How does neuromyelitis optica spectrum disorder (NMOSD) affect women?

NMOSD is associated with a marked female predominance, with some studies reporting a female-to-male ratio as high as 9:1 in aquaporin-4 antibody (AQP-4 IgG) seropositive cases.1 The age at onset of NMOSD tends to be later than in multiple sclerosis (MS) (around age 40-50), though childhood onset is possible and women of childbearing age are frequently affected.2

What data are there to support management modifications related to women’s health in NMOSD?

Utilization of immunosuppressive therapy in patients with NMOSD is critical to prevent further disease activity; however, data pertaining to sex differences with use of the currently available therapies is lacking. Given there are limited data to guide management of family planning, pregnancy, and the post-partum phases of the female reproductive lifecycle in NMOSD, the general approach outlined below is similar to that in the Mellen Center Approach titled “Management of Multiple Sclerosis During Pregnancy”, with disease-specific commentary included where appropriate within this document.

What are the recommendations for preconception counseling?

Plans for pregnancy must be considered when choosing between various immunosuppressive therapy types.3 Similar to what has been suggested in the MS literature, symptoms should ideally be adequately controlled and disease activity is stable for at least 6-12 months prior to conception.4 Women who are planning to become pregnant are advised to take prenatal vitamins, including folic acid and vitamin D.5

NMOSD and fertility and assisted reproductive technology (ART)

No data currently exist regarding fertility or the use, safety, or outcomes of fertility / ART treatments in women with NMOSD. One prior study of women with NMOSD demonstrated reduced levels of anti-Mullerian hormone (often used as a surrogate marker of ovarian reserve) which was associated with increased disease activity but did not assess the impact of fertility / ART treatments.6 Another study demonstrated no significant difference in rates of infertility amongst NMOSD patients compared to healthy controls.7 We advise that in general there are no significant differences in conception or fertility rates between patients with NMOSD and the general population, and that fertility treatments and ART can be utilized on a case-by-case basis. However, disease activity and disability may indirectly impact reproductive choices and outcomes. If fertility treatment is considered, multidisciplinary collaboration between the patient’s treating neurologist and reproductive medicine is recommended for individualized risk assessment.

What are the recommendations for contraception?

Women of childbearing potential with NMOSD on immunosuppressive therapy are encouraged to use some form of contraception. In general, all contraceptive methods are safe, though progestin-only and combined hormonal contraceptives may not be recommended in patients that have significant mobility limitations due to the risk of venous thromboembolism.8 Patients using any immunosuppressive treatment should ideally have a negative pregnancy test within one week of starting treatment and repeated as needed if unprotected intercourse occurs prior to continuation of treatment. Mycophenolate mofetil may theoretically reduce efficacy of oral contraceptives, and patients using this medication should use a combination of two forms of contraception.9 There are no known major interactions between the other commonly used immunosuppressive therapies used for treatment of NMOSD and oral contraceptives. Potential interactions of symptomatic therapies with contraceptives should be considered.

What is the risk of relapse in pregnant patients with NMOSD?

Limited prior studies evaluating pregnancy outcomes in women with NMOSD have demonstrated increased disease activity during pregnancy, with possible further / heightened risk of both relapse and worsening disability in the postpartum period.10-13

What is the impact of NMOSD on pregnancy outcomes?

The increased risk of relapse and worsening disability during pregnancy in women with NMOSD has been associated with adverse pregnancy outcomes including increased risk of miscarriage, preeclampsia, preterm birth, intrauterine growth restriction, and low birth weight.10,12-14 Therefore, women with NMOSD who become pregnant should establish care with a high-risk obstetrician / maternal-fetal medicine specialist early in the pregnancy course so that proper monitoring strategies can be implemented in a timely manner.

What treatments for NMOSD are safe for use during pregnancy?

In women with NMOSD where pregnancy is associated with an increased risk of adverse outcomes and recovery from relapses is typically less favorable, strategically timed or continued use of rituximab may be considered to reduce the risk of pregnancy-related relapses and disability worsening, though data supporting use during pregnancy is limited and neonatal implications need to be carefully considered.12,13,15-17 Given the lack of robust data pertaining to fetal / neonatal risk with use of more recently approved therapies (satralizumab, eculizumab, inebilizumab), rituximab may still be the preferred treatment when indicated. However, based on prescribing information / limited studies indicating limited fetal risk, satralizumab may also be a reasonable consideration. Azathioprine has historically been used in NMOSD patients during pregnancy, though the risk-benefit profile is not thought to be as favorable and therefore is not routinely used.

What treatments require a washout (discontinuation period) in patients considering pregnancy?

