This document discusses vaccination in preterm and low birth weight infants. It notes that preterm infants have an underdeveloped immune system which makes them more susceptible to vaccine-preventable diseases. The document provides an overview of various vaccines including BCG, OPV, IPV, Hep B, DPT, Hib, PCV, RVV, and influenza. It discusses the immunogenicity, safety, feasibility of administering in the NICU, and recommendations for each vaccine in preterm infants. It also talks about strategies like maternal immunization, passive immunization with HBIG and RSV palivizumab, and "cocooning" to provide indirect protection to preterm infants. Factors causing delays in vaccination

1. Presented by – Dr Rashi
Moderated by – Dr Swati Upadhyay
ABVIMS and RML Hospital, New Delhi

2. Background
Burden of VPD in Preterm
Immunological differences in Preterm
Recommended Schedule
Overview of Individual vaccines
Other methods to Protect Preterm
FAQ
Factors leading to Delay
Way to Strengthen Immunization rate at discharge

3. 15 million babies are born premature worldwide
Out of them- 3.5 million are born in India.
Situation is alarming as India accounts for 23.4% of the global
preterm births
WHO

4. Vaccination NFHS4 ( 12 to 23 months ) - %
BCG 91.9
DPT 1/2/3 89.5/ 85.7/ 78.4
OPV 0/1/2/3 79.1/90.8/ 86.0/ 72.8
Measles 81.1
All Basic Vaccination 62.0
No Vaccination 6.0
Coverage in LBW and Preterm No Data Available
NFHS 4

5. Age-appropriate immunization rates
3% to 15% lower for LBW infants
17% to 33% lower for ELBW
infants in the first 6 months after birth.
87% of ELBW infants are still underimmunized by 12 months of
age.

6. Only 51% were fully up to date with immunizations at NICU
discharge ( CDC )
Langkamp et al demonstrated that VLBW were more likely to be
underimmunized at 12, 24, and 36 months.
Davis RL 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 JAMA 1999
Langkamp DL. Delays in receipt of immunizations in low-birth-weight children: a nationally representative
sample. Arch Pediatr Adolesc Med 2001
No Study accessing the immunization rates at
discharge from NICU available from India!!

7. Incomplete
Vaccination
Increased
susceptibiity
to VPD
Increased
Mortality
Why are we WORRIED about IMMUNIZATION specially in
PRETERMS?

8. In comparison to FT + NBW infants, PT +LBW infants - at an
increased risk of hospitalization and mortality from VPD
Importantly, the literature suggests that an increased risk of
infection positively correlates with the degree of prematurity and
LBW.

9. Disease Type of Study Results
Pertussis
Riise ØR. Risk of Pertussis in Relation to Degree of
Prematurity in Children Less Than 2 Years of Age. Pediatr
Infect Dis J. 2017
Retrospective cohort
study
Increased risk of incidence - IRR = 1.65 (95% CI:
1.32-2.07)
Increased risk of hospitalization in preterm - IRR =
1.99 (95% CI: 1.47-2.71)
Vaccine effective the same after 3rd dose ( 88% vs 93
% ) 1
Tetanus
Lambo et al. Prognostic factors for mortality in neonatal
tetanus: A systematic review and meta-analysis. International
journal of infectious diseases. 2020.
Metanalysis accessing
prognostic factors
-LBW
-Age at onset
LBW were more likely to have an increased odds of
death (OR 2.09, 95% confidence interval (CI) 1.29-
3.37)
This mortality risk was exacerbated for low birth
weight neonates with age at onset ≤6 days (OR 6.80,
95% CI 2.42-19.11)2
Meningitis (Hib)
Hviid A. The impact of birth weight on infectious disease
hospitalization in childhood. Am J Epidemiol. 2007 April.
Population based
cohort study
Risk of hospitalization increased 9% for each 500-g
reduction in birth weight (increase in rate ratio =
1.09, 95% confidence interval: 1.09, 1.11).

