Adverse Events After MMR or MMRV Vaccine in Infants

In This Article

Abstract and Introduction

Abstract

Background: In the United States, measles is resurging, with more than 700 confirmed cases since January 2014. During measles outbreaks, vaccination as early as at 6 months of age is sometimes recommended for infants who are at risk for exposure.

Methods: We searched the Vaccine Adverse Event Reporting System for reports of measles, mumps and rubella vaccine combined or measles, mumps, rubella and varicella vaccine combined vaccination in children less than 9 months of age. We performed a clinical assessment of each report and summarized the frequency, range, onset time and severity of adverse events.

Results: After excluding 346 reports because they were duplicates or because they contained insufficient information about the child's age or vaccine(s), we retained 204 reports in the analysis, including 35 (17%) that were serious. Among the 169 nonserious reports, more than half (88; 52%) described a vaccination error without any adverse event per se. Other nonserious reports described fever, injection reactions and gastrointestinal symptoms. Serious adverse events included developmental disorders, fever and fussiness. There were 44 reports of fever, but only 4 cases began 5–12 days after immunization, the peak risk window. The vast majority of fever reports listed concomitant vaccines, such as diphtheria and tetanus toxoids, acellular or whole-cell pertussis vaccine.

Conclusions: This review did not identify any major safety concerns. These findings may facilitate discussions about the risks and benefits of vaccinating infants who are potentially exposed to this life-threatening disease.

Introduction

In the United States, measles has reached a high record because indigenous circulation was eliminated in 2000, with more than 700 confirmed cases since January 2014.^[1–3] Pneumonia, hepatitis and other serious complications have resulted in hospitalization.^[1] In outbreaks in the United States since 2008, confirmed cases of measles have affected more than 100 infants.^[3] Thus, measles remains a critical public health concern.^[4]

The Advisory Committee on Immunization Practices in the United States currently recommends that the first dose of measles, mumps and rubella (MMR) virus vaccine combined be given to children on or after their first birthday.^[5] During outbreaks or before travel to a measles-endemic area,^[6] vaccination as early as at 6 months of age (followed by routine vaccination at 12–15 months and 4–6 years of age) may be recommended.^[5,6] Measles vaccine was initially licensed for routine use at 9 months of age.^[7] Because monovalent measles vaccine is no longer distributed in the United States,^[5] MMR vaccine is used for active immunization against measles. Although effectiveness and immunogenicity of monovalent measles vaccine at 6 months of age have been evaluated,^[8–11] few trials evaluating the safety of MMR in very young infants have been performed. In a randomized trial among infants 8 and 12 months old, He et al^[12] evaluated the safety of an MMR vaccine manufactured by the Shanghai Institute of Biological Products Company (Shanghai, China). However, similar trials using the US-licensed MMR vaccine have not been conducted.

Because of the resurgence of measles in the United States,^[1–3] immunization of young infants may be necessary under certain circumstances. Understanding the adverse event profile of MMR in this age group is therefore a matter of public health exigency. To address this important question, we searched the Vaccine Adverse Event Reporting System (VAERS) and reviewed reports following MMR or measles, mumps, rubella and varicella (MMRV) virus vaccine combined immunization in infants younger than 9 months of age.

Table 1. Adverse Events Reported After MMR or MMRV Vaccination Among Infants <9 Mo of Age
Principal Clinical Condition or Category*	Nonserious (n = 169)	Serious† (n = 35)	Total (n = 204)
Vaccination error; no adverse event reported	88	1	89
Fever	37	7	44
Injection site reaction	13	0	13
Gastrointestinal signs/symptoms	10	0	10
Developmental disorder	2	9	11
Fussiness/agitation	4	5	9
Rash or other dermatologic condition	5	2	7
Seizure/altered level of consciousness	4	3	7
Respiratory condition	1	2	3
Adverse event attributed to concomitant vaccine	2	2	4
Other‡	3	4	7

*Primary adverse event based on clinical review of the VAERS report, follow-up reports, medical records and other relevant documents.
†Events reported as disabling, life-threatening, fatal, requiring hospital admission, prolonging a hospital stay, resulting in a congenital anomaly or requiring medical intervention to prevent such an outcome¹⁶ and other medically important conditions¹⁶ are also included.
‡Nonserious: torticollis, day-night inversion and nonspecific tremor; serious: anemia, measles, anorexia and unspecified adverse event

Table 2. Fever Reported After MMR or MMRV Vaccination Among Infants <9 Mo of Age
Feve	n = 44
Age (mo)
Age < 3 mo	12 (27%)
3 ≤ age < 6 mo	14 (32%)
6 ≤ age < 9 mo	18 (41%)
Mean	4.5
Median	4
Sex
Female	14 (32%)
Male	30 (68%)
Seriousness
Nonserious	37 (84%)
Serious*,¹⁶	7 (16%)
Report origin
United States	39 (89%)
Foreign or unknown	5 (11%)
Vaccines administered
MMR or MMRV alone	10 (23%)
MMR or MMRV with concomitant vaccines†	34 (77%)
Maximum temperature (°C)
n‡	24
Median	39.4
Mean	39.1
Range	37.2–41.1
Time to symptom onset
n‡	34
Median	9 h
Mean	3.5 d
Range	0–23 d
Fever beginning 5–12 d after MMR or MMRV⁶	4 (9%)
Febrile seizure occurring 5–12 d after MMR or MMRV⁶	1 (2%)

*Events reported as disabling, life-threatening, fatal, requiring hospital admission, prolonging a hospital stay, resulting in a congenital anomaly or requiring medical intervention to prevent such an outcome16 and other medically important conditions16 are also included.
†Among concomitant vaccines, the most commonly reported were diphtheria and tetanus toxoids, acellular or whole-cell pertussis vaccine, Haemophilus influenzae type b vaccine and hepatitis B vaccine.
‡In some cases, the maximum temperature and symptom onset time were not reported.