Abstract
Background:
Newborn screening (NBS) is an established screening procedure in many countries worldwide, aiming at the early detection of inborn errors of metabolism. For decades, dried blood spots have been the standard specimen for NBS. The procedure of blood collection is well described and standardized and includes many critical pre-analytical steps. We examined the impact of contamination of some anticipated common substances on NBS results obtained from dry spot samples. This possible pre-analytical source of uncertainty has been poorly examined in the past.
Methods:
Capillary blood was obtained from 15 adult volunteers and applied to 10 screening filter papers per volunteer. Nine filter papers were contaminated without visible trace. The contaminants were baby diaper rash cream, baby wet wipes, disinfectant, liquid infant formula, liquid infant formula hypoallergenic (HA), ultrasonic gel, breast milk, feces, and urine. The differences between control and contaminated samples were evaluated for 45 NBS quantities. We estimated if the contaminations might lead to false-positive NBS results.
Results:
Eight of nine investigated contaminants significantly altered NBS analyte concentrations and potentially caused false-positive screening outcomes. A contamination with feces was most influential, affecting 24 of 45 tested analytes followed by liquid infant formula (HA) and urine, affecting 19 and 13 of 45 analytes, respectively.
Conclusions:
A contamination of filter paper samples can have a substantial effect on the NBS results. Our results underline the importance of good pre-analytical training to make the staff aware of the threat and ensure reliable screening results.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Therrell BL, Padilla CD, Loeber JG, Kneisser I, Saadallah A, Borrajo GJ, et al. Current status of newborn screening worldwide: 2015. Semin Perinatol 2015;39:171–87.10.1053/j.semperi.2015.03.002Search in Google Scholar PubMed
2. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963;32:338–43.10.1542/peds.32.3.338Search in Google Scholar
3. George RS, Moat SJ. Effect of dried blood spot quality on newborn screening analyte concentrations and recommendations for minimum acceptance criteria for sample analysis. Clin Chem 2016;62:466–75.10.1373/clinchem.2015.247668Search in Google Scholar PubMed
4. Karaceper MD, Chakraborty P, Coyle D, Wilson K, Kronick JB, Hawken S, et al. The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study. Orphanet J Rare Dis 2016;11:12.10.1186/s13023-016-0391-5Search in Google Scholar PubMed PubMed Central
5. Tarini BA, Clark SJ, Pilli S, Dombkowski KJ, Korzeniewski SJ, Gebremariam A, et al. False-positive newborn screening result and future health care use in a state Medicaid cohort. Pediatrics 2011;128:715–22.10.1542/peds.2010-2448Search in Google Scholar PubMed PubMed Central
6. Kwon C, Farrell PM. The magnitude and challenge of false-positive newborn screening test results. Arch Pediatr Adolesc Med 2000;154:714–8.10.1001/archpedi.154.7.714Search in Google Scholar PubMed
7. Rohrer TR, Gassmann KF, Pavel ME, Dorr HG. Pitfall of newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Biol Neonate 2003;83:65–8.10.1159/000067007Search in Google Scholar PubMed
8. Filippi L, Pezzati M, Cecchi A, Poggi C. Dopamine infusion: a possible cause of undiagnosed congenital hypothyroidism in preterm infants. Pediatr Crit Care Med 2006;7:249–51.10.1097/01.PCC.0000216680.22950.D9Search in Google Scholar PubMed
9. Lawson AJ, Bernstone L, Hall SK. Newborn screening blood spot analysis in the UK: influence of spot size, punch location and haematocrit. J Med Screen 2016;23:7–16.10.1177/0969141315593571Search in Google Scholar PubMed
10. Adam BW, Alexander JR, Smith SJ, Chace DH, Loeber JG, Elvers LH, et al. Recoveries of phenylalanine from two sets of dried-blood-spot reference materials: prediction from hematocrit, spot volume, and paper matrix. Clin Chem 2000;46:126–8.10.1093/clinchem/46.1.126Search in Google Scholar
11. Slazyk WE, Phillips DL, Therrell BL, Jr, Hannon WH. Effect of lot-to-lot variability in filter paper on the quantification of thyroxin, thyrotropin, and phenylalanine in dried-blood specimens. Clin Chem 1988;34:53–8.10.1093/clinchem/34.1.53Search in Google Scholar
12. Fingerhut R, Dame T, Olgemoller B. Determination of EDTA in dried blood samples by tandem mass spectrometry avoids serious errors in newborn screening. Eur J Pediatr 2009;168:553–8.10.1007/s00431-008-0788-9Search in Google Scholar
13. Holtkamp U, Klein J, Sander J, Peter M, Janzen N, Steuerwald U, et al. EDTA in dried blood spots leads to false results in neonatal endocrinologic screening. Clin Chem 2008;54:602–5.10.1373/clinchem.2007.096685Search in Google Scholar
14. Nordenstrom A, Wedell A, Hagenfeldt L, Marcus C, Larsson A. Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants. Pediatrics 2001;108:E68.10.1542/peds.108.4.e68Search in Google Scholar
15. G-BA. Richtlinien über die Früherkennung von Krankheiten bei Kindern bis zur Vollendung des 6. Lebensjahres (“Kinder-Richtlinien”): http://www.g-ba.de/downloads/62-492-506/RL_Kinder_2010-12-16.pdf; 2010.Search in Google Scholar
16. Fuda F, Narayan SB, Squires RH, Jr, Bennett MJ. Bile acylcarnitine profiles in pediatric liver disease do not interfere with the diagnosis of long-chain fatty acid oxidation defects. Clin Chim Acta 2006;367:185–8.10.1016/j.cca.2005.11.027Search in Google Scholar
17. Boyer JL. Bile formation and secretion. Compr Physiol 2013;3:1035–78.10.1002/cphy.c120027Search in Google Scholar
18. Moder M, Kiessling A, Loster H, Bruggemann L. The pattern of urinary acylcarnitines determined by electrospray mass spectrometry: a new tool in the diagnosis of diabetes mellitus. Anal Bioanal Chem 2003;375:200–10.10.1007/s00216-002-1654-7Search in Google Scholar
19. Wong ET, Brown DR, Ulstrom RA, Steffes MW. Urinary 17 alpha-hydroxyprogesterone in diagnosis and management of congenital adrenal hyperplasia. J Clin Endocrinol Metab 1979;49:377–80.10.1210/jcem-49-3-377Search in Google Scholar
20. Herrera E, Amusquivar E. Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev 2000;16:202–10.10.1002/1520-7560(200005/06)16:3<202::AID-DMRR116>3.0.CO;2-#Search in Google Scholar
21. Martin CR, Ling P-R, Blackburn GL. Review of infant feeding: key features of breast milk and infant formula. Nutrients 2016;8:279. doi:10.3390/nu8050279.10.3390/nu8050279Search in Google Scholar
22. Giovannini M, Agostoni C, Salari PC. Is carnitine essential in children? J Int Med Res 1991;19:88–102.10.1177/030006059101900202Search in Google Scholar PubMed
23. Vieira Neto E, Fonseca AA, Almeida RF, Figueiredo MP, Porto MA, Ribeiro MG. Analysis of acylcarnitine profiles in umbilical cord blood and during the early neonatal period by electrospray ionization tandem mass spectrometry. Braz J Med Biol Res 2012;45:546–56.10.1590/S0100-879X2012007500056Search in Google Scholar
Supplemental Material:
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2017-0270).
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