Preterm Immunization: Current Concepts and Challenges

Preterm Immunization: Current Concepts and ChallengesWorldwide, every year nearly 15 million premature babies are born and out of them, 3.5 million are born in India, i.e., nearly 1/4th of the global prematurity burden is being handled by India itself.Approximately, 20% of them are either very low birth weight (LBW) (<1500 g) or very preterm (<33 weeks) who often have prolonged stay in neonatal intensive care unit (NICU) after birth due to prematurity and its associated complications.Epidemiological studies show that premature infants have an increased incidence and severity of vaccine-preventable diseases (VPD) such as pertussis, invasive pneumococcal diseases, and Haemophilus influenzae type b (HiB).The exact burden of VPD in lower and middle-income countries is not known.Although several governing bodies have advised for timely vaccination of premature infants using the same schedule as recommended for full-term infants without any correction for prematurity and LBW, still their vaccination is often delayed.Some of the notable reasons for this undue delay could be due to the lack of knowledge among healthcare professionals (HCP) as well among parents regarding the safety and efficacy of vaccines in these premature infants.The concern could be due to the occurrence of adverse events such as fever, irritability, seizure, or risk increase in cardiorespiratory instability, e.g., apnea and tachycardia.Vaccinations are affordable preventive measures to reduce the burden of infections in infants and to save millions of lives.Preterm infants are at particular risk for vaccine-preventable diseases, i.e., 2.5-5-fold relative risk to suffer from severe rotavirus infection, invasive pneumococcal disease or pertussis.However, the historical scepticism to vaccinate most susceptible preterm infants has hampered schedule-based vaccinations according to chronological age in many neonatal intensive care units (NICUs), special care nurseries and outpatient settings.Particular reasons for this delay include assumptions on (i) "deficient" vaccineinduced immune responses, (ii) tipping the balance toward proinflammation through vaccines during vulnerable periods of disease trajectories (e.g., infection risk, developmental window for neurological sequelae, chronic lung disease and retinopathy) or (iii) potential harm of immunizations in the timeframe of expected interventions (i.e., surgery).The observational data from large preterm cohorts such as the German Neonatal Network (GNN) indicate that timing of vaccinations based on recommended schedule does not aggravate the risk for prematurity-related diseases such as retinopathy of prematurity (ROP) and CLD in verylow-birth-weight infants (VLBWI).Despite evidence about the tolerability, safety, immunogenicity and efficacy of immunizations, the real-life implementation of schedule-based vaccinations by healthcare professionals and parents still remains a challenge.Preterm infants are at particularly high risk for infectious diseases.As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations.However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants' distinct immunological features.A significant proportion of infants remains un-or under-immunized when discharged from primary hospital stay.Educating healthcare professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants.The fetal immune system is highly specialized which is to generate both tolerogenic and protective immune responses to tolerate both self and maternal antigens.For a number of antigens, the antibody response to initial doses of vaccines may be lower in preterm infants than in term infants, but protective concentrations are often achieved and memory successfully induced.Vaccines are immunogenic, safe and well tolerated in preterm infants.Preterm infants should be vaccinated using the same schedules as those usually recommended for full-term infants, with the exception of the hepatitis B vaccine.