Neonatal FVRCP vaccination was associated with lower 90-day mortality and no detected adverse events in shelter kittens: a 5-year retrospective cohort study

Neonatal kittens in animal shelters face high mortality from infectious diseases, yet vaccination before 4 weeks of age remains controversial due to concerns about safety, immunologic immaturity, and maternal antibody interference. To evaluate the safety of neonatal vaccination and its association with all-cause mortality in shelter kittens. This retrospective cohort study analyzed records of 1,708 kittens admitted at <28 days of age to a high-volume municipal shelter (2021–2025), excluding same-day transfers and animals dead on arrival. Kittens were classified by age at first modified live virus feline viral rhinotracheitis, calicivirus and panleukopenia (FVRCP) dose: neonatal (<4 weeks; \(n = 397\) ), standard ( \(\ge\) 4 weeks; \(n = 1{,}010\) ), or never vaccinated ( \(n = 301\) ). Because standard-timing vaccination required survival to 4 weeks of age, the primary comparator was all kittens not vaccinated neonatally ( \(n = 1{,}311\) ). The primary outcome was 90-day all-cause mortality, modeled with a time-varying exposure Cox model adjusted for age at intake and intake year, with litter-level cluster-robust standard errors. Secondary outcomes were disease-specific morbidity (including panleukopenia and upper respiratory infection) and vaccine safety. Neonatal vaccination was associated with 90-day mortality of 7% (29/397) compared to 15% (200/1,311) in the combined no neonatal vaccination group (risk ratio 0.48; 95% CI 0.33–0.70; \(p < 0.001\) ). The primary time-varying Cox model yielded an adjusted hazard ratio of 0.51 (95% CI 0.28–0.93; \(p = 0.028\) ). All pre-specified sensitivity analyses gave point estimates favoring vaccination. Thirteen panleukopenia cases were documented, twelve of them across three litter-level outbreaks. No vaccine-associated adverse events were documented among the 397 neonatally vaccinated animals, including no cases of cerebellar hypoplasia and no treated acute vaccine reactions. Neonatal vaccination of shelter kittens was not associated with any documented vaccine-attributed adverse event and was associated with lower adjusted 90-day mortality. While a retrospective design cannot establish causation, the association was consistent in direction across all 5 years and across modeling approaches. These findings support consideration of vaccinating shelter kittens on entry before 4 weeks of age in high-risk settings, while prospective multi-site studies are warranted.