Between 1984 and 1996, Sweden experienced an “epidemic” of clinical celiac disease in children <2 years of age, attributed partly to changes in infant feeding. Whether infant feeding affects disease occurrence and/or the clinical presentation remains unknown. We investigated and compared the total prevalence of celiac disease in 2 birth cohorts of 12-year-olds and related the findings to each cohort’s ascertained infant feeding.
A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios.
The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60–0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding).
A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable.
Comments
Celiac disease and infant feeding: conclusions not supported by study findings? Letter in response to: Ivarsson et al. Prevalence of Childhood Celiac Disease and Changes in Infant Feeding. Pediatrics. 2013;131(3):March 2013. Epub 2013 Feb 2013
To the Editor
We read with interest the recent article by Ivarsson and colleagues(1). The study adds to several from this group investigating the association of various factors, including infant feeding and timing of introduction of gluten, with subsequent development of celiac disease(2- 4). The information provided is derived from a larger dataset and is not new but a novel aspect is the comparison between the prevalence of celiac disease in two birth cohorts. The authors contend, based on their findings, that early introduction of gluten from 4 months with concurrent breastfeeding can potentially prevent celiac disease. We have several concerns that question this conclusion.
The pre-specified null hypothesis is curious considering the cohorts selected for comparison ('Swedish epidemic' 1993 cohort and a 1997 cohort). Results (higher rates of celiac disease in the 1993 cohort) confirmed what the authors already thought a priori. The authors have previously published on the decreased risk for celiac disease in children in whom gluten was introduced while breastfeeding was continued(3, 4). The present study was unlikely to report contrary findings.
The prevalence of celiac disease was determined from a combination of clinically detected cases and screening of asymptomatic children. Whether the children sampled were representative could be challenged as just over two-thirds invited participated in the study, and of these, only two- thirds of families completed the feeding questionnaire. It is unknown if these were from the same children that were screened. Importantly, the authors have previously showed regional differences in incidence rates for celiac disease(5). Although the ethics of screening asymptomatic children is perhaps initially questionable, the fact the authors detected a significant number of cases in these children is interesting.
Given the main aim was to correlate infant feeding patterns with risk of celiac disease, the methodology was overly focused on the screening strategy. Limited information was provided regarding the questionnaire and the information obtained was not correlated with risk of developing celiac disease on an individual basis. No formal analyses were included to establish the relationship between infant feeding patterns with subsequent development of celiac disease, adjusted for cohort.
The authors' conclusion regarding the timing of introducing gluten (4 months) is not supported by their data, as there was no difference between cohorts in the median age at which gluten was introduced. The authors are quick to ascribe this to recall bias but accept accurate recall of the duration of breastfeeding.
The discussion is lengthy and the authors provide multiple hypotheses as to why the timing of and the amount of gluten introduced may influence the risk of developing celiac. The most interesting finding, namely the high proportion of asymptomatic children that screened positive and the implications, if any, this may have on a population level is not discussed.
While the authors have shown a difference in the prevalence of celiac disease between two birth cohorts, we urge caution given the limited data provided, in accepting the conclusion that infant feeding patterns are primarily responsible.
H Hernstadt S Kazi, S Vidmar, C Nguyen, T Connell
References 1. Ivarsson A, Myleus A, Norstrom F, van der Pals M, Rosen A, Hogberg L, et al. Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics. 2013;131(3):e687-94. Epub 2013/02/20. 2. Myleus A, Hernell O, Gothefors L, Hammarstrom ML, Persson LA, Stenlund H, et al. Early infections are associated with increased risk for celiac disease: an incident case-referent study. BMC pediatrics. 2012;12:194. Epub 2012/12/20. 3. Carlsson A, Agardh D, Borulf S, Grodzinsky E, Axelsson I, Ivarsson SA. Prevalence of celiac disease: before and after a national change in feeding recommendations. Scandinavian journal of gastroenterology. 2006;41(5):553-8. Epub 2006/04/28. 4. Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. The American journal of clinical nutrition. 2002;75(5):914-21. Epub 2002/04/27. 5. Olsson C, Stenlund H, Hornell A, Hernell O, Ivarsson A. Regional variation in celiac disease risk within Sweden revealed by the nationwide prospective incidence register. Acta Paediatr. 2009;98(2):337-42. Epub 2008/11/04.
Conflict of Interest:
None declared