Delaying MMR, MMRV vaccines doubled febrile seizure risk

WASHINGTON – Delaying some early childhood vaccinations seems to double the risk that a child will experience a vaccine-related febrile seizure.

The finding is concerning as more and more parents ask about delaying or spacing out vaccines to avoid perceived harm from giving "too many [vaccines], too close together," Dr. Simon J. Hambidge said at the annual meeting of the Pediatric Academic Societies.

The observed risk in febrile seizures with vaccine delays may be explained physiologically by the child’s increased ability to mount a vigorous immune response. When children mount a better immune response, they’re more likely to have a fever. Further, febrile seizures begin to rise in toddlers between the ages of 16 and 23 months.

"It’s a complicated relationship. ... I think it’s clear that there is something going on at this time of life that’s increasing the risk of febrile seizures," said Dr. Hambidge, professor of pediatrics at the Colorado School of Public Health, Denver.

Dr. Hambidge examined the rate of vaccine-related febrile seizures in a cohort of 324,000 children who were born from 2004-2008. The study population was derived from eight large health care sites, all of which participate in the Vaccine Safety DataLink program. All children were seen in an emergency department or hospital for a febrile seizure at 93-730 days of age.

A self-controlled case series analysis accounted for associations between time (pre- and post vaccination) and exposure (vaccinated or not during the exposure windows). Based on known risks for fever after vaccination, the exposure risk window was set at 0-2 days after vaccination for inactive vaccines; the exposure risk window was 7-10 days afterward for live vaccines. The final measure was an incidence rate ratio (IRR).

The first analysis examined febrile seizures in the group that had infant vaccines administered according to the usual schedule. These included the DTaP (diphtheria, tetanus, and pertussis), conjugated pneumococcal, polio, coronavirus, Haemophilus influenzae type b, and rotavirus vaccines.

"There were no statistically significant differences in the IRR after any of these vaccines, whether they were given on time or delayed," Dr. Hambidge said. "I think this reflects the paucity of seizures generally seen during the first year of life."

For vaccines given during the second year of life, the IRR was examined for measles, mumps, rubella (MMR) and for measles, mumps, rubella, and varicella (MMRV) given on the usual schedule (12-15 months) and on a delayed schedule (16-23 months).

For babies who got the MMR on schedule, the IRR was 2.5, "corresponding to an attributable risk of about 1 [febrile seizure] in 4,000 doses," Dr. Hambidge said. When the MMR was delayed until the baby was 16-23 months old, the IRR significantly increased to 7.7 – an attributable risk of about 2 seizures per 4,000 doses.

A similar doubling of risk with the delayed schedule occurred with the MMRV vaccine, he said. Given at the normal schedule of 12-15 months, the IRR was 4.6, a risk of about one febrile seizure for every 2,000 vaccine doses. But when the MMRV was given at 16-23 months, the IRR rose to just above 15 – doubling the attributable risk to about 2 febrile seizures per 2,000 doses.

Parents should understand these risks but can be somewhat reassured that a febrile seizure isn’t generally a sign of something more sinister, Dr. Hambidge said in an interview.

"Kids with postvaccination febrile seizures have acute febrile seizures. None have gone on to develop epilepsy or have lasting problems. So the seizures are scary for parents, but typically result in a trip to the emergency department and then recovery. Still, it’s better to get the vaccines on time, rather than late, to minimize this risk," he said.

This study was funded through a subcontract with America’s Health Insurance Plans from the Centers for Disease Control and Prevention. Dr. Hambidge had no financial disclosures.

[email protected]

WASHINGTON – Delaying some early childhood vaccinations seems to double the risk that a child will experience a vaccine-related febrile seizure.

The finding is concerning as more and more parents ask about delaying or spacing out vaccines to avoid perceived harm from giving "too many [vaccines], too close together," Dr. Simon J. Hambidge said at the annual meeting of the Pediatric Academic Societies.

The observed risk in febrile seizures with vaccine delays may be explained physiologically by the child’s increased ability to mount a vigorous immune response. When children mount a better immune response, they’re more likely to have a fever. Further, febrile seizures begin to rise in toddlers between the ages of 16 and 23 months.

"It’s a complicated relationship. ... I think it’s clear that there is something going on at this time of life that’s increasing the risk of febrile seizures," said Dr. Hambidge, professor of pediatrics at the Colorado School of Public Health, Denver.

Dr. Hambidge examined the rate of vaccine-related febrile seizures in a cohort of 324,000 children who were born from 2004-2008. The study population was derived from eight large health care sites, all of which participate in the Vaccine Safety DataLink program. All children were seen in an emergency department or hospital for a febrile seizure at 93-730 days of age.

A self-controlled case series analysis accounted for associations between time (pre- and post vaccination) and exposure (vaccinated or not during the exposure windows). Based on known risks for fever after vaccination, the exposure risk window was set at 0-2 days after vaccination for inactive vaccines; the exposure risk window was 7-10 days afterward for live vaccines. The final measure was an incidence rate ratio (IRR).

The first analysis examined febrile seizures in the group that had infant vaccines administered according to the usual schedule. These included the DTaP (diphtheria, tetanus, and pertussis), conjugated pneumococcal, polio, coronavirus, Haemophilus influenzae type b, and rotavirus vaccines.

