The opportunity to diagnose CF by newborn screening is an opportunity to intervene early in life. One of the earliest consequences of CFTR dysfunction and the clinical syndrome of CF is malnutrition which begins in infancy (1). The long term sequelae of malnutrition are significant and include permanent stunting of stature (2, 3), cognitive dysfunction linked to vitamin E deficiency (4, 5) and more rapid decline in pulmonary function. Recently published Guidelines for the Clinical Management of Infants with Cystic Fibrosis (6) emphasize nutritional management while exposing a scarcity of evidence to dictate care. We have a range of effective treatments to control disease in patients with CF but our lack of reproducible, objective outcome measures in infants has prevented these treatments from being studied early in life. Furthermore, as new mutation-specific interventions are developed, we hope to be able to study these in the youngest of patients. Nutritional status as measured by weight-for-length or body mass index is tightly correlated with lung function. Infancy is a time of rapid growth, thus growth parameters are likely to be responsive to clinical changes. We hypothesize that incremental weight gain and linear growth in infants with CF is not equal to a reference population of healthy infants and that certain health-related parameters and biomarkers will identify CF infants with poor growth. We intend to show that growth can be effectively characterized in a safe, feasible manner in a multi-center study and that certain factors will be associated with sub-optimal growth during the first year of life. We also expect that one or more of these growth measures will emerge as a strong, reproducible endpoint for further evaluation of nutritional deficiency in this population. If we are successful in developing reliable, valid and responsive growth measurements that can be performed at care centers around the country, these could be used as efficacy outcomes for future interventional studies in infants with CF.
Cystic fibrosis (CF) is a life-shortening disease that causes breathing and digestive problems, but can now be diagnosed at the time of birth. Lung function is very hard to measure in infants, but growth is not. In this study we aim to define growth in infants with CF in the first year of life with research quality precision and understand factors tht interfere with good growth. If we are successful, these growth measures can be used to show whether treatments for CF are effective and safe when used early in life.
|Heltshe, Sonya L; Cogen, Jonathan; Ramos, Kathleen J et al. (2017) Cystic Fibrosis: The Dawn of a New Therapeutic Era. Am J Respir Crit Care Med 195:979-984|
|Gelfond, Daniel; Heltshe, Sonya L; Skalland, Michelle et al. (2017) Pancreatic Enzyme Replacement Therapy use in infants with Cystic Fibrosis Diagnosed by Newborn Screening. J Pediatr Gastroenterol Nutr :|
|Leung, Daniel H; Heltshe, Sonya L; Borowitz, Drucy et al. (2017) Effects of Diagnosis by Newborn Screening for Cystic Fibrosis on Weight and Length in the First Year of Life. JAMA Pediatr 171:546-554|
|Heltshe, Sonya L; Goss, Christopher H (2016) Optimising treatment of CF pulmonary exacerbation: a tough nut to crack. Thorax 71:101-2|
|Borowitz, Drucy (2015) CFTR, bicarbonate, and the pathophysiology of cystic fibrosis. Pediatr Pulmonol 50 Suppl 40:S24-S30|
|Borowitz, Drucy; Gelfond, Daniel (2015) Equivalent substrates enable simultaneous study of gastrointestinal pH and CF-related diabetes. J Cyst Fibros 14:e6-8|
|Heltshe, Sonya L; Borowitz, Drucy S; Leung, Daniel H et al. (2014) Early attained weight and length predict growth faltering better than velocity measures in infants with CF. J Cyst Fibros 13:723-9|
|Goss, Christopher H; Mayer-Hamblett, Nicole (2013) The yin and yang of indoor airborne exposures to endotoxin. Am J Respir Crit Care Med 188:1181-3|