Outcomes of an Individualized Hybrid Model for Repair of Infants With Congenital Diaphragmatic Hernia Requiring Extracorporeal Life Support.

Introduction: Timing of repair for infants with congenital diaphragmatic hernia (CDH) requiring extracorporeal life support (ECLS) remains controversial. Approaches include early repair on ECLS, late repair on ECLS, or repair after ECLS decannulation; all have potential risks and benefits. To mitigate risk and maximize benefit, our group developed an individualized hybrid model in 2016 in which approach is based on prenatal risk stratification.

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.

Patterns and Outcomes of Epoprostenol Use in Infants with Congenital Diaphragmatic Hernia Requiring Extracorporeal Life Support.

Objective: To describe our experience utilizing epoprostenol for pulmonary hypertension (PH) in infants with congenital diaphragmatic hernia (CDH) requiring extracorporeal life support (ECLS).

Study Design: We retrospectively reviewed infants diagnosed with CDH who required ECLS at our institution from 2013 to 2023. Data collected included demographics, disease characteristics, medication administration patterns, and hospital outcomes.

Surgical approaches to congenital diaphragmatic hernia.

Surgical repair of the diaphragm is essential for survival in congenital diaphragmatic hernia (CDH). There are many considerations surrounding the operation - why the operation matters, optimal timing of repair and its relation to extracorporeal life support (ECLS) use, minimally invasive versus open approaches, and strategies for reconstruction. Surgery is both affected by, and affects, the physiology of these infants and is an important factor in determining long-term outcomes.

The role of fetal hemoglobin in the artificial placenta: A premature ovine model.

Introduction: A radical paradigm shift in the treatment of premature infants failing conventional treatment is to recreate fetal physiology using an extracorporeal Artificial Placenta (AP). The aim of this study is to evaluate the effects of changing fetal hemoglobin percent (HbF%) on physiology and circuit function during AP support in an ovine model.

Methods: Extremely premature lambs ( = 5) were delivered by cesarean section at 117-121 d estimated gestational age (EGA) (term = 145d), weighing 2.

Thoracoscopic Patch Repair of Congenital Diaphragmatic Hernia: Can Smaller Incisions Treat Larger Defects?

Introduction: Thoracoscopic CDH repair is increasingly performed for Type A and small Type B defects that are amenable to primary repair. However, the thoracoscopic approach is controversial for larger defects necessitating a patch due to technical complexity, intraoperative acidosis, and recurrence risk. We aim to compare clinical outcomes between thoracoscopic and open patch repair of Type B/C defects, using a standardized technique.

The new frontier in ECLS: Artificial placenta and artificial womb for premature infants.

Outcomes for extremely low gestational age newborns (ELGANs), defined as <28 weeks estimated gestational age (EGA), remain disproportionately poor. A radical paradigm shift in the treatment of prematurity is to recreate the fetal environment with extracorporeal support and provide an environment for organ maturation using an extracorporeal VV-ECLS artificial placenta (AP) or an AV-ECLS artificial womb (AW). In this article, we will review clinical indications, current approaches in development, ongoing challenges, remaining milestones and ethical considerations prior to clinical translation.

Prenatal Measurements of Congenital Lung Malformations: Can They Predict Postnatal Size?

Introduction: Prenatally diagnosed congenital lung malformations (CLMs) are monitored via ultrasound and measured by congenital pulmonary airway malformation volume ratios (CVRs) which can predict postnatal respiratory symptoms. This study compared CVR to postnatal lesion size to help guide prenatal counseling.

Methods: A retrospective chart review evaluated the prenatal imaging and postnatal outcomes for patients who were prenatally diagnosed with CLMs and had a postnatal computed tomography (CT) scan at one institution.

Ethical challenges in first-in-human trials of the artificial placenta and artificial womb: not all technologies are created equally, ethically.

Artificial placenta and artificial womb technologies to support extremely premature neonates are advancing toward clinical testing in humans. Currently, no recommendations exist comparing these approaches to guide study design and optimal enrollment eligibility adhering to principles of research ethics. In this paper, we will explore how scientific differences between the artificial placenta and artificial womb approaches create unique ethical challenges to designing first-in-human trials of safety and provide recommendations to guide ethical study design for initial human translation.

Extracorporeal life support without systemic anticoagulation: a nitric oxide-based non-thrombogenic circuit for the artificial placenta in an ovine model.

Background: Clinical translation of the extracorporeal artificial placenta (AP) is impeded by the high risk for intracranial hemorrhage in extremely premature newborns. The Nitric Oxide Surface Anticoagulation (NOSA) system is a novel non-thrombogenic extracorporeal circuit. This study aims to test the NOSA system in the AP without systemic anticoagulation.

