EXPERT ANALYSIS AT THE CMSC ANNUAL MEETING
INDIANAPOLIS (FRONTLINE MEDICAL NEWS) – If you feel overwhelmed by the notion of managing multiple sclerosis patients who seek your guidance in navigating their pregnancy, you’re not alone.
Comprehensive management programs for pregnant MS patients currently do not exist, even within most dedicated MS centers and clinics, Dr. Maria K. Houtchens said at the annual meeting of the Consortium of Multiple Sclerosis Centers.
“Individual providers have an interest in this area, but there are no guidelines for most physicians or nurse practitioners to follow yet,” she said. “The level of care these patients receive varies dramatically, from one part of the country to another and from one provider to the next.”
An estimated 50% of all pregnancies in the United States and about 40% of all pregnancies worldwide are unplanned.
“I believe that women with MS should receive support and counseling from their MS specialist on issues about possible pregnancy,” said Dr. Houtchens, a neurologist who directs the Women’s Health Program at the Partners MS Center at Brigham and Women’s Hospital, Boston. “I believe that we should all feel comfortable discussing with our patients the effects of pregnancy on their MS course and the reciprocal effect on pregnancy outcomes of their disease, the genetic risk of disease in their offspring, and optimal conception timing. We need to be able to talk to them freely about disease control before, during, and after pregnancy.”
Dr. Houtchens, one of the authors of a recent multinational systematic review on the topic noted that increasing numbers of MS patients with stable disease are choosing not to become pregnant ( Obstet. Gynecol. 2014;124:1157-68 ). Others “want to get pregnant and feel cheated out of their life goal,” she said.
A large survey of female patients with MS from Canada found that more than three-quarters had not become pregnant since being diagnosed with the disease. The most common contributing factor across both MS-related and non–MS-related categories was completion of families prior to an MS diagnosis (53%). The top MS-related reasons that contributed to not having children were symptoms interfering with parenting, burdening the partner, and finances ( Mult. Scler. 2013;19:351-8 ).
“It’s only in the last 2-3 decades that this issue has come to the forefront in caring for MS patients,” she said. “Previous to that, a lot of colleagues would discourage patients from becoming pregnant. Some of those attitudes persist to this day. There’s a perception of disapproval from health care providers on the part of the patient, and from their family and peers, and historic misconceptions. Our goal as physicians is to help women live lives to their fullest potential with a disease that can’t be cured. We should not discourage our patients from becoming pregnant.”
To optimize chances of conception, she recommended that oral contraceptives be stopped 2-3 months prior to conception attempts, and patients should be advised to transition to mechanical birth control. The optimal “fertility window” is a 6-day period, ending with the ovulation day. This window can be estimated based on duration of menstrual cycle, cervical mucus, and basal body temperature, as well as commercially available ovulation kits. Intercourse is most likely going to result in a pregnancy if attempted within a 3-day period, ending with the ovulation day. Moderate alcohol consumption, smoking, drug use, and vaginal lubricant use decrease the chance of contraception, she said.
Assisted reproductive technologies, if associated with failed pregnancy attempts, can lead to an increased relapse rate.
“If somebody really wants to have a child and are not able to conceive on their own, they may certainly consider ART; it’s all about education,” Dr. Houtchens said. “You just need to tell them what to expect and that they might have a higher risk of relapses if their attempt is unsuccessful.”
According to the medical literature, an MS patient’s prepregnancy annualized relapse rate predicts her risk for relapse during the postpartum period. “From that perspective, if you have the luxury of time, you ideally try to make sure that her disease is stabilized for the year before she becomes pregnant,” she said. “That means if she has an active MRI or has had a couple of attacks on whatever drug she’s taking, you talk to her about that, and you change the medication and repeat the MRI after the medication is changed to try to make sure that her disease is stable before she becomes pregnant. Hopefully that will help prevent postpartum attacks.”
Dr. Houtchens recommends standard preconception care including prenatal vitamins with 0.4 mg-1 mg of daily folate, smoking and alcohol cessation, improved sleep hygiene, and vitamin D3 supplementation. Low levels of vitamin D3 are associated with adverse pregnancy outcomes, and a poorer clinical and radiologic MS course. Low levels may also be associated with increased MS risk in offspring.
