Placental Location in Maternal-Fetal Surgery for Myelomeningocele.

INTRODUCTION: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes. OBJECTIVE: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure. METHODS: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations. RESULTS: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location. CONCLUSIONS: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes.

Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia.

BACKGROUND: Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking. METHODS: In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women. RESULTS: The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09). CONCLUSIONS: In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).

Analgesia for fetal pain during prenatal surgery: 10 years of progress.

Some doubts on the necessity and safety of providing analgesia to the fetus during prenatal surgery were raised 10 years ago. They were related to four matters: fetal sleep due to neuroinhibitors in fetal blood, the immaturity of the cerebral cortex, safety, and the need for fetal direct analgesia. These objections now seem obsolete. This review shows that neuroinhibitors give fetuses at most some transient sedation, but not a complete analgesia, that the cerebral cortex is not indispensable to feel pain, when subcortical structures for pain perception are present, and that maternal anesthesia seems not sufficient to anesthetize the fetus. Current drugs used for maternal analgesia pass through the placenta only partially so that they cannot guarantee a sufficient analgesia to the fetus. Extraction indices, that is, how much each analgesic drug crosses the placenta, are provided here. We here report safety guidelines for fetal direct analgesia. In conclusion, the human fetus can feel pain when it undergoes surgical interventions and direct analgesia must be provided to it. IMPACT: Fetal pain is evident in the second half of pregnancy. Progress in the physiology of fetal pain, which is reviewed in this report, supports the notion that the fetus reacts to painful interventions during fetal surgery. Evidence here reported shows that it is an error to believe that the fetus is in a continuous and unchanging state of sedation and analgesia. Data are given that disclose that drugs used for maternal analgesia cross the placenta only partially, so that they cannot guarantee a sufficient analgesia to the fetus. Safety guidelines are given for fetal direct analgesia.

Anesthesia for Maternal-Fetal Interventions: A Consensus Statement From the American Society of Anesthesiologists Committees on Obstetric and Pediatric Anesthesiology and the North American Fetal Therapy Network.

Maternal-fetal surgery is a rapidly evolving specialty, and significant progress has been made over the last 3 decades. A wide range of maternal-fetal interventions are being performed at different stages of pregnancy across multiple fetal therapy centers worldwide, and the anesthetic technique has evolved over the years. The American Society of Anesthesiologists (ASA) recognizes the important role of the anesthesiologist in the multidisciplinary approach to these maternal-fetal interventions and convened a collaborative workgroup with representatives from the ASA Committees of Obstetric and Pediatric Anesthesia and the Board of Directors of the North American Fetal Therapy Network. This consensus statement describes the comprehensive preoperative evaluation, intraoperative anesthetic management, and postoperative care for the different types of maternal-fetal interventions.

Percutaneous Intratumor Laser Ablation for Fetal Sacrococcygeal Teratoma.

OBJECTIVE: To evaluate the efficiency of percutaneous intratumor laser ablation for fetal solid sacrococcygeal teratoma (SCT). SUBJECTS AND METHODS: We carried out percutaneous ultrasound-guided intratumor laser ablation through a 17-gauge needle using an output of 40 W in 7 fetuses with large solid SCT and reviewed the literature for minimally invasive therapy for this condition. RESULTS: Laser ablation was carried out at a median gestational age of 20 (range 19-23) weeks, and in all cases there was elimination of obvious vascularization within the tumor and improvement in cardiac function. Three (43%) babies survived and had surgical excision of the tumor within 2 days of birth, 3 liveborn babies died within 5 days of birth and before surgery, and 1 fetus died within 2 weeks after the procedure. In previous series of various percutaneous interventions for predominantly solid SCT the survival rate was 33% (2/6) (95% CI 9.7-70%) for endoscopic laser to superficial vessels, 57% (4/7) (95% CI 25-84%) for intratumor laser, 67% (8/12) (95% CI 39-86%) for intratumor radiofrequency ablation, and 20% (1/5) (95% CI 3.6-62%) for intratumor injection of alcohol. CONCLUSIONS: In solid SCT, the reported survival from intratumor laser or radiofrequency ablation is about 50%, but survival does not mean success, and it remains uncertain whether such interventions are beneficial or not because the number of fetuses is small and there were no controls that were managed expectantly.

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

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

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

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

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Shunt-Dependent Hydrocephalus in Infants With Myelomeningocele After Prenatal Versus Postnatal Repair.