10. Vaccine Study Type Results
Rotavirus
Newman RD. Perinatal risk factors for infant
hospitalization with viral gastroenteritis. Pediatrics.
1999
Population Based Case Control VLBW - at the highest risk (OR- 2.6
)
LBW - at intermediate risk (OR 1.6)
Influenza
Garcia MN. Clinical predictors of disease severity during
the 2009-2010 A(HIN1) influenza virus pandemic in a
paediatric population. Epidemiol Infect. 2015.
Retrospective Pre-existing factors associated
with disease severity included
premature birth (OR 2·53),
Invasive Pneumococcal
Shinefield H. Efficacy, immunogenicity and safety of
heptavalent pneumococcal conjugate vaccine in low birth
weight and preterm infants. Pediatr Infect Dis J 2002
Double Blind Randomized Control
Trial
LBW vs NBW- RR -2.6 (P = 0.03)
PT vs FT – RR - 1.6 (P = 0.06)
VE - 100%
Polio
Diptheria
Hep B
TB
No data was found for these
diseases
It is assumed that there is an
increased risk due to immature
immune system of the preterm and
LBW infant

13. Type of Immunity Components FT vs Preterm
Innate - Physical Barriers Skin
Mucosal surfaces of GIT and
Respiratory system
Underdeveloped + Prone for rupture
Antimicrobial peptides-producing flora are
reduced in number leading to penetration of
pathogens
Innate - Passive Maternal IgG transfer Decreased in Preterm as it increases with fetal
age
( Mainly > 32 weeks )
Innate - Phagocytosis Neutrophils
Monocytes
- Reduced pool including precursors due G-CSF
and GM-CSF
- Decreased phagocytic activity
- Decreased respiratory burst
Adaptive B cells
T cells
Maturation occurs mostly after term birth
Deficient in T-cell activation, cytokine
production and cytolytic activity,
Decreased B cell Ig production,
Low cooperation between T and B-cells
Santosh Soans. Vaccination in preterm and low birth weight infants in India, Human Vaccines & Immunotherapeutics. 2021

14.  Protective Immunological Response
 Good Safety Profile
 Safe to administer in NICU except for LIVE ORAL Vaccines

16. Age of Vaccination? – Chronological age
with differences in HepB, RVV and OPV
2019-2020

17. OVERVIEWING INDIVIDUAL
VACCINES
-Immunogenicity
-Safety
-Feasibility of administering inside NICU
-Recommendation

18. Characteristics
Immunogenicity ✔
Safety ✔
Feasibility of administering inside NICU ✔
Recommendation NIS – At Birth
IAP – At Birth
WHO- > 31 weeks and BW < 2500 g - healthy and
clinically stable can receive BCG vaccination at birth,
or at the latest, upon discharge.

19. WHO recommendation.
Asymptomatic neonates born to mothers with bacteriologically confirmed
PTB should receive INH for 6 months
BCG to be given at the end of IPT treatment considering the baby is TB
negative.
RNTCP -2019 guidelines
Advises vaccination at birth irrespective of maternal TB status.

20. Characteristics
Immunogenicity ✔
Safety ✔
Feasibility of administering inside NICU No Studies regarding safety during NICU stay ( Risk
of Enteral Transmission )
Recommendation NIS – Birth, 6-10-14 weeks
IAP – At Birth
WHO- OPV is safe to be given to sick children ( No
recommendation during NICU stay )

21. Characteristics
Immunogenicity ✔
Safety ✔
Feasibility of administering inside NICU ✔
Recommendation NIS – Fractionated at 6 and 14 week
IAP – 6,10,14 week ( B-16-18m)

22. Characteristics
Immunogenicity Less Immunogenic
Safety ✔
Feasibility of administering inside NICU ✔
( Depending on Birth Weight )
Recommendation Depending on maternal HBsAg status

23.  Dose of HBIg in 100 IU in neonates
 HBIg should be stored at 2–8°C and should not be frozen.
 HBIg provides temporary protection lasting 3–6 months .
 Should be given IM anterolateral thigh and in the opposite side of
administration of Hep B vaccine

24. Characteristics
Immunogenicity ✔
Safety ✔
Feasibility of administering inside NICU ✔
Recommendation NIS – 6, 10, 14 week
IAP – 6,10,14 week
WHO- 6,10,14 week

25. Characteristics
Immunogenicity ✔
Safety ✔
Feasibility of administering inside NICU Cannot be given in NICU ( Risk of Enteral
transmission )
Recommendation NIS – 6,10,14 week
IAP – 6,10,14 week
WHO- At discharge as per chronological age

26. Characteristics
Immunogenicity Less but Protective
Safety ✔
Feasibility of administering inside NICU ✔
Recommendation NIS – 6, 10, 14 week
IAP – 6,10,14 week
WHO- 6,10,14 week

