World first: treatment of a vascular malformation in utero


(actualité UCLouvain)

Vascular malformations have a major impact on the quality of life of those affected, and require very specific treatment. Teams from the Vascular Malformations Centre and the Obstetrics Department at Cliniques Saint-Luc, together with the Human Molecular Genetics Laboratory of the de Duve Institute at UCLouvain and the WEL Research Institute, treated a foetus with a lymphatic malformation in utero. Begun 6 years ago, this multidisciplinary treatment has been accompanied by long-term follow-up, which represents a world first. Today, the child is doing well and growing normally. The results of this exceptional operation are published in the journal Nature Cardiovascular Research.

Considered a rare disease, lymphatic malformations are lesions consisting of abnormal lymphatic vessels. Patients with these malformations suffer from deformities, severe pain, functional impotence, muscle weakness and bleeding. Their quality of life is considerably impaired.
In 2016, a multidisciplinary team from the Centre for Vascular Malformations (headed by Professor Laurence Boon) and the Obstetrics Department (multidisciplinary antenatal diagnosis team) at Saint-Luc treated a mother whose foetus had a major lymphatic malformation in the cervical region, threatening its development. During the pregnancy, this lesion led to compression of the foetus' airways and risked terminating the pregnancy.

Caring for the baby... via the mother

For the first time in the world, the vascular malformation was treated in utero using a drug (Sirolimus) administered directly to the mother during her pregnancy. The multidisciplinary team drew on its own experience and on the work of the human molecular genetics laboratory of the de Duve Institute at UCLouvain and the WEL Research Institute (directed by Professor Miikka Vikkula). Several studies carried out by this laboratory have highlighted the properties of Sirolimus in the treatment of low-flow vascular malformations such as lymphatic malformations. This work has led to the development of numerous clinical studies to evaluate and confirm the efficacy of Sirolimus at Cliniques Universitaires Saint-Luc.
As the drug had few side effects, it was administered to the mother to reach the foetus through the placental barrier, under the supervision of Dr Emmanuel Seront, from the Medical Oncology Department, and Professor Ann Van Damme, from the Paediatric Oncology and Haematology Department. Between the 29th and 34th weeks of pregnancy, the size of the lesion diminished considerably and the delivery proceeded normally.

In addition to sclerotherapy (injection of a drug into the abnormal vessels to dry them out) at 11 months, followed by an operation at 15 months, the child's treatment continued for several years. Now aged 6, the child is doing well and growing normally.
This medical feat is the result of a multidisciplinary collaboration between a number of clinicians and researchers. The results of this exceptional operation are published in the journal Nature Cardiovascular Research.

Towards more care in utero?

By puncturing the foetal cord during treatment, the team was able to identify a correlation between the amount of Sirolimus taken by the mother and the level of this drug in the foetal blood.
This is a major advance in the management of foetuses suffering from major vascular malformations. While the team at the Vascular Malformation Centre stresses the need for medical indications and multidisciplinary management before such treatments can be carried out, this medical prowess opens the way for many other disciplines to consider the possibility of initiating treatment as early as possible.

Article describing this research:

A case report of sirolimus use in early fetal management of lymphatic malformation
Seront E, Biard JM, Van Damme A, Revencu N, Lengelé B, Schmitz S, de Toeuf C, Clapuyt P, Veyckemans F, Prégardien C, Vikkula M, Bernard P & Boon L.
Nature Cardiovascular Research (2023)

Treatment of a vascular malformation in utero: more than 25 years of collaboration

The world first announced on June 5 by Cliniques universitaires Saint-Luc and UCLouvain's de Duve Institute is the result of more than twenty-five years of research and very close collaboration between the Vascular Anomalies Centre coordinated by Prof Laurence Boon and the Human Molecular Genetics Laboratory directed by Prof Miikka Vikkula. The constant interaction between fundamental and clinical research is one of the keys to this success and to the worldwide reputation of both teams.

Creation of the multidisciplinary Centre for Vascular Malformations at Cliniques universitaires Saint-Luc, dedicated to patients with vascular anomalies (angiomas). To date, it has seen around 300 new patients and 2,000 consultations a year. Weekly seminars bring together specialists in surgery, dermatology, radiology, genetics, etc. to improve patient care. Treatment depends on the type and location of the angioma. The Vascular Malformations Centre, coordinated by Professor Laurence Boon, chairs the VASCern-VASCA European reference network for vascular anomalies.

