Emory大学のDr. Meador らは、1999-2004年に米英の25のてんかんセンターで抗てんかん薬治療を受けている303人の妊婦を調査した。252人から生まれた258人の2-3才の子どもに認知評価を行った。そのうち53人がバルプロ酸を服用していた。子どものＩＱスコアは、バルプロ酸服用の母親を除き、母親のＩＱスコアに関連していた。３才時の平均ＩＱスコアは、バルプロ酸服用の母親の子どもは92だったが、ラモトリジンで101、フェニトインで99、カルバマゼピンで98 だった。
I.Q. Harmed by Epilepsy Drug in Utero
By RONI CARYN RABIN
Published: April 15, 2009
Pregnant women who took a popular epilepsy drug, also widely used to treat migraines, pain and psychiatric disorders, had children whose I.Q. scores were significantly lower than those whose mothers took a different antiseizure medication, a new study has found.
The drug, Valproate, sold generically and under the brand name Depakote, remains the second-most-popular antiseizure medication used for epilepsy, but earlier studies found that use during pregnancy also increased the risk of developmental delays and major malformations.
All epilepsy drugs may pose risks to pregnant women, experts say. While some are likely to be safer than others, there have not been enough studies to guide patients and their doctors. About half of the women who take valproate are not epileptics.
The new study is to be published on Thursday in The New England Journal of Medicine.
Three-year-olds whose mothers had taken valproate during pregnancy had I.Q. scores that were nine points lower on average than children whose mothers had taken a different antiseizure medication, lamotrigine. The I.Q. scores of toddlers whose mothers took valproate were also lower than scores of children whose mothers took two other antiseizure medications, phenytoin and carbamazepine.
Physicians involved in the study warned that valproate should never be the first choice for use in women of childbearing age, though exceptions may be made if a woman’s epileptic seizures cannot be controlled with other available medications.
“My thought is that if I make a mistake and the patient has a breakthrough seizure, I can change the medication and switch the patient to valproate,” said Dr. Kimford J. Meador, professor of neurology at Emory University School of Medicine in Atlanta, and first author of the new report. “If I put the patient on valproate as a first choice and the baby has cognitive impairment or a malformation, I can’t repair that.”
Dr. Meador and his colleagues enrolled 303 pregnant women who were each using an antiepileptic drug and were treated at 25 epilepsy centers in the United States and Britain from October 1999 to February 2004.
Cognitive assessments were conducted in 258 2- and 3-year-olds born to 252 mothers, of whom 53 had taken valproate.
Over all, children’s I.Q. scores were strongly related to mothers’ I.Q. scores, except among the children of mothers treated with valproate, the study found.
At age 3, children exposed to valproate in utero had a mean I.Q. of 92, compared to 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, and 98 for those exposed to carbamazepine, the study found.
Some 13,000 to 21,000 babies each year are born to women with epilepsy, and the vast majority are healthy, researchers and advocates emphasized.
Experts warned that women should not stop taking valproate without talking to their doctors.
“It’s important to stress to readers that if they become frightened, they should not simply stop taking the drug, because that can be even more dangerous,” said Eric Hargis, president of the Epilepsy Foundation in Washington.
Epilepsy Drug Impairs Baby's Intelligence
When taken during pregnancy, valproate lowers IQ, study finds.
By Serena Gordon
WEDNESDAY, April 15 (HealthDay News) -- When a pregnant woman takes the epilepsy medication valproate, her child's intelligence may be lowered for at least three years, and possibly beyond, a new study suggests.
Photo: Epilepsy drug Depakote in pregnancy linked to lower IQ in kids; drug already tied to defects
Toddlers of moms who took the epilepsy drug valproate during pregnancy had lower IQs than the children of women who used other anti-seizure medicines, according to a new study.
(ABC News Photo Illustration)
Reporting in the April 16 issue of the New England Journal of Medicine, researchers found that when tested at age 3, children who were exposed to valproate in the womb had IQ scores up to nine points lower than children exposed to other epilepsy medications in utero.
The problem is, many women with epilepsy can only get good control of their seizures with valproate.
"We're not saying never use valproate, but try other drugs first," said the study's lead author, Dr. Kimford Meador, a professor of neurology at Emory University School of Medicine in Atlanta. "We don't think that valproate should be used as a first choice for any woman of childbearing age. Other drugs should be used first."
Meador said the recommendation pertains to all women of childbearing age, not just pregnant women, because more than half of all pregnancies are unplanned, and any damage that may occur to the baby may occur before a woman even realizes that she's pregnant. Additionally, the drug has been shown to cause congenital birth defects in about 10 percent of children exposed to it in the womb, according to Meador.
For women currently taking valproate, sold under the brand name Depakote, Meador emphasized that no one should stop taking epilepsy medication abruptly, because this could result in seizures.
"Don't stop taking any medications without talking to your doctor," Meador stressed. "But, if you're on this medication, ask your doctor about it."
