Vaccination for preterm infants

Preterm (premature) infants are those born at <37 weeks gestation. Extremely preterm infants are born at <28 weeks gestation.

Prematurity can increase the child’s risk of vaccine-preventable diseases.^1-3

Despite their immunological immaturity, preterm infants generally respond well to vaccines.^4-6 Provided they are medically stable and there are no contraindications to vaccination, preterm infants should receive vaccines according to the recommended schedule at their chronological age, without correction for prematurity.^7-9

Consider the child’s birth weight, the precise gestational age and the presence of any chronic medical condition(s) before giving vaccines.

Vaccination is associated with an increased risk of apnoea in preterm infants who receive vaccines in hospital, particularly those receiving complex medical care or with a history of apnoea.

Apnoea is generally self-limiting in this setting, but is an expected adverse event following immunisation. Take measures to manage it by:^10-12 

• monitoring hospitalised preterm infants for apnoea or bradycardia for up to 48 hours after vaccination^12,13
• in infants who have a history of apnoea after vaccination, considering giving future vaccines under medical supervision^14,15

Vaccination is not associated with an increased risk of sudden infant death syndrome.^16,17

All preterm infants born at <28 weeks gestation are recommended to receive 4 doses of 13vPCV (13-valent pneumococcal conjugate vaccine) and 2 doses of 23vPPV (23-valent pneumococcal polysaccharide vaccine).

The doses of 13vPCV should be given at 2, 4, 6 and 12 months of age.

The 1st dose of 23vPPV  should be given at 4 years of age, and the 2nd dose given at least 5 years later. 

Children who were born at <28 weeks gestation do not need more pneumococcal vaccine doses after 5 years of age if they:

• do not have a chronic medical condition(s) and are not Aboriginal or Torres Strait Islander, and therefore are not at ongoing increased risk of pneumococcal disease 
• have received the extra pneumococcal vaccine doses to 5 years of age as recommended above

However, all children and adults who have chronic lung disease or certain other chronic medical conditions (whether related to preterm birth or not) should receive extra pneumococcal vaccine doses up to and beyond the age of 5 years. 

For more details, see:

• Pneumococcal disease
• Table. Catch-up schedule for 13vPCV for Aboriginal and Torres Strait Islander children living in NT, Qld, SA or WA ONLY, and all children with risk conditions for pneumococcal disease, aged <5 years
• List. Risk conditions for pneumococcal disease

Low-birthweight preterm infants do not respond as well to hepatitis B–containing vaccines as full-term infants.^13,18,19

Low-birthweight infants (<2000 g) and/or infants born at <32 weeks gestation (irrespective of weight) are recommended to receive:

• hepatitis B vaccine at birth
• 3 doses of a hepatitis B–containing vaccine, at 2, 4 and 6 months of age
• a booster dose at 12 months of age 

There is no need to measure the hepatitis B surface antibody (HBs) titre after the primary series.

However, if measuring the antibody titre, do this at least 1 month after the 6-month dose. If the anti-HBs titre is <10 mIU per mL, give a booster dose.

Preterm infants born to hepatitis B surface antigen (HBsAg)–positive mothers should receive hepatitis B vaccine and hepatitis B immunoglobulin, as specified in Hepatitis B (see Hepatitis B).

Preterm infants have a high rate of underlying medical conditions that increase the risk of complications from influenza.²⁰ These can include respiratory, cardiac and neurologic conditions. 

Preterm infants should receive influenza vaccine every year, starting at ≥6 months of age. 

Infants should receive 2 vaccine doses, at least 4 weeks apart, the 1st time they receive influenza vaccine, then 1 dose every year after that (see Influenza).

Preterm infants can receive rotavirus vaccine at their chronological age without correction for prematurity. This includes hospitalised infants who are medically stable.

Strict upper age limits for vaccination apply, depending on which rotavirus vaccine the infant receives (see Rotavirus).

