Apnea after immunization of preterm infants*

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Objective: To determine the frequency of adverse reactions, particularly the occurrence of apnea, among preterm infants after immunization with diphtheria and tetanus toxoids and whole cell pertussis vaccine adsorbed (DTP) and Haemophilus influenzae type b conjugate (HibC) vaccine in the neonatal intensive care unit.

Study design: After the occurrence of apnea in two preterm infants following immunization with DTP and HibC, a prospective surveillance of 97 preterm infants younger than 37 weeks of gestation who were immunized with DTP (94 also received HibC at the same time) in the neonatal intensive care unit was performed to assess the frequency of adverse reactions and in particular, the occurrence of apnea. For each infant, data were recorded for a 3-day period before and after receipt of the immunization.

Results: The majority of preterm infants tolerated immunizations with DTP and HibC without ill effects. However, 12 (12%) infants experienced a recurrence of apnea, and 11 (11%) had at least a 50% increase in the number of apneic and bradycardic episodes in the 72 hours after immunization. This occurred primarily among smaller preterm infants who were immunized at a lower weight (p=0.01), had experienced more severe apnea of prematurity (p=0.01), and had chronic lung disease (p=0.03).

Conclusion: The temporal association observed between immunization of preterm infants and a transient increase or recurrence of apnea after vaccination merits further study. Cardiorespiratory monitoring of these infants after immunization may be advisable.

Section snippets

METHODS

The study population for the prospective evaluation of the potential adverse effects of immunization on preterm infants consisted of 101 consecutive premature infants younger than 37 weeks of gestation who received an intramuscular injection of DTP vaccine (0.5 ml, Lederle Laboratories) in the NICU at Parkland Memorial Hospital during a 17-month period (Nov. 14, 1991, through April 21, 1993).

Four of the 101 infants were excluded from the study analysis. One had CLD and oxygen requirement at 58

Patient characteristics

The study population consisted of 97 infants; there were 50 girls and 47 boys. The mean birth weight was 991 ± 296 gm (range 460 to 2620 gm) and mean gestational age was 28 ± 2 weeks (range 24 to 34 weeks). Median Apgar scores were 4 and 7 at 1 and 5 minutes, respectively. The majority of the subjects were black (47%) and Latin-American infants (33%).

The majority (62/97, 64%) of infants had hyaline membrane disease; in 41 (42%) CLD developed. Ninety-three (96%) infants had experienced apnea of

DISCUSSION

In this prospective evaluation, we found that there was a transient recurrence (12%) or increase in apneic episodes (11%) observed in immunized preterm infants that coincided with the administration of DTP immunization. Because systemic and local reactions are significantly more frequent after immunization with DTP than after diphtheria and tetanus toxoids vaccine (adsorbed) alone,8, 9 it could be postulated that the apnea is related to the pertussis component of the vaccine, but this is an

Acknowledgements

We thank Maria Paris, MD, for assistance in performing the statistical analyses; Fiker Zeray, RN, and N. Kristine Leos, BS, for assistance in data collection and entry; and John D. Nelson, MD, for review of the manuscript.

References (17)

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*

Presented in part at the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), New Orleans, La., Oct. 17–20, 1993.

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