Raman spectroscopy analysis of human amniotic fluid cells from fetuses with myelomeningocele.

Prenatal surgery for the treatment of spina bifida (myelomeningocele, MMC) significantly enhances the neurological prognosis of the patient. To ensure better protection of the spinal cord by large defects, the application of skin grafts produced with cells gained from the amniotic fluid is presently studied. In order to determine the most appropriate cells for this purpose, we tried to shed light on the extremely complex amniotic fluid cellular composition in healthy and MMC pregnancies. We exploited the potential of micro-Raman spectroscopy to analyse and characterize human amniotic fluid cells in total and putative (cKit/CD117-positive) stem cells of fetuses with MMC in comparison with amniotic fluid cells from healthy individuals, human fetal dermal fibroblasts and adult adipose derived stem cells. We found that (i) the differences between healthy and MMC amniocytes can be attributed to specific spectral regions involving collagen, lipids, sugars, tryptophan, aspartate, glutamate, and carotenoids, (ii) MMC amniotic fluid contains two particular cell populations which are absent or reduced in normal pregnancies, (iii) the cKit-negative healthy amniocyte subpopulation shares molecular features with human fetal fibroblasts. On the one hand we demonstrate a different amniotic fluid cellular composition in healthy and MMC pregnancies, on the other our work confirms micro-Raman spectroscopy to be a valuable tool for discriminating cell populations in unknown mixtures of cells.

Pain scores after open fetal spina bifida repair and caesarean section - a longitudinal cohort study.

INTRODUCTION: In fetal surgery, successful pain management is crucial for postoperative mobilization, prophylaxis of contractions, and fast recovery. This study analyzed patient's pain experience after open fetal spina bifida (fSB) repair in comparison to pain scores after the subsequent Caesarean section (C-section). MATERIALS AND METHODS: Data was collected with a questionnaire given to 91 women, who had fSB repair and then C-section at our center between 2019 and 2022. It comprised 12 questions covering different aspects of pain experience and satisfaction with pain therapy and was answered by 67 women after fSB repair and 53 after C-section. Postoperative pain was rated on a Likert scale from 0 (slight/rarely) to 100 (strongest/always). Outcomes after fSB repair were compared to those after C-section. Additionally, subgroup analysis compared outcomes of women with different pain levels (group 1-5) after fSB repair. RESULTS: Compared to women after C-section women after fSB repair reported significantly higher maximum pain scores (MPS) (p = 0.03), higher sleep disturbance due to pain (p = 0.03), and sedation rates (p = 0.001) as side effect from pain therapy. No differences were found regarding feelings of insecurity (p = 0.20) or helplessness (p = 0.40), as well as involvement in (p = 0.3) and satisfaction with pain therapy (p = 0.5). Subgroup analysis revealed that women with higher MPS after fSB repair were significantly more often non-Caucasians (p = 0.003) and more often affected by pain while lying in bed (p = 0.007) and during mobilization (p = 0.005). Additionally they reported higher rates of dizziness (p = 0.02) and lower satisfaction rates with pain therapy (p = 0.03). Postoperative complication rate did not differ among groups. CONCLUSION: Although women after fSB repair reported higher MPS compared to after C-section, the current pain management was generally perceived as satisfactory.

Enhanced Recovery after Surgery in Open Fetal Spina Bifida Repair.

