What have studies into MS and pregnancy found?
A number of reviews, including a meta-analysis of 23 papers reporting on 13,144 women with MS, have found that:
This confirms findings from a study in British Columbia that reviewed the records of 432 births to women with MS. Compared to control groups, there were no differences in gestational age, birth weight, or rates of assisted vaginal delivery or caesarean section. However, an estimated 50% to 90% of people with MS experience symptoms of sexual dysfunction, which affect conception rates.
MS relapses during pregnancy
Pregnancy is associated with a reduced relapse rate, particularly during the third trimester. The Pregnancy and Multiple Sclerosis (PRIMS) trial, which looked at 269 pregnancies, found that pregnancy resulted in:
- A 70% reduction in relapse rate in the third trimester
- A corresponding increase in the relapse rate in the three months after childbirth
Despite the relative increase in relapses in the postnatal period, 72% of women experienced no relapses during this period. Predictors for postpartum relapses included:
- Increased relapse rate in the year before pregnancy or during pregnancy
- Higher EDSS score at the onset of pregnancy
In the longer term, there is evidence that pregnancy may be beneficial for women with MS:
- A 10-year follow-up study found a lower relapse rate in women with pregnancies after MS onset compared to those without pregnancies after MS onset
- A prospective 5-year study compared the rate of progression in disability between childless women, women who had onset of MS after childbirth, and women who had onset before or during pregnancy. Disability rates increased most rapidly in women with no children
Pregnancy after onset of MS is associated with a longer duration until wheelchair dependence develops, as compared to never-pregnant women or those who had children only before onset of the disease, and less risk of conversion to secondary progressive MS.
Oral contraceptive use and childbirth are associated with a later age of MS onset. An Australian study found that the risk of women developing MS drops by half with each child born and is unaffected by time since last birth, suggesting that the protective effect is due to pregnancy and is lifelong.
What expecting mothers who have MS should eat in pregnancy
The importance of a mother’s diet has been extensively studied, and findings support the OMS recommendation for a diet rich in omega-3s and vitamin D and folic acid supplementation.
A recent review confirmed that: “Maternal DHA [one of the fatty acids in fish oil] intake during pregnancy and/or lactation can prolong high-risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye coordination, attention, problem solving and information processing.”
Increasing omega-3s in the diet is also likely to reduce illnesses caused by an overactive and inflammatory immune system. Studies have shown that fish oil consumed during pregnancy reduces asthma, allergy and dermatitis in the offspring.
Conversely, diets low in fish and vegetables have been linked to low birth weights. However, because mercury and other toxic substances collect in fish, pregnant women should limit fish consumption in the following ways:
- Don't eat shark, marlin and swordfish, because they contain high mercury levels
- Limit weekly tuna intake to no more than two steaks or four medium cans
- Eat no more than two portions of oily fish a week, including fresh tuna, salmon, mackerel, sardines, and trout. It is best, as per the OMS approach, to eat plant-based omega-3s; i.e., flaxseed oil
Effects of a mother’s high-fat diet on offspring
Maternal high-fat diets appear to have harmful effects in lowering the age of puberty, increasing the risk of breast cancer in offspring and their children, and increasing anxiety in offspring. This applies only to saturated and trans-fats, not omega-3s.
Studies show that food choices made in pregnancy can directly affect the offspring’s own food choices. Mothers who eat healthy foods are likely to have children who also prefer healthy foods. These findings offer a persuasive explanation for the rising incidence of breast cancer, the falling age of puberty, and high anxiety levels in industrialized countries.
They also support the argument for a plant-based diet of whole foods, supplemented with omega-3s.
Mind-body connection and pregnancy
Stress and stress management are closely linked to the development of MS and relapses.
In a recent randomized controlled trial (RCT), those taking part in a stress-reduction program reduced the onset of new lesions. This effect was seen during the period of the program but not when the participants stopped. This followed previous work, again an RCT, which confirmed that mindfulness-based stillness meditation (MBSM) improves quality of life in MS, including reducing depression, fatigue and anxiety.
Stress negatively affects a mother and her developing baby. This has previously been looked at in epidemiological and prospective studies. More recent studies have looked at stress-reduction interventions with positive results.
