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IntroductionThe Management of Myelomeningocele Study demonstrated that in utero repair of myelomeningocele improved motor outcomes compared with postnatal repair. However, even after in utero repair, many children were still unable to walk. We have previously demonstrated that augmentation of in utero repair with early-gestation placental mesenchymal stromal cells (PMSCs) improves motor outcomes in lambs compared with standard in utero repair. The neuroprotective potential of PMSCs of all gestational ages has not been evaluated previously.MethodsPMSCs were isolated from discarded first trimester (n=3), second trimester (n=3), and term (n=3) placentas by explant culture. Cytokine array analysis was performed. Secretion of two neurotrophic factors, brain-derived neurotrophic factor and hepatocyte growth factor, was evaluated by enzyme-linked immunosorbent assay. An invitro neuroprotective assay demonstrated to be associated with invivo function was performed.ResultsAll cell lines secreted immunomodulatory and neuroprotective cytokines and secreted the neurotrophic factors evaluated. Increased neuroprotective capabilities relative to no PMSCs were demonstrated in two of the three first trimester cell lines (5.61, 4.96-6.85, P&nbsp

IntroductionFetal myelomeningocele (MMC) repair improves lower extremity motor function. We have previously demonstrated that augmentation of fetal MMC repair with placental mesenchymal stromal cells (PMSCs) seeded on extracellular matrix (PMSC-ECM) further improves motor function in the ovine model. However, little progress has been made in improving bowel and bladder function, with many patients suffering from neurogenic bowel and bladder. We hypothesized that fetal MMC repair with PMSC-ECM would also improve bowel and bladder function.MethodsMMC defects were surgically created in twelve ovine fetuses at median gestational age (GA) 73 days, followed by defect repair at GA101 with PMSC-ECM. Fetuses were delivered at GA141. Primary bladder function outcomes were voiding posture and void volumes. Primary bowel function outcome was anorectal manometry findings including resting anal pressure and presence of rectoanal inhibitory reflex (RAIR). Secondary outcomes were anorectal and bladder detrusor muscle thickness. PMSC-ECM lambs were compared to normal lambs (n=3).ResultsEighty percent of PMSC-ECM lambs displayed normal voiding posture compared to 100% of normal lambs (p=1). Void volumes were similar (PMSC-ECM 6.1ml/kg vs. normal 8.8ml/kg, p=0.4). Resting mean anal pressures were similar between cohorts (27.0mmHg PMSC-ECM vs. normal 23.5mmHg, p=0.57). RAIR was present in 3/5 PMSC-ECM lambs that underwent anorectal manometry and all normal lambs (p=0.46). Thicknesses of anal sphincter complex, rectal wall muscles, and bladder detrusor muscles were similar between cohorts.ConclusionOvine fetal MMC repair augmented with PMSC-ECM results in near-normal bowel and bladder function. Further work is needed to evaluate these outcomes in human patients.

Pain is a complex phenomenon that involves more than a simple physical response to external stimuli. In maternal-fetal surgical procedures, fetal analgesia is used primarily to blunt fetal autonomic responses and minimize fetal movement. The purpose of this Consult is to review the literature on what is known about the potential for fetal awareness of pain and to discuss the indications for and the risk-benefit calculus involved in the use of fetal anesthesia and analgesia. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we suggest that fetal paralytic agents be considered in the setting of intrauterine transfusion, if needed, for the purpose of decreasing fetal movement (GRADE 2C); (2) although the fetus is unable to experience pain at the gestational age when procedures are typically performed, we suggest that opioid analgesia should be administered to the fetus during invasive fetal surgical procedures to attenuate acute autonomic responses that may be deleterious, avoid long-term consequences of nociception and physiological stress on the fetus, and decrease fetal movement to enable the safe execution of procedures (GRADE 2C); and (3) due to maternal risk and a lack of evidence supporting benefit to the fetus, we recommend against the administration of fetal analgesia at the time of pregnancy termination (GRADE 1C).

Summary Introduction The purpose of this study was to determine the incidence of lower urinary tract surgery in patients with myelomeningocele (MMC) operated in utero as well as in the subgroup of patients with a minimum age of 5 years. Methods We use a previously published protocol to categorize bladder patterns and propose the treatment: high risk pattern-anticholinergics and clean intermittent catheterization (CIC); incontinent and normal patterns-clinical surveillance and underactivity pattern- CIC. Non-response to clinical treatment with maintenance of detrusor pressure higher than 40 cmH20 with worsening of hydronephrosis or recurrent urinary infection were imperative indications for surgery and urinary incontinence due to sphincter deficiency and leakage pressure below 40 cmH20 in patients aged 5 years and older were possible indications too. We identified the prevalence of urinary tract surgery and concomitant treatment of constipation and refractory fecal incontinence by convenience, the technique performed and surgery outcomes. Results A total of 122 patients are part of the prospective protocol. The first UE was performed in 119 patients (median age of 4 months). The categorization of the bladder pattern was high risk in 52.1%, incontinent in 25.2%, hypocontractile 4.2% and normal in 18.5%. Current follow-up was 29.9 months (1–99 months). Surgery was performed on 10 patients (8.4%): 3 vesicostomies, 2 surgeries to treat vesicoureteral reflux, 6 bladder augmentations, 3 ACE and a sling surgery. Considering only patients older than 5 years, we identified 65 patients and seven surgeries performed (10.8%). Discussion Most bladder reconstruction studies are case series of single institutions or cooperative services, most of which are retrospective. The prospective clinical interpretation and imaging and urodynamic exams over time allowed us prospectively to define the risk of surgery in patients with myelomeningocele operated in utero. It must be considered that the response to the initial urological treatment and even the failure that leads to the need for surgery have to be evaluated in a context of follow-up time. For this reason we have studied separately patients over 5 years-old and also the group considered to be at greatest risk for surgery, the high-risk group of the categorization already described. Conclusion We found an incidence of 10.8% of surgeries in patients over 5 years-old and 12.9% for the high-risk group. This information may be useful to educate parents when stating urological treatment. Download : Download high-res image (644KB) Download : Download full-size image Summary Figure . Continent catheterizable ileal reservoir (Macedo's Technique) - procedure steps.

