(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?
Adalimumab (Humira®) is a type of medicine called a TNF-alpha inhibitor and may also be referred to as a biologic, or a monoclonal antibody. It works by blocking molecules that cause inflammation in the body and is prescribed to treat a number of different auto-immune conditions including rheumatoid arthritis, ankylosing spondylitis, psoriasis, Crohn’s disease, and ulcerative colitis.
Is it safe to take adalimumab in pregnancy?
There is no yes or no answer to this question. When deciding whether to take adalimumab during pregnancy it is important to weigh up how necessary adalimumab 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 adalimumab on a baby in the womb.
What if I have already taken adalimumab 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 adalimumab 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.
Only one study of 69 pregnant women who took adalimumab during the first trimester of pregnancy has investigated the risk of birth defects in the baby. This study showed that babies whose mothers took adalimumab in pregnancy were no more likely to have a birth defect than babies of women with similar illnesses but who were not taking adalimumab. However, more information needs to be collected from women taking adalimumab during pregnancy to confirm this result.
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 adalimumab but they were not studied separately. The findings of these studies may therefore not be directly relevant to women taking adalimumab but are included for interest. All of these studies showed that women taking TNF-alpha inhibitors were not at increased risk of having a baby a birth defect. Although one of these studies suggested that use of TNF-alpha inhibitors in pregnancy may be linked to having a baby with multiple birth defects, there were problems with the way in which the information was collected and analysed and it is unlikely that there is any true link but this needs to be confirmed by further research.
Can taking adalimumab in pregnancy cause miscarriage?
No increased risk of miscarriage was seen in two small studies of pregnant women taking adalimumab.
Two further studies of women who took any TNF-alpha inhibitor in early pregnancy also showed no increased risk of miscarriage. Some of these women in these studies were taking adalimumab, but because they were not studied separately, the findings may not be directly relevant to women taking adalimumab.
Miscarriage rates have been studied in only a small number of women taking adalimumab, and studying this is complex as some of the underlying illnesses that adalimumab is used to treat may themselves increase the chance of miscarriage. Much more research into this subject is therefore required.
Can taking adalimumab in pregnancy cause stillbirth?
A single study of 261 pregnant women taking adalimumab did not show that they were at increased risk of stillbirth.
There are two studies of pregnant women taking any TNF-alpha inhibitor. One showed no increased risk of stillbirth, although 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 adalimumab, they were not studied separately, so the findings of these studies may not apply to adalimumab.
Can taking adalimumab in pregnancy cause preterm birth, or my baby to be small at birth (low birth weight)?
Some of the underlying illnesses that adalimumab 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 adalimumab has an effect on these outcomes.
The studies that investigated whether pregnant women taking adalimumab were at increased risk of having a preterm birth or a low birth weight baby have produced mixed results. One study provided no evidence of any increase in risk of preterm birth. A second study showed a possible increased risk of preterm birth and of having a low birth weight baby, but did not account for the underlying illness in the mother, and so any effects may have been due to this rather than to adalimumab.
Five studies have investigated whether pregnant women taking any TNF-alpha inhibitor are more likely to have a preterm birth or a baby with a low birth weight. 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. These studies however, did not account for the underlying illness in the mother, and so any effects may have been due to this rather than to the TNF-alpha inhibitors. The two further studies did not provide any evidence that women taking TNF-alpha inhibitors had a higher chance of having a preterm or low birth weight baby.
Further research into the specific effects of adalimumab on these pregnancy outcomes is required but there is currently no proof that adalimumab use in pregnancy increases the chance of preterm birth or the baby having a low birth weight.
Can taking adalimumab 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 adalimumab while in the womb, however no studies have been carried out to specifically investigate this. A handful of case reports describe normal development up to four years of age in children who were exposed to adalimumab in the womb but larger scientific studies are needed to study this accurately.
A single small study showed no differences in the reaching of development milestones between babies who had been exposed in the womb to TNF-alpha inhibitors and those not exposed to any medicines. No other studies have investigated this which is why more information needs to be collected.
Infections after birth and risk to newborn babies with live vaccines
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 adalimumab in the womb may be more likely to develop infections after birth. There is one study that has assessed infection risk in babies exposed in the womb to adalimumab specifically and one study of babies exposed to any TNF-alpha inhibitor. Neither study found any evidence that exposure to adalimumab or TNF-alpha inhibitors was linked to an increased risk of infection in the child after birth, but further research is required to confirm these findings.
There are also concerns that babies who are exposed to adalimumab 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 adalimumab recommends that live vaccines are avoided in infants who were exposed to adalimumab in the womb for five months after the mother’s final pregnancy dose.
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 adalimumab in pregnancy is not expected to cause problems that would require extra monitoring of your baby. However, women with some of the illnesses that adalimumab 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 adalimumab?
A small study that found that none of six babies fathered by men who had taken adalimumab up to three months before conception were born with malformations. Most experts agree that the majority of medicines used by the father are unlikely harm the baby through affects on the sperm. However, more research on the effects of adalimumab 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.