By Elizabeth Salas, MPH, Teratology Information Specialist, MotherToBaby California

“My husband and I have been trying to conceive for years, and we’re finally expecting. What can you tell me about the medications I’ve been taking?”

This question is one we receive every day on our MotherToBaby phone line. On this particular day, I was speaking to a pregnant woman who had struggled for years to conceive with MS. She was now doing well, and together with her partner decided to try again. After a preconception appointment with a high-risk obstetrician, speaking with her neurologist, and researching medications and pregnancy, they began trying and were surprised when they conceived right away. This caller wanted to know how safe the medications she was taking would be for her developing baby. I started by reminding her that in every pregnancy a woman has a 3-5% chance of having a baby with a birth defect; the question was whether any of the medications she was taking increased the chance of a birth defect above this background risk.

“What do you know about muscle relaxants?”

Currently two muscle relaxants have received indications by the Food and Drug Administration (FDA) for the treatment of MS. The older of the two medications, Baclofen, can improve mobility and reduce spasticity in MS patients. Although it was first approved for use in the United States in 1977, there is limited information regarding use in human pregnancy. It is not known at this time if treatment during pregnancy could increase the risk for birth defects above the background risk. There are individual published reports of babies born with normal outcomes as well as babies born with abnormal outcomes.

The largest collection of cases compared 134 pregnancies exposed to baclofen in the first trimester to 400 non-exposed pregnancies. There were more elective terminations and birth defects reported among the baclofen exposed pregnancies; in addition, 4 of the 34 babies who were exposed to baclofen until delivery experienced withdrawal symptoms.1 However, there are some important limitations to this study. First, no information was provided regarding the mother’s use of other medications or exposures that could have contributed to birth defects or a decision to terminate. Second, the mothers of the 4 infants who experienced withdrawal symptoms were also being treated with psychiatric medications, which may also cause withdrawal depending on the medication. More studies are clearly needed to better determine the safety of baclofen use in pregnancy.

If baclofen is used in pregnancy, various sources suggest that administration with an intrathecal pump may be preferred. An intrathecal pump is a small device implanted in the abdomen that connects to a small plastic tube (catheter); this tube delivers the medication directly into the spinal column. Because of this direct route to the spinal column, a much smaller dose of baclofen (only 1% of the oral dose) is needed for treatment.7,8

Baclofen used during breastfeeding may transfer into breast milk in small amounts that are not expected to negatively affect an infant. If a mom is receiving doses of baclofen through an intrathecal pump, it is very unlikely medication would transfer to her infant via breast milk.5,6

Tizanidine (Zanaflex®) is a muscle relaxant first used in the US in 1996. Information about its use in pregnancy is limited to animal data and a 2014 report on 6 exposed human pregnancies. Of the 6 human pregnancies, 2 ended in miscarriage and 4 resulted in normal births.4 At this time, there is not enough information to determine the safety of tizanidine use in pregnancy.

The use of tizanidine has not been studied during breastfeeding. The medication would likely transfer into breast milk, but it has not been measured in breast milk studies to determine how much would transfer. More information is needed to determine the safety of tizanidine while breastfeeding.5,6

“What about corticotropin?”

Corticotropin is a medication that contains a hormone called adrenocorticotropic hormone (ACTH). ACTH naturally exists in the body and is normally released by the pituitary gland. This medication can suppress the immune system and have anti-inflammatory effects that can be helpful in treating MS.2 It was first approved for use in the United States in 1950, but has not been well studied during pregnancy. To date there are no studies of corticotropin treatment in human pregnancy, so the safety of this medication when used in pregnancy is not known.7,8

Corticotropin has not been measured in breast milk. Since the medication is quickly broken down, transfer into breast milk is very unlikely. If any medication were to transfer, it is expected to be easily destroyed in the baby’s digestive tract.5,6

“Last, do you know anything about Ampyra®?”

