(Date of issue: May 2015. Version: 2)
This factsheet has been written for members of the public by the UK Teratology Information Service (UKTIS). UKTIS is a not-for-profit organisation funded by Public Health England on behalf of UK Health Departments. UKTIS has been providing scientific information to health care providers since 1983 on the effects that medicines, recreational drugs and chemicals may have on the developing baby during pregnancy.
What is it?
Carbamazepine (Tegretol®, Carbagen®) is used to treat epilepsy, sometimes in combination with other epilepsy medicines. Carbamazepine is also sometimes used in the treatment of bipolar disorder, certain types of nerve pain, and during alcohol detoxification to control certain withdrawal symptoms.
Is it safe to take carbamazepine in pregnancy?
There is no yes or no answer to this question. When deciding whether or not to take carbamazepine during pregnancy it is important to weigh up how necessary carbamazepine is to your health against the possible risks to you or your baby, some of which will depend on how many weeks pregnant you are. Remaining well is particularly important during pregnancy and whilst caring for a baby. It is vital that epilepsy is well-controlled during pregnancy as seizures can harm both the mother and unborn child. For some pregnant women treatment with carbamazepine may be necessary.
This leaflet summarises the scientific studies relating to the effects of carbamazepine on a baby in the womb. It is advisable to consider this information if you are taking carbamazepine and are pregnant or could become pregnant in the future.
Your doctor is the best person to help you decide what is right for you and your baby.
What if I have already taken carbamazepine during pregnancy?
If you have taken or are taking any medicines it is always a good idea to let your doctor know that you are pregnant so that you can decide together whether you still need the medicines that you are on and, if so, to make sure that you are taking the lowest dose that works and only for as long as you need to.
It is very important that you do not suddenly stop taking carbamazepine as this could be dangerous to you, and also to your baby if you are already pregnant. Do not make any changes to your medication without first talking to your doctor.
Because of the normal bodily changes that occur as pregnancy progresses your doctor may advise closer monitoring of your health to assess whether your carbamazepine dose needs to be adjusted during your pregnancy for it to remain effective. You should not change the dose of any prescribed medicine without medical supervision.
Why has my doctor recommended that I take high dose folic acid?
Carbamazepine can cause low folic acid levels. Folic acid is necessary for a baby’s growth and development in the womb. Women who have low folic acid levels in early pregnancy are much more likely to have a baby with a birth defect of the spine called a neural tube defect. It is therefore recommended in the UK that all women taking carbamazepine also take high dose folic acid (5mg/day) instead of the standard dose of 400mcg whilst trying to conceive and during the first trimester of pregnancy. High dose folic acid has to be prescribed by a doctor.
Although it is very clear that taking folic acid in pregnancy protects against neural tube defects in general, there is not yet any scientific evidence to show that taking folic acid supplements at either high or standard doses can protect against any of the birth defects or other problems that may be specifically caused by carbamazepine. However, until more scientific information is available, high dose folic acid is advised. For more information, please see the folic acid bumps leaflet.
Can taking carbamazepine in pregnancy cause birth defects in the baby?
A baby’s body and most internal organs are formed during the first 12 weeks of pregnancy. It is mainly during this time that some medicines are known to cause birth defects. Some studies have shown that carbamazepine use in pregnancy may increase the risk of certain birth defects in the baby. However other studies have not agreed with these findings and further research is therefore required. For more information, see the sections below.
Neural tube defects, e.g. spina bifida
Five studies have investigated whether carbamazepine use in pregnancy increases the chance of the baby having a neural tube defect (defect of the brain or spine) including spina bifida. Two of the studies showed a possible link but the other three studies did not. Information from four studies was then combined in a further type of analysis that is considered to be one of the most reliable ways of analysing scientific data. This study (called a meta-analysis) showed that women taking carbamazepine in pregnancy are about four times more likely to have a baby with spina bifida than women not taking carbamazepine. This suggests that around one out of every 500 women who take carbamazepine in early pregnancy will have a baby with spina bifida, compared to one out of every 2,000 women in the general population.
