The Australian Register of Antiepileptic Drugs in Pregnancy: The first 1002 pregnancies

Vajda, F. J. E.; Hitchcock, Alison; Graham, Janet; O’Brien, Terence J.; Lander, Cecilie M.; Eadie, Mervyn J.

doi:10.1111/j.1479-828x.2007.00781.x

Cited by 92 publications

(72 citation statements)

References 19 publications

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“…The fetal complications of maternal epilepsy range from malformation to milder ones, but increase childhood mortality and morbidity, including low birth weight (LBW), being small for gestational age (SGA) and preterm delivery [7,8]. Major malformation was documented as being linked to AED exposure (especially polypharmacy and valproate) and may be dose related [4,[9][10][11]. However, the rate of LBW, SGA and preterm delivery among epileptic women is debated.…”

Section: Introductionmentioning

confidence: 97%

No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs

et al. 2009

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The objectives of this study were (1) to investigate the incidence of adverse pregnancy outcomes among the epileptic and general populations, including small for gestational age (SGA), low birth weight (LBW) and preterm delivery, using two large-scale nationwide population-based databases, and (2) to compare the risk of these adverse pregnancy outcomes between epileptic women who did and who did not receive antiepileptic drug (AED) treatment during pregnancy. This study used two national datasets: the National Health Insurance Research Dataset and birth certificate registry. We identified a total of 1,182 women who gave birth from 2001 to 2003 in Taiwan who had been diagnosed with epilepsy within the 2 years preceding the index delivery, together with 5,910 matched women as a comparison cohort. Multivariate logistic regression analyses were performed for estimation of risk. We found that approximately 14% of women with epilepsy received AED treatment during gestation. The adjusted odds of LBW, preterm births and SGA for epileptic women not receiving AED treatment during pregnancy were 1.31 (95% CI, 1.02-1.68), 1.35 (95% CI, 1.07-1.71) and 1.23 (95% CI, 1.03-1.46) times that of women without epilepsy, respectively. In contrast, no significant difference in the risk of LBW infants, preterm births and SGA babies was observed between epileptic mothers receiving AED treatment during pregnancy and women without epilepsy. Our study documents an increased risk of adverse pregnancy outcomes for epileptic women who do not receive AED treatment during pregnancy, but none for epileptic women who do receive treatment.

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Section: Introductionmentioning

confidence: 97%

No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs

et al. 2009

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“…We now know that some AEDs increase the risk of congenital malformations, and that the risk appears to be higher when treatment involves high doses of sodium valproate (VPA) or polytherapy (Tomson et al, 2007;Vajda et al, 2007). There are fewer studies on the longer term effects of prenatal AED exposure on children's development, yet this is an area of significant interest and concern.…”

Section: Introductionmentioning

confidence: 98%

The Australian Brain and Cognition and Antiepileptic Drugs Study: IQ in School-Aged Children Exposed to Sodium Valproate and Polytherapy

Nadebaum

Anderson

Vajda

et al. 2010

J Int Neuropsychol Soc

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Prenatal exposure to sodium valproate (VPA) and polytherapy has been linked with increased risk of birth defects and cognitive impairment in young children. We evaluated the cognitive impact of prenatal exposure to VPA and polytherapy in school-aged children. Fifty-seven children exposed to VPA (n 5 23), polytherapy with VPA (n 5 15), or polytherapy without VPA (n 5 19) were assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. Information on maternal epilepsy, pregnancy, and medical history was obtained prospectively through the Australian Pregnancy Register for Women with Epilepsy and Allied Disorders. All groups had elevated frequencies of Extremely Low (,70) or Borderline (70-79) Full-Scale IQ (15.8-40.0%). Verbal Comprehension and Working Memory scores in all groups fell significantly below the standardized test mean, while Perceptual Reasoning and Processing Speed scores were relatively intact. Multivariate analysis of covariance analysis revealed significant main effects of VPA on Verbal Comprehension and Working Memory, and of polytherapy on Verbal Comprehension and Processing Speed. Our results suggest that VPA has a dose-dependent negative impact on verbal intellectual abilities, and may also affect working memory. The possibility that inclusion of VPA in many polytherapy regimens may underlie reduced mean scores of polytherapyexposed children is discussed. (JINS, 2011, 17, 133-142)

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“…4 The APR commenced prospective data collection about AED use by pregnant women in 1999. The register is voluntary, and women across all Australian states and territories are eligible to participate; all contact is by telephone.…”

Section: Participantsmentioning

confidence: 99%

“…[1][2][3] Sodium valproate appears to carry a heightened risk, particularly at higher doses. 4,5 Early concerns about a possible link between fetal exposure to AEDs and neurobehavioral problems, specifically autism spectrum disorders (ASDs) arose from case report, and retrospective and animal studies. [6][7][8][9][10] More recently, Bromley et al 11 found an increased rate of ASD among children exposed prenatally to AEDs, with 7 (2.8%) of the 249 AED-exposed children in their sample receiving diagnoses independently of the study.…”

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confidence: 99%

Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy

et al. 2015

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Summary Purpose The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well‐characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug‐exposure status. Methods Participants were 105 Australian children aged 6–8 years who were recruited via the Australian Pregnancy Register for Women on Antiepileptic Medication. Maternal epilepsy, pregnancy, and medical history data were obtained prospectively. Autism traits were assessed using the Childhood Autism Rating Scale (CARS). Results Eleven children (10.5%) had elevated CARS scores. Two were exposed to valproate monotherapy (2/26; 7.7%), two to carbamazepine monotherapy (2/34; 5.9%), and seven to valproate in polytherapy (7/15; 46.7%). Linear regression analysis showed that the mean valproate dose during pregnancy was a significant predictor of CARS scores after controlling for polytherapy, mean carbamazepine dose, folic acid use, seizures during pregnancy, tobacco and marijuana use, maternal intelligence quotient (IQ), and socioeconomic status. First trimester folic acid supplementation and marijuana use were also significant predictors of CARS scores. Significance Using direct assessment of children in our prospective study, we found an elevated rate of autism traits across the sample. The most important determinant of association with autistic traits was higher doses of sodium valproate exposure. The use of valproate in women who may become pregnant is now generally avoided; however, there are insufficient data regarding the risk of ASD with low‐dose valproate. If this risk is no greater than with other antiepileptic drugs (AED)s, it may enable women with genetic generalized epilepsy to retain optimal seizure control as well as minimize harm to their unborn child.

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The Australian Register of Antiepileptic Drugs in Pregnancy: The first 1002 pregnancies

Abstract: The Register has already produced important information for the management of pregnant women with epilepsy in Australia, but greater rates of recruitment into the Register are desirable to allow it to achieve its full potential.

Cited by 92 publications

References 19 publications

No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs

No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs

The Australian Brain and Cognition and Antiepileptic Drugs Study: IQ in School-Aged Children Exposed to Sodium Valproate and Polytherapy

Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy

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