Clinical trial NCT04770805: In Utero Fetoscopic Repair Program for Sacral Myelomeningoceles and Mye-LDM
Official title: In Utero Fetoscopic Repair Program for Sacral Myelomeningoceles and Mye-LDM
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Sacral Myelomeningocele
Neural Tube Defects
Spina Bifida
Keywords: Sacral Myelomeningocele
MyeLDM
Fetal surgery
Fetoscopic Repair Program
Neural Tube Defect
Spina bifida
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2021-02-25
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single arm clinical study. All participants will undergo laparotomy with exteriorization of the uterus followed by fetoscopic repair of the fetal MMC/MyeLDM lesion.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the feasibility and the maternal, fetal and postnatal outcomes of sacral myelomeningocele (MMC) and Myelic Limited Dorsal Myeloschisis (MyeLDM) fetoscopic repair at Trousseau Hospital (Paris, France).

Detailed description: Myelomeningocele and Myelic limited dorsal myeloschisis (MyeLDM) correspond to neural tube defects which lead to lifelong disabilities including lower extremity paralysis, sphincters deficiency, and cerebral complications (Chiari 2 malformation and hydrocephalus). It is demonstrated that fetal surgery repair of MMC with upper limit between the first thoracic vertebra (T1) and the first sacral vertebra (S1) improves motor and cerebral prognosis. Nowadays, this fetal surgery is performed either after maternal laparotomy and hysterotomy (open fetal surgery) or using fetoscopy. the investigators, at Trousseau Hospital (APHP, Paris), initiated an open fetal surgery of MMC program called PRIUM1 and 16 fetuses has been currently operated.

Fetoscopic repair of MMC is proposed by several international groups in order to prevent from maternal and obstetric morbidity related to the hysterotomy and improve the mother's obstetrical prognosis by allowing vaginal delivery. Results of fetoscopic MMC repair are very satisfying, both in terms of repair surgery efficacy and in terms of obstetrical prognosis. The research team believe that it is justified to propose this minimally invasive repair technique using fetoscopy, for represented by sacral MMC (level S1 and lower) as well as for intermediate forms between open and closed dysgraphisms, represented by MyeLDM. Indeed, these dysraphism are associated with the same cerebral complications than MMC with upper limit between T1 and S1 which could be corrected with prenatal repair. In addition, the spinal cord protection offered by prenatal surgery could prevent from the neuroepithelium destruction observed during pregnancy, with a potential motor benefit for the children.

The main objective of PRIUM 2 is to evaluate the success of fetoscopic surgical repair of sacral MMC or MyeLDM with a birth after 32 weeks of gestation and without severe perinatal morbidity and mortality.

The secondary objectives of PRIUM 2 are to evaluate the complications of pregnancy related to fetoscopic surgery as well as to evaluate the prenatal and postnatal evolution of the cerebral complications (Chiari 2 malformation and hydrocephalus) after fetoscopic repair surgery of the dysraphism (up to 12 months of age).

In this protocol, fetal sacral MMC/ MyeLDM repair surgery will be performed using gas fetoscopy before 26 weeks. After an exteriorization of the uterus through a laparotomy, humidified and warmed gas will be insufflated with low pressure (6 to 8mmHg mmHg). Fetoscopic repair surgery will be performed by a multidisciplinary team (maternal fetal medicine specialists, pediatric neurosurgeons, pediatric surgeons).

After discharge, patients will be followed weekly by a midwife and every two weeks by a referring obstetrician who will perform a clinical examination and a fetal ultrasound.A post procedure MRI will be performed 4 weeks after the surgery. If there is no obstetrical contraindication, vaginal delivery will be authorized.

The children will be followed according to the conventional management of children with dysraphisms and consultations at 8 weeks of life and 12 months of life will be scheduled at Trousseau Hospital, with the multidisciplinary team (pediatric neurosurgeons, physical medicine and rehabilitation specialists, pediatric orthopedic surgeons). During these two consultations, the children will have a complete clinical examination, a cerebral and spinal MRI and an ultrasound of the urinary tract.

