title: Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  At least one immunization between the ages of 53 and 110 days.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: DeMeo
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Sudha R
authors.initials: SR
authors.lastname: Raman
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina2Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hornik
authors.affiliation: Greenville Hospital System, Greenville, South Carolina.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Wilson
authors.affiliation: Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida.
authors.forename: Reese
authors.initials: R
authors.lastname: Clark
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina2Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
mesh_terms: D015331:Cohort Studies; D005260:Female; D006801:Humans; D007114:Immunization / Q000009:adverse effects*; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007442:Intubation, Intratracheal; D008297:Male; D012121:Respiration, Artificial; D012189:Retrospective Studies; D018805:Sepsis / Q000209:etiology*