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.
Conclusion: 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. |
Similar content being viewed by others
Abbreviations
- 17-OHP:
-
17α-Hydroxyprogesterone
- CAH:
-
Congenital adrenal hyperplasia
- LBW:
-
Low birth weight
- LOESS:
-
Local regression
- NBS:
-
Newborn screening
- NYC:
-
New York City
- NYS:
-
New York State
- PPV:
-
Positive predictive value
- SV:
-
Simple virilizing
- SW:
-
Salt wasting
References
Allen DB, Hoffman GL, Fitzpatrick P, Laessig R, Maby S, Slyper A (1997) Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr 130:128–133
al-Nuaim AR, Abdullah MA, Stevens B, Zain M (1995) Effect of gender, birth weight and gestational age on serum 17-hydroxyprogesterone concentration and distribution among neonates in Saudi Arabia. Indian J Pediatr 62:605–609
Barra CB, Silva IN, Pezzuti IL, Januário JN (2012) Neonatal screening for congenital adrenal hyperplasia. Rev Assoc Med Bras 58:459–464
Chan CL, McFann K, Taylor L, Wright D, Zeitler PS, Barker JM (2013) Congenital adrenal hyperplasia and the second newborn screen. J Pediatr 163:109–113
Gidlöf S, Wedell A, Guthenberg C, von Döbeln U, Nordenström A (2014) Nationwide neonatal screening for congenital adrenal hyperplasia in Sweden: a 26-year longitudinal prospective population-based study. JAMA Pediatr 168:567–574
González EC, Carvajal F, Frómeta A, Arteaga AL, Castells EM, Espinosa T, Coto R, Pérez PL, Tejeda Y, Del Río L, Segura MT, Almenares P, Robaina R, Fernández JL (2013) Newborn screening for congenital adrenal hyperplasia in Cuba: six years of experience. Clin Chim Acta 421:73–78
Gruñieiro-Papendieck L, Chiesa A, Mendez V, Prieto L (2008) Neonatal screening for congenital adrenal hyperplasia: experience and results in Argentina. J Clin Endocrinol Metab 21:73–78
Gruñieiro-Papendieck L, Prieto L, Chiesa A, Bengolea S, Bergada C (1998) Congenital adrenal hyperplasia and early newborn screening: 17α-hydroxyprogesterone (17α-OHP) during the first days of life. J Med Screen 5:24–26
Heather NL, Seneviratne SN, Webster D, Derraik JG, Jefferies C, Carll J, Jiang Y, Cutfield WS, Hofman PL (2015) Newborn screening for congenital adrenal hyperplasia in New Zealand, 1994–2013. J Clin Endocrinol Metab 100:1002–1008
Hofman LF, Klaniecki JE, Smith EK (1985) Direct solid-phase radioimmunoassay for screening 17 alpha-hydroxyprogesterone in whole-blood samples from newborns. Clin Chem 31:1127–1130
Kay DM, Maloney B, Hamel R, Pearce M, DeMartino L, McMahon R, McGrath E, Krein L, Vogel B, Saavedra-Matiz CA, Caggana M, Tavakoli NP (2016) Screening for cystic fibrosis in New York State: considerations for algorithm improvements. Eur J Pediatr 175:181–193
Kloosterboer M, Hoffman G, Rock M, Gershan W, Laxova A, Li Z, Farrell PM (2009) Clarification of laboratory and clinical variables that influence cystic fibrosis newborn screening with initial analysis of immunoreactive trypsinogen. Pediatrics 123:e338–e346
Lando VS, Batista MC, Nakamura IT, Mazi CR, Mendonca BB, Brito VN (2008) Effects of long-term storage of filter paper blood samples on neonatal thyroid stimulating hormone, thyroxin and 17-alpha-hydroxyprogesterone measurements. J Med Screen 15:109–111
Lange-Kubini K, Zachmann M, Kempken B, Torresani T (1996) 15 beta-hydroxylated steroids may be diagnostically misleading in confirming congenital adrenal hyperplasia suspected by a newborn screening programme. Eur J Pediatr 155:928–931
Morikawa S, Nakamura A, Fujikura K, Fukushi M, Hotsubo T, Miyata J, Ishizu K, Tajima T (2014) Results from 28 years of newborn screening for congenital adrenal hyperplasia in Sapporo. Clin Pediatr Endocrinol 23:35–43
