Embryology · Teratology and prenatal diagnosis
Valproate, carbamazepine and phenytoin !
- Teratogen
Some medicines for epilepsy and bipolar disorder raise the risk of neural tube, facial and heart defects; the plan is made before pregnancy.
Updated 2026-11-01
See it in 3D: Spinal cord · Sacrum
What it is
Several classic antiseizure drugs cross the placenta and are teratogenic. Valproate carries the highest risk: neural tube defects, heart defects, facial clefts and neurodevelopmental effects. Carbamazepine and phenytoin have their own patterns. Because uncontrolled seizures also harm mother and fetus, any change is planned with the treating professional, ideally before conception.
Key facts
- Risk rises with several antiseizure drugs at once and with higher doses.
- Topiramate is linked to cleft lip and palate.
- Some newer antiseizure drugs carry a lower risk, though none is completely risk-free.
- Phenytoin and carbamazepine are converted to reactive metabolites (epoxides and free radicals) that damage DNA.
- The embryo's ability to clear those metabolites varies with its genotype: an example of the genotype principle.
Critical period and mechanism
- Critical period: first trimester; for the neural tube, week 4 after fertilization (days 21–28).
- Valproate: interferes with folate metabolism, inhibits histone deacetylases (altering gene expression) and generates reactive oxygen species.
- Carbamazepine: its epoxide metabolite damages DNA.
- Phenytoin: is activated to a free radical in the embryo and causes oxidative DNA damage.
Prevention
- Preconception counselling with neurology or psychiatry to choose the lowest-risk treatment that controls the disease.
- Folic acid supplement before conception; the amount is set by the treating professional.
- Medicines in pregnancy are decided with the treating professional; stopping them on one's own risks dangerous seizures.
What it does to the embryo and fetus
- Spina bifida and other neural tube defects (valproate, carbamazepine).
- Atrial septal defect and other heart defects, cleft lip or palate, hypospadias, polydactyly and craniosynostosis (valproate).
- Small nails and distal phalanges, short nose, hypertelorism, growth deficiency and intellectual disability (phenytoin).
- Valproate: lower IQ and higher risk of autism spectrum disorder.
In the lab
- Anatomy scan focused on the neural tube, face and heart; maternal AFP in the second trimester.
Test yourself
Think of the answer, then tap the question to see it.
Which antiseizure drug carries the highest teratogenic risk, and what is its most typical defect?
Valproate; its most typical defect is spina bifida.
Which hand finding is characteristic of fetal hydantoin syndrome?
Hypoplasia of the distal phalanges and nails.
Why is an antiseizure drug not stopped on one's own when pregnancy is discovered?
Uncontrolled seizures also harm mother and fetus; the change is planned by the treating professional.
See it in 3D
The structures of Durgical's 3D anatomy where it is found.
Related
- Neural tube defects: anencephaly, spina bifida and encephalocele
- Neurulation and closure of the neural tube
- Folic acid and neural tube defect prevention
- Cleft lip and cleft palate
- Hypospadias and epispadias
- Craniosynostosis
- Principles of teratology: critical periods, dose and genotype
Related conditions
- Spina bifida (myelomeningocele)
- Epilepsy and seizures
- Bipolar disorder
- Cleft lip and palate
- Hypospadias
- Autism spectrum disorder (ASD)
In Pharmacology
Educational content on embryonic development; not a guide to prenatal diagnosis or to medicines in pregnancy and no substitute for a health professional's advice. No doses are given.
Sources: Teratogenic Medications (StatPearls Publishing (NCBI Bookshelf), 2024); Langman's Medical Embryology, 13th ed., ch. 9: Birth Defects and Prenatal Diagnosis (Wolters Kluwer, 2015).
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Representative model, for educational purposes only.