As above, in select women with NMOSD a provider may contemplate continued use of rituximab to reduce the risk of pregnancy-related relapses following an extensive risks-benefits discussion with the patient.12,13 When treatment discontinuation is deemed appropriate (taking the characteristics of the patient’s level of disease activity into consideration), washout periods are considered for all immunosuppressive therapies (Table 1). Recommended washout periods are based on the pharmacology of individual treatments. Whenever feasible, treatment and conception timing are coordinated, with the aim of keeping washout periods as short as possible to mitigate the risk of relapse.

Anti-CD20 agents infused intravenously (rituximab-pvvr and rituximab) confer prolonged protective effects against relapses for several months (6-9 m) following administration. They are not recommended to be routinely administered during pregnancy but can be administered prior to conception in patients with highly active disease. The FDA-approved prescribing information recommends that women continue contraception 12 months following the last treatment of rituximab. However, in some cases (particularly women with highly active disease prior to initiation of treatment) continued treatment may be necessary for minimization of time off immunosuppressive therapy. These patients may receive an infusion and then discontinue contraception/attempt to become pregnant after 1-3 months.18,19 The rationale for this is that these therapies are eliminated by 3.5-4.5 months after an infusion (based on half-life).20 In the first trimester, there is minimal placental transfer of IgG.21 Therefore, if a patient conceives 1-3 m after the last dose of anti-CD20 therapy, the risk of fetal exposure in the second trimester is low.18 The main risk to an exposed fetus is transient B cell lymphopenia. A pregnancy test should be checked prior to subsequent dosing. Decision-making regarding anti-CD20 therapy and pregnancy planning needs to consider the patient’s degree of disease activity and their individual preferences.

What if a patient becomes pregnant while on immunosuppressive therapy?

Patients with NMOSD are recommended to have an extensive risk-benefits conversation with their multidisciplinary care providers to determine if treatment should be continued. Patients who become pregnant on IVIg or B-cell depleting therapies do not require additional monitoring during pregnancy (Table 2). Those becoming pregnant on azathioprine, mycophenolate mofetil, or methotrexate are referred for an early ultrasound to screen for major malformations, and patients may consider being followed by a high-risk obstetrician. All pregnancy exposures should be registered through appropriate registries (Table 2).

How should relapses be managed during pregnancy?

Management of relapses during pregnancy is discussed and coordinated with the patient’s obstetrician. Mild relapses (with non-disabling symptoms or spontaneous improvement) may not require intervention. When indicated (for moderately to severely disabling relapses), the recommended first-line pharmacological treatment for relapses during pregnancy is high-dose corticosteroids. This therapy is used for clinically significant relapses, as it does carry a slightly increased risk for adverse fetal outcomes (specifically cleft palate and low birthweight).22 Corticosteroid use is avoided during the first trimester when possible. Plasma exchange may be considered for patients with disabling steroid-refractory relapses.11,23

Is magnetic resonance imaging (MRI) safe for pregnant or breastfeeding patients with NMOSD?

Routine MRI during pregnancy is not recommended but can be done if necessary. There are no studies to date which have demonstrated adverse outcomes or harms attributable to MRI during any trimester of pregnancy.24 However, gadolinium-based contrast use during pregnancy is contraindicated, as prior studies have demonstrated an increased risk of stillbirth, neonatal death, and various inflammatory conditions.25 Although it was previously recommended to abstain from use while breastfeeding, the American College of Radiology,26 American Academy of Pediatrics,27 and American College of Obstetricians and Gynecologists28 no longer recommend avoidance of gadolinium-based contrast, nor do they recommend discarding breastmilk after having received gadolinium-based contrast.

Are there special considerations for delivery?

For most women, we have no special recommendations for delivery. Additional considerations depend on the individual patient’s needs, such as planning for use of assisted delivery methods and/or Caesarean section in women with significant disease-related disabilities. The use of any anesthetic type is acceptable when clinically indicated.

How should patients be managed during the postpartum period?

Women with NMOSD should receive routine obstetric postpartum care. Given the rapid shift in gestation-related hormones, patients may be at increased risk for both clinical and MRI disease activity following delivery. We recommend that an MRI be obtained following delivery to evaluate radiographic disease activity if new symptoms arise. Because most NMOSD patients will ultimately resume immunosuppressive therapy following delivery, a plan for prompt resumption of neurological care (within 3 months) should be planned prior to delivery.

When should therapy be resumed after delivery?