INTRODUCTION: For open fetal spina bifida (fSB) repair, a maternal laparotomy is required. Hence, enhanced maternal recovery after surgery (ERAS) is paramount. A revision of our ERAS protocol was made, including changes in operative techniques and postoperative pain management. This study investigates eventual benefits. METHODS: Our study included 111 women with open fSB repair at our center. The old protocol group (group 1) either received a transverse incision of the fascia with transection of the rectus abdominis muscle (RAM) or a longitudinal incision of the fascia without RAM transection, depending on placental location. The new protocol required longitudinal incisions in all patients (group 2). Postoperative pain management was changed from tramadol to oxycodone/naloxone. Outcomes of the two different protocol groups were analyzed and compared regarding the primary endpoint, the length of hospital stay (LOS) after fetal surgery, as well as regarding the following secondary endpoints: postoperative pain scores, day of first mobilization, removal of urinary catheter, bowel movement, and the occurrence of maternal and fetal complications. RESULTS: Out of 111 women, 82 (73.9%) were in group 1 and 29 (26.1%) were in group 2. Women in group 2 showed a significantly shorter LOS (18 [14-23] days vs. 27 [18-39] days, p = 0.002), duration until mobilization (3 [2-3] days vs. 3 [3-4] days, p = 0.03), and removal of urinary catheter (day 3 [3-3] vs. day 4 [3-4], p = 0.004). Group 2 less often received morphine subcutaneously (0% vs. 35.4%, p < 0.001) or intravenously (0% vs. 17.1%, p = 0.02) but more often oxycodone (69.0% vs. 18.3%, p < 0.001). No significant differences were seen regarding pain scores, bowel movement, and maternal and/or fetal complications. CONCLUSION: The new ERAS protocol that combined changes in surgical technique and pain medication led to better outcomes while reducing LOS. Continuous revisions of current ERAS protocols are essential to improve patient care continuously.

Fetal Spina Bifida Repair in Obese Mothers: Is Maternal and Fetal Safety Compromised?

INTRODUCTION: The Management of Myelomeningocele Study (MOMS) eligibility criteria preclude in utero surgery for fetal spina bifida (fSB) when the maternal body mass index (BMI) is ≥35 kg/m2. Some centers still respect this criterion, while others, like ours, do not. This study aimed to assess whether maternal and fetal safety is compromised with higher maternal BMIs. METHODS: Data of 192 patients with open fSB repair at our center were retrospectively analyzed. According to their BMI, patients were divided into three groups: group 1 (BMI <30 kg/m2), group 2 (BMI 30-35 kg/m2), and group 3 (BMI >35 kg/m2). Subgroup analysis was performed to assess differences in maternal and fetal outcomes. Additionally, complications were divided into grades 1 to 5 according to their severity and outcome consequences and compared among groups. RESULTS: Out of 192 patients, 146 (76.0%) had a BMI <30 kg/m2, 28 (14.6%) had a BMI 30-35 kg/m2, and 18 (9.4%) had a BMI >35 kg/m2. Significant differences occurring more often in either group 2 or 3 compared to group 1 were maternal wound seroma (50% or 56% vs. 32%, p = 0.04), amniotic fluid leakage (14% or 6% vs. 2%, p = 0.01) as well as vaginal bleeding (11% or 35% vs. 9%, p = 0.01). On the contrary, duration of tocolysis with atosiban was shorter in patients with BMI >30 kg/m2 (4 or 5 vs. 6 days, p = 0.01). When comparing severity of maternal or fetal complications, grade 1 intervention-related complications occurred significantly more often in group 3 compared to group 1 or 2 (78% vs. 45% or 57%, p = 0.02). Gestational age at delivery was around 36 weeks in all groups without significant differences. CONCLUSION: This investigation did not identify clinically relevant maternal and/or fetal outcome problems related to BMIs >35 kg/m2. Additional studies are however needed to confirm our results.

Prenatal Spina Bifida Repair: Defendable Trespassing of MOMS Criteria Results in Commendable Personalized Medicine.

