No increase in cardiorespiratory events seen after diphtheria-tetanus-acellular pertussis immunization

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• Carbone T, McEntire B, Kissin D, Kelly D, Steinschneider A, Violaris K, et al. Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study. Pediatrics 2008;121:e1085-90
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Carbone T, McEntire B, Kissin D, Kelly D, Steinschneider A, Violaris K, et al. Absence of an increase in cardiorespiratory events after diphtheria-tetanus-acellular pertussis immunization in preterm infants: a randomized, multicenter study. Pediatrics 2008;121:e1085-90 

Question Among preterm infants (<37 weeks gestational age), does the administration of diphtheria-tetanus-acellular pertussis (DTaP) vaccine result in an increased number of cardiorespiratory events?

Design Randomized controlled trial.

Setting Ten neonatal intensive care units in the United States.

Participants A total of 191 preterm infants who were 56 to 60 days chronologic age at the time of enrollment.

Intervention The intervention group received DTaP vaccine, and the control group had their vaccination delayed by 4 days.

Outcomes The presence and number of prolonged apnea and prolonged bradycardia episodes, as detected by a 48-hour recording after immunization.

Main Results In the DTaP group, 16.1% experienced at least 1 episode of prolonged apnea compared with 20.4% of control infants (P > .05). One or more prolonged bradycardia events occurred in 58.1% of immunized infants and 56.1% of the control infants (P > .05). The immunization group and the control group each had an average of 0.5 episodes of prolonged apnea. The mean number of prolonged bradycardia episodes was 2.6 in the immunization group and 2.7 in the control group.

Conclusions Preterm infants who received DTaP at 2 months after birth were no more likely to experience prolonged apnea and bradycardia than were control infants. This study supports the American Academy of Pediatrics recommendation regarding DTaP immunization at 2 months of age for preterm infants.

Commentary This study is important because it is the first randomized trial to look at a possible relationship between the administration of DTaP in a population of preterm infants and the occurrence of prolonged episodes of apnea or bradycardia. Previous case reports and retrospective studies had shown an increase in these events, leading primary care physicians to delay vaccination of preterm infants, a practice which has conflicted with guidelines from the American Academy of Pediatrics. Notably, the authors found no difference in the overall rates of these events, either the total number or the number of more severe events. There are a couple of important caveats to these findings. First, these infants were all in neonatal intensive care units, so the results cannot be generalized to all preterm infants. Second, the study was not powered a priori. Post-hoc power calculations show that they were able to detect only rather large differences between the groups (at least an 89% increase in prolonged apnea and at least a 35% increase in prolonged bradycardia). It would be more reassuring to have a study with the power to detect even smaller differences. Third, there was a high dropout rate (18%), but the authors did a good job of accounting for all of the patients at the conclusion of the trial. This study is somewhat reassuring, but we need a larger trial, and one that also includes preterm infants who are home at 2 months.