RESUMEN
The Renal Anhydramnios Fetal Therapy (RAFT) trial is a study of serial amnioinfusions to prevent lethal neonatal pulmonary hypoplasia from early renal anhydramnios. Infant neurologic outcomes were not originally evaluated. We describe the high incidence of stroke observed among infants in the treatment arm of the trial at our center.
Asunto(s)
Accidente Cerebrovascular , Humanos , Femenino , Incidencia , Accidente Cerebrovascular/epidemiología , Embarazo , Recién Nacido , Masculino , Terapias Fetales/métodos , Oligohidramnios/epidemiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Pulmón/diagnóstico por imagen , Pulmón/anomalías , Anomalías MúltiplesRESUMEN
30% of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared inter-twin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia polycythemia sequence, providing management recommendations based on the available evidence. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the inter-twin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by post-treatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery should not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia polycythemia sequence minimally requires either middle cerebral artery Doppler peak systolic velocity values >1.5 multiples of the median and <1.0 multiples of the median in donor and recipient twins, respectively, or an inter-twin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); (14) consultation with a specialized fetal care center is recommended when twin anemia polycythemia sequence progresses to a more advanced disease stage (≥ stage II) prior to 32 weeks of gestation or when concern arises for co-existing complications such as twin-twin transfusion syndrome (Best Practice).
RESUMEN
Bilateral renal agenesis (BRA) is a fetal anomaly which leads to anhydramnios and resultant pulmonary hypoplasia. Historically, this anomaly was universally fatal early in the neonatal period due to the severity of the associated lung disease. Over the last 30 years, innovations in fetal therapies-specifically, serial amnioinfusions-have led to instances of infant pulmonary survival and initiation of postnatal dialysis, raising the possibility that early neonatal death may not be inevitable. Amnioinfusions are not without risk, and maternal complications can include prelabor rupture of membranes, preterm labor, infection, and bleeding. The data detailing neonatal outcomes are still limited and actively being collected. Two case series and one non-randomized clinical trial have supplied most of the known outcome data for infants with BRA after prenatal amnioinfusion. Although there are survivors reported in the literature, mortality remains high, with many deaths in infancy due to dialysis-associated sepsis. In addition, previously unknown morbidities have been documented in these infants, including neurologic injury. These challenges, in addition to the mechanical difficulties of providing dialysis to extremely small infants, can result in significant burdens for patients and their caregivers and moral distress for the health care team. The present review aims to explain the pathophysiology of BRA, detail the historical context and rationale for serial amnioinfusions to treat the pulmonary insufficiency associated with BRA, describe the available data regarding outcomes of infants born following prenatal amnioinfusions, discuss ethical issues surrounding this fetal intervention, and describe critical aspects of prenatal counseling for patients considering the intervention.
RESUMEN
OBJECTIVE: Risks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long-term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies. METHOD: We used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies. RESULTS: Clinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk-benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place. CONCLUSION: Considering these points may advance the interests of fetuses, future children, and their families.
Asunto(s)
Terapias Fetales , Atención Prenatal , Embarazo , Femenino , Niño , Humanos , Feto , Medición de Riesgo , Terapias en InvestigaciónRESUMEN
OBJECTIVE: Fetal megacystis generally presents as suspected lower urinary tract obstruction (LUTO), which is associated with severe perinatal morbidity. Genetic etiologies underlying LUTO or a LUTO-like initial presentation are poorly understood. Our objectives are to describe single gene etiologies in fetuses initially ascertained to have suspected LUTO and to elucidate genotype-phenotype correlations. METHODS: A retrospective case series of suspected fetal LUTO positive for a molecular diagnosis was collected from five centers in the Fetal Sequencing Consortium. Demographics, sonograms, genetic testing including variant classification, and delivery outcomes were abstracted. RESULTS: Seven cases of initially prenatally suspected LUTO-positive for a molecular diagnosis were identified. In no case was the final diagnosis established as urethral obstruction that is, LUTO. All variants were classified as likely pathogenic or pathogenic. Smooth muscle deficiencies involving the bladder wall and interfering with bladder emptying were identified in five cases: MYOCD (2), ACTG2 (2), and MYH11 (1). Other genitourinary and/or non-genitourinary malformations were seen in two cases involving KMT2D (1) and BBS10 (1). CONCLUSION: Our series illustrates the value of molecular diagnostics in the workup of fetuses who present with prenatally suspected LUTO but who may have a non-LUTO explanation for their prenatal ultrasound findings.
