Placental Gene Therapy for Fetal Growth Restriction and Preeclampsia: Preclinical Studies and Prospects for Clinical Application.

In the last three decades, gene therapy has demonstrated significant progress. Over 700 active investigational new drug (IND) applications have been reported. Research on in utero gene therapy has advanced, but ethical and safety concerns persist.

Common variants increase risk for congenital diaphragmatic hernia within the context of de novo variants.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly often accompanied by other structural anomalies and/or neurobehavioral manifestations. Rare de novo protein-coding variants and copy-number variations contribute to CDH in the population. However, most individuals with CDH remain genetically undiagnosed.

Successful Postnatal Tracheobronchoplasty for Unilateral Congenital High Airway Obstruction Syndrome due to Mainstem Bronchial Atresia.

Introduction: Unilateral congenital high airway obstruction syndrome (CHAOS) is caused by a complete obstruction of a mainstem bronchus with resulting hyperinflation and accelerated growth of one lung, severe mediastinal shift, and hydrops. Spontaneous perforation of the atresia has been observed in CHAOS which allows hydrops to resolve but hyperinflation, mediastinal shift and a critical airway obstruction persists as the perforation is usually pinhole-sized.

Case Presentation: We present a case of unilateral CHAOS presenting at 26 2/7 weeks with observed-to-expected total lung volume (O/E TLV) of 203% with spontaneous perforation occurring at 28 weeks with resolution of hydrops but persistence of hyperinflation and mediastinal shift with an O/E TLV of 60.

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

Objective: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed.

Methods: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients.

Prenatal Recognition of Hepatopulmonary Fusion in Right-Sided Congenital Diaphragmatic Hernia for Successful Operative Planning.

Introduction: Hepatopulmonary fusion (HPF) is a rare anomaly specifically associated with right-sided congenital diaphragmatic hernia (CDH). Fewer than 50 cases of HPF have been reported, most at the time of surgery or postmortem with an associated high morbidity and mortality rate. Prenatal diagnosis and optimal management of these rare cases have not been established.

Being small for gestational age is not an independent risk factor for mortality in neonates with congenital diaphragmatic hernia: a multicenter study.

Background: Congenital diaphragmatic hernia (CDH) accounts for 8% of all major congenital anomalies. Neonates who are small for gestational age (SGA) generally have a poorer prognosis. We sought to identify risk factors and variables associated with outcomes in neonates with CDH who are SGA in comparison to neonates who are appropriate for gestational age (AGA).

Amniotic Fluid microRNA in Severe Twin-Twin Transfusion Syndrome Cardiomyopathy-Identification of Differences and Predicting Demise.

Twin-twin transfusion syndrome (TTTS) is a rare but serious cause of fetal cardiomyopathy with poorly understood pathophysiology and challenging prognostication. This study sought a nonbiased, comprehensive assessment of amniotic fluid (AF) microRNAs from TTTS pregnancies and associations of these miRNAs with clinical characteristics. For the discovery cohort, AF from ten fetuses with severe TTTS cardiomyopathy were selected and compared to ten normal singleton AF.

Pediatric mediastinal mass algorithm: A quality improvement initiative to reduce time from presentation to biopsy.

Background: Mediastinal masses in children may present with compression of the great vessels and airway. An interdisciplinary plan for rapid diagnosis, acute management, and treatment prevents devastating outcomes and optimizes care. Emergency pretreatment with steroids or radiation is more likely to be administered when care is variable, which may delay and complicate diagnosis and treatment.

Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes.

Purpose: Congenital diaphragmatic hernia (CDH) is associated with significant mortality and long-term morbidity in some but not all individuals. We hypothesize monogenic factors that cause CDH are likely to have pleiotropic effects and be associated with worse clinical outcomes.

Methods: We enrolled and prospectively followed 647 newborns with CDH and performed genomic sequencing on 462 trios to identify de novo variants.

Comparative outcomes of right versus left congenital diaphragmatic hernia: A multicenter analysis.

Background: Congenital diaphragmatic hernia (CDH) occurs in 1 out of 2500-3000 live births. Right-sided CDHs (R-CDHs) comprise 25% of all CDH cases, and data are conflicting on outcomes of these patients. The aim of our study was to compare outcomes in patients with right versus left CDH (L-CDH).

Error traps in fetal surgery.

