Interactive Case Studies 20618_A5

Managing pregnancy in an MS clinic: An interactive case-based approach Based on patient cases supplied by Dr Doriana Landi, MD, PhD, Consultant, Neurology, Department of Neuroscience, Policlinico Tor Vergata / University of Rome Tor Vergata HQ/MED/17/0100 Date of preparation: October 2017

Instructions This exercise will enable you to identify effective approaches for counselling women with MS on a range of pregnancy- related topics using case studies based on real-life patients Each patient requires an individualised approach based on their personal characteristics Use the touchscreen to work your way through the cases Press on the right arrow to continue

Instructions Use the touch screen to choose which patient you would like to counsel For each patient there will be multiple choice questions. Choose your appropriate response and press for the recommended answer Press at any time to return to the introduction Press on the right arrow to continue

Choose your patient HELEN clare ANA Helen is looking to start Clare is four months pregnant Ana’s first child is four years old a family and is worried about and is concerned that having and she has been trying to have what impact her MS will have on an epidural may affect her MS. She is also unsure whether her another baby for the last two her pregnancy. treatment will enable her to years. Does her MS affect her breastfeed, and how long should fertility? Should she undergo she wait until resuming her ART* or will it increase her risk treatment. of relapses? *Abbreviation: ART = assisted reproductive techniques.

Helen AGE: MS Co-morbidities: Disease DIAGNOSIS: severity: 29 Cutaneous 2009 psoriasis MILD Helen is looking to start a family and is worried about what impact her MS will have on her pregnancy

Managing patients with MS who desire a family, requires which of the following? Multidisciplinary Counselling An individual All anwers apply collaboration patients at every approach to clinical encounter treatment

Managing patients with MS who desire a family, requires which of the following? All anwers apply Collaboration between multiple disciplines such as neurologists, gynaecologists, midwifes etc. is essential for effective communication.1 Counselling patients at every clinical encounter will enable you to discuss any pregnancy-related issues and alleviate patient fears that might persist.1 Clinical management should be individualised to optimise both the mother’s reproductive outcomes and MS course.2 1. Vukusic et al. Nat Rev Neurol 2015; 11: 280–89; 2.Bove et al. Obstet Gynecol. 2014; 124(6): 1157–68.

What is the lifetime risk of Helen’s child developing MS? Same as general 25% 10% <3% population

What is the lifetime risk of Helen’s child developing MS? <3% MS is not considered to be hereditary.1 A child of a parent with MS has a <3% lifetime risk of developing MS themselves.1 The lifetime risk of MS in the general population is 0.3% for men and 0.5% for women.1 1. Nielsen et al. Am J Epidemiol. 2005;162(8):774–8.

MS is associated with complications to which aspects of Helen’s pregnancy? The foetus Labour and Epidurals No answers delivery apply

MS is associated with complications to which aspects of Helen’s pregnancy? No answers The available evidence does not point to any major apply deleterious effect of MS on pregnancy.1 No differences have been seen in gestational age, Apgar score, birth weight, increased incidence of foetal complications, or increased labour duration in patients with MS.2–5 1. Amato et al. CNS Drugs. 2015;29(3):207–20; 2. Miller et al. Mult Scler. 2014; 20(5):527–36; 3. van der Kop et al. Ann Neurol. 2011;70(1):41–50; 4. Ghezzi et al. Expert Rev Clin Immunol. 2013; 9(7):683–91. 5. Pasto et al. BMC Neurology 2012, 12:165.

Does having MS increase Helen’s risk of miscarriage? No Yes Risk increases Data are with IFNβ /GA not available treatments* *Abbreviation: IFN = interferon, GA = glatiramer acetate.

Does having MS increase Helen’s risk of miscarriage? Studies from pregnancy registries have shown that IFNβ and GA during the first trimester of pregnancy do not seem to significantly influence the risk of miscarriage and No pre-term birth or any other adverse pregnancy outcomes.1,2 We can therefore advise patients that the risk of miscarriage is exactly the same as the general population. 1. Thiel et al. Mult Scler 2016;22:801–9. 2. Herbstritt et al. Mult Scler 2016;22:810–6 3. ‫למידע נוסף יש לעיין בעלון לרופא כפי שאושר על ידי משרד הבריאות‬

Clare AGE: MS Co-morbidities: Disease DIAGNOSIS: severity: 32 None 2012 Moderate Clare is four months pregnant and concerned that having an epidural may affect her MS. She is also unsure whether her treatment will enable her to breastfeed and how long should she wait until resuming her treatment.