Asunto(s)
Enfermedades Fetales , Obstrucción Uretral , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Enfermedades Fetales/diagnóstico , Obstrucción Uretral/diagnóstico por imagen , Obstrucción Uretral/genética , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/anomalías , Ultrasonografía , Ultrasonografía PrenatalRESUMEN
INTRODUCTION: Fetal aqueductal stenosis (AS) affects approximately 1:1,000 pregnancies. Obstruction of cerebral spinal fluid circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus and macrocephaly, which often necessitates cesarean section (CS). The purpose of this study was to describe maternal outcomes associated with fetal AS. METHODS: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects with a prenatal diagnosis of severe fetal central nervous system ventriculomegaly were recruited and followed longitudinally. Maternal events around the delivery of fetuses with AS were recorded and analyzed. RESULTS: Thirty-seven subjects with fetal AS confirmed by neonatal neuroimaging were analyzed. The average gestational age at delivery was 36.7 weeks. Overall, 86% were delivered by CS, and 62% of these were elective. Ninety-one percent of CSs were performed through a Pfannenstiel abdominal incision. A classical uterine incision was required in 13% of cesarean deliveries. The peripartum complication rate was 27%. CONCLUSION: Women carrying a fetus with AS were at risk for preterm birth, cesarean delivery, a classical uterine incision, and peripartum complications. These data highlight the maternal morbidity associated with fetal AS and the potential benefit of in utero therapy not only for neonatal outcomes but also for maternal outcomes.
RESUMEN
INTRODUCTION: The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early-onset fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches. METHODS: A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Anhydramnios Fetal Therapy (RAFT) trial. During the external pilot, higher amnioinfusion volumes were given less frequently; in the feasibility study, smaller volume amnioinfusions were administered more frequently. Procedural details, complications, and obstetric outcomes were compared between the two groups using Pearson's χ2 or Fisher's exact tests for categorical variables and Student's t tests or Wilcoxon rank-sum tests for continuous variables. The adjusted association between procedural details and chorioamniotic separation was obtained through a multivariate repeated measure logistic regression model. RESULTS: Eleven participants underwent 159 amnioinfusions (external pilot: 3 patients, 21 amnioinfusions; feasibility: 8 patients, 138 amnioinfusions). External pilot participants had fewer amnioinfusions (7 vs. 19.5 in the feasibility group, p = 0.04), larger amnioinfusion volume (750 vs. 500 mL, p < 0.01), and longer interval between amnioinfusions (6 [4-7] vs. 4 [3-5] days, p < 0.01). In the external pilot, chorioamniotic separation was more common (28.6% vs. 5.8%, p < 0.01), preterm prelabor rupture of membranes (PPROM) occurred sooner after amnioinfusion initiation (28 ± 21.5 vs. 75.6 ± 24.1 days, p = 0.03), and duration of maintained amniotic fluid between first and last amnioinfusion was shorter (38 ± 17.3 vs. 71 ± 19 days, p = 0.03), compared to the feasibility group. While delivery gestational age was similar (35.1 ± 1.7 vs. 33.8 ± 1.5 weeks, p = 0.21), feasibility participants maintained amniotic fluid longer. CONCLUSION: Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.
