Fetal Surgery Interview Study: Parental Perceptions of Fetal Surgery
Fetal Surgery Interview Study: Parental Perceptions of Fetal Surgery
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).

 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, itself associated with significant neonatal mortality and
 morbidity and long-term consequences. Balancing these competing risks is challenging.

 For an intervention to be effective it also needs to be acceptable to women and their
 families. "Acceptability" can be defined as a multi-faceted construct that reflects the
 extent to which people delivering or receiving a healthcare intervention consider it to be
 appropriate, based on anticipated or experienced cognitive and emotional responses to the
 intervention.

 With this study it is the aim to assess how women (and their partners) perceive the
 acceptability of a fetal surgical intervention for MMC and CDH. Participants will be asked to
 share their thoughts, views, feelings and experiences with regards to the decision to
 participate in fetal surgery. Data are collected by the use of in-depth face-to-face
 interviews. In-depth interviews are used to understand the participant's perspectives and
 perceptions of a situation they are in. It explicitly includes participants interpretation
 and understanding of an event

 The interviews will be held in two or three moments in time (for parents opting for fetal
 surgery, there will be one additional interview, after the intervention while admitted in
 hospital): after counselling for options, but before eventual intervention; for intervention
 group shortly after the intervention, and 12 weeks after birth of the baby, or termination of
 pregnancy.
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.

 A meta-analysis suggests that FETO improves survival, but the procedure remains to
 be considered investigational and is therefore currently evaluated within a
 randomized controlled clinical trial (www.totaltrial.eu).

 3. Acceptability For an intervention to be effective it also needs to be acceptable to
 women and their families. "Acceptability" can be defined as a multi-faceted
 construct that reflects the extent to which people delivering or receiving a
 healthcare intervention consider it to be appropriate, based on anticipated or
 experienced cognitive and emotional responses to the intervention. Based on this
 definition a theoretical framework of acceptability comprising seven components has
 been developed: affective attitude, burden, perceived effectiveness, ethicality,
 intervention coherence, opportunity costs, and self-efficacy. Successful
 implementation of an intervention means that it is acceptable for both recipients
 and deliverers. This study focuses on the recipients; measurement of acceptability
 for deliverers will be considered as other facets of the wider GIFT-Surg project.

 Timing is an important factor in the assessment as the relationship to perceived and
 actual experiences may differ. Acceptability is therefore assessed in two or three
 moments in time: prospective acceptability, concurrent acceptability and retrospective
 acceptability.

 2. Trial objectives

 Primary objective: to assess how women (and their partners) perceive the acceptability
 of a fetal surgical intervention for MMC and CDH. Participants will be asked to share
 their thoughts, views, feelings and experiences with regards to the decision to
 participate in fetal surgery.

 3. Trial Design

 This is a qualitative in-depth interview study, to include approximately 48
 women/couples at University Hospital Leuven for two fetal conditions (MMC and CDH),
 given all data on these 48 patients are complete. An estimated dropout rate of 50% means
 that in total 4 patients per treatment option (fetal surgery, expectant management,
 termination), and per condition (MMC or CDH) will be available for analysis.

 As not all parents opt for fetal surgery, after referral and counselling for prenatal
 diagnosed isolated spinal defects and congenital diaphragmatic hernia, patients fall
 into three groups: 1. Parents opting for fetal surgery, 2. Parents opting for
 termination of pregnancy and 3. Parents opting for expectant management. To assess
 acceptability of the intervention, it is of value to assess acceptability of the
 intervention in all three groups. In particular, knowledge of non-acceptability
 important.

 4. Trial Intervention

 Data collection will take place by executing face-to-face interviews. The interviews
 will be held in three moments in time: before, during (i.e. shortly after the
 intervention) and after the intervention. Prospective acceptability will be assessed,
 after patients have been first counselled and assessed, but before the intervention at
 stake. Concurrent acceptability, patients will be interviewed shortly after the
 intervention while still admitted for post-surgery observation, and retrospective
 acceptability three months after delivery.