Objectives (1) To investigate the reproducibility of total fetal lung volume (TFLV) measurements using a free 3D modeling software (3DSlicer); (2) To correlate these measurements with lung-to-head ratio (LHR) or TFLV measured using PACS and; (3) To determine the role of 3DSlicer in predicting perinatal outcomes in cases with congenital diaphragmatic hernia (CDH) who had fetal tracheal occlusion (FETO). Methods Retrospective cohort study between 2012 and 2017 at Texas Children’s Hospital (2011–2017), including all patients who underwent FETO for CDH. LHR was measured by ultrasound and TFLV was measured by MRI at the time of referral and 6 weeks after FETO using 3DSlicer and PACS. We evaluated intra- and inter-rater reliability of TFLV measurement using 3DSlicer, infant survival to 1 year, need for ECMO and pulmonary hypertension. Results The intra- and inter-rater reliability of TFLV measured with 3DSlicer was excellent before and after FETO (Intra-class correlation coefficient: 0.98−0.99 and 0.94−0.99, respectively). There was a good correlation between TFLV measured with PACS and with 3DSlicer before and after FETO (r = 0.78 and r = 0.99, respectively). Similarly, there was a good correlation between TFLV measurements using PACS or 3DSlicer and LHR after FETO (r = 0.86 and r = 0.88, respectively). Infants who survived to 1 year had a significantly higher TFLV evaluated with 3DSlicer before FETO compared to non-surviving infants (OR = 1.16[1.1–1.3], p = 0.03) as well as a significantly higher TFLV evaluated by 3DSlicer after FETO (OR = 1.2[1–1.4], p = 0.04). Conclusion Lung volume measurements using free 3DSlicer in infants with severe CDH who underwent FETO are reproducible and reliable, and have comparable predictive capability for survival as those measured using conventional software.

To estimate the significance of the association between mid-trimester maternal serum alpha-fetoprotein (MSAFP) level and fetal neuroanatomic findings in cases of open neural tube defect (ONTD).Retrospective study of patients referred for prenatal ONTD repair between 2012 and 2018. Cases were classified into three groups based on their MSAFP level: 1)High MSAFP (3.8MoM - n = 22), 2)Moderately high MSAFP (≤3.8 and ≥2.5MoM - n = 28), 3)Normal MSAFP (2.5MoM - n = 18). MRI scans at the time of referral were used to assess the relationship between MSAFP and: A)Type of ONTD; B) Ventriculomegaly; C) Size of the myeloschisis lesion; D) Volume of myelomeningocele; E) Anatomical level of the lesion (LL).Having a high MSAFP level was more likely to be associated ventriculomegaly at mid-gestation than a moderately high or normal MSAFP level (OR = 8.4;CI95[0.9-73.4];p = 0.05 and OR = 2.8;CI95[0.9-8.8];p = 0.07). There were no differences between the three groups regarding type of lesion, size of the myeloschisis lesion, anatomic LL, or volume of the myelomeningocele sac. Myeloschisis cases with normal MSAFP had a larger surface area when compared to myeloschisis cases with moderately high MSAFP (219.8[104.4-551] vs 155.4[38.5-502.4] mm², p = 0.04).A 2nd trimester MSAFP level3.8MoM in a fetus with ONTD is associated with mid-gestation ventriculomegaly.

Two unique aspects of antenatal care occur in the setting of fetal surgery and multiple gestations. As fetal interventions increase, so do the number of cases of iatrogenic preterm prelabor rupture of membranes (PPROM). Because of the amniotic sac's inability to heal, the risk of PPROM after surgery is directly correlated with the number of interventions, the size of the defect, and the surgery performed. Higher order gestations also carry an increased risk of PPROM. This paper reviews the risks and management of PPROM in the setting of the various prenatal interventions as well as in the setting of multiple gestations.

Continuous fetal hemodynamic monitoring during in-utero surgery is desirable, but it is often not feasible without intermittent interruption. We report the use of a fetal spiral electrode for continuous heart rate monitoring during fetal myelomeningocele repair. Fetal echocardiography and a fetal spiral electrode were used to monitor fetal heart rate during in-utero repair at 25 weeks' gestation. We observed good agreement between echocardiographic and spiral electrode heart rate measurements. Using the Bland-Altman approach, the mean (SD) difference between measurements was 1.8 (3.5) beats per minute with limits of agreement of -5.3 to 8.8 beats per minute. This case illuminates a potential role for a fetal spiral electrode as a real-time adjunct in fetal interventions.

Open spina bifida is often diagnosed during pregnancy. In the last 20 years, fetal repair has been shown to have benefits to the neonate and child, and is now widely available, including within the UK. This article briefly examines the background, evidence, benefits and risks of fetal surgery for spina bifida.

Fetal spina bifida, the most common nonlethal birth defect of the central nervous system, results in substantial neurologic morbidity. The unified theory describes the complex relationship between local spinal lesions and development of Chiari 2 malformation, contributing to hydrocephalus. Prenatal ultrasonography reliably allows diagnosis, but fetal MR imaging is an important complement to identify additional brain abnormalities. Fetal surgery improves neurologic and motor outcomes, but various approaches, either open hysterotomy or minimally invasive to the uterus, carry substantial obstetric risks. Optimization of the fetoscopic approach aims to minimize maternal and obstetric risks, but data regarding longer-term outcomes are awaited.

The most common congenital defect of the central nervous system is myelomeningocele (MMC), which results in significant physical limitations for those affected. Neurologic injury associated with MMC begins with abnormal neurulation and is perpetuated by subsequent traumatic and toxic injury sustained in utero. Treatment historically has involved surgical closure of the MMC after birth along with neonatal management of the associated sequelae including cerebrospinal fluid diversion by ventricular shunting. With improvements in prenatal diagnosis, a defined antenatal natural history, and the concept of fetal intervention to arrest or reverse ongoing in utero damage, maternal-fetal surgery for MMC closure developed as a feasible therapy. Animal studies and early human studies investigating in utero MMC closure were promising, leading to Management of Myelomeningocele Study (MOMS trial). This prospective randomized multicenter trial comparing in utero fetal MMC (fMMC) closure to routine postnatal closure demonstrated a decreased need for shunting, reversal of hindbrain herniation, and improved neurologic function in the prenatal repair group, although maternal complications and prematurity were more frequently encountered. Because of the conclusion of the MOMS trial, fMMC closure has become a standard of care option for pregnancies complicated by a prenatal diagnosis of spina bifida. This article will provide background to the scope of MMC, review the MOMS trial data, and highlight the current clinical status of open fMMC closure.

Prenatal repair of open spina bifida reduces shunt rates and may improve postnatal motor and neurodevelopmental outcomes. The hysterotomy required for the open fetal surgery leaves subsequent pregnancies at risk of uterine rupture. Hysterotomy site rupture confers significant morbidity and mortality risks for both mother and fetus. Fetoscopic repair is feasible and seems to achieve at least the same, postnatal neurological outcomes as those of the open repair. Fetoscopy can be accomplished by a laparotomy-based approach, or it can be entirely percutaneous. Thus far, the laparotomy-based approach leads to less PPROM and higher gestational age of delivery than the percutaneous-based one. However, the percutaneous approach is being modified, and outcomes are continuing improving, now delivery reached 35 weeks. Surgical techniques for the repair of the defect are not yet standardized, and the type of defect repair may affect long-term outcomes, especially regarding neurogenic bladder and cord tethering. The role of open fetal surgery in the management of spina bifida may be restricted to selected cases in the near future.

