Adverse event rates rise after immunization of extremely low-birth-weight infants

Last Updated: 2015-06-02

By Will Boggs MD

NEW YORK (Reuters Health) - Rates of some adverse events more than double in the days following routine immunization of extremely low-birth-weight (ELBW) infants, according to a multicenter retrospective study.

"These findings should not impact the recommendations around immunization schedules," Dr. P. Brian Smith, from Duke University School of Medicine, Durham, North Carolina, told Reuters Health by email. "I think neonatologists should be aware of these adverse events and consider less sepsis evaluations and closer monitoring of the infants that have events following immunizations."

Immunization of ELBW infants (those weighing 1000 g or less) has been associated with fever and adverse cardiorespiratory events in the immediate post-immunization period, and this has led to delayed immunization of hospitalized premature infants.

Dr. Smith and colleagues used the Pediatrix Medical Group's neonatal intensive care unit (NICU) database, including 13,926 ELBW infants born at 28 weeks' gestation or less.

Sepsis evaluations more than tripled, from 5.4 per 1000 patient-days in the preimmunization period to 19.3 per 1000 patient-days in the two days following immunizations, though positive blood culture results were uncommon (2.1% in the preimmunization period and 3.8% in the post immunization period).

The need for increased respiratory support doubled, from 6.6 events per 1000 patient-days preimmunization to 14.0 events per 1000 patient-days post immunization, and intubations increased by 80% (from 2.0 to 3.6 per 1000 patient-days).

The incidence of sepsis evaluations, increased respiratory support, and intubations decreased from 30 days before immunization until five to seven days before immunization, followed by a sharp decrease leading up to the day of immunization, according to the June 1 JAMA Pediatrics online report.

Sepsis evaluations in the post immunization period were more common among younger (23-24 weeks' gestation) infants than among older (27-28 weeks' gestation) infants, as was the incidence of intubations.

Five children died in the three days after immunization: one with bowel perforation, one with necrotizing enterocolitis and presumed sepsis, and two with pneumonia and respiratory failure. Diagnoses of the other two were not available in the data set.

"These outcomes, while not trivial, are short-term outcomes," Dr. Smith said. "We know that immunization delay is bad. These findings should not influence a decision to immunize premature infants."

"Further studies are needed to determine whether the order and timing of specific immunizations affect the incidence of adverse events in the post immunization period and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants," the researchers concluded.

"Common adverse events of immunizations in ELBW infants, such as fever and increased cardiorespiratory events, are usually transient and non-life-threatening," Dr. Michael W. Kuzniewicz and Dr. Nicola P. Klein, from Kaiser Permanente Northern California, Oakland, California, wrote in an accompanying editorial. "Perhaps what we need is to alter our response to these adverse events."

"Given the low prior probability of sepsis, the development of nonspecific symptoms after immunizations probably does not alter the posterior probability of sepsis significantly, because these symptoms could be attributed to the immunizations themselves," they noted.

"Overall, this study may suggest that physicians should have a higher threshold for sepsis evaluations in previously healthy infants in the immediate period after immunizations, particularly if infants are experiencing typical adverse effects after immunizations," they wrote.

"Furthermore, future studies describing what constitutes typical adverse events and characterizing the expected risk interval during which these events should occur (e.g., 1 day, 2 days, and so on) would have great value to physicians," Dr. Kuzniewicz and Dr. Klein wrote. "The real challenge from this and other studies is to create criteria to differentiate signs of sepsis from expected adverse events after immunizations."

The U.S. Department of Health and Human Services and the U.S. National Center for Advancing Translational Sciences supported this research. One coauthor reported consulting for industry on neonatal and pediatric drug development.

SOURCE: http://bit.ly/1KKaSLh and http://bit.ly/1Q3wHJg

JAMA Pediatr 2015.