Last updated:
2/3/2026
Years published: 2026
NORD gratefully acknowledges Christianne Senechal, MS, University of Connecticut Institute for Systems Genomics, UConn Health, OTIS, MotherToBaby CT and Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for their assistance with the preparation of this report.
Summary
Fetal carbamazepine syndrome (FCS) is a group of birth defects seen in some babies whose mothers took the anti-seizure medication carbamazepine during early pregnancy. Reported features may include subtle facial differences; thin, short, or partially formed fingernails or toenails (nail hypoplasia); and developmental delays, such as learning, speech, or motor skills, in children exposed in the womb.1
Use of carbamazepine during the first trimester of pregnancy has also been associated with a small but increased risk of major birth defects, particularly conditions that affect the spine, called neural tube defects, such as spina bifida.2,3
Treatment for FCS focuses on detecting and treating any structural differences (such as spina bifida or heart defects) and supporting a child’s growth, development, and learning with early intervention and school-based services. Because many pregnancies exposed to carbamazepine result in healthy children, care is unique to each individual and balances effective treatment for the mother with potential risks to the developing fetus (fetal risks).2,4-6
Introduction
Carbamazepine is an anti-seizure medication that has been used since the early 1960s to treat seizures and epilepsy, bipolar disorder, and certain pain conditions, such as trigeminal neuralgia (severe facial nerve pain). Brand names for carbamazepine include Tegretol®, Carbatrol®, Equetro®, and Epitol®, among others.
Anti-seizure medications, including carbamazepine, can have some structural, functional, or developmental abnormalities in a fetus resulting from exposure to a substance during pregnancy, particularly in the first trimester. These are called teratogenic effects. A teratogen is any agent (like drugs, alcohol, chemicals, viruses, or even certain maternal conditions) that a pregnant person is exposed to, which can disrupt a fetus’s normal development, leading to abnormalities in organs, limbs, or the brain. Teratogenic effects are similar to those from fetal hydantoin syndrome and fetal valproate syndrome.1-5,7-9
Children who were exposed to carbamazepine during pregnancy can have a wide range of possible effects. Much of what we know about these effects comes from medical reports and research studies that have followed children with this exposure.1-3,10,12-19 Not all children are affected in the same way, and the type and severity of features can vary from child to child. Importantly, many children exposed to carbamazepine before birth are healthy. Also, many of the children who were exposed and have problems do not develop the full pattern of findings known as fetal carbamazepine syndrome (FCS). 2-5
Features that may be present at birth include subtle facial differences (minor craniofacial defects), such as a small or slightly flattened nasal bridge, mild changes around the eyes, or other subtle facial features.1 These changes are often mild and may only be recognized by a specialist. Infants may also have fingernails or toenails that are short, thin, or partially formed (nail hypoplasia).1,13
Some babies of epileptic women who took carbamazepine (as well as some other anti-seizure medications) during pregnancy are born smaller than expected for how far along the pregnancy was at birth (small for gestational age) or have an abnormally small head size (microcephaly).20-23
Babies exposed to carbamazepine in the womb may have an increased risk of certain birth defects, including spina bifida.3, 24, 25 Spina bifida is a type of neural tube defect, which occurs when the structure that later forms the brain and spinal cord does not close properly during early development. In spina bifida, the spine does not fully form, leaving part of the spinal cord exposed. This condition can result in neurological problems affecting the brain and spinal cord, as well as difficulties with learning and thinking.
Among major birth defects, spina bifida is the only one that has been consistently and significantly associated with carbamazepine used alone during pregnancy.3 Other structural birth defects more rarely seen in FCS include:
Many studies have not shown significant developmental delays or decreases in the intellectual quotient (IQ) in kids who were exposed to carbamazepine in the womb.12,26-31 However, some of these children may have some subtle problems with language, memory or planning (executive) skills.27,28,31
Children exposed to carbamazepine seem to have fewer behavioral difficulties as a group when compared to other anti-seizure medication exposures, although individual children could still be affected.32 Exposure to anti-seizure medications in general during pregnancy have been linked to a modestly increased risk of neurodevelopmental conditions such as autism and attention-deficit/hyperactivity disorder (ADHD).9,33-35
Fetal carbamazepine syndrome (FCS) occurs when a developing fetus is exposed to carbamazepine due to maternal use of carbamazepine during pregnancy.
Carbamazepine (CBZ) is a medication commonly used to treat epilepsy (a condition that causes seizures), bipolar disorder (a mental health condition with mood swings), trigeminal neuralgia (severe facial nerve pain), and some types of chronic pain (long-lasting pain). 5,7,36
Many women of childbearing age use carbamazepine to control seizures. Compared with some older seizure medicines, such as phenobarbital, phenytoin, primidone, or valproic acid, carbamazepine is generally considered less toxic, meaning it usually causes fewer serious side effects.1,2,4,5,7-9,31
Carbamazepine is fat-soluble, which means it can easily pass through the placenta (the organ that connects a pregnant person to the developing fetus).11 Because of this, the fetus can be exposed to the medication during pregnancy.
