JAMA: Adverse Drug Effects Topic Collection

Risks of In Utero Exposure to Valproate Risks of In Utero Valproate Exposure

Meador KJ, Loring DW. — Wed, 24 Apr 2013 00:00:00 GMT

Antiepileptic medications are among the most commonly prescribed teratogenic drugs among women of childbearing potential. However, determining the exact number of women of childbearing age exposed to antiepileptic medications is difficult. One estimate, based on data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, suggests that from 2005-2007, there were 7 900 000 annual prescriptions for antiepileptic medications among girls and women aged 15 to 44 years, including 926 000 for valproate (12% of all antiepileptic medication prescriptions, irrespective of indication). For those treated for epilepsy or seizures, there were 989 000 annual prescriptions, of which 177 000 were for valproate (18% of all prescriptions of antiepileptic medications for epilepsy or seizures).

Diabetes Drugs Investigated

Kuehn BM. — Wed, 24 Apr 2013 00:00:00 GMT

The US Food and Drug Administration (FDA) is investigating unpublished data suggesting that incretin mimetics used to treat type 2 diabetes may increase the risk of pancreatitis or precancerous changes in the pancreas (http://tinyurl.com/437wln9).

Patients Given Fungus-Tainted Injections Continue to Face Uncertainty, Illness

Kuehn BM. — Wed, 24 Apr 2013 00:00:00 GMT

Questions from patients and their relatives streamed in to a recent Centers for Disease Control and Prevention (CDC) conference call for clinicians about the ongoing outbreak of rare fungal infections linked to contaminated steroids from the New England Compounding Center (NECC), a compounding pharmacy in Framingham, Mass.

Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism Prenatal Valproate and Autism

Christensen J, Grønborg T, Sørensen M, et al. — Wed, 24 Apr 2013 00:00:00 GMT

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.