In general, we recommend that plans for breastfeeding and the timing of immunosuppressive therapy resumption be discussed prior to delivery. The decision about when to resume treatment is an individual decision for each patient and needs to account for both previous disease activity and personal breastfeeding plans. Re-initiation of immunosuppressive therapy early in the postpartum period should be considered for patients who had very active disease prior to conception, had relapse(s) during pregnancy, or have a poor prognostic profile. See sections pertaining to the use of immunosuppressive therapy during breastfeeding (below).

Is breastfeeding safe for patients taking immunosuppressive therapies?

The decision to breastfeed and the duration of breastfeeding is deferred to the patient’s decision after conferring with their obstetrician/pediatrician. Exclusive breastfeeding is recommended in most cases for about 6 months due to known benefits to the infant.

No immunosuppressive therapy is considered completely safe for use during breastfeeding. There have been no studies to date regarding the presence of IVIg in human milk or its effects on milk production.29 Mycophenolate mofetil and methotrexate have been shown to be excreted in breast milk of rats and humans and should not be used while breastfeeding. Women taking methotrexate should refrain from breastfeeding until one week after the final dose is taken.30

Monoclonal antibodies, such as anti-CD20 agents, are larger molecules (on the scale of 100,000 kDa), though the transfer to breast milk does occur and may have clinically significant implications for the infant (B-cell depletion and impaired vaccine responses). The low oral bioavailability is likely to limit the absorption by the newborn (with a relative infant dose of less than 10%).31 Therefore, it is reasonable to resume treatment with rituximab (at least 14-21 days following delivery to ensure full benefits of colostrum have been transferred to the infant).

If a patient develops a relapse while breastfeeding, use of corticosteroids may be considered. Transfer of methylprednisolone through breastmilk is thought to be minimal and may be further minimized by delaying breastfeeding for 2-4 hours after infusion (as levels peak in approximately 2 hours and rapidly decline thereafter).32 For patients receiving oral steroids, the dose ingested by the infant through breast milk is thought to be negligible. It is no longer thought necessary to discard breastmilk following treatment, though individual mothers may choose to do so for 24-48 hours out of an abundance of caution.

Are there any considerations for men with NMOSD about childbearing?

Male patients treated with mycophenolate mofetil, and methotrexate need to practice effective contraception until after the medication is cleared by metabolism, which takes approximately 3 months.9,30 Female partners of male patients on mycophenolate mofetil are also counseled on the potential risks of fetal exposure as well as use of effective contraceptive therapy. All men treated with these therapies are counseled on the importance of (and adherence to) contraceptive use for at least three months following the last dose, even when pregnancy is not planned, given the significant potential risks.

References

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  9. Administration FaD. CellCept (mycophenolate mofetil). FDA Drug Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050722s021,050723s019,050758s019,050759s024lbl.pdf.
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  12. Budtarad N, Ongphichetmehta T, Siritho S. Insights into neuromyelitis optica spectrum disorder and pregnancy from a single-center study in Thailand. Sci Rep. Feb 01 2025;15(1):4011. doi:10.1038/s41598-025-88624-x
  13. Shosha E, Pittock SJ, Flanagan E, Weinshenker BG. Neuromyelitis optica spectrum disorders and pregnancy: Interactions and management. Mult Scler. Dec 2017;23(14):1808-1817. doi:10.1177/1352458517740215
  14. Collongues N, Alves Do Rego C, Bourre B, et al. Pregnancy in Patients With AQP4-Ab, MOG-Ab, or Double-Negative Neuromyelitis Optica Disorder. Neurology. Apr 13 2021;96(15):e2006-e2015. doi:10.1212/WNL.0000000000011744
  15. Shi B, Zhao M, Geng T, Qiao L, Zhao Y, Zhao X. Effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy. J Neurol Sci. Jun 15 2017;377:72-76. doi:10.1016/j.jns.2017.03.051
  16. Yoshida T, Watanabe O, Nomura M, Yoshimoto Y, Maki Y, Takashima H. Neuromyelitis optica spectrum disorder safely and successfully treated with satralizumab during pregnancy and breastfeeding: a case report. Front Neurol. 2023;14:1322412. doi:10.3389/fneur.2023.1322412
  17. Yaguchi H, Miyagawa S, Nakada R, Yamamoto S, Goto R, Funaki S. Safe Childbirth in a Patient with Neuromyelitis Optica Spectrum Disorder Treated with Satralizumab. Intern Med. Aug 14 2025;doi:10.2169/internalmedicine.5870-25
  18. Dobson R, Hellwig K. Use of disease-modifying drugs during pregnancy and breastfeeding. Curr Opin Neurol. Jun 01 2021;34(3):303-311. doi:10.1097/WCO.0000000000000922
  19. Langer-Gould AM. Pregnancy and Family Planning in Multiple Sclerosis. Continuum (Minneap Minn). Jun 2019;25(3):773-792. doi:10.1212/CON.0000000000000745
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  23. Wind M, Gaasbeek AGA, Oosten LEM, et al. Therapeutic plasma exchange in pregnancy: A literature review. Eur J Obstet Gynecol Reprod Biol. May 2021;260:29-36. doi:10.1016/j.ejogrb.2021.02.027
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  26. Media ACoDaC. ACR Manual on Contrast Media. American College of Radiology.
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Table 1: Immunosuppressive Therapies in Pregnancy

