Maternal Sirolimus Therapy for Fetal Extensive Lymphatic Cystic Malformation: Selection Criteria, Management, and Outcomes in a Series of Six Cases

OBJECTIVE: Maternal sirolimus therapy has emerged as a potential prenatal treatment for extensive fetal lymphatic malformations, particularly when associated with the risk of neonatal airway compromise. Data on prenatal indications, pharmacokinetics, and outcomes remain limited. We aimed to describe patient selection, treatment management, maternal and fetal safety, and early outcomes. METHODS: Between December 2023 and May 2025, 15 fetuses with extensive cystic or mixed vascular anomalies suggestive of lymphatic malformations were referred to a national reference center. Prenatal ultrasound and fetal magnetic resonance imaging were performed. After maternal evaluation and informed consent, sirolimus was administered with weekly dose adjustments based on maternal trough levels. Tolerance, drug concentrations at delivery, obstetric outcomes, and neonatal evolution were assessed. Decrease in lesion extent was assessed using a semi-quantitative 0-4 imaging scale. RESULTS: Six fetuses received therapy after the exclusion of nine cases. Treatment began between 24 and over 30 weeks' gestation. Maternal adverse effects were mild. Transplacental drug transfer was observed with variable maternal-fetal ratios. Mean gestational age at birth was 38.1 weeks. Partial or marked lesion regression occurred in five newborns. CONCLUSIONS: Maternal sirolimus therapy appears feasible and well tolerated for extensive fetal lymphatic malformations, demonstrating transplacental transfer and encouraging early perinatal outcomes in carefully selected pregnancies overall.