In this issue of Pediatrics, Zalot et al present the results of a prospective cohort study examining the consequences of routine administration of pentavalent rotavirus vaccine (RV5) in a neonatal intensive care unit (NICU).1 To prevent severe rotavirus disease and its sequelae (including health care visits and hospitalization), the Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of US infants, using either RV5 or a monovalent rotavirus vaccine (no preference is expressed).2 The maximum age for dose 1 (of either vaccine) is 14 weeks and 6 days, and the maximum age for the last dose is 8 months and 0 days.2 Both ACIP and the American Academy of Pediatrics concluded that because of a theoretical risk of transmission of vaccine strains of rotavirus to infants in a NICU who are acutely ill or not age-eligible for vaccination, the risk outweighed the benefits of vaccinating infants who will remain in the NICU and therefore supported vaccination at discharge.2,3 In that context, some infants in the NICU will miss the opportunity to be immunized before reaching the maximum age for vaccination. What have we learned from the new data presented by Zalot et al?
There are at least 3 important points to acknowledge based on this prospective cohort study. First, shedding of vaccine-strain rotavirus occurs among patients vaccinated in the NICU. These are live, oral vaccines, and shedding after vaccination has been well documented. With RV5, shedding is most frequent after dose 1.4 This pattern was seen in the current study; RV5 was detected in 70% of stool samples collected from vaccinated infants during the first week after vaccination, and the latest detection after dose 1 was 60 days after the dose.
Second, putative transmission of vaccine-strain rotavirus to unvaccinated infants in the NICU does occur. This point is important because in some prior studies with smaller sample sizes, no transmission in the NICU was observed.5,–7 In this new 1-year study, 5 of 686 unvaccinated patients (<1%) who contributed at least 1 stool sample during hospitalization tested positive for RV5, and 4 of these 5 patients shared a health care worker or care team member with a recently vaccinated patient. The estimated rate of presumed transmission to unvaccinated infants was 2.2 events per 1,000 patient-days (95% CI, 0.7-5.2). Interpretation of this rate is slightly complicated because each stool collected was considered to contribute 1 patient-day at risk, but collection of stool samples was attempted only weekly and did not always occur (despite this fact, the authors should be applauded for undertaking this large and important study). Hand hygiene reliability among NICU staff during the study period was not presented, and it is not possible to know whether the use of empirical contact precautions for 2 to 3 weeks after vaccination, as recommended for infants admitted to a NICU after receipt of rotavirus vaccine, would have prevented all transmission.3 Nonetheless, in the context of this measure not being in place, most unvaccinated patients never tested positive.
Third, and perhaps most importantly, this infrequent transmission of vaccine-strain virus had no apparent clinical consequence for infants in the NICU. Of the 5 transmission recipients, none had symptoms of gastroenteritis or unexplained fever within 1 week before or after their first RV5-positive stool. The most likely explanation for this observation is the attenuated nature of the vaccine strains3; in clinical trials, the incidence of solicited adverse events in preterm infants was similar between RV5 and placebo recipients.2 In a prior NICU study evaluating unvaccinated infants residing in the same pod as vaccinated infants, 1.2% had clinical status changes within a 15-day exposure period, all of which were judged to be related to concomitant medical conditions.8 Rotavirus infection also may be asymptomatic, and some infants in a NICU may have acquired passive maternal antibody that reduces the likelihood of symptomatic infection.9 In the Zalot study, only 2 of the 5 transmission recipients had been born preterm, and detailed information about underlying comorbidities was not provided; it remains possible that severely ill preterm infants might be more adversely affected by the vaccine strain.
There are potential negative consequences to deferral of rotavirus vaccination, and the risk may accrue primarily after discharge from the NICU. An outbreak of rotavirus in a pediatric subacute care facility affected 22 of 26 patients, and 1 child died.10 Only 2 children at the facility were fully vaccinated against rotavirus; among 17 unvaccinated and 5 partially vaccinated children, 12 (55%) were in an intensive care unit at the time the vaccine was due and had become age-ineligible by the time of discharge.
These new prospective data are a valuable addition to our knowledge about rotavirus vaccination in the NICU. Although rare transmission of attenuated vaccine-strain rotavirus can occur, it likely results in minimal impact for most infants. The theoretical harm appears to be outweighed by the population benefit of vaccination. It is time for us to turn lost opportunity into action by updating guidelines and recommending routine administration of rotavirus vaccine to age-eligible infants in the NICU.
Dr Sandora drafted the commentary and reviewed it critically for important intellectual content, approved the final manuscript as submitted, and agrees to be accountable for all aspects of the work.
CONFLICT OF INTEREST DISCLOSURES: The author has no conflicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2024-067621.
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