The teratogenicity of the newer antiepileptic drugs - an update

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

doi:10.1111/ane.12280

Cited by 77 publications

(89 citation statements)

References 16 publications

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“…Of the 13 studies investigating major malformations, ten controlled for factors that play an important part in the occurrence or prevention of birth defects [27,28], such as FA supplementation or chromosomal abnormalities [21,24,[29][30][31][32][33][34][35][36], and 12 studies controlled for additional relevant factors such as maternal age, family history of congenital malformations [37,38], or alcohol consumption [39] during pregnancy [21,24,[29][30][31][32][33][34][35][36][40][41][42]. Six of those studies reported the general timing of the fetal exposure [24,29,31,33,35,42], five recorded the dosage of lamotrigine that subjects were taking [24,30,33,34,41], and three stated the severity of the underlying disease, i.e., frequency of epileptic seizures during the pregnancy [21,32,34]. While two of the studies [21,34] reported the frequency of women experiencing epileptic seizures (2...…”

Section: Comparabilitymentioning

confidence: 99%

Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

et al. 2017

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Section: Comparabilitymentioning

confidence: 99%

Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

et al. 2017

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“…MCM rates are reported as 4.2 % to 4.9 % for monotherapy use, with an increased risk of cleft lip and cleft palate and hypospadias [11,12]. The Australian pregnancy register reported a particularly high rate of MCMs for TPM when used as polytherapy, at 14.1 % with a relative risk of 4.32 (95 % CI 1.57-11.05) compared with no AED exposure [13]. Another major concern is a high rate of small for gestational age (SGA) births following in utero exposure to TPM; the NAAPR reported that 17.9 % of TPMexposed infants were SGA with a relative risk of 2.4 (95 % CI 1.8-22) compared with LTG [14].…”

Section: Tpmmentioning

confidence: 99%

Use of Antiepileptic Drugs During Pregnancy: Evolving Concepts

Pennell

2016

Neurotherapeutics

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Although prenatal exposure to antiepileptic drugs (AEDs) is known to impart relatively higher risks of major congenital malformations, prospective studies have provided refined data that allow us to differentiate the risks of different types and doses of AEDs. As the number of AED prescriptions has dramatically increased in reproductive-aged women with a variety of neuropsychiatric indications, the evolving concepts learned from studies in women with epilepsy can be applied to a much larger group of pregnant women to improve child outcomes while maintaining maternal disease control. In addition to careful selection of the type of medication, the amount of fetal exposure at conception and in the first trimester probably matters across all AEDs. Some AED polytherapy regimens are not associated with a higher risk of malformations, although other outcomes have not yet been formally studied. The individual woman's drug target concentration should be established preconception and maintained during pregnancy, to prevent seizure worsening. Substantial pharmacokinetic changes occur with many of the medications during pregnancy and postpartum, and interindividual variability supports the use of therapeutic drug monitoring for most AEDs. During pregnancy, vigilance and close monitoring should also include intrauterine fetal growth, obstetric complications, and neonatal complications. Breastfeeding can provide additional neurodevelopmental benefit and should be an option for women on AEDs. Knowledge of these key principles enhances our ability to make treatment recommendations with resultant improved maternal and child outcomes. Additional prospective studies are needed to further define the risk-benefit ratio across a variety of medications, dosing strategies, and neuropsychiatric disorders.

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“…Converging evidence from registry studies indicates that teratogenic risks are higher with valproate, followed by carbamazepine and topiramate. Among other commonly prescribed AEDs, older generation agents such as phenobarbitone and phenytoin have been associated with higher risks compared with lamotrigine, levetiracetam, clonazepam and gabapentin (Vajda et al, 2014;Voinescu and Pennell, 2015). Evidence-based recommendations include the avoidance of valproate and AED polytherapy during pregnancy, especially during the first trimester, in order to reduce the risk of congenital malformations.…”

Section: Women With Epilepsy: Clinically Relevant Issuesmentioning

confidence: 99%

Women with epilepsy: clinically relevant issues

Bangar¹,

Shastri²,

El‐Sayeh³

et al. 2016

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SummaryWomen with epilepsy (WWE) face specific challenges throughout their lifespan due to the effects of seizures and antiepileptic drugs on hormonal function, potentially affecting both sexual and reproductive health. This review article addresses the most common issues of practical relevance to clinicians treating WWE: epidemiology and clinical presentations (including catamenial epilepsy), contraception, reproductive and sexual dysfunction, pregnancy, lactation, menopause-related issues (including bone health), and mental health aspects. Awareness of these gender-specific issues and implementation/adaptation of effective interventions for WWE results in significantly improved health-related quality of life in this patient population.

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The teratogenicity of the newer antiepileptic drugs - an update

Abstract: Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose-related anatomical teratogenesis, as valproate is already known to be.

Cited by 77 publications

References 16 publications

Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

Use of Antiepileptic Drugs During Pregnancy: Evolving Concepts

Women with epilepsy: clinically relevant issues

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