The growth of the field of fetal surgery over the last two decades driven by new indications and data from prospective randomized trials supporting prenatal intervention has resulted in techniques protocols and methodologies that have gained confidence by insuring good outcomes. Error traps are methods or techniques that usually work well in most of the cases, but which are apt to fail under certain specific circumstances. The very confidence the surgeon develops in these techniques or methodologies makes them a trap for the unwary surgeon.

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders.

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study.

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.

Intrauterine growth restriction decreases NF-κB signaling in fetal pulmonary artery endothelial cells of fetal sheep.

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia, a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis; however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The NF-κB pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NF-κB-regulated proangiogenic targets in fetal PAEC.

Impact of Objective Echocardiographic Criteria for Timing of Congenital Diaphragmatic Hernia Repair.

Objective: To assess the impact of specific echocardiographic criteria for timing of congenital diaphragmatic hernia repair on the incidence of acute postoperative clinical decompensation from pulmonary hypertensive crisis and/or acute respiratory decompensation, with secondary outcomes including survival to discharge, duration of ventilator support, and length of hospitalization.

Study Design: The multidisciplinary congenital diaphragmatic hernia management team instituted a protocol in 2012 requiring the specific criterion of echocardiogram-estimated pulmonary artery pressure ≤80% systemic blood pressure before repairing congenital diaphragmatic hernias. A retrospective review of 77 neonatal patients with Bochdalek hernias repaired between 2008 and 2015 were reviewed: group 1 included patients repaired before protocol implementation (n = 25) and group 2 included patients repaired after implementation (n = 52).

Modified Hysterotomy Closure Technique for Open Fetal Surgery.

Objective: We reviewed our experience with open fetal surgical myelomeningocele repair to assess the efficacy of a new modification of the hysterotomy closure technique regarding hysterotomy complication rates at the time of cesarean delivery.

Methods: A modification of the standard hysterotomy closure was performed on all patients undergoing prenatal myelomeningocele repair. The closure consisted of an interrupted full-thickness #0 polydioxanone (PDS) retention suture as well as a running #0 PDS suture to re-approximate the myometrial edges, and the modification was a third imbricating layer resulting in serosal-to-serosal apposition.

Case report of myometrial window following fetoscopic treatment of twin-twin transfusion syndrome: indications of underlying collagen vascular disease?

Intraperitoneal amniotic fluid leak is a known complication of fetoscopic procedures that usually resolves spontaneously with expectant management. Intraperitoneal amniotic fluid leak may persist after fetoscopic procedures due to a myometrial window as well as to persistent chorioamniotic membrane disruption, which may be amenable to surgical repair.

Ex utero Intrapartum Treatment to Ventricular Pacing: A Novel Delivery Strategy for Complete Atrioventricular Block with Severe Bradycardia.

Fetuses with anti-SSA-mediated complete atrioventricular block (CAVB) are at high risk for perinatal death if they present at <20 weeks of gestation and develop ventricular rates of <55 beats per minute (bpm), cardiac dysfunction, or hydrops [Izmirly et al.: Circulation 2011;124:1927-1935; Jaeggi et al.: J Am Coll Cardiol 2002;39:130-137; Eliasson et al.

Fetal Treatment 2017: The Evolution of Fetal Therapy Centers - A Joint Opinion from the International Fetal Medicine and Surgical Society (IFMSS) and the North American Fetal Therapy Network (NAFTNet).

More than 3 decades ago, a small group of physicians and other practitioners active in what they called "fetal treatment" authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful reassessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with a brief discussion of the necessary minimum expertise and systems base for the provision of different types of interventions for both the mother and fetus.

Pediatric Intraocular Immature Teratoma Associated With Sacrococcygeal Teratoma.

Intraocular teratomas are rare neoplasms with only three previously reported cases. We present the fourth case of intraocular teratoma and the second associated with sacrococcygeal teratoma. While the nature of the association between intraocular teratomas and sacrococcygeal teratomas is unclear, it suggests a need for careful ophthalmologic follow-up of infants with congenital sacrococcygeal teratomas.

A definition of gentle ventilation in congenital diaphragmatic hernia: a survey of neonatologists and pediatric surgeons.

Ventilation practices have changed significantly since the initial reports in the mid 1980 of successful use of permissive hypercapnia and spontaneous ventilation [often called gentle ventilation (GV)] in infants with congenital diaphragmatic hernia (CDH). However, there has been little standardization of these practices or of the physiologic limits that define GV. We sought to ascertain among Diaphragmatic Hernia Research and Exploration; Advancing Molecular Science (DHREAMS) centers' GV practices in the neonatal management of CDH.