Any baby born before the 37th week of pregnancy is considered to be preterm. About 12 of every 100 of births in the United States are preterm.

Maternal antibodies

Preterm babies acquire lesser quantities of antibodies through the placenta than full-term babies. Since these antibodies are present at lower levels, they do not last as long as those of full-term babies. Because preterm infants rely on their own immune systems for protection sooner than full-term babies, it is important that they receive needed vaccinations so they can protect themselves against disease.

Chronologic age

Vaccines should be given according to a baby's chronologic age — the time since delivery.

Hepatitis B vaccine

If a preterm infant is born to someone infected with hepatitis B, they should receive the hepatitis B vaccine at or shortly after birth due to the chance of being infected during delivery. If the baby weighs less than 2,000 grams, the dose should not be counted as part of the hepatitis B series, and the baby should start the three-dose series one month after birth.

If a preterm infant is born to someone known not to be infected with hepatitis B, they should get the vaccine one month after birth.

Preterm babies discharged before 1 month of age may get the vaccine at discharge as long as they are considered medically stable and have been consistently gaining weight.

In both cases, later doses should be given at least four weeks after the dose at 1 month of age. The third dose should be given at least 16 weeks after the first dose and at least eight weeks after the second dose, but not before 6 months of age.

Respiratory syncytial virus (RSV) protection

Respiratory syncytial virus, or RSV, is a seasonal virus that causes a respiratory infection in virtually all young children at some point. It is a particularly dangerous infection for premature infants because of the immaturity of their lungs. Two means of protecting preterm babies from RSV are available:

1. Pregnant people can be vaccinated against RSV. If vaccination occurs at least two weeks prior to delivery, antibodies will pass to the baby, so the baby is protected at time of birth. In the event the mother does not receive vaccine, or if delivery occurs less than two weeks after vaccination, the newborn should not be considered protected by this option.
2. If the baby is not protected at birth, they should receive Beyfortus, a monoclonal antibody. For infants born during RSV season, this should be administered at or closely after birth. For those born prior to the start of RSV season, they should receive the antibody at the start of RSV season in their area. In the event that Beyfortus is unavailable, certain high-risk premature infants will be eligible for Synagis, another monoclonal antibody product that requires multiple doses throughout RSV season.

Vaccines typically administered at 2 months

In addition to hepatitis B, 2-month-old babies require vaccinations against diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b (Hib), pneumococcus and rotavirus. Preterm infants should receive these vaccines at the chronologic age of 2 months, even if they are still hospitalized.

These vaccines should continue to be given at the appropriate chronologic ages according to the Centers for Disease Control and Prevention's vaccine schedule until each series is completed.

Other vaccines

Other vaccines should also be given according to the recommended schedule; these include vaccines for influenza, COVID-19, measles, mumps, rubella, varicella (chickenpox) and hepatitis A.

Influenza and COVID-19 vaccines are not recommended until 6 months of age. At 6 months of age, the baby may get the inactivated version of the influenza vaccine. Healthcare workers and family members in contact with a baby less than 6 months old should be immunized to lessen the baby's chance of being infected with these infections.

References 

Acellular pertussis vaccine and prematurity

Schloesser RL, Fischer D, Otto W, Rettwitz-Volk W, Herden P, et al. Safety and immunogenicity of an acellular pertussis vaccine in premature infants. Pediatrics 1999;103(5):e60.
The authors prospectively evaluated the safety and immunogenicity of an acellular pertussis vaccine in preterm infants compared with full-term infants at 2 months of age, followed by two additional doses at four and eight weeks after the initial dose. Immune responses to the acellular pertussis vaccine were decreased in preterm compared with term infants, but vaccine efficacy was high. Acellular pertussis vaccine was well tolerated in both groups and the incidence of systemic adverse reactions was limited to one patient in each group having a fever > 38.5C.