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria :

* Pregnant women age 18 years and older who are able to consent
* Singleton pregnancy before 26 weeks of gestation,
* Sacral MMC (upper level S1 or below) or MyeLDM diagnosed on ultrasound and MRI, 4. Absence of associated malformation apart from the anomalies usually observed in cases of open dysraphisms (i.e. feet malpositions, associated cerebral signs) or chromosomal anomaly if verification of the karyotype was desired by the couple
* Affiliated to health insurance, understanding and speaking French
* Written consent of the patient for the surgery and representatives of the parental authority for the postnatal follow-up of the child
* Patient who made the choice to continue the pregnancy

Exclusion Criteria:

* Abnormal angulation of the fetal spine,
* risk factors for prematurity: cervical length less \< 15mm, history of late miscarriage before 22 weeks, pre-existing rupture of the membranes at inclusion,
* Placenta praevia,
* BMI greater than 35 kg / m2,
* Abnormality of the uterus: large fibroid, uterine malformation, history of uterine body surgery
* Maternal infection at risk of maternal-fetal transmission: HIV, HBV, HCV,
* Surgical or anesthetic contraindication.
* Participation in another interventional research protocol,
* Patients under legal protection (guardianship, curatorship).
* Allergies to drugs used in the research

Primary outcomes:
measure: Ability to perform fetoscopic sacral MMC/MyeLDM repair without severe perinatal morbidity and mortality
timeFrame: From time of surgery to 8 weeks of life (up to 28 weeks)
Secondary outcomes:
measure: Adverse Maternal outcome
timeFrame: during the surgery
measure: Maternal obstetric outcome as evidenced by preterm labor leading to delivery at less than 37 weeks of gestation
timeFrame: From time of surgery until 37 weeks of gestation
measure: Maternal obstetric outcome as evidenced by preterm premature rupture of membranes
timeFrame: From time of surgery until 37 weeks of gestation
measure: Maternal obstetric outcome as evidenced by chorioamnionitis
timeFrame: From time of surgery until 37 weeks of gestation
measure: Maternal obstetric outcome as evidenced by antenatal betamethasone treatment
timeFrame: From time of surgery until 34 weeks of gestation
measure: Other Maternal obstetric outcome as evidenced by hypertensive disorders, preeclampsia, gestational diabetes
timeFrame: From time of surgery until 37 weeks of gestation
measure: Prenatal evolution of brain abnormalities associated with open dysraphism, after fetoscopic repair
timeFrame: From time of surgery until birth
measure: Prenatal evolution of brain abnormalities associated with open dysraphism, after fetoscopic repair (1)
timeFrame: From time of surgery until birth
measure: Prenatal evolution of brain abnormalities associated with open dysraphism, after fetoscopic repair (2)
timeFrame: From time of surgery until birth
measure: Prenatal evolution of brain abnormalities associated with open dysraphism, after fetoscopic repair (3)
timeFrame: From time of surgery until birth
measure: Maternal obstetric outcome as evidenced by gestational age at delivery (1)
timeFrame: From time of surgery until delivery
measure: Maternal obstetric outcome as evidenced by gestational age at delivery (2)
timeFrame: From time of surgery until delivery
measure: Maternal obstetric outcome as evidenced by the ability to deliver vaginally
timeFrame: From time of surgery until delivery
measure: Proportion of postpartum hemorrhages
timeFrame: From time of surgery until delivery
measure: Need for maternal transfusion (number of blood cells transfused)
timeFrame: From time of surgery until delivery
measure: Adverse neonatal outcome at birth (1)
timeFrame: at birth
measure: Adverse neonatal outcome at birth (2)
timeFrame: at birth
measure: Adverse early childhood outcome as evidenced by need for a neurosurgical intervention
timeFrame: From the time of birth until 8 weeks of life
measure: Postnatal evolution of brain abnormalities associated with open dysraphism
timeFrame: From the time of birth until 12 months of life
measure: Postnatal evolution of brain abnormalities associated with open dysraphism (1)
timeFrame: From the time of birth until 12 months of life
measure: Postnatal evolution of brain abnormalities associated with open dysraphism (2)
timeFrame: From the time of birth until 12 months of life
measure: Postnatal evolution of brain abnormalities associated with open dysraphism (3)
timeFrame: From the time of birth until 12 months of life
Other outcomes:
Locations:
city: Paris
country: France
facility: Service médecine foetale-Hôpital Trousseau
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Lucie GUILBAUD, MD
role: PRINCIPAL_INVESTIGATOR
References: