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Apnea After 2-Month Vaccinations in Hospitalized Preterm Infants: A Randomized Clinical Trial
Rachel G Greenberg1,2, Wes Rountree3, Mary Allen Staat4
1Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
Insights
Vaccinating preterm infants at 2 months increases the risk of apnea, but the number and duration of events remain similar to unvaccinated infants. Current vaccination guidelines for preterm infants are appropriate, with clinicians advised to provide anticipatory guidance on apnea risk.
Area of Science:
- Neonatal Medicine
- Pediatric Vaccinology
- Clinical Trials
Background:
- Preterm infants typically receive vaccinations at the same age as term infants.
- There are inconsistent findings regarding the risk of postvaccination apnea in preterm infants.
Purpose of the Study:
- To compare the incidence of apnea and adverse events in hospitalized preterm infants within 48 hours after receiving 2-month vaccinations versus no vaccinations.
Main Methods:
- A randomized, open-label clinical trial involving preterm infants (<33 weeks gestational age) at 6-12 weeks postnatal age.
- Infants were randomized to receive 2-month vaccines or no vaccines during the study period.
- Cardiorespiratory monitoring was conducted for 48 hours post-vaccination or randomization.
Main Results:
- The proportion of infants experiencing apnea was higher in the vaccinated group (24%) compared to the unvaccinated group (10%) (aOR, 2.70; P=.01).
- No significant differences were observed in the mean number or duration of apneic episodes between the groups.
- No serious adverse events were reported during the 48-hour monitoring period.
Conclusions:
- Hospitalized preterm infants show an increased odds of apnea post-vaccination, but the clinical significance appears minimal.
- The findings support the current vaccination schedule for preterm infants, emphasizing the need for continued evidence-based anticipatory guidance on potential apnea.
- The study highlights the safety of routine immunizations in this vulnerable population.
Importance:
Preterm infants are recommended to receive most vaccinations at the same postnatal age as term infants. Studies have inconsistently observed an increased risk for postvaccination apnea in preterm infants.
Objective:
To compare the proportions of hospitalized preterm infants with apnea and other adverse events in the 48 hours after 2-month vaccinations vs after no vaccinations.
Design, Setting, And Participants:
This randomized, open-label clinical trial took place at 3 US neonatal intensive care units between August 2018 and October 2021. Infants between 6 and 12 weeks' postnatal age who were born at less than 33 weeks' gestational age and were eligible to receive 2-month vaccines were included.
Intervention:
Infants were randomized 1:1 to vaccinated (received vaccines within 12 hours of randomization) or unvaccinated (no vaccines received during the study period) groups. Cardiorespiratory data were collected during the 48 hours after vaccination or randomization (unvaccinated group).
Main Outcomes And Measures:
The primary outcome was apnea, defined as a respiration pause greater than 20 seconds or a respiration pause greater than 15 seconds with associated bradycardia less than 80 beats per minute. Other outcomes included the number and duration of apnea episodes, serious adverse events, respiratory support escalation, and receipt of positive pressure ventilation.
Results:
Of 223 randomized infants (117 female; median [range] gestational age, 27.6 [23.0-32.9] weeks), 107 (48%) were vaccinated, and 116 (52%) were unvaccinated. For 2 infants in the vaccinated group, the primary outcome was unable to be assessed. The proportion of infants with 1 or more apnea event was 25 of 105 (24%) in the vaccinated group vs 12 of 116 (10%) in the unvaccinated group (adjusted odds ratio, 2.70; 95% CI, 1.27 to 5.73; P = .01). The mean number of apneic episodes did not significantly differ (model point estimate of difference, 0.54; 95% CI, -0.12 to 1.21) between the vaccinated (2.72) and unvaccinated (2.00) groups. The mean duration of apneic episodes did not significantly differ (model point estimate of difference, 4.6; 95% CI, -5.4 to 14.7) between the vaccinated (27.7) and unvaccinated (32.3) groups. No serious adverse events occurred during the 48-hour monitoring period. Other outcomes were not significantly different between groups.
Conclusions And Relevance:
In hospitalized preterm infants, the odds of apnea within 48 hours were higher after 2-month vaccinations vs after no vaccinations. The similar number and duration of apneic events and lack of serious adverse events suggest that current vaccination recommendations for hospitalized preterm infants are appropriate. Neonatal clinicians should continue providing evidence-based anticipatory guidance about postvaccination apnea risk.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03530124.