Neonatal pneumothorax in congenital diaphragmatic hernia: Be wary of high ventilatory pressures.

Background: Patients with congenital diaphragmatic hernia (CDH) require invasive respiratory support and higher ventilator pressures may be associated with barotrauma. We sought to evaluate the risk factors associated with pneumothorax in CDH neonates prior to repair.

Methods: We retrospectively reviewed newborns born with CDH between 2014 and 2019 who developed a pneumothorax, and we matched these cases to patients with CDH without pneumothorax.

Milestones for clinical translation of the artificial placenta.

Despite significant advances in the treatment of prematurity, premature birth results in significant mortality and morbidity. In particular, extremely low gestational age newborns (ELGANs) defined as <28 weeks estimated gestational age (EGA) suffer from disproportionate mortality and morbidity. A radical paradigm shift in the treatment of prematurity is to recreate fetal physiology using an extracorporeal VV-ECLS artificial placenta (AP) or an AV-ECLS artificial womb (AW).

Updates in Neonatal Extracorporeal Membrane Oxygenation and the Artificial Placenta.

Extracorporeal life support, initially performed in neonates, is now commonly used for both pediatric and adult patients requiring pulmonary and/or cardiac support. Data suggests the clinical feasibility of Extracorporeal Membrane Oxygenation for premature infants (29-33 weeks estimated gestational age [EGA]). For extremely premature infants less than 28 weeks EGA, an artificial placenta has been developed to recreate the fetal environment.

Care Levels for Fetal Therapy Centers.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties.

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).

Hepatic Function in Premature Lambs Supported by the Artificial Placenta and Total Parenteral Nutrition.

The artificial placenta (AP) promotes organ development and reduces organ injury in a lamb model of extreme prematurity. This study evaluates hepatic outcomes after AP support with total parenteral nutrition (TPN) administration. Premature lambs (116-121 days estimated gestational age; term = 145) were cannulated for 7 days of AP support.

A single institution's experience with the management of peripheral bronchial atresia.

Purpose: Peripheral bronchial atresia is a pulmonary abnormality diagnosed on postnatal computed tomography after prenatal imaging reveals a congenital lung lesion. Debate regarding management of this abnormality prompted us to review our institution's practice patterns and outcomes.

Methods: All patients diagnosed with bronchial atresia were assessed from 6/2014 to 7/2020.

Image-based prenatal predictors correlate with postnatal survival, extracorporeal life support use, and defect size in left congenital diaphragmatic hernia.

Objective: To evaluate the association between prenatal imaging predictors of patients with left-sided congenital diaphragmatic hernia (LCDH) and postnatal outcomes.

Study Design: CDH study group data were reviewed for LCDH infants born 2015-2019. Prenatal ultrasound (US) and magnetic resonance imaging (MRI) data were collected and correlated with postnatal information including CDHSG defect size (A through D or non-repair (NR)).

Development of an artificial placenta for support of premature infants: narrative review of the history, recent milestones, and future innovation.

Over 50 years ago, visionary researchers began work on an extracorporeal artificial placenta to support premature infants. Despite rudimentary technology and incomplete understanding of fetal physiology, these pioneering scientists laid the foundation for future work. The research was episodic, as medical advances improved outcomes of premature infants and extracorporeal life support (ECLS) was introduced for the treatment of term and near-term infants with respiratory or cardiac failure.

Conjoined twins: an obstetrician's guide to prenatal care and delivery management.

Objective: Obstetricians infrequently encounter conjoined twins. Much of the clinical care literature focuses on postnatal management from a neonatology and pediatric surgery perspective; guidance on obstetrical management is limited. We outline steps for prenatal evaluation, obstetrical care, and delivery planning.

Fetal hemoglobin levels in premature newborns. Should we reconsider transfusion of adult donor blood?

Purpose: The aim of this study was to assess the percent decrease in fetal hemoglobin (HbF) after transfusion of adult-derived donor packed red blood cell (pRBC) units in extremely low gestational age newborns (ELGANs).

Methods: Control percent fetal hemoglobin (%HbF) levels were measured in newborn cord blood or peripheral blood samples in non-transfused patients prior to elective surgery. ELGANs were followed prospectively and %HbF was measured on residual post-test complete blood count (CBC) specimens.

Switching to centrifugal pumps may decrease hemolysis rates among pediatric ECMO patients.

Recent advances in ECLS technology have led to the adoption of centrifugal pumps for the majority of patients worldwide. Despite several advantages of centrifugal pumps, they remain controversial because a number of studies have shown increased rates of hemolysis. The aim of this study was to assess the impact of transitioning from roller to centrifugal pumps on hemolysis rates at our center.