for additional raw data or adjusted estimates on the following potential confounding variables: birth weight, gestational age, maternal age, birth order, maternal diabetes, maternal type 1 diabetes and breastfeeding. Adjusted ORs for each of these variables were calculated for individual studies using logistic regression, conditional logistic regression or Poisson regression according to the study design.
Data were extracted independently by two reviewers. Methods of synthesis Pooled odds ratios with 95% confidence intervals (CI) were calculated using a random-effects model. Adjusted pooled odds ratios were calculated for potential confounding variables. Heterogeneity was calculated using the Χ2 and I2 statistic. Publication bias was assessed using funnel plots; any bias was adjusted for using the trim and fill method. Sensitivity analyses were carried out according to whether or not population-based randomly selected controls were used. Results of the review Twenty studies were included for review (n=2,133,236): 17 case-control studies (n=25,125) and three cohort studies (n=2,108,111). Methodological quality was not assessed, but four studies used controls that were not randomly selected or population-based.
The incidence of caesarean section delivery was significantly higher in participants who had type 1 diabetes mellitus compared to those who did not have type 1 diabetes (OR 1.23, 95% CI: 1.15, 1.32, p<0.001). There was no evidence of statistical heterogeneity and little evidence of publication bias. A sensitivity analysis including only those studies that used randomly selected population based controls did not alter the findings.
The relationship between caesarean section delivery and type 1 diabetes remained significant when adjusted for birthweight (OR 1.24, p<0.001), gestational age (OR 1.19, p<0.001), maternal age (OR 1.19, p<0.001), birth order (OR 1.21, p<0.001), maternal diabetes (OR 1.17, p=0.003) and breastfeeding (OR 1.26, p<0.001), and after adjusting for all potential confounders simultaneously (OR 1.19, 95% CI: 1.04, 1.36, p=0.01). There was no evidence of significant heterogeneity for these outcomes. Authors' conclusions There is a small but significant risk of increased risk of type 1 diabetes following caesarean section. CRD commentary The review addressed a clear question, though inclusion criteria were broadly stated. Three relevant databases were searched. It was unclear whether language restrictions were applied, so language bias could not be ruled out. Attempts did not appear to have been made to identify unpublished material, but publication bias was assessed and no evidence of bias was found. Appropriate steps were taken in the study selection and data extraction processes to minimise reviewer error and bias. A validity assessment did not appear to have been carried out, so it was not possible to determine the quality of included studies. The inclusion of retrospective studies only may have undermined the strength of the findings. Appropriate methods were used to pool the studies and statistical heterogeneity was assessed. Given the lack of validity assessment and the retrospective nature of the included studies, the reliability of the authors' conclusions was unclear. Implications of the review for practice and research Practice: The authors did not state any implications for practice.
Research: The authors did not state any implications for further research. Bibliographic details Cardwell C R, Stene L C, Joner G, Cinek O, Svensson J, Goldacre M J, Parslow R C, Pozzilli P, Brigis G, Stoyanov D, Urbonaite B, Sipetic S, Schober E, Ionescu-Tirgoviste C, Devoti G, de Beaufort C E, Buschard K, Patterson C C. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia 2008; 51(5): 726-735 Indexing Status Subject indexing assigned by NLM MeSH Adult; Age of Onset; Birth Order; Birth Weight; Cesarean Section /adverse effects; Child; Diabetes Mellitus, Type 1 /epidemiology /genetics; Female; Humans; Infant, Newborn; Maternal Age; Pregnancy; Risk Factors AccessionNumber 12008104845 Date bibliographic record published 01/12/2008 Date abstract record published 06/05/2009 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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