Preterm infants do not need a change to the usual schedule for Haemophilus influenzae type b (Hib) vaccines conjugated with tetanus (PRP-T), including Infanrix hexa. Preterm infants produce good antibody responses to all the antigens in Infanrix hexa following administration at 2, 4 and 6 months of age. However, the responses to hepatitis B and Hib are not quite as high as in full-term infants.¹

If an extremely preterm and/or low-birthweight baby (<28 weeks gestation or <1500 g birth weight) received Hib vaccine conjugated to the outer membrane protein of Neisseria meningitidis (PRP-OMP) for their primary doses, they should receive an extra dose at 6 months of age. That is, they should receive doses at 2, 4, 6 and 18 months of age.

1. Shinefield H, Black S, Ray P, et al. Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants. Pediatric Infectious Disease Journal 2002;21:182-6.
2. Langkamp DL, Davis JP. Increased risk of reported pertussis and hospitalization associated with pertussis in low birth weight children. Journal of Pediatrics 1996;128:654-9.
3. Crowcroft NS, Andrews N, Rooney C, Brisson M, Miller E. Deaths from pertussis are underestimated in England. Archives of Disease in Childhood 2002;86:336-8.
4. Bonhoeffer J, Siegrist CA, Heath PT. Immunisation of premature infants. Archives of Disease in Childhood 2006;91:929-35.
5. D'Angio CT. Active immunization of premature and low birth-weight infants: a review of immunogenicity, efficacy, and tolerability. Pediatric Drugs 2007;9:17-32.
6. Omeñaca F, Merino JM, Tejedor JC, et al. Immunization of preterm infants with 10-valent pneumococcal conjugate vaccine. Pediatrics 2011;128:e290-8.
7. Davis RL, Rubanowice D, Shinefield HR, et al. Immunization levels among premature and low-birth-weight infants and risk factors for delayed up-to-date immunization status. JAMA 1999;282:547-53.
8. Langkamp DL, Hoshaw-Woodard S, Boye ME, Lemeshow S. Delays in receipt of immunizations in low-birth-weight children: a nationally representative sample. Archives of Pediatrics and Adolescent Medicine 2001;155:167-72.
9. Slack MH, Thwaites RJ. Timing of immunisation of premature infants on the neonatal unit and after discharge to the community. Communicable Disease and Public Health 2000;3:303-4.
10. Klein NP, Massolo ML, Greene J, et al. Risk factors for developing apnea after immunization in the neonatal intensive care unit. Pediatrics 2008;121:463-9.
11. 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 Pediatrics 2006;6:20.
12. Ellison VJ, Davis PG, Doyle LW. Adverse reactions to immunization with newer vaccines in the very preterm infant. Journal of Paediatrics and Child Health 2005;41:441-3.
13. Saari TN, American Academy of Pediatrics Committee on Infectious Diseases. Immunization of preterm and low birth weight infants. Pediatrics 2003;112:193-8.
14. Clifford V, Crawford NW, Royle J, et al. Recurrent apnoea post immunisation: informing re-immunisation policy. Vaccine 2011;29:5681-7.
15. 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. Journal of Pediatrics 2008;153:429-31.
16. Vennemann MM, Butterfaß-Bahloul T, Jorch G, et al. Sudden infant death syndrome: no increased risk after immunisation. Vaccine 2007;25:336-40.
17. Jonville-Béra AP, Autret-Leca E, Barbeillon F, Paris-Llado J, French Reference Centers for SIDS. Sudden unexpected death in infants under 3 months of age and vaccination status – a case-control study. British Journal of Clinical Pharmacology 2001;51:271-6.
18. Gołębiowska M, Kardas-Sobantka D, Chlebna-Sokół D, Sabanty W. Hepatitis B vaccination in preterm infants. European Journal of Pediatrics 1999;158:293-7.
19. Blondheim O, Bader D, Abend M, et al. Immunogenicity of hepatitis B vaccine in preterm infants. Archives of Disease in Childhood. Fetal and Neonatal Edition 1998;79:F206-8.
20. Munoz FM. Influenza virus infection in infancy and early childhood. Paediatric Respiratory Reviews 2003;4:99-104.