Four Component Meningococcal Capsular Group B Vaccine in Preterm Infants

To the Editor—The four component meningococcal capsular group B vaccine (4CMenB) was introduced into the routine immunization schedule in the United Kingdom in September 2015 to protect against group B Neisseria meningitidis meningitis and septicemia. The vaccine is reactogenic in young infants, causing fever in 51% to 65% when coadministered with other vaccines [1, 2]. This finding led to the unprecedented recommendation that all infants be given prophylactic paracetamol (acetaminophen) with the vaccine. Preterm infants are immunized at the same chronological age and on the same schedule as are term infants, but they have higher rates of postimmunization adverse events (AEs), particularly infants born at <28 weeks’ gestation who are hospitalized in a neonatal unit when immunized [3]. Preterm infants were excluded from 4CMenB vaccine prelicensure trials, and no such trials have been registered with ClinicalTrials.gov (as of October 14, 2016). The administration of a reactogenic vaccine in this population has led to heightened concern about AEs, which might affect use of the vaccine in very preterm infants until they are discharged home and delay protection of this vulnerable group against meningococcal disease. For a study of rotavirus vaccine (RotaNeo) in hospitalized preterm infants, we recruited infants before and after introduction of the 4CMenB vaccine in the United Kingdom (ClinicalTrials.gov identifier NCT02252029), which provided a unique opportunity for us to compare preterm infants who did and those who did not receive the 4CMenB vaccine. The primary study objective was to establish the duration of fecal rotavirus vaccine excretion after immunization. Solicited and unsolicited AE reports were recorded from parents, nursing staff, and medical records contemporaneously up to 7 days after immunization. Sixty-four postimmunization data points were collected for each participant; we had no missing data. Of 17 infants who completed the study, 8 received the 4CMenB vaccine, and 9 did not; all of them received other routine immunizations. The overall mean gestational age at birth was 27.1 weeks (range, 24.0–29.6 weeks), and their mean age at immunization was 9.5 weeks; we found no differences between the infants who did and those who did not receive the 4CMenB vaccine (Table 1). Only 3 infants who were given the 4CMenB vaccine received paracetamol. Of the 5 who did not, 1 had a postimmunization fever and 3 had a low temperature in the 2 days after immunization. None of the infants who did not receive the 4CMenB vaccine had temperature instability. Overall, 4CMenB vaccine recipients were significantly more likely to have any temperature instability (50% vs 0%; P = .029). Decreased feeding and reduced activity were more common in the 4CMenB group, whereas irritability and crying occurred more frequently in the infants who did not receive the 4CMenB vaccine (Table 1), which might be attributable in part to the use of paracetamol in some of the 4CMenB vaccine recipients. Demographics and Rates of Postimmunization AEs in Infants Who Did and Those Who Did Not Receive 4CMenB Vaccine up to 2 and 7 Days After Immunization Abbreviation: 4CMenB, four component meningococcal capsular group B; AE, adverse event; GA, gestational age at birth; NA, not applicable; SD, standard deviation. Comparison of the 4CMenB versus non-4CMenB groups was performed using Fisher’s exact test. Bold type indicates a significant result (P < .05). One AE was classified as severe (day 1 after immunization). One AE was classified as severe (day of immunization). Three AEs were classified as severe (all on day 1 after immunization). Apnea, bradycardia, and desaturation. Apnea and desaturation in 1 infant and desaturation only in 3 infants. Event on day 7 after immunization required reintubation. Demographics and Rates of Postimmunization AEs in Infants Who Did and Those Who Did Not Receive 4CMenB Vaccine up to 2 and 7 Days After Immunization Abbreviation: 4CMenB, four component meningococcal capsular group B; AE, adverse event; GA, gestational age at birth; NA, not applicable; SD, standard deviation. Comparison of the 4CMenB versus non-4CMenB groups was performed using Fisher’s exact test. Bold type indicates a significant result (P < .05). One AE was classified as severe (day 1 after immunization). One AE was classified as severe (day of immunization). Three AEs were classified as severe (all on day 1 after immunization). Apnea, bradycardia, and desaturation. Apnea and desaturation in 1 infant and desaturation only in 3 infants. Event on day 7 after immunization required reintubation. This study has provided the first data on AEs in hospitalized preterm infants after being given the 4CMenB vaccine, and our results suggest an increase in some AEs with the 4CMenB vaccine, most notably temperature instability. Larger studies (with ~70 infants per group for 90% power with a 5% α value based on these data) are needed to inform guidance for monitoring postimmunization AEs in these infants and the use of prophylactic paracetamol, because low temperature was more common than fever. Disclaimer. The views presented in this article do not necessarily represent the views of the UK Department of Health or the Joint Committee on Vaccination and Immunization. Financial support. The RotaNeo study was funded by a grant awarded to M. S. by the University of Oxford Medical Research Fund (grant MRF/MT2013/2066). Potential conflicts of interest. M. S. has been an investigator on investigator-initiated research studies funded by Pfizer. A. J. P. is a Jenner Investigator and James Martin Senior Fellow and previously conducted research on behalf of Oxford University funded by vaccine manufacturers. M. S. and A. J. P. have not received any personal remuneration from vaccine manufacturers. A. J. P. is chair of the UK Department of Health’s (DH) Joint Committee on Vaccination and Immunization (JCVI). The other authors report no conflicts of interest. All authors have submitted the ICMJE Form for Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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