The growth of the field of fetal surgery over the last two decades driven by new indications and data from prospective randomized trials supporting prenatal intervention has resulted in techniques protocols and methodologies that have gained confidence by insuring good outcomes. Error traps are methods or techniques that usually work well in most of the cases, but which are apt to fail under certain specific circumstances. The very confidence the surgeon develops in these techniques or methodologies makes them a trap for the unwary surgeon. The purpose of this article is to discuss common error traps in fetal interventions, including ultrasound guided procedures, fetoscopic surgery, open fetal surgery and EXIT procedures. Awareness of these error traps and approaches to avoid them may enhance fetal surgical outcomes and reduce complications rates.

Background Patients with a prenatal diagnosis of lower urinary tract obstruction (LUTO) may undergo prenatal interventions, such as vesicoamniotic shunt (VAS) placement, as a temporary solution for relieving urinary tract obstruction. A recent FDA communication has raised awareness of the potential neurocognitive adverse effects of anesthesia in children. We hypothesized as to whether a prenatal LUTO staging system was predictive of the number of anesthesia events for prenatally diagnosed LUTO patients. Methods We retrospectively reviewed the prenatal and postnatal clinical records for patients with prenatally diagnosed LUTO from 2012 to 2015. Patients were stratified by prenatal VAS status and by LUTO disease severity according to Ruano et al. (Ultrasound Obstet Gynecol. 2016). Results 31 patients were identified with a prenatal LUTO diagnosis, and postnatal records were available for 21 patients (seven patients in each stage). When combining prenatal and postnatal anesthesia, there was a significant difference in the number of anesthesia encounters by stage (1.6, 3.7, and 6.7 for Stage I, II, and III respectively, p = .034). Upon univariate analysis, higher gestational age (GA) at birth was associated with a decreased number of anesthesia events in the first year (p = .031). Conclusions The majority of infants with prenatally diagnosed LUTO will undergo postnatal procedures with general anesthesia exposure in the first year of life. Patients with higher prenatal LUTO severity experienced a higher number of both prenatal and postnatal anesthesia encounters. In addition, higher GA at birth was associated with fewer anesthesia encounters in the first year. Level of evidence This is a prognostic study with Level IV evidence.

Background Myelomeningocele (MMC) results in lifelong neurologic and functional deficits. Currently, prenatal repair of MMC closes the defect, resulting in a 50% reduction in postnatal ventriculoperitoneal shunting. However, this invasive fetal surgery is associated with significant morbidities to mother and baby. We have pioneered a novel reverse thermal gel (RTG) to cover MMC defects in a minimally invasive manner. Here, we test in-vitro RTG long-term stability in amniotic fluid and in vivo application in the Grainy head-like 3 (Grhl3) mouse MMC model. Materials and methods RTG stability in amniotic fluid (in-vitro) was monitored for 6 mo and measured using gel permeation chromatography and solution–gel transition temperature (lower critical solution temperature). E16.5 Grhl3 mouse fetuses were injected with the RTG or saline and harvested on E19.5. Tissue was assessed for RTG coverage of the gross defect and inflammatory response by immunohistochemistry for macrophages. Results Polymer backbone molecular weight and lower critical solution temperature remain stable in amniotic fluid after 6 mo. Needle injection over the MMC of Grhl3 fetuses successfully forms a stable gel that covers the entire defect. On harvest, some animals demonstrate >50% RTG coverage. RTG injection is not associated with inflammation. Conclusions Our results demonstrate that the RTG is a promising candidate for a minimally invasive approach to patch MMC. We are now poised to test our RTG patch in the large preclinical ovine model used to evaluate prenatal repair of MMC.

Background Congenital pleural effusion is a rare condition with an incidence of approximately one per 15,000 pregnancies. The development of secondary hydrops is a poor prognostic indicator and such cases can be managed with a thoracoamniotic shunt (TAS). Our objective is to describe postnatal outcomes in survivors after TAS placement for congenital pleural effusions. Materials and methods A retrospective study of all cases with fetal pleural effusions treated between 2006 and 2016. Patients with dominant unilateral or bilateral pleural effusions complicated by secondary hydrops fetalis received TAS placement. The results are reported as median (range). Results A total of 29 patients with pleural effusion with secondary hydrops underwent TAS placement. The gestational age at the initial TAS placement was 27.6 (20.3-36.9) wk. Before delivery, hydrops resolved in 17 (58.6%) patients. The delivery gestational age was 35.7 (25.4-41.0) wk and the overall survival rate was 72.4%. Among the 21 survivors, 19 (90.5%) required admission to the neonatal intensive care unit for 15 (5-64) d. All 21 survivors had postnatal resolution of the pleural effusions. All 21 children were long-term survivors, with a median age of survivorship of 3 y 3 mo (9 mo-7 y 6 mo) at the time of last reported follow-up. Conclusions Thoracoamniotic shunting in fetuses with a dominant pleural effusion(s) and secondary hydrops resulted in a 72% survival rate. Nearly all survivors required admission to the neonatal intensive care unit. However, a majority did not have significant long-term morbidity.

BACKGROUND Because of the progressive nature of twin-to-twin transfusion syndrome, difficulties in healthcare access during the COVID-19 pandemic may lead to delayed diagnosis and referral to fetal surgery centers, which may have repercussions on outcomes. OBJECTIVE This study aimed to assess the clinical impact of the COVID-19 pandemic on pregnancies complicated with twin-to-twin transfusion syndrome. STUDY DESIGN A retrospective cohort study of consecutive monochorionic diamniotic twin pregnancies complicated with twin-to-twin transfusion syndrome evaluated in our national referral fetal surgery center at Queretaro, Mexico, for possible surgical fetoscopy was conducted. Maternal-fetal characteristics and perinatal outcomes of cases evaluated during the first year of the World Health Organization's COVID-19 pandemic declaration (March 11, 2020 to March 10, 2021) were retrospectively compared with outcomes of cases evaluated during the same period in the previous year (March 11, 2019 to March 10, 2020). RESULTS Overall, 109 consecutive twin-to-twin transfusion syndrome cases were evaluated during the 2-year study period, 54 during the COVID-19 pandemic and 55 in the previous year. In the former group, a higher proportion of cases with fetal surveillance interval longer than 2 weeks (70.4% vs 47.3%; P=.01); twin-to-twin transfusion syndrome complications precluding laser therapy, such as intrauterine fetal demise, preterm rupture of membranes, or cervical dilatation with prolapsed amniotic membranes (18.5% vs 1.8%; P

Advances made in the last several decades in the care of the fetus and newborn have had a significant impact on morbidity and mortality. Delayed umbilical cord clamping in the preterm newborn results in fewer transfusions for anemia, decreased intraventricular hemorrhage, and decreased necrotizing enterocolitis. Because of advances made in fetal ultrasound diagnosis and technological advances, fetal surgeries to treat congenital diaphragmatic hernia, myelomeningocele, twin-to-twin transfusion syndrome, fetal lower urinary tract obstructions, amniotic band syndrome, and congenital cystic adenoid malformation or congenital pulmonary airway malformations have improved the quality of life and survival for these patients.

