Successful antenatal treatment of MAGED2-related Bartter syndrome and review of treatment options and efficacy.

A new form of transient antenatal Bartter syndrome (aBS) was recently identified that is associated with the X-linked MAGED2 variant. Case reports demonstrate that this variant leads to severe polyhydramnios that may result in preterm birth or pregnancy loss. There is limited but promising evidence that amnioreductions may improve fetal outcomes in this rare condition. We report a woman with two affected pregnancies. In the first pregnancy, the patient was diagnosed with mild-to-moderate polyhydramnios in the second trimester that ultimately resulted in preterm labor and delivery at 25 weeks with fetal demise. Whole exome sequencing of the amniotic fluid sample resulted after the pregnancy loss and revealed a c.1337G>A MAGED2 variant that was considered diagnostically. The subsequent pregnancy was confirmed by chorionic villi sampling to also be affected by this variant. The pregnancy was managed with frequent ultrasounds and three amnioreductions that resulted in spontaneous vaginal delivery at 37 weeks and 6 days of a viable newborn with no evidence of overt electrolyte abnormalities suggesting complete resolution. A detailed review of the published cases of MAGED2-related transient aBS is provided. Our review focuses on individuals who received antenatal treatment. A total of 31 unique cases of MAGED2-related transient aBS were compiled. Amnioreduction was performed in 23 cases and in 18 cases no amnioreduction was performed. The average gestational age at delivery was significantly lower in cases without serial amnioreduction (28.7 vs. 30.71 weeks, p = 0.03). Neonatal mortality was seen in 5/18 cases without serial amnioreduction, and no mortality was observed in the cases with serial amnioreduction. In cases of second trimester severe polyhydramnios without identifiable cause, whole exome sequencing should be considered. Intensive ultrasound surveillance and serial amnioreduction is recommended for the management of MAGED2-related transient aBS.

Maternal-fetal comorbidities and obstetrical outcomes of fetal single ventricle cardiac defects: 10 years' experience with a multidisciplinary management protocol at a single center.

OBJECTIVES: To describe and compare maternal and fetal comorbidities and obstetrical outcomes in pregnancies with hypoplastic left and right heart (HLHS and HRH) single ventricle cardiac defects (SVCD) from a single center under a multidisciplinary protocol. METHOD: A single center retrospective review of fetal SVCD from 2013 to 2022. Maternal-fetal comorbidities, delivery, and postnatal outcomes were compared between HLHS and HRH using descriptive statistics and univariate and multivariate analyses. RESULTS: Of 181 SVCD pregnancies (131 HLHS; 50 HRH), 9% underwent termination, 4% elected comfort care, 5 died in utero and 147/152 liveborns survived to the first cardiac intervention. Cesarean delivery occurred in 57 cases (37%), planned in 36 and unplanned in 21. Comorbidities, which did not differ between HLHS and HRH, included fetal growth restriction (FGR, 17%), prematurity (14%), maternal hypertension (9%), maternal obesity (50%), fetal extracardiac anomalies and chromosome anomalies (12%, 13%). In multivariate analysis, only earlier gestational age at delivery and oligohydramnios predicted decreased odds of survival at one year. CONCLUSION: Maternal-fetal comorbidities are common in both HLHS and HRH. Earlier gestational age at delivery and oligohydramnios predict lower postnatal survival. FGR, even with severe early onset, did not significantly impact short- or long-term neonatal survival in single ventricle conditions.

Piloting a multidisciplinary approach to improve outcomes of fetal whole exome sequencing: An overview of workflow and case example.

INTRODUCTION: Whole exome sequencing (WES) has increasingly become integrated into prenatal care and genetic testing pathways. Current studies of prenatal WES have focused on diagnostic yield. The possibility of obtaining a variant of uncertain significance and lack of provider expertise are frequently described as common barriers to clinical integration of prenatal WES. We describe the implementation and workflow for a multidisciplinary approach to effectively integrate prenatal WES into maternal-fetal care to overcome these barriers. METHODS: A multidisciplinary team reviews and approves potential cases for WES. This team reviews WES results, reclassifying variants as appropriate and provides recommendations for postnatal care. A detailed description of this workflow is provided, and a case example is included to demonstrate effectiveness of this approach. Our team has approved 62 cases for WES with 45 patients ultimately pursuing WES. We have achieved a diagnostic yield of 40% and the multidisciplinary team has played a role in variant interpretation in 50% of the reported variants of uncertain significance. CONCLUSIONS: This approach facilitates communication between prenatal and postnatal care teams and provides accurate interpretation and recommendations for identified fetal variants. This model can be replicated to ensure appropriate patient care and effective integration of novel genomic technologies into prenatal settings.

Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles.

OBJECTIVE: Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO. METHOD: A single-institution retrospective review of GO evaluated between 2012 and 2022 was performed. Fetal MRI TLV between 32 and 36 weeks' gestation and O/E TLV throughout gestation were calculated and correlated with postnatal outcomes. RESULTS: 86 fetuses with omphaloceles were evaluated; however, only 26 met strict inclusion criteria. MRIs occurred between 18 and 36 weeks' gestation. Those requiring delivery room intubation had significantly lower late gestation TLV and O/E TLV. O/E TLV predicted tracheostomy placement and survival. Neither TLV nor O/E TLV predicted the length of hospitalization or supplemental oxygen after discharge. Three fetuses had a TLV less than 35 mL: one died of respiratory failure, and the other two required tracheostomy. CONCLUSIONS: Fetal MRI TLV measured between 32 and 36 weeks' gestation and O/E TLV predict the need for delivery room intubation and tracheostomy. O/E TLV correlated with survival. These data support fetal MRI as a prognostic tool to predict GO associated pulmonary morbidity.

Third-trimester percentage predicted lung volume and percentage liver herniation as prognostic indicators in congenital diaphragmatic hernia.

BACKGROUND: Over the last two decades, fetal imaging has greatly improved, and new prenatal imaging measurements have been developed to characterize congenital diaphragmatic hernia (CDH) severity. OBJECTIVE: To determine the best prenatal imaging predictor of postnatal CDH outcomes, including use of extracorporeal membrane oxygenation (ECMO) and in-hospital mortality, with particular attention to the percentage of liver herniation (%LH) as a predictor. Additionally, we sought to guide best practices across hospital systems including improved models of prenatal risk assessment. MATERIALS AND METHODS: We conducted a retrospective review of infants with left CDH who were prenatally diagnosed. We analyzed prenatal imaging measurements including observed-to-expected (O/E) lung-to-head ratio (LHR) on US, percentage predicted lung volume (PPLV) on MRI, and O/E total fetal lung volume (TFLV) and %LH on MRI. We compared prenatal imaging characteristics for infants with (1) in-hospital postnatal mortality and (2) use of ECMO. Then we performed multivariate logistic regression to determine independent predictors of postnatal outcomes. RESULTS: We included 63 infants with a median gestation of 34 weeks at the time of prenatal MRI. Low O/E LHR (31.2 vs. 50, P < 0.0001), PPLV (14.7 vs. 22.6, P < 0.0001) and O/E TLFV (24.6 vs. 38.3, P < 0.0001) and high %LH (15.1 vs. 2.1, P = 0.0006) were associated with worse postnatal outcomes; however, only PPLV was predictive of survival and need for ECMO on multivariable analysis. PPLV survival to discharge model showed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.86, 0.99), P < 0.0001; and an odds ratio of 68.7 (95% CI: 6.5-2,302), P = 0.003. PPLV need for ECMO model showed AUC = 0.87 (95% CI: 0.78, 0.96), P < 0.0001; and odds ratio = 20.1 (95% CI: 3.1-226.3), P = 0.011. CONCLUSION: Low O/E LHR, PPLV and O/E TFLV and high %LH in the third trimester are associated with worse postnatal outcomes. PPLV most strongly predicted outcome using a logistic regression model. Percentage of liver herniation was not an independent predictor of outcomes.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

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.

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.

Visualization of the fetal anus by prenatal ultrasound for the diagnosis of anorectal malformations: is it feasible?

