Josephine van Dongen

Chapter 5 128 ( chapter 4 ). This raises the question whether the benefits of rotavirus vaccination outweigh the possible risks of vaccine related SAE in this par ticular population, especially in a setting with low rotavirus incidence as currently seen in the Netherlands. 26,27 Alternatively, protecting these infants through herd immunity by implementing universal infant vaccination against rotavirus may be a strategy wor th considering. It has been shown that herd immunity effects can reduce the risk of severe rotavirus acute gastroenteritis by 48% among unvaccinated infants. 28 Impor tant limitations should be mentioned. First, for the observed vaccine related SAE we cannot confirm or exclude causality between the event and administration of HRV. In our evaluation, we relied on clinical judgement by the treating physician, considering timing of the event in relation to vaccine administration and/or type of SAE and patient comorbidities. At most, we can therefore conclude that a causal link is plausible. For some vaccine related SAE, other vaccines co-administered with HRV may also have triggered the event. Second, our results on tolerability assessment are based on parent repor ted solicited AE, which may be subject to variability in perception between parents. Although fever, vomiting and loose stools can be assessed quite objectively, we cannot rule out that repor ting may have been influenced by whether infants received the newly introduced HRV, which could increase parent’s attentiveness to AE.This effect is likely small as percentages of parent repor ted AE between the two groups were similar. Differences were only observed for gastrointestinal adverse events, which is in line with previous results on tolerability of HRV. Third, data were missing on some covariates and vaccinations in approximately 10% of infants. Our analyses are based on complete cases only, by comparison of infants with missing versus complete data, we explored the potential of bias this induced. Although family educational level was lower among infants with missing data, educational level was not associated with AE in univariate analysis and therefore complete case analysis is justified and results are generalizable to the broader population of vulnerable premature infants. Conclusion In conclusion, we observed higher incidence of vaccine related SAE following HRV among vulnerable premature infants than repor ted in literature. Clinicians should be aware and must outweigh the risks and benefits of HRV for this par ticular group. HRV administration is generally well tolerated, also in infants < 27 weeks of GA, but associated with approximately ten percent higher risk of gastrointestinal AE when co-administered with NIP vaccines.