Antiepileptic drug use of women with epilepsy and congenital malformations in offspring

Artama, Miia; Auvinen, Anssi; Raudaskoski, Tytti; Isojärvi, I.; Isojärvi, Jouko

doi:10.1212/01.wnl.0000163771.96962.1f

Cited by 272 publications

(190 citation statements)

References 25 publications

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“…16 A study using the Finnish National Medical Birth Registry examined 2,350 births in women with epilepsy and showed an increase risk of malformations for VPA compared with nonexposed and children exposed in utero to other AEDs; the rate of malformations for VPA monotherapy was 10.7%. 17 The United Kingdom Pregnancy Registry, which included 3,607 pregnancies, found a malformation rate of 6.2% for VPA monotherapy, which was significantly greater than CBZ (2.2%). 18 Four other prospective studies all exhibited a trend toward higher malformations for VPA despite their relatively low power.…”

Section: Discussionmentioning

confidence: 99%

In utero antiepileptic drug exposure

et al. 2006

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Section: Discussionmentioning

confidence: 99%

In utero antiepileptic drug exposure

et al. 2006

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“…Numerous studies suggest that NSCLP results from the complex interaction of both genes and environmental factors. Folic acid deficiency, maternal smoking and anticonvulsant medications are some of the environmental influences that have been associated with NSCLP (3)(4)(5). Evidence for involvement of genes in NSCLP comes from family studies which show that: (1) the heritability of NSCLP in a Caucasian population is approximately 76%, (2) the rate of concordance is higher in monozygotic (25-40%) than dizygotic (3-6%) twins and (3) there is an increased relative risk to siblings (λ s = 30-40) compared to the general population (1,6).…”

Section: Introductionmentioning

confidence: 99%

CRISPLD2: a novel NSCLP candidate gene

Chiquet¹,

Lidral²,

Stal³

et al. 2007

Human Molecular Genetics

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Non-syndromic cleft lip with or without cleft palate (NSCLP) results from the complex interaction between genes and environmental factors. Candidate gene analysis and genome scans have been employed to identify the genes contributing to NSCLP. In this study, we evaluated the 16q24.1 chromosomal region, which has been identified by multiple genome scans as an NSCLP region of interest. Two candidate genes were found in the region: interferon regulatory factor 8 (IRF8) and cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2). Initially, Caucasian and Hispanic NSCLP multiplex families and simplex parent-child trios were genotyped for single nucleotide polymorphisms (SNPs) in both IRF8 and CRISPLD2. CRISPLD2 was subsequently genotyped in a data set comprised of NSCLP families from Colombia, South America. Linkage disequilibrium analysis identified a significant association between CRISPLD2 and NSCLP in both our Caucasian and Hispanic NSCLP cohorts. SNP rs1546124 and haplotypes between rs1546124 and either rs4783099 or rs16974880 were significant in the Caucasian multiplex population (P = 0.01, P = 0.002 and P = 0.001, respectively). An altered transmission of CRISPLD2 SNPs rs8061351 (P = 0.02) and rs2326398 (P = 0.06) was detected in the Hispanic population. No association was found between CRISPLD2 and our Colombian population or IRF8 and NSCLP. In situ hybridization showed that CRISPLD2 is expressed in the mandible, palate and

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“…Thus, the teratogenicity of PHT has been established amongst clinicians and basic scientists for almost 40 years. As is often the case, some studies found significant associations between in utero PHT exposure and MCMs [Kaneko et al, 1999;Vajda et al, 2006;Wide et al, 2004], while others failed to find such associations [Artama et al, 2005;Morrow et al, 2006;Vajda et al, 2007Vajda et al, , 2012 (Table II).…”

Section: Antiepileptic Drugsmentioning

confidence: 82%

Antiepileptic Drugs and Pregnancy Outcomes

Wlodarczyk

Palacios

George³

et al. 2012

Obstetrical &Amp; Gynecological Survey

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The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer and neuropathic pain. Despite the fact that the majority of pregnancies of women with epilepsy who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when antiepileptic drugs (AEDs) are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of women with epilepsy, and to provide information on the latest experimental and human epidemiological studies of the effects of antiepileptic drugs in the exposed embryos.

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Antiepileptic drug use of women with epilepsy and congenital malformations in offspring

Abstract: Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).

Cited by 272 publications

References 25 publications

In utero antiepileptic drug exposure

In utero antiepileptic drug exposure

CRISPLD2: a novel NSCLP candidate gene

Antiepileptic Drugs and Pregnancy Outcomes

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