PURPOSE: The goal of this study was to determine the feasibility of identifying the anal dimple (AD) on routine prenatal ultrasound. Using the presence, absence, appearance, and location of the anal dimple as an indirect sign for possible underlying anorectal malformations (ARM), we hypothesize that evaluation of the anal dimple as part of the fetal anatomic survey may increase the sensitivity in detecting less severe ARMs. METHODS: In a prospective longitudinal observational study, pregnant women who underwent prenatal ultrasound (US) at the Colorado Fetal Care Center between January 2019 and 2020 were enrolled. The variables recorded included gestational age, singleton versus multiple pregnancy, gender of the fetus, visualization of the AD, and reason for non-visualization of the AD. RESULTS: A total of 900 ultrasounds were performed, evaluating 1044 fetuses, in 372 different pregnant women. Gestational ages ranged from 16 to 38 weeks. The AD was visualized in 612 fetuses (58.6%) and not seen in 432 (41.4%). The two most common reasons for non-visualization were extremes in gestational age (n = 155; 36%) and fetal position (n = 152; 35.3%). The optimal gestational age range for AD visualization was 28-33 weeks + 6 days, with 78.1% visualization rate. CONCLUSION: Visualization of the anal dimple by ultrasound is feasible and may aid in the detection of less severe ARMs, ultimately impacting pregnancy management and family counseling. The optimal timing for anal dimple visualization is late second and third trimester.

Anesthesia for Maternal-Fetal Interventions: A Survey of Fetal Therapy Centers in the North American Fetal Therapy Network.

INTRODUCTION: A wide range of fetal interventions are performed across fetal therapy centers (FTCs). We hypothesized that there is significant variability in anesthesia staffing and anesthetic techniques. METHODS: We conducted an online survey of anesthesiology directors at every FTC within the North American Fetal Therapy Network (NAFTNet). The survey included details of fetal interventions performed in 2018, anesthesia staffing models, anesthetic techniques, fetal monitoring, and postoperative management. RESULTS: There was a 92% response rate. Most FTCs are located within an adult hospital and employ a small team of anesthesiologists. There is heterogeneity when evaluating anesthesiology fellowship training and staffing, indicating there is a multidisciplinary specialty team-based approach even within anesthesiology. Minimally invasive fetal interventions were the most commonly performed. The majority of FTCs also performed ex utero intrapartum treatment (EXIT) and open mid-gestation procedures under general anesthesia (GA). Compared to FTCs only performing minimally invasive procedures, FTCs performing open fetal procedures were more likely to have a pediatric surgeon as director and performed more minimally invasive procedures. CONCLUSIONS: There is considerable variability in anesthesia staffing, caseload, and anesthetic techniques among FTCs in NAFTNet. Most FTCs used maternal sedation for minimally invasive procedures and GA for EXIT and open fetal surgeries.

Variability in antenatal prognostication of fetal diaphragmatic hernia across the North American Fetal Therapy Network (NAFTNet).

OBJECTIVE: To evaluate variability in antenatal sonographic prognostication of congenital diaphragmatic hernia (CDH) within the North American Fetal Therapy Network (NAFTNet). METHODS: NAFTNet centre were invited to complete a questionnaire and participate in videoconference calls, during which participants were observed while measuring lung area by ultrasound using the anteroposterior (AP) method, longest method, and trace method. Each center identified 1-2 experienced fetal medicine specialist(s) or medical imaging specialists locally to participate in the study. Practices were compared among NAFTNet centre within and without the fetal endoscopic tracheal occlusion (FETO) consortium. RESULTS: Nineteen participants from 9 FETO center and 30 participants from 17 non-FETO center completed the survey and 31 participants were interviewed and observed while measuring sonographic lung area. All Centres measured observed-to-expected lung-to-head ratio (o/e LHR) or LHR for CDH prognostication. Image selection criteria for lung area measurement were consistent, including an axial section of the chest with clear lung borders and a 4-chamber cardiac view. Lung area measurement methods varied across NAFTNet, with most centre using longest (4/9 FETO vs. 13/29 non-FETO) or trace (3/9 FETO vs. 11/29 non-FETO) method. Centres differed in expected reference ranges for o/e LHR determination and whether the lowest, highest or average o/e LHR was utilized. CONCLUSION: Variability in antenatal sonographic prognostication of CDH was identified across NAFTNet, indicating a need for consensus-based standardization.

Outcomes of Airway Management in Micrognathia and Retrognathia Patients Born at Fetal versus Nonfetal Centers.