The risk for FCS is greatest during the first trimester when the fetal organs are developing (a process called organogenesis).1-4 Maternal seizures and other illnesses that can be treated with carbamazepine can also affect fetal outcomes. This makes it difficult to determine how much risk is related to the medication itself and how much is related to the underlying medical condition.12,26,34
Some studies suggest the risk for birth defects can be dose-related for several anti-seizure medications, and the risk is often higher when more than one medication is used.2,5,7,37,38 For carbamazepine, increased rates of birth defects have been observed, but the risks are generally lower than those seen with other anti-seizure drugs, such as valproate, at common doses.3-5,7-9
Doctors do not fully understand exactly how carbamazepine can affect a fetus. One possibility is that when the body breaks down the medication, some of the by-products (called metabolites) may interfere with normal fetal development. The pattern of effects seen in FCS looks similar to another medication-related condition called fetal hydantoin syndrome. This suggests that the breakdown products (metabolites) of certain seizure medicines may play a role in causing these effects.1,11,39
Neural tube defects are serious birth defects that affect the brain and spinal cord. They happen very early in pregnancy, often before someone knows they are pregnant. The first well-known example is spina bifida, where the spine does not close completely. Exposure to carbamazepine during early pregnancy increases the chance of neural tube defects like spina bifida.3,24,25
Some medications are known as folate antagonists, meaning they interfere with how the body uses (metabolizes) folate. These medications are linked to a higher risk of neural tube defects and other major birth defects.40,41 Carbamazepine is not considered a classic folate antagonist. However, research suggests it may still affect folate-related pathways (the body’s internal systems that use folate to help cells grow, divide, and develop properly), which could help explain why the risk of neural tube defects is higher with this medication. This is why folic acid supplementation is often recommended for people who take anti-seizure medications and could become pregnant.
The exact frequency of the full FCS pattern (the group of features that may occur together – subtle differences in facial appearance, underdeveloped fingernails or toenails, and developmental delays) is unknown. Not every child exposed to carbamazepine in the womb has all these features, and many children have none at all.1,12
About 1% (1 in 100) infants exposed to carbamazepine will have a neural tube defect, such as spina bifida.36 In some small studies, about 11-13% of exposed fetuses had the FCS facial characteristic differences, 20% had developmental delay, and 26% had underdeveloped fingernails.1,12 There is no clear evidence that FCS affects one sex (males or females) or ethnic group more than another.2,3,5,9
There is no diagnostic laboratory or genetic test that can identify FCS. Instead, the diagnosis is made based on the mother’s medical history regarding the use of carbamazepine during pregnancy, and the presence and identification of the symptoms and features of FCS in an infant.1,9,12,13,20,22,23,26-30,32 FCS is also a diagnosis of exclusion, meaning that other similar disorders must be ruled out before a diagnosis of FCS can be made.
Treatment
There is no cure for FCS. Instead, clinical care focuses on reducing risk before and during pregnancy (prevention) and supporting children’s health and development when symptoms and features of FCS are present.
Prevention
Prevention strategies aim to reduce the chance of birth defects and developmental effects in an infant related to carbamazepine exposure while maintaining seizure control (or psychiatric support) for the person who is pregnant.
Individuals taking carbamazepine who are planning a pregnancy are encouraged to discuss treatment options with their healthcare providers before conception. Some anti-seizure medications might be preferred in pregnancy over carbamazepine, if possible. When treatment is needed during pregnancy, many studies suggest that using a single anti-seizure medication (monotherapy) is associated with lower rates of birth defects than using multiple anti-seizure medications together (polytherapy).37,46
Suddenly stopping carbamazepine during pregnancy is not recommended, as uncontrolled seizures might pose serious risks to both the person who is pregnant and the developing fetus. Treatment decisions should be individualized and closely supervised by a healthcare provider.47,48 Neural tube defects, such as spina bifida, are among the most consistently reported birth defects associated with FCS. Research supports the use of folic acid before and during early pregnancy to reduce the chance of neural tube defects. Many experts recommend folic acid supplementation for people taking anti-seizure medicines.36,40,41
MotherToBaby is a free service that provides evidence-based information and counseling about carbamazepine and other medications and exposures during pregnancy.
Treatment
The treatment of FCS is directed toward the specific symptoms and features that are evident in the affected child. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, oral surgeons, plastic surgeons, neurologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan the treatment for a child with FCS.1-3,24
Infants with FCS might benefit from early developmental intervention to ensure that they reach their potential in childhood. Children may benefit from occupational, physical and speech therapy. Various methods of rehabilitation and behavioral therapy may be beneficial. Additional medical, social, and/or vocational services may be necessary. Psychosocial support for the entire family is essential as well.26,27,32
Structural birth defects, such as spina bifida, heart defects, or an opening in the roof of the mouth (cleft palate) are treated according to standard pediatric care and might involve multiple medical specialists and surgery.1-3,24
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
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For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
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