A HIGH SENSITIVITY, HIGH-THROUGHPUT NEWBORN SCREENING ASSAY FOR CONGENITAL CYTOMEGALOVIRUS -IS IT TIME FOR UNIVERSAL SCREENING IN THE UK?

Helen Payne ^1* Mikko Aaltoranta ² Ville Veikkolainen ² Natalie Kent ³ TRIANTA Gkouleli ³ Alexander Lennon ⁴ Tejswurree Ramgoolam ^4,5 Stuart Paul Adams ³

• ¹ Imperial College London, London, United Kingdom
• ² Research and Development, Revvity Inc., Turku, Finland
• ³ SIHMDS-Haematology, Great Ormond Street Hospital for Children NHS Foundation Trust,, London, United Kingdom
• ⁴ Department of Virology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, London, United Kingdom
• ⁵ Department of Infection, Immunity and Inflammation, Institute of Child Health, 30 Guilford St, London WC1N 1EH., London, United Kingdom

Introduction: Congenital cytomegalovirus (cCMV) is the leading cause of neurodevelopmental and hearing impairment from in-utero infection affecting over a million infants globally every year. Early antiviral treatment can limit sequalae, however most newborns are diagnosed late, or not at all, due to the absence of universal screening. It is critical that appropriate screening tools are available to facilitate accurate and timely cCMV diagnostics.Methods: A high-sensitivity, high-throughput, commercial CMV PCR kit targeting the RRP30 control gene and a conserved region of CMV DNA, was provided by Revvity and tested in three population groups: (1) leftover dried blood spot (DBS) from the UK newborn screening programme, (2) DBS from blood of children with CMV viraemia not due to cCMV, (3) DBS and dried saliva from infants with and without cCMV.Results: Of 3345 anonymised newborn DBSs analysed, 22 detected CMV (0.66%) with mean cycle threshold values for CMV 36.70 (range 31.87 - 41.68). The assay development demonstrated sensitivity of 2.04 CMV IU per reaction. This level of sensitivity was replicated using DBS prepared from infant/child blood with known levels of CMV, suggesting the sensitivity reflects 2000-3000 CMV IU/ml blood.Discussion: We demonstrated a high analytical sensitivity of the qPCR assay with an optimal extraction protocol that could be used as an effective cCMV screening strategy using DBS. These data suggest a potential incidence rate of cCMV in up to 0.66% in the UK, equivalent to 3960 infants per year, 25% of whom will have long-term sequelae that could be improved with early diagnosis and treatment.