Why is the combo MMRV (Measles, Mumps, Rubella, Varicella) vaccine not recommended for 12-month-old children?

From the Guidelines

The MMRV (Measles, Mumps, Rubella, Varicella) combination vaccine is not recommended for 12-month-old children due to an increased risk of febrile seizures. Instead, healthcare providers recommend administering the MMR and varicella vaccines separately at this age. Studies have shown that children aged 12-23 months who receive the MMRV vaccine have approximately twice the risk of developing fever and febrile seizures compared to those who receive the MMR and varicella vaccines separately, with approximately one extra febrile seizure for every 2,300–2,600 MMRV vaccine doses 1. This risk is highest 5-12 days after vaccination. The separate administration approach provides the same protection against these diseases while reducing this specific safety concern. For older children, typically those 4-6 years receiving their second dose, the MMRV vaccine is considered appropriate as the risk of febrile seizures is much lower in this age group. Some key points to consider when making vaccination decisions include:

• The benefits and risks of both vaccination options should be discussed with parents or caregivers, as recommended by the CDC 1.
• A personal or family history of seizures is a precaution for MMRV vaccination, and children with such a history should generally be vaccinated with MMR and varicella vaccines separately 1.
• The American Academy of Pediatrics recommends that either MMR and varicella vaccines separately or the MMRV be used for the first dose of measles, mumps, rubella, and varicella vaccines administered at 12 through 47 months of age, but use of MMRV vaccine generally is preferred over separate injections of MMR and varicella vaccines for the second dose at any age (15 months to 12 years) or for the first dose at age ≥48 months 1. Parents should discuss their child's specific health history with their healthcare provider when making vaccination decisions, as individual factors may influence the recommendation. Key considerations for healthcare providers include:
• The epidemiology of febrile seizures, with approximately 97% of febrile seizures occurring in children aged ≤47 months 1.
• The importance of using tools such as Vaccine Information Statements to help parents or caregivers understand the risks and benefits of vaccination options 1.

From the Research

Risk of Febrile Seizures

• The combination measles-mumps-rubella-varicella (MMRV) vaccine may increase the risk of febrile seizures relative to the separate vaccines (MMR and varicella) previously administered 2, 3.
• Studies have shown that the risk of seizures 7 to 10 days after vaccination is twice as high with MMRV as with MMR+V (relative risk 1.99,95% confidence interval 1.30-3.05) 2.
• The excess absolute risk of seizures was 3.52 seizures per 10 000 doses of MMRV relative to MMR+V 2.
• Another study found that MMRV vaccine recipients had a higher risk of seizure during days 7 to 10 after vaccination compared to those who received MMR + varicella vaccines (relative risk: 1.98,95% confidence interval: 1.43-2.73) 3.

Recommendations and Practices

• The Advisory Committee on Immunization Practices (ACIP) recommended in 2009 the use of measles, mumps and rubella vaccine (MMR) and varicella vaccines (V) given separately (MMR+V) rather than combination MMRV as the first dose of MMR-containing vaccine to infants 4.
• A survey of pediatricians and family physicians found that few physicians would recommend MMRV to a healthy 12-15-month-old child after being informed of the increased risk of febrile seizures 5.
• The factor most frequently reported as "very important" in the decision to recommend MMRV or MMR+V was ACIP/AAFP/AAP recommendations 5.

Immunogenicity and Tolerability

• The immunogenicity of MMRV vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster vaccines 6.
• The tolerability profile of MMRV vaccine was comparable to that of separately administered MMR plus varicella zoster vaccines or of MMR vaccine alone 6.
• Injection-site redness and fever were the most frequent adverse events in both groups 6.