(Date of issue: July 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?
Azathioprine (Imuran®) is used to treat severe eczema that has not responded to other treatments, a number of auto-immune illnesses such as lupus, inflammatory bowel disease, rheumatoid arthritis and psoriasis, and to prevent the rejection of transplanted organs. Another form of the same medicine called mercaptopurine (Puri-Nethol®, Xaluprine®) is used to treat certain forms of leukaemia, and occasionally inflammatory bowel disease.
Is it safe to take azathioprine/mercaptopurine in pregnancy?
There is no yes or no answer to this question. When deciding whether to take azathioprine/mercaptopurine during pregnancy it is important to weigh up how necessary azathioprine/mercaptopurine is to your health against any possible risks to you or your baby, some of which may depend on how many weeks pregnant you are. Use of azathioprine/mercaptopurine in pregnancy may sometimes be considered necessary to prevent the rejection of a transplanted organ, or to keep leukaemia or a serious autoimmune illness under control for the benefit of both the mother and her unborn baby. Your doctor is the best person to help you decide what is right for you and your baby.
This leaflet summarises the scientific studies relating to the effects of azathioprine/mercaptopurine on a baby in the womb.
What if I have already taken azathioprine/mercaptopurine during pregnancy?
If you have taken 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 to make sure that you are taking the lowest dose that works.
Can taking azathioprine/mercaptopurine in pregnancy cause my baby to be born with birth defects?
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.
None of the twelve studies that have investigated this have shown that babies whose mothers took azathioprine in the first trimester of pregnancy are any more likely to have a birth defect than babies of healthy women who did not take azathioprine.
Two studies investigated whether a number of specific birth defects were more likely in babies exposed to azathioprine in the womb. Neither of these studies showed that azathioprine use in early pregnancy increases the chance of the baby having a heart defect, a genital defect (in one study) or hypospadias (where the opening of the penis is on the underside rather than the tip) in the other study.
Can taking azathioprine/mercaptopurine in pregnancy cause miscarriage?
None of the seven studies that have investigated this have provided evidence of an increased risk of miscarriage in pregnant women taking azathioprine/mercaptopurine. Although this is reassuring, none of these studies used the most up-to-date and accurate methods to study miscarriage rates. Further research is therefore required to confirm this finding.
Can taking azathioprine/mercaptopurine in pregnancy cause stillbirth?
Five studies, which together included a total of around 400 pregnant women taking azathioprine/mercaptopurine, have measured how often stillbirth occurred either in comparison to women in the general population or to pregnant women not taking azathioprine/mercaptopurine. None of these studies showed that treatment with azathioprine/mercaptopurine in pregnancy increases the chance of stillbirth. Some of the studies were not as scientifically good as the others so stillbirth rates need to be studied in more pregnant women taking azathioprine/mercaptopurine.
Can taking azathioprine/mercaptopurine in pregnancy cause preterm birth, or my baby to be small at birth (low birth weight)?
Some of the underlying illnesses that azathioprine/mercaptopurine are used to treat may themselves increase the chance of preterm birth (before 37 weeks) and/or of a baby having a low birth weight (less than 2,500g). This complicates investigations of whether azathioprine/mercaptopurine has an effect on these outcomes.
The thirteen studies that have investigated whether use of azathioprine in pregnancy increases the risk of preterm birth have produced mixed results. However, most of the better studies that accounted for how the underlying illness in the mother might affect a baby’s health in the womb found no link between azathioprine use in pregnancy and preterm birth.
All of the nine studies that investigated whether pregnant women taking azathioprine/mercaptopurine were at increased risk of having a low birth weight baby, and that accounted for the effects of the underlying illnesses in the mother, showed no link between azathioprine use and low birth weight in the baby.
There is therefore currently no proof that azathioprine/mercaptopurine use in pregnancy increases the chance of or of preterm birth or of the baby having a low birth weight.
Can taking azathioprine/mercaptopurine in pregnancy cause other health problems in the child?