Summary Purpose of the study The purpose of our study was to investigate the effects of ovine umbilical cord-derived mesenchymal stromal cells (UC-MSCs) seeded in a fibrin patch as an adjuvant therapy for fetal myelomeningocele repair in the ovine model. Materials and methods MMC defects were surgically created at 75 days of gestation and repaired 15 days later with UC-MSCs patch or an acellular patch. At birth, motor function, tail movements, and voiding abilities were recorded. Histological and immunohistochemical analysis included study of MMC defect's healing, spinal cord, UC-MSCs survival, and screening for tumors. Results Six lambs were born alive in each group. There was no difference between the two groups on the median sheep locomotor rating score but all lambs in the control group had a score between lower than 3 compared to 50% in UC-MSCs group. There were more lambs with tail movements and voiding ability in UC-MSCs group (83% vs 0% and 50% vs 0%, respectively). gray matter area and large neurons density were higher in UC-MSCs group (2.5 vs 0.8 mm2 and 19.3 vs 1.6 neurons/mm2 of gray matter, respectively). Fibrosis thickness at the myelomeningocele scar level was reduced in UC-MSCs group (1269 µm vs 2624 µm). No tumors were observed. Conclusion Fetal repair of myelomeningocele using allogenic UC-MSCs patch provides a moderate improvement in neurological functions, gray matter and neuronal preservation and prevented from fibrosis development at the myelomeningocele scar level.

Animal models are essential to cancer research, but current xenograft models are limited in their utility especially due to the lack of an immune system. Here we demonstrate that a xenograft tumor model can be developed in immunocompetent mice by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were injected into day E14 fetuses and after birth mice were challenged with A375 cells to determine their ability to develop tumors. Intravenous injections of cells resulted in metastatic-like lung tumors, which were verified to be human in origin by immunohistochemistry and PCR. These results were replicated with several other human tumor types: BxPC3 (human pancreatic adenocarcinoma), MDA-MB-231 (human breast adenocarcinoma), M21 (human melanoma), and HeLa (human cervical adenocarcinoma). Development of an immunocompetent xenograft tumor model would allow the further elucidation of the interaction of the immune system with therapy in both preclinical research and patient derived xenografts.

Pediatric surgeons play an essential role in prenatal consultation for congenital anomalies likely to require surgery in the newborn period. The involvement of pediatric surgeons during multi-disciplinary prenatal meetings has been an important part of the evolution of comprehensive fetal care, characterized by detailed prenatal evaluation, diagnosis, prognosis, and planned perinatal and post-natal care. Advances in fetal diagnostics and treatments, as well as complex postnatal medical care and decision-making create a broad range of care options for pregnant women with fetal surgical anomalies. Ethical challenges involve the availability and risks/benefits of maternal-fetal surgery, and diagnostic and prognostic uncertainty for the newborn. Clinical scenarios illustrate cases that pediatric surgeons may encounter in practice, with discussions highlighting the ethical principles involved as well as considerations for management.

BACKGROUND Prenatal repair of open spina bifida via the percutaneous fetoscopic approach does not require maternal laparotomy, hysterotomy, or exteriorization of the uterus. This technique requires intrauterine partial CO2 insufflation. Limited data exist on the physiological effects of CO2 insufflation on human fetuses, with no data on open spina bifida repair performed using the entirely percutaneous fetoscopic surgical technique. OBJECTIVE Our aim was to examine the effects of intrauterine partial CO2 insufflation on fetal blood gases after percutaneous fetoscopic open spina bifida repair. STUDY DESIGN This was a prospective study of patients who underwent percutaneous fetoscopic open spina bifida repair from February 2019 to July 2020. Fetal cordocentesis of the umbilical vein was performed in cases with favorable access to the umbilical cord. The umbilical vein cord blood samples were obtained under ultrasound guidance immediately at the conclusion of the open spina bifida repair. Simultaneous maternal arterial blood gas samples were also obtained. The results are reported as median (range). RESULTS Of the 20 patients who underwent percutaneous fetoscopic open spina bifida repair during the study period, 7 patients (35%) underwent fetal blood sampling. The gestational age at the time of surgery was 27.4 (24.0–27.9) weeks and the operative time was 183 (156–251) minutes. The CO2 exposure time was 122 (57–146) minutes with maximum pressure of 13.5 (12.0–15.0) mm Hg. Fetal umbilical vein results were as follows: pH 7.35 (7.30–7.39), partial pressure of O2 56.2 (47.1–99.9) mm Hg, partial pressure of CO2 43.8 (36.2–53.0) mm Hg, HCO3 23.9 (20.1–25.6) mmol/L, and base excess −2.2 (−4.5 to −0.4) mmol/L. Simultaneous maternal arterial blood gas results were as follows: pH 7.37 (7.28–7.42), partial pressure of O2 187.5 (124.4–405.2) mm Hg, partial pressure of CO2 36.6 (30.7–46.0) mm Hg, HCO3 21.3 (18.0–22.8) mmol/L and base excess −3.2 (−5.9 to −1.8) mmol/L. CONCLUSION Despite prolonged CO2insufflation of the uterus, fetal umbilical vein pH and base excess values did not approach those associated with potentially pathologic fetal acidemia.

Fetal surgery corrects severe congenital anomalies in utero to prevent their severe consequences on fetal development. The significant risk of open fetal operations to the pregnant mother has driven innovation toward minimally invasive procedures that decrease the risks inherent to hysterotomy. In this article, we discuss the basic principles of minimally invasive fetal surgery, the general history of its development, specific conditions and procedures used to treat them, and the future of the field.