Concomitant or combination vaccine receipt and prematurity

Omenaca F, Vazquez L, Garcia-Corbeira P, Mesaros N, Hanssens L, et al. Immunization of preterm infants with GSK’s hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated poliovirus and Haemophilus influenzae type b conjugate vaccine: a review of safety and immunogenicity. Vaccine 2018;36:986-996.
The authors reviewed 10 clinical studies and 15 years of post-marketing safety surveillance data regarding immunization with hexavalent vaccine (DTaP/HepB/IPV/Hib) when administered alone or in combination with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with a history of prematurity or low birthweight (LBW). At least 92% of infants with a history of LBW or as young as 24 weeks gestational age responded to all vaccine antigens after the three-dose vaccination series. Between 13% and 30% of medically stable infants with a history of prematurity or LBW developed apnea after vaccination, typically after the first dose. The occurrence of post-immunization cardiorespiratory events was influenced by the severity of underlying neonatal conditions, though most events resolved spontaneously or required minimal intervention.  The hexavalent vaccine was well tolerated in co-administration regimens.

Montague EC, Hilinski JA, Williams HO, McCracken CE, Giannopoulos HT, et al. Respiratory decompensation and immunization of preterm infants. Pediatrics 2016;137(5):e20154225.
The authors retrospectively evaluated the safety of routine infant vaccinations (DTaP, IPV, HepB, Hib, PCV, and rotavirus) and influenza vaccine to 240 premature infants born at less than 32 weeks of gestation who were immunized during their hospital stay over a 6.5-year period. Fewer than 10% of infants required increased respiratory support within 72 hours of vaccination. Two percent (2%) of infants required reintubation, all of whom had bronchopulmonary dysplasia (BPD) and a birthweight of less than 650 grams (1 pound 6 ounces). An increased incidence of apnea/bradycardia/desaturation events was observed in infants with and without BPD, but no differences existed between groups.  Most infants received three or more vaccines per day, though the number of vaccines administered in a day was not associated with an increase of adverse events after immunization. The authors concluded that respiratory decompensation requiring clinical intervention after immunization of preterm infants both with and without BPD was uncommon and immunization should not be delayed.

DeMeo SD, Raman SR, Hornik CP, Wilson CC, Clark R, et al. Adverse events after routine immunization of extremely low-birth-weight infants. JAMA Pediatr 2015;169(8):740-745.
The authors retrospectively evaluated the incidence of adverse events after vaccination between the ages of 53 and 100 days in more than 13,000 infants born at 28 weeks of gestation or less and birthweight ≤ 1000 grams. More than 90% of infants received three or more vaccines. Infants who were born at 23 to 24 weeks gestation had a higher risk of sepsis evaluation and intubation after immunization. No increase in the incidence of seizures was detected. The post-immunization incidence of adverse events was similar across immunization types, including combination vaccines when compared with single-dose vaccines. 

Faldella G, Galleti S, Corvaglia L, Ancora G, Alessandroni R. Safety of DTaP-IPV-Hib-HBV hexavalent vaccine in very premature infants. Vaccine 2007;25:1036-1042.
In this prospective, observational study, the safety of DTaP-IPV-Hib-HBV hexavalent vaccine was evaluated in 45 preterm newborns less than 31 weeks of gestation admitted to the NICU who received the vaccine between day of life 49 and 112. Vaccination was generally well tolerated, with 11% showing either a transient recurrence of or increase in apnea and bradycardia episodes following immunization, but intervention was limited to tactile stimulation, supplemental oxygen or bag and mask ventilation, and no patients were intubated. All patients with cardiorespiratory events had chronic diseases. The authors also specifically evaluated cardiac disturbances (QTc interval) and cerebral blood flow effects but found no differences in these parameters before and after vaccination or in those infants who experienced cardiorespiratory events.

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.
In this retrospective study, the authors investigated the frequency of apnea, bradycardia and desaturations in approximately 250 hospitalized very preterm infants (mean gestational age 26 weeks) to determine if incidences of these events were increased following the first dose of DTP/DTaP-IPV-Hib vaccine. A significant increase in the incidence of cardiorespiratory events was detected after vaccine administration compared with unvaccinated infants, though most events were clinically insignificant and the need for intervention was not different between the groups.