Maternal stress during pregnancy is associated with a number of negative outcomes for the baby including:
- Types 1 and 2 diabetes
- Increased risk of asthma
- ADHD and autistic traits in childhood
- Cerebral palsy
- Miscarriage, preterm labor, malformations and asymmetric growth retardation
Depressive symptoms in pregnant women are associated with elevated pro-inflammatory cytokines, including IL-6 and TNF-alpha, which are increased in active relapsing-remitting MS. In addition, raised levels of stress hormones are associated with pre-eclampsia and hypertension.
Stress reduction interventions in pregnancy
Studies on stress reduction programs in pregnancy have found improvements in many of the issues above, including:
- Reduced anxiety and depression
- Improved sleep
- Reduced discomfort
- Improvements in blood pressure
- Fewer preterm pregnancies
- Reduced hospital admissions
- Improved birth weights
- Improvements in maternal asthma
- Shorter labor times
In 2010, an RCT showed that a brief intervention of progressive muscle relaxation or guided imagery reduced anxiety and stress. Indian studies have shown that yoga and meditation improve birth weight and reduce preterm labor, blood pressure, diabetes and pre-eclampsia, while reducing growth abnormalities compared to standard treatment. These studies confirm that balance and reduced stress improve health.
Pregnancy and MS medications
The current advice is often to discontinue DMTs prior to conception, although studies have found only very minor adverse effects of beta-interferons (Avonex, Rebif and Betaferon or Betaseron) and no effect of glatiramer (Copaxone) and no association with fetal anomalies.
People with more aggressive MS may be prescribed natalizumab (Tysabri) or fingolimod (Gilenya). It is currently advised that these medications be ceased (three and two months, respectively) prior to conception. Ocrelizumab is currently advised to stop 12 month prior to pregnancy.
Short courses of steroids have generally been regarded as safe in pregnancy. Treatment with intravenous immunoglobulins (IVIg) looks promising in the period around childbirth. (See the Immunoglobulins section.) These are naturally produced by the immune system and have been used to treat a variety of neurological diseases, including MS. As well as being effective at reducing relapse rates, they appear to have no significant side effects or detrimental effects on pregnancy. At present, this treatment is not widely available.
For further information and specific DMD guidance in pregnancy, please refer to the 2019 ABN Guidance on pregnancy in multiple sclerosis. https://pn.bmj.com/content/practneurol/19/2/106.full.pdf
Breast-feeding and MS
Studies suggest a reduction in relapse rates among women who breast-feed for at least 2 months after childbirth.
A recent meta-analysis found that women who breast-fed were half as likely to experience a postpartum relapse, compared to women who did not. There are other well-established reasons why breast-feeding is preferable if possible: considered the optimal nutrition for babies, it helps protect them from many illnesses, including type 1 diabetes, asthma, dermatitis and Crohn’s disease.
It also appears to provide protection against MS. A German study showed that breast-feeding for at least 4 months halves a baby’s risk of developing MS later in life.
MS and IVF
Although MS has not been shown to affect fertility, approximately 15% of all couples have trouble conceiving. Given that the hormonal changes of pregnancy affect MS, it is to be expected that the hormonal changes induced by IVF would affect the disease.
Three studies have addressed this issue. It seems that one type of medication used, GnRH (gonadotropin releasing hormone) agonists (LONG protocol), may increase relapse rates. This increase is present for at least 3 months following treatment. Failure of IVF was also shown to be associated with an increased relapse rate.
Given that some of the DMTs (IFN and particularly GA) appear safe in the perinatal period, some authorities now advocate continuing these when having IVF.
In MS, it is generally thought best to use the ANTAGONIST or SHORT protocol, if possible, as this has no effect on relapse rates. It is worth discussing this with your gynaecologist at an early stage in the IVF process.
Interestingly, low-dose naltrexone (LDN) has been shown to be an effective treatment for infertility in people with polycystic ovarian syndrome. Given its possible benefits in MS, this warrants further research.
The evidence cited above suggests that following the OMS Program can provide a number of benefits. During pregnancy, the mother will experience reduced MS disease activity and progression over and above the benefits derived from pregnancy alone. She will also have a reduced risk of:
- Gestational diabetes
- Preterm delivery
- Prolonged labor
Children will have improved neurological development and a reduced risk of:
- Type 1 diabetes
- Rheumatoid arthritis
- Ulcerative colitis
- SLE (lupus)
- Respiratory tract infections
- Allergic dermatitis
- Breast cancer
- Anxiety-like behaviors
Research suggests that these benefits will be passed on for at least two generations.
