AEs More Often Looked For, Found in Preemies After Vaccinations

Immunizations don't stop docs from checking for sepsis

  • by Contributing Writer

Action Points

  • Extremely low-birth-weight (ELBW) babies experienced increased adverse event screening and incidence after vaccinations.
  • ELBW infants had a higher incidence of sepsis evaluations, need for increased respiratory support, and intubation in the 3 days after immunization relative to the 3 days before immunization.

Extremely premature babies were associated with increased rates of adverse event screening and incidence following immunizations, according to a large retrospective, population-based study.

Stephen D. DeMeo, DO, of the Department of Pediatrics at Duke University, and colleagues reported an increase in the rate of sepsis evaluations for extremely low-birth-weight (ELBW) infants born with ≤28 weeks gestation, from 5.4 to 19.3 per 1,000 patient-days after immunization (adjusted rate ratio 3.7, 95% CI 3.2-4.4).

Positive blood culture results for sepsis also increased from five out of 235 (2.1%) to 39 out of 1,035 (3.8%) following immunization, they wrote in JAMA Pediatrics.

While sepsis evaluation was the study's primary outcome, the authors also found a higher incidence of increased respiratory support to 6.6 to 14.0 per 1,000 patient days (ARR 2.1, 95% CI 1.9-2.5) and an increase in intubation from 2.0 to 3.6 per 1,000 patient days (ARR 1.7, CI 1.3-2.2) for ELBW infants.

The rate ratio was adjusted for gestational age at birth, small for gestational age status, history of sepsis, postnatal age, and postnatal weight.

Age and history played varying roles in determining the rate of sepsis evaluation following immunization. "Younger" infants (23-24 weeks) had an increased incidence of sepsis evaluation (ARR 1.2, 95% CI 1.0-1.3) and intubation (ARR 1.5, 95% CI 1.2-2.0) compared with "older" infants (27-28 weeks).

Not surprisingly, ELBW infants with a history of sepsis were more likely to receive sepsis evaluation (ARR 1.4, 95% CI 1.2-1.5), but were not associated with an increased incidence of intubation (ARR 1.3, 95% CI 1.0-1.9) nor increased respiratory support (ARR 1.0, 95% CI 0.8-1.2).

The authors also noted that infants with a history of gram-positive sepsis before day 53 had an increased risk of sepsis evaluation (ARR 1.3, 95% CI 1.1-1.5), but that was not the case for infants with a history of gram-negative sepsis (ARR 1.2, 95% CI 0.9-1.5).

The most severe post-immunization events included three incidences of seizure compared with nine prior to immunization (0.1 and 0.2 per 1,000 patient-days, respectively) and five deaths. Three out of the five deaths were associated with a separate diagnosis: a bowel perforation, necrotizing enterocolitis and presumed sepsis, and pneumonia/respiratory failure.

Co-author Brian Smith, MD, also of Duke University, told MedPage Today that sepsis evaluations are the first step for neonatologists whenever a premature baby is sick, but he and his colleagues wanted to confirm how often they were performed. However, he added that he was surprised at the rate of sepsis evaluation following immunization.

"In the back of my mind, I was thinking we may not actually see something because I think most neonatologists would think, 'Oh, the kid got his immunizations yesterday, so the reason he's acting up today is because he got his immunizations,' so they might not do the sepsis evaluation, and yet we still found that association," he said.

The study found the actual number of sepsis evaluations, intubations, and incidences of increased respiratory support declined steadily from 30 days until 5-7 days prior to immunization, dropped sharply until the day of immunization, and then spiked again 0-2 days afterwards. In an accompanying editorial, Michael W. Kuzniewicz, MD and Nicola P. Klein, MD, PhD, both of Kaiser Permanente, questioned why the threshold for a sepsis evaluation was so much lower following a vaccination.

"Common adverse events of immunizations in ELBW infants, such as fever and increased cardiorespiratory events are usually transient and non-life-threatening," they wrote. "Perhaps what we need to alter is our response to these adverse events."

Researchers examined discharge data from 348 NICUs in the Pediatrix Medical Group from January 2007 to December 2012, comprising 13,926 infants receiving 48,853 immunizations. Data was included if the infant's birth weight was ≤1,000 g, a gestational age ≤28 weeks and had received at least one immunization between the ages of 53 and 110 days. Of those, 91.2% (n=12,703) received three or more immunizations. Pneumococcal conjugate was the most commonly administered vaccine, though the authors found similar adverse events across immunization types, with sepsis evaluation being the most common.

Limitations to the study include that the data was taken from an electronic medical record, making it difficult to know if a blood culture or respiratory support was needed because of fever or sepsis evaluations or cardiorespiratory events. The authors cite a potential bias in physicians being more likely to record adverse events closer to immunization, and that the study did not include data about vaccine timing.

Kuzniewicz and Klein also note that the study does not contain detailed descriptions of post-immunization fever response and suggested that might be a topic for later examination.

"Future studies describing information such as the percentage of infants who developed fever, the timing of the fever in relation to the immunization, and the maximum temperature will help physicians discriminate between transient minor adverse effects of immunizations and early signs of sepsis," they concluded.

Smith concluded the most important takeaway of the study was that immunizations should not be delayed just because of these outcomes.

"These were really short-term outcomes, but in the grand scheme of things, they're not that important," he said. "They're not death, they're not neurologic impairment, they're just some short-term adverse events that don't outweigh the benefits when you're measuring adverse events versus the benefits of on-time immunizations."

The study was supported in part by grants from the U.S. Department of Health and Human Services, the National Center for Advancing Translation Sciences of the National Institutes of Health.

Dr. Smith reported receiving consulting fees from industry for neonatal and pediatric drug development.

Dr. Klein reported receiving research support from Merck and Co., GlaxoSmithKline, Pfizer, Novartis, Sanofi-Pasteur, MedImmune, and Nuron Biotech.

None of the remaining authors reported conflicts of interest.


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