Josephine van Dongen

2 Acute gastroenteritis disease burden among infants with medical risk conditions 29 by parents detailing healthcare usage, medication, total days with symptoms, lost parental work-days and daycare absenteeism. All monthly questionnaires and medical records were additionally checked for AGE symptoms that had not been repor ted to the study team. And identified as AGE episode if they met the AGE definition and no other cause for symptoms was provided. In this way, we were able to retrieve additional AGE episodes that had not been actively repor ted by parents. However these episodes were incomplete on pathogen and MVS severity information. Outcomes The primary aim was to quantify the AGE burden of disease in rotavirus unvaccinated medical risk infants until 18 months of age.This was based on 1) the incidence rate (IR) of all-cause and virus specific AGE, 2) the AGE related healthcare usage and, 3) the severity of AGE episodes, scored by the MVS scale (more detailed in supplement). A secondary aim of our study was the societal burden, expressed as daycare absenteeism and parental work loss as well as secondary cases that occurred within the household. For these analyses, we used data from the 14-day AGE questionnaire. To evaluate possible risk factors for severe AGE occurrence, we compared patient and household characteristics between infants with at least one AGE episode to those without any AGE during follow-up. Statistical analysis Descriptive statistics were performed using Chi-square or Fisher’s Exact tests for categorical data, t-tests for normally distributed continuous data and non-parametric test (Mann-Whitney U) for non-normally distributed continuous data. A p-value < 0.05 was considered statistically significant. TheAGE IRs were calculated by dividing all AGE episodes by the total persontime of observation and corresponding 95% confidence intervals (95% CI) were computed using the Fisher’s exact method. For virus specific IRs, estimates were adjusted for the propor tion of AGE episodes for which no fecal sample was obtained. We used multiple imputation, by chained equations, for missing virus status of episodes without a stool sample collected (see supplement for specifications). To fur ther explore potential risk factors for severe AGE, we modeled the association between time to first severe AGE with baseline factors and AGE occurrence in seasonal months of known highest circulation of norovirus and rotavirus in the Netherlands (October – April) 23. We used a Cox regression model with age as time axis. All potential covariates were tested univariate; those with a significant effect were used for the multivariate model. Model selection