27. Characteristics
Immunogenicity Less Immunogenic
Nullified after Booster
Safety ✔
Feasibility of administering inside NICU ✔
Recommendation NIS – 6, 14 week and Booster at 9 months
IAP – 6,10,14 week and Booster 12- 18 months
WHO- 6,10,14 week and Booster 12- 18 months

28. Characteristics
Immunogenicity ✔
Safety ✔
Feasibility of administering inside NICU Not Applicable
Recommendation Two doses of inactivated flu virus vaccine may be
considered at the beginning of flu season in preterm
infants after 6 months of age

29. Vaccine Immunogenicity Safety Inside NICU Schedule
( NIS)
BCG
✔
✔ ✔ At Birth
OPV ✔ ✔ No ( More studies) After Discharge
IPV ✔ ✔ ✔ fIPV at 6,14
Hep B ✔ ✔ ✔ As explained
DPT ✔ ✔ ✔ 6,10,14
Hib Slightly lower in PT ✔ ✔ 6,10,14
(Booster imp)
PCV ✔ ✔ ✔ 6,14
RVV ✔ ✔ No 6,10,14
Inlfuenza ✔ ✔ ✔ Same
All the other vaccines which include MMR, Typhoid, Hepatitis A , JE and Varicella- Recommendations are the
same

30. Maternal
immunization
Passive
Immunization
Cocconing

31. Vaccine Recommendation
Tdap( Combination Vaccine ) 3rd trimester of every pregnancy
( AAP, ACOG, CDC )
Indian *
Inactivated Influenza Vaccine ( IIV) 3rd trimester
Tdap + IIV Can be safely given together
If NOT given during pregnancy Administer in the immediate postpartum period to
prevent newborn exposure

33. Palivizumab- Humanized monoclonal antibody against the RSV F glycoprotein.
Indications
( Ref. The Red Book)
Preterm who develop CLD of Prematurity ( PT < 32
weeks who required oxygen of > 21% at 28 days of
life )
Hemodynamically significant CHD – Pharmacological
requirement for control of CHF / CHD ass with
Moderate to severe pulmonary hypertension
Preterm without CHD or CLD – PT < 29 weeks who
are less than 12 months before the start of first RSV
season
Dose 15 mg/kg/ dose i.m. every 30 days
Duration For 5 months

34. CDC, WHO, AAP

35. A cocoon vaccination strategy is vaccinating people from the immediate
environment of those patients who are susceptible to an illness but cannot be
vaccinated as
- they are too young to have completed the primary dose
- have no vaccine recommended for their age.
Mainly applicable to pertussis and influenza vaccines
Works on the principle of Herd immunity
Recommended by CDC
Presently no recommendations regarding the same in India
Immunization in Preterm. Neoreviews 2015

36. Regarding Preterm
immunization

37. Q- Is there increased risk of adverse events after vaccination in
preterm neonates?
A- No. There is no increase in the incidence of classic vaccine-
related adverse effects in preterms as compared to their term
counterparts

38. Factors associated with increased risk of post vaccination apnoea
include –
1. Apnoea 24 hours prior to Vaccination
2. Younger age
3. Weight less than 2 kg at the time of vaccination
4. SNAP Score of more than 10 24 hours prior to vaccination
Red Book

39. Q – For how long should the babies be observed for post
vaccination apnoea?
A – For 48 hours

40. Q – Due to less muscle mass in preterms should i.m injection be
avoided in them?
A - True, Preterm Neonates do have less muscle mass.
Thin and shorter needle (5/8 inch) should be used for
i.m. injections in them

42. Q – What should I do if the neonate is due for vaccination as per
chronological age but sick?
A - Defer till medically stable
Medically Stable
Who do not require on-going management for serious infection,
metabolic disease or any acute systemic illness
Who demonstrate a clinical course of sustained recovery
Who show a pattern of steady growth

44. Stetson RC, Improving Infant Vaccination Status
in a Level IV Neonatal Intensive Care Unit.
Pediatrics. 2019
Factors Responsible for
Delay
- Providers Knowledge of
immunization and
failure to order
- Perception that patient
is too ill for vaccine
- Parents hesitancy and
availability

45. Part of Unit SOP’s
Part of Pre Discharge
Checklist
Sensitization of Health Care
Providers
Adequate Follow up