Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants | Cardiology | JAMA Pediatrics | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Denizot  S, Fleury  J, Caillaux  G, Rouger  V, Rozé  JC, Gras-Le Guen  C.  Hospital initiation of a vaccinal schedule improves the long-term vaccinal coverage of ex-preterm children.  Vaccine. 2011;29(3):382-386.PubMedGoogle ScholarCrossref
Navar-Boggan  AM, Halsey  NA, Golden  WC, Escobar  GJ, Massolo  M, Klein  NP.  Risk of fever and sepsis evaluations after routine immunizations in the neonatal intensive care unit.  J Perinatol. 2010;30(9):604-609.PubMedGoogle ScholarCrossref
Flatz-Jequier  A, Posfay-Barbe  KM, Pfister  RE, Siegrist  CA.  Recurrence of cardiorespiratory events following repeat DTaP-based combined immunization in very low birth weight premature infants.  J Pediatr. 2008;153(3):429-431.PubMedGoogle ScholarCrossref
Anderson  J, Noori  K, Morris  SA.  Apnoea after the 2-month immunisation in extremely preterm infants: what happens with the 4-month immunisation?  J Paediatr Child Health. 2013;49(3):E217-E220.PubMedGoogle ScholarCrossref
Gad  A, Shah  S.  Special immunization considerations of the preterm infant.  J Pediatr Health Care. 2007;21(6):385-391.PubMedGoogle ScholarCrossref
Offit  PA, Quarles  J, Gerber  MA,  et al.  Addressing parents’ concerns: do multiple vaccines overwhelm or weaken the infant’s immune system?  Pediatrics. 2002;109(1):124-129.PubMedGoogle ScholarCrossref
Langkamp  DLH-WS, Hoshaw-Woodard  S, Boye  ME, Lemeshow  S.  Delays in receipt of immunizations in low-birth-weight children: a nationally representative sample.  Arch Pediatr Adolesc Med. 2001;155(2):167-172.PubMedGoogle ScholarCrossref
Davis  RL, Rubanowice  D, Shinefield  HR,  et al; Centers for Disease Control and Prevention Vaccine Safety Datalink Group.  Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status.  JAMA. 1999;282(6):547-553.PubMedGoogle ScholarCrossref
Ellison  VJ, Davis  PG, Doyle  LW.  Adverse reactions to immunization with newer vaccines in the very preterm infant.  J Paediatr Child Health. 2005;41(8):441-443.PubMedGoogle ScholarCrossref
D’Angio  CT.  Active immunization of premature and low birth-weight infants: a review of immunogenicity, efficacy, and tolerability.  Paediatr Drugs. 2007;9(1):17-32.PubMedGoogle ScholarCrossref
Wynn  JL, Li  L, Cotten  CM,  et al.  Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants.  J Perinatol. 2013;33(8):613-618.PubMedGoogle ScholarCrossref
Wynn  JL, Hansen  NI, Das  A,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Early sepsis does not increase the risk of late sepsis in very low birth weight neonates.  J Pediatr. 2013;162(5):942-948.e1.PubMedGoogle ScholarCrossref
Wynn  JL, Scumpia  PO, Winfield  RD,  et al.  Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists.  Blood. 2008;112(5):1750-1758.PubMedGoogle ScholarCrossref
Sánchez  PJ, Laptook  AR, Fisher  L, Sumner  J, Risser  RC, Perlman  JM.  Apnea after immunization of preterm infants.  J Pediatr. 1997;130(5):746-751.PubMedGoogle ScholarCrossref
Botham  SJ, Isaacs  D, Henderson-Smart  DJ.  Incidence of apnoea and bradycardia in preterm infants following DTPw and Hib immunization: a prospective study.  J Paediatr Child Health. 1997;33(5):418-421.PubMedGoogle ScholarCrossref
Schulzke  S, Heininger  U, Lücking-Famira  M, Fahnenstich  H.  Apnoea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines.  Eur J Pediatr. 2005;164(7):432-435.PubMedGoogle ScholarCrossref
Hacking  DF, Davis  PG, Wong  E, Wheeler  K, McVernon  J.  Frequency of respiratory deterioration after immunisation in preterm infants.  J Paediatr Child Health. 2010;46(12):742-748.PubMedGoogle ScholarCrossref
Carbone  T, McEntire  B, Kissin  D,  et al.  Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study.  Pediatrics. 2008;121(5):e1085-e1090.PubMedGoogle ScholarCrossref
Furck  AK, Richter  JW, Kattner  E.  Very low birth weight infants have only few adverse events after timely immunization.  J Perinatol. 2010;30(2):118-121.PubMedGoogle ScholarCrossref
Klein  NP, Massolo  ML, Greene  J, Dekker  CL, Black  S, Escobar  GJ; Vaccine Safety Datalink.  Risk factors for developing apnea after immunization in the neonatal intensive care unit.  Pediatrics. 2008;121(3):463-469.PubMedGoogle ScholarCrossref
Clifford  V, Crawford  NW, Royle  J,  et al.  Recurrent apnoea post immunisation: Informing re-immunisation policy.  Vaccine. 2011;29(34):5681-5687.PubMedGoogle ScholarCrossref
Faldella  G, Galletti  S, Corvaglia  L, Ancora  G, Alessandroni  R.  Safety of DTaP-IPV-HIb-HBV hexavalent vaccine in very premature infants.  Vaccine. 2007;25(6):1036-1042.PubMedGoogle ScholarCrossref
Original Investigation
August 2015

Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants

Author Affiliations
  • 1Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
  • 2Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
  • 3Greenville Hospital System, Greenville, South Carolina
  • 4Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida
JAMA Pediatr. 2015;169(8):740-745. doi:10.1001/jamapediatrics.2015.0418

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.