BACKGROUND: Myelomeningocele (MM) is a condition that is responsible for considerable morbidity in the pediatric population. A significant proportion of the morbidity related to MM is attributable to hydrocephalus and the surgical management thereof. Postnatal repair remains the most common form of treatment; however, increased rates of prenatal diagnosis, advances in fetal surgery, and a hypothesis that neural injury continues in utero until the MM defect is repaired have led to the development and evaluation of prenatal surgery as a means to improve outcomes in afflicted infants. OBJECTIVE: The objective of this guideline is to systematically evaluate the literature to determine whether there is a difference in the proportion of patients who develop shunt-dependent hydrocephalus in infants who underwent prenatal MM repair compared to infants who had postnatal repair. METHODS: The Guidelines Task Force developed search terms and strategies used to search PubMed and Embase for relevant literature published between 1966 and September 2016. Strict inclusion/exclusion criteria were used to screen abstracts and to develop a list of relevant articles for full-text review. Full-text articles were then reviewed, and when appropriate, included as evidence. RESULTS: A total of 87 abstracts were identified and reviewed by 3 independent reviewers. Thirty-nine full-text articles were selected for analysis. Three studies met selection criteria and were included in the evidence table. CONCLUSION: Class I evidence from 1 study and class III evidence from 2 studies suggest that, in comparison to postnatal repair, prenatal surgery for MM reduces the risk of developing shunt-dependent hydrocephalus. Therefore, prenatal repair of MM is recommended for those fetuses who meet specific criteria for prenatal surgery to reduce the risk of developing shunt-dependent hydrocephalus (level I). Differences between prenatal and postnatal repair with respect to the requirement for permanent cerebrospinal fluid diversion should be considered alongside other relevant maternal and fetal factors when deciding upon a preferred method of MM closure. The full guideline can be found at https://www.cns.org/guidelines/guidelines-spina-bifida-chapter-2.

MOMS Plus: Single-Institution Review of Outcomes for Extended BMI Criteria for Open Fetal Repair of Myelomeningocele.

BACKGROUND: In utero repair has become an accepted therapy to decrease the rate of ventriculoperitoneal shunting and improve neurologic function in select cases of myelomeningocele. The Management of Myelomeningocele Study (MOMS) trial excluded patients with a BMI >35 due to concerns for increased maternal complications and preterm delivery, limiting the population that may benefit from this intervention. OBJECTIVES: The aim of this study was to evaluate outcomes associated with extending the maternal BMI criteria to 40 in open fetal repair of myelomeningocele. METHOD: Retrospective review of fetal closure of myelomeningocele at a quaternary referral center between 2013 and 2016 with maternal BMI ranging from 35 to 40. RESULTS: Eleven patients with a BMI >35 were identified. The average BMI was 37. The average maternal age at the time of evaluation was 27 years. The average gestational age at fetal surgery was 24 weeks. Gestational age at birth was an average of 32 weeks. There was one perinatal death immediately following the fetal intervention. The shunt rate at 1 year was 45% (5/11 patients). CONCLUSIONS: In this single-institution review of expanded BMI criteria for fetal repair of myelomeningocele, we did not observe any adverse maternal outcomes associated with maternal obesity; however, the gestational age at delivery was 2 weeks earlier compared to the MOMS trial.

Anesthesia for predelivery procedures: ex-utero intrapartum treatment/intrauterine transfusion/surgery of the fetus.

PURPOSE OF REVIEW: The aim of this study was to review the current literature on anesthesia for predelivery procedures and to summarize recent findings on anesthesiological methods used. RECENT FINDINGS: Ex-utero intrapartum treatment (EXIT)-procedures are performed to secure the newborn's oxygenation in case of severe airway obstruction due to multiple conditions. A key feature of EXIT is continued intactness of the maternofetal circulation by uterine relaxation achieved by general anesthesia with high doses of anesthetic gases. A dose reduction may be achieved by combining inhaled anesthesia with propofol. After intrauterine transfusion the anesthesia team needs to be prepared for a potential need of emergency cesarean section. Temporary fetal endoluminal tracheal occlusion and laser coagulation for twin-to-twin transfusion syndrome may be either performed in monitored anesthesia care or neuraxial anesthesia. Neuraxial anesthesia also is a method of choice for fetal valvuloplasty and amniotic band release. Fetal myelomenigocele repair requires general anesthesia with tocolysis. SUMMARY: Predelivery procedures require a differentiated anesthesia approach depending on the invasiveness of the intervention. Anesthesia ranges from monitored care to neuraxial anesthesia and general anesthesia. Depending on the procedure uterine relaxation and fetal immobilization are crucial for technical success. Interdisciplinary consultation optimizes the anesthesia plan for complex procedures.