OBJECTIVES: There is a paucity of evidence to guide the perinatal management of difficult airways in fetuses with micrognathia. We aimed to (1) develop a postnatal grading system based on the extent of airway intervention required at birth to assess the severity of micrognathic airways and (2) compare trends in airway management and outcomes by location of birth [nonfetal center (NFC), defined as a hospital with or without an NICU and no fetal team, versus fetal center (FC), defined as a hospital with an NICU and fetal team]. METHODS: We retrospectively reviewed the prenatal and postnatal records of all neonates diagnosed with micrognathia from January 2010 to April 2018 at a quaternary children's hospital. We developed a novel grading scale, the Micrognathia Grading Scale (MGS), to grade the extent of airway intervention at birth from 0 (no airway intervention) to 4 (requirement of EXIT or advanced airway instrumentation for airway securement). RESULTS: We identified 118 patients with micrognathia. Eighty-nine percent (105/118) were eligible for grading using the MGS. When the MGS was applied, the airway grades were as follows: grade 0 (30%), grade 1 (10%), grade 2 (9%), grade 3 (48%), and grade 4 (4%). A quarter of micrognathic patients with grade 0-2 airways had postnatal hospital readmissions for airway obstruction after birth, of which all were born at NFC. Over 40% of patients with grade 3-4 micrognathic airways required airway intervention within 24 h of birth. Overall, NFC patients had a readmission rate of (27%) for airway obstruction after birth compared to FC patients (17%). CONCLUSIONS: Due to the high incidence of grade 3-4 airways on the MGS in micrognathic patients, fetuses with prenatal findings suggestive of micrognathia should be referred to a comprehensive fetal care center capable of handling complex neonatal airways. For grade 0-2 airways, infants frequently had postnatal complications necessitating airway intervention; early referral to a multidisciplinary team for both prenatal and postnatal airway management is recommended.

Examination of Prenatal Sonographic Findings: Intra-Abdominal Bowel Dilation Predicts Poor Gastroschisis Outcomes.

BACKGROUND: Gastroschisis is an anterior abdominal wall defect with variable outcomes. There are conflicting data regarding the prognostic value of sonographic findings. OBJECTIVES: The aim of this study was to identify prenatal ultrasonographic features associated with poor neonatal outcomes. METHOD: A retrospective review of 55 patients with gastroschisis from 2007 to 2017 was completed. Ultrasounds were reviewed for extra-abdominal intestinal diameter (EAID) and intra-abdominal intestinal diameter (IAID), echogenicity, visceral content within the herniation, amniotic fluid index, defect size, and abdominal circumference (AC). Ultrasound variables were correlated with full enteral feeding and the diagnosis of a complex gastroschisis. RESULTS: Bivariate analysis demonstrated an increased time to full enteral feeds with increasing number of surgeries, EAID, and IAID. Additionally, there was a significant relationship between IAID and AC percentile with the diagnosis of complex gastroschisis. On multivariate analysis, only IAID was significant and increasing diameter had a 2.82 (95% CI 1.02-7.78) higher odds of a longer time to full enteral feeds and a 1.2 (95% CI 1.05-1.36) greater odds of the diagnosis of a complex gastroschisis. CONCLUSIONS: Based on these findings, IAID is associated with a longer time to full enteral feeding and the diagnosis of complex gastroschisis.

Size and shape of the four-chamber view of the fetal heart in fetuses with an estimated fetal weight less than the tenth centile.

