Active immunization of premature and low birth-weight infants: a review of immunogenicity, efficacy, and tolerability.

Preterm infants are at increased risk of disease and hospitalization from a number of vaccine-preventable diseases. However, these same infants have immunologic immaturities that may impact vaccine responses. 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 enough between full-term and premature infants that clinical consequences are unlikely to result. However, the immunogenicity of Haemophilus influenzae type b conjugate vaccines varies widely among studies of premature infants, and may be affected by the choice of conjugate protein, inclusion in a combination vaccine, and by an infant's overall health. Pneumococcal conjugate vaccine is efficacious in larger premature infants, but little information is available about immunogenicity in smaller premature infants. Meningococcal group C conjugate vaccine appears immunogenic in even very premature infants, but the duration of immunity may be limited. Hepatitis B vaccine given at birth appears poorly immunogenic in infants with birth weights <1500-2000 g, with delay in the administration of the first dose yielding improved immunogenicity. Few data on influenza vaccine in premature infants are available, but infants with pulmonary disease may respond less robustly than others. Bacille Calmette Guérin vaccine appears to be most immunogenic if delayed until at least 34-35 weeks' postmenstrual age in very premature infants, although there may be non-specific advantages to its earlier administration. Premature infants may have persistently lower antibody titers than full-term infants, even years after initial immunization. Sick premature infants experience increased episodes of apnea or cardiorespiratory compromise following vaccine administration, necessitating careful monitoring. Specific factors that impair immune response, quality of the immune response, and safety and immunogenicity evaluation of new vaccines in premature infants are topics needing further research. 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.