Josephine van Dongen

Chapter 5 120 par ticipating secondary pediatric hospitals. Eligible infants included those with prematurity, low bir th weight and/or, presence of a severe congenital disorder (list added in chapter 4 ). Eligibility fur ther required an inpatient hospital stay or a planned outpatient visit between six and 14 weeks postnatal age, allowing for first dose rotavirus vaccine administration on site within the appropriate age-window. The target population therefore represented infants with medical risk conditions who required prolonged pediatric care after bir th.Within par ticipating hospitals, a prospective cohor t study was set-up star ting enrollment from one year before rotavirus vaccination implementation (rotavirus unvaccinated infants), until 12-18 months post-implementation (rotavirus vaccinated infants). Par ticipating infants were followed from approximately six weeks until 18 months of age for occurrence of acute gastroenteritis to evaluate vaccine effectiveness as primary outcome. In addition, all vaccinations received and solicited AE were prospectively documented for tolerability assessment as secondary outcome. To guide recommendations of rotavirus vaccination, tolerability was analyzed for subgroups of infants with medical risk conditions separately. Data collection Safety assessment was a secondary outcome of the RIVAR project.The research staff reviewed medical records for each rotavirus vaccination eligible infant at approximately five months of age to check rotavirus vaccination dates and documentation of any vaccine related serious vaccine adverse reaction (SAE) following administration. Vaccine related SAE was defined as any reaction that was fatal, life threatening, disabling or incapacitating, required in-patient treatment or prolonged existing hospitalization, or which required intervention to prevent the previously stated outcomes and, considered related to rotavirus vaccination as judged by the treating physician and documented in the patient medical record ( Figure 1 ). All eligible infants with at least one HRV administration were included in the analysis. In addition, we described “vaccine failure” when rotavirus acute gastroenteritis led to hospitalization and occurred at least 14 days after second HRV dose. For tolerability assessment, we used data from par ticipants of the before-after cohor t study. Monthly parental questionnaires contained date and type of the NIP primary series and/or HRV immunizations received, the occurrence of solicited AE and, whether they sought healthcare, in the seven days following administration. Solicited AE were fever, rash, irritability, loss of appetite, vomiting, looser and/or, bloody stools. We defined vaccine administration concomitant when vaccination dates were identical for at least one NIP and HRV (NIP+HRV) vaccination or if they were with a maximum of three days apar t, such that the seven-day post-vaccination period for repor ting solicited AE covered both vaccinations. All monthly data from cohor t par ticipants that included information on type and date of vaccination and AE repor ting were included in the analysis.The standard vaccination schedule is shown in Figure 1 .