This study found a modest increased risk of later CD in individuals born in summer months. More importantly, the upper 95% CI was 1.08, ruling out a large effect of summer birth on the risk of CD. Overall, seasonal variation in food intake and infectious disease exposures are therefore unlikely to be a major cause of CD.
Of the four earlier studies on this topic, three found a positive association between CD and summer birth in subsets of study participants with CD.[13
While Ivarsson et al found a 1.4-fold increased risk of future CD in children born in the summer and aged <2 years at diagnosis, they did not see an increased risk in children diagnosed with CD at the age of 2–15 years (relative risk=0.96; 0.81–1.1).[18
] Interestingly enough, Lewy et al also found a seasonality pattern in girls diagnosed with CD before 24 months of age but not after,[20
] and even if there was a seasonality pattern in boys with CD both before and after 24 months of age, the patterns differed.[20
Data from a longitudinal study in Denver (54 cases with CD) found that 53% of CD cases vs. 48% of controls were born April-September.[13
] A study from Massachusetts, published in abstract form, examined 382 children with CD and reported an increased risk of CD in individuals diagnosed <15 years, but not in individuals diagnosed 15–19 years of age.[19
] Kokkonen et al examined 226 Finnish children but observed no association between birth season and risk of CD.[17
The main difference between our and earlier studies lies in the number of patients with CD. Our study involved more than 29,000 patients with CD compared to 3244 patients in the five earlier studies combined.[13
] This allowed for stratified analyses where we were able to detect a positive association between summer birth and CD in all age strata although only for children diagnosed <2 years, and adults diagnosed ≥18 years were these associations statistically significant. Another difference is our use of matched controls. Using conditional logistic regression approach we could examine study participants per stratum (one individual with CD compared to his or her matched controls), and we were hence able to eliminate the effect of gender, age, calendar period and county on our risk estimates.
We used biopsy data to ascertain CD. An earlier validation study has found that 96% of all Swedish adult gastroenterologists and 100% of all paediatricians biopsy patients with CD before diagnosis.[25
] Hence our study is likely to have identified a very high proportion of patients with diagnosed CD. However we did not screen the Swedish population for CD and hence we were unable to study the association between birth season and undiagnosed CD.
It is unlikely that our findings are due to chance. Of the six summer months in this study, there was a positive association with CD in five (August being the exception). Our risk estimate was highly statistically significant (OR 1.06; 95% CI 1.03–1.08, p<0.0001). Still, we urge caution when interpreting our data, as the mechanism for this small association is unknown, it did not occur in the last calendar period, and our findings should therefore not influence how parents plan their conception and pregnancy.
The positive association between summer birth and future CD was only seen in children born until 1999. We cannot explain the lack of association in children born thereafter. One potential explanation is that the lack of statistical significance here is a chance finding, just as the opposite, statistically significant associations, may occur when many comparisions are performed. It is also possible that individuals diagnosed after 1999 are phenotypically different from children born earlier, due to the advent of easily available CD screening tools such as endomysium and tissue transglutaminase antibodies. If summer birth is associated with CD primarily in children with classic symptoms, this could also explain why we saw the highest OR in children diagnosed with CD before 2 years of age (when disease onset often consists of malabsorptive symptoms).
In this study we did not have access to data on exposures to infectious disease, age at gluten introduction and breastfeeding duration. However, we speculate that children born in summer are more exposed to viral infections at time of gluten introduction (winter). In our recent paper on 9,408 children with prospective data on nutrition and infectious disease, infection at time of gluten introduction was associated with an increased risk of future CD although the risk estimate failed to attain statistical significance (adjusted OR=1.8, 95%CI=0.9–3.6).[8
] Infections (either viral or bacterial) could potentially increase the risk of CD in several ways. They may influence the microbiota, thereby compromising the mucosal barrier function.[27
] Infections may also lead to the release of interferon gamma increasing HLA expression. [28
] Importantly, some infections seem to influence tissue transglutaminase release,[29
] which is a crucial factor in CD.
Another possible mechanism is the effect of low vitamin D levels both in the mother due to lack of UV light exposure in mid-pregnancy or in the child at the time of gluten introduction or viral infection.[22
In conclusion, summer birth was associated with an increased risk of later CD, but the excess risk was small, largely limited to children diagnosed before age 2, and was not seen in the last calendar period. Seasonal exposures early in life, such as infectious diseases, are unlikely to be a major cause of CD. Future studies should focus on testing putative mechanisms underlying this modest association between birth season and risk of CD.