Preterm and low birth weight infants face a higher risk of infections and often experience delayed vaccinations due to safety concerns. Although their immune response may be lower, most can still generate sufficient immunity from vaccines, and specific immunization recommendations have been outlined according to age and clinical stability. Key vaccines include BCG, polio, hepatitis B, DTaP, and pneumococcal, with careful monitoring advised for high-risk infants after vaccination.

1. Immunization in Preterm and
Low Birth Weight Infants
Dr Padmesh V
DNB(Ped), DM(Neonatology)

2. • INTRODUCTION:
• Preterm infants are at increased risk of infections with
increased incidence and severity.
• Vaccination is often delayed in preterm infants due to
– Lack of knowledge about safety and effectiveness of vaccines in
preterm infants among healthcare workers and parents.
– Fear or adverse events, as an increase in cardiorespiratory
events following immunization in the very preterm is reported.
• Accordingly, several recommendations were made to
closely observe hospitalized extremely-low-birth-weight
infants for significant adverse events for up to 72 hours.

3. • Causes for decreased immunity in preterms:
• Decreased keratinization of skin (initial barrier against
infection). Stratum corneum develops fully between
weeks 32 and 34 of gestation and matures rapidly within
2 weeks of delivery.
• Gastric acidity, another nonspecific means of immune
defense, is decreased.
• Decreased secretory IgA production until week 29 of
gestation.
• Decreased complement activity, decreased neutrophil
stores, and neutrophil adhesion.

4. • Causes for decreased immunity in preterms:
• Reduced ability of CD4+ lymphocytes to stimulate
humoral immunity.
• Decreased activity by cytotoxic CD8 T cells.
• Passive immunity, rendered by maternal transfer of IgG
to the fetus via pinocytosis, occurs primarily in the last
trimester of development.
• Favorable intestinal micobiota derived from maternal
human or donormilk may be deprived in preterms who
are on IV Fluids alone.

5. • Deficits in virtually all aspects of the immune system
render premature infants vulnerable to nosocomial and
vaccine-preventable infections.
• In general, generation of the antibody response after
vaccination directly correlates with chronologic age,
gestational age, and birthweight.
• Immunocompetence in newborns depends on prenatal
maturation as each additional week of gestation sees an
increased response to antigens.
• Postnatal maturation, which begins upon exposure to
environmental antigens, occurs in preterm infants at a
speed comparable to that of full-term infants.

6. • Although studies have shown decreased immune
responses to several vaccines administered to VLBW
babies and extreme preterms, most of them, including
infants who receive dexamethasone for chronic lung
disease, produce sufficient vaccine-induced immunity to
prevent disease. (Sufficient, although decreased)
• Vaccine dosages administered to term infants should not
be reduced or divided when given to preterm or low
birth weight infants.

7. • ADVERSE EFFECTS IN PRETERM VACCINATIONS:
• Some studies show that cardiorespiratory events may
increase in ELBW/VLBW who receive selected vaccines.
• Risk factors for post-immunization apnea:
– Apnea within 24 hours prior to immunization
– Younger age
– Weight <2000 g at the time of immunization
– History of apnea during previous vaccination
– Very sick at birth
• It may be prudent to monitor infants with these
characteristics for 48 hours after immunization if they are
still in the hospital.

8. • RECOMMENDATIONS:
• Medically stable preterm infants who remain in the hospital
at 2 months of chronologic age should receive all inactivated
vaccines recommended at that age.
[A medically stable infant is defined as one who does not require ongoing management
for serious infection; metabolic disease; or acute renal, cardiovascular, neurologic, or
respiratory tract illness and who demonstrates a clinical course of sustained recovery and
a pattern of steady growth. ]
• All immunizations required at 2 months of age can be
administered simultaneously to preterm or low birth weight
infants, except for oral rotavirus vaccine, which should be
deferred until the infant is being discharged from the hospital
to prevent the potential health care-associated spread of this
live vaccine virus.

9. • RECOMMENDATIONS:
• The number of injections of other vaccines at 2 months of age
can be minimized by using combination vaccines.
• When it is difficult to administer 3 or 4 injections
simultaneously to hospitalized preterm infants because of
limited injection sites, the vaccines recommended at 2
months of age can be administered at different times. To
avoid superimposing local reactions, 2-week intervals may be
reasonable. [Redbook 2018]
• The choice of needle lengths used for IM vaccine
administration is determined by available muscle mass of the
preterm.

10. • RECOMMENDATIONS:
Preterm/LBW Immunizations
Regular vaccines Special considerations
1. BCG 1. Influenza
2. Polio 2. Palivizumab
3. Hepatitis B
4. DTaP
5. Hib
6. Rotavirus
7. Pneumococcal

11. • INDIVIDUAL VACCINES:
• BCG:
• There are various recommendations regarding the timing of BCG in
preterms/LBW.
• Some guidelines recommend BCG to be given at 34 weeks
corrected GA.
• IAP recommends administering BCG to stable preterms at the time
of discharge.
• Safety and Immunogenicity of Early Bacillus Calmette-Guérin
Vaccination in Infants Who Are Preterm and/or Have Low Birth
Weights-A Systematic Review and Meta-analysis (Nov 2018)
recommends early (within 7 days of birth) vaccination in stable
preterms and LBW.