INTRODUCTION: We hypothesize that after publication of the quintessence of the MOMS trial, eligibility criteria for prenatal spina bifida (SB) repair may be modified if a tenable argumentation underlies this decision. METHODS: Our first 154 fetal surgery patients were analyzed with particular focus on how many, which, and why the original eligibility criteria, set forth by the MOMS Trial Protocol, were disobeyed, and what the eventually detectable, negative and positive impacts of these deviations on outcomes were. RESULTS: A total of 152 patients (2 missing consent) were included (100%). In 69 patients (45.4%), a total of 89 eligibility criteria were disobeyed. In 54 (35.6%) cases, the following maternal criteria were concerned: gestational age at operation of >25+6 weeks in 17 (11.2%), uterine pathologies in 13 (8.6%) women, preoperative BMI ≥35 kg/m2 in 12 (7.9%), previous hysterotomy in 7 (4.6%), previous prematurity in 3 (2%), HIV/hepatitis B in 2 (1.3%), psychosocial issues in 2 (1.3%), and placenta praevia in 1 (0.7%). In 32 (21.1%) cases, fetal criteria were disobeyed 34 times: Fetal anomaly unrelated to SB in 19 (12.5%), no/minimal evidence of hindbrain herniation in 13 (8.6%), and severe kyphosis in 2 (1.3%). We could not identify cases where non-observation of criteria led to clear-cut maternal and/or fetal disadvantages. CONCLUSION: This study shows that MOMS trial eligibility criteria for prenatal SB repair should be modified or even abandoned with adequate medical and ethical argumentation, and with written parental informed consent after non-directive, full disclosure counseling. This clear-cut change of paradigm is a necessity as it leads toward personalized medicine, allowing more fetuses to benefit from fetal surgery than would have benefitted with the former, published, MOMS criteria in place.

Stage 2: The Vaginal Flora in Women Undergoing Fetal Spina Bifida Repair and Its Potential Association with Preterm Rupture of Membranes and Preterm Birth.

INTRODUCTION: Vaginal dysbiosis affects pregnancy outcomes, however, the relevance of abnormal findings on pre/post-surgical vaginal culture in women undergoing fetal spina bifida (fSB) repair is unknown. OBJECTIVES: To describe the incidence of normal and abnormal pre- and post-surgical vaginal microorganisms in fSB patients and to investigate potential associations between the type of vaginal flora and the occurrence of preterm prelabour rupture of membranes (PPROM) and preterm birth (PTB). METHODS: 99 women undergoing fSB repair were eligible (2010-2019). Pre-surgical vaginal culture was routinely taken before surgery. Post-surgical cultures were taken on indication. Vaginal flora was categorized into four categories: healthy vaginal flora (HVF), bacterial vaginosis (BV), desquamative inflammatory vaginitis (DIV), and yeast infection. RESULTS: The incidence of HVF, BV, DIV, or yeast infections was not statistically different between the pre- and postoperative patients. Furthermore, an abnormal pre/post-surgical vaginal flora was not associated with PPROM (OR 1.57 (0.74-3.32), p = 0.213)/OR 1.26 (0.62-2.55), p = 0.515), or with PTB (OR 1.19 (0.82-1.73), p = 0.315)/(OR 0.86 (0.60-1.24), p = 0.425). CONCLUSIONS: Abnormal vaginal microbiome was not associated with PPROM and PTB when appropriate treatment was performed.

Subsequent Pregnancy Outcomes after Open in utero Spina Bifida Repair.

INTRODUCTION: Fetal spina bifida (SB) repair is a distinct therapeutic option in selected cases. Since this procedure may not only be associated with short-term obstetrical complications, the aim of this study was to assess the outcomes of subsequent pregnancies after open fetal SB repair. METHODS: 138 patients having had open fetal SB repair at our center received a questionnaire regarding the occurrence, course, and outcome of subsequent pregnancies. Additionally, medical records were reviewed. All subsequent pregnancies with complete outcome data that progressed beyond 20 gestational weeks (GW) were included for further analysis. RESULTS: 70% of all women answered the questionnaire. Out of this cohort, 35 subsequent pregnancies were reported in 29% of women. The rate of early pregnancy loss including elective terminations was 14%. All 29 pregnancies processing >20 GW ended in live births without preterm births <34th GW. Mean gestational age at delivery was 37.3 ± 1.4 GW. Uterine rupture occurred in two cases (7%) and uterine thinning/dehiscence was present in six cases (21%). No maternal transfusions were required. CONCLUSION: When counseling women undergoing open fetal SB repair, one should consider possible risks for subsequent pregnancies, especially the one of uterine dehiscence and rupture that is similar compared to numbers reported after classical cesarean deliveries.

Fetal-Maternal Surgery for Spina Bifida in a HIV-Infected Mother.

