“Newborn screening is a public health initiative. The goal is to look for disease where early identification makes a difference in the outcome as compared to identifying it symptomatically later in life.”- Dr. Jerry Vockley, UPMC Children’s Hospital, Speaker at PMWC Pittsburgh Sep. 23-24, 2021 (Program)

From Blood to Diagnosis in 13.5 Hours.
Newborn screening started with phenylketonuria (PKU), a rare inherited disorder that causes phenylalanine to build up in the body. Classical PKU is an autosomal recessive disorder in the gene phenylalanine hydroxylase (PAH) that creates the enzyme needed to break down phenylalanine. Not treating the disease early on results in intellectual, delayed development, and behavioral and emotional disorders. Recognizing PKU early can help prevent major health problems and offers the chance to completely reverse or avoid those symptoms. The baby is usually placed on a low phenylalanine diet for the rest of its life. Today, babies in the U.S. and many other countries are screened for PKU soon after birth.

The technology for newborn screening has changed over the last decade, but the goal has not
Today newborn screening is much more extensive–– depending on the U.S. state, 30-50 diseases are regularly assessed.

Dr. Stephen Kingsmore, Director & CEO Rady Children’s Institute of Genomic Medicine, Speaker at PMWC Pittsburgh: “15% of 250,000 U.S. NICU and PICU infants have 1 of 14,000 genetic diseases. The paradigm of standard of care medicine does not work for these children because there are 14,000 genetic diseases and they are inevitably misdiagnosed and mistreated.”

Whole genome sequencing is the hero of this story. Applying whole genome sequencing (WGS) in Newborn Intensive Care Units (NICUs) and in Pediatric Intensive Care Units (PICU) for the rapid diagnosis of critically ill newborns via fast data analysis has resulted in success stories that were unthinkable just a few years ago. WGS is revolutionizing the field of rare disease diagnosis and none of this would be possible without the underlying technological advancements. A recent New England Journal of Medicine letter nicely demonstrates how these advancements can be life-saving due to differences in treatments based on an understanding of underlying mechanisms. Combining different technologies and applying them to the critical need of an expedited diagnosis (within 13.5 hours) for newborns who are struggling to hold on to life, is anything but a straightforward task. Like most aspects of medicine, the real complexity reveals itself in the implementation and in overcoming the challenges of wide-spread adoption. Rapid clinical WGS, however, is imperative in light of growing evidence of its utility in acute care, such as in diagnosis of genetic diseases in very ill infants, and in instances of genotype-guided choice of chemotherapy at cancer relapse. This is especially true in situations when delayed clinical decisions may mean the difference between life and death.

Dr. Stephen Kingsmore: “Among high-risk infants with rare, genetically determined diseases, time-to-treatment is crucial.”

In order to successfully achieve acceptance and uptake of WGS in the clinic, we need secure, scalable, and fast solutions, in addition to knowledge extraction tools that diagnose and explain a disease, or help make decisions regarding the correct treatment choice. We have an entire session planned that focuses on newborn screening with the following set of speakers:
• Dr. Tom Diacovo (UPMC) – session chair
o A recognized leader in thrombosis research who led the development of pharmacological agents and devices specifically designed for neonatal intensive care patients with congenital heart disease who are at high risk for forming blood clots.
o Talk title: Overview of Newborn Screening: Past to Present
• Dr. Ronald J. Wapner (Columbia University Irving Medical Center)
o An internationally known physician and researcher specializing in reproductive genetics.
o Talk title: Advantages of Prenatal Sequencing
• Dr. Stephen Kingsmore (President/CEO at Rady Children’s Institute for Genomic Medicine)
o A leader in this most critical sector for the last decade as is evidenced by the implementation of a clinical WGS-based workflow that has become a model in the NICU/PICU setting.
o Talk title: Impact of Rapid Whole Genome Sequencing on Children’s Morbidity and Mortality in ICU
• Dr. Jerry Vockley (UPMC, Children’s Hospital)
o A recognized leader in the field of inborn errors of metabolism. His current research focuses on mitochondrial energy metabolism, novel therapies for disorders of fatty acid oxidation and amino acid metabolism, and population genetics of the Plain communities in the United States.
o Talk title: NICU sequencing at UPMC: GEMINI vs PISCES studies and steps to standard of care
• Dr. Vasu Rangadass (CEO, L7 Informatics)
o Talk title: Digital Transformation of Precision Medicine Pathways: A NICU Case Study
• Dr. Robert Green (Harvard Medical School)
o Dr. Green leads empirical research studies to establish the medical, behavioral and economic impact of using genetic risk information. His work has provided early data on the clinical utility and cost-effectiveness of genomic sequencing in healthy adults (the MedSeq Project), in active duty military personnel (the MilSeq Project) and most recently in healthy newborn infants (the BabySeq Project).
o Talk title: BabySeq: The Path to Universal Newborn Sequencing and Disease Prevention

Dr. Stephen Kingsmore: ” We have not yet attacked the knowledgebase and only by doing numbers will we see improvements in terms of individualized medicines, efficacy, and outcomes.”

Join this expert-rich session that discusses the latest technological advancements in pediatric genetics, current barriers in the industry and ways to overcome them, as well as methods to prepare practitioners for the future of pediatric genetic care.