1. 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

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

3. 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 disorders, by 1st Jan additional.
CF conditionally advised: first pilot study, start May 2011

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

5. 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.

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

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

9. 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

10. USA heelprick conditions 2011

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

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

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

14. Research for potential new NBS conditions
Frequency of MCADD?

15. 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

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

17. HIV prevalence in the UK: 1990-2002.

18. 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?

19. 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.

20. 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

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

22. Survey: support if transparent!
Survey link posted on the Nine Months Fair website
Feb 10th - Mar 1st,
Van Teeffelen/ Douglas/Van El @VUMC
Likert scales
EMGO Instituut - Care and Prevention 22

23. 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