Neonatology pp 944-948 | Cite as

Vaccinations and Neonatal Immunity

  • Alberto G. Ugazio
  • Alberto E. Tozzi


The fetus can be compared to a haploidentical graft, sharing only half of the histocompatibility antigens of the “mother host”. As such, the fetus should be rejected by the immune system of the mother. At the same time, since the fetal immune system starts developing around the 9th week of gestation, the fetus should also mount a “graft-versus-host” reaction against those histocompatibility antigens that it has not inherited from the “mother host”. It follows that survival of the fetus - indeed of all mammalian species - is strictly dependent on a wide variety of mechanisms preventing graft rejection by the mother and graft-versus-host reaction by the fetus [1]. Among the latter, a major role is certainly played by the slow intrauterine maturation of the fetal immune function, ultimately resulting in the physiological immune deficiency of the neonate that involves both innate and adaptive immunity. This immune immaturity - more severe in preterm and in very low birth weight infants - results in a weak immune response to antigen challenge and in the production of a poor immunological memory [2].


Pertussis Vaccine Histocompatibility Antigen Preterm Child Vaccine Administration Inactivate Polio Vaccine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Koch CA, Platt JL (2007) T cell recognition and immunity in the fetus and mother. Cell Immunol 248: 12–7PubMedCrossRefGoogle Scholar
  2. 2.
    Lewis DB (2004) The physiologic immunodeficiency of immaturity. In: Stiehm ER, Ochs HD, Winkelstein JA (eds) Immunologic disorders in infants and children, 5th edn. Elsevier Saunders, Philadelphia, pp 687–760Google Scholar
  3. 3.
    Langkamp DL, Hoshaw-Woodard S, Boye ME, Lemeshow S (2001) Delays in receipt of immunizations in low-birth-weight children: a nationally representative sample. Arch Pediatr Adolesc Med 155: 167–172PubMedGoogle Scholar
  4. 4.
    Davis RL, Rubanowice D, Shinefield HR et al (1999) Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status. Centers for Disease Control and Prevention Vaccine Safety Datalink Group. JAMA 282: 547–553Google Scholar
  5. 5.
    McKechnie L, Finlay F (1999) Uptake and timing of immunisations in preterm and term infants. Prof Care Mother Child 9: 19–21PubMedGoogle Scholar
  6. 6.
    Moyes C (1999) Immunisation of preterm babies. N Z Med J 112: 263–264PubMedGoogle Scholar
  7. 7.
    Saari TN, Committee on Infectious Diseases (2003) Immunization of preterm and low birth weight infants. Pediatrics 112: 193–198CrossRefGoogle Scholar
  8. 8.
    Kroger AT, Atkinson WL, Marcuse EK et al (2006) General recommendations on immunization recommendations of the advisory committee on immunization practices ( ACIP ). MMWR Recomm Rep 55: 1-48Google Scholar
  9. 9.
    Pfister RE, Aeschbach V, Niksic-Stuber V et al (2004) Safety of DTaP-based combined immunization in very-low-birth-weight premature infants: frequent but mostly benign cardiorespiratory events. J Pediatr 145: 58–66PubMedCrossRefGoogle Scholar
  10. 10.
    Schulzke S, Heininger U, Lucking-Famira M et al (2005) Apnoea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines. Eur J Pediatr 164: 432–435PubMedCrossRefGoogle Scholar
  11. 11.
    Ellison VJ, Davis PG, Doyle LW (2005) Adverse reactions to immunization with newer vaccines in the very preterm infant. J Paediatr Child Health 41: 441–443PubMedCrossRefGoogle Scholar
  12. 12.
    Lee J, Robinson JL, Spady DW (2006) Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanuspertussis- inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. BMC Pediatrics 6: 20PubMedCrossRefGoogle Scholar
  13. 13.
    Sen S, Cloete Y, Hassan K, Buss P (2001) Adverse events following vaccination in premature infants. Acta Pediatr 90: 916–920CrossRefGoogle Scholar
  14. 14.
    Pourcyrous M, Korones SB, Arheart KL, Bada HS (2007) Primary immunization of premature infants with gestational age <35 weeks: cardiorespiratory complications and c-reactive protein responses associated with administration of single and multiple separate vaccines simultaneously. J Pediatr 151:167–172PubMedCrossRefGoogle Scholar
  15. 15.
    Klein NP, Massolo ML, Greene J et al (2008) Vaccine Safety Datalink. Risk factors for developing apnea after immunization in the neonatal intensive care unit. Pediatrics 121:463–439PubMedCrossRefGoogle Scholar
  16. 16.
