Newborn Genomic Medicine Research

New DNA sequencing technologies have evolved rapidly over the last decade. The cost for whole genome sequencing has dropped from thousands to hundreds of dollars. What used to take months to accomplish requiring a tablespoon of blood is now possible to process in a few days (from the extraction of DNA out of just a few drops of blood to an interpreted report) making NGS a relevant clinical tool for the Neonatologist to diagnose and treat sick newborns.

We aim to more rapidly provide accurate diagnoses to parents and shorten the length of diagnostic odysseys, length of hospital stays, and time to initiation of the most appropriate therapies using these genomic technologies. Our program will allow our clinicians to access state-of-the-art diagnostic test methods and to consider genetic etiologies for difficult to identify newborn diseases. Using appropriate genomic technologies by highly trained staff, our multidisciplinary team aims to advance clinical care standards, improve systems that coordinate the transfer of maternal and fetal genomic information from our BWH maternal fetal medicine colleagues to our Pediatric staff, and eventually generate the genomic information via core facilities already in place within BWH.

Our Newborn Genomics Program investigators have focused on implementation advanced clinical practices. Some of these projects are as follows:

1. Cystic Fibrosis Newborn Screening: Dr. Parad worked with the Massachusetts CF Newborn Screening (NBS) Program to implement the first CF NBS algorithm in the US to incorporate a DNA multi-variant panel for statewide CF screening.
2. Timeliness in NBS: a QI project funded by the CF foundation evaluated an intervention that was successful in reducing the number of state mandated NBS samples sent beyond 48h of life by 50%.
3. In 2015, Dr. Bhattacharjee published the first description of an optimized DNA extraction protocol using newborn dried blood spots for diagnostic targeted NGS panels.
4. Menkes Project: This project focused on a first-tier DNA sequencing based NBS concept for identifying presymptomatic newborns with Menkes disease (a copper transport disorder) – a disorder for which there is no current newborn screen, but for which a therapy is now available.
5. BabySeq Project: This groundbreaking NIH funded randomized trial of genomic newborn screening studied the impact of returning whole exome sequencing information on babies and their care, their parents, and their pediatricians.
6. Supplemental Duchenne Muscular Dystrophy (DMD) NBS Program: This program offers an optional DMD screening test to all babies born at Brigham and Women’s Hospital using a muscle biomarker (Creatine Kinase-MM). If CK is elevated, reflex sequencing of the DMD gene is automatically performed. There are now multiple approved treatments for Duchenne and DMD NBS is now being in several states and Dr. Parad has contributed to nominating the disorder to be added to the universal screening panel recommended by the US Secretary of Health. To date, this program has screened more than 12,000 newborns.
7. Newborn screening for genes associated with cancer predisposition syndromes (CPS) that lead to very early onset childhood cancers: This vanguard program, funded by a Bridge grant from MIT and DFCI, is developing a targeted NGS panel to be piloted as an optional NBS.
8. Targeted NGS newborn screening panel developed to use DNA as the primary NBS analyte for a list of 500 actionable disorders as a member of the BWH International Center for Genetic Disease public health outreach program genomics for low income countries that currently do not have NBS programs. This panel, currently under development, will be piloted at BWH.