Background: Mechanistic target of rapamycin (mTOR) inhibitors are being used off-label showing promising results in patients with vascular anomalies. Children with lymphatic malformations (LMs) involving the airway benefit from sirolimus therapy soon after birth, reducing the need of tracheostomy. Available information about efficacy and side effects in neonates remains poor. We present seven newborns with severe head and neck LM showing response to sirolimus with no significant toxicity.

Methods and Results: We performed a retrospective review of neonates with head and neck LM who received sirolimus between January 2014 and May 2018 with upper airway involvement needing ventilatory support. We analyzed type of LM, involved anatomical area, symptoms and response to sirolimus, including dosage, blood levels, response, side effects, and complications. Seven neonates received primary treatment with sirolimus in the context of cervical LM. Sirolimus was started at the recommended dose of 0.8 mg/m²/12 h and adjusted to maintain blood levels between 4 and 12 ng/mL. Median follow-up was 32 months (4–43) with a median treatment duration of 12 months (3–43). One patient had complete resolution of the malformation, one had complete resolution of symptoms, and five had partial resolution of the malformation with significant improvement in their respiratory conditions. Two patients required additional subtotal surgical resection and one tracheostomy. Four patients remain under treatment. Toxicity was not observed.

Conclusions: Sirolimus is a safe drug in neonates and can be considered the first therapeutical option in newborns at high risk of respiratory failure before sclerosis or surgery. Close follow-up is mandatory to identify side effects at long-term use.