Cleft lip and/or palate
Two studies have shown a possible link between carbamazepine use in pregnancy and cleft lip and/or palate (a split in the lip and/or the roof of the mouth) in the baby, but a further two studies did not show any link. More research is therefore required to determine whether or not taking carbamazepine in pregnancy increases the chance of cleft lip and /or palate in the baby or whether other factors explain the findings of the first two studies.
Defects of the urinary tract and hypospadias
A single study showed a possible link between carbamazepine use in pregnancy and defects of the urinary tract (kidneys, bladder and connecting tubes), although two further studies provided no evidence of such a link.
One further study suggested that boys born to women who took carbamazepine in pregnancy may be more likely to have hypospadias (where the opening of the penis is on the underside rather than the tip). No other studies have looked at this.
More information therefore needs to be collected to accurately assess whether there are links between carbamazepine use in pregnancy and defects of the urinary tract, or hypospadias.
Particular facial features
A number of studies have suggested that babies who are exposed to carbamazepine in the womb have a similar facial appearance to each other. These facial features are generally very subtle, and might include their eyes being slightly wider apart, their nose being smaller, broader and flatter than the rest of the family, tiny skin folds at the inner corner of the eyes (epicanthal folds), and the groove above the top lip (philtrum) being longer and smoother than usual. These features may only be picked up by specialists who are trained to look for them and generally become less obvious in later childhood.
Other birth defects
Various studies have suggested a possible link between carbamazepine use in pregnancy and a number of very different birth defects including defects of the breathing system, a type of rare heart defect called anomalous venous return, and diaphragmatic hernia (a hole in the baby’s diaphragm, which is the muscular sheet that separates the lungs and the abdomen or tummy). However, each of these findings is from a single study and there is therefore currently no scientific proof that carbamazepine use in pregnancy causes any of these birth defects in the baby.
A number of studies have shown that carbemazepine use in pregnancy may be linked to subtle features in the baby such as abnormal fingers (usually a slightly shorter 5th finger) and nails.
Does taking carbamazepine in combination with other anti-epileptic medicines increase the chance of birth defects in the baby?
Carbamazepine is sometimes taken in combination with other medicines to treat epilepsy. Some studies have suggested that women taking more than one type of anti-epileptic medicine may be more likely to have a baby with a birth defect than women taking only one anti-epileptic medicine. However, it is now thought that this finding may be due to the fact that many of the women in these studies were taking combinations of anti-epileptics that included sodium valproate (Epilim®), an antiepileptic medicine which is known to cause birth defects.
Although some studies have suggested that women taking carbamazepine in combination with other anti-epileptic medicines may be at an increased risk of having a baby with a birth defect compared to women who just take carbamazepine, most of these studies did not record the type of anti-epileptic drug that the women were taking in addition to carbamazepine. More research is therefore required to determine whether taking carbemazepine in combination with other anti-epileptic medicines poses a greater risk to the baby than taking carbamazepine on its own.
If you are taking more than one medicine to control epilepsy you should discuss any concerns that you may have with your doctor. Do not stop or alter the dose of any medicine you are taking without first speaking to your doctor. Making changes to your medicine yourself may be more harmful to both you and your baby than continuing to take that medicine.
Can taking carbamazepine in pregnancy cause miscarriage or stillbirth?
There is currently no convincing scientific evidence to show that carbamazepine use in pregnancy causes miscarriage or stillbirth. However, this has not been extensively studied and so more research is required before any links can be ruled out.
Can taking carbamazepine in pregnancy cause preterm birth or my baby to be small at birth (low birth weight)?
It is currently unclear whether taking carbamazepine in pregnancy is linked to preterm birth (before 37 weeks of pregnancy) or having a low birth weight baby (<2,500g), because the results of the studies that have investigated these outcomes do not agree.
Nine small studies that assessed whether preterm birth was more likely in pregnant women who took carbamazepine all showed no increase in risk. However, one large study of over 1,000 pregnant women taking carbamazepine found that women who took carbamazepine in pregnancy were more likely to give birth prematurely. Although larger studies are generally considered to be more accurate, because all of the other nine studies do not agree with this finding, further carefully planned large studies are required to answer this question.