 The interviews assessing prospective and concurrent acceptability will always be planned
 along visits to the treatment hospital so parents never have to come on purpose to the
 hospital for an interview, and will be held in Dutch or English. The interviews are
 expected to last approximately 30-60 minutes and will follow an interview guide. As it
 is acknowledged women (and their partners) go through an intensive and emotionally
 upsetting process, interviews will only be carried out if the patient is capable of
 participating in an interview, based on the patient's personal assessment as well as
 their doctor's assessment. For retrospective acceptability, depending on participant's
 preference, the interview can take place through teleconference or phone.

 Data-collection Data are collected by the use of in-depth interviews. In-depth
 interviews are used to understand the participant's perspectives and perceptions of a
 situation they are in. It explicitly includes participants interpretation and
 understanding of an event. The style of interviewing will be 'responsive'; this style
 emphasises on the importance of building a relationship of trust between interviewer and
 interviewee. This is done by creating a quiet and calm environment, an empathically
 neutral position of the interviewer and an open approach by using verbal and non-verbal
 communication. There will not be a set list of questions, but an interview guide based
 on one main-question, with different themes for probing, based on the seven components
 of the framework of acceptability. The interview will follow six stages as described by
 Yeo et al.: arrival and introduction: establish rapport, 'host' the interaction(stage
 1); introducing the research (aims and objectives, confidentiality, voluntary, scope of
 interview (participant in control), no right or wrong answers(stage 2); beginning of the
 interview: discuss contextual background information for reference and set the tone
 (stage 3); during the interview (start recording: breadth and depth of subject)(stage
 4); ending the interview: advance notice of end and opportunity for respondent to raise
 anything important not yet discussed (stage 5); and after the interview: thanking and
 emphasize on value of sharing their experience, how information is treated and used,
 follow up and further meetings to be scheduled (stage 6)(interview guide).

 The interviews will be recorded digitally with an audio recorder. Subsequently,
 interviews will be transcribed and coded transcripts will be translated into English and
 used for analysis. Back-translation will be used for a sample of 5 transcripts in Dutch
 to ensure accuracy.

 5. Sample size

 Intended sample size in Belgium is 12 women for MMC and 12 for CDH at study completion;
 in the UK the investigators expect to include 10 women for MMC and 5 for CDH. This
 sample size has been determined from interviewing clinical stakeholders. Sample size in
 qualitative research are usually small, as in analysis there will be at some point a
 moment in which no new information is obtained from additional interviews. This is also
 called saturation. The aim of this research is not to determine statistically
 significant discriminatory variables, but to get an in-depth understanding of the views
 and preferences of the participants, and to assess acceptability of the intervention.
 Exact sample size will depend on saturation

 6. Analysis

 The analysis is purely qualitative. The interviews will be transcribed verbatim by the
 researcher. Content analyses will be performed by using the qualitative software programme.
 First, initial content and subjects of interest are identified, the so-called familiarization
 with the data. This first step is followed by the initial construct of a framework. The
 framework constructs the headings under which respondent's views, feelings, experiences and
 perceptions can be organized. The framework is than used for labelling the data: quotes or
 pieces of text are ordered according to the different themes to fit in. The next step will be
 further refinement of the framework by making connections between categories and placing them
 in a broader context related to the framework of acceptability. To improve the quality of the
 analysis, at various moments interim analyses will be discussed among co-authors with a
 background in psychology and qualitative analysis. Thereafter, all previously analyzed
 transcripts will be reviewed to check that the content is consistent with this concept
 (thematic analysis).
Inclusion Criteria:

 -  Women/partners eligible for one of the two fetal surgery procedures studied (open
 fetal surgery for spina bifida closure, tracheal balloon occlusion for congenital
 diaphragmatic hernia (Fetoscopic Endoluminal Tracheal Occlusion, FETO), as clinical
 care

 -  Have given written informed consent for participation

 Exclusion:

 -  Women less than 18 years or over 65 years of age

 -  Partners less than 18 years or over 65 years of age

 -  Women or their partners who are unable to communicate in either English or the local
 language (if different)