BACKGROUND: Fetuses with an estimated fetal weight below the 10th centile have an increased risk of adverse perinatal and long-term outcomes as well as increased rates of cardiac dysfunction, which often alters cardiac size and shape of the 4-chamber view and the individual ventricles. As a result, a simple method has emerged to screen for potential cardiac dysfunction in fetuses with estimated fetal weights <10th centile by measuring the size and shape of the 4-chamber view and the size of the ventricles. OBJECTIVE: To determine the number of fetuses with an abnormal size and shape of the 4-chamber view and size of the ventricles in fetuses with an estimated fetal weight <10th centile. MATERIALS AND METHODS: This was a retrospective study of 50 fetuses between 25 and 37 weeks of gestation with an estimated fetal weight <10th centile. Data from their last examination were analyzed. From an end-diastolic image of the 4-chamber view, the largest basal-apical length and transverse width were measured from their corresponding epicardial borders. This allowed the 4-chamber view area and global sphericity index (4-chamber view length/4-chamber view width) to be computed. In addition, tracing along the endocardial borders with speckle tracking software enabled measurements of the right and left ventricular chamber areas and the right ventricle/left ventricle area ratios to be computed. Doppler waveform pulsatility indices from the umbilical (umbilical artery pulsatility index) and middle cerebral arteries (middle cerebral artery pulsatility index) were analyzed, and the cerebroplacental ratio (middle cerebral artery pulsatility index/umbilical artery pulsatility index) computed. Umbilical artery pulsatility indices >90th and cerebroplacental ratios <10th centile were considered abnormal. Using data from the control fetuses, the centile for each of the cardiac measurements was categorized by whether it was <10th or >90th centile, depending upon the measurement. RESULTS: Of the 50 fetuses with estimated fetal weight <10th centile, 50% (n = 25) had a normal umbilical artery pulsatility index and cerebroplacental ratio. These fetuses had significantly more (P < 0.02 to <0.0001) abnormalities of the size and shape of the 4-chamber view than controls. In all, 44% had a 4-chamber view area >90th centile, 32% had a 4-chamber view global sphericity index <10th centile, 56% had a 4-chamber view width >90th centile, and 80% had 1 or more abnormalities of size and/or shape. The remaining 50% of fetuses (n = 25) had abnormalities of 1 or both for the umbilical artery pulsatility index and/or cerebroplacental ratio. These fetuses had significantly higher rates of abnormalities (P <0.05 to <0.0001) than controls for the following 4-chamber view measurements: 36% had a 4-chamber view area >90th centile; 28% had a 4-chamber view global sphericity index <10th centile; and 68% had a 4-chamber view width >90th centile. Only those fetuses with an abnormal umbilical artery pulsatility index had significant changes in ventricular size; 56% had a left ventricular area <10th centile; 28% had a right ventricular area <10th centile; 36% had right ventricular/left ventricular area ratio >90th centile. One or more of the above abnormal measurements were present in 92% of the fetuses. CONCLUSION: Higher rates of abnormalities of cardiac size and shape of the 4-chamber view were found in fetuses with an estimated fetal weight <10th centile, regardless of their umbilical artery pulsatility index and cerebroplacental ratio measurements. Those with a normal umbilical artery pulsatility index and an abnormal cerebroplacental ratio had larger and wider measurements of the 4-chamber view. In addition, the shape of the 4-chamber view was more globular or round than in controls. These fetuses may have an increased risk of perinatal complications and childhood and/or adult cardiovascular disease. Screening tools derived from the 4-chamber view, acting as surrogates for ventricular dysfunction, may identify fetuses who could benefit from further comprehensive testing and future preventive interventions.

Subsequent pregnancy outcomes after open maternal-fetal surgery for myelomeningocele.

BACKGROUND: Open maternal-fetal surgery for fetal myelomeningocele results in reduction in neonatal morbidity related to spina bifida but may be associated with fetal, neonatal, and maternal complications in subsequent pregnancies. OBJECTIVE: The objective of this study was to ascertain obstetric risk in subsequent pregnancies after open maternal-fetal surgery for fetal myelomeningocele closure. STUDY DESIGN: An international multicenter prospective observational registry created to track and report maternal, obstetric, fetal/neonatal, and subsequent pregnancy outcomes following open maternal-fetal surgery for fetal myelomeningocele was evaluated for subsequent pregnancy outcome variables. Institutional Review Board approval was obtained for the registry. RESULTS: From 693 cases of open maternal-fetal surgery for fetal myelomeningocele closure entered into the registry, 77 subsequent pregnancies in 60 women were identified. The overall live birth rate was 96.2%, with 52 pregnancies delivering beyond 20 weeks gestational age and median gestational age at delivery of 37 (36.3-37.1) weeks. The uterine rupture rate was 9.6% (n = 5), resulting in 2 fetal deaths. Maternal transfusion was required in 4 patients (7.7%). CONCLUSION: The risk of uterine rupture or dehiscence in subsequent pregnancies with associated fetal morbidity after open maternal-fetal surgery is significant, but is similar to that reported for subsequent pregnancies after classical cesarean deliveries. Future pregnancy considerations should be included in initial counseling for women contemplating open maternal-fetal surgery.

A New Modified Surgical Technique of In Situ Reverse Arterialization: Leaving the Distal Saphenous Side Branches Open of Nonreconstructable Ischemic Leg Leads to Full Recovery.

