Large prospective clinical trials are underway or planned that examine the clinical utility and cost effectiveness of genome-based newborn screening (gNBS). One gNBS platform, BeginNGS, currently screens 53,575 variants for 412 severe childhood genetic diseases with 1,603 efficacious therapies. Retrospective evaluation of BeginNGS in 618,290 subjects suggests adequate sensitivity and positive predictive value (PPV) to proceed to prospective studies.
View Article and Find Full Text PDFObjective: The objective of this study is to describe the impact of rapid and ultra-rapid whole genome sequencing (rWGS/urWGS) on the care of neonatal intensive care (NICU) patients who require extracorporeal membrane oxygenation (ECMO).
Study Design: This is a retrospective cohort study at a single-center NICU in a tertiary children's hospital. The study population includes NICU patients treated with ECMO from May 2017 to September 2023.
Heritable pulmonary arterial hypertension (HPAH) is a rare progressive condition that includes patients with an identified genetic cause of pulmonary arterial hypertension (PAH). HPAH and idiopathic PAH (IPAH) have an estimated combined incidence of 0.5-0.
View Article and Find Full Text PDFPulmonary hypertension in the neonatal population can be acute or chronic and carries significant risk for morbidity and mortality. It can be idiopathic but more often is associated with comorbid pulmonary and heart disease. There are several pharmacotherapeutics aimed at pulmonary vasodilation.
View Article and Find Full Text PDFWhile many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance.
View Article and Find Full Text PDFGenetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility of broad clinical deployment has not been established.
View Article and Find Full Text PDFBackground/purpose: The purpose of this study was to evaluate the characteristics of neonates with congenital diaphragmatic hernia (CDH) undergoing enteral access procedures (gastrostomy or jejunostomy) during their initial hospitalization, and establish a clinical scoring system based on these characteristics.
Methods: Data were obtained from the multicenter, multinational CDH Study Group database (CDHSG Registry) between 2007 and 2019. Patients were randomly partitioned into model-derivation and validation subsets.
Genetic disorders presenting in the neonatal period can have a significant impact on morbidity and mortality. Early diagnosis can facilitate timely prognostic counseling to families and possibility of precision care, which could improve outcome. As availability of diagnostic testing expands, the required knowledge base of the neonatologist must also expand to include proper application and understanding of genetic testing modalities, especially where availability of clinical genetics consultation is limited.
View Article and Find Full Text PDFThe second Newborn Sequencing in Genomic Medicine and Public Health study was a randomized, controlled trial of the effectiveness of rapid whole-genome or -exome sequencing (rWGS or rWES, respectively) in seriously ill infants with diseases of unknown etiology. Here we report comparisons of analytic and diagnostic performance. Of 1,248 ill inpatient infants, 578 (46%) had diseases of unknown etiology.
View Article and Find Full Text PDFBy informing timely targeted treatments, rapid whole-genome sequencing can improve the outcomes of seriously ill children with genetic diseases, particularly infants in neonatal and pediatric intensive care units (ICUs). The need for highly qualified professionals to decipher results, however, precludes widespread implementation. We describe a platform for population-scale, provisional diagnosis of genetic diseases with automated phenotyping and interpretation.
View Article and Find Full Text PDFThe umbilical cord is tissue that is normally discarded after the delivery of the infant, but it has been shown to be a rich source of stem cells from the cord blood, Wharton's jelly, and umbilical endothelial cells. Patient-specific human induced pluripotent stem cells (hiPSCs) reprogrammed from patient specific human umbilical vein endothelial cells in the neonatal intensive care unit (NICU) population (specifically, premature neonates) have not been shown in the literature. This unit describes a protocol for the generation and expansion of hiPSCs originating from umbilical cords collected from patients in the NICU.
View Article and Find Full Text PDFObjective: To test the hypothesis that an educational intervention would improve the resuscitator's ability to provide on-target volume ventilation during pulmonary compliance changes.
Study Design: Neonatal professionals (n = 27) ventilated an electromechanical lung model simulating a 3-kg baby while targeting a tidal volume of 4-6 mL/kg. In this preintervention and postintervention study, a one-on-one educational intervention aimed to improve the primary outcome of on-target tidal volume delivery during high and low compliance.