JAMA Pediatrics
August 2015, Vol 169, No. 8
http://archpedi.jamanetwork.com/issue.aspx

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Editorial | August 2015
Differentiating Sepsis From Adverse Events After Immunization in the Neonatal Intensive Care Unit – How Is a Physician to Know?
Michael W. Kuzniewicz, MD, MPH1,2,3; Nicola P. Klein, MD, PhD1,4
Extract
In this issue of JAMA Pediatrics, DeMeo et al1 report on the incidence of adverse effects after immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU). They report that there is an increase in the incidence of sepsis evaluations, respiratory support, and intubation after immunization.
The findings of this study confirm what a number of other retrospective studies have found—that ELBW infants appear to have an increase in cardiorespiratory events after vaccination. The main strength of this study and what makes it unique is its large sample size of infants born at less than 28 weeks’ gestation, including those born at the most premature ages (ie, gestational ages [GAs] of 23-24 weeks). This study’s large size further allowed evaluation of single antigen vs combination vaccines, with the authors concluding that there was no difference in the incidence of adverse events after varying vaccine types. This finding should provide some reassurances to neonatologists and parents….

Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants
Stephen D. DeMeo, DO; Sudha R. Raman, PhD; Christoph P. Hornik, MD, MPH; Catherine C. Wilson, DNP, NNP-BC, FNP-BC; Reese Clark, MD; P. Brian Smith, MD, MPH, MHS
Abstract
Importance
Immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events, including fever and apnea or bradycardia, in the immediate postimmunization period. These adverse events present a diagnostic dilemma for physicians, leading to the potential for immunization delay and sepsis evaluations.
Objective
To compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days before and after immunization.
Design, Setting, and Participants
In this multicenter retrospective cohort study, we studied 13 926 ELBW infants born at 28 weeks’ gestation or less who were discharged from January 1, 2007, through December 31, 2012, from 348 NICUs managed by the Pediatrix Medical Group.
Exposures At least one immunization between the ages of 53 and 110 days.
Main Outcomes and Measures
Incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death.
Results
Most of the 13 926 infants (91.2%) received 3 or more immunizations. The incidence of sepsis evaluations increased from 5.4 per 1000 patient-days in the preimmunization period to 19.3 per 1000 patient-days in the postimmunization period (adjusted rate ratio [ARR], 3.7; 95% CI, 3.2-4.4). The need for increased respiratory support increased from 6.6 per 1000 patient-days in the preimmunization period to 14.0 per 1000 patient-days in the postimmunization period (ARR, 2.1; 95% CI, 1.9-2.5), and intubation increased from 2.0 per 1000 patient-days to 3.6 per 1000 patient-days (ARR, 1.7; 95% CI, 1.3-2.2). The postimmunization incidence of adverse events was similar across immunization types, including combination vaccines when compared with single-dose vaccines. Infants who were born at 23 to 24 weeks’ gestation had a higher risk of sepsis evaluation and intubation after immunization. A prior history of sepsis was associated with higher risk of sepsis evaluation after immunization.
Conclusions and Relevance
All ELBW infants in the NICU had an increased incidence of sepsis evaluations and increased respiratory support and intubation after routine immunization. Our findings provide no evidence to suggest that physicians should not use combination vaccines in ELBW infants. Further studies are needed to determine whether timing or spacing of immunization administrations confers risk for the developing adverse events and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants.