妊娠中のバルプロ酸服用による自閉症のリスク
妊娠中のバルプロ酸服用による自閉症のリスク
デンマークでの70万人の子どもの研究により、妊娠中の抗てんかん薬バルプロ酸服用により、自閉症スペクトラム障害ASDの発症リスクは3倍以上となる可能性があるという。
これまでの研究で、先天性障害や知能障害の発症がぞうかすることはわかっていたが、新たに自閉症との関連についてこれまでで最強の証拠が出たことになる。
1996-2006年にデンマークで生まれた子ども656,000人を追跡し、母親の約6,600人がてんかんを持ち、508人は妊娠中にバルプロ酸を服用していた。2010年までに、その4.4%がASDと診断され、2.5%は自閉症だった。
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Epilepsy drug in pregnancy tied to autism risk
http://www.reuters.com/article/2013/04/23/us-epilepsy-drug-idUSBRE93M1C020130423
By Genevra Pittman
NEW YORK | Tue Apr 23, 2013 4:53pm EDT
(Reuters Health) - Women who take the epilepsy drug valproate during pregnancy are three times more likely to have a child with an autism spectrum disorder, suggests new research based on close to 700,000 babies born in Denmark.
Previous studies have found more birth defects and lower intelligence among children of mothers who took valproate, but the new work represents the "strongest evidence to date" of a link between the drug and autism, according to an editorial published with the study on Tuesday.
The results don't prove the generic drug, also sold as valproic acid, causes autism. But researchers were able to account for a number of underlying factors - such as the age and health of the mothers and the babies' fathers - that make the study more convincing, Christopher Stodgell said.
"This finding isn't necessarily a brand new finding, but it's an important finding in that (researchers studied) really a much larger population, and they also looked at some other underlying drivers," said Stodgell, who studies the origins of autism at the University of Rochester Medical Center but wasn't involved in the new research.
Women "need to be very diligent about what the effects are if they're taking valproic acid," he told Reuters Health.
About one in 88 children has an autism spectrum disorder, or ASD, according to the U.S. Centers for Disease Control and Prevention. Those conditions range from autism itself to less disabling ones such as Asperger's syndrome.
For the new study, researchers tracked 656,000 kids born in Denmark between 1996 and 2006. Using a large prescription drug database, they found that just under 6,600 of the mothers of those children had epilepsy and 508 women took valproate while pregnant.
By 2010, 4.4 percent of the kids whose mothers had taken valproate during pregnancy were diagnosed with any ASD, including 2.5 percent with autism.
In contrast, 1.5 percent of all babies in the study had an ASD and 0.5 percent had autism, the study team reported in the Journal of the American Medical Association.
Mothers' underlying epilepsy didn't fully explain the link, according to Jakob Christensen from Aarhus University and his colleagues. In addition, autism rates were higher among children of women who used valproate during pregnancy than those who had previously used the drug but stopped before conceiving.
CONSIDER RISKS, BENEFITS
"Valproate is an effective drug, but it appears that it is being prescribed for women of childbearing potential at a rate that does not fully consider the ratio of benefits to risks," wrote Dr. Kimford Meador and David Loring from Emory University in Atlanta, in a linked editorial.
Valproate could affect maturation of a fetus's brain, Christensen suggested, including the signal-sending neurotransmitters.
Women who may become pregnant "certainly should discuss with their doctor if there are alternative treatments that would be reasonable," he told Reuters Health.
For those with certain syndromes or generalized epilepsy, there aren't necessarily other good options. Stopping valproate in that case isn't a good idea, Christensen said.
"It's also a risk if you have seizures, both for the mother and the unborn child. (Stopping medication) is not a thing that you take lightly," he said.
"Even those that are exposed to this drug, there's still a good chance - more than a 95-percent chance - that their child will never develop signs of autism."
The study didn't take into account whether women drank during pregnancy, or if they took folic acid - which has been tied to a lower risk of some birth defects.
Christensen said there are steps pregnant women on valproate can take to lower any risks to their baby, such as using the lowest possible dose and dividing it up during the day.
SOURCE: Journal of the American Medical Association, online April 23, 2013.
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Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism
Jakob Christensen, PhD; Therese Koops Gronborg, MSc; Merete Juul Sorensen, PhD; Diana Schendel, PhD; Erik Thorlund Parner, PhD; Lars Henning Pedersen, PhD; Mogens Vestergaard, PhD
[+] Author Affiliations
JAMA. 2013;309(16):1696-1703. doi:10.1001/jama.2013.2270.
ABSTRACT
Importance Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism.
Objective To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring.
Design, Setting, and Participants Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.
Main Outcomes and Measures Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy.
Results Of 655 615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate.
Conclusions and Relevance Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.
デンマークでの70万人の子どもの研究により、妊娠中の抗てんかん薬バルプロ酸服用により、自閉症スペクトラム障害ASDの発症リスクは3倍以上となる可能性があるという。これまでの研究で、先天性障害や知能障害の発症がぞうかすることはわかっていたが、新たに自閉症との関連についてこれまでで最強の証拠が出たことになる。
1996-2006年にデンマークで生まれた子ども656,000人を追跡し、母親の約6,600人がてんかんを持ち、508人は妊娠中にバルプロ酸を服用していた。2010年までに、その4.4%がASDと診断され、2.5%は自閉症だった。
-----------------------------------------------------
Epilepsy drug in pregnancy tied to autism risk
http://www.reuters.com/article/2013/04/23/us-epilepsy-drug-idUSBRE93M1C020130423
By Genevra Pittman
NEW YORK | Tue Apr 23, 2013 4:53pm EDT
(Reuters Health) - Women who take the epilepsy drug valproate during pregnancy are three times more likely to have a child with an autism spectrum disorder, suggests new research based on close to 700,000 babies born in Denmark.
Previous studies have found more birth defects and lower intelligence among children of mothers who took valproate, but the new work represents the "strongest evidence to date" of a link between the drug and autism, according to an editorial published with the study on Tuesday.
The results don't prove the generic drug, also sold as valproic acid, causes autism. But researchers were able to account for a number of underlying factors - such as the age and health of the mothers and the babies' fathers - that make the study more convincing, Christopher Stodgell said.
"This finding isn't necessarily a brand new finding, but it's an important finding in that (researchers studied) really a much larger population, and they also looked at some other underlying drivers," said Stodgell, who studies the origins of autism at the University of Rochester Medical Center but wasn't involved in the new research.
Women "need to be very diligent about what the effects are if they're taking valproic acid," he told Reuters Health.
About one in 88 children has an autism spectrum disorder, or ASD, according to the U.S. Centers for Disease Control and Prevention. Those conditions range from autism itself to less disabling ones such as Asperger's syndrome.
For the new study, researchers tracked 656,000 kids born in Denmark between 1996 and 2006. Using a large prescription drug database, they found that just under 6,600 of the mothers of those children had epilepsy and 508 women took valproate while pregnant.
By 2010, 4.4 percent of the kids whose mothers had taken valproate during pregnancy were diagnosed with any ASD, including 2.5 percent with autism.
In contrast, 1.5 percent of all babies in the study had an ASD and 0.5 percent had autism, the study team reported in the Journal of the American Medical Association.
Mothers' underlying epilepsy didn't fully explain the link, according to Jakob Christensen from Aarhus University and his colleagues. In addition, autism rates were higher among children of women who used valproate during pregnancy than those who had previously used the drug but stopped before conceiving.
CONSIDER RISKS, BENEFITS
"Valproate is an effective drug, but it appears that it is being prescribed for women of childbearing potential at a rate that does not fully consider the ratio of benefits to risks," wrote Dr. Kimford Meador and David Loring from Emory University in Atlanta, in a linked editorial.
Valproate could affect maturation of a fetus's brain, Christensen suggested, including the signal-sending neurotransmitters.
Women who may become pregnant "certainly should discuss with their doctor if there are alternative treatments that would be reasonable," he told Reuters Health.
For those with certain syndromes or generalized epilepsy, there aren't necessarily other good options. Stopping valproate in that case isn't a good idea, Christensen said.
"It's also a risk if you have seizures, both for the mother and the unborn child. (Stopping medication) is not a thing that you take lightly," he said.
"Even those that are exposed to this drug, there's still a good chance - more than a 95-percent chance - that their child will never develop signs of autism."
The study didn't take into account whether women drank during pregnancy, or if they took folic acid - which has been tied to a lower risk of some birth defects.
Christensen said there are steps pregnant women on valproate can take to lower any risks to their baby, such as using the lowest possible dose and dividing it up during the day.
SOURCE: Journal of the American Medical Association, online April 23, 2013.
-----------------------------------------------------
Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism
Jakob Christensen, PhD; Therese Koops Gronborg, MSc; Merete Juul Sorensen, PhD; Diana Schendel, PhD; Erik Thorlund Parner, PhD; Lars Henning Pedersen, PhD; Mogens Vestergaard, PhD
[+] Author Affiliations
JAMA. 2013;309(16):1696-1703. doi:10.1001/jama.2013.2270.
ABSTRACT
Importance Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism.
Objective To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring.
Design, Setting, and Participants Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.
Main Outcomes and Measures Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy.
Results Of 655 615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate.
Conclusions and Relevance Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.
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