Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation‐wide, population‐based register study

Abstract

Aim: Antiepileptic drugs (AEDs) are known teratogens. Some specificity between different AEDs has been noted in the literature. The aim was to compare the teratogenic effect of valproic acid (VPA) and carbamazepine (CBZ) in monotherapy. Methods: Infants exposed to AEDs (n= 1398) in early pregnancy were identified from the Swedish Medical Birth Registry. The number of infants with congenital malformations and exposed to AED was compared with the expected number estimated from all infants born (n= 582656). Results: 90% (1256) of the AED exposed children were exposed to AEDs in monotherapy, 56% were exposed to CBZ and 21% to VPA. The odds ratio (OR) for having a malformation in the AED exposed group was 1.86 [95% confidence interval (95% CI) 1.42‐2.44]. Exposure to VPA in monotherapy compared with CBZ in monotherapy gave OR = 2.51 (95% CI 1.43‐4.68) for a neonatal diagnosis of malformations. However, there is no information available on the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups. Conclusion: There was a small increase in the risk of having a major malformation after exposure to AEDs in monotherapy. Exposure to VPA seems to carry a higher risk than exposure to CBZ.

Unilateral multicystic dysplastic kidney in infants exposed to antiepileptic drugs during pregnancy

“…The risk of congenital malformations has been associated with all the AEDs, but recent studies suggest differences in teratogenic effects between various AEDs. The teratogenic effect of valproic acid (VPA) has been well established, MCM incidence being increased ten-fold in the offspring of VPAtreated pregnant women [9]. Therefore, CBZ and PHB represented the drugs of choice for the treatment of virtually all types of epilepsy in the last decade.…”

Teratogenicity of Antiepileptic Drugs

“…There is evidence in literature to suggest that the ratio of major malformation increases due to VPA monotherapy or polytherapy including VPA, especially with higher doses, and has a negative impact on the long-term cognitive development of the child. 18,[33][34][35][36][37][38] There was one child with autism while 28 children were below the age of two, hence impossible to diagnose at the time of the study. Therefore, the ratio of autism in our sample needs to be revised at a later date.…”

Psychotropic Medications in Pregnancy and the Postpartum Period

“…55,56 Other malformations reported are facial clefting, hypospadias, and skeletal abnormalities. 57 Additionally, VPA has been clearly shown to have effects on the cognitive, verbal, behavioral, and neurodevelopmental abilities, 56,58 and the FDA released a drug-safety announcement regarding these findings in 2011. In general, it is highly recommended that women in their reproductive years be counseled regarding the effects of VPA on a fetus, and, if desiring pregnancy, should attempt to change to another medication for BPD control.…”

“…The risk is dose dependent and is increased when used with other AEDs, especially if the patient has already delivered an affected child. 54,56 Neural tube defects, which are typically lumbosacral in nature, are among its most devastating effects, and the risk of NTDs can reach 1%-2%. 55,56 Other malformations reported are facial clefting, hypospadias, and skeletal abnormalities.…”

“…54,56 Neural tube defects, which are typically lumbosacral in nature, are among its most devastating effects, and the risk of NTDs can reach 1%-2%. 55,56 Other malformations reported are facial clefting, hypospadias, and skeletal abnormalities. 57 Additionally, VPA has been clearly shown to have effects on the cognitive, verbal, behavioral, and neurodevelopmental abilities, 56,58 and the FDA released a drug-safety announcement regarding these findings in 2011.…”