Background and objectives: The temporary fetal tracheal occlusion performed by fetoscopy accelerates lung development and reduces neonatal mortality. The aim of this paper is to present an anesthetic experience in pregnant women, whose fetuses have diaphragmatic hernia, undergoing fetoscopic tracheal occlusion (FETO). Method: Retrospective, descriptive study, approved by the Institutional Ethics Committee. Data were obtained from medical and anesthetic records. Results: FETO was performed in 28 pregnant women. Demographic characteristics: age 29.8 ± 6.5; weight 68.64 ± 12.26; ASA I and II. Obstetric: IG 26.1 ± 1.10 weeks (in FETO); 32.86 ± 1.58 (reversal of occlusion); 34.96 ± 2.78 (delivery). Delivery: cesarean section, vaginal delivery. Fetal data: Weight (g) in the occlusion and delivery times, respectively (1045.82 ± 222.2 and 2294 ± 553); RPC in FETO and reversal of occlusion: 0.7 ± 0.15 and 1.32 ± 0.34, respectively. Preoperative maternal anesthesia included ranitidine and metoclopramide, nifedipine (VO) and indomethacin (rectal). Preanesthetic medication with midazolam IV. Anesthetic techniques: combination of 0.5% hyperbaric bupivacaine (5–10 mg) and sufentanil; continuous epidural predominantly with 0.5% bupivacaine associated with sufentanil, fentanyl, or morphine; general. In 8 cases, there was need to complement via catheter, with 5 submitted to PC and 3 to BC. Thirteen patients required intraoperative sedation; ephedrine was used in 15 patients. Fetal anesthesia: fentanyl 10–20 mg.kg−1 and pancuronium 0.1–0.2 mg.kg−1 (IM). Neonatal survival rate was 60.7%. Conclusion: FETO is a minimally invasive technique for severe congenital diaphragmatic hernia repair. Combined blockade associated with sedation and fetal anesthesia proved safe and effective for tracheal occlusion. Resumo: Justificativa e objetivos: A oclusão traqueal fetal temporária feita por meio da fetoscopia acelera o desenvolvimento pulmonar e reduz a mortalidade neonatal. O objetivo deste trabalho é apresentar experiência anestésica em gestantes cujos fetos eram portadores de hérnia diafragmática e foram submetidos à oclusão traqueal por fetoscopia (FETO). Método: Estudo retrospectivo, descritivo, aprovado pelo Comitê de Ética da Instituição. Os dados foram obtidos das fichas anestésicas e dos prontuários. Resultados: A FETO foi feita em 28 gestantes. Características demográficos: idade 29,8 ± 6,5; peso 68,64 ± 12,26; ASA I e II. Obstétricas: IG 26,1 ± 1,10 semana (na FETO); 32,86 ± 1,58 (desoclusão); 34,96 ± 2,78 (parto). Via de parto: cesárea, parto vaginal. Dados fetais: peso (g) nos momentos da oclusão e nascimento, respectivamente (1.045,82 ± 222,2 e 2294 ± 553); RPC na FETO e desoclusão: 0,7 ± 0,15 e 1,32 ± 0,34, respectivamente. Anestesia materna: pré-operatório incluiu ranitidina e metoclopramida; nifedipina (VO) e indometacina (retal). Medicação pré-anestésica com midazolam EV. Técnicas anestésicas: bloqueio combinado com bupivacaína 0,5% hiperbárica 5-10 mg associada ao sufentanil; peridural contínua predominantemente com bupivacaína 0,5% associada a sufentanil, fentanil ou morfina; geral. Em oito casos houve necessidade de complementação pelo cateter, cinco nas submetidas a PC e três a BC. No intraoperatório 13 pacientes necessitaram de sedação; efedrina foi usada em 15 pacientes. Anestesia fetal: fentanil 10 a 20 mg.kg−1 e pancurônio 0,1-0,2 mg.kg−1 (IM). A taxa de sobrevida neonatal foi de 60,7%. Conclusão: A FETO constitui técnica minimamente invasiva para correção de hérnia diafragmática congênita grave. O bloqueio combinado associado à sedação e anestesia fetal se mostrou seguro e eficaz para a oclusão traqueal. Keywords: Congenital diaphragmatic hernia, Prenatal diagnosis, Tracheal occlusion, Fetoscopy, Fetal surgery, Anesthesia, Palavras-chave: Hérnia diafragmática congênita, Diagnóstico pré-natal, Oclusão traqueal, Fetoscopia, Cirurgia fetal, Anestesia

Background and objectives: The temporary fetal tracheal occlusion performed by fetoscopy accelerates lung development and reduces neonatal mortality. The aim of this paper is to present an anesthetic experience in pregnant women, whose fetuses have diaphragmatic hernia, undergoing fetoscopic tracheal occlusion (FETO). Method: Retrospective, descriptive study, approved by the Institutional Ethics Committee. Data were obtained from medical and anesthetic records. Results: FETO was performed in 28 pregnant women. Demographic characteristics: age 29.8 ± 6.5; weight 68.64 ± 12.26; ASA I and II. Obstetric: IG 26.1 ± 1.10 weeks (in FETO); 32.86 ± 1.58 (reversal of occlusion); 34.96 ± 2.78 (delivery). Delivery: cesarean section, vaginal delivery. Fetal data: Weight (g) in the occlusion and delivery times, respectively (1045.82 ± 222.2 and 2294 ± 553); RPC in FETO and reversal of occlusion: 0.7 ± 0.15 and 1.32 ± 0.34, respectively. Preoperative maternal anesthesia included ranitidine and metoclopramide, nifedipine (VO) and indomethacin (rectal). Preanesthetic medication with midazolam IV. Anesthetic techniques: combination of 0.5% hyperbaric bupivacaine (5-10 mg) and sufentanil; continuous epidural predominantly with 0.5% bupivacaine associated with sufentanil, fentanyl, or morphine; general. In 8 cases, there was need to complement via catheter, with 5 submitted to PC and 3 to BC. Thirteen patients required intraoperative sedation; ephedrine was used in 15 patients. Fetal anesthesia: fentanyl 10-20 mg.kg-1 and pancuronium 0.1-0.2 mg.kg-1 (IM). Neonatal survival rate was 60.7%. Conclusion: FETO is a minimally invasive technique for severe congenital diaphragmatic hernia repair. Combined blockade associated with sedation and fetal anesthesia proved safe and effective for tracheal occlusion. Resumo Justificativa e objetivos: A oclusão traqueal fetal temporária feita por meio da fetoscopia acelera o desenvolvimento pulmonar e reduz a mortalidade neonatal. O objetivo deste trabalho é apresentar experiência anestésica em gestantes cujos fetos eram portadores de hérnia diafragmática e foram submetidos à oclusão traqueal por fetoscopia (FETO). Método: Estudo retrospectivo, descritivo, aprovado pelo Comitê de Ética da Instituição. Os dados foram obtidos das fichas anestésicas e dos prontuários. Resultados: A FETO foi feita em 28 gestantes. Características demográficos: idade 29,8 ± 6,5; peso 68,64 ± 12,26; ASA I e II. Obstétricas: IG 26,1 ± 1,10 semana (na FETO); 32,86 ± 1,58 (desoclusão); 34,96 ± 2,78 (parto). Via de parto: cesárea, parto vaginal. Dados fetais: peso (g) nos momentos da oclusão e nascimento, respectivamente (1.045,82 ± 222,2 e 2294 ± 553); RPC na FETO e desoclusão: 0,7 ± 0,15 e 1,32 ± 0,34, respectivamente. Anestesia materna: pré-operatório incluiu ranitidina e metoclopramida; nifedipina (VO) e indometacina (retal). Medicação pré-anestésica com midazolam EV. Técnicas anestésicas: bloqueio combinado com bupivacaína 0,5% hiperbárica 5-10 mg associada ao sufentanil; peridural contínua predominantemente com bupivacaína 0,5% associada a sufentanil, fentanil ou morfina; geral. Em oito casos houve necessidade de complementação pelo cateter, cinco nas submetidas a PC e três a BC. No intraoperatório 13 pacientes necessitaram de sedação; efedrina foi usada em 15 pacientes. Anestesia fetal: fentanil 10 a 20 mg.kg-1 e pancurônio 0,1-0,2 mg.kg-1 (IM). A taxa de sobrevida neonatal foi de 60,7%. Conclusão: A FETO constitui técnica minimamente invasiva para correção de hérnia diafragmática congênita grave. O bloqueio combinado associado à sedação e anestesia fetal se mostrou seguro e eficaz para a oclusão traqueal.