INTRODUCTION: In select cases, in utero surgery for myelomeningocele (MMC) leads to better outcomes than postnatal repair. However, maternal HIV infection constitutes a formal exclusion criterion due to the potential of vertical HIV transmission. Encouraged by a previous case of a successful fetal spina bifida repair in a Hepatitis Bs antigen-positive woman, a plan was devised allowing for fetal surgery. CASE REPORT: In utero MMC repair was performed although the mother was HIV-infected. To minimize the risk of in utero HIV transmission, the mother was treated by highly active antiretroviral therapy throughout gestation as well as intravenous zi-dovudine administration during maternal-fetal surgery. The mother tolerated all procedures very well without any sequelae. The currently 20 month-old toddler is HIV negative and has significantly benefitted from fetal surgery. DISCUSSION/CONCLUSION: This case shows that maternal HIV is not a priori a diagnosis that excludes fetal surgery. Rather, it might be a surrogate for moving towards personalized medicine and away from applying too rigorous exclusion criteria in the selection of candidates for maternal-fetal surgery.

Determination of Anatomical Levels in Spina Bifida Fetuses with Ultrasound and MRI.

PURPOSE: The goal of this study was to assess the accuracy of prenatal anatomical level determination by ultrasound (US) and magnetic resonance imaging (MRI) by analyzing the congruence with the "true" anatomical level identified by postnatal MRI. PATIENTS AND METHODS: The first 60 patients undergoing fetal myelomeningocele surgery at The Zurich Center for Fetal Diangosis and Therapy were included in this study. Anatomical levels (i. e., first dysraphic vertebra) determined by prenatal US and MRI were compared to postnatal MRI. The level of agreement between the imaging modalities was evaluated with a Cohen's kappa test. Results > 0.6 were interpreted as good agreement, > 0.8 as excellent. RESULTS: The exact congruence between prenatal US and MRI compared to postnatal MRI was 33 % and 48 %, respectively, for an accuracy within one level difference of 80 % and 90 %, and within two levels difference of 95 % and 98 %, respectively. The level of agreement of prenatal US and MRI compared to postnatal MRI was 0.62 and 0.79, respectively. Most of the prenatally incorrectly assigned levels were assigned too high (worse) than the "true" level (US 88 % vs. MRI 65 %). CONCLUSION: Reliable exact prenatal level determination by US and MRI is not possible. However, the prenatal determination of the anatomical level of the lesion is good within one level margin of error. Prenatal US as well as MRI demonstrate a systematic error towards higher levels. The above considerations must be integrated into prenatal counselling.

Are Cervical Length and Fibronectin Predictors of Preterm Birth after Fetal Spina Bifida Repair? A Single Center Cohort Study.

Background: A remaining risk of fetal spina bifida (fSB) repair is preterm delivery. This study assessed the value of preoperative cervical length (CL), CL dynamics (∆CL) and fetal fibronectin (fFN) tests to predict obstetric complications and length of stay (LOS) around fSB repair. Methods: 134 patients were included in this study. All patients had CL measurement and fFN testing before fSB repair. ∆CL within the first 14 days after intervention and until discharge after fSB repair were compared in groups (∆CL ≥ 10 mm/<10 mm; ≥20 mm/<20 mm). CL before surgery, ∆CL's, and positive fFN tests were correlated to obstetric complications and LOS. Results: Mean CL before surgery was 41 ± 7 mm. Mean GA at birth was 35.4 ± 2.2 weeks. In the group of ∆CL ≥ 10 mm within the first 14 days after intervention, LOS was significantly longer (p = 0.02). ∆CL ≥ 10 mm until discharge after fSB was associated with a significantly higher rate of GA at birth <34 weeks (p = 0.03). The 3 positive fFN tests before fSB repair showed no correlation with GA at birth. Conclusion: Perioperative ∆CL influences LOS after fetal surgery. ∆CL ≥ 10 mm until discharge after fSB repair has a 3-times higher rate of preterm delivery before 34 weeks. Preoperative fFN testing showed no predictive value for preterm birth after fSB repair and was stopped.