Dalfampridine (Ampyra®) is a potassium channel blocker and was first approved for use in 2010 for the treatment of MS. This medication can improve walking in patients with MS and is thought to help with the function of nerve cells.2 No human pregnancy cases or studies have been published in the medical literature. At this time the safety of use of Ampyra® in pregnancy or breastfeeding is not known.7

The Best Decision

If you are currently pregnant, it’s important to keep in mind that one of the best decisions you can make for your developing baby is to take care of yourself. In the work we do at MotherToBaby, we have to remind expecting mothers that in some cases, stopping treatment may not be an option and may be worse for the pregnancy than continuing. Staying healthy, asking questions, having good communication with your providers, and understanding your options are all very important during pregnancy. If your providers have different opinions, ask them to communicate with each other. Your obstetrician is the pregnancy expert, but your neurologist is the MS expert; you’ll need both of them to help get you through the tough decisions.

WHERE CAN I GET MORE INFORMATION?

Finally, don’t forget that the MotherToBaby experts are here for you as well. We can give you the latest update on any medication or exposure in pregnancy or breastfeeding. Our service is free and confidential. You can speak with a MotherToBaby counselor by calling us toll free at (866) 626-6847. In addition, little is known about the safety of MS medications during pregnancy, but together we can so something to change that. If you’d like to participate or learn more about current MS pregnancy registries, please contact one of our MotherToBaby Pregnancy Studies experts toll free at (877) 311-8972.

Stay tuned for my next blog, where I’ll discuss potential exposures by a father who is being treated for MS.

Elizabeth Salas is the Lead Teratology Information Specialist for MotherToBaby California, a non-profit that provides information to healthcare providers and the general public about medications and more during pregnancy and breastfeeding. She is based at the University of California, San Diego, and is passionate about the work MotherToBaby is doing to promote healthy moms, healthy pregnancies and healthy babies.

Interested in more information about MS and pregnancy? Check out MotherToBaby’s March 2014 blog, “MS: The Diagnosis that Doesn’t Mean Missing Out on Motherhood!” and the December 2014 blog, “For Women with MS: Making Decisions about Pregnancy, Breastfeeding, and More”

MotherToBaby is a service of the international Organization of Teratology Information Specialists (OTIS), a suggested resource by many agencies including the Centers for Disease Control and Prevention (CDC). If you have questions about medications, vaccines, diseases, or other exposures, call MotherToBaby toll-FREE at 866-626-6847 or call the Pregnancy Studies team directly at 877-311-8972. You can also visit MotherToBaby.org to browse a library of fact sheets, as well as visit our Multiple Sclerosis and Pregnancy page at MotherToBaby Pregnancy Studies, www.PregnancyStudies.org.

References:

1. Bernard, N.; Beghin, D.; Huttel, E.; Dunstan H.; Ieri, A.; Te Winkel, B.; Jonville-Bera, A.-P.; Damase-Michel, C.; Vial, T. and the network of French pharmacovigilance centers.: Pregnancy outcome after in utero exposure to baclofen: An ENTIS collaborative study. Birth Defects Res. A Clin. Mol. Teratol. 100(7):525, 2014 [abstract].
2. Clinical Pharmacology [database online]. Tampa, FL: Elsevier/Gold Standard, Inc.; 2015. URL:http://www.clinicalpharmacology.com

1. Drugs in Pregnancy and Lactation 9th Edition [database online]. Briggs G.G., Freeman R.K., & Yaffe S.J. Wolters Kluwer Health – Lippincott Williams & Wilkins; 2015. URL: http://solution.lww.com/briggsdrugsinpregnancy9e
2. Eleftheriou, G.; Butera, R.; Lorenzi, F. and Farina, M.L.: Tizanidine use in pregnancy. Birth Defects Res. A Clin. Mol. Teratol. 100(7):532, 2014 [abstract].
3. Hale, TW, & Rowe, HE. Medications & Mother’s Milk – A Manual of Lactational Pharmacology 16th Edition. Plano, TX: Hale Publishing, 2014.

1. LACTMED® [database online]. Bethesda (MD): National Library of Medicine (US); 2015. Available from : http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm

1. REPROTOX® [database online]. Reproductive Toxicology Center. (2015). URL:http://www.reprotox.org/Default.aspx

1. TERIS & Shepard’s: A Catalog of Teratogenic Agents © [database online]. (2015). URL: http://depts.washington.edu/terisweb/teris/index.html