Medication

Recommended Washout

Special Considerations

Use in Pregnancy

Azathioprine33

2 weeks

DO NOT USE

Mycophenolate Mofetil34

6 weeks

Male patients should discontinue treatment for 3 months prior to conception

DO NOT USE

Methotrexate30

6 months

Male patients should discontinue treatment for 3 months prior to conception

DO NOT USE

IVIg35

None

Use if benefit outweighs risks

Rituximab20

1 - 3 months*

Use if benefit outweighs risks

Eculizumab36

5 months

DO NOT USE

Inebilizumab37

1 - 3 months*

Use if benefit outweighs risks

Satralizumab38

3 months

Use if benefit outweighs risks

Tocilizumab39

3 months

DO NOT USE

This table reflects our clinical practice and our review of combined recommendations for the prescribing information, and key articles. Pregnancy testing is recommended before commencement or re-infusion for all therapies in women of childbearing potential.

* See the corresponding paragraph for in-depth discussion regarding anti-CD20 therapies and pregnancy timing.

Table 2. Summary of Risks and Management Recommendations for Fetal Exposure to Immunosuppressive Therapies during Pregnancy

Medication

First Trimester Exposure

Exposure Risks

Pregnancy Registry

Azathioprine33

Early ultrasound for major malformations may be considered

Some animal models have shown teratogenicity with associated skeletal malformations and visceral abnormalities. Neonatal lymphopenia, hypogammaglobulinemia, CMV infection, and decreased thymic shadow have been reported. Human studies have demonstrated possible increased risk of preterm birth and fetal growth restriction.

Contact manufacturer

Mycophenolate Mofetil9

Early ultrasound for major malformations recommended

Known teratogen with risk of first trimester pregnancy loss and congenital malformations including external ear and facial abnormalities, anomalies of distal limbs, heart, esophagus, and kidneys.

1-800-617-8191

Methotrexate30

Early ultrasound for major malformations recommended

Known teratogen with risk of embryo-fetal toxicity and fetal death, spontaneous abortion, and diverse congenital malformations including skull, facial, central nervous system, limb, and cardiac anomalies. Intellectual impairment, intrauterine growth restriction, and functional abnormalities have also been reported.

1-800-FDA-1088

IVIg35

No additional fetal or neonatal monitoring

Animal reproduction studies have not been conducted – it is unknown whether IVIg causes fetal harm, including major birth defects or miscarriage. IVIg crosses the placental increasingly after 30 weeks' gestation.

NA

Rituximab20

No additional fetal or neonatal monitoring

Risk of B-cell depletion in fetus/infant with 2nd and 3rd-trimester exposure (typically with normalization within 6 months); risk of neonatal infections. There are no clear teratogenic effects in animal studies.

Contact manufacturer

Eculizumab36

No additional fetal or neonatal monitoring

There are no clear teratogenic effects in animal studies. Limited human studies have not suggested safety concerns. Risk of impaired immune function in fetus/infant with 2nd and 3rd trimester exposure; risk of neonatal infections.

1-888-765-4747

Inebilizumab37

No additional fetal or neonatal monitoring

Risk of B-cell depletion in fetus/infant with 2nd and 3rd-trimester exposure; risk of neonatal infections.

1-303-724-4644

Satralizumab38

No additional fetal or neonatal monitoring

Limited data have not shown adverse effects on maternal animals or fetal development. Risk of impaired immune function in fetus/infant with 2nd and 3rd trimester exposure; risk of neonatal infections.

1-833-277-9338

Tocilizumab39

No additional fetal or neonatal monitoring

Limited animal data have demonstrated risk of abortion / embryo-fetal death, and prior animal studies have suggested that inhibition of IL-6 signaling may interfere with cervical ripening and dilation. No clear teratogenic effects in animal studies have been demonstrated. Risk of impaired immune function in fetus/infant with 2nd and 3rd trimester exposure; risk of neonatal infections.

Contact manufacturer

This table reflects our clinical practice and our review of combined recommendations, prescribing information, and key articles.