In vivo Sealing of Fetoscopy-Induced Fetal Membrane Defects by Mussel Glue.

INTRODUCTION: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated. METHODS: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods. RESULTS: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue. CONCLUSION: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed.

Minimally Invasive Precise Application of Bioadhesives to Prevent IPPROM on a Pregnant Sheep Model.

INTRODUCTION: Iatrogenic preterm premature rupture of the membrane remains the Achille's heel of fetoscopy. The aim of this study was to show in vivo feasibility of fetal membrane (FM) defect sealing by the application of tissue glues with umbrella-shaped receptors. METHODS: First, we adapted our previously described ex vivo strategy and evaluated the adhesion strength of different tissue glues, Histoacryl® and Glubran2®, by bonding polytetrafluoroethylene or silicone encapsulated nitinol glue receptor to human FM. Then, we exposed pregnant sheep uterus through a laparotomy and placed a 10-French trocar into the amniotic cavity through which the umbrella-shaped glue receptor (n = 9) was inserted and fixated onto the FM with the tissue glues (n = 8). The tightness of the sealed defects was assessed 4 h post-surgery. RESULTS: Both tissue glues tested resulted in adhesion of the glue receptors to the FM ex vivo. In vivo, all glue receptors opened in the amniotic cavity (n = 9) and all successfully placed glue receptors sealed the FM defect (n = 8). Four hours post-surgery, 2 treatment sites showed minimal leakage whereas the negative control without glue (n = 1) showed substantial leakage. DISCUSSION: This in vivo study confirms that fetoscopically induced FM defects can be sealed by the application of tissue adhesives.

Emerging magnetic resonance imaging techniques in open spina bifida in utero.

Magnetic resonance imaging (MRI) has become an essential diagnostic modality for congenital disorders of the central nervous system. Recent advancements have transformed foetal MRI into a clinically feasible tool, and in an effort to find predictors of clinical outcomes in spinal dysraphism, foetal MRI began to unveil its potential. The purpose of our review is to introduce MRI techniques to experts with diverse backgrounds, who are involved in the management of spina bifida. We introduce advanced foetal MRI postprocessing potentially improving the diagnostic work-up. Importantly, we discuss how postprocessing can lead to a more efficient utilisation of foetal or neonatal MRI data to depict relevant anatomical characteristics. We provide a critical perspective on how structural, diffusion and metabolic MRI are utilised in an endeavour to shed light on the correlates of impaired development. We found that the literature is consistent about the value of MRI in providing morphological cues about hydrocephalus development, hindbrain herniation or outcomes related to shunting and motor functioning. MRI techniques, such as foetal diffusion MRI or diffusion tractography, are still far from clinical use; however, postnatal studies using these methods revealed findings that may reflect early neural correlates of upstream neuronal damage in spinal dysraphism.

Long-Term Outcome of Monochorionic Twins after Fetoscopic Laser Therapy Compared to Matched Dichorionic Twins.

INTRODUCTION: The only causal therapy is fetoscopic laser surgery (FLS). The aims of this study were to analyze the long-term outcome of monochorionic twins treated by FLS, including their school career, need for therapy and special aid equipment, and free-time activities, and compare their outcome to matched dichorionic twins. MATERIAL AND METHODS: Among the 57 women treated at a single fetal treatment center between 2008 and 2017 with FLS because of twin-to-twin transfusion syndrome, 25 women with 42 children were included in the FLS group. The control group consisted of 16 dichorionic twin pairs matched for birth year, gestational age (GA), birth weight, and sex. The long-term outcome was assessed by a parental questionnaire and a standardized neurodevelopmental examination for children born before 32 gestational weeks or with a birth weight lower than 1500 g. They were also registered into the Swiss Neonatal Network database. The primary outcome was event-free survival, defined as normal neurology, behavior, vision, and hearing. The secondary outcomes were school career, need for therapy and special aid equipment, and free-time activities. RESULTS: An event-free survival was found in 32 children (76%) in the laser and in 24 children (75%) in the control group (p = 0.91). Neurological anomalies were found in 5 children (12%) in the laser group and 3 children (9%) in the control group (p = 1.00). Multiple logistic regression analysis showed that GA at delivery was the only predictive factor for event-free survival. There were no significant differences regarding school career, therapies, or special aid equipment between the 2 groups. We found that children without FLS were involved in more free-time activities and needed fewer breaks during physical activity than children with FLS during pregnancy. CONCLUSION: The outcome of monochorionic twins treated with FLS is comparable to the outcome of dichorionic twins. Long-term neurodevelopment in the cohort was mainly dependent on GA at birth.

