1. Immunization of Preterm and Low Birth Weight Infants
Marietta Vázquez, MD, FAAP
Yale University School of Medicine

2. No conflict of interest

3. Immunization of Preterm and Low Birth Weight Infants
The development of a safe and effective childhood immunization schedule has effectively reduced morbidity and mortality from vaccine-preventable diseases worldwide.
Studies demonstrate that vaccines are SAFE in preterm and low birth weight infants.  [pre-term--gestational age <37 weeks; low birthweight as <2,500 g ]
Vaccine Safety--Immunization in these infants is safe and effective. However, post-vaccination apnea with or without associated bradycardia up to 48 hours post-immunization may be increased in some groups.

4. Vaccine Safety Apnea and Premies After Immunization
Factors possibly associated with an increased incidence of post- immunization apnea
•Apnea within the 24 hour period before immunization
• More severe illness at birth
• Chronological age less than 67 days and/or earlier gestational age in infants with a birth weight of less than 1500g
• An apneic episode following the first immunization event
No long term sequelae have been associated with post immunization apneic events.
Immunization should not be withheld or delayed.

5. Immunization of Preterm and Low Birth Weight Infants Vaccine Immunogenicity
Studies demonstrate that vaccines are IMMUNOGENIC in preterm infants. 
Vaccine immunogenicity --Although the magnitude of immune responses may sometimes be lower for specific vaccines in preterm infants, protective and durable responses are achieved in most cases. Evidence suggests their response is still protective.

6. Immunization of Preterm and Low Birth Weight Infants
Preterm infants are at increased risk of experiencing complications of vaccine-preventable diseases, which are particularly severe in young infants, especially those born preterm (gestational age <37 weeks) or low birthweight (<2,500 g) infants. 
The increased risk from infections is mainly because immune defenses are functionally impaired in early life.
The seriousness of the infectious problems of premature infants is proportional to how premature they are, but irrespective of this, they are more serious than those of full-term infants because their immune system is compromised to a greater extent. 

7. Passive Immunity in Preterm Infants
Transplacental transfer of maternal immunoglobulin G (IgG) that can protect an infant against some vaccine preventable diseases is affected by a range of factors including the mother’s past exposure to the disease and vaccination history, antibody half-life and the infant’s gestational age.
Infants born at less than 32 weeks gestation have significantly less IgG compared with those born at weeks. Furthermore, IgG wanes more rapidly rendering preterm infants at increased and earlier risk for vaccine preventable diseases

8. Immunization of Preterm and Low Birth Weight Infants
Larger premature infants mount immune responses to vaccines similar to those of full-term infants, but very premature infants (<28-32 weeks' gestation at birth) may have specific defects in vaccine responsiveness.
Although there are minor differences in immunogenicity, the immune responses to diphtheria, tetanus, pertussis, and polio antigens are similar between full-term and premature infants.
Few data on influenza vaccine in premature infants are available, but infants with pulmonary disease may respond less robustly than others.
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.

9. Immunization of Preterm and Low Birth Weight Infants Diphtheria, Tetanus, Pertussis, H flu and Polio
Several studies conducted in the past decade have confirmed previous findings of acceptable safety, immunogenicity, and efficacy of DTaP, diphtheria and tetanus toxoids and whole-cell pertussis (DTaP), Hib, oral poliovirus (OPV), and IPV vaccines in preterm infants (including those of ELBW) beginning at a chronologic age of 2 months.
The safety of DTaP, Hib, and IPV vaccines given to PT and LBW infants is comparable to that in FT infants, with no increase in vaccine adverse events noted

10. Immunization of Preterm and Low Birth Weight Infants Pneumococcal conjugate vaccine
Pneumococcal conjugate vaccine is efficacious in premature infants.
Nearly 38,000 infants participated in clinical trials using PCV7, many of whom were preterm and low birth weight. After the initial 3 doses of PCV7, PT infants demonstrated immune responses to all 7 pneumococcal serotype components of PCV7 that were equivalent to those found in FT infants. None of the PT and LBW infants receiving PCV7 in the trial contracted invasive pneumococcal disease attributable to vaccine serotypes.
The safety and immunogenicity PCV13 were shown to be non-inferior to that of Prevenar® in full term healthy infants and toddlers, a condition of licensure. Equivalent safety, tolerability and immunogenicity profiles of PCV13 in preterm and/or low birth weight infants can be inferred from the profile for Prevenar®

11. Immunization of Preterm and Low Birth Weight Infants 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 1st 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.