RESUMEN
BACKGROUND: Intrauterine transfusion (IUT) is an invasive but critical and potentially life-saving intervention for severe fetal anemia with demonstrated improvement in outcomes. The fetus is vulnerable to hemodynamic alterations and transfusion-related adverse events; therefore, special consideration must be given to blood component selection and modification. There is widespread IUT practice variability, and existing guidance primarily relies on expert opinion and single center experiences. STUDY DESIGN AND METHODS: Experts in Maternal Fetal Medicine, Pediatric Hematology, and Transfusion Medicine from centers across the United States, collectively performing about 120 IUT annually, offer a multidisciplinary perspective on the performance of IUT and preparation of blood components. This perspective includes strategies for identifying an at-risk fetus, communicating between disciplines, determining the necessary blood volume, selecting and processing blood components, documenting the procedure in medical record, and managing the neonate. RESULTS: Identifying an at-risk fetus relies on review of the clinical history, non-invasive monitoring, and laboratory evaluation. We recommend the use of relatively fresh, group O, cytomegalovirus-safe, freshly irradiated, red blood cells (RBC) that are Hemoglobin S negative and antigen-negative for any maternal antibody, if indicated. These RBC units should be concentrated to remove additives and increase the hematocrit thus minimizing fluctuations in fetal volume status. The units intended for IUT should be labeled clearly and the documentation of transfusion differentiated in the maternal medical record. DISCUSSION: An awareness of the technical, logistical, and regulatory considerations for IUT performance will facilitate improved communication and patient care, especially when rare units of RBC are required.
Asunto(s)
Anemia , Eritroblastosis Fetal , Enfermedades Fetales , Femenino , Recién Nacido , Niño , Embarazo , Humanos , Eritroblastosis Fetal/terapia , Eritroblastosis Fetal/etiología , Transfusión de Sangre Intrauterina/efectos adversos , Eritrocitos , Anemia/etiologíaRESUMEN
OBJECTIVE: To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning. METHODS: The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks' gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments. RESULTS: Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities. CONCLUSIONS: This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.
Asunto(s)
Meningomielocele , Espina Bífida Quística , Embarazo , Femenino , Humanos , Meningomielocele/diagnóstico por imagen , Meningomielocele/cirugía , Placenta/diagnóstico por imagen , Placenta/cirugía , Espina Bífida Quística/cirugía , Fetoscopía/métodos , Feto/diagnóstico por imagen , Feto/cirugíaRESUMEN
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.
Asunto(s)
Terapias Fetales , Soluciones Isotónicas , Enfermedades Renales , Enfermedades Pulmonares , Oligohidramnios , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Terapias Fetales/métodos , Edad Gestacional , Riñón/diagnóstico por imagen , Enfermedades Renales/complicaciones , Enfermedades Renales/congénito , Enfermedades Renales/mortalidad , Enfermedades Renales/terapia , Estudios Prospectivos , Infusiones Parenterales/métodos , Oligohidramnios/etiología , Oligohidramnios/mortalidad , Oligohidramnios/terapia , Enfermedades Fetales/etiología , Enfermedades Fetales/mortalidad , Enfermedades Fetales/terapia , Enfermedades Pulmonares/congénito , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/terapia , Soluciones Isotónicas/administración & dosificación , Soluciones Isotónicas/uso terapéutico , Ultrasonografía Intervencional , Resultado del Embarazo , Resultado del Tratamiento , Nacimiento Prematuro/etiología , Nacimiento Prematuro/mortalidadRESUMEN
BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.
Asunto(s)
Atención Prenatal , Espina Bífida Quística/cirugía , Adolescente , Adulto , Femenino , Fetoscopía , Salud Global , Humanos , Histerotomía , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Guías de Práctica Clínica como Asunto , Embarazo , Sociedades Médicas , Adulto JovenRESUMEN
Since the completion of the Management of Myelomeningocoele Study, maternal-fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high-grade evidence.
