primary and secondary use of dried blood spots Neonatal screening: primary and secondary use of dried blood spots 40 years and/or farewell Gerard Loeber RIVM Bilthoven 25th May 2012 Martina Cornel, MD, PhD Professor of community genetics & public health genomics Community Genetics, Dept Clinical Genetics

Neonatal screening (heelprick) In NL usually combined with screening for hearing loss, therefore >96 hours=after 4 days.

Neonatal screening NL 2006-2007 PKU (1974) Congenital hypothyroidism (1981) Congenital Adrenal Hyperplasia (2001) Medication or diet to avoid mental retardation or sudden death Biotinidase deficiency Cystic fibrosis (conditional; pilot 2008; start 2011) Galactosemia Glutaric aciduria type I HMG-CoA-lyase deficiency Holocarboxylase synthase deficiency Homocystinuria Isovaleric acidemia Long-chain hydroxyacyl CoA dehydrogenase deficiency Maple syrup urine disease MCAD deficiency 3-methylcrotonyl-CoA carboxylase deficiency Sickle cell disease Tyrosinemia type I Very-long-chain acylCoA dehydrogenase deficiency In 2006 3 disorders, by 1st Jan 2007 14 additional. CF conditionally advised: first pilot study, start May 2011

Why more diseases? More treatment available Early detection: less health damage More tests available (high throughput) MS/MS Many more promises: how to proceed?

Sir Muir Gray (Nat Scr Comm UK) All screening programmes do harm. Some do good as well and, of these, some do more good than harm at reasonable cost.

To screen or not to screen? How to balance pros and cons?

Primary and secondary use??? First of all: protect children Secondary use: research etc

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

USA heelprick conditions 2011

SCID: immunodeficiency; stemcells! Stemcells from cord blood to cure SCID TRECs as fast high throughput test (DNA; PCR) McGhee 2005

SCID: immunodeficiency; stemcells! Not only a treatable condition Cure! (Potentially the first curable condition in NBS)

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?

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 15

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 Diagnosis in individual child at later stage: congenital CMV? Identify victims

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

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 22

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