what is teratogenesity in antiepileptic treatment

by Prof. Theresia Legros V Published 2 years ago Updated 2 years ago

Teratogenicity of antiepileptic drugs The risk of adverse fetal effects differs in relation to the type of AED and for some AEDs also the daily dose. Although for MCMs the risk is primarily associated with the first trimester of gestation, influences on cognitive and behavioral development could extend throughout pregnancy. Available in …

Antiepileptic drugs (AED) have chronic teratogenic effects, the most common of which are congenital heart disease, cleft lip/palate, urogenital and neural tube defects.

Full Answer

Are antiepileptic drugs teratogenic?

Feb 28, 2017 · Epilepsy ranks first among neurological disorders requiring continuous treatment during pregnancy, since antiepileptic drugs (AEDs) have frequent chronic teratogenic effects, the most common of which are congenital heart disease, cleft lip/palate, urogenital defects, and neural tube defects.1–4) A two to three fold increase in major malformations was shown in …

What is the pathophysiology of Pb teratogenicity?

What are antiepileptic drugs used to treat?

Teratogenicity of antiepileptic medications Abstract Antiepileptic drugs (AEDs) are frequently used to treat several conditions that are common in women of childbearing age, including epilepsy, headaches, and mood disorders.

What is the teratogenicity of carbamazepine?

Teratogenicity of AEDs Carbamazepine Carbamazepine (CBZ) is an iminostilbene derivative used primarily in the management of epilepsy and trigeminal neuralgia. Observational studies have shown that the use of CBZ in pregnancy is associated with a higher risk of MCMs in the exposed offspring [ 12, 13 ].

What is teratogenicity in pharmacology?

Teratogenicity is the ability of a drug to cause fetal abnormalities or deformities.

Which antiepileptic is teratogenic?

Valproate is the drug with the highest risk, whereas prevalence of MCMs is lowest with lamotrigine, levetiracetam, and oxcarbazepine. For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent.

Are all anticonvulsants teratogenic?

Animal research also suggests that most anticonvulsants are teratogenic in experimental animals when large doses are used, but the effect of valproate sodium on the fetus is poorly known. Cleft lip and palatal defects have been most extensively studied, but defects have also been noted in eyes, heart, and limb buds.

What is the teratogenic effect of valproic acid?

Abstract. Valproic acid is a recently identified human teratogen now clearly associated with neural tube defects in offspring of exposed pregnant women. Other recent studies have suggested an increased risk for congenital heart disease and facial clefts.Apr 1, 1984

What are the teratogenic drugs?

Teratogenic drugs: A teratogen is an agent that can disturb the development of the embryo or fetus. Teratogens halt the pregnancy or produce a congenital malformation (a birth defect). Classes of teratogens include radiation, maternal infections, chemicals, and drugs.

Why are ACE inhibitors teratogenic?

Angiotensin converting enzyme (ACE) inhibitors are thought to produce a fetopathy by inhibiting fetal urine production and therefore only do so when taken in the second and third trimesters: the drugs have been considered safe in the first trimester.

What is a teratogenic effect?

Teratogens are drugs, chemicals, or even infections that can cause abnormal fetal development. There are billions of potential teratogens, but only a few agents are proven to have teratogenic effects. These effects can result in a baby being born with a birth defect.Mar 3, 2016

Which anti epileptic drug has the least teratogenic potential?

Evidence of LMT's teratogenicity remains uncertain, but the limited existing data suggest that LMT is less teratogenic than either valproic acid (VPA) or phenytoin (PHT), with respect to inducing structural abnormalities (Table 1) [1,25].

Which drug is contraindicated in pregnancy and epilepsy?

Valproate is contraindicated in women of childbearing potential unless a pregnancy prevention programme is in place.Jan 7, 2021

Why is sodium valproate teratogenic?

VPA has been associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism.

What is fetal anticonvulsant syndrome?

Foetal anticonvulsant syndrome is a group of malformations that can affect some babies if they are exposed to certain medicines, known as antiepileptic drugs (AEDs), while in the womb. Malformations include spina bifida, cleft palate, heart defects, learning problems and autism spectrum disorder.Apr 11, 2022

How common is anticonvulsant syndrome?

One study showed that approximately 3 babies out of 100 born to these women, would have a malformation. For women who are taking AEDs, the risk of their baby having a major problem (congenital malformation) depends on the type, number and dose of the medication.Feb 16, 2017

Does valproate cause cognitive impairment?

Prenatal exposure to valproate has also been confirmed to cause an increased risk of cognitive impairments and autistic traits . In a population-based study, the risk of AED-induced autistic traits was attenuated by periconceptional folate supplementation.

Is valproate a dose dependent drug?

For valproate, phenobarbital, phenytoin, carbamazepine, and lamotrigine, the risk of MCMs is dose-dependent. Prenatal exposure to valproate has also been confirmed to cause an increased risk of cognitive impairments and autistic traits.

Dose-dependent, drug-specific, or both?

From the Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala State, India.

Abstract

Objective To determine the relative risk (RR) of major congenital malformations (MCMs) in infants with antenatal exposure to antiepileptic drug (AED) dual therapy and to explore the influence of specific AEDs vs dose.

Footnotes

Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

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Can epilepsy be treated during pregnancy?

Most women with active epilepsy need treatment with anti epileptic drugs during pregnancy. Antiepileptic drugs are also frequently used for other indications, such as migraine, pain syndromes, and psychiatric disorders, which are prevalent among women of childbearing age. Possible teratogenic effects of antiepileptic drugs are therefore ...

How old is cognitive function after fetal exposure?

Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. is a carefully designed prospective study that aims to compare cognitive outcomes at 6 years of age after exposure to monotherapy with valproate, carbamazepine, lamotrigine, or phenytoin, but does not include an unexposed control group.

Why is it so difficult to estimate the rate of spontaneous abortions in women receiving AEDs?

Estimating the rate of spontaneous abortions in women receiving AEDs is difficult because many occur in early pregnancy and can pass unrecognised. Additionally, in general, a large proportion of spontaneous abortions are associated with chromosomal abnormalities, but these abnormalities have not been studied in populations with epilepsy. Published data on obstetric risks in women with epilepsy are also scarce and conflicting.

What is the association between AEDs and dysmorphic features of a child?

Many investigators have described an association between exposure to certain AEDs and dysmorphic features of the child, sometimes in combination with major malformations and learning and behavioural problems. Such syndromes have been described in association with phenytoin,

When are major congenital malformations found?

Such structural abnormalities are established during organogenesis, within the first 8–10 weeks of gestation, often before the woman is aware that she is pregnant. Findings from several studies have confirmed greater risks of such malformations in children exposed to AEDs in utero; the risk was about three times that in the children of healthy women, according to a systematic review.

What are the effects of congenital malformations?

Major congenital malformations include a wide range of malformations with different effects on function and quality of life, ranging from hypospadias to severely disabling neural tube defects. Comparing overall malformation rates might therefore be misleading with regard to the consequences of exposure to different drugs, in particular if some AEDs are associated with more severe malformations than others.

Can AEDs affect pregnancy?

Maternal use of AEDs during pregnancy has also been suggested to affect the behaviour of the exposed child. A retrospective study assessed 242 children aged between 6 and 16 years whose mothers had epilepsy during pregnancy.

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