1. Finkelsztejn A, Brooks JBB, Paschoal FM Jr, et al. What can we really tell women with multiple sclerosis regarding their pregnancy? A systematic review and meta-analysis of the literature. BJOG 2011;118:790–7
2. Tsui A, Lee MA. Multiple sclerosis and pregnancy. Curr Opin Obstet Gynecol
3. Coyle PK. Pregnancy and multiple sclerosis. Neurol Clin. 2012 Aug;30(3):877-88. Epub 2012 Jun 22
4. van der Kop ML, Pearce MS, Dahlgren L, et al. Neonatal and delivery outcomes in
women with multiple sclerosis. Ann Neurol 2011;70:41–50
5. Dwosh E, Guimond C, Sadovnick AD. Reproductive counselling for MS: a rationale. Int MS J 2003; 10:52–59
6. Vukusic S, Hutchinson M, Hours M, et al. For the pregnancy in multiple sclerosis group. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of postpartum relapse. Brain 2004; 127:1353–1360
7. Vukusic S, Ionescu I, El-Etr M, et al. The prevention of postpartum relapses with
Progestin and Estradiol in multiple sclerosis (POPART’MUS) trial: rationale, objec
tives and state of advancement. J Neurol Sci 2009;286:114–8
8. Roullet E, Verdier-Taillefer MH, Amarenco P, Gharbi G, Alpe- rovitch A, Marteau R (1993) Pregnancy and multiple sclerosis: a longitudinal study of 125 remittent patients. J Neurol Neurosurg Psychiatry 56(10):1062–1065
9. Stenager E, Stenager EN, Jensen K. Effect of pregnancy on the prognosis for multiple sclerosis. A 5-year follow up investigation. Acta Neurol Scand 1994;90:305–8 10. Verdru P, Theys P, D'Hooghe MB, Carton H: Pregnancy and multiple sclerosis: the influence on long term disability. Clin Neurol Neurosurg 1994, 96:38–41 11. D'hooghe MB, Haentjens P, Nagels G, D'Hooghe T, De Keyser J: Menarche, oral contraceptives, pregnancy and progression of disability in relapsing onset and progressive onset multiple sclerosis. J Neurol 2012, 259: 855–861
12. Runmarker B, Andersen O. Pregnancy is associated with a lower risk of onset and a better prognosis in multiple sclerosis. Brain 1995; 118:253– 261
13. Holmqvist P, Hammar M, Landtblom AM, et al. Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis. Fertil Steril 2010;94:2835–7
14. Ponsonby, AL and Lucas, RM and van der Mei, IA and Dear, K and Valery, PC and Pender, MP and Taylor, BV and Kilpatrick, TJ and Coulthard, A and Chapman, C and Williams, D and McMichael, AJ and Dwyer, T, Offspring number, pregnancy, and risk of a first clinical demyelinating event: The AusImmune Study,Neurology-, 78, (12) pp. 867-874
15. Morse N.L. Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation. Nutrients. 2012; 4(7):799-840
16. Palmer DJ, Sullivan T, Gold MS, Prescott SL, Heddle R, Gibson RA, et al. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomised controlled trial. BMJ 2012;344:e184
17. Olsen SF, Osterdal ML, Salvig JD, Mortensen LM, Rytter D, Secher NJ, et al. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr 2008;88:167-75
18. Miyake Y, Sasaki S, Tanaka K, et al. (2009) Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese infants aged 16–24 months: the Osaka Maternal and Child Health Study. Thorax 64, 815–821
19. Romieu I, Torrent M, Garcia-Esteban R, et al. (2007) Maternal fish intake during pregnancy and atopy and asthma in infancy. Clin Exp Allergy 37, 518–525 20. Fitzsimon N, Fallon U, O’Mahony D, et al. (2007) Mothers’ dietary patterns during pregnancy and risk of asthma symptoms in children at 3 years. Ir Med J 100, 27–32
21. Miyake Y, Sasaki S, Tanaka K, Ohya Y, Miyamoto S, Matsunaga I, Yoshida T, Hirota Y, Oda H and the Osaka Maternal and Child Health Study Group. Fish and fat intake and prevalence of allergic rhinitis in Japanese females: the Osaka maternal and child health study. J Am Coll Nutr 2007;26:279-287