Asunto(s)
Fetoscopía/normas , Meningomielocele/cirugía , Procedimientos Neuroquirúrgicos/normas , Adulto , Femenino , Fetoscopía/métodos , Fetoscopía/estadística & datos numéricos , Humanos , Meningomielocele/epidemiología , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Embarazo , Disrafia Espinal/cirugíaRESUMEN
INTRODUCTION: Prenatal closure of open spina bifida via open fetal surgery improves neurologic outcomes for infants in selected pregnancies. Fetoscopic techniques that are minimally invasive to the uterus aim to provide equivalent fetal benefits while minimizing maternal morbidities, but the optimal technique is undetermined. We describe the development, evolution, and feasibility of the laparotomy-assisted 2-port fetoscopic technique for prenatal closure of fetal spina bifida in a newly established program. METHODS: We conducted a retrospective cohort study of women consented for laparotomy-assisted fetoscopic closure of isolated fetal spina bifida. Inclusion and exclusion criteria followed the Management of Myelomeningocele Study (MOMS). Team preparation involved observation at the originating center, protocol development, ancillary staff training, and surgical rehearsal using patient-matched models through simulation prior to program implementation. The primary outcome was the ability to complete the repair fetoscopically. Secondary maternal and fetal outcomes to assess performance of the technique were collected prospectively. RESULTS: Of 57 women screened, 19 (33%) consented for laparotomy-assisted 2-port fetoscopy between February 2017 and December 2019. Fetoscopic closure was completed in 84% (16/19) cases. Over time, the technique was modified from a single- to a multilayer closure. In utero hindbrain herniation improved in 86% (12/14) of undelivered patients at 6 weeks postoperatively. Spontaneous rupture of membranes occurred in 31% (5/16) of fetoscopic cases. For completed cases, median gestational age at birth was 37 (range 27-39.6) weeks and 50% (8/16) of women delivered at term. Vaginal birth was achieved in 56% (9/16) of patients. One newborn had a cerebrospinal fluid leak that required postnatal surgical repair. CONCLUSION: Implementation of a laparotomy-assisted 2-port fetoscopic spina bifida closure program through rigorous preparation and multispecialty team training may accelerate the learning curve and demonstrates favorable obstetric and perinatal outcomes.
Asunto(s)
Meningomielocele , Disrafia Espinal , Femenino , Fetoscopía/efectos adversos , Humanos , Lactante , Recién Nacido , Laparotomía , Meningomielocele/cirugía , Embarazo , Estudios Retrospectivos , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/cirugíaRESUMEN
OBJECTIVE: We sought to evaluate the performance of exome sequencing (ES) in determining an underlying genetic etiology for cases of fetal pleural effusions. STUDY DESIGN: We examined a prospective cohort series of fetal pleural effusions visualized sonographically between 1 April 2016 and 31 August 2017. Fetal pleural effusions attributed to twin sharing, anemia, or structural anomalies were excluded, as were all cases with a genetic diagnosis established by karyotype or chromosomal microarray analysis. The remaining cases with pleural effusions of unclear etiology were offered ES. ES was performed by clinical sequencing and/or sequencing under the Baylor-Hopkins Center for Mendelian Genomics' (BHCMG) research platform. All cases were evaluated for novel genes or phenotypic expansion of disease-causing genes. RESULTS: ES was performed on six probands affected by pleural effusions. A pathogenic variant was identified in one case (16.7%). Four additional cases had variants of uncertain significance (VUS) in candidate genes of pathological interest. Neither clinical nor candidate genes were evident in the final case. CONCLUSION: ES should be considered in the evaluation of prenatally detected idiopathic pleural effusions when other diagnostic workup for a genetic etiology has failed.
Asunto(s)
Secuenciación del Exoma , Enfermedades Fetales/genética , Derrame Pleural/genética , Actinina/genética , Moléculas de Adhesión Celular/genética , Estudios de Cohortes , Proteínas de la Matriz Extracelular/genética , Pestañas/anomalías , Femenino , Enfermedades Fetales/diagnóstico por imagen , Factores de Transcripción Forkhead/genética , Humanos , Linfedema/diagnóstico , Linfedema/genética , Derrame Pleural/diagnóstico por imagen , Embarazo , Estudios Prospectivos , Receptor EphB4/genética , Canal Liberador de Calcio Receptor de Rianodina/genéticaRESUMEN
BACKGROUND: The "double bubble" sign is an ultrasonographic finding that commonly represents duodenal atresia and is associated with trisomy 21. OBJECTIVES: We sought to evaluate the positive predictive value of a prenatally identified double bubble sign for duodenal atresia and the genetic etiologies associated with it. METHODS: We examined a retrospective cohort with prenatal double bubble sign between January 1, 2008, and June 30, 2017. Postnatal diagnoses were determined by review of operative reports and additional postnatal evaluation including cytogenetic analysis, molecular analysis, and/or clinical genetic evaluation. RESULTS: All live births at our institution with a prenatal double bubble sign had confirmed duodenal atresia. Additional anatomic anomalies and/or genetic abnormalities were identified in 62% of cases. Out of 21 cases, 6 had trisomy 21. Of the remaining 15 cases, 8 were nonisolated duodenal atresia, 3 of which had a heterotaxy syndrome. In the 7 isolated cases, 1 likely pathogenic chromosomal microdeletion was identified. CONCLUSIONS: Prenatal double bubble sign is a reliable predictor of duodenal atresia. In addition to trisomy 21, heterotaxy may be encountered. ZIC3 mutations as well as microdeletion of 4q22.3 may be underlying genetic etiologies to be considered in the diagnostic evaluation of a prenatal double bubble sign.