While the majority of children born to women with epilepsy are normal, animal studies have suggested that exposure to epilepsy medications might be associated with "cognitive and behavioral difficulties," according to background information in the study.
To assess what effects these medications might have on babies, the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study was begun. The study includes 309 children from 25 epilepsy centers in the United Kingdom and the United States. All of the children's mothers were taking one of four epilepsy medications during pregnancy, including valproate, carbamazapine, lamotrigine and phenytoin.
The researchers plan to assess the children periodically until they're 6 years old. The current report focuses on outcomes when the children were 3 years old.
After compensating for other factors that might influence a child's intelligence -- such as maternal IQ, maternal age, the dose of anti-epileptic medication, gestational age at birth and the mother's intake of folic acid -- the researchers found that children exposed to valproate during pregnancy had significantly lower IQ scores than the children exposed to the other medications.
The average IQ for children exposed in the womb to lamotrigine was 101, for phenytoin it was 99, and for carbamazepine it was 98. Children exposed to valproate in the womb scored an average of 92 on the IQ test, according to the study.
The researchers also found that the drug's effect on IQ was "dose-dependent," meaning that the higher the dose of medication, the more effect on the child's intelligence.
Meador said the researchers suspect that the medication may cause a loss of brain cells in the baby, like fetal alcohol syndrome does.
"The take-away message from this study is that the danger of neurocognitive impairment is real with the use of valproic acid (valproate)," said Dr. Inna Vaisleib, a pediatric neurologist and epileptologist at Children's Hospital of Pittsburgh.
"Not using valproic acid in women of childbearing age is a good idea, as approximately half of all pregnancies are unplanned," she said, adding that "epilepsy is common, and about one in 200 pregnant women are receiving anti-epileptic drugs."
Vaisleib cautioned strongly against stopping any medications without first consulting a neurologist, because seizures can also be damaging to a growing fetus, as well as to the expectant mother.
To learn more about epilepsy and pregnancy, visit the Epilepsy Foundation.
SOURCES: Kimford Meador, M.D., professor of neurology, Emory University School of Medicine, Atlanta; Inna Vaisleib, M.D., pediatric neurologist and epileptologist, Children's Hospital of Pittsburgh; April 16, 2009, New England Journal of Medicine
Copyright 2009 HealthDayNews, Inc. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
NEJM Volume 360:1597-1605 April 16, 2009 Number 16
Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs
Kimford J. Meador, M.D., Gus A. Baker, Ph.D., Nancy Browning, Ph.D., Jill Clayton-Smith, M.D., Deborah T. Combs-Cantrell, M.D., Morris Cohen, Ed.D., Laura A. Kalayjian, M.D., Andres Kanner, M.D., Joyce D. Liporace, M.D., Page B. Pennell, M.D., Michael Privitera, M.D., David W. Loring, Ph.D., for the NEAD Study Group
Background Fetal exposure of animals to antiepileptic drugs at doses lower than those required to produce congenital malformations can produce cognitive and behavioral abnormalities, but cognitive effects of fetal exposure of humans to antiepileptic drugs are uncertain.
Methods Between 1999 and 2004, we enrolled pregnant women with epilepsy who were taking a single antiepileptic agent (carbamazepine, lamotrigine, phenytoin, or valproate) in a prospective, observational, multicenter study in the United States and the United Kingdom. The primary analysis is a comparison of neurodevelopmental outcomes at the age of 6 years after exposure to different antiepileptic drugs in utero. This report focuses on a planned interim analysis of cognitive outcomes in 309 children at 3 years of age.
Results At 3 years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs. After adjustment for maternal IQ, maternal age, antiepileptic-drug dose, gestational age at birth, and maternal preconception use of folate, the mean IQ was 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, 98 for those exposed to carbamazepine, and 92 for those exposed to valproate. On average, children exposed to valproate had an IQ score 9 points lower than the score of those exposed to lamotrigine (95% confidence interval [CI], 3.1 to 14.6; P=0.009), 7 points lower than the score of those exposed to phenytoin (95% CI, 0.2 to 14.0; P=0.04), and 6 points lower than the score of those exposed to carbamazepine (95% CI, 0.6 to 12.0; P=0.04). The association between valproate use and IQ was dose dependent. Children's IQs were significantly related to maternal IQs among children exposed to carbamazepine, lamotrigine, or phenytoin but not among those exposed to valproate.
Conclusions In utero exposure to valproate, as compared with other commonly used antiepileptic drugs, is associated with an increased risk of impaired cognitive function at 3 years of age. This finding supports a recommendation that valproate not be used as a first-choice drug in women of childbearing potential.
|<< 前記事(2009/04/16)||ブログのトップへ||後記事(2009/04/18) >>|
|<< 前記事(2009/04/16)||ブログのトップへ||後記事(2009/04/18) >>|