Middle Cerebral Artery Doppler before and after Fetal Spina Bifida Repair: An Indirect Sign of Hindbrain Compression and Decompression?

INTRODUCTION: Reduced middle cerebral artery resistance indices (MCA-RI) in fetuses with spina bifida (fSB) are commonly observed. Compression of neuronal pathways in the brainstem due to hindbrain herniation (HH) and disturbed cerebrospinal fluid circulation likely cause an imbalance of the autonomic nervous system. This may increase systemic vasoconstriction and compensatory increase cerebral vasodilation (like brain sparing). The aim of this study was to systematically analyze all fetal MCA-RI before and after fSB repair and to compare their correlation with the presence and postsurgical resolution of HH. METHODS: 173 patients were included. Standardized ultrasound examinations including MCA and umbilical artery (UA) Doppler as well as assessment of HH presence and regression were performed. Fetuses with MCA-RI <5th percentile (P) before fetal surgery were compared to the group with normal MCA-RI and correlated to the presence of HH before and its regression after fSB repair. RESULTS: 30% (49/161) fetuses showed RI's <5th P before fSB repair. All fetuses had normal UA-RI. 99.4% of fetuses (160/161) showed normal of MCA-RI before delivery. Normalization occurred within a mean of 1.3 ± 1.2 weeks. HH regression was observed in 97% in the group with normal MCA-RI and in 96% in the group with MCA-RI <5th P before surgery (p = 0.59). Time lapse to HH regression after fSB repair was 1.8 ± 1.7 and 1.9 ± 1.6 weeks, respectively. CONCLUSION: In fetuses with MCA-RIs <5 P before fSB repair, a parallel timely course of MCA-RI normalization and HH regression was noted. To suggest common pathogenic factor(s), more studies are needed. However, normalization of the fetal cerebral circulation could be a further benefit of fSB repair.

Duration of labor in consecutive deliveries: a retrospective data analysis.

PURPOSE: Labor is shorter in multiparous women. However, there are no individualized data on differences in duration of labor for consecutive deliveries in the same parturient. METHODS: We conducted a retrospective data analysis from 2004 to 2021 at the University Hospital of Zurich and included all women with 2 or more vaginal deliveries of a singleton child in cephalic position, between 22 and 42 weeks of gestation. Descriptive statistics were performed with SPSS version 25.0 (IBM, SPSS Inc., USA). The primary endpoint was the ratio between durations of labor stages in consecutive deliveries of the same parturient. RESULTS: A total of 3344 women with 7066 births (2601 first [P0], 2987 s [P1], 1176 third [P2], and 302 fourth [P3]) were included. The ratio of duration of the active first stage of labor between P1 and P0 was 0.49 (95% CI 0.47-0.51, p < 0.001) meaning that the active first stage of labor was 51% shorter. The second stage of labor with a ratio of 0.26 (95% CI 0.24-0.27, p < 0.001) was 74% shorter in P1 compared to P0. Higher birthweight of the first child led to an even greater decrease in duration of the second stage of labor in P1 compared to P0 (p = 0.003). Neuraxial anesthesia was an independent risk factor for a longer duration of labor, irrespective of parity (p < 0.001). Birthweight and HC of the neonates did not significantly differ between the children born by the same women. However, higher birthweight in of the first child significantly augmented the rate of second stage of labor between P0 and P1 (p = 0.003). DISCUSSION: Up to the third delivery, duration of labor decreased with each consecutive delivery of the same parturient. An individualized assessment of the expected duration of labor in multiparous women should be encouraged.

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.

The Role of Pancreatic Stone Protein (PSP) as a Biomarker of Pregnancy-Related Diseases.

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions.

Serum Pancreatic Stone Protein Reference Values in Healthy Pregnant Women: A Prospective Cohort Study.

