Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.

Evaluation of the Fetal Therapy Evidence in Lower Urinary Tract Obstruction: Would an ERAS Guideline Improve Outcomes?

<b><i>Background:</i></b> Pregnancies that are prenatally identified to have fetal anomalies are complex and require expert multidisciplinary care. As many conditions can impact the fetus prenatally and require intervention, an enhanced recovery after surgery (ERAS) for lower urinary tract obstruction (LUTO) is being evaluated to determine the level of evidenced-based data available. <b><i>Problem:</i></b> The percutaneous ultrasound-guided fetal surgery procedure for bladder neck obstruction is the focus for elements of preoperative counseling, intraoperative procedure/risk complications, and postoperative management. <b><i>Methods:</i></b> A quality improvement review Squire 2.0 (2000–2020) was undertaken for the percutaneous LUTO fetal surgery shunting (lower urinary tract obstruction), process and procedure which require 2 process pathways, one to evaluate the fetal candidate and a second to treat. This structured review is focused on identifying the process elements to allow the determination of the number of evidenced-based elements that would allow for audit and measurement of the clinical element variance for comparative feedback to the individual surgical provider or surgery center. <b><i>Interventions:</i></b> Titles and abstracts were screened to identify potentially relevant articles with priority given to meta-analyses, systematic reviews, randomized controlled studies, nonrandomized controlled studies, reviews, and case series. <b><i>Results:</i></b> A series of potential clinical elements for the diagnostic fetal evaluation and for the 3 protocol areas of surgical care for the procedures (pre-, intra-, and postoperative care) are identified using an ERAS-like process. <b><i>Conclusions:</i></b> The identified clinical elements have the potential for ERAS-LUTO fetal therapy guideline. Multidisciplinary collaboration (surgeon, anesthesia, nursing, imaging, and laboratory) is required for ERAS quality improvement in the pre-, intra-, and postoperative processes. Process elements in each of the operative areas can be audited, evaluated, compared, and modified/improved.

Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis

The purpose of the study was to use exome sequencing (ES) to study the contribution of single-gene disorders to recurrent non-immune hydrops fetalis (NIHF) and retrospectively evaluate the value of genetic diagnosis on prenatal management and pregnancy outcome. From January 2012 to October 2018, a cohort of 28 fetuses with recurrent NIHF was analyzed by trio ES. Fetuses with immune hydrops, non-genetic factors (including infection, etc.), karyotype, or CNV abnormalities were excluded. Variants were interpreted based on ACMG/AMP guidelines. Fetal therapy was performed on seven fetuses. Of the 28 fetuses, 10 (36%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in eight genes (GBA, GUSB, GBE1, RAPSN, FOXC2, PIEZO1, LZTR1, and FOXP3). Five (18%) fetuses had variant(s) of uncertain significance (VUS). Of the 10 fetuses with definitive molecular diagnosis, five (50%) were diagnosed with inborn errors of metabolism. Among the seven fetuses who received fetal therapy, two had definitive molecular diagnosis and resulted in neonatal death. Among the remaining five fetuses with negative results, four had newborn survival and one had intrauterine fetal death. Trio ES could facilitate genetic diagnosis of recurrent NIHF and improve the prenatal management and pregnancy outcome.

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

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusions:</i></b> 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.