Josephine van Dongen

Chapter 4 94 Study setting Dutch hospitals with a neonatal intensive care unit (NICU) or post-intensive care (IC)/High Care (HC) ward were invited to par ticipate in the project. Hospitals could par ticipate if they were willing to 1) implement rotavirus vaccination for MRC infants in their routine neonatal care and, 2) recruit and enroll eligible infants in the before-after cohor t study. Thir teen Dutch hospitals, at 15 locations, with a NICU or post-IC/HC unit par ticipated in the RIVAR study. Hospitals enrolled in a stepped-wedge order. The first hospitals enrolled in November 2014 and the last in April 2016. Implementation of a hospital-based selective rotavirus vaccination program Following enrollment, each hospital entered a preparatory pre-implementation year during which local operational procedures were developed for patient selection, rotavirus vaccine delivery, administration and, documentation. In the second year, rotavirus vaccination was locally implemented, at different time-points, for all infants with a qualifying MRC and was continued throughout the study. At the star t of the pre-implementation year, the par ticipating site initiated screening of all hospitalized infants less than 14 weeks of age for prematurity (gestational age before 36 weeks), low bir thweight (LBW, under 2500 grams) and/or, presence of a severe congenital disorder (for qualifying conditions, see figure S1 in appendix). Infants still hospitalized or receiving outpatient care between six to 14 weeks of postnatal age (corresponding with the age-window for first dose rotavirus vaccination) were eligible. Following implementation, the human rotavirus vaccine (HRV, containing attenuated human rotavirus G1P8 genotype, licensed by GSK, Belgium, since 2006) was used throughout the project and given as two oral doses. Before-after cohort study Parents of eligible infants were approached for par ticipation in the cohor t study with active follow-up for occurrence of AGE until 18 months of age. Enrollment star ted early in the pre- implementation year and continued in each hospital until 12-18 months after implementation of the selective rotavirus vaccination program. The ‘before’ cohor t thus included infants who received standard of care only. The ‘after’ cohor t included infants who were routinely offered rotavirus vaccination.Throughout follow-up, next to monthly questionnaires and medical char t review, parents were asked to notify the study team whenever symptoms of AGE developed in their child. Parents were instructed to collect a fecal sample from their child as soon as possible and to complete a symptom diary for seven days and a questionnaire on healthcare attendance. For a schematic overview of the study outline and procedures, see figure 1 .