    Bonhoeffer J, Siegrist C-A, Heath PT (2006) Immunisation of premature infants. Arch Dis Child 91: 929–935PubMedCrossRefGoogle Scholar
  17. 17.
    Flatz-Jequier A, Posfay-Barbe KM, Pfister RE, Siegrist CA (2008) Recurrence of cardiorespiratory events following repeat DTaPbased combined immunization in very low birth weight premature infants. J Pediatr 153: 429–431PubMedCrossRefGoogle Scholar
  18. 18.
    Carbone T, McEntire B, Kissin D et al (2008) Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study. Pediatrics 121: e1085–e1090PubMedCrossRefGoogle Scholar
  19. 19.
    Gaudelus J, Lefèvre-Akriche S, Roumegoux C et al (2007) Immunization of the preterm infants. Arch Pédiatr 14 (Suppl 1): S24–S30PubMedCrossRefGoogle Scholar
  20. 20.
    Negrete-Esqueda L, Vargas-Origel A (2007) response to Bacillus Calmette-Guerìn vaccine in full term and pre term infants. Am J Perinatol 24: 183–189Google Scholar
  21. 21.
    Salious P, Aijan N, Guérin N (2002) Efficacy and tolerance of vaccinations in premature infants. Arch Pediatr 9: 629–637CrossRefGoogle Scholar
  22. 22.
    Okan F, Karagoz S, Nuhoglu A (2006) Bacillus Calmette-Guerìn vaccination in preterm infants. Int J Tuberc Lung Dis 10: 1337–1341PubMedGoogle Scholar
  23. 23.
    American Academy of Pediatrics (2003) Hepatitis B. In: Pickering LK (ed) Red Book: 2003 Report of the Committee on Infectious Diseases, 26th ed. Elk Grove Village, Illinois, pp 318–336Google Scholar
  24. 24.
    Lau YL, Tam AY, Ng KW et al (1992) Response of preterm infants to hepatitis B vaccine. J Pediatr 121: 962–965PubMedCrossRefGoogle Scholar
  25. 25.
    Mast EE, Margolis HS, Fiore AE et al (2005) A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP); part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep 54: 1–31PubMedGoogle Scholar
  26. 26.
    Patel DM, Butler J, Feldman S et al (1997) Immunogenicity of hepatitis B vaccine in healthy very low birth weight infants. J Pediatr 131: 641–643PubMedCrossRefGoogle Scholar
  27. 27.
    Kim SC, Chung EK, Hodinka RL et al (1997) Immunogenicity of hepatitis B vaccine in preterm infants. Pediatrics 99: 534–536PubMedCrossRefGoogle Scholar
  28. 28.
    Schloesser RL, Fischer D, Otto W et al (1999) Safety and immunogenicity of an acellular pertussis vaccine in premature infants. Pediatrics 103: e60Google Scholar
  29. 29.
    Omeñaca F, Garcia-Sicilia J, García-Corbeira P et al (2005) Response of preterm newborns to immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio and Haemophilus influenzae type b vaccine: first experiences and solutions to a serious and sensitive issue. Pediatrics 116: 1292–1298PubMedCrossRefGoogle Scholar
  30. 30.
    Slack MH, Cade S, Schapira D et al (2005) DT5aP-Hib-IPV and MCC vaccines: preterm infants’ response to accelerated immunisation. Arch Dis Child 90: 338–341PubMedCrossRefGoogle Scholar
  31. 31.
    Vázquez L, Garcia F, Rüttimann R et al (2008) Immunogenicity and reactogenicity of DTPa-HBV-IPV/Hib vaccine as primary and booster vaccination in low-birth-weight premature infants. Acta Paediatr 97: 1243–1249PubMedCrossRefGoogle Scholar
  32. 32.
    Faldella G, Galletti S, Corvaglia L et al (2007) Safety of DTaPIPV- HIb-HBV hexavalent vaccine in very premature infants. Vaccine 25: 1036–1042PubMedCrossRefGoogle Scholar
  33. 33.
    Linder N, Yaron M, Handsher R et al (1995) Early immunization with inactivated poliovirus vaccine in premature infants. J Pediatr 127: 128–130PubMedCrossRefGoogle Scholar
  34. 34.
    Adenyi-Jones SC, Faden H, Ferdon MB et al (1992) Systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine in premature and term infants. J Pediatr 120: 686–689PubMedCrossRefGoogle Scholar
  35. 35.
    D’Angio CT, Maniscalco WM, Pichichero ME (1995) Immunologic response of extremely premature infants to tetanus, Haemophilus influenzae, and polio immunizations. Pediatrics 96: 18–22Google Scholar
  36. 36.
    Conway S, James J, Balfour A, Smithells R (1994) Immunisation of the preterm baby. J Infect 28: 143–150CrossRefGoogle Scholar
  37. 37.
    Berrington JE, Cant AJ, Matthews JN et al (2006) Haemophilus influenzae type b immunization in infants in the United Kingdom: effects of diphtheria/tetanus/acellular pertussis/Hib combination vaccine, significant prematurity, and a fourth dose. Pediatrics. 117: e717–e724PubMedCrossRefGoogle Scholar
  38. 38.
    Omeñaca F, Garcia-Sicilia J, García-Corbeira P et al (2007) Antipolyribosyl ribitol phosphate response of premature infants to primary and booster vaccination with a combined diphtheriatetanus- acellular pertussis-hepatitis B-inactivated polio virus/ Haemophilus influenzae type b vaccine. Pediatrics 119: e179–e185PubMedCrossRefGoogle Scholar