Fetal primary cardiac tumors are rare, but they may cause complications, which are sometimes life threatening, including arrhythmias, hydrops fetalis, ventricular outflow/inflow obstruction, cardiac failure, and even sudden death. Among fetal primary cardiac tumors, rhabdomyomas are most common, followed by teratomas, fibromas, hemangiomas, and myxomas. Everolimus, a mammalian target of rapamycin inhibitor, has been reported to be an effective drug to cause tumor remission in three neonates with multiple cardiac rhabdomyomas. Neonatal cardiac surgery for the resection of primary cardiac tumors found by fetal echocardiography has been reported sporadically. However, open fetal surgery for pericardial teratoma resection, which was performed successfully via a fetal median sternotomy in one case report, could be a promising intervention to rescue these patients with large pericardial effusions. These recent achievements undoubtedly encourage further development in early management of fetal cardiac tumors. Owing to the rarity of fetal primary cardiac tumors, relevant information in terms of prenatal diagnosis, treatment, and prognosis remains to be clarified.

Rodent studies on the effect of general anesthesia during the third trimester on neurocognitive outcomes are mixed, but primate studies suggest that a clinically relevant exposure to anesthetic agents during the third trimester can trigger neuronal and glial cell death. Human studies are conflicting and the evidence is weak. This is an up-to-date review of the literature on the neurodevelopmental effects of anesthetic agents administered during the third trimester. Early brain development and critical periods of neurodevelopment as it relates to neurotoxicity are highlighted. Rodent, nonhuman primate, and population studies are discussed and placed in the context of clinical practice.

Over the last few decades, the fields of fetal surgery and maternal-fetal medicine have developed interventions aimed at modifying severe diseases in utero. Innovations in fetal approaches to congenital diaphragmatic hernia and myelomeningocele have shown considerable promise in modifying the clinical course with fetal intervention. Patients who present to fetal centers to be evaluated for these interventions face challenging decisions that directly relate to questions of mortality and quality of life. This article explores how clinicians might apply the tools and principles of fetal palliative care to supporting a woman and her family who are considering fetal surgery.

Objective Fetal myelomeningocele closure results in better infant outcomes than postnatal closure at the cost of potential prematurity and maternal morbidity. Our aim is to describe the setup of a fetal myelomeningocele closure program in Canada and document its outcomes. Methods We conducted a retrospective review of all open fetal myelomeningocele closure surgeries performed at the Ontario Fetal Centre in its first 3 years of operation (2017–2020). Maternal and fetal baseline characteristics, surgical details, pregnancy outcomes, and infant follow-up until 1 year of age were recorded. Results Twenty-seven women underwent fetal myelomeningocele closure surgery, 10 of whom (37%) resided outside of Ontario. Mean gestational age at surgery was 25.0 ± 0.7 weeks. All surgeries were technically uncomplicated and no fetal deaths occurred. There was a significant negative correlation between increasing experience and skin-to-skin surgical time (R² = 0.36; P = 0.001). Of the 26 patients who have delivered, 4 (15.4%) experienced preterm prelabour rupture of membranes. Mean gestational age at delivery was 34.9±3.0 weeks. All but 1 patient delivered by cesarean. Maternal complications occurred in 9 women (34.6%). There were no maternal deaths, but 3 (11.5%) infant deaths. Of the 14 surviving infants who have reached at least 1 year of age, 5 (35.7%) underwent ventriculo-peritoneal shunting. Of the 9 infants who have not yet reached 1 year of age, 3 (33.3%) underwent endoscopic third ventriculostomy and none underwent shunting. Conclusion Fetal open spina bifida closure can be performed in Canada, with results similar to those reported by other international expert centres. Long-term follow-up is ongoing.

Recent warnings postulate a possible damaging effect of volatile anesthetics on the fetus. In our archive of fetal surgeries, we found wide variation in dosing of volatile anesthetics during spina bifida surgeries. We hypothesized that there was an association between volatile anesthetic exposure and uterine activity.Sixty anesthesia records from spina bifida operations were assessed. We analyzed the course of the administered volatile anesthetic during surgery and calculated from each patient's anesthesia record the volatile anesthetic exposure expressed in vol%h. We divided the records into two post hoc groups of the 20 lowest exposure (Group L) versus the 20 highest exposure (Group H), and compared them for uterine activity and fetal heart rate.The number of contractions per hour was significantly greater in Group H (mean 1.3, SD ± 1.2) compared with Group L (mean 0.5, SD ± 0.6, P=0.049). There was no difference between the groups for the administration of the tocolytic drug atosiban (P=0.29). The course of the mean arterial pressure did not significantly differ but group H needed significantly more vasoactive medication (P0.05).We found that a lower intra-operative volatile anesthetic exposure than recommended in the MOMS-trial (i.e.2.0 minimum alveolar concentration [MAC]) was not associated with an increase in intra-operative uterine activity. This is an indication that during spina bifida surgery, 2.0 MAC may not be necessary to avoid potentially harmful uterine activity.

Background For pregnancies complicated by fetal myelomeningocele who meet the established criteria, prenatal closure is a viable management option. Prenatal closure is an open procedure, with some techniques requiring greater dissection of maternal tissue than cesarean delivery; pain control is an important postoperative goal. Given the rising rates of opioid dependence and concerns regarding the fetal and neonatal effects of opioid use, our practice has turned to nonopioid pain management techniques. Objective This study aimed to compare postoperative opioid use and pain scores in women undergoing open fetal myelomeningocele repair with and without continuous local bupivacaine wound infusion. Study Design This was a retrospective, single-center chart review of all consecutive patients who underwent open myelomeningocele repair from March 2013 to December 2019. Women were enrolled at the time of referral and locally followed for 2 weeks postoperatively. The control group received patient-controlled epidural analgesia for 48 hours with acetaminophen and oral and intravenous opioids as needed. The treatment group received patient-controlled epidural analgesia for 24 hours with acetaminophen, oral and intravenous opioids, and continuous local bupivacaine infusion. Pain scores, medication use, and postoperative milestones and complications through discharge were abstracted from the chart and compared. Results Of 72 subjects, 51 were in the control group and 21 in the treatment group. Total opioid use, including intravenous doses (165 vs 52.5 mg; P=.001) and daily average oral opioid use (30 vs 10.5 mg; P=.002) were lower in the treatment group. In addition, 24% of women in the treatment group used no opioid postoperatively, compared with 4% in the control group. There was no difference in postoperative day 1 to 4 pain scores, antiemetic use, or bowel function; the treatment group was discharged significantly earlier. Conclusion Postoperative opioid use was reduced in women who received continuous local wound infusion of bupivacaine for incisional pain control after prenatal myelomeningocele repair. Pain control is paramount following open myelomeningocele repair; local bupivacaine wound infusion is an important adjunct to reduce opioid use postoperatively.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 45 - N° 7 - p. 738-744