Eighteen studies have investigated whether taking carbamazepine in pregnancy can affect the baby’s birth weight. While twelve studies showed no effect of carbamazepine on a baby’s birth weight, six studies showed that women taking carbamazepine in pregnancy may be more likely to have babies that are smaller than expected at birth. Many factors can affect a baby’s growth in the womb and more research is therefore required to assess whether carbamazepine use in pregnancy may cause a baby to have a lower birth weight.
Can taking carbamazepine in pregnancy cause other health problems in the child?
Withdrawal symptoms at birth (neonatal withdrawal)
Withdrawal symptoms are thought to occur when a newborn baby’s body has to adapt to no longer getting certain types of medicines through the placenta.
Carbamazepine works in a similar way to other medicines that are known to cause neonatal withdrawal. The only study that has investigated how a baby may be affected after birth, found that babies exposed to carbamazepine in the womb were more likely to need help with their breathing after birth. Close monitoring of your baby for a few days after birth may therefore be advised if you have taken carbamazepine regularly in the weeks before delivery. Monitoring of your baby may be particularly important if you have taken carbamazepine in combination with other anti-epileptic medicines or medicines that act on the brain.
Bleeding problems in the newborn baby
Carbamazepine is similar to medicines that reduce the ability of blood to clot. Although no studies have specifically investigated whether bleeding problems are any more common in babies whose mothers took carbamazepine in pregnancy, because of the possible (theoretical) risk of serious bleeding problems, it is currently recommended that all babies born to women who took carbamazepine in pregnancy receive an injection of vitamin K at birth to help to protect against blood clotting problems.
Learning and behavioural problems
A baby’s brain continues to develop right up until the end of pregnancy. It is therefore possible that taking certain medicines at any stage of pregnancy could have a lasting effect on a child’s learning or behaviour. Because carbamazepine acts upon the brain there have been concerns that its use in pregnancy may affect a baby’s brain development.
It is currently unclear whether carbamazepine exposure in the womb causes lasting alterations to learning and behaviour. The majority of studies do not show that children who were exposed to carbamazepine in the womb are more likely to have problems with co-ordination, movement, learning, and behaviour compared to children not exposed to carbamazepine. However, some studies have shown that exposure to carbamazepine in the womb may affect a child’s overall development, fine motor skills (the way that the brain controls small muscle movements usually of the hands and fingers), and may increase the likelihood of poor attention, and aggressive behaviour in the child.
There is currently no convincing evidence that children exposed to carbamazepine in the womb have a higher chance of having autism spectrum disorder (ASD) although ASD rates have been studied in only small numbers of children, and further research is therefore required to confirm this.
More studies are needed before we can say whether carbamazepine use in pregnancy affects the child’s learning and behaviour.
Will my baby need extra monitoring?
As part of their routine antenatal care most women will be offered a scan at around 20 weeks of pregnancy to look for birth defects and to check the baby’s growth. Women with epilepsy are likely to be more closely monitored during pregnancy to ensure that they remain well throughout and that their baby is growing and developing as expected.
Because there is a possibility that carbamazepine taken in the first trimester increases the chance of certain birth defects in the baby, your doctor may offer you the option of having more detailed anomaly scans around 12 weeks of pregnancy. It is however, harder to see birth defects when the baby is still so small, which is why the main scan for birth defects is generally offered at around 20 weeks of pregnancy. It is important to understand that scans are not able to pick up all birth defects and cannot predict whether a baby will have problems with learning and behaviour.
Carbamazepine can affect blood clotting, which may lead to bleeding problems in the baby after birth (see above). Pregnant women taking carbamazepine may therefore be offered vitamin K injections in the later stages of pregnancy to help prevent this.
If you have taken carbamazepine around the time of delivery your baby may require extra monitoring after birth because of the risk of neonatal withdrawal.
Are there any risks to my baby if the father has taken carbamazepine?
We would not expect any increased risk to your baby if the father took carbamazepine before or around the time you became pregnant.
Who can I talk to if I have questions?
If you have any questions regarding the information in this leaflet please discuss them with your health care provider. They can access more detailed medical and scientific information from www.uktis.org.