Risk Factors for Preterm Birth following Open Fetal Myelomeningocele Repair: Results from a Prospective Cohort.

BACKGROUND: Fetal myelomeningocele (fMMC) repair is a therapeutic option in selected cases. This study aimed to identify risk factors for preterm birth (PTB) following open fMMC repair. METHODS: Sixty-seven women underwent fMMC repair and delivered a baby between 2010 and 2018 at our center. Demographic, surgical, and pregnancy complications, including potential risk factors for PTB such as preterm premature rupture of membranes (PPROM), chorioamniotic membrane separation (CMS), and placental abruption were evaluated. RESULTS: Maternal body mass index, maternal age, parity, previous uterine surgery, gestational age at fetal surgery, total surgery duration, surgical subcutaneous hematoma, oligohydramnios, and amniotic fluid leakage were not identified as risk factors for PTB. CMS (p = 0.028, 92 vs. 52%) and PPROM (p = 0.001, 95 vs. 52%) were highly associated with PTB. Placental abruption was found more often in women after fMMC repair than in a general obstetrical population (12 vs. 1%) and ended in premature birth in all cases (p = 0.024, 100 vs. 60%). However, the majority of women delivered at a gestational age >35 weeks. CONCLUSIONS: In our study cohort, risk factors for PTB were PPROM, CMS, and placental abruption, whereas surgery duration did not influence outcome. We conclude that the surgery technique should aim to minimize CMS and amniotic fluid leakage.

Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida.

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

Outcome after fetoscopic laser coagulation in twin-twin transfusion syndrome - is the survival rate of at least one child at 6 months of age dependent on preoperative cervical length and preterm prelabour rupture of fetal membranes?

Purpose: Twin-to-twin transfusion syndrome (TTTS) complicates 10-15% of all monochorionic twin pregnancies. Selective laser coagulation of placental anastomoses is the only causal therapy. The aim of this study was to analyze the neonatal survival, the survival rate of at least one child at 6 months of age, and maternal outcome after laser therapy in a Swiss cohort.Material and methods: Between 2008 and 2014, 39 women were treated with fetoscopic laser procedure due to TTTS. Two women were excluded from the study because of missing informed consent or loss of follow-up. The women were divided into two groups: group 1 with a cervical length >25 mm and group 2 with a cervical length ≤25 mm. The primary end point was the survival rate of at least one child at 6 months of age and its dependence on maternal preoperative cervical length or the time interval between operation (OP)-preterm prelabour rupture of fetal membranes (PPROM). Secondary outcomes were neonatal complications and maternal complications due to the procedure. Statistical analysis was performed using the program SPSS 22. A p-value of <.05 was considered statistically significant.Results: Mean gestational age (GA) at OP of group 1 (20.3 ± 3 GW) was comparable with group 2 (21.5 ± 2.4 GW; p = .27). The GA at birth was significantly higher in group 1 (31.5 ± 5.9 GW) than in group 2 (27.0 ± 4.7 GW: p = .02). The survival rate of at least one child at 30 days and 6 months of age was 81% in group 1 and only 60% in group 2 (p = .1). PPROM <32 GW occurred in 43%. The survival rate of at least one child was significantly higher if the OP-PPROM interval was >28 days (93 versus 43%; p = .02). Major brain injury was observed in 11% of infants. Severe maternal complications (pulmonary edema) occurred in three cases (8%).Conclusions: Our survival rate of at least one child at 30 days and 6 months of age and the outcome of the mothers is well comparable to other international studies. A preoperative maternal cervical length of >25 mm and an occurrence of PPROM more than 28 days after the laser therapy is associated with a higher survival rate of at least one child at 6 months of age.