Asunto(s)
Obstrucción Duodenal/diagnóstico por imagen , Atresia Intestinal/diagnóstico por imagen , Ultrasonografía Prenatal , Deleción Cromosómica , Cromosomas Humanos Par 4 , Síndrome de Down/genética , Obstrucción Duodenal/genética , Predisposición Genética a la Enfermedad , Edad Gestacional , Síndrome de Heterotaxia/genética , Humanos , Atresia Intestinal/genética , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de RiesgoAsunto(s)
Transfusión de Sangre Intrauterina , Eritroblastosis Fetal , Embarazo , Femenino , Humanos , Hidropesía Fetal , PartoRESUMEN
OBJECTIVE: Improvements in imaging and surgical technological innovations have led to the increasing implementation of fetal surgical techniques. Open fetal surgery has demonstrated more favorable clinical outcomes in children born with open myelomeningocele (MMC) than those following postnatal repair. However, primarily because of maternal risks but also because of fetal risks, fetal surgery for MMC remains controversial. Here, the authors evaluated the contemporary management of MMC in the hope of identifying barriers and facilitators for neurosurgeons in providing fetal surgery for MMC. METHODS: An online survey was emailed to members of the Congress of Neurological Surgeons (CNS) and the International Society for Pediatric Neurosurgery (ISPN) in March 2019. The survey focused on 1) characteristics of the respondents, 2) the practice of counseling on and managing prenatally diagnosed MMC, and 3) barriers, facilitators, and expectations of fetal surgery for MMC. Reminders were sent to improve the response rate. RESULTS: A total of 446 respondents filled out the survey, most (59.2%) of whom specialized in pediatric neurosurgery. The respondents repaired an average of 9.6 MMC defects per year, regardless of technique. Regardless of the departments in which respondents were employed, 91.0% provided postnatal repair of MMC, 13.0% open fetal repair, and 4.9% fetoscopic repair. According to the surgeons, the most important objections to performing open fetal surgery were a lack of cases available to become proficient in the technique (33.8%), the risk of maternal complications (23.6%), and concern for fetal complications (15.2%). The most important facilitators according to advocates of prenatal closure are a decreased rate of shunt dependency (37.8%), a decreased rate of hindbrain herniation (27.0%), and an improved rate of motor function (18.9%). Of the respondents, only 16.9% agreed that open fetal surgery should be the standard of care. CONCLUSIONS: The survey results showed diversity in the management of patients with MMC. In addition, significant diversity remains regarding fetal surgery for MMC closure. Despite the apparent benefits of open fetal surgery in selected pregnancies, only a minority of centers and providers offer this technique. As a more technically demanding technique that requires multidisciplinary effort with less well-established long-term outcomes, fetoscopic surgery may face similar limited implementation, although the surgery may pose fewer maternal risks than open fetal surgery. Centralization of prenatal treatment to tertiary care referral centers, as well as the use of sophisticated training models, may help to augment the most commonly cited objection to the implementation of prenatal closure, which is the overall limited caseload.