22. Hitomi Okubo, Yoshihiro Miyake, Satoshi Sasaki, Keiko Tanaka, Kentaro Murakami, Yoshio Hirota and Osaka Maternal and Child Health Study Group. Maternal dietary patterns in pregnancy and fetal growth in Japan: the Osaka Maternal and Child Health Study. British Journal of Nutrition / Volume107 / Issue10 / May 012, pp 1526-1533
23. Hilakivi-Clarke, L. et al. A maternal diet high in n-6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring. Proc. Natl Acad. Sci. USA 94, 9372–9377 (1997)
24. de Assis, S. et al. High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring. Nat. Commun. 3:1053 doi: 10.1038/ncomms2058 (2012)
25. Sullivan EL, Grayson B, Takahashi D, et al. Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring. Journal of Neuroscience. 2010;30(10):3826–3830
26. Peleg-Raibstein D, Luca E, Wolfrum C. (2012) Maternal high-fat diet in mice programs emotional behavior in adulthood. Behav Brain Res. 233(2):398-404
27. Nakashima Y: Fish-oil high-fat diet intake of dams after day 5 of pregnancy and during lactation guards against excessive fat consumption of their weaning pups. J Nutr Sci Vitaminol (Tokyo) 2008;54:46–53
28. Bayol SA, Farrington SJ, Stickland NC: A maternal 'junk food' diet in pregnancy and lactation promotes an exacerbated taste for “junk food” and a greater propensity for obesity in rat offspring. Br J Nutr 2007;98:843– 851
29. Mohr DC, Lovera J, Brown T, et al. A randomized trial of stress management for the prevention of new brain lesions in MS. Neurology 2012;79:412– 419
30. Grossman P, Kappos L, Gensicke H, et al. MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial. Neurology 2010;75:1141– 1149
31. Virk J, Li J, Vestergaard M, Obel C, Lu M, et al. (2010) Early Life Disease Programming during the Preconception and Prenatal Period: Making the Link between Stressful Life Events and Type-1 Diabetes. PLoS ONE 5(7): e11523. doi:10.1371/journal.pone.0011523
32. Li J, Olsen J, Vestergaard M, Obel C, Kristensen JK, et al. (2012) Prenatal Exposure to Bereavement and Type-2 Diabetes: A Danish Longitudinal Population Based Study. PLoS ONE 7(8): e43508. doi:10.1371/journal.pone.0043508
33. Fang F, Olgart Höglund C, Arck P, Lundholm C, Långström N, et al. (2011) Maternal Bereavement and Childhood Asthma—Analyses in Two Large Samples of Swedish Children. PLoS ONE 6(11): e27202. doi:10.1371/journal.pone.0027202
34. Mothers' anxiety during pregnancy is associated with asthma in their children. Cookson H, Granell R, Joinson C, Ben-Shlomo Y, Henderson AJ. J Allergy Clin Immunol. 2009 Apr; 123(4):847-53.e11
35. Ronald A, Pennell CE, Whitehouse AJ. Prenatal Maternal Stress Associated with ADHD and Autistic Traits in early Childhood. Front Psychol. 2010; 1:223. [PubMed: 21833278]
36. Li J, Vestergaard M, Obel C, Precht DH, Christensen J, et al. (2009) Prenatal stress and cerebral palsy: a nationwide cohort study in Denmark. Psychosom Med 71:615–618
37.Mulder EJ, Robles de Medina PG, Huizink AC, Van den Bergh BR, Buitelaar JK, Visser GH. Prenatal maternal stress: Effects on pregnancy and the (unborn) child. Early Hum Dev 2002; 70:3–14
38. Christian, L. M., Franco. A, Glaser. R, and Iams, J. D. (2009). Depressive symptoms are
associated with elevated serum proinflammatory cytokines among pregnant women. Brain, Behavior, and Immunity, 23; 750-754
39. Hautecoeur P, Forzy G, Gallois P, et al: Variations of IL2, IL6, TNF-alpha plasma levels in relapsing–remitting multiple sclerosis. Act Neuro Belg 1997; 97:240–243
40. Laatikainen, T., Virtanen, T., Kaaja, R., Salminen-Lappalainen, K., 1991. Corticotropin-releasing hormone in maternal and cord plasma in pre-eclampsia. Eur. J. Obstet. Gynecol. Reprod. Biol. 39, 19-24
41. Hernandez-Valencia, M., Rivera Montes, A.M., Vargas Lopez, C., Paez Angulo, J.A., Vargas Giron, A., Zarate, A., 2007. Catecholamines level variation during pregnancy in women with diabetes and preeclampsia. Ginecol. Obstet. Mex. 75, 454-458