Do epidural analgaesia influence disease reactivation? Yes No No, but general Yes, if the patient anesthaesia has spinal cord should be lesions preferred

Do epidural analgaesia influence disease reactivation? A 2012 study showed no correlation between epidural analgaesia or caesarean delivery and No an increase in postpartum relapses.* Therefore these procedures can both be safely applied in MS patients. *Annualised relapse-rate before, during and after pregnancy in patients who underwent epidural analgaesia. 1. Pasto et al. BMC Neurology 2012;12:165.

In what way can exclusive breastfeeding in women with MS affect their disease course? Reduces post- Increases post- May reduce post- Does not partum relapses partum relapses partum relapses, influence post- but it should be partum relapses discussed with the neurologist

In what way can exclusive breastfeeding in women with MS affect their disease course? May reduce post- Despite very conflicting results in the past, we partum relapses, know today that exclusive breastfeeding does but it should be not determine worsening of disease activity. discussed with Although breastfeeding may reduce the the neurologist postpartum relapse, the decision should be based on the prognostic factors of each patient and therefore discussed with a neurologist. 1. Hellwig et al. JAMA Neurol 2015;72:1132–8.

In Clare’s case, how long would you normally wait to restart disease-modifying treatment after giving birth? As soon as 1–3 months 6 months Depends on possible individual prognostic factors

In Clare’s case, how long would you normally wait to restart disease-modifying treatment after giving birth? Depends on There are no guidelines about when to start treatment individual after delivery, therefore this decision should be based prognostic on individual pregnancy factors. factors Relapse rate falls by as much as 70% during the third trimester, followed by a rapid postpartum increase greater than the original pre-pregnancy rate, with a higher risk period between 1–3 months after delivery.1–3 The relapse rate then returns back to a pre-pregnancy rate within a year.1–3 1.Confavreux et al. N Engl J Med. 1998; 339(5): 285–91. 2. Ghezzi et al. Expert Rev Clin Immunol. 2013; 9(7): 683–91. 3. Saraste et al. Gend Med. 2007; 4(1): 45–55.

Ana AGE: MS Co-morbidities: Disease DIAGNOSIS: Hypertension severity: 39 2014 Severe Ana’s first child is four years old and she has been trying to have another baby for the last two years. Does her MS affect her fertility? Should she undergo ART, or will it increase her risk of relapses?

Can Ana’s MS impair her fertility? Depends Yes No on other Not sure factors

Can Ana’s MS impair her fertility? In Western countries, 10–20% of all couples suffer from infertility.1 Evidence on MS and fertility is conflicting, with some research suggesting fertility is reduced prior to MS onset.2,3 No However, ~43% of women with MS have been shown to become pregnant after their diagnosis.4 Overall, fertility does not seem to be impaired in women with MS.3 1. Gnoth et al. Hum Reprod. 2005; 20(5): 1144–7; 2. Hedström et al. Mult Scler. 2014; 20(4): 406–11; 3. Amato et al. CNS Drugs. 2015;29(3): 207–20. 5. Carvalho et al. Rev Neurol. 2014;59(12):537–42.

Do ART increase the risk of relapse? Yes, because MS Yes, because Yes, because there All answers apply treatment has to hormonal therapy is a high risk of miscarriage be stopped may reactivate the immune response

Do ART increase the risk of relapse? Yes, because Some increased relapse risk has been reported in hormonal therapy women with MS using ART, particularly with gonadotropin-releasing hormone agonists.1 may reactivate Patients who may be considering using ART should be the immune counselled on this potential risk.2 response ART leads to changes in levels of: GnRH; oestrogen and progesterone; and IL-8, VEGF, chemokine CXCL-12.* 1 *Abbreviations: GnRH= Gonadotropin-releasing hormone, IL = interleukin, VEGF = vascular endothelial growth factor. 1. Hellwig et al. J. Clin Immunol. 2013;149:219–24. 2. Miller et al. Mult Scler. 2014;20:527–536.

Should treatment for MS be interrupted before conception? Yes, all No The benefit/risk In case of unsafe treatments profile of each treatments, it is should be treatment should convenient to interrupted be evaluated de-escalate/switch to a more safe treatment to protect maternal and foetal health

Should treatment for MS be interrupted before conception? The benefit/risk Most women are advised to stop disease-modifying profile of each treatment when planning conception and during treatment should pregnancy, unless the benefit-risk balance favours be evaluated continuing treatment.1 In the case of a severe relapse during pregnancy, female patients could be treated with a short high dose of corticosteroids to hasten recovery. However, in the first trimester, corticosteroids are associated with a risk of foetal cleft palate.1 1. Miller et al. Mult Scler. 2014;20:527–36;