Autoimmune conditions, such as psoriasis, inflammatory bowel disease and rheumatoid arthritis have the potential to significantly complicate pregnancy.
Both planned and unplanned pregnancies are a major issue for women with these diseases, concerned their baby may be at risk from the highly active medications they take to control their condition. Symptoms of an autoimmune disease can improve, worsen, or remain unchanged when a woman becomes pregnant, depending upon the autoimmune disease in question.
Nowadays, however, the vast majority of pregnancies in women with autoimmune disease proceed safely, but there is a delicate balance that must be achieved between maintaining disease control and limiting potential toxicity to the infant.
The risks relating to medications, as well as disease activity, in pregnancy are being closely looked at by clinicians and researchers. One of those is Megan Clowse, Associate Professor of Medicine, and Director of the Duke Autoimmunity in Pregnancy Registry, at the Duke University Medical Centre in North Carolina, US. She has been exploring the area of medication in pregnancy for those autoimmune diseases, and explains that balancing the risk to the baby and the health of the mother is the most important thing.
She runs the Duke Autoimmunity in Pregnancy (DAP) Registry, a study with over 375 pregnancies in women with a range of rheumatic diseases, and explains that she and her team are using this registry to better understand the roles that disease activity and medications play in pregnancy success. Dr Clowse is also working with ArthritisPower and CreakyJoints.org to develop an online survey about reproductive health among women with inflammatory arthritis, as well as several ongoing projects studying pregnancy and fertility among women with rheumatoid arthritis and psoriatic arthritis. She has also recently participated in studies of the transfer of certilizumab, a biologic medication, across the placenta and into breast milk, the results of which are due in the coming months.
“My main concerns for a woman with arthritis who becomes pregnant surround controlling her arthritis with medications that are safe in pregnancy,” she explains to PMI Blog.
“We have data that suggests allowing the arthritis to flare leads to higher rates of pregnancy complications – more preterm deliveries and smaller babies. There are medications that are considered safe in pregnancy that can control arthritis well. Therefore, we think that the best way to have a healthy baby is to control arthritis with these safe medications.”
According to Clowse, she generally considers medications such as hydroxychloroquine, sulfasalazine, and tumour necrosis factor (TNF)-inhibitors as the best options for controlling arthritis during pregnancy; “I try to use the steroid prednisone infrequently – it appears to cause more complications than these other medications,” she adds.
Until recently, however, there was not a clear consensus on whether biologic medications, such as the TNF inhibitors were safe in pregnancy. As the number of women on these medications and become pregnant grows, the literature on the topic has also swelled. Most people and datasets now agree that TNF inhibitors are safe in pregnancy, says Clowse.
“They have been used for years in women with inflammatory bowel disease (IBD), such as Crohn’s disease or ulcerative colitis, and a registry of over 1,000 pregnancies in women with IBD shows no increase in pregnancy complications or problems for babies with TNF-inhibitor exposure. That was the PIANO registry.”
The rheumatologist explains that, in some cases, reducing the frequency of the dose is possible during pregnancy.
“I allow women to take TNF inhibitors in pregnancy and some are able to space out the dosing as their arthritis improves.”
Some women, however, simply dislike the idea of taking medication during pregnancy, and in some cases this can lead to significant problems. In addition, there is a misconception that autoimmune conditions tend to improve during pregnancy – this can certainly happen, but not in the vast majority of cases. Dr Clowse says that women who cease their normal medication may suffer greatly by doing so – and at greater risk to the baby.
“Almost all women that I’ve cared for who have decided to stop their TNF inhibitor have a significant flare of arthritis and end up with a lot of pain, inflammation, and on prednisone – the pregnancy would likely be more successful if they had stayed on the TNF-inhibitor to control their arthritis.”
Some of the biologic agents do cross the placenta, however; therefore, their dosage must be reduced to zero in the later stages of pregnancy, explains Clowse.
“Most TNF-inhibitors cross the placenta starting around week 16 and, when delivered at term, the baby has a higher concentration of drug than the mother. Therefore, I recommend stopping infliximab, adalimumab, golimumab around 30-32 weeks gestation. Etanercept may cross less, so I generally stop this around 34 weeks. Certilizumab crosses even less, so can be continued through delivery.”
So what happens after pregnancy? According to Clowse, restarting medication at an early stage is vital in order to pre-empt the “post-partum flare” – a worsening in condition that typically occurs four to eight weeks after delivery.
“I typically have women restart their TNF-inhibitor soon after delivery – one week after a vaginal delivery and two weeks after a Caesarean section if they are healing well. This gets the drug started prior to the post-partum flare. With this, I see minimal post-partum flare symptoms,” she notes.
The evidence may be there to support the use of biologic agents during pregnancy, but the issue of taking medication while pregnant is a very personal one, and not all expectant mothers are privy to the most up-to-date information. Is the decision-making process for a woman with an autoimmune condition difficult?
Clowse says it is, particularly when obstetricians and rheumatologists or gastroenterologists may have differing views.
“Many women can’t find clear answers and get conflicting guidance from their rheumatologists and obstetricians. This isn’t surprising given the limited available data and the infrequency that these physicians are faced with a pregnant patient. Many women feel most comfortable stopping all drugs in pregnancy, but for women with chronic diseases, that might not be the best approach to having a healthy baby.”