Murphy JF, Joyce BG, Dyas J, Hughes IA (1983) Plasma 17-OHP concentrations in ill newborn infants. Arch Dis Child 58:532–534
Odenwald B, Dörr HG, Bonfig W, Schmidt H, Fingerhut R, Wildner M, Nennstiel-Ratzel U (2015) Classic congenital adrenal hyperplasia due to 21-hydroxylase-deficiency: 13 years of neonatal screening and follow-up in Bavaria. Klin Pädiatr 227:278–283
Olgemöller B, Roscher AA, Liebl B, Fingerhut R (2003) Screening for congenital adrenal hyperplasia: adjustment of 17-hydroxyprogesterone cut-off values to both age and birth weight markedly improves the predictive value. J Clin Endocrinol Metab 88:5790–5794
Pang SY, Wallace MA, Hofman L, Thuline HC, Dorche C, Lyon IC, Dobbins RH, Kling S, Fujieda K, Suwa S (1988) Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 81:866–874
Pearce M, DeMartino L, McMahon R, Hamel R, Maloney B, Stansfield D-M, McGrath MC, Occhionero A, Gearhart A, Caggana M, Tavakoli NP (2016) Newborn screening for congenital adrenal hyperplasia in New York State. Mol Genet Metab Rep 7:1–7
Petsos P, Ratcliffe WA, Anderson DC (1985) Assessment of corpus luteum function by direct radioimmunoassay for progesterone in blood spotted on filter paper. Clin Chem 31:1289–1293
Ryckman KK, Berberich SL, Shchelochkov OA, Cook DE, Murray JC (2013) Clinical and environmental influences on metabolic biomarkers collected for newborn screening. Clin Biochem 46:133–138
Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC, Endocrine Society (2010) Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 95:4133–4160
Therrell BL, Berenbaum SA, Manter-Kapanke V, Simmank J, Korman K, Prentice L, Gonzalez J, Gunn S (1998) Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient congenital adrenal hyperplasia. Pediatrics 101:583–590
Török D, Mühl A, Votava F, Heinze G, Sólyom J, Crone J, Stöckler-Ipsiroglu S, Waldhauser F (2002) Stability of 17alpha-hydroxyprogesterone in dried blood spots after autoclaving and prolonged storage. Clin Chem 48:370–372
White PC (2009) Neonatal screening for congenital adrenal hyperplasia. Nat Rev Endocrinol 5:490–498
Wilson K, Hawken S, Ducharme R, Potter BK, Little J, Thébaud B, Chakraborty P (2014) Metabolomics of prematurity: analysis of patterns of amino acids, enzymes, and endocrine markers by categories of gestational age. Pediatr Res 75:367–373
Acknowledgements
Newborn screening is funded by the State of New York. The authors wish to thank the Photography Unit at Wadsworth Center for assistance with the figures.
Authors’ contributions
MP was involved in acquisition of data and revising the manuscript. ED and AGD performed statistical analysis and were involved in revising the manuscript. MC was involved in interpreting data and revising the manuscript. NPT was involved in design of the work, analysis, and interpreting of data and drafting and finalizing the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The manuscript is a retrospective case report that does not require ethics committee approval at our institution (Wadsworth Center, NYSDOH). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Communicated by Beat Steinmann
Rights and permissions
About this article
Cite this article
Pearce, M., Dauerer, E., DiRienzo, A.G. et al. The influence of seasonality and manufacturer kit lot changes on 17α-hydroxyprogesterone measurements and referral rates of congenital adrenal hyperplasia in newborns. Eur J Pediatr 176, 121–129 (2017). https://doi.org/10.1007/s00431-016-2814-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-016-2814-7