In utero Hepatitis B Immunization during Fetal Surgery for Spina Bifida.

BACKGROUND: Fetal surgery for spina bifida aperta may lead to significantly better outcomes than postnatal repair, particularly regarding shunt-dependent hydrocephalus, independent ambulation, and voiding functions. The "Management of Myelomeningocele Study" (MOMS) represents the current benchmark, also in terms of eligibility criteria. CASE REPORT: A positive maternal hepatitis B virus (HBV) status is a MOMS exclusion criterion. Here, we report on the first successful active and passive in utero HBV vaccination of a spina bifida fetus carried by a HBV-positive mother undergoing maternal-fetal surgery. The now 2-year-old infant is healthy, HBV negative, and drew maximal benefit from prenatal surgery. DISCUSSION AND CONCLUSION: Taken together, this patient benefitted maximally from fetal surgery for spina bifida, despite meeting an exclusion criterion. Thus, generally speaking, eligibility criteria for fetal surgery can be challenged under certain circumstances for the benefit of the patient.

Bioengineering and in utero transplantation of fetal skin in the sheep model: A crucial step towards clinical application in human fetal spina bifida repair.

An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations. Eight sheep fetuses of four time-mated ewes underwent fetoscopic skin biopsy at 65 days of gestation. Fibroblasts and keratinocytes isolated from the biopsy were used to create fetal dermo-epidermal skin substitutes. These were transplanted on the fetuses by open fetal surgery at 90 days of gestation on skin defects (excisional wounds) created during the same procedure. Pregnancy was allowed to continue until euthanasia at 120 days of gestation. The graft area was analyzed macroscopically and microscopically. The transplanted fetal dermo-epidermal skin substitutes was well discernable in situ in three of the four fetuses available for analysis. Histology confirmed healed grafts with a close to natural histological skin architecture four weeks after in utero transplantation. This experimental study generates evidence that laboratory grown autologous fetal skin analogues can successfully be transplanted in utero. These results have clinical implications as an analogous procedure might be applied in human fetuses undergoing prenatal repair to facilitate primary skin closure. Finally, this study may also fertilize the field of fetal tissue engineering in general, particularly when more interventional, minimally invasive, and open fetal surgical procedures become available.

Open Intrauterine Fetal Myelomeningocele Repair: Changes in the Surgical Procedure and Perinatal Complications during the First 8 Years of Experience at a Single Center.

INTRODUCTION: Open fetal myelomeningocele (fMMC) repair is nowadays a therapeutic option in selected cases. We aimed to evaluate changes in maternal and fetal outcome after fMMC repair during the first 8 years of experience at a tertiary referral fetal medicine center in Switzerland. -Materials and Methods: Between 2010 and 2018, fMMC repair and delivery of the neonate via planned cesarean section was performed in 67 cases. Cases were retrospectively stratified into 2 groups: a "training phase" (TP) with supervision from an external surgeon during 11 operations (2010-2014, 15 cases) followed by an "experienced phase" (EP, 2014-2018, 52 cases); each phase lasted about 4 years. Both phases were compared with regard to various maternal and fetal outcome parameters. RESULTS: Analyses did not reveal differences between TP and EP in major outcome parameters such as gestational age at delivery, chorionic membrane separation, or the incidence of placental abruption. Although more complex surgical techniques were applied in EP (e.g., dermal closure using a rotational flap), surgery time was not different from TP. At the same time, surgical complications such as oligohydramnios (27 vs. 8%, p = 0.046) with MRI-confirmed leakage (13 vs. 4%, nonsignificant) and subchorionic hematoma (20 vs. 2%, p = 0.009) were less common in EP than TP. CONCLUSIONS: This study shows that the level of competence at our center with regard to major perinatal outcome parameters was already high in the first years of fMMC repair. However, more complex surgical techniques and significantly less minor complications were observed during the most recent years.