From the Departments of *Anesthesia and Perioperative Care and †Pediatrics, University of California, San Francisco, CA; ‡Department of Pediatric Cardiology, Children’s Heart Center Linz, Kepler University Clinic, Linz, Austria; §Hadassah Hebrew University Medical Center, Jerusalem, Israel; ‖Children’s Hospital of Los Angeles, Los Angeles, CA; and ¶Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO. Address reprint requests to Marla B. Ferschl, MD, Department of Anesthesia and Perioperative Care, University of California, San Francisco, Department of Anesthesia, Box 3216, 550 16th St. 5th floor, San Francisco, CA 94143. E-mail: ferschlm@anesthesia.ucsf.edu Published by Elsevier Inc. 1053-0770/2602-0033$36.00/0 http://dx.doi.org/10.1053/j.jvca.2016.03.155 FETAL SURGERY IS AN evolving discipline that aims to improve neonatal outcomes in patients who would otherwise have significant morbidity or mortality without treatment prior to birth. The goal of fetal intervention is to correct a primary defect at an early stage in development in order to halt or reverse subsequent secondary effects of the lesion. Disorders amenable to fetal intervention require both the ability to obtain an early accurate diagnosis and well-understood disease progression. Though a new discipline, the safety and efficacy of fetal surgery for open fetal myelomeningocele were shown in a landmark 2011 article. This study demonstrated improved motor developmental outcomes as well as a decreased need for a ventriculo-peritoneal shunt in children randomized to a fetal myelomeningocele repair v standard postnatal repair. The benefits of fetal intervention also have been evaluated in other congenital anomalies, including chest masses and diaphragmatic hernia, as well as for cardiac lesions. In congenital cardiac disease, a few select lesions may be due to a primary defect that subsequently leads to hemodynamic perturbations that evolve into secondary, more complicated malformations. By intervening during the fetal period rather than waiting until after birth, the goal is to prevent or reduce the impact of these secondary deformities and provide an improved clinical outcome. Three congenital cardiac lesions currently are considered appropriate targets for fetal therapy: (1) aortic stenosis (AS) with evolving hypoplastic left-heart syndrome (eHLHS), (2) hypoplastic left-heart syndrome (HLHS) with intact (or highly restrictive) atrial septum, and (3) pulmonary atresia with intact ventricular septum. Importantly, no prospective trials have demonstrated the efficacy of fetal therapy for these malformations. Of the 3 lesions, aortic balloon dilation for AS is the most commonly performed, and, in fact, several centers throughout the world have experience with percutaneous intervention for this indication. Below, the authors present the case of a percutaneous fetal balloon valvuloplasty of the aortic valve in a fetus with AS.

Introduction Radiofrequency ablation (RFA) is increasingly utilized in minimally invasive fetal intervention. However, the response of different fetal tissues to RFA is poorly characterized. We sought to determine the extent of RFA damage in a fetal environment. Methods 90Day gestation Yorkshire piglets (term 115days) were subjected to RFA of the chest and abdominal viscera under various temperatures and wattages. The extent of tissue damage was determined by NADPH diaphorase histochemistry. Results Tyne temperature was widely variable and displayed varying responses between lung and liver tissue. Tyne exposure to amniotic fluid resulted in an increase in amniotic fluid temperature. Collateral damage, even across the diaphragm, was readily seen, and ultrasonography did not always reflect this injury. Conclusions Utilization of extracorporeal tynes heats fluid at a greater rate than solid tissue and reliance on temperature sensitive probes may result in overheating. The extent of injury may extend beyond damage observed by ultrasound examination and varies for different tissues. Additional studies on the use of devices that regulate tyne temperature are needed to define optimal conditions and better define the extent of adjacent tissue injury.

Congenital diaphragmatic hernia (CDH) remains one of the most elusive birth defects to treat. Despite greater knowledge of disease and advances in technology, approximately one-third of CDH children born today still die. Consequently, clinicians and researchers have struggled to find the optimal treatment strategies for CDH. Without further innovations in postnatal treatment, many have focused an antenatal approach to improve pulmonary function. Fetoscopic Endoluminal Tracheal Occlusion (FETO) for CDH has evolved to the bedside after decades of research. While still under clinical investigation, FETO remains a promising adjunct to the treatment of CDH.

Certain life-threatening congenital malformations have the opportunity to be treated with minimally invasive fetal surgery. In recent years fetoscopic surgery had a triggered interest. During the fetoscopic surgery all interventions effecting uteroplasental blood flow and eventually fetal oxygenation, may occur as complications like cardiac depression, maternal hypotension or pulmonary edema. Liaise with the increase in cardiac output and heart rate, the pregnant patient may display increased sensitivity to muscle relaxants and inhalational anesthetics. Due to incomplete myelination and synaptic activation, the fetus becomes more sensitive to volatile agents and analgesics. A goal directed therapy is necessary for both maternal and fetal well-being. According to goal directed therapy, perioperative fluid, vasopressor and inotropic agent titration is recommended to be used taking into account the systemic and pulmonary vascular hemodynamics of patients as well as the pulmonary vascular permeability and fluid content. Perioperative anesthesia management with hemodynamic monitorization, airway management and postoperative pain therapy are key features that make up the secrets of anesthesia. The patient's postoperative suffering from pain also leads to fetal and maternal stress by causing uterine contractions. Thus, appropriate treatment of postoperative pain should be provided using intravenous or epidural patient-controlled analgesia. One of the most important issues in the postoperative period is to prevent patient's premature contraction and not to trigger a premature birth.

Summary Purpose Since the early 1980s with the inception of fetal intervention for obstructive uropathy, there have been creative attempts to improve both perinatal and long-term outcomes. Despite advances in technology and an improved understanding of lower urinary tract obstruction (LUTO) in the fetus, the results for these therapeutic interventions remain guarded and the long-term renal morbidity among survivors remains problematic. Recent findings Fetal LUTO represents a range of disorders but the most common of these is posterior urethral valves (PUVs). Selection criteria for candidates of possible intervention have improved with our understanding of fetal renal physiology. Serial urinalysis has marginally improved our ability to predict those that may ultimately respond to treatment [1,2], but the potential in the development of biomarkers for renal development or maldevelopment holds greater promise [3]. Advancements in fetal surgery may result in less fetal and maternal morbidity, but limited long-term improvement in outcomes highlights the controversial nature of the various interventions [4–10]. We must counsel families that fetal surgery offers hope but we cannot allow them to hold unrealistic expectations for cure. Summary In appropriately selected fetuses, intervention may improve perinatal survival but not without risk to mother and fetus. Long-term renal outcomes remain problematic amongst survivors. In the case of PUV, postnatal primary valve ablation remains the cornerstone of treatment for nephron preservation; however, our ability to mimic these results in the prenatal population remains poor [11]. Disease severity has likely predetermined those that will survive through the perinatal period with or without intervention. Nonetheless, our drive to assess and manage fetal obstructive uropathy perseveres so that we may ultimately relieve obstruction and preserve renal and lung function. We must maintain optimism that continued advances will ultimately improve outcomes, but also be realistic with our current expectations. This paper reviews the status of current in utero interventions and outcomes.

