title: The influence of seasonality and manufacturer kit lot changes on 17α-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns.
abstract: Newborn screening for congenital adrenal hyperplasia (CAH) is performed by measuring the concentration of 17α-hydroxyprogesterone (17-OHP) in dried blood spots. Unfortunately, the level of 17-OHP varies due to multiple factors, and therefore, the false positive rate for the test is a challenge. We analyzed screening data from 2007 to 2015 to determine the effect of seasonal changes and manufacturer kit lot changes on 17-OHP values and on numbers of infants referred. Data from screening 2.2 million infants over a 9-year period indicates that in the NYS during the colder months, daily mean 17-OHP values are higher, more retests are performed, and more infants are referred even though fewer infants are born. The practice of using fixed cutoffs for referring infants for CAH leads to more false positive results in colder months. In addition, there was an overall 10% increase in the daily mean 17-OHP values from the 2 years before and after a manufacturer kit lot change that occurred in November 2013, suggestive of a functional change in the kit at that time.
  
  
  CONCLUSIONS
  Newborn screening programs should be cognizant of seasonal temperature variations and (un)anticipated manufacturer kit changes because they may affect 17-OHP values and CAH referral rates. What is Known: • Newborn screening for congenital adrenal hyperplasia is generally performed by measuring 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots. • 17-OHP concentrations are affected by gestational age/weight of infant when specimen is collected, specimen collection time after birth, as well as race and sex of infant. What is New: • Seasonal temperature variations and unanticipated manufacturer kit changes affect 17-OHP levels and consequently referral rates in programs that use fixed cutoffs. • Daily mean 17-OHP is generally higher when the ambient temperature is lower.
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, 120, New Scotland Ave., Albany, 12208, NY, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Pearce
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, State University of New York, Albany, NY, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Dauerer
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, State University of New York, Albany, NY, USA.
authors.forename: A Gregory
authors.initials: AG
authors.lastname: DiRienzo
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, 120, New Scotland Ave., Albany, 12208, NY, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Caggana
authors.affiliation: Division of Genetics, Wadsworth Center, New York State Department of Health, 120, New Scotland Ave., Albany, 12208, NY, USA. norma.tavakoli@health.ny.gov.|Department of Biomedical Sciences, School of Public Health, State University of New York, Albany, NY, USA. norma.tavakoli@health.ny.gov.
authors.forename: Norma P
authors.initials: NP
authors.lastname: Tavakoli
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood*; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis*; D006801:Humans; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods*; D011933:Reagent Kits, Diagnostic; D012189:Retrospective Studies; D012621:Seasons; D012680:Sensitivity and Specificity
chemical_list: D011933:Reagent Kits, Diagnostic; D019326:17-alpha-Hydroxyprogesterone
keywords: 17α-Hydroxyprogesterone; Congenital adrenal hyperplasia; Newborn screening; Positive predictive value; Seasonal variation