Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia

James R Bonham; Rachel S Carling; Martin Lindner; Leifur Franzson; Rolf Zetterstrom; Francois Boemer; Roberto Cerone; Francois Eyskens; Laura Vilarinho; David M Hougaard; Peter C J I Schielen

doi:10.3390/ijns4010008

Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia

Int J Neonatal Screen. 2018 Feb 10;4(1):8. doi: 10.3390/ijns4010008. eCollection 2018 Mar.

Authors

Affiliations

¹ Sheffield Children's NHS FT, Sheffield, S10 2TH, UK.
² South East Thames Regional Newborn Screening Laboratory, Biochemical Sciences, Viapath, Guy's & St. Thomas' NHS FT, London, SE1 7EH, UK.
³ Division for Neuropediatrics and prevention, Department of General Pediatrics, University of Frankfurt/Main, 60590 Frankfurt, Germany.
⁴ Department of Genetics and Molecular Medicine, University of Iceland, Landspitali, 101 Reykjavik, Iceland.
⁵ Centre for Inherited Metabolic Diseases, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17176 Stockholm, Sweden.
⁶ Biochemical Genetics Laboratory, Department of Human Genetics, CHU Sart-Tilman, University of Liège, 4000 Liège, Belgium.
⁷ Department of Pediatrics, Giannina Gaslini Institute, Largo Gaslini 5, 16147 Genoa, Italy.
⁸ PCMA vzw Centre for Inherited Metabolic Disorders in Children, Antwerp University Hospital UZA, 2650 Antwerpen-Edegem, Belgium.
⁹ Newborn Screening, Metabolism & Genetics Unit, Human Genetics Department, National Institute of Health Dr Ricardo Jorge, 4049-019 Porto, Portugal.
¹⁰ Danish Center for Neonatal Screening, Director Department for Congenital Disorders, Statens Serum Institut, 2300 Copenhagen Denmark.
¹¹ Reference Laboratory for Neonatal Screening, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.

Abstract

While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.

Keywords: C5 acylcarnitine; IVA interference tandem mass spectrometry; antibiotic; isovaleric acidaemia; moisturing cream; pivalate; pivoloyl.