Josephine van Dongen

5 Safety and Tolerability of Human Rotavirus Vaccination 119 Introduction Premature infants are at increased risk of severe rotavirus acute gastroenteritis. 1–4 Therefore prevention of rotavirus disease is par ticularly impor tant for premature infants. Since 2006 two rotavirus vaccines have been licensed; RotaTeq© (Merck and Co, USA) and, Rotarix© (GSK, Belgium). Both vaccines were previously studied in premature infants and demonstrated efficacy and immunogenicity. 5,6 Findings on rotavirus vaccine safety and tolerability from these studies indicate that rates of adverse events (AE) are similar to those observed among term infants. 6,7 However the trials included a limited number of infants with gestational ages (GA) less than 30 weeks, and for Rotarix (GSK), no infants with GA < 27 weeks were included. Moreover, inclusion criteria required premature infants were healthy and medically stable at time of enrollment. This relatively healthy study population may not be representative, as a complicated postnatal course, is common in (very) premature infants, and may influence AE rates. 6,7 Very premature infants (GA <30 weeks) can experience more and different vaccine AE following routine vaccines other than rotavirus vaccination. A recent review found that cardiorespiratory events (apnea, bradycardia and desaturation) occurred in 13-30% of very premature infants following DTaP-IPV-Hib-HepB vaccine. 8 In addition vomiting and hypotonia occurred more frequently in premature infants, while rates of local and other general symptoms were comparable. 8 More real-world data on safety and tolerability of rotavirus vaccination in these infants, with or without concurrent administration of other routine immunizations, is needed to guide clinicians in the individual assessment of risks and benefits and to counsel parents on anticipated AE. In the Netherlands, a national rotavirus vaccination policy has not been introduced yet, but a pilot was conducted in 13 Dutch hospitals implementing rotavirus vaccination in routine neonatal care for medical risk infants, including premature infants (Risk-group Infant Vaccination Against Rotavirus [RIVAR] project). This selective vaccine strategy was supposed to prevent those infants most at risk of severe disease. 2 Within this setting we evaluated the safety and tolerability of rotavirus vaccination among medical risk infants. Here we focus on premature infants with gestational ages between 27-37 weeks. Because infants with GA below 27 weeks are vaccinated off-label, and the decision to offer HRV was based on local policy, the group was analysed and described separately. Data on infants with other medical risk conditions are described in supplementary material. Patients and methods Study setting and subjects For a full description of the RIVAR project we refer to chapter 4 and the Dutch trial registry. 9 In brief, an implementation project for selective rotavirus vaccination was conducted in