# Impact of prenatal sirolimus on cardiac rhabdomyomas and brain tubers

## TL;DR

The study examines how prenatal sirolimus affects fetal heart tumors and brain tubers, finding that early treatment reduces tumor size but has limited impact on brain lesions.

## Contribution

The study provides new evidence on the efficacy of prenatal sirolimus in reducing cardiac rhabdomyoma size and complications.

## Key findings

- Prenatal sirolimus treatment for more than 7 days reduced cardiac tumor size and resolved complications in some cases.
- Discontinuation of treatment led to rebound tumor growth in two cases.
- Brain tubers showed limited change with treatment, but the sample size was too small for a definitive conclusion.

## Abstract

To document the natural progression of fetal cardiac rhabdomyomas and evaluate the impact of prenatal sirolimus (PNS) on tumor size, cardiac complications and brain‐tuber size.

This was a single‐center retrospective cohort study of pregnancies with suspected fetal cardiac rhabdomyoma referred to our center from April 2013 to May 2024. Serial ultrasound and echocardiography reports were reviewed to obtain tumor characteristics, such as diameter and location, and cardiac complications, including inflow or outflow obstruction, arrhythmia and hydrops. The tumor‐to‐femur length (TFL) ratio was calculated to correct for fetal growth. Prenatal neurosonography reports were collected from clinical records. Pre‐ and postnatal brain magnetic resonance imaging (MRI) scans were reviewed by two observers who were blinded to PNS treatment. Brain‐lesion severity was assessed based on the presence of subependymal nodules, the EPISTOP score, the maximum diameter of the largest subcortical tuber, the maximum diameter of the largest subependymal giant cell astrocytoma (SEGA) and the diameter of the largest lateral ventricle. Prenatal or postnatal genetic testing results were documented when available.

Twenty‐seven pregnancies were included in the study, seven of which received PNS. Prior to initiation of treatment, the diameter of the largest cardiac tumor at diagnosis was similar between the non‐PNS and PNS groups (mean, 15.2 mm vs 14.3 mm; P = 0.72), with the left ventricle the most frequently affected location. Without treatment, rhabdomyomas grew rapidly from 20 + 0 to 27 + 6 weeks' gestation (mean, 2.58 mm/week) but growth slowed after 28 weeks (mean, 0.44 mm/week). Hydrops was reported in four cases and occurred at a mean tumor diameter of 31.7 ± 6.2 mm, mean TFL ratio of 0.68 ± 0.15 and at a mean growth rate of 4.3 ± 1.7 mm/week. In the seven women treated with PNS, treatment for > 7 days (n = 3) resulted in tumor regression and/or resolution of outflow obstruction, and a reduction in TFL ratio; however, prenatal cessation of treatment resulted in rebound growth (n = 2). Treatment for ≤ 7 days (n = 4) did not impact tumor size or resolve existing cardiac complications. Among the 12 cases that underwent prenatal MRI, the median EPISTOP score was 7 (interquartile range (IQR), 1–15) and the median largest lateral ventricle diameter was 8.9 (IQR, 7.0–9.7) mm; subcortical tubers and subependymal nodules were each identified in 67% of cases, and SEGAs were identified in 58%. Among the 13 cases that underwent postnatal MRI, the median EPISTOP score was 14 (IQR, 3–16) and the median largest lateral ventricle diameter was 7 (IQR, 7–8) mm; brain tubers were identified in 92% of cases. In cases with both pre‐ and postnatal MRI findings who received PNS for > 7 days (n = 3), on postnatal MRI compared with prenatal MRI, one patient showed no change in findings, one demonstrated a mild increase in the largest subcortical tuber diameter and one had no detectable brain tubers.

Early and sustained PNS treatment was associated with reduced cardiac rhabdomyoma size and/or resolution of cardiac complications. Rebound tumor growth was observed after discontinuation of treatment. Brain tubers appeared unchanged with PNS treatment, although the sample size was too small to draw a definitive conclusion. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.