Preterm Infant Immunizations Are Safe Despite Apnea Risk

Source: Greenberg RG, Rountree W, Staat MA, et al. Apnea after 2-month vaccinations in hospitalized preterm infants: a randomized clinical trial. JAMA Pediatr. 2025;179(3):246-254; doi: 10.1001/jamapediatrics.2024.5311.Investigators from multiple institutions conducted a randomized clinical trial to assess the risk of apnea following 2-month vaccinations in preterm infants. Infants born at <33 weeks’ gestation who were 6–12 weeks old were enrolled in the study at 3 US NICUs. At enrollment, participants were randomized 1:1 to the vaccinated or unvaccinated groups. Those randomized to the vaccinated group received 13-valent pneumococcal conjugate, diphtheria and tetanus toxoids and acellular pertussis (DTaP), hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccines. Infants received continuous cardiorespiratory and oximetry monitoring for 48 hours after receiving vaccines, or for 48 hours after randomization for those in the unvaccinated group. The primary outcome was occurrence in the 48-hour monitoring period of ≥1 apneic episode, defined as a respiratory pause of ≥20 seconds or one of ≥15 seconds accompanied by a drop in heart rate to less than 80 beats per minute. The risk of apnea among infants in the vaccinated and unvaccinated groups were compared using the Mantel-Haenzel method, with stratification by site. Subgroup analyses were conducted in infants with a postmenstrual age (PMA) <37 or ≥37 weeks. Secondary outcomes included number of apneic episodes during the 48-hour monitoring period and duration of apneic episodes.There were 223 infants enrolled in the study, with 107 assigned to the vaccinated and 116 to the unvaccinated group. The median gestational age at birth in patients in the 2 treatment groups were 27.7 and 27.3 weeks, respectively, and the median PMA was 36.6 weeks in both groups. The proportion of infants in the vaccinated group with ≥1 apneic episode during the 48-hour monitoring period was 24% vs 10% in those randomized to the unvaccinated group (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.27, 5.73). Among those with a PMA ≥37 weeks, 30% of those receiving vaccines had ≥1 apneic episode, compared to 6% of those in the unvaccinated group (OR, 5.29; 95% CI, 1.39, 20.21). There was no significant increased risk of apnea in infants in the vaccinated group with a PMA <37 weeks (rates of apnea 20% compared to 13% for those in the unvaccinated group; OR, 1.84; 95% CI, 0.69, 4.95). There also were no significant differences between groups in mean number of apnea episodes or duration of episodes.The authors conclude that receipt of 2-month vaccines in preterm infants was associated with an increased risk of apnea in the 48-hour period following vaccination.Dr Beam has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Vaccination of preterm infants in the NICU is important but often challenging. Preterm infants are at increased risk of vaccine-preventable diseases but often underimmunized.1 One concern is the belief that immunizations may result in increased adverse events, including apneic events. Preterm infants often receive vaccinations over several days in order to decrease the risk of adverse events, such as apnea, without evidence that this decreases post-immunization effects.2 The authors in the current study aimed to determine if preterm infants receiving 2-month immunizations experienced an increase in apneic events and found that there was a statistically significant increase in apneic events in the 48 hours following 2-month immunizations in infants <33 weeks’ gestational age at birth. However, this did not result in any additional evaluation, including blood culture, and no serious adverse events, including increase in respiratory support.Prior evaluations of effects of immunizations in preterm infants have been published and range from no increase in apneic events3 to an increase in apneic events to increased sepsis evaluations.4 Overall, however, the authors of these publications continue to point to the safety and importance of immunization in preterm infants.There is variability in immunization practices for preterm infants, including waiting longer to administer the first set of immunizations, spacing them out over several days, and delaying vaccination in the setting of clinical instability or illness.2 However, for this group of infants at highest risk for serious adverse events from the vaccine-preventable illness itself, it is imperative to ensure appropriate and timely vaccination.Preterm infants ought to receive vaccinations in accordance with the CDC immunization schedule. Although there may be an increase in apneic episodes in the 48 hours post-immunization, this does not correlate with an increase in serious adverse events.It is important to note that the results of the current study apply only to hospitalized preterm infants and not to those who are outpatients.