How should a woman with relapsing‑remitting multiple sclerosis who is pregnant or planning pregnancy be managed, including disease‑modifying therapy choices, relapse treatment, delivery planning, and postpartum considerations?

Management of Multiple Sclerosis in Pregnancy

Women with relapsing-remitting MS who are pregnant or planning pregnancy should continue or restart highly effective disease-modifying therapies (DMTs) when disease activity is present, with beta-interferons, glatiramer acetate, and natalizumab being the safest options during pregnancy, followed by immediate postpartum treatment reinitiation to prevent relapses.

Pre-Pregnancy Planning

Disease-Modifying Therapy Strategy

The approach to DMTs depends on disease activity and risk stratification:

For women with stable, low-risk disease:

• Beta-interferons, glatiramer acetate, or dimethyl fumarate can be continued until conception 1
• Beta-interferons and glatiramer acetate may even be continued throughout pregnancy if needed 1
• No washout period required for these agents

For women with highly active disease:

• Natalizumab should be continued until 34 gestational weeks, preferably dosed every 6-8 weeks 1
• This strategy dramatically reduces relapse risk: only 3.7% of women relapsed during pregnancy and 4.9% postpartum when natalizumab was continued actively (≥28 weeks gestation, restarted ≤1 month postpartum) 2
• In contrast, conservative natalizumab strategies (stopped ≤4 weeks gestation, restarted >1 month postpartum) resulted in 15.9% pregnancy relapses and 30.5% postpartum relapses 2

For women on other DMTs:

• Most DMTs require effective contraception and pre-specified washout periods before conception 1
• Ocrelizumab and rituximab show excellent safety profiles: 0% pregnancy relapse rate with ocrelizumab and only 4.1% postpartum relapse 2
• Anti-CD20 therapies (ocrelizumab, rituximab) are allowed during lactation 1

Critical Pitfall to Avoid

Do not delay DMT initiation or discourage pregnancy planning 1. The outdated approach of stopping all DMTs before pregnancy significantly increases relapse risk and long-term disability progression 3.

Risk Stratification

Women at highest risk for pregnancy/postpartum relapses:

• Spinal lesions at diagnosis or prior to conception 3
• No DMT exposure before pregnancy (66.7% vs 87.3% DMT exposure in relapse vs non-relapse groups) 3
• Higher baseline disability at conception 3

During Pregnancy

Monitoring and Relapse Management

• Relapses during pregnancy occur in approximately 7-16% of women depending on DMT strategy 2
• Peak relapse risk is in the first postpartum trimester (60.5% of peripartum relapses occur postpartum) 3

For acute relapses during pregnancy:

• Corticosteroids are the treatment of choice 4
• Azathioprine can be added for severe relapses 4

MRI and Imaging

• MRI without contrast should be performed if new neurological symptoms develop 5
• Routine surveillance MRI is not addressed in the evidence, but symptom-driven imaging is appropriate

Medications to Avoid

The following are contraindicated during pregnancy:

• Cyclophosphamide 4
• Mycophenolate mofetil (MMF) 4
• ACE inhibitors and ARBs 6, 7

If a woman becomes pregnant while on MMF, immediately switch to azathioprine 4.

Delivery Planning

• Vaginal delivery is appropriate for most women with MS 5
• Cesarean section is only indicated for standard obstetric reasons or if there is a neurological deficit that precludes vaginal delivery or recent hemorrhage 5
• Pregnancy outcomes are generally favorable: 95.4% term births with no significant differences in delivery mode between women with versus without relapses 3

Postpartum Management

Immediate Treatment Reinitiation

This is the most critical intervention to prevent postpartum relapses:

• Restart DMT immediately postpartum, ideally within 1 month 2
• Women who delayed natalizumab restart >1 month postpartum had 30.5% relapse rates versus 4.9% with early restart 2
• Do not taper corticosteroids or azathioprine during pregnancy or for at least 3 months after delivery if the patient is receiving these medications 4

Breastfeeding Considerations

Exclusive breastfeeding should be encouraged 1, with the following DMTs considered safe:

• Beta-interferons
• Glatiramer acetate
• Anti-CD20 monoclonal antibodies (ocrelizumab, rituximab) 1

Postpartum Relapse Prevention

Low-dose aspirin (81-100 mg daily) starting in the first trimester may reduce complications, particularly in women with additional risk factors 7.

Long-Term Disability Implications

Relapses during pregnancy or the postpartum year are associated with accelerated disability progression:

• 25.8% of women with peripartum relapses experienced disability progression within the first postpartum year versus only 5.5% without relapses 3
• Sustained EDSS differences persist at two years postpartum 3
• Postpartum MRI shows higher lesion load and more contrast-enhancing lesions in women who relapsed 3

This underscores the critical importance of maintaining effective DMT coverage throughout the peripartum period to preserve long-term neurological function and quality of life.

Fertility Considerations

• MS does not affect fertility 8
• Men taking DMTs should continue treatment when attempting conception—no evidence of teratogenicity or fertility impairment 9
• Contraception is mandatory before starting cytotoxic or teratogenic agents, but should not be continued longer than necessary as DMT withdrawal increases MS activity risk 10