BACKGROUND: In non-pregnant populations, pancreatic stone protein (PSP) has been reported to have a higher diagnostic performance for identifying severe inflammatory and infectious disease than other established biomarkers. OBJECTIVE: To generate reference values for serum PSP in pregnancy and compare them to the values of the general healthy population. DESIGN: A prospective cohort study. SETTING: A single center. POPULATION: Healthy women with singleton and multiple pregnancies. METHODS: This is a prospective single-center cohort study. Between 2013 and 2021, samples of 5 mL peripheral blood were drawn from 440 healthy pregnant women. Therein, 393 cases were singletons and 47 were multiple pregnancies. Serum PSP levels were measured by specific enzyme-linked immunosorbent assay. The main outcome measures were serum PSP level (ng/mL) reference values in healthy pregnant women. RESULTS: The mean PSP reference values in women with singleton pregnancies were 7.9 ± 2.6 ng/mL (95% CI; 2.69-13.03 ng/mL). The PSP values in women with multiple pregnancies (9.17 ± 3.06 ng/mL (95% CI; 3.05-15.28 ng/mL)) were significantly higher (p = 0.001). The PSP values in the first trimester (6.94 ± 2.53 ng/mL) were lower compared to the second (7.42 ± 2.21 ng/mL) and third trimesters (8.33 ± 2.68 ng/mL, p = 0.0001). Subgroup analyses in singletons revealed no correlations between PSP values, maternal characteristics, and pre-existing medical conditions. CONCLUSION: The PSP values in healthy pregnant women (4-12 ng/mL) were in the range of the reference values of the general healthy population (8-16 ng/mL). This insight blazes a trail for further clinical studies on the use of PSP as a potential novel biomarker for the early detection of pregnancy-related diseases such as chorioamnionitis.

Tissue Glue-Based Sealing Patch for the in vivo Prevention of Iatrogenic Prelabor Preterm Rupture of Fetal Membranes.

INTRODUCTION: One of the main concerns for all fetal surgeries is the risk of preterm delivery due to the preterm prelabor rupture of the fetal membranes (iPPROM). Clinical approaches to seal fetal membrane (FM) defects are missing due to the lack of appropriate strategies to apply sealing biomaterials at the defect site. METHODS: Here, we test the performance of a previously developed strategy to seal FM defects with cyanoacrylate-based sealing patches in an ovine model up to 24 days after application. RESULTS: Patches sealed tightly the fetoscopy-induced FM defects and remained firmly attached to the defect over 10 days. At 10 days after treatment, 100% (13/13) of the patches were attached to the FMs, and 24 days after treatment 25% (1/4) of the patches placed in CO2 insufflation, and 33% (1/3) in NaCl infusion remained. However, all successfully applied patches (20/24) led to a watertight sealing at 10 or 24 days after treatment. Histological analysis indicated that cyanoacrylates induced a moderate immune response and disrupted the FM epithelium. CONCLUSION: Together, these data show the feasibility of minimally invasive sealing of FM defects by locally gathering tissue adhesive. Further development to combine this technology with refined tissue glues or healing-inducing materials holds great promise for future clinical translation.

Information Gathering about Pregnancy, Birth, and Puerperium-Good and Fake Information.

Recent research on the subject of information-gathering processes among pregnant women has revealed a shift towards online sources. Health professionals' knowledge about sources of information has been shown to improve the understanding and counseling of patients. The objective of this study was to create an overview of all types of sources relevant to information gathering and to put their role and perception into perspective. METHODS: A total of 249 women were included in this study and recruited over a period of one month at the University Hospital of Zurich (USZ). Exclusion criteria included cases of fetal demise and late abortions. The survey on information-gathering processes was divided into three stages: pregnancy, birth, and puerperium. The different sources of information were compared based on women's characteristics. RESULTS: The response rate was 78% (n = 197). The main findings include a significant difference in information gathering based on varying levels of education, with women at the lowest educational level using the Internet the least during pregnancy (p = 0.029). During puerperium, significant differences could be observed in the involvement of the gynecologist. Primipara women as well as women of lower educational levels contacted their gynecologist less in contrast to multipara women (p = 0.006) and women of higher educational levels (p = 0.011). Overall, health professionals were considered to be the most important source of information. CONCLUSIONS: This study demonstrates that parity and educational level influence the information-gathering process. As the most important source for information gathering, health professionals must use this advantage to better assist their patients in accessing reliable information.

Second systolic peak in fetal middle cerebral artery Doppler after intrauterine transfusion.

OBJECTIVE: To evaluate functional relationship between fetal circulatory response to intrauterine transfusion (IUT) as a circulatory challenge and appearance of second systolic peak (P2) in middle cerebral artery (MCA) based on hemodynamic principles. METHODS: According to the concept of pulse wave (PW) propagation and reflection in adults, PWs arrive twice at cerebral circulation, as primary wave caused by left ventricle ejection and secondary after reflection in peripheral arteries. Thus adults show a biphasic contour of systolic blood flow in cerebral arteries. Similar waveforms may appear in fetal MCA-Doppler, as a response to IUT as a circulatory challenge. This is a proof-of-principle study, applying classical hemodynamic principles to fetal circulation. Accordingly, appearance of MCA-P2 may indicate vasoconstriction with increased PW reflection and timing of P2(Δt) should agree with the additional PW travel time down to reflection and return (Tr). To test this agreement, we searched our database for IUTs performed for severe fetal anemia, and compared Δt, obtained by Doppler, with Tr, obtained by hemodynamic calculation using human fetal data. Level of agreement was assessed using Bland-Altman-Plots. RESULTS: We identified 21 fetuses with adequate Doppler quality for Δt evaluation. In four cases (19%) MCA-P2 was observed before the intervention, and in 17 interventions (81%) thereafter; a highly significant association between IUT and P2 appearance (p < 0.001). In these 17 interventions good agreement of P2 timing was found between Doppler assessment: Δt = 80 ± 8 ms, and hemodynamic calculation: Tr = 76 ± 4 ms. CONCLUSION: P2 appearance in fetal MCA-Doppler seems to indicate PW reflection due to increased vasoconstriction after IUT. Thus hemodynamic considerations might enable Doppler monitoring of fetal vasoconstriction.