Schulzke S, Heininger U, Lucking-Famira M, Fahnenstich H. Apnea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines. Eur J Pediatr 2005;164:432-435. 
In this retrospective study, the authors investigated the incidence of apnea and bradycardia in respiratory-stable preterm infants (mean gestational age 28 weeks and postnatal age ~ 2 months) following a combination DTaP/Hib/IPV or DTaP/Hib/IPV/HepB. Vaccination was generally well tolerated, with 13% showing either a transient recurrence of or increase in apnea and bradycardia episodes following immunization, but intervention was limited to tactile stimulation, supplemental oxygen or bag and mask ventilation, and no patients were intubated.

DTaP vaccine and prematurity

Carbone T, McEntire B, Kissin D, Kelly D, Steinschneider A, 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.
In this randomized, controlled, prospective study, the authors examined the relationship between DTaP and cardiorespiratory events in approximately 200 preterm infants (mean post-conception age of 35 weeks) at 2 months of age. Preterm infants who received DTaP at 2 months of age were not more likely to experience prolonged apnea and bradycardia in the 48-hour post-immunization period than infants who did not receive DTaP. 

Pfister RE, Aeschbach V, Niksic-Stuber V, Martin BC, Siegrist CA. 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. 
The authors evaluated the safety of DTaP-IPV-Hib immunization in very low birthweight preterm infants (mean gestational age 28 ± 2 weeks; range 24-34 weeks) when administered prior to hospital discharge during the first two to four months of life. Nearly half of the infants had a reappearance or increase in either apnea, bradycardia, or desaturations after vaccination, though all infants returned to baseline within 48-72 hours and most events resolved spontaneously or after brief stimulation. No event resulted in a detrimental impact on the infants’ clinical course, reintubation or a delay in discharge. The authors concluded that timely vaccine receipt in this fragile population is safe.

Hib vaccine and prematurity

Omenaca F, Garcia-Sicilia J, Carcia-Corbeira P, Boceta R, Romero A. 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 2005;116(6):1292-1298.
The authors prospectively evaluated the safety and immunogenicity of a hexavalent DTaP/HepB/IPV/Hib vaccine in approximately 200 preterm and full-term infants at 2, 4, and 6 months of age. Preterm and full-term infants displayed good immune responses to all antigens. Protective immune responses against Hib occurred in more than 90% of preterm infants, though these responses were less than those of term infants. An increased risk of oxygen desaturations or bradycardia was observed in preterm infants born < 28 weeks with birth weights less than or equal to 1000 grams in the 72 hours after their first dose of vaccine, and reintubation was not reported.

Pfister RE, Aeschbach V, Niksic-Stuber V, Martin BC, Siegrist CA. 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. 
The authors evaluated the safety of DTaP-IPV-Hib immunization in very low birthweight preterm infants (mean gestational age 28 ± 2 weeks; range 24-34 weeks) when administered prior to hospital discharge during the first two to four months of life. Nearly half of the infants had a reappearance or increase in either apnea, bradycardia, or desaturations after vaccination, though all infants with increased events returned to baseline within 48-72 hours and most of these events resolved spontaneously or after brief stimulation. No event resulted in a detrimental impact on the infants’ clinical course, reintubation or a delay in discharge. The authors concluded that timely vaccine receipt in this fragile population is safe.

Influenza vaccine and prematurity

Esposito S, Pugni L, Daleno C, Ronchi A, Valzano A, et al. Influenza A/H1N1 MF59-adjuvanted vaccine in preterm and term children aged 6 to 23 months. Pediatrics 2011;127(5):e1161-e1168.
In this prospective, randomized study, the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine was evaluated in approximately 100 children aged 6 to 23 months of age, including those born at less than 32 weeks of gestation. Regardless of gestational or postnatal age, all children developed protective immune responses after two doses, and all but one child was protected after the first dose. The vaccine was generally well tolerated, with fever recorded as the only adverse event; no differences were detected when comparing infants with differing gestational ages (< 32 weeks versus 32-36 weeks versus 37-42 weeks). Local reactions were minimal (less than 4% occurrence) and did not differ between gestational age groups, indicating the tolerability of the MF59 adjuvant. No severe adverse events occurred in any patient.

