Paediatr Drugs. 2025 Jul 6. doi: 10.1007/s40272-025-00708-3. Online ahead of print.
ABSTRACT
INTRODUCTION: Congenital capillary-lymphatic-venous malformations (CLVMs) often result in life-threatening complications, which may begin in utero. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been successfully used in children and adults with CLVMs due to its antiproliferative and antiangiogenic properties. However, only two cases of prenatal sirolimus treatment of fetal CLVMs have been published to date, with very limited data on optimal therapeutic scheme and drug dosing.
CASE REPORTS: Here we report two cases of effective prenatal and postnatal sirolimus treatment of extensive, complicated fetal CLVMs. The CLVMs were diagnosed prenatally by ultrasound and confirmed by magnetic resonance. The pregnancies were complicated with intralesional bleeding in both cases and polyhydramnios in one. The pregnant women received oral sirolimus from the 32nd and 33rd weeks of gestation to delivery (for 11 and 31 days, respectively). The dose of oral sirolimus for the pregnant women ranged from 2 to 6 mg/day, with a target trough whole-blood level of 7-12 ng/mL, which resulted in the umbilical cord arterial blood levels of 3.8 and 6.4 ng/mL, respectively. Therapeutic effects of prenatal sirolimus were observed in both fetuses: one experienced reduced intralesional bleeding, while the other had a significant decrease in CLVM size. The sirolimus treatment has been continued postnatally in both children, currently aged 20 and 9 months. The mothers and children experienced no adverse events from the treatment.
CONCLUSIONS: Administration of sirolimus during pregnancy with maternal blood drug-level monitoring seems to be an efficient and safe treatment option that should be considered in high-risk fetal CLVMs.
PMID:40618300 | DOI:10.1007/s40272-025-00708-3