M-Sign in Middle Cerebral Artery Doppler Waveforms: A Sign of Fetal Vasoconstriction Before and After Open Fetal Spina Bifida Repair.

BACKGROUND: Increased pulse wave reflection in the fetal arterial system, illustrated by a second systolic peak (M-sign) in middle cerebral artery (MCA) Doppler waveforms, allows interpretation of fetal systemic vasoconstriction. Little is known about fetal vascular regulation during fetal spina bifida (fSB) repair. Therefore, the aim of this study was to analyze MCA-Doppler waveform changes before, during, and after fSB repair. PATIENTS AND METHODS: 31 pregnant women who underwent fSB repair were included. Fetal MCA-Doppler waveforms were prospectively analyzed before, during and after fSB repair, and categorized as follows: normal systolic downslope, systolic shoulder, second systolic peak (M-sign), and concave systolic downslope. These MCA waveforms were related to maternal and fetal characteristics, to anesthetic medication, and to umbilical artery (UA) waveforms. RESULTS: Before fSB repair, all fetuses repeatedly presented M-signs. After initiation of desflurane for general anesthesia, systolic shoulder and the M-sign vanished in 24/31 (78%) fetuses and 19/31 (61%) showed transient UA ARED flow. A significant association between these two Doppler findings was found (p=0.007). After fSB repair, signs of increased pulse wave reflection reappeared but resolved over time (23 days ± 20, SD) in all fetuses. CONCLUSION: Both fSB and intrauterine repair influence fetal vascular regulation. This phenomenon can be illustrated by MCA-Doppler waveforms. While anesthetic agents transiently eliminated M-signs and often provoked a UA ARED flow, fSB repair finally led to normalization of MCA-Doppler waveforms indicating return to normal fetal vascular regulation.

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.

Biomaterial-based treatments for the prevention of preterm birth after iatrogenic rupture of the fetal membranes.

Minimally invasive interventions to ameliorate or correct fetal abnormalities are becoming a clinical reality. However, the iatrogenic preterm prelabor rupture of the fetal membranes (FMs) (iPPROM), which may result in preterm birth, remains a main complication. Despite the cause of iPPROM not being fully known, the puncture created by the fetoscope remains unhealed until the end of the pregnancy, which permits chorioamniotic separation and amniotic fluid leakage. Hence, there is an urgent need to develop strategies to treat the FMs after minimally invasive interventions. However, none of the previously tested strategies has been clinically translated. Here, we review the current knowledge about the FMs starting from their development and present the different models that have been developed both in vitro and ex vivo. We also systematically review and summarize the different approaches that have been investigated to plug, seal, heal or suture the FMs both in preclinical and clinical studies and discuss their limitations, outcomes, and future directions.

Miniaturized Bioengineered Models for Preterm Fetal Membrane Healing.

INTRODUCTION: The reason for the absence of fetal membrane (FM) healing after a fetoscopic intervention is still unknown. We hypothesize that the lack of robust miniaturized models to study preterm FM functions is currently hampering the development of new treatments for FM healing. Specifically, miniaturized models to study preterm FM healing with minimal amounts of tissue are currently lacking. METHODS: In this study, we collected FMs from planned cesarean deliveries and developed different ex vivo models with an engineered biomaterial to study FM healing. Then, the effect of platelet-derived growth factor BB (PDGF-BB) on the migration of cells from preterm and term FMs was evaluated. RESULTS: FMs could be viably cultured ex vivo for 14 days. In a model of punctured FMs, migration of cells into FM defects was less pronounced than migration out of the tissue into the biomaterial. In a miniaturized model of preterm cell migration, PDGF-BB promoted migration of preterm amnion cells into the biomaterial. DISCUSSION AND CONCLUSION: By using a novel miniaturized model of preterm tissue, we here successfully demonstrate that PDGF-BB can promote preterm FM cell migration of microtissues encapsulated in a three-dimensional environment.

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.