Valproate Should be Used Cautiously in Childbearing Women

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Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study confirmed the fetal exposure to valproate results in lower Intelligence Quotient (IQ) in children [1]. This primary outcome for the study was presented at the American Epilepsy Society (AES) 65th Annual Meeting.

Valproate is an FDA-approved antiepileptic and mood stabilizing drug used commonly to treat epilepsy and/or bipolar disorder. It may also be used to treat migraine headaches and schizopherenia.

Valproate is a teratogen which is known to cause birth defects including neural tube defects, congenital heart defects, limb defects, genitourinary defects, brain, eye and respiratory anomalies, and abdominal wall defects [2]. Keeping this in mind, the valproate is now also found to cause cognitive disabilities and impairment of IQ levels in children who get exposed to valproate in utero [1][3].

This particular study I am concerned about, found IQ levels 8 to 11 points lower in children at the age of 6 years, whose mothers received antiepileptic drug monotherapy during pregnancy. The study also found the negative impact of the drug valproate to be dose-dependent.

This particular study and the other studies to date conclude that, valproate should be contraindicated in pregnancy and women of childbearing age. Further, it should be used in lowest possible doses indicated if the patient at risk only responds to valproate.

Early cognitive development in children born to women with epilepsy is of concern and children to such mothers should be monitored throughout their childhood to allow for early interventions if needed.

Further research is needed to not only reassess the negative impact of valproate in children exposed to it in utero but also to establish the role of other antiepileptic drugs in neurodevelopmental outcome of exposed children.

Neurodevelopmental outcome is also found to be endangered in the children who are breast-fed by epileptic mothers [4] but such findings are inconsistent and need further evaluation before they are being put in the literature.

REFERENCES AND FURTHER READINGS:

1. Allison Shelley. Valproate Linked to Cognitive Delay, Autism in Children. From Medscape Medical News > Neurology

2. Ozkan H, Cetinkaya M, Köksal N, Yapici S. Severe fetal valproate syndrome: combination of complex cardiac defect, multicystic dysplastic kidney, and trigonocephaly. J Matern Fetal Neonatal Med. 2011 Mar;24(3):521-4.

3. Nadebaum C, Anderson V, Vajda F, Reutens D, Barton S, Wood A. The Australian brain and cognition and antiepileptic drugs study: IQ in school-aged children exposed to sodium valproate and polytherapy. J Int Neuropsychol Soc. 2011 Jan;17(1):133-42. Epub 2010 Nov 19.

4. Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology. 2010 Nov 30;75(22):1954-60. Epub 2010 Nov 24.

Rafia Afzal is a 4th year medical student of Dow University of Health Sciences, Karachi, Pakistan. She has keen interest in surgery.