(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?
Etanercept (Enbrel®) is a type of medicine called a TNF-alpha inhibitor and may also be referred to as a biologic or monoclonal antibody therapy. It works by blocking molecules in the immune system that cause inflammation. It is therefore prescribed to treat a number of different auto-immune conditions including rheumatoid arthritis, ankylosing spondylitis and psoriasis. It is occasionally also prescribed to women who have previously had recurrent miscarriages or unsuccessful IVF to increase their chance of having a baby.
Is it safe to take etanercept in pregnancy?
There is no yes or no answer to this question. When deciding whether to take etanercept during pregnancy it is important to weigh up how necessary etanercept 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. 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 etanercept on a baby in the womb.
What if I have already taken etanercept 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 etanercept 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.
Taking etanercept (or another TNF-alpha inhibitor) in pregnancy has not been shown to cause birth defects in the baby. However, because only small numbers of pregnant women taking these medicines have been studied, more information needs to be collected to confirm these results. The studies that have investigated this are summarised below.
Two small studies investigated the risk of birth defects in a total of 129 babies of pregnant women who took etanercept during the first trimester. The first study showed that babies whose mothers took etanercept in pregnancy were no more likely to have a birth defect than babies of women in the general population. The second study showed that birth defect rates were similar in babies born to women taking etanercept and babies born to women with similar illnesses but who were not taking etanercept.
Four studies have investigated babies born to groups of women who took any TNF-alpha inhibitor in early pregnancy. Some of the women in these studies were taking etanercept but they were not studied separately. The findings of these studies may therefore not be directly relevant to women taking etanercept but are included for interest. All of these studies showed that women taking TNF-alpha inhibitors were no more likely to have a baby a birth defect than women who did not take these medicines. In one of these studies, use of TNF-alpha inhibitors was more common amongst mothers of babies with multiple birth defects, however this finding is thought to have occurred because of the way in which the information for this study was collected and analysed. When all the scientific studies are considered together they do no show that TNF-alpha inhibitors cause birth defects.
Can taking etanercept in pregnancy cause miscarriage?
Studying miscarriage rates in women taking etanercept and other TNF-alpha inhibitors is complex as some of the mother’s illnesses that these medicines are used to treat are known to increase the chance of miscarriage.
No studies have specifically assessed miscarriage rates in pregnant women taking etanercept.
Two studies have investigated this in women who took any TNF-alpha inhibitor in early pregnancy. Neither shows an increased risk of miscarriage. Although some of the women in these studies were taking etanercept, they were not studied separately and the findings of these studies may therefore not be directly relevant to women taking etanercept.
More research is therefore required to determine whether use of etanercept in pregnancy affects the chance of miscarriage.
Can taking etanercept in pregnancy cause stillbirth?
No studies have specifically analysed stillbirth rates in pregnant women taking etanercept.
There are two studies of pregnant women taking any TNF-alpha inhibitor. One showed no increased risk of stillbirth, the second smaller study provided very weak evidence of a possible increased risk of stillbirth. More research into this subject is therefore required. It should also be noted that while some of the women in these studies were taking etanercept, they were not studied separately so the findings of these studies may not apply to etanercept.
Can taking etanercept in pregnancy cause preterm birth, or my baby to be small at birth (low birth weight)?
Some of the underlying illnesses that etanercept and other TNF-alpha inhibitors 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). It is therefore very difficult to say whether TNF-alpha inhibitors have an effect on these outcomes.
No scientific studies have specifically investigated whether pregnant women taking etanercept are at increased risk of having a preterm birth or a low birth weight baby.
Five studies have investigated whether pregnant women taking any TNF-alpha inhibitor are more likely to have either a preterm birth or a baby with a low birth weight. These studies have produced mixed results, possibly because most studies did not account for the effects of the mother’s underlying illness.
Two of the studies suggested that rates of both preterm birth and low birth weight babies were increased in women taking TNF-alpha inhibitors in pregnancy. One further study showed that while rates of low birth weight infants were increased in women taking TNF-alpha inhibitors, rates of preterm birth were not. The two further studies did not provide any evidence that women taking TNF-alpha inhibitors had a higher chance of having a low birth weight baby.
Further research that takes into account the effects of the underlying illness in the mother is required before we can say whether use of etanercept and other TNF-alpha inhibitors in pregnancy increases the chance of preterm birth or of having a baby with a low birth weight.
Can taking etanercept in pregnancy cause other health problems in the child?
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.
No link with learning and behavioural problems, e.g. autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), is known about in children who were exposed to etanercept while in the womb, however no studies have been carried out to specifically investigate this.
A single small study showed no difference in the developmental milestones of babies who had been exposed in the womb to TNF-alpha inhibitors and those not exposed to any medicines. No other studies have investigated developmental effects, which is why more information needs to be collected.
Infections and live vaccines in the baby after birth
TNF-alpha inhibitors work by reducing or inactivating antibodies and other molecules that are important to fight off infections. There are therefore concerns that babies who are exposed to etanercept in the womb may be more likely to develop infections after birth. No studies have assessed infection risk in babies specifically exposed in the womb to etanercept. The only study of babies exposed to any TNF-alpha inhibitor did not find any evidence that exposure was linked to an increased risk of infection in the child after birth, but further research is required to confirm this finding.
There are also concerns that babies who are exposed to TNF-alpha inhibitors in the womb could become ill if they receive a live vaccine. Live vaccines (e.g. rubella, measles, mumps, rotavirus) contain modified versions of the live viruses or bacteria that they protect against. They do not cause illness in people with healthy immune systems but are often not advised in people with low immunity. As a precaution, the manufacturer of etanercept recommends that infants who were exposed to etanercept in the womb are not given live vaccinations until 16 weeks after the mother’s final pregnancy dose of etanercept.
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 etanercept in pregnancy is not expected to cause problems that would require extra monitoring of your baby. However, women with some of the illnesses that etanercept 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 etanercept?
A small study found that one out of forty babies fathered by men who had taken etanercept up to three months before conception was born with malformations. This malformation rate is similar to that expected in the background population. Most experts agree that the majority of medicines used by the father are unlikely to harm the baby through affects on the sperm. However, more research on the effects of etanercept specifically, and medicine use in men around the time of conception generally, is needed.
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.