Storing dried blood spots in NL Neonatal screening: Storing dried blood spots in NL 27th Oct 2016 Dublin Ireland Martina Cornel, MD, PhD Professor of community genetics & public health genomics Community Genetics, Dept Clinical Genetics

Neonatal screening in the Netherlands Starting 1974 with PKU (nationwide) 1981 Congenital hypothyroidism (nationwide) 1987 PhD on Congenital Adrenal Hyperplasia 2002 Nationwide CAH Source: 40 years of NBS in NL

Leftover cards? Some laboratories discarded them shortly after completion of the analyzes due to lack of storage space, some kept all cards for an indefinite period. In 1993 the Netherlands Society of Clinical Genetics requested to the LBCs to keep all cards for a long time, eg. five years, aiming for further scientific research. RIVM was regarded as a suitable location. No further demands were formulated concerning the storage conditions, such as annealing temperature and humidity. After consultation with the RIVM the LBCs agreed to the request. Actually, it was not clear who had the reponsibility over the cards. LBCs = national screening committees – per disorder (PKU, CHT)

Fireworks disaster Enschede 13th May 2000 Children amongst 23 victims Identification? Heelprick cards? -> discussion in media undermining trust

Dried bloodspots for identification? DBS card collection was suggested as a possible means of identification cards were not used journalists took the RIVM to task on informed consent, privacy and especially transparency, as parents were unaware that the cards had been stored

Response Information in five national newspapers Parents withdrew about 550 cards New regulations on who the administrator would be, how to use the cards for research, five years retention

Big Brother Award On the left dr. J. G. Loeber (head reference laboratory) and on the right dr. D. Ruwaard (Sector Director of Health) who on behalf of the RIVMt have received the Big Brother Award 2002 awarded by the Foundation Bits of Freedom.

Current policy The current policy was implemented in 2002: DBS are kept for 1 year for the purposes of the screening program (including quality control), followed by optional storage for 4 years to enable anonymous ‘secondary use’ such as prevalence research, adding up to a maximum storage length of 5 years. tick box on the DBS card to opt out

Neonatal screening – opt out for research

Primary and secondary use??? First of all: identify infants with diseases in whom timely treatment can prevent irreversible damage to health Secondary use: given the dynamics of biotechnology (including genomics): investigate potentially new heelprick conditions Other (public health) research Diagnosis in individual child at later stage: congenital CMV? Identify victims

Research for potential new NBS conditions Can tests, available in clinic, be developped for screening purposes? (High througput, extremely high sensitivity & specificity) (Pompe)

Research for potential new NBS conditions Frequency of MCADD?

Research for other purposes? A similar long term study question: Did HIV occur decades ago?

HIV prevalence in the UK: 1990-2002.

Primary and secondary use??? First of all: identify infants with diseases in whom timely treatment can prevent irreversible damage to health Second: given the dynamics of biotechnology (including genomics): investigate potentially new heelprick conditions Other (public health) research Diagnosis in individual child at later stage: congenital CMV?

Does this child have congenital CMV? CMV is the leading cause of congenital infection in most developed countries, with a frequency of 0.4%–2.3% of live births causes congenital sensory hearing loss and delayed mental development most of those neonates are asymptomatic extraction of CMV DNA from dried blood spots on filter paper … allows the diagnosis of congenital CMV infection Yamagishi J. Med. Virol. 78:923–925, 2006.

Primary and secondary use??? First of all: identify infants with diseases in whom timely treatment can prevent irreversible damage to health Second: given the dynamics of biotechnology (including genomics): investigate potentially new heelprick conditions Other (public health) research Diagnosis in individual child at later stage: congenital CMV? Identify victims

Soon after the new policy came into effect Scientists wanted to keep cards longer: Prevalence/epidemiological studies and specifically allele frequencies and genetic drift, Identification, Screening in later phases of life on stored cards (although the implied linking to health record was not explicitly mentioned) LP ten Kate et al. Medisch Contact 2005

A New Vision: From Population Health Screening to Biological Resource for Research “Another possibility mentioned is to keep an entire year’s worth of cards, in order to later, perhaps in thirty years, study the genetic drift in the population.” Contact between Forum Biotech and Neonatal Screening Committee of the Centre for Population Screening and Ministry: Issues raised: Uses for 1, Prevalence/epidemiological studies and specifically allele frequencies and genetic drift, 2 Identification, 3) Screening in later phases of life on stored cards (although the implied linking to health record was not explicitly mentioned) Such a collection should in theory not be managed by the government nor any governmental body. Danish model referred to but not American lawsuits Optimal is at least 80 years storage 19

Survey: support if transparent! Survey link posted on the Nine Months Fair website Feb 10th - Mar 1st, 2011. Van Teeffelen/ Douglas/Van El @VUMC Likert scales EMGO Instituut - Care and Prevention 20

Etiology but also identify victims – many “fully agree” NB companies involved in test development – less support

Primary and secondary use: conclusion First of all: identify infants with diseases in whom timely treatment can prevent irreversible damage to health Second: New heelprick conditions Other (public health) research Diagnosis in individual child Identify victims Parental support is high Transparency needed

How to move forward? Involve all stakeholders Represent parents of healthy infants and affected infants Similar to biobanks? BBMRI? Models have been proposed in literature Community Values Advisory Board Participant Association to select a Participant Board

Thank you!