Post-doctoral fellows at Harvard Medical School (Boston), Miikka Vikkula and Laurence Boon have discovered that a gene is mutated in the hereditary form of venous malformations (TEK). (Cell)

Prof. Miikka Vikkula set up a human genetics research group at the Institut de Duve, now the Human Molecular Genetics Laboratory.

Vikkula and Boon's teams have discovered the mechanism of a genetic anomaly that explains one of the forms of non-hereditary vascular malformation. This crucial first step is leading scientists at the Institut de Duve and other teams around the world to identify new genetic causes of several vascular anomalies. (Nature Genetics)

Fonds InBev - Baillet Latour awards its annual Clinical Research Prize to Profs Miikka Vikkula and Laurence Boon for their research into vascular diseases and lymphoedema.


A world first (August): the teams led by Profs Vikkula and Boon discover a drug therapy that impressively improves patients' quality of life (by 30-90%), reduces pain, in some cases stops bleeding and reduces the size of lesions. Rapamycin, or sirolimus, which has long been used to treat other pathologies, is an inhibitor of the mTOR molecule, one of the proteins that is abnormally hyperactive in venous malformations (Journal of Clinical Investigation).

Involvement of adult and paediatric oncologists in the Centre to ensure better management of these new therapies based on the cause of the malformations.
The same year (December), the teams discovered a gene whose mutations explain 20% of cases of venous malformation (American Journal of Human Genetics). Today, scientists can establish the cause of 60 to 80% of vascular malformations; there are more than 40 variants, both vascular and lymphatic.

Prof. Vikkula is the first winner of the Generet Prize, managed by the King Baudouin Foundation, for his research into rare diseases. This is one of the most important awards for medical research in Belgium.

The de Duve Institute's Human Genetics Laboratory has discovered a new gene involved in primary lymphoedema, a chronic, severely disabling disease resulting from the development or abnormal function of the lymphatic system (lymph is not drained and accumulates, most often in the legs and arms, causing swelling, fibrosis and a predisposition to secondary infections). (Science Translational Medicine)

The two teams were testing the potential effects of thalidomide - a drug that was criticised for its effects on pregnant women but has since been re-evaluated for its action on blood vessels. The results are impressive: used alone or combined with other treatments, it reduces pain, heals ulcers, reduces the volume of malformations, stops bleeding and resolves heart failure.(Nature Cardiovascular Research)

Prof. Vikkula has been awarded the Earl P. Benditt Award by the North American Vascular Biology Organization. The prize will be officially presented to him in October in Newport, Rhode Island, in the United States.

In the press (+ video) - Première belge dans le soin d'un foetus, in utero, atteint d'une malformation - 05/06/2023 (+ video) - L'autre option, c'était l'avortement: Shanti, la maman du premier fœtus soigné in utero, témoigne - 05/06/2023 (+ video) - Première mondiale : le traitement d’une malformation vasculaire in utero grâce à la maman - 05/06/2023 - Un fœtus atteint d’une malformation vasculaire traité in utero: la prouesse d’une équipe belge - 05/06/2023 - « Première mondiale » en Belgique avec le traitement d’une malformation vasculaire in utero - 05/06/2023 - “Première mondiale” et “prouesse médicale” en Belgique avec le traitement d’une malformation vasculaire in utero - 05/06/2023 - «Première mondiale»: une malformation vasculaire traitée in utero - 05/06/2023 - Belgique: Traitement in utero d'une malformation vasculaire, une première mondiale - 05/06/2023 - Première belge : un anticancéreux traite avec succès une malformation chez un fœtus - 06/06/2023 - Première mondiale : traitement d’une malformation vasculaire in utero par des équipes des Cliniques Saint-Luc et de l’Institut de Duve (UCLouvain) - 07/06/2023

Aussi sur,,,,,,,,,,,, - “Wereldprimeur” voor België met in utero-behandeling van lymfatische afwijking - 05/06/2023

Ook op - World first: Belgian hospitals treated abnormality of baby in the womb - 06/06/2023