Newborn Screening

Screening newborn babies should fulfil the Wilson criteria. The following modified Wilson criteria were used in the HTA assessment below:¹

• Clinically and biochemically well-defined disorder
• Known incidence in populations relevant to the UK
• Disorder associated with significant morbidity or mortality
• Effective treatment available
• Period before onset during which intervention improves outcome
• Ethical, safe, simple and robust screening test
• Cost-effectiveness of screening

The routine neonatal examination and subsequent 6 week check

This is used to screen for:

• Congenital heart disease
• Other congenital malformations including congenital dislocation of the hip, cryptorchidism and undescended testes
• Congenital cataracts and other media opacities
• Anatomical abnormalities

Newborn hearing screening

• This is offered to all babies in the UK by 4-5 weeks of age.²
• For babies that have spent more than 48 hours in NICU or SCBU the hearing test should be offered by 44 weeks gestational age.
• A combination of automated otoacoustic emissions ( AOAE) and automated auditory brainstem response (AABR) is used.
• This is similar to testing previously only offered to high risk groups.
• There is also a parental checklist for reference after the testing.

Screening for inborn errors of metabolism

These are also part of routine UK neonatal screening.³They are performed on a heel prick blood sample taken from all neonates by midwife/HV at age 6-14 days.
The gold standard to judge other tests is the PKU test - which on cost-benefit analysis justifies the current national heelprick screening program on its own!

• Phenylketonuria (PKU):
  • Incidence 1:12 000.^4,5
  • Current tests look for a combination of total biopterin and dihydropteridine reductase from neonatal blood spots.
  • The original "Guthrie" test (semi-quantitative and difficult to automate) is being gradually superseded by chromatography, fluorometry or mass spectrometry.
  • Early diagnosis and treatment reduces risk of neurological handicap from 80-90% to 6-8% (population baseline risk 2%).⁶
• Congenital hypothyroidism:
  • Incidence approximately 1:3000.⁷
  • Currently established on same heelprick sample as above.
• Sickle Cell Disease:
  • Universal laboratory screening offered in trusts covering high prevalence populations since 2005.⁸
  • Form of screening for haemoglobin variants depends on the prevalence of the condition.
  • All other areas required to offer, as a minimum, laboratory testing for variants (based on an assessment of risk) since 2006.
  • Risk determined by questioning women about their ethnic origin.
• Cystic Fibrosis (CF):
  • 1 in 2,500 babies born in the UK have CF.⁹
  • Carrier rate is 1 in 25.
  • Incidence varies around the country.
  • Biochemical screening is being phased in and should be uniform by April 2007. Initial screening detects raised levels of immune reactive trypsinogen (IRT), which is the followed by DNA analysis.¹⁰
  • The commonest mutation is in the DF 508 gene in 95% of affected individuals in the UK.
• Medium-chain acyl CoA dehydrogenase (MCAD) deficiency:
  • Estimated incidence 1:8000-1:15,000¹¹
  • The Department of Health have funded a pilot study in six UK centres screening more than 700,000 babies.³
  • The remaining 7 centres will be funded from April 2009.

Not currently recommended by UK National Screening Committee, but available in some countries.³The strongest cases can be made for screening for the following, although tandem mass spectrometry needs to be widely available:

• Glutaric aciduria type 1 (GA1) - estimated incidence 1:40,000^12,13
• Galactosaemia (incidence 1:44,000) although neonatal mortality can be reduced with screening and early detection; long term outcome is still poor¹⁴
• Biliary atresia - population screening using heel prick blood tests not discriminatory enough.

Others include:

• Biotinidase deficiency:
  • Incidence approximately 1:110,000-160,000¹⁵
  • Can be identified via blood spot analysis hence would be straightforward to implement, and dietary supplementation prevents neurological deficit - but UK incidence is current thought to be too low to justify nationwide screening.
• Congenital adrenal hyperplasia (CAH):
  • Incidence 1:17,000¹⁶
  • Caused by 21-hydroxylase deficiency
  • Screening shown to be beneficial in other countries
• Disorders of organic acid and fatty acid metabolism:
  • Rare and diverse recessively inherited conditions, some of which may be candidates for screening in the future¹

The modified Wilson criteria above are not currently met for the following conditions, hence not recommended by the UK National Screening Committee:

• Non-PKU amino acidopathies e.g. tyrosinaemia type 1, homocystinuria and maple syrup urine disease¹⁷
• Familial hypercholesterolaemia
• Other metabolic disorders e..g. peroxisomal, lysosomal, purine or pyrimidine, urea cycle or trace metal disorders¹