“A pregnancy test should be administered prior to every treatment with a chemotherapeutic or cytotoxic agent in a woman of child-bearing age, even if she thinks her periods have ceased as a result of chemotherapy treatment,” she said. “They may have ceased due to pregnancy, and we don’t want to treat our pregnant patients with chemotherapy.”
The approximate risk of MS is 1 in 500 in the general population, 1 in 100 in people with an affected second-degree relative, 1 in 50 with an affected first-degree relative, and 1 in 4 in monozygotic twins born to an affected mother, according to Dr. Houtchens.
Babies born to MS moms face a risk of being slightly smaller for gestational age by weight (odds ratio, 1.45) but their Apgar scores are the same as their healthy mom counterpart babies. MS moms face a slight risk for operative deliveries but no increased risk for birth defects or other adverse fetal outcomes specifically related to MS. The method of labor and delivery does not impact the postpartum course of the disease, she said.
“Epidural anesthesia is perfectly safe and does not impact the postpartum course of MS,” Dr. Houtchens said. “There’s still an ongoing misconception [about this], especially among obstetric providers and anesthesiologists. Multiple studies have been published stating that there is no increased risk of relapse in these patients after they get an epidural. If they don’t want an epidural, that’s okay, but they shouldn’t be denied it because they have MS.”
Secondary MS symptoms may be affected by pregnancy, including fatigue, bladder symptoms, and mobility difficulty due to increased weight. IV corticosteroids are used widely to treat MS relapses during pregnancy, as well as in obstetrics to speed fetal lung maturity.
Steroids “cross the placental barrier and may increase the risk of cleft palate when used in the first trimester or may cause lower birth weight in the baby and earlier than expected delivery. They could also in theory delay healing for the mother after giving birth,” she said.
However, prednisone, prednisolone, and methylprednisolone can be administered with low levels of fetal exposure. “These agents are metabolized to inactive forms by 11 beta-hydroxysteroid dehydrogenase in the placenta, allowing less than 10% of the maternal dose to reach the fetus,” she said. Betamethasone and dexamethasone cross the placenta with minimal metabolism, leading to direct full-dose effects on the fetus.
Dr. Houtchens cautioned that none of the available MS drugs should be used in pregnant patients.
“It appears that pregnancy itself is protective enough that we don’t need to use a drug to keep them healthier,” she said.
For a nonlactating patient, it’s safe to resume MS therapy within 1 week after birth. For a lactating patient with previously active disease, it may be safe to administer monthly steroids or monthly IVIG, instructing them to discontinue breastfeeding for 24 hours after treatment. In breast milk, beta-interferon agents are found at 0.006% of the maternal dose. Oral small molecules such as fingolimod and dimethyl fumarate “are freely passed in breast milk at a lower level than in sera but are more likely to directly affect the infant’s immune/neurological systems,” Dr. Houtchens said. “Hepatic clearance is slower in infants. We don’t have anyone at our MS center taking any MS medications and breastfeeding. Is this the right thing to do? I don’t know. But if you have someone who really wants to breastfeed, you could theoretically put them on an injectable medication.”
MRI should be repeated within 6 months postpartum to assess radiographic disease activity, she recommended.
Dr. Houtchers pointed out that postpartum depression is common in mothers with MS, “and it’s probably under-studied in general.” In fact, the lifetime prevalence of major depressive disorder in people with MS is estimated to be approximately 50%, while the rate of suicides among people with MS is 7.5 times greater than that of the general population.
Helping MS patients navigate conception, pregnancy, and the postpartum period is just the beginning.
“You’re still going to be her doctor,” Dr. Houtchens said. “She’s still going to have that child for the rest of her life. How is she going to deal with raising the child with all of the symptoms of her disease over time? How is she going to relate to her child? You’re going to walk this road with your patients, as one of their most important health care providers.”
Dr. Houtchens disclosed that she has received research grants from Genzyme Sanofi, Biogen Idec, and Novartis. She has also served as a consultant for Teva Pharmaceuticals, Genzyme Sanofi, Questcor, Biogen Idec, and Novartis.
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