Asunto(s)
Meningomielocele/cirugía , Neurocirujanos , Procedimientos Neuroquirúrgicos , Rombencéfalo/anomalías , Femenino , Fetoscopía/métodos , Feto/cirugía , Humanos , Procedimientos Neuroquirúrgicos/métodos , EmbarazoRESUMEN
INTRODUCTION: The insertion site of the fetoscope for laser occlusion (FLOC) treatment of twin-twin transfusion syndrome (TTTS) determines the likelihood of treatment success. We assessed a standardized preoperative ultrasound approach for its ability to identify critical landmarks for successful FLOC. METHODS: Three surgeons independently performed preoperative ultrasound and deduced the likely orientation of the intertwin membrane (ITM) and vascular equator (VE) based on the sites of the cord insertion, the lie of the donor, and the size discordance between twins. At FLOC, these landmarks were visually verified and compared to preoperative assessments. RESULTS: Fifty consecutive FLOC surgeries had 127 preoperative assessments. Basic ITM and VE orientation were accurately predicted in 115 (90.6%), 109 (85.8%), and 105 (82.7%) assessments. Predictions were anatomically correct in 96 (75.6%), 70 (55.1%), and 58 (45.7%) assessments with no differences in accuracy between operators of different training level. The ITM/VE relationship was most poorly predicted in stage-3 TTTS (χ2, p = 0.016). CONCLUSION: In TTTS, preoperative ultrasound identification of placental cord insertion sites, lie of the donor twin, and size discordance enables preoperative prediction of key landmarks for successful FLOC.
Asunto(s)
Transfusión Feto-Fetal/cirugía , Fetoscopía/métodos , Coagulación con Láser/métodos , Embarazo Gemelar , Cuidados Preoperatorios/métodos , Ultrasonografía Prenatal/métodos , Femenino , Transfusión Feto-Fetal/diagnóstico por imagen , Fetoscopía/tendencias , Humanos , Recién Nacido , Coagulación con Láser/tendencias , Valor Predictivo de las Pruebas , Embarazo , Cuidados Preoperatorios/tendencias , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía Prenatal/tendenciasRESUMEN
INTRODUCTION: To evaluate if the volume-corrected renal artery pulsatility index (vcRA-PI) is more closely related to the amniotic fluid level than the uncorrected or the gestational age (GA)-adjusted RA-PI. METHODS: RA-PI and kidney volume were measured in low- and high-risk pregnancies at 17-38 weeks. Fetal anomalies associated with nonrenal causes of abnormal amniotic fluid volume were excluded. The vcRA-PI was calculated by dividing the RA-PI by the renal volume. The RA-PI was adjusted for GA, to obtain the GA-adjusted RA-PI. The uncorrected, GA-adjusted, and the vcRA-PI were related to the amniotic fluid level using nonparametric tests and receiver operating characteristic (ROC) curve analyses. RESULTS: 146 examinations from 59 pregnancies were reviewed. Of these, 16 had oligo- and 15 had polyhydramnios. A higher vcRA-PI was associated with oligohydramnios (OR 2.54, 95% CI 1.67-3.86, p < 0.001), while the uncorrected RA-PI and GA-adjusted RA-PI were not able to predict oligohydramnios. ROC curve analysis showed a high predictive accuracy of the vcRA-PI for oligohydramnios (AUC 0.84, 95% CI 0.72-0.94). On the other hand, the uncorrected RA-PI and GA-adjusted RA-PI significantly predicted polyhydramnios (p = 0.04 and 0.02, respectively), while the vcRA-PI did not. CONCLUSION: The vcRA-PI is superior to the uncorrected and the GA-adjusted RA-PI in predicting oligohydramnios.
Asunto(s)
Líquido Amniótico/diagnóstico por imagen , Riñón/irrigación sanguínea , Flujo Pulsátil , Arteria Renal/fisiología , Femenino , Humanos , Riñón/diagnóstico por imagen , Riñón/embriología , Embarazo , Estudios Retrospectivos , Ultrasonografía PrenatalRESUMEN
Fetomaternal hemorrhage (FMH) is a rare condition that requires early diagnosis and appropriate treatment due to its potentially severe consequences. We report a case of massive FMH presenting as decreased fetal movement, fetal hydrops, and intracranial hemorrhage at 24 weeks. Treatment considerations were made and amniocentesis, fetal blood sampling, and fetal blood transfusion via cordocentesis were performed. Recurrent FMH required subsequent fetal transfusion 2 days later. Surveillance was continued twice weekly until the patient delivered a viable infant at 38 weeks after spontaneous labor. Recurrent FMH was unpredictable due to its unclear etiology and absence of precipitating events, however close surveillance proved effective.