Low blood count at birth
A well-known side effect of treatment with azathioprine or mercaptopurine in non-pregnant people is that it can cause low levels of certain types of blood cells that are important to fight infection and for blood clotting. A few case studies have been published in medical journals that describe babies who were exposed to azathioprine/mercaptopurine in the womb being born with low blood counts. So far no large studies have been carried out so it is not known how likely it is that treatment with azathioprine/mercaptopurine in pregnancy will affect a baby’s blood cells. If your baby shows any symptoms (such as anaemia, unexpected infections, or problems with blood clotting), his/her blood count may be checked after birth.
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.
Three small studies have investigated whether children exposed to azathioprine/mercaptopurine in the womb are more likely to have learning and behavioural problems. Two of these studies which assessed children up to the age of six did not show that exposure to azathioprine/mercaptopurine in the womb was linked to learning and behavioural problems. The third study showed that children over two years old who were exposed to azathioprine/mercaptopurine in the womb were slightly more likely to require educational support but was too small to know whether this was just a chance finding. Larger scientific studies are needed to accurately study learning and behaviour in children exposed to azathioprine/mercaptopurine in the womb.
Will my baby need extra monitoring during pregnancy?
Most women will be offered a scan at around 20 weeks of pregnancy to look for birth defects as part of their routine antenatal care. Taking azathioprine/mercaptopurine in pregnancy is not expected to cause problems that would require extra monitoring of your baby. However, women with some of the illnesses that azathioprine/mercaptopurine is used to treat may be more closely monitored during pregnancy to ensure that they remain well throughout, and that their baby is growing and developing as expected.
Are there any risks to my baby if the father has taken azathioprine/mercaptopurine?
There is currently no evidence that problems are more common in babies fathered by men who were being treated with azathioprine or mercaptopurine at the time of conception. However, not very much scientific information is available (see below) and because of the way that these medicines work there is a theoretical worry that they may cause changes in the sperm’s genetic code that could then cause health problems for the baby, either at birth or later on in life.
As a precaution, men on azathioprine or mercaptopurine are advised to use contraception. Before attempting to father a child, some men may be given the option to stop their treatment with azathioprine or mercaptopurine or to switch to a different medicine. As it takes around three months for sperm to develop, use of contraception will be advised for six months after azathioprine/mercaptopurine treatment is stopped.
Although there have been individual case studies of babies being born with birth defects after their fathers used azathioprine/mercaptopurine around the time of conception reassuringly six out of seven scientific studies have now shown that birth defects are no more common in babies whose fathers took azathioprine/mercaptopurine around the time of conception. Studies carried out so far have also not shown links between the father using azathioprine and miscarriage, preterm delivery, and low birth weight in the baby. It is important that information continues to be collected so that couples in the future can make informed choices based on facts.
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.
Up to 1 out of every 5 pregnancies ends in a miscarriage, and 1 in 40 babies are born with a birth defect. These are referred to as the background population risks. They describe the chance of these events happening for any pregnancy before taking factors such as the mother’s health during pregnancy, her lifestyle, medicines she takes and the genetic make up of her and the baby’s father into account.
Medicines use in pregnancy
Most medicines used by the mother will cross the placenta and reach the baby. Sometimes this may have beneficial effects for the baby. There are, however, some medicines that can harm a baby’s normal development. How a medicine affects a baby may depend on the stage of pregnancy when the medicine is taken. If you are on regular medication you should discuss these effects with your doctor/health care team before becoming pregnant.
If a new medicine is suggested for you during pregnancy, please ensure the doctor or health care professional treating you is aware of your pregnancy.
When deciding whether or not to use a medicine in pregnancy you need to weigh up how the medicine might improve your and/or your unborn baby’s health against any possible problems that the drug may cause. Our bumps leaflets are written to provide you with a summary of what is known about use of a specific medicine in pregnancy so that you can decide together with your health care provider what is best for you and your baby.
Every pregnancy is unique. The decision to start, stop, continue or change a prescribed medicine before or during pregnancy should be made in consultation with your health care provider. It is very helpful if you can record all your medication taken in pregnancy in your hand held maternity records.