Background In our fetal lamb model of lower urinary tract obstruction, a pressure limited shunt preserves bladder function and renal development. This study investigates the effects on pulmonary histology. Methods We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130–145 days). We compared pulmonary histology in 4 groups: group A, OU without shunt; group B, pressure limited shunt; group C, non-valved shunt. Shunts were inserted 3 weeks post-obstruction. Group D were normal controls. Results We compared 27 fetuses: 7 fetuses in group A, 4 fetuses in group B, 2 fetuses in group C, and 14 fetuses in group D. There was no significant difference in lung volume in any group. In group A, there were some areas of atelectasis and incomplete alveolar formation histologically. The alveoli in group A lambs lungs had a predominance of type II cells, whereas group B lambs lungs were lined by type I epithelial cells and were essentially indistinguishable from controls. Conclusions This study suggests that using a pressure-limited vesico-amniotic shunt in OU may preserve the renal tract and the lungs.

Both the improvement of pathophysiological knowledge of major fetal anomalies and the development of therapeutic tools have allowed in some specific cases in utero therapy by foetoscopy. We discuss the state of art and recent advances for four major anomalies: twin-to-twin transfusion syndrome, congenital diaphragmatic hernia, myelomeningocele and lower urinary tract obstruction. Fetoscopic laser surgery for twin-to-twin transfusion syndrome has become the gold standard for treatment of TTS. In terms of fetal surgery, severe congenital diaphragmatic hernia and myelomeningocele are the two main indications, even if open fetal surgery is still the gold standard for management of myelomeningocele. New techniques using fetal cystoscopy are currently under development. Although the maternal morbidity associated with foetoscopy is low, preterm rupture of membranes and preterm delivery remain an important problem. Long-term evaluation of those neonates remains mandatory.

We investigated the ability of cryopreserved human amniotic membrane (hAM) scaffold sealed with an underwater adhesive, bio-inspired by marine sandcastle worms to promote healing of iatrogenic fetal membrane defects in a pregnant swine model.Twelve Yucatan miniature pigs underwent laparotomy under general anesthesia at 70 days gestation (term = 114 days). The gestational sacs were assigned to uninstrumented (n = 24) and instrumented with 12 Fr trocar, which was further randomized into four different arms-no hAM patch, (n = 22), hAM patch secured with suture (n = 16), hAM patch with no suture (n = 14), and hAM patch secured with adhesive (n = 9). The animals were euthanized 20 days after the procedure. Gross and histological examination of the entry site was performed for fetal membrane healing.There were no differences in fetal survival, amniotic fluid levels, or dye-leakage from the amniotic cavity between the groups. The fetal membranes spontaneously healed in instrumented sacs without hAM patches. In sacs with hAM patches secured with sutures, the patch was incorporated into the swine fetal membranes. In sacs with hAM patches without sutures, 100% of the patches were displaced from the defect site, whereas in sacs with hAM patches secured with adhesive 55% of the patches remained in place and showed complete healing (p = 0.04).In contrast to humans, swine fetal membranes heal spontaneously after an iatrogenic injury and thus not an adequate model. hAM patches became incorporated into the defect site by cellular ingrowth from the fetal membranes. The bioinspired adhesive adhered the hAM patches within the defect site.

Fetal surgery is a fascinating field that will continue to evolve as we develop a more refined understanding of the underlying biology of various birth defects. Since preterm labor is a frequent outcome of fetal intervention, examining the mechanisms that lead to a breakdown in maternal-fetal tolerance is vital to developing strategies to overcome this limitation. The trafficking of cells between the mother and fetus during pregnancy plays a critical role in the education of the fetal immune system and may have implications for postnatal transplantation tolerance. Maternal cells may also be the ideal source for transplantation into the fetus to treat congenital stem cell disorders.

Over the past 20 years, prenatal detection of congenital diaphragmatic hernia (CDH) has improved worldwide, reaching up to 60% in Europe. Pulmonary hypoplasia and persistent pulmonary hypertension are the two main determinants of neonatal mortality and morbidity, so new tools have been focused on their evaluation. Fetal surgery for severe cases requires proper evaluation of the prognosis of fetuses with CDH. Observed-to-expected lung-to-head ratio, liver position, and total lung volume measured by magnetic resonance are the prognostic factors most often used, and have been shown to correlate not only with neonatal mortality but also with morbidity. In daily practice, pulmonary hypertension by itself, although most often associated with lung hypoplasia, is more difficult to predict.

Congenital diaphragmatic hernia (CDH) may be isolated or associated with other structural anomalies, the latter with poor prognosis. The defect allows viscera to herniate through the defect into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. When isolated, survival chances can be predicted by antenatal measurement of lung size and liver herniation. Chromosomal microarrays and exome sequencing contribute to understanding genetic factors underlying isolated CDH. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion (FETO) under local anesthesia. The Tracheal Occlusion To Accelerate Lung growth trial (www.totaltrial.eu) is an international randomized trial investigating the role of fetal therapy for severe and moderate pulmonary hypoplasia. Despite an apparent increase in survival following FETO, the search for lesser invasive and more potent prenatal interventions must continue.

Background In our fetal lamb model of lower urinary tract obstruction, a valved shunt preserves bladder function. This study investigates the effects on renal histology. Methods We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130–145days). We compared renal histology in 4 groups: group A—OU without shunt, group B—low-pressure shunt (15–54mmH 2 O), group C—high-pressure shunt (95–150mmH 2 O). Shunts were inserted 3weeks post-obstruction. Group D were normal controls. Results We delivered 32 fetuses from 23 ewes: 13 fetuses in group A (9 survived), 6 fetuses in group B (5 survived), 7 fetuses in group C (5 survived), and 6 fetuses in group D. Histologically, we found renal tubular distention, vacuolated degeneration of tubular epithelial cells in 7 lambs, and cyst formation in 4 lambs in group A. There was renal tubular distention in two lambs, and cyst formation in one lamb in both groups B and C, with vacuolated degeneration of tubular epithelial cells observed in all but 1 lamb in each group. Conclusions V-A shunting prevents multicystic dysplastic kidney (MCDK). Some lambs have renal tubular distention and vacuolated degeneration of renal tubular epithelial cells.