Measles vaccine and prematurity

McClure D, Jacobsen SJ, Klein NP, Naleway AL, Kharbanda EO, et al. Similar relative risks of seizures following measles containing vaccination in children born preterm compared to full-term without previous seizures or seizure-related disorders. Vaccine 2019;37(1):76-79.
The authors retrospectively evaluated the incidence of febrile seizures following measles vaccine at age 12 through 23 months over a 13-year period in more than 530,000 children to determine if the risk is affected by prematurity. The overall incidence of febrile seizures was low and no differences were found in the risk of febrile seizure between children born preterm versus full term. 

Pneumococcal vaccine and prematurity

Martinón-Torres F, Czajka H, Center KJ, Wysocki J, Majda-Stanislawska E, et al. 13-valent pneumococcal conjugate vaccine (PCV13) in preterm versus term infants. Pediatrics 2015;135(4):e876-e886.
In this prospective study, the authors compared the safety and efficacy of PCV13 age when administered with other routine vaccines (e.g., DTaP, hepatitis B, IPV, Hib, meningococcal group C conjugate vaccine) in term and preterm infants. Immune responses to PCV13 were lower in preterm infants, though the majority of subjects in both groups achieved protective antibody levels. PCV13 was well tolerated in both term and preterm infants, with the most common problem being irritability or decreased sleep in the preterm group.

Esposito S, Pugni L, Bosis S, Proto A, Cesati L, et al. 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 2005;23:1703-1708.

In this prospective study, the authors assessed the immunogenicity, safety and tolerability of PCV7 administered at 3, 5 and 11 months of age in preterm and full-term infants. PCV7 was immunogenic in both groups when given as a three-dose series. PCV7 was generally well tolerated with irritability and drowsiness occurring regardless of gestational age.

Shinefield H, Black S, Ray P, Fireman B, Schwalbe J, et al. Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants. Pediatr Infect Dis J 2002;21:182-186.
In this randomized, double bind trial, more than 37,000 infants were given either PCV7 or meningococcal serogroup C conjugate vaccine (MCV), including approximately 6,000 low birth weight or preterm infants. The vaccine was efficacious in 100% of infants. PCV7 was well tolerated by all infants, regardless of gestational age or birthweight. An increased incidence of hives was found in the low birthweight and preterm groups who received PCV compared with those who received MCV. Preterm infants receiving PCV also had an increased risk of vomiting, irritability, loss of appetite, and diarrhea compared with those receiving MCV.

Rotavirus vaccine and prematurity

Omenaca F, Sarlangue J, Szenborn L, Nogueira M, Suryakiran PV, et al. Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European infants: a randomized phase IIIB study. Pediatr Infect Dis J 2012;31(5):487-493.
In this randomized, placebo-controlled trial, the safety and efficacy of rotavirus vaccine (Rotarix®) was evaluated in approximately 1,000 preterm infants (mean gestational age 33 weeks). Immunologic responses to the vaccine were comparable to full-term infants evaluated in previous studies. No differences in the incidence of serious adverse events were detected when comparing vaccine and placebo recipients, with the most common reported finding being fever (less than 5%). Gastroenteritis episodes were also similar between vaccine and placebo recipients. No intussusception cases were reported. 

Goveia MG, Rodriguez ZM, Dallas MJ, Itzler RF, Boslego JW, et al. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine in healthy premature infants. Pediatr Infect Dis J 2007;26(12):1099-1104.
In this randomized, placebo-controlled trial, the safety and efficacy of rotavirus vaccine (Rotateq®) was evaluated in approximately 70,000 healthy infants 6-12 weeks of age, including more than 2,000 born prematurely. Rotavirus vaccine was well tolerated among preterm infants, including those born at less than 32 weeks of gestation. No differences in the incidence of serious adverse events were detected between preterm vaccine and placebo recipients. No cases of intussusception in any premature infant were found during the study. These results support vaccinating healthy premature infants on the same schedule as term infants.