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Canadian Immunization Guide

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Part 3
Vaccination of Specific Populations

Immunization of Infants Born Prematurely

Best practices

Premature infants (defined as infants born before 37 weeks of gestational age) in stable clinical condition, regardless of birth weight, should be immunized with age-appropriate doses of vaccine at the same chronological age and according to the same schedule as full-term infants, with some exceptions as outlined below. Healthy premature infants weighing 1,500 grams or more at birth generally tolerate immunizations well, with rates of adverse events similar to the low rates of full-term infants.

Passive transfer of maternal antibodies occurs after the 28th week of gestation. Therefore, premature infants born after 28 weeks of gestation will have maternally derived antibodies, but at lower concentrations and for a shorter duration than full-term newborns. Premature infants of less than 28 weeks gestation are not expected to have significant amounts of maternal antibody. Thus, premature infants may experience increased frequency and severity of vaccine preventable illnesses and should be protected from vaccine preventable disease through timely immunization.

Antibody response to immunization is generally a function of chronological age. Some studies have shown that premature infants seem to have lower antibody responses to vaccines than full-term infants; however, vaccine efficacy in premature infants remains high. Therefore, immunization of premature infants should not be delayed. Neonatal intensive care units and other hospital areas where premature infants may remain hospitalized for prolonged periods should have immunization programs in place.

Premature infants, especially those weighing less than 1,500 grams at birth, are at higher risk of apnea and bradycardia following vaccination compared to full-term infants. Any increase or recurrence of apnea and bradycardia following vaccination of a premature infant is generally self-limited, subsides within 48 hours, and does not alter the infant's overall clinical progress. Hospitalized premature infants should have continuous cardiac and respiratory monitoring for 48 hours after their first immunization.

Hepatitis B vaccine

Premature infants of mothers who are hepatitis B surface antigen (HBsAg) negative

The response to hepatitis B (HB) vaccine may be diminished in premature infants with birth weight less than 2,000 grams. In jurisdictions where the first dose of HB vaccine is routinely given at birth, routine HB immunization of infants should be delayed until the infant reaches 2,000 grams or upon hospital discharge if discharge occurs before the infant has reached 2,000 grams.

Premature infants of mothers who are HBsAg-positive

All premature infants, regardless of weight, born to women who are HBsAg positive should receive HB immune globulin (HBIg) and monovalent HB vaccine within 12 hours of birth.

Premature infants weighing 2,000 grams or more at birth should receive 3 doses of HB vaccine, given at birth, 1 and 6 months of age. Monovalent HB vaccine should be given for the doses at birth and 1 month; diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type b (pediatric) (DTaP-HB-IPV-Hib) vaccine can be used for the 6 month dose. Premature infants weighing less than 2,000 grams at birth should receive 4 doses of HB vaccine, given at birth, 1, 2 and 6 months of age. The final dose in the vaccine series should not be administered before 24 weeks of age. Monovalent HB vaccine should be given for the doses at birth and 1 month; DTaP-HB-IPV-Hib vaccine can be used for the 2 and 6 month doses.

All premature infants of HBsAg positive mothers should have an assessment of the antibody to HBsAg (anti-HBs) 4 weeks after their series of HB vaccine has been completed to assess the success of immunoprophylaxis. If HBsAg is present, the child will likely become a chronic hepatitis B carrier. If the infant is negative for both HBsAg and anti-HBs (vaccine non-responder), additional doses of HB vaccine (up to a second full series) should be given with repeated serologic testing for antibody response.

Premature infants of mothers with unknown HBsAg status

If maternal HBsAg status is not available within 12 hours of delivery, consideration should be given to administering HB vaccine and HBIg to the infant while the results are pending, taking into account the mother's risk factors and erring on the side of providing HB vaccine and HBIg if there is any suspicion that the mother could be infected.

Refer to Hepatitis B Vaccine in Part 4 and Passive Immunizing Agents in Part 5 for additional information.

Pneumococcal vaccine

Prematurity is associated with an increased risk of chronic lung disease. Children with chronic lung disease are at increased risk of invasive pneumococcal disease (IPD). A 4 dose pneumococcal conjugate vaccine schedule (at 2, 4, 6 and 12-15 months of age) is recommended for premature infants with chronic lung disease or other conditions resulting in high risk of IPD. The first dose of pneumococcal conjugate vaccine should be given at 2 months of age, even if the infant is still hospitalized. Refer to Pneumococcal Vaccine in Part 4 for additional information.

Rotavirus vaccine

Available data indicate that rotavirus vaccine (RV) is safe and effective in preterm infants. Given the potential complications of RV infections in premature infants and the benefits of vaccination, RV vaccines are recommended for healthy premature infants starting at 6 weeks of chronological age, with the first dose administered before 15 weeks of chronological age. The vaccination series should be completed before 8 months of chronological age. When providing RV vaccine to hospitalized infants, discussion with infection control services and neonatologiss is advised. Refer to Immunization of Patients in Health Care Institutions in Part 3 for more information about the administration of RV vaccine in the hospital setting. Refer to Rotavirus Vaccine in Part 4 for additional general information about RV vaccine.

Bacille Calmette-Guérin (BCG) Vaccine

Infants born prematurely may receive BCG vaccine any time after 31 weeks of chronological age, if indicated. Refer to Bacille Calmette-Guérin (BCG) Vaccine in Part 4 for additional information.

Monoclonal anti-respiratory syncytial virus (RSV) antibody (palivizumab)

To decrease the likelihood of serious RSV infection requiring hospitalization and supplemental oxygen therapy, palivizumab is recommended for infants born prematurely who are 6 months of chronological age or younger at the start of the RSV season. Refer to Passive Immunizing Agents in Part 5 for additional information.

Selected References

  • Bonhoeffer J, Siegrist C-A, Heath PT. Immunisation of premature infants. Arch Dis Child 2006;91:929-935.
  • 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:e1085-e1090.
  • Centers for Disease Control and Prevention. General recommendations on immunization
    Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2011;60(RR-2):1-61.
  • D'Angio C. Active immunization of premature and low birth-weight infants. A review of immunogenicity, efficacy and tolerability. Pediatr Drugs 2007;9(1):17-32.
  • Flatz-Jequier A, Posfay-Barbe K, Pfister R et al. Recurrence of cardiorespiratory events following repeat DTaP-based combined immunization in very low birth weight premature infants. J Pediatr 2008;153:429-31.
  • Gad A, Shah S. Special immunization considerations of the preterm infant. J Pediatr Health Care 2007;21:385-91.
  • Klein N, Massolo M, Greene J et al. Risk factors for developing apnea after immunization in the neonatal intensive care unit. Pediatrics 2008;121:463-69.
  • Lee J, Robinson JL, Spady DW. Frequency of apnea, bradycardia, and desaturations following first diphtheria-tetanus-pertussis-inactivated polio-Haemophilus influenzae type B immunization in hospitalized preterm infants. BMC Pediatr 2006;6(20).
  • Pfister R, Aeschback V, Niksic-Stuber V et al. Safety of DTaP-based combined immunization in very-low-birth-weight premature infants: frequent but mostly benign cardiorespiratory events. J Pediatr 2004;145:58-66.
  • Pourcyrous M, Korones S, Arheart K et al. 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 2007;151:167-72.

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