  39. 39.
    Heath PT, Booy R, McVernon J et al (2003) Hib vaccination in infants born prematurely. Arch Dis Child 88: 206–210PubMedCrossRefGoogle Scholar
  40. 40.
    Huang FY, Lee PI, Lee CY et al (2007) Hepatitis B vaccination in preterm infants. Arch Dis Child Fetal Neonatal Ed 77: F135–F138CrossRefGoogle Scholar
  41. 41.
    Esposito S, Pugni L, Bosis S et al (2005) Immunogenicity, safety and tolerability of heptavalent pneumococcal conjugate vaccine administered at 3, 5 and 11 months post-natally to pre- and full-term infants. Vaccine 23: 1703–1708Google Scholar
  42. 42.
    Shinefield H, Black S, Ray P et al (2002) Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants. Pediatr Infect Dis J 21: 182–186PubMedCrossRefGoogle Scholar
  43. 43.
    Ruggeberg JU, Collins C, Clarke P et al (2007) Immunogenicity and induction of immunological memory of the heptavalent pneumococcal conjugate vaccine in preterm UK infants. Vaccine 25: 264–271PubMedCrossRefGoogle Scholar
  44. 44.
    Slack MH, Schapira D, Thwaites RJ et al (2001) Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines. J Infect Dis 184: 1617–1620PubMedCrossRefGoogle Scholar
  45. 45.
    Collins CL, Ruggeberg JU, Balfour G et al (2005) Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in premature infants. Pediatr Infect Dis J 24: 966–968PubMedCrossRefGoogle Scholar
  46. 46.
    D’Angio CT, Boohene PA, Mowrer A et al (2007) Measles-mumpsrubella and varicella vaccine responses in extremely preterm infants. Pediatrics 119: e574–e579PubMedCrossRefGoogle Scholar
  47. 47.
    Vesikari T, Matson DO, Dennehy P et al (2006) Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 354: 23–33PubMedCrossRefGoogle Scholar
  48. 48.
    Groothuis JR, Levin MJ, Lehr MV et al (1992) Immune response to split-product influenza vaccine in preterm and full-term young children. Vaccine 10: 221–225PubMedCrossRefGoogle Scholar
  49. 49.
    Robinson MJ, Heal C, Gardener E et al (2004) Antibody response to diphtheria-tetanus-pertussis immunization in preterm infants who receive dexamethasone for chronic lung disease. Pediatrics 113: 733–737PubMedCrossRefGoogle Scholar
  50. 50.
    Clarke P, Powell PJ, Goldblatt D, Robinson MJ (2003) Effect of a fourth Haemophilus influenzae type b immunisation in preterm infants who received dexamethasone for chronic lung disease. Arch Dis Child Fetal Neonatal Ed 88: F58–F61PubMedCrossRefGoogle Scholar
  51. 51.
    Clarke P, Robinson MJ, Ahmad I et al (2006) Response of steroidtreated former preterm infants to a single dose of meningococcal C conjugate vaccine. Vaccine 24: 3273–3278PubMedCrossRefGoogle Scholar
  52. 52.
    European Agency for the Evaluation of Medicinal Products (2009) EMEA public statement on thiomersal containing medicinal products, July 8, 1999. pus/2096299EN.pdfGoogle Scholar
  53. 53.
    Centers for Disease Control and Prevention (1999) Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service. MMWR Morb Mortal Wkly Rep 48: 563–565Google Scholar
  54. 54.
    McCormick M, Bayer R, Berg A (2004) Report of the Institute of Medicine: Immunization Safety Review–Vaccines and Autism. National Academy Press, Washington DCGoogle Scholar
  55. 55.
    Thompson WW, Price C, Goodson B et al (2007) Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med 357: 1281–1292PubMedCrossRefGoogle Scholar
  56. 56.
    Tozzi AE, Bisiacchi P, Tarantino V et al (2009) Neuropsychological performance 10 years after immunization in infancy with thimerosalcontaining vaccines. Pediatrics 123: 475–482PubMedCrossRefGoogle Scholar
  57. 57.
    Klinman DM (2004) Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 4: 249–258PubMedCrossRefGoogle Scholar
  58. 58.
    Plotkin S (2005) Vaccines: past, present, and future. Nature Medicine 11: S5–S11PubMedCrossRefGoogle Scholar
  59. 59.
    Munoz FM, Piedra PA, Glezen WP (2003) Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Vaccine 21: 3465–3467PubMedCrossRefGoogle Scholar
  60. 60.
    Baker CJ, Paoletti LC, Rench MA et al (2004) Immune response of healthy women to 2 different group B streptococcal type V capsular polysaccharide-protein conjugate vaccines. J Infect Dis 189: 1103–1112PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Alberto G. Ugazio
    • 1
  • Alberto E. Tozzi
  1. 1.Department of Pediatric MedicineBambino Gesù HospitalRomeItaly

Personalised recommendations