New Research Leverages Newborn Screening for Cystic Fibrosis

In 2017, University of Wisconsin Department of Pediatrics faculty and their collaborators launched two new projects that build on existing research and leverage the potential of newborn screening (NBS) to improve treatment for children with cystic fibrosis (CF).

Philip Farrell, MD, PhD, and Mei Baker, MD, received a three-year, $717,000 grant from the Legacy of Angels Foundation to investigate whether coupling whole-genome sequencing with NBS can improve outcomes for the nearly one-third of children with CF who, despite receiving early diagnosis, do not respond well to current therapies. Genomic sequencing affords the opportunity to identify both the genetic modifiers of CF and the pharmacogenomic factors that might influence responses to drug therapies. It is one of the first prospective clinical studies applying knowledge gained in the $3 billion Human Genome Project.

Dr. Baker and the team at the Wisconsin Newborn Screening Laboratory were the first to perform routine sequencing of the CFTR gene on DNA samples from screened newborns. This project extends that strategy using whole-genome sequencing on approximately 200 children with CF who are enrolled in the six-center “Feeding Infants Right… from the Start (FIRST)” study (PI: HuiChuan Lai, PhD, RD; funded by a five-year, $3.5 million National Institutes of Health grant through 2021).

The investigators hope to use this data to identify genomic variants that impact disease onset and progression, which ultimately may help clinicians create more personalized, effective treatments for children with CF. In addition, Dr. Farrell and Dr. Lai, a nutritional scientist with a joint appointment in the UW Department of Pediatrics, along with co-investigator Michael Rock, MD, the long-time director of the UW Cystic Fibrosis Center, continue their well-established partnership through a new three-year, $1 million project supported by Cystic Fibrosis Foundation Therapeutics (CFFT).

This project also builds on the FIRST study, which investigates whether exclusive breastfeeding is nutritionally adequate for infants with CF and aims to better understand which aspects of neonatal malnutrition contribute to the disease’s onset and severity.

In the CFFT study, investigators will use two highly sensitive techniques—chest computed tomography (CT) scans scored by the well-established Brody method and lung-clearance index measurements—to detect and quantify early lung disease in children enrolled in the FIRST study when they reach 5 to 6 years of age.

They will then analyze those measurements against indicators of nutritional status obtained during the FIRST study, and share their observations so that clinicians can develop optimal nutritional care plans for infants with CF. Applying these new, precise technologies will enable the FIRST study to become the most comprehensive longitudinal assessment of outcomes in children with CF and have a strong influence on future treatment strategies.