"There were no statistically significant differences in the IRR after any of these vaccines, whether they were given on time or delayed," Dr. Hambidge said. "I think this reflects the paucity of seizures generally seen during the first year of life."

For vaccines given during the second year of life, the IRR was examined for measles, mumps, rubella (MMR) and for measles, mumps, rubella, and varicella (MMRV) given on the usual schedule (12-15 months) and on a delayed schedule (16-23 months).

For babies who got the MMR on schedule, the IRR was 2.5, "corresponding to an attributable risk of about 1 [febrile seizure] in 4,000 doses," Dr. Hambidge said. When the MMR was delayed until the baby was 16-23 months old, the IRR significantly increased to 7.7 – an attributable risk of about 2 seizures per 4,000 doses.

A similar doubling of risk with the delayed schedule occurred with the MMRV vaccine, he said. Given at the normal schedule of 12-15 months, the IRR was 4.6, a risk of about one febrile seizure for every 2,000 vaccine doses. But when the MMRV was given at 16-23 months, the IRR rose to just above 15 – doubling the attributable risk to about 2 febrile seizures per 2,000 doses.

Parents should understand these risks but can be somewhat reassured that a febrile seizure isn’t generally a sign of something more sinister, Dr. Hambidge said in an interview.

"Kids with postvaccination febrile seizures have acute febrile seizures. None have gone on to develop epilepsy or have lasting problems. So the seizures are scary for parents, but typically result in a trip to the emergency department and then recovery. Still, it’s better to get the vaccines on time, rather than late, to minimize this risk," he said.

This study was funded through a subcontract with America’s Health Insurance Plans from the Centers for Disease Control and Prevention. Dr. Hambidge had no financial disclosures.

[email protected]

WASHINGTON – Delaying some early childhood vaccinations seems to double the risk that a child will experience a vaccine-related febrile seizure.

The finding is concerning as more and more parents ask about delaying or spacing out vaccines to avoid perceived harm from giving "too many [vaccines], too close together," Dr. Simon J. Hambidge said at the annual meeting of the Pediatric Academic Societies.

The observed risk in febrile seizures with vaccine delays may be explained physiologically by the child’s increased ability to mount a vigorous immune response. When children mount a better immune response, they’re more likely to have a fever. Further, febrile seizures begin to rise in toddlers between the ages of 16 and 23 months.

"It’s a complicated relationship. ... I think it’s clear that there is something going on at this time of life that’s increasing the risk of febrile seizures," said Dr. Hambidge, professor of pediatrics at the Colorado School of Public Health, Denver.

Dr. Hambidge examined the rate of vaccine-related febrile seizures in a cohort of 324,000 children who were born from 2004-2008. The study population was derived from eight large health care sites, all of which participate in the Vaccine Safety DataLink program. All children were seen in an emergency department or hospital for a febrile seizure at 93-730 days of age.

A self-controlled case series analysis accounted for associations between time (pre- and post vaccination) and exposure (vaccinated or not during the exposure windows). Based on known risks for fever after vaccination, the exposure risk window was set at 0-2 days after vaccination for inactive vaccines; the exposure risk window was 7-10 days afterward for live vaccines. The final measure was an incidence rate ratio (IRR).

The first analysis examined febrile seizures in the group that had infant vaccines administered according to the usual schedule. These included the DTaP (diphtheria, tetanus, and pertussis), conjugated pneumococcal, polio, coronavirus, Haemophilus influenzae type b, and rotavirus vaccines.

"There were no statistically significant differences in the IRR after any of these vaccines, whether they were given on time or delayed," Dr. Hambidge said. "I think this reflects the paucity of seizures generally seen during the first year of life."

For vaccines given during the second year of life, the IRR was examined for measles, mumps, rubella (MMR) and for measles, mumps, rubella, and varicella (MMRV) given on the usual schedule (12-15 months) and on a delayed schedule (16-23 months).

For babies who got the MMR on schedule, the IRR was 2.5, "corresponding to an attributable risk of about 1 [febrile seizure] in 4,000 doses," Dr. Hambidge said. When the MMR was delayed until the baby was 16-23 months old, the IRR significantly increased to 7.7 – an attributable risk of about 2 seizures per 4,000 doses.

A similar doubling of risk with the delayed schedule occurred with the MMRV vaccine, he said. Given at the normal schedule of 12-15 months, the IRR was 4.6, a risk of about one febrile seizure for every 2,000 vaccine doses. But when the MMRV was given at 16-23 months, the IRR rose to just above 15 – doubling the attributable risk to about 2 febrile seizures per 2,000 doses.

Parents should understand these risks but can be somewhat reassured that a febrile seizure isn’t generally a sign of something more sinister, Dr. Hambidge said in an interview.

"Kids with postvaccination febrile seizures have acute febrile seizures. None have gone on to develop epilepsy or have lasting problems. So the seizures are scary for parents, but typically result in a trip to the emergency department and then recovery. Still, it’s better to get the vaccines on time, rather than late, to minimize this risk," he said.

This study was funded through a subcontract with America’s Health Insurance Plans from the Centers for Disease Control and Prevention. Dr. Hambidge had no financial disclosures.

[email protected]