Sweat Testing Following Newborn Screening for Cystic Fibrosis John Massie, PhD FRACP, 1 * Kevin Gaskin, MD, FRACP, 2 Peter Van Asperen, MD, FRACP, 1 and Bridget Wilcken, MBChB, FRACP 3 Summary. Sweat testing remains the “gold standard” for the diagnosis of cystic fibrosis (CF) and is a critical component of newborn screening programs. We retrospectively reviewed sweat test results reported to a neonatal screening program for CF with respect to completeness of re- ported results and the values recorded for sweat chloride (Cl - ) and sodium (Na + ) concentrations and the Cl - :Na + ratio in screened infants. Thirty-nine of 85 F508 homozygous (F508/F508) and 270 of 274 F508 heterozygous (F508/-) infants had sweat tests reported to the screening program. Of those, 30 and 213 sweat test reports, respectively, were complete, i.e., sweat weight, sweat chloride, and sodium were reported. Three centers accounted for 37 of 68 (54%) incomplete results, and 4 centers performed 4 or less post-screening sweat tests in the study period. There were 6 F508 het- erozygous infants with sweat Cl - concentrations of 40–60 mmol/L and 4 had CF confirmed by additional genotyping (n = 2) or clinical and repeat sweat Cl results (n = 2). Forty-one percent of F508/-infants with sweat Cl - <40 mmol/L had Cl:Na >1. We conclude that the reporting of incomplete sweat tests is common following newborn screening for CF. Infants with sweat Cl - levels of 40–60 mmol/L require further investigation and review, but they almost certainly have CF. The Cl - :Na + ratio does not appear useful in estab- lishing a diagnosis of CF in infants. Pediatr Pulmonol. 2000;29:452–456. © 2000 Wiley-Liss, Inc. Key words: sweat test; cystic fibrosis; immunoreactive trypsinogen; newborn screening. INTRODUCTION The sweat test remains the principle investigation for the confirmation of the diagnosis of cystic fibrosis (CF). 1,2 Since 1993, newborn screening for CF in the state of New South Wales (NSW), Australia, has in- cluded F508 mutation analysis on all infants with an elevated neonatal immunoreactive trypsinogen (IRT). 3 Over 370,000 infants have so far been screened with this protocol. Infants homozygous for F508 have cystic fi- brosis, while infants heterozygous for F508 are referred for sweat testing. The sweat test is usually performed around 6 weeks of age, and adequate amounts of sweat can be collected at this age by an experienced center. 4 Close attention to technique is essential, and measure- ment errors can result in false-positive and false-negative results, with serious consequences. 5,6 The chloride value is the most sensitive sweat electrolyte for diagnosis, al- though measurement of sodium provides a valuable in- ternal control, as the two values are usually similar. 7 The usefulness of the relationship between chloride and so- dium is unclear. 8–10 While sweat testing of infants after newborn screening has been reported as useful, 4,11 the sweat tests were per- formed under study conditions, which does not necessar- ily reflect clinical practice. We reviewed the sweat test 1 Department of Respiratory Medicine, Royal Alexandra Hospital for Children, Sydney, Australia. 2 James Fairfax Institute of Paediatric Nutrition, Royal Alexandra Hos- pital for Children, Sydney, Australia. 3 Biochemical Genetics and New South Wales Newborn Screening, Royal Alexandra Hospital for Children, Sydney, Australia. Grant sponsor: National Health and Medical Research Council. *Correspondence to: R.J.H. Massie, Ph.D., F.R.A.C.P., Department of Respiratory Medicine, Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia. E-mail: massiej@cryptic.rch. unimelb.edu.zau. Received 2 October 1998; Accepted 17 December 1999. Pediatric Pulmonology 29:452–456 (2000) © 2000 Wiley-Liss, Inc.