13. Immunization of Preterm and Low Birth Weight Infants Influenza Vaccine
As with all children, PT and LBW infants are at increased risk of excess morbidity from influenza virus infections.
Few data on influenza vaccine in premature infants are available, but infants with pulmonary disease may respond less robustly than others.
Although cell-mediated responses often were depressed in PT infants with more advanced CLD, nearly all PT infants, regardless of their health status and previous influenza immunization history, were able to achieve and sustain protective concentrations of antibody to the 3 strains of influenza virus contained in influenza vaccine.

14. Outside of the US Bacille Calmette Guérin vaccine
Bacille Calmette Guérin vaccine appears to be most immunogenic if delayed until at least weeks' postmenstrual age in very premature infants, although there may be non-specific advantages to its earlier administration.

15. Immunization of Preterm and Low Birth Weight Infants
Preterm infants are also less likely to receive immunizations on time.
Premature infants are not adequately immunized because of fear of adverse reactions and poor antibody response to the immunizations, lack of adequate muscle mass for the injections, or the premature infant simply being "too small" or "too sick" to immunize.
Despite established recommendations that preterm infants be immunized on the same schedule as term infants, with a few exceptions for specific vaccines, considerable immunization delays are reported. 
Do not adjust age for preterm birth
Neonatal intensive care units and other hospital areas where premature infants may remain hospitalized for prolonged periods should have immunization programs in place.

16. Immunization of Preterm and Low Birth Weight Infants
Premature infants are at significant risk for decisions from healthcare providers that delay beginning and completing their vaccine regimens. A major challenge facing those who care for these infants is the provision of timely immunization.
Overall, the data indicate that premature infants should follow the same vaccination schedule as that generally used for full-term infants, without correcting for prematurity and regardless of birth weight.
Vaccination of very-low-birth-weight infants in the US and elsewhere is significantly delayed, especially in infants with a birth-weight of < 1000 g and lower gestational age.
Urgent educational interventions targeting physicians and nurses should be implemented in order to improve vaccination rates and timing in these high risk populations.

18. SUMMARY
Timing
Medically stable PT and LBW infants should receive all routinely recommended childhood vaccines at the same chronologic age as recommended for FT infants. Under most circumstances, gestational age at birth and birth weight should not be limiting factors when deciding whether a PT or LBW infant is to be immunized on schedule. Infants with birth weight less than 2000 g, however, may require modification of the timing of hepatitis B immunoprophylaxis depending on maternal HBsAg status.
Dosing
Vaccine dosages normally given to FT infants should not be reduced or divided when given to PT and LBW infants.

19. OTHER STRATEGIES…. What else can we do?
For other vaccine-preventable diseases that specifically target (eg, group B Streptococcus) or are particularly severe (eg, pertussis) in preterm and term infants or for which no vaccine is licensed in this age group (eg, influenza), other immunization strategies such as maternal immunization or targeted immunization may reduce morbidity and mortality.

20. Cocoon Strategy and The Newborn
What Does it Mean to Cocoon a Newborn?
I urge parents to cocoon their babies; that is, provide a family of surrounding protection by having every single child and adult immunized against whooping cough, influenza, and other vaccine- preventable illnesses.
By surrounding a baby with only immunized people, you cocoon the baby against serious infections.

21. The Importance of Cocconing
Whooping cough is a highly infectious respiratory illness spread by sneezing and coughing that can be deadly to young infants. Getting a tetanus, diphtheria, acellular pertussis (Tdap) shot is the best way to avoid getting whooping cough.
Amid an epidemic, we worry most about newborns because they are most vulnerable to complications and lack vaccine protection.
If every child and adult who surrounds a newborn gets a Tdap shot, the likelihood of the baby getting whooping cough approaches zero.
Most newborns get whooping cough from their family or adults around them.

22. summary
If preterm babies get the infections that vaccines can prevent, they have a greater chance of having disease-related problems.
All of the available vaccines are safe when given to preterm and low birth weight babies.
Any side effects associated with the vaccines are similar in both full- term and preterm babies.

23. Immunization of Preterm and Low Birth Weight Infants, Thomas N
Immunization of Preterm and Low Birth Weight Infants, Thomas N. SaariPediatrics 2003;112;193