Investigators Explore Safety of Rotavirus Vaccine in NICU

Clinicians in neonatal intensive care units across the country are uncertain about when to administer rotavirus vaccination to infants whose medical conditions require prolonged hospital stays, so experts at The Children’s Hospital of Philadelphia conducted a study published in Pediatrics to explore safety concerns that remain unsettled.

Rotavirus (RV) affects nearly all children at some point, often with significant diarrhea. In premature infants it can lead to severe and potentially life-threatening diarrhea and dehydration. Preterm infants are more vulnerable to the infection, in part because they miss the transfer of maternal antibody in the third trimester of pregnancy. In early infancy they are not protected against common forms of rotavirus.

RotaTeq vaccine (RV5), which was developed at CHOP, is effective at preventing rotavirus gastroenteritis, but it must be administered by 104 days of age (14 weeks, six days). Current immunization guidelines state, “preterm infants in NICUs or nurseries who are age-eligible and clinically stable may be immunized at the time of discharge.”

These recommendations put hospitals with large NICUs that often handle complicated cases of prematurity or congenital abnormalities in a time squeeze because they tend to care for babies who must stay in the hospital longer than 104 days.

“We have a population that is at extraordinary risk because they have health problems beyond prematurity and longer lengths of stay, so many would miss out on receiving the vaccine,” said Kelly C. Wade, MD, PhD, MSCE, a neonatologist at CHOP. “We would be discharging babies into the community who don’t have rotavirus protection.”

After careful consideration and discussion, a team of CHOP experts from the Divisions of Neonatology, Infectious Disease, and Pharmacology decided in 2007 to include RV5 with inpatient routine two-month vaccinations to infants receiving some enteral nutrition, also known as tube feeding, regardless of length of NICU hospitalization.

“We believe that the benefit of protecting infants against rotavirus infections outweighs the minimal risk in administering rotavirus vaccine to NICU inpatients,” said Heather M. Monk Bodenstab, PharmD, a CHOP clinical pharmacist. “We are one of very few institutions that actually do this.”

The main reason the American Academy of Pediatrics (AAP) discourages rotavirus vaccination during hospitalization is the possibility that live attenuated virus theoretically could be transmitted to neighboring unvaccinated infants also residing in the NICU. While shedding of attenuated virus has been demonstrated in immunized infants’ stools, Dr. Monk pointed out that symptomatic disease transmission is rare.

Since CHOP’s policy is not in line with the AAP recommendations, Dr. Monk Bodenstab and Dr. Wade conducted the current study in order to give some guidance and build support for the safety of inpatient RV5 vaccination as a CHOP standard of practice. The investigators performed a retrospective chart review of electronic medical records of NICU patients who CHOP routinely vaccinated with RV5 between September 2008 and 2010. They also reviewed records for any unvaccinated patients who shared the same NICU area and nurses as the vaccinated infants within 15 days of vaccination. In particular, the study team wanted to identify any unvaccinated infants who had gastrointestinal symptoms and physician orders for bowel rest, abdominal imaging, and antibiotics within 24 hours of each other, which would suggest a strong clinical suspicion of viral gastroenteritis.

“One of the most interesting findings was that there were such a small percentage of unvaccinated infants who had clinical status changes, and those could be attributed to pre-existing gastrointestinal processes or other clinical conditions,” Dr. Monk Bodenstab said. “That was reassuring for us.”

Due to the study’s design limitations, however, the results do not indicate whether or not RV5 vaccination increased the risk of virus shedding or transmission in a NICU environment. The goal of future prospective studies will be to determine how long a baby who receives the vaccine is potentially shedding the virus, if universal precautions such as diligent hand hygiene can control the spread, and if other infants are exposed, whether or not they become sick.

“None of us has any data to say for sure what would be good practice,” Dr. Wade said. “I think the policy we have at CHOP is well thought out, and it is working for us, but it is not ready for complete dissemination.  We cannot say it is what every NICU should do because you have to factor in different levels of attention to hand hygiene, nurse-to-patient ratios, and room geography.”