Qualitative In-depth Interviews With Women and Their Partners Concerning the Acceptability of Fetal Surgery

1. Background and rationale Fetal surgery is a highly technical procedure carried out by only a few specialised teams around the world. Fetal surgery improves outcomes for key conditions, but at significant procedure related fetal and maternal risk. Open maternal-fetal surgery is currently used on fetuses with myelomeningocele (MMC). Fetoscopic or minimal access fetal surgery is also being used to treat fetuses with congenital diaphragmatic hernia (CDH). By combining improved instrumentation, imaging, clinical training and public engagement The Guided Instrumentation for Fetal Therapy and Surgery (GIFT-Surg) project aims to provide fetal surgeons with tools to make fetal surgery safer and more efficient. The UZ and KU Leuven team participates in this engineering project.

Following accurate diagnosis of a congenital malformation such as MMC or CDH, prospective parents face a range of uncertainties regarding the future of their unborn child, and the options provided require major ethical considerations. In the situation under study, termination of pregnancy may be for some parents an alternative option to expectant prenatal management. Fetal therapy provides a tantalising third option for some, where procedures are undertaken to reduce the likelihood of a more complicated neonatal course, potentially improving long term outcome, but at risk of amniotic fluid leakage, infection and most importantly very preterm delivery, associated with significant neonatal mortality and morbidity and long-term consequences. Balancing these competing risks is challenging.

1. Myelomeningocele Prevalence, incidence, clinical presentation Myelomeningocele (MMC) or spina bifida is a congenital abnormality arising 28 days post-conception when part of the neural tube fails to close. Open spina bifida can present either with a flat defect without a fluid filled sac covering (myeloschisis), or membranous covering with extrusion of the cord into the sac (myelomeningocele). Its prevalence is approximately 4.9 per 10,000 live births in Europe. Myelomeningocele is a severe, yet non-lethal congenital abnormality affecting the central nervous system, with complex physical and neurodevelopmental sequelae. In most cases it is also associated with the Chiari Type II malformation (hindbrain herniation) and ventriculomegaly.

Therapy, risks and (long-term) outcome Until recently, the only options available to parents, once a diagnosis was made prenatally, were expectant management with delivery and postnatal surgery, or a pregnancy termination. But over the last thirty years, it became obvious that the condition is progressive in utero, as is suggested by the "two-hit" hypothesis; an initial embryonic failure in neurulation followed by secondary changes because of continuous exposure of the spinal cord to the intrauterine environment and the suction gradient on the hindbrain. This led to the concept of fetal intervention to arrest or reverse this natural course. Successful fetal coverage of MMC with improved functional outcome in the lamb model was first described in the late 1990s. This was translated clinically with encouraging early results in several case series and eventually led to the randomized controlled Management of Myelomeningocele Study (MOMS). This study demonstrated that mid-gestational layered repair reduces the need for ventriculoperitoneal shunting, improves the degree of hindbrain herniation, and preserves motor function better than postnatal surgery. However, fetal surgery for spina bifida comes with substantial maternal and fetal risks. The fetus is at increased risk of premature birth and its sequelae including sepsis, intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis and death. Besides there is the risk for maternal complications and the corporeal scar compromises uterine integrity. 2. Congenital diaphragmatic hernia Prevalence, incidence, clinical presentation Due to a defect in the diaphragm during embryonic development, abdominal organs herniate through the defect into the thoracic cavity, interfering with lung growth, resulting in developmental arrest of both airways and pulmonary vasculature. Congenital diaphragmatic hernia (CDH) occurs in 1/2500 to 1/5000 births, depending on whether stillbirths are included. Although the diaphragmatic defect is correctable after birth, the prenatal arrest of airway and vessel development is the main reason for postnatal problems, leading to respiratory failure and pulmonary hypertension (PHT) in the neonatal period. Although prenatal referral to specialist centers, high throughput and advanced neonatal care has improved survival, still 20-30% of all cases die. Besides, survivors experience ongoing pulmonary and nutritional morbidity.

Therapy, risks and (long-term) outcome In fetuses with poor prognosis, fetal lung growth can be stimulated by fetoscopic endoluminal tracheal occlusion (FETO) with a balloon. The fetal lung is a net secretor of fluid into the amniotic cavity and the lungs are maintained at a small positive pressure in normal development. Fetal tracheal occlusion (TO) prevents egress of lung liquid, leading to increased back pressure, in turn promoting stretch-induced growth of airways and vessels. TO appears to trigger sufficient lung growth to protect the lung from developing pulmonary hypoplasia. In utero reversal of the occlusion prompts pulmonary maturation. Experimentally an endoscopic technique of tracheal occlusion using a balloon was developed. In 2004, it was first applied clinically and referred to as Fetoscopic Endoluminal Tracheal Occlusion (FETO).

The major risk following the procedure is spontaneous pre-labour rupture of membranes before 37 weeks (PPROM). Gestational age at delivery logically is an important predictor of survival and morbidity in CDH fetuses, also when undergoing fetal therapy.