Pregnancy and Infant Outcomes in Multiple Sclerosis: Findings From the MAPLE-MS Pharmacovigilance Program

Pregnancy planning is part of almost every neurologist’s discussion with young women newly diagnosed with MS. Therapies like cladribine offer potent disease control but come with clear warnings: avoid pregnancy for at least six months after treatment. Yet real life often more complicated, and some pregnancies occur within that window. Until recently, we had little data to guide the conversation that follows.

Now, we have something more concrete. The year seven interim results from the MAPLE-MS global pharmacovigilance program—published in Neurology: Neuroimmunology & Neuroinflammation in 2025—offer the most comprehensive picture to date of pregnancy and infant outcomes following exposure to cladribine tablets.

MAPLE-MS is a 10-year post-marketing surveillance program collecting data from across 50+ countries, tracking pregnancy outcomes in patients with MS who were exposed to cladribine tablets either within six months of conception or during pregnancy.

In this seventh-year analysis, 383 pregnancy cases were reported: 336 with maternal exposure and 47 with paternal exposure. Of the maternal cases, 157 had known outcomes. The numbers may sound modest, but this is already the largest dataset of its kind for cladribine.

Low Malformation Risk, No New Signals

Among 89 live births in the maternal exposure group, just one case of a major congenital anomaly (MCA) was reported: an atrial septal defect. That translates to a prevalence of 1.1%—well below the 3%–5% rates reported in general population studies and MS pregnancy registries.

Preterm birth occurred in about 6.7% of live births, and only one case (1.1%) was small for gestational age. No stillbirths were reported among maternal exposures.

The spontaneous abortion rate was 20.4%, which aligns with general epidemiologic ranges (10%–24%) but is higher than what’s been seen in some MS DMT-specific registries, like those tracking dimethyl fumarate or interferon beta.

Elective terminations accounted for 21% of known maternal cases. Notably, half of those were patient choice; just one was a confirmed termination for fetal anomaly.

What About Paternal Exposure?

While most safety conversations center on maternal drug exposure, MAPLE-MS also captured 16 paternal cases with known outcomes.

The results included no MCAs, one stillbirth, and an 81.3% live birth rate. It’s a small cohort, but in a space with almost no existing data on paternal cladribine exposure, even small numbers matter.

Table: Key Outcomes in MAPLE-MS Year 7 Report

Looking Ahead

About 30% of maternal cases are still pending or lost to follow-up, so prevalence estimates may shift slightly with future analyses. That said, the current report covers a significant number of prospective cases—where outcomes were unknown at the time of reporting—so selection bias is likely limited.

What’s also notable is that MAPLE-MS, unlike many registries, includes both spontaneous and solicited reports and follows outcomes for up to one year after birth. That long view strengthens the validity of the results and gives clinicians more confidence when making time-sensitive decisions.

For patients navigating MS and reproductive decisions, uncertainty is one of the hardest parts. MAPLE-MS doesn’t remove all of it, but it does offer clarity where before there was little more than caution. For providers, this means counseling with greater nuance, more evidence, and less reliance on hypotheticals.

Reference

Hellwig K, Tilson HH, Thiel S, et al. Pregnancy and infant outcomes in multiple sclerosis: Findings from the global MAPLE-MS pharmacovigilance program. Neurol Neuroimmunol Neuroinflamm. 2025;12(5):e200438. doi:10.1212/NXI.0000000000200438