AUTHOR=Van Neste Martje , Nauwelaerts Nina , Ceulemans Michael , Cuppers Benedikte , Annaert Pieter , Smits Anne , Allegaert Karel TITLE=Very low monomethyl fumarate exposure via human milk: a case report—a contribution from the ConcePTION project JOURNAL=Frontiers in Public Health VOLUME=12 YEAR=2024 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1393752 DOI=10.3389/fpubh.2024.1393752 ISSN=2296-2565 ABSTRACT=Introduction

While breastfeeding is recommended, knowledge regarding medicine transfer to human milk and its safety for nursing infants is limited. Only one paper has previously described dimethyl fumarate (DMF) transfer during breastfeeding in two patients at 5 and 6 months postpartum, respectively. The current case report describes maternal pharmacokinetic data of monomethyl fumarate (MMF), the active metabolite of DMF, and infant exposure estimations of MMF at 3 months postpartum.

Methods

A 32-year-old Caucasian woman started DMF therapy (120 mg, 2x/day) for multiple sclerosis at 3 months postpartum, after weaning her infant from breastfeeding. On day 99 after birth, the patient collected four milk samples over 24 h after 6 days of treatment at the initial dose. Additionally, a single maternal blood sample was collected to calculate the milk-to-plasma (M/P) ratio. The samples were analyzed using liquid chromatography coupled with the mass spectrometry method.

Results

A wide range of measured steady-state concentrations of MMF (5.5-83.5 ng/mL) was observed in human milk samples. Estimated daily infant dosage values for MMF, calculated with 150 and 200 mL/kg/day human milk intake, were 5.76 and 7.68 μg/kg/day, and the relative infant doses were 0.16 and 0.22%. The observed mean M/P ratio was 0.059, similar to the M/P ratio predicted using the empirical Koshimichi model (0.06).

Discussion

Combining this case report with the two previously described cases, the estimated infant exposure is low, albeit with relevant intra- and inter-patient variabilities. Research should further focus on infant exposure and safety.