BACKGROUND: Arterialization of the foot veins in patients with ischemic foot usually result in excessive foot edema, wound infection, venous gangrene, long hospitalization duration, and a high rate of amputation. We herein present an improved method of foot revascularization via the superficial venous system by in situ reverse arterialization (ISRA) of the foot venous bed, leaving the distal saphenous side branches open. METHODS: A 69-year-old patient with toe wet gangrene and end-stage peripheral vascular disease with absence of foot target arteries underwent ISRA procedure, using the great saphenous vein, which was anastomosed end-to-side to the proximal superficial femoral artery. Only proximal saphenous tributaries were ligated until arterial flow reached the pedal superficial veins. RESULTS: Postoperatively, the foot regained normal pulsation over the superficial venous system. The patient did not experience foot edema. On-table subtraction angiography demonstrated arterial flow through the long saphenous and dorsal foot veins, with returned venous flow through the anterior and posterior tibial veins. Methoxyisobutylisonitrile scan conducted 4 weeks postoperatively demonstrated positive oxygen uptake of the pedal muscles, which was absent before surgery. Electron microscopy of the muscles at the level of the transmetatarsal amputation demonstrated regeneration of muscle tissue with mitosis 6 weeks postoperatively. During 1,000 days of follow-up postsurgery, the flow was reduced and the transcutaneous pO2 level of the foot increased up to 76 mm Hg. CONCLUSIONS: This new modified surgical technique of ISRA, in which only proximal saphenous tributaries were ligated in order to prevent high systemic pressure in the foot venous low pressure system, resulted in increased levels of transcutaneous pO2 and reduced flow, leading to full recovery of the ischemic foot.

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair.

INTRODUCTION: The use of perioperative tocolytic agents in fetal surgery is imperative to prevent preterm labor. Indomethacin, a well-known tocolytic agent, can cause ductus arteriosus (DA) constriction. We sought to determine whether a relationship exists between preoperative indomethacin dosing and fetal DA constriction. MATERIALS AND METHODS: This is an IRB-approved, single-center retrospective observational case series of 42 pregnant mothers who underwent open fetal myelomeningocele repair. Preoperatively, mothers received either 1 (QD) or 2 (BID) indomethacin doses. Maternal anesthetic drug exposures and fetal cardiac dysfunction measures were collected from surgical and anesthesia records and intraoperative fetal echocardiography. Pulsatility Index was used to calculate DA constriction severity. Comparative testing between groups was performed using t- and chi-square testing. RESULTS: DA constriction was observed in all fetuses receiving BID indomethacin and in 71.4% of those receiving QD dosing (p = 0.0002). Severe DA constriction was observed only in the BID group (35.7%). QD indomethacin group received more intraoperative magnesium sulfate (p < 0.0001). Minimal fetal cardiac dysfunction (9.5%) and bradycardia (9.5%) were observed in all groups independent of indomethacin dosing. CONCLUSIONS: DA constriction was the most frequent and severe in the BID indomethacin group. QD indomethacin and greater magnesium sulfate dosing was associated with reduced DA constriction.

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.

Natural History of Fetal Lower Urinary Tract Obstruction with Normal Amniotic Fluid Volume at Initial Diagnosis.

OBJECTIVE: The aim of this study was to define the natural history of lower urinary tract obstruction (LUTO) with normal midgestational amniotic fluid volumes. MATERIALS AND METHODS: We performed a retrospective review of 32 consecutive patients with LUTO with normal midgestational amniotic fluid volume followed at 11 North American Fetal Therapy Network (NAFTNet) centers from August 2007 to May 2012. Normal amniotic fluid volume was defined as an amniotic fluid index (AFI) of ≥9 cm. RESULTS: The mean gestational age (GA) and AFI at enrollment were 23.1 ± 2.1 weeks and 15.8 ± 3.9 cm, respectively. The mean GA at delivery was 37.3 ± 2.8 weeks. The mean creatinine level at discharge was 1.2 ± 0.8 mg/dL. Perinatal survival was 97%. Twenty-five patients returned for serial postnatal assessment. Renal replacement therapy (RRT) was required in 32%. Development of oligohydramnios and/or anhydramnios, development of cortical renal cysts, posterior urethral valves, prematurity, and prolonged neonatal intensive care unit stay were associated with need for RRT (p < 0.05) by univariate analysis. By multivariate analysis, preterm delivery remained predictive of need for RRT (p = 0.004). CONCLUSION: Prenatal diagnosis of LUTO with normal midgestational amniotic fluid volumes is associated with acceptable renal function in the majority of patients. Approximately one-third of these children require RRT. Surrogate markers of disease severity appear to be predictive of need for RRT.