Routine vaccines linked to higher risk of apnoea in hospitalized preterm infants

Hospitalized preterm infants who received routine 2-month vaccinations were more likely to experience an apnoea episode within 48 hours than those who did not receive any vaccinations, according to a recent study.

“Our findings of increased apnoeic events following vaccination in preterm infants are consistent with previous observational studies and warnings present in vaccine package inserts,” said the researchers.

The researchers conducted a multicentre, prospective, open-label trial involving 223 preterm infants (median gestational age 27.6 weeks) hospitalized since birth between August 2018 and October 2021 at three NICUs in the US. The participants were randomized 1:1 to receive 2 months of vaccination (n=107) or not (n=116). PCV13*, DTaP**, HBV***, IPV⁺, and HiB⁺⁺ were administered to the vaccinated groups within 12 hours of randomization. [JAMA Pediatr;doi:10.1001/jamapediatrics.2024.5311]

During the 48-hour monitoring period, a significantly higher proportion of vaccinated infants experienced ≥1 apnoea event than those who were unvaccinated (24 percent vs 10 percent; adjusted odds ratio [adjOR], 2.70; p=0.01).

Accordingly, when the primary and secondary outcomes were reanalysed in the intention-to-treat (ITT) and per-protocol populations, the adjusted odds of apnoea remained significantly higher in the vaccinated group than in the unvaccinated group (adjORs, 2.86 [ITT] and 3.22 [per-protocol]).

When the analysis was further stratified by postmenstrual age (PMA), infants with ≥1 apnoea event were also higher among the vaccinated group compared with the unvaccinated group, regardless of whether the infants were ≥37 (30 percent vs 6 percent; adjOR, 5.29) or <37 (20 percent vs 13 percent; adjOR, 1.84) weeks’ PMA.

“Notably, the association between vaccination and apnoea appeared to be stronger in infants with PMA ≥37 weeks compared with those with <37 weeks,” said the researchers. “While the trial was not designed to identify the reason for this apparent difference related to PMA, we hypothesize that this difference in association could be due to less caffeine exposure and a greater proportion of infants without respiratory support in the older PMA group.”

“Therefore, further study is warranted to explore whether prophylactic use of caffeine or respiratory support could reduce the incidence of apnoea following vaccination,” they noted.

As for secondary endpoints, no statistically significant differences were observed between the vaccinated and unvaccinated groups in terms of the number and duration of apnoeic episodes (mean 2.72 vs 2 and 27.7 vs 32.3 seconds, respectively).

In addition, the proportion of other secondary and exploratory outcomes did not differ between the two groups, the researchers noted.

“Overall, despite the higher odds of apnoea in the vaccinated group, the overall incidence of secondary outcomes, including escalation in respiratory support or receipt of positive pressure ventilation, was low,” said the researchers. “Apnoeic episodes were brief, and no infants experienced serious adverse events during the 48-hour monitoring period.”

“The study supports the current Advisory Committee on Immunization Practices recommendations to vaccinate hospitalized preterm infants at 2 months chronological age in most situations according to the same schedule and using the same contraindications and precautions as for full-term infants and children,” they noted.