Rheumatoid Arthritis & Pregnancy
Rheumatoid arthritis (RA) is more common in females and often presents at an age when people are considering starting families. The management of RA before, during and after pregnancy is an important topic. Managing rheumatoid arthritis in pregnancy has the potential to be complex for several reasons:
• Rheumatoid arthritis disease activity and some of the medications used to control it have the potential to affect fertility, development in the womb and the newborn immune system.
• Pregnancy has the potential to affect rheumatoid arthritis disease activity.It is important to remember that while RA has the potential to affect your pregnancy, pregnancy itself also has the potential to affect your RA. This guide aims to cover some common concerns that women with RA may have about their pregnancy journey.
Historically, it was believed that RA itself might affect fertility, or the body’s ability to conceive. However, if RA disease activity is well controlled, there is no particular reason why most women with RA will not be able to fall pregnant and enjoy a successful pregnancy. As with any normal pregnancy, planning ahead is important and you should discuss your plans as early as possible with your rheumatologist. Following a healthy lifestyle will increase your chances of conceiving and reduce potential problems during pregnancy.
The risk of adverse pregnancy outcomes, such as miscarriage, for women with RA is not significantly greater than for any other pregnant women as long as the RA is well controlled. Some women may be concerned about ‘passing on’ their RA to their child. RA affects just under 1% of the population and having a first degree relative with RA is thought to double this risk, so the increased risk for a child born to a mother with RA is very small.
All women who are pregnant or planning a baby should take folic acid supplements (0.4mg/day) to decrease the risk of spina bifida and this can be especially important if you have been treated with drugs such as methotrexate. Some medications used to treat RA can be continued while trying to conceive although there are a few (such as higher dose prednisolone) that have the potential to reduce fertility. There are also some medications that may have to be stopped for a while before trying to conceive to ensure they are eliminated from the body. Fortunately, the British Society for Rheumatology (BSR) guidelines and European League Against Rheumatism (EULAR) recommendations concerning prescribing anti-rheumatic drugs in pregnancy were published in 2016.
RA during pregnancy:
Some women find that the pain and swelling associated with RA improves throughout pregnancy. However, some women’s symptoms of RA do not improve in pregnancy and some women’s symptoms even get worse (perhaps relating to the cessation of some of their anti-rheumatic drugs). It is therefore important to ensure that there is a clear plan of action in place in case your symptoms do get worse. During the later stages of pregnancy, swelling, backaches and tiredness are common regardless of whether someone has RA or not. It is important that these normal pregnancy symptoms are not mistaken for symptoms of RA, but should be discussed with your doctor and/or midwife if you have any concerns.
Use of drugs in pregnancy:
Most medications are labelled ‘not for use in pregnancy’ as, by and large, drugs are not tested on pregnant women. It is therefore difficult to guarantee that drugs are safe for use in pregnancy, especially with newer drugs, where the number of pregnancies studied is still low. In addition to this, animal studies that may have been carried out are often not applicable to humans. Although you may be concerned about the possible harmful effects of taking anti-rheumatic drugs whilst pregnant, it is important to remember that uncontrolled RA during pregnancy can potentially lead to adverse pregnancy events (such as low birth weight). As RA will vary between individuals it is always advisable to speak to your GP/rheumatologist about your situation and consult them prior to stopping any drugs. Some of the concerns about the use of common drugs used to treat RA during pregnancy are listed below.
Non-Steroidal Anti-inflammatory Drugs (NSAIDs):
Many women and men take NSAIDs for relief of pain and stiffness associated with RA. High dose NSAIDs have been associated with reduced fertility in women so this should be considered when planning a pregnancy. NSAIDs are considered safe to take in the first and second trimesters of pregnancy (although we recommend their use in the lowest dose possible). NSAIDs should be avoided after week 32 as they can potentially interfere with the way a baby in the womb transitions from a mother’s blood supply to their own in preparation for birth. NSAIDs are safe to take while breastfeeding and many women find them beneficial to treat pain after childbirth (i.e. following caesarean section). Men do not need to avoid NSAIDs at any time while their partners are trying to conceive.
Selective COX-2 inhibitors (e.g. celecoxib, etoricoxib):
Some women and men will be prescribed COX-2 inhibitors instead of NSAIDs. There is no good quality data about their safety during conception, pregnancy or breastfeeding. Therefore, it is advised that both men and women avoid these medications while trying to conceive and women continue to avoid during pregnancy and whilst breastfeeding.
Corticosteroids (e.g. prednisolone):
Low to moderate doses of corticosteroids can be safely used during conception, pregnancy and breast-feeding. Corticosteroids should be used in the lowest dose possible to control the disease, as higher doses have been linked to adverse pregnancy outcomes (such as premature rupture of membranes) as well as an increased risk of hypertension and gestational diabetes. If you have been using steroids for a long time, it may be necessary to receive a ‘stress dose’ in the birthing period. There is a suggestion that prednisolone doses >7.5mg/day may reduce fertility in women trying to conceive although corticosteroids are safe to use by males whilst their partners are trying to conceive.
Hydroxychloroquine is safe to continue throughout pregnancy and is compatible with breast-feeding. It is also not thought to affect fertility.
Sulfasalazine (at doses up to 2g/day) with folate supplementation is safe to continue whilst trying to conceive and throughout pregnancy. Sulfasalazine is also compatible with breast-feeding in a healthy, full-term infant. Sulfasalazine has been linked to a temporary reduction in sperm count in males so men may consider stopping sulfasalazine if their partner is struggling to conceive.
