BACKGROUND: The risk of infectious mononucleosis (IM) is affected both by crowding and by sibship structure, i.e., number and signed age differential between an index child and a sibling. Siblings provide protection against IM by pre-empting delayed primary Epstein-Barr virus infection with its associated high risk of IM. The association between childcare attendance and risk of IM, on the other hand, has never been studied in a large, well-characterized cohort.

METHODS: Danish children born in July 1992 through 2016 with a completely known simple childcare attendance history before age 1.5 years (n = 908,866) were followed up for a hospital contact with an IM diagnosis at ages 1.5-26 years. Hazard ratios (HRs) of IM for an additional year of exposure were obtained from stratified Cox regression analyses, stratified by sex and year of birth, with age as the underlying time scale, adjusted for sibship structure, and sociodemographic variables including parental ethnicity and maternal age.

RESULTS: An additional year of exclusively attending a daycare home (max 5 children) yielded HR = 0.90 (95% confidence interval 0.81-1.00), and similarly, each year of exclusively attending a childcare institution (e.g., crèche) yielded HR = 0.94 (0.84-1.06).

CONCLUSIONS: Forwarding enrollment in childcare by a year lowers the risk of IM later in life much less than having an additional sibling of comparable age and has no practical public health implications. We find our results suggestive of a random threshold for successful Epstein-Barr virus infection that is more easily reached by a sibling than the collective of playmates in daycare homes or childcare institutions.