The Use of Indomethacin with Complete Amniotic Fluid Replacement and Classic Hysterotomy for the Reduction of Perinatal Complications of Intrauterine Myelomeningocele Repair.

OBJECTIVE: This study presented outcomes of classical hysterotomy with modified antiprostaglandin therapy for intrauterine repair of foetal myelomeningocele (fMMC) performed in a single perinatal centre. STUDY DESIGN: Forty-nine pregnant women diagnosed with fMMC underwent classic hysterotomy with anti-prostaglandin management, complete amniotic fluid replacement and high dose indomethacin application. RESULTS: The average gestational age (GA) at delivery was 34.4 ± 3.4 weeks, with no births before 30 weeks GA. There were 2 foetal deaths. Complete reversal of hindbrain herniation (HH), assessed in magnetic resonance imaging at 30-31 weeks GA was found in 72% of foetuses (mostly with HH grade I prior to fMMC repair). Our protocol resulted in rare use of magnesium sulphate (6%), low incidence of chorioamniotic membrane separation - chorioamniotic membrane separation (6%), preterm premature rupture of membranes - preterm premature rupture of membranes (pPROM; 15%) and preterm labour - preterm labour (PTL; 17%). The postoperative wound continuity of the uterus was usually stable (in 72% of patients), with low frequency of scar thinning (23%). CONCLUSION: Our protocol results in rare use of tocolytics, and the low occurrences of CMS, pPROM and PTL in relation to other study cohorts: Management of Myelomeningocele Study, Children's Hospital of Philadelphia, and Vanderbilt University Medical Centre.

Open fetal surgery for neural tube defects.

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.

Biomaterials in fetal surgery.

Fetal surgery and fetal therapy involve surgical interventions on the fetus in utero to correct or ameliorate congenital abnormalities and give a developing fetus the best chance at a healthy life. Historical use of biomaterials in fetal surgery has been limited, and most biomaterials used in fetal surgeries today were originally developed for adult or pediatric patients. However, as the field of fetal surgery moves from open surgeries to minimally invasive procedures, many opportunities exist for innovative biomaterials engineers to create materials designed specifically for the unique challenges and opportunities of maternal-fetal surgery. Here, we review biomaterials currently used in clinical fetal surgery as well as promising biomaterials in development for eventual clinical translation. We also highlight unmet challenges in fetal surgery that could particularly benefit from novel biomaterials, including fetal membrane sealing and minimally invasive myelomeningocele defect repair. Finally, we conclude with a discussion of the underdeveloped fetal immune system and opportunities for exploitation with novel immunomodulating biomaterials.

Ultrasound-guided in Utero Transplantation of Placental Stem Cells into the Liver of Crigler-Najjar Syndrome Model Rat.

BACKGROUND: Advances in prenatal screening and early diagnosis of genetic disease will potentially allow for preemptive treatment of anticipated postnatal disease by in utero cell transplantation (IUCT). This strategy carries potential benefits over postnatal treatment, which might allow for improved engraftment and function of the transplanted cells. Congenital metabolic disorders may be an ideal target for this type of therapy, as in most cases, they require replacement of a single deficient hepatic enzyme, and multiple small-animal models exist for preclinical testing. METHODS: The Gunn rat, a Crigler-Najjar syndrome model animal lacking UDP-glucuronosyltransferase (UGT1A1), was used as recipient. Human amniotic epithelial cells (hAECs), which possess hepatic differentiation potential, were transplanted into the midgestation fetal Gunn rat liver via ultrasound-guided IUCT. The impact of IUCT on live birth and postnatal survival was evaluated. Human cell engraftment was immunohistochemically analyzed on postnatal day 21. RESULTS: Ultrasound-guided IUCT was conducted in rat fetuses on embryonic day 16. Following IUCT, the antihuman mitochondria-positive cells were detected in the liver of recipient rats at postnatal day 21. CONCLUSIONS: Here, we have introduced ultrasound-guided IUCT of hAEC using a small-animal model of a congenital metabolic disorder without immunosuppression. The immunological advantage of IUCT was demonstrated with xenogeneic IUCT. This procedure is suitable to conduct preclinical studies for exploring the feasibility and efficacy of ultrasound-guided transuterine cell injection using rodent disease models.

Urinary and Fecal Continence in 5-Year-Old Patients Who Underwent in utero Myelomeningocele Repair: A Prospective Study.