Methotrexate (MTX) is associated with an increased risk of miscarriage as well as birth defects such as spina bifida. MTX should therefore be stopped in women at least 3-months before trying for a baby. MTX can reduce folate levels, so taking folic acid supplementation is important. Women should remain off MTX throughout pregnancy and whilst breastfeeding. MTX, at the doses we use to treat RA, is now believed to be safe to use in males whose partners are trying to conceive (although this is based on limited evidence).
There is very little evidence surrounding leflunomide exposure in pregnancy in humans. Currently, leflunomide is not recommended in women planning pregnancy and a washout procedure using cholestyramine and measurement of drug levels is recommend prior to conception. Data with regards to breast-feeding whilst on leflunomide, as well as paternal exposure to the drug is lacking.
Anti-TNF biologic drugs:
Anti-TNF biologic drugs include etanercept, infliximab, adalimumab, certolizumab pegol and golimumab. Studies have demonstrated that there is no increase in adverse pregnancy outcomes (such as foetal abnormalities) in babies whose mothers fell pregnant while on anti-TNF medication. However, it is important to remember that all the anti-TNF drugs have slightly different structures so do not necessarily behave in the same way. Anti-TNF therapies are considered safe for women to take whilst trying to conceive and generally up until the end of the second trimester, although guidance does vary between drugs.
Studies have shown that certolizumab pegol does not cross the placenta and is therefore considered safe to use throughout pregnancy if clinically needed. Certolizumab pegol (Cimzia) has a European Medicines Agency (EMA) licence wording change to reflect this. However, like all anti-TNF drugs, it should be stopped shortly prior to delivery to reduce the risk of infection in the mother during the delivery period.
Both etanercept (Enbrel) and adalimumab (Humira) have also recently had an EMA licence wording change stating that they are considered safe to use throughout pregnancy if clearly needed. However both of these drugs do cross the placenta in varying amounts and both therefore have the potential to affect a baby’s immune system if taken by their mother in the third trimester. To make things more complicated, it should also be noted that these licence changes are not yet reflected in bio-similars of etanercept or adalimumab.
If you do receive anti-TNF drugs in pregnancy, ensure that your baby’s GP, paediatrician and health visitor are aware of this as it could affect some of the live vaccines your child is offered (i.e. rotavirus and tuberculosis vaccination). It is also worth discussing this ahead of giving birth if possible, with your rheumatologist and obstetrician, who will know about the effects of these drugs and will be able to discuss the options in terms of vaccinations, so that when the time comes to talk things through with your baby’s GP and health visitor (who will not necessarily be as familiar with these drugs), you will have had a discussion about this decision in advance.
Anti-TNF drugs are considered safe to take whilst breast-feeding (although there is limited data available for some of these drugs).
Other biologic therapies and JAK inhibitors:
There is limited to no pregnancy or fertility data available for other biologic therapies used for the treatment of RA (such as abatacept, rituximab and tocilizumab) and no human data available for the new JAK inhibitors (baracitinib and tofacitinib). Rituximab has not been shown to cause foetal abnormalities but exposure later in pregnancy is associated with a low B-cell count in the newborn. Overall, due to the limited data available, it is currently felt that these biologic therapies and JAK inhibitors should be stopped prior to conception and should only be considered for use in pregnancy when no other pregnancy-compatible drug can effectively control disease activity in the mother.
Delivery and after:
For many women with RA, labour is much the same as for any other normal pregnant woman. However, occasionally there may be concerns if your RA has severely affected your hips or your mobility and it is important to discuss any concerns with your midwife/consultant prior to delivery. There is some evidence to suggest that women with RA have a slightly increased risk of adverse pregnancy outcomes (such as premature delivery) or having a caesarean section but these are largely related to how active your RA is. Many women with RA find that their RA returns or experience a flare 2-3 months after delivery (probably related to hormonal excesses that occur in pregnancy returning to normal). Coping with a newborn baby can be tiring for all mothers and this may be more so for women with RA because of the additional worries of RA flaring up. It is important to have sufficient support and help during this period, from those around you as well as your GP/rheumatologist/rheumatology nurse specialist.
There is no specific reason why having RA should affect your ability to breast-feed should you wish to. Even if it is only for a few weeks it is a healthy start to life but you should not feel guilty if you are not able to breast-feed for any reason.
If you do decide to breastfeed, you can get a lot of support with doing so from organisations such as The Breastfeeding Network.
As some drugs can pass through into the breast milk it is important to discuss which drugs are best to take with your GP/rheumatologist. It is also important to remember that, in the long-term, it may be more beneficial for you (and your child) to take medication to control your RA rather than not take them in order to breast-feed. This may not be an easy decision to take at the time. More specific information on drugs whilst breast-feeding is available elsewhere on this website and others.
As RA will vary between individuals the most important thing is to plan ahead and discuss the pros and cons of drugs for your own situation with your GP/rheumatologist in order to achieve a happy and healthy pregnancy. However, if you do find that you have unexpectedly become pregnant while taking drugs for your arthritis, don’t panic and contact your GP/rheumatologist as soon as possible.
For more information on medication and pregnancy/breastfeeding, see the British Society for Rheumatology (BSR) guidelines:
References available on request