42. Beddoe AE, Lee KA. Mind-body interventions during pregnancy. J Obstet Gynecol Neonatal Nurs. 2008;37(2):165-75
43. Urech, C., Fink, N.S., Hoesli, I., Wilhelm, F.H., Bitzer, J., Alder, J., 2010. Effects of relaxation on psychobiological wellbeing during pregnancy: a randomized controlled 586 trial. Psychoneuroendocrinology 35, 1348–1355
44. Narendran, S., Nagarathna, R., Narendran, V., Gunasheela, S., Nagendra, H.R., 2005. Efficacy of yoga on pregnancy outcome. J. Altern. Complement Med. 11, 237-244
45. The effects of yoga in prevention of pregnancy complications in high-risk pregnancies: A randomized controlled trial. Rakhshani A, Nagarathna R, Mhaskar R, Mhaskar A, Thomas A, Gunasheela S. Prev Med. 2012 Oct;55(4):333-40. doi: 10.1016/j.ypmed.2012.07.020. Epub 2012 Aug 2
46. Giannini et al.: Pregnancy and fetal outcomes after Glatiramer Acetate exposure in patients with multiple sclerosis: a prospective observational multicentric study. BMC Neurology 2012 12:124
47. Amato MP, Portaccio E, Ghezzi A, et al. Pregnancy and foetal outcomes after interferon-beta exposure in multiple sclerosis. Neurology 2010; 75:1794–1802
48. Lu, E., Wang, BW., Guimond, C., Synnes, A., Sadonvick, D. & Tremlett, H. Disease-modifying drugs for multiple sclerosis in pregnancy: A systematic review. Neurology. Sep 11, 2012; 79(11):1130–1135
49. Hellwig K, Haghikia A, Gold R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult Scler 2011; 17:958–963
51. Gur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A: Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study. Reprod Toxicol 2004, 18:93–101
52. Anders Hviid and Ditte Mølgaard-Nielsen. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ cmaj.101063; published ahead of print April 11, 2011, doi:10.1503/cmaj.101063
53. Haas J. High dose IVIG in the post partum period for prevention of exacer- bation of MS. Mult Scler 2000; 6 (Suppl 2):S18–S20; discussion S33
54. Achiron A, Kishner I, Dolev M, et al. Effect of intravenous immunoglobulin treatment on pregnancy and post partum-related relapses in multiple sclero- sis. J Neurol 2004; 251:1133–1137
55. CONFAVREUX, C., HUTCHINSON, M., HOURS, M.M., CORTINOVIS-TOURNIAIRE, P. and AL, E., 1998. Rate of pregnancy-related relapse in multiple sclerosis. The New England journal of medicine, 339(5), pp. 285-91
56. Langer-Gould A, Huang SM, Gupta R, et al. Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch Neurol 2009;66: 958 –963
57. Airas L, Jalkanen A, Alanen A, et al. Breastfeeding, postpartum and prepregnancy disease activity in multiple sclerosis. Neurology 2010; 75:474-476
58. Vukusic S, Hutchinson M, Hours M, et al. Pregnancy and multiple sclerosis (the
PRIMS study): clinical predictors of postpartum relapse. Brain 2004;127:
59. Pakpoor J, Disanto G, Melanie VL, Hellwig K, Giovannoni G, Sreeram VR. Breastfeeding and multiple sclerosis relapses: A meta-analysis. J Neurol. 2012;259(10):2246-8
60. Breastfeeding is associated with lower risk for multiple sclerosis. Conradi S, Malzahn U, Paul F, Quill S, Harms L, Then Bergh F, Ditzenbach A, Georgi T, Heuschmann P, Rosche B .Mult Scler. 2012; Sep 4. PMID: 22951352
61. Laplaud DA, Leray E, Barrière P, Wiertlewski S, Moreau T: Increase in
multiple sclerosis relapse rate following in vitro fertilization. Neurology
62. Hellwig K, Schimrigk S, Beste C, Muller T, Gold R: Increase in relapse rate
during assisted reproduction technique in patients with multiple
sclerosis. Eur Neurol 2009; 61:65-68
63. Michel L, Foucher Y, Vukusic S, et al. Increased risk of multiple sclerosis relapse after in vitro fertilisation J Neurol Neurosurg Psychiatry 2012; 83: 796-802. doi: 10.1136/jnnp-2012-302235
64. Ahmed MI, Duleba AJ, El Shahat, et al. Naltrexone treatment in clomiphene resistant women with polycystic ovary syndrome. Hum. Reprod 2008; 23(11):2564-2569