INTRODUCTION: After the successful results of in utero myelomeningocele (MMC) repair presented by the Management of Myelomeningocele Study, the concept of fetal surgery was introduced in our institution in 2011. Since then, we have been able to follow prospectively a group of patients with attention to urological care. In the present study, we were interested in estimating urinary and fecal continence in this new subset of patients. MATERIAL AND METHODS: We selected from our database patients aged 5 years or older for evaluation of urinary and fecal continence. We reviewed all charts and completed a questionnaire to study aspects of urinary and fecal continence. RESULTS: We identified 14 patients, i.e., 4 (28.6%) males and 10 (71.4%) females. The mean age at MMC surgery was 25.6 gestational weeks. The uro-dynamic class was high-risk in 6 (42.9%), incontinent in 4 (28.6%), hypocontractile in 1 (7.1%), and normal in 3 (21.4%) patients. Three patients had undergone surgery (2 augmentations, i.e., 1 in association with a left colon ACE Macedo-Malone procedure and 1 mini-sling urethroplasty). Twelve patients underwent clean intermittent catheterization (CIC) (85.7%). Only 3 (21.4%) patients had no urinary leakage. Eleven patients (78.6%) used diapers. Eight patients (57.2%) underwent retrograde rectal irrigation and 11 (78.6%) complained of fecal loss. Eleven patients (78.6%) did not report an impact on their self-esteem. CONCLUSION: Despite the use of CIC in 85.7% of the cases, the continence rate in MMC patients operated on in utero was low and 78.6% of the patients used diapers. This data can be used to educate parents about future conditions of their 5-year-old children and may stimulate the debate regarding further attempts (surgical or not) to improve fecal and urinary continence.

Congenital urinary tract obstruction.

Congenital bladder neck obstruction (or lower urinary tract obstruction [LUTO]) describes a heterogeneous group of congenital anomalies presenting with similar prenatal ultrasonographic findings of dilated posterior urethra, megacystis, hydronephrosis, oligohydramnios and often with associated renal dysplasia. Untreated LUTO has high rate of perinatal morbidity and mortality from associated pulmonary hypoplasia and early-onset renal failure in infancy. Ultrasonographic features and prospective fetal urinalysis may help in predicting the overall prognosis of congenital LUTO. Currently, fetal vesicoamniotic shunt (of various designs), and fetal cystoscopy and fulguration of the obstruction are potential prenatal interventions. Retrospective and prospective cohort studies and a relatively small randomized controlled trial have demonstrated these treatments may possibly improve perinatal survival. Despite this, concerns remain as to the high rates of renal impairment observed in paediatric survivors. A clinical prospective scoring/staging system may improve prenatal diagnostic criteria and case selection for fetal therapy.

Management of fetal tumors.

In this review article, we discuss the most common fetal tumors, their prenatal management, and outcomes. Overall, the most important outcome predictors are tumor histology, size, vascularity, and location. Very large lesions, lesions causing cardiac failure, and hydrops and lesions obstructing the fetal airway have the poorest outcome, as they may cause fetal death or complications at the time of delivery. Fetal therapy has been developed to improve outcomes for the most severe cases and can consist of transplacental therapy (sirolimus for rhabdomyomas or steroids for hemangiomas and microcystic lung lesions) or surgical intervention (shunting of cystic masses, tumor ablation, occlusion of blood flow or airway exploration, and protection). Given the rarity of fetal tumors, patients should be referred to expert centers where care can be optimized and individualized to allow the best possible outcomes.

Long-Term Neurodevelopmental and Respiratory Outcome after Intrauterine Therapy for Fetal Thoracic Abnormalities.

INTRODUCTION: The aim of this study is to evaluate long-term neurodevelopmental and respiratory outcome after fetal therapy for fetal pleural effusion, congenital cystic adenomatoid malformation, and bronchopulmonary sequestration. METHODS: Children ≥18 months of age underwent an assessment of neurologic, motor, and cognitive development. Medical records were reviewed to determine respiratory outcome. Behavioral outcome was assessed using the Child Behavioral Checklist. RESULTS: Between 2001 and 2016, 63 fetuses with fetal hydrops secondary to thoracic abnormalities were treated at our center. Overall perinatal survival was 64% (40/63). Twenty-six children were included for follow-up (median age 55 months). Severe neurodevelopmental impairment (NDI) was detected in 15% (4/26). Three out of 4 children with severe NDI had associated causes contributing to the impairment. Overall adverse outcome, including perinatal mortality or NDI, was 55% (27/49). Fifteen percent (4/26) had severe respiratory sequelae. Parents did not report more behavioral problems than Dutch norms. DISCUSSION: Our results suggest that severe NDI in this specific high-risk cohort occurs in 15%, which is above the range of the incidence of NDI reported in case series treated with other fetal therapies (5-10%). Large multicenter studies and an international web-based registry are warranted to prospectively gather outcome data at fixed time points.