12. • INDIVIDUAL VACCINES:
• Polio:
• IAP recommends that birth dose of OPV can be effectively
given to low birth weight and preterm babies after
stabilization and preferably at the time of discharge.
• IPV or combination vaccination should be used on a
regular schedule as per chronological age.

13. • INDIVIDUAL VACCINES:
• HEPATITIS B:
• In <2kg babies: If mother is HBsAg Negative, delay first dose of
hepatitis B vaccine until 1 month of age or hospital discharge,
whichever is earlier. (Redbook,2018)
• In babies <2 kg born to a hepatitis B positive mother, hepatitis B
vaccine should be given along with HBIG within 12 hours of birth
(this dose is not counted as part of primary series) and 3 more
doses at 1, 2 and 6 months are recommended.
• Hepatitis B vaccine is the only vaccine known to have a significantly lower
response in preterms compared to full term infants (45%-85% vs 90%-
100% when given at birth). Hence to ensure maximum protection, we
delay giving it until 1 month or at discharge whichever is earlier.

14. • INDIVIDUAL VACCINES:
• DTaP:
• The immune response to the acellular pertussis vaccine
components in preterm infants has been shown to be lower than
in those born at full term, but still expected to be higher than that
required for protection.
• DTaP can be given according to the chronological age in preterms.
• Acellular vaccines have fewer side effects than whole-cell vaccines.

15. • INDIVIDUAL VACCINES:
• Tdap for care givers:
• Preterm infants who haven't completed the primary series are at
increased risk of pertussis infection and pertussis related
complications.
• Therefore tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis (Tdap) vaccine should be administered to all pregnant
women (optimally, early in the interval between weeks 27 and 36
of gestation, to yield high antibody levels in the infant) during
every pregnancy.
• Tdap should be administered immediately postpartum for women
who never have received a previous dose of Tdap.

16. • INDIVIDUAL VACCINES:
• Rotavirus vaccine:
• Oral rotavirus vaccine should be deferred until the infant is being
discharged from the hospital to prevent the potential health care-
associated spread of this live vaccine virus.
• The first dose of rotavirus vaccine should be administered from 6
weeks through 14 weeks+6 days of age (the maximum age for the
first dose is 14 weeks+6 days).
• All doses of rotavirus vaccine should be administered by 8 months,
0 days of age.

17. • INDIVIDUAL VACCINES:
• Pneumococcal vaccine:
• Preterms may show lower antibody levels to pneumococcal
vaccine after a primary dose but are adequate for protection.
• The booster dose is strongly advised in preterms to help maintain
protection.
• Both the 10-valent (PCV10/Synflorix) and 13-valent pneumococcal
conjugate (PCV13/Prevenar 13) vaccines have been shown to be
immunogenic in preterms.
• Administer these vaccines as per chronological age.

18. • INDIVIDUAL VACCINES:
• Hemophilus Influenza b vaccine:
• Even though premature infants develop lower antibody
concentrations than term infants following Hib conjugate
vaccination, the antibody level is sufficient to confer a high level of
protection to premature babies.
• Hib vaccines should be administered according to chronological
age.

19. • INDIVIDUAL VACCINES:
• Influenza virus:
• Because all preterm infants are considered at increased risk of
complications of influenza, 2 doses of inactivated influenza
vaccine, administered 1 month apart, should be offered for all
preterm infants beginning at 6 months of chronologic age.
• No effective vaccine is available for infants <6 months, so the focus
should be on maternal and caregiver immunization. It is very
important that household contacts, child care providers, and
hospital nursery personnel caring for preterm infants receive
influenza vaccine annually.
• Once the infant is age 6 months, the vaccine should be given to the
preterm too regardless of maternal immunization.

20. • INDIVIDUAL VACCINES IN PRETERMS / LBW:
VACCINE WHEN GIVEN
BCG At time of discharge
Polio At time of discharge
Hepatitis B (Mother
negative)
At time of discharge, or 1
month age whichever is
earlier
Hepatitis B (Mother
Positive)
Within 12 hours of birth. (Do
not count as part of series)
DTaP Chronological age
Rotavirus On discharge
Hib Chronological age
Pneumococcal Chronological age
Influenza Chronological age

21. • INDIVIDUAL IMMUNOPROPHYLAXIS:
• Palivizumab
• Humanized monoclonal antibody against the RSV F glycoprotein.
• For prevention of serious RSV lower respiratory tract disease in
children at high risk of RSV disease.
• Palivizumab does not interfere with response to routine
immunization with live virus vaccines (eg, measles, mumps,
rubella, varicella).
• Preterm infants born before 29 weeks gestation; infants born with
certain congenital heart defects; and certain infants with chronic
lung disease of prematurity or hemodynamically significant heart
disease may benefit from monthly immunoprophylaxis with
palivizumab.

22. • Targeted immunisation or cocooning
• Most infants acquire diseases such as whooping cough
and influenza from family members.
• “Cocooning” or “targeted immunisation” involves
ensuring siblings are up to date with their immunisations,
and immunising the infant’s close contacts (parents,
grandparents and care givers) to reduce the risk of
disease exposure for the infant.
• Important vaccines to consider include pertussis-
containing vaccines and influenza vaccines.

23. • REFERENCES:

24. THANK YOU!