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.
They are performed on a heel prick blood sample taken from all neonates by midwife/HV at age 5-8 days.

• Phenylketonuria (PKU):
  • Incidence 1:12 000.^3,4
  • 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  • The original "Guthrie" test (semi-quantitative and difficult to automate) is being gradually superseded by chromatography, fluorometry or mass spectrometry.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%).⁵
• Congenital hypothyroidism:
  • Incidence approximately 1:3000.⁶
  • Currently established on same heelprick sample as above.
• Sickle Cell Disease and Thalassaemia:
  • Universal laboratory screening offered since 2005.
  • Form of screening for haemoglobin variants depends on the prevalence of the condition.
  • The programme allows the offer of sickle cell screening to all infants as an integral part of the newborn bloodspot screening.⁷
• Cystic Fibrosis (CF):
  • 1 in 2,500 babies born in the UK have CF.⁸
  • 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.
  • 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 1:8000-1:15,000⁹
  • The Department of Health have funded a pilot study in six UK centres screening more than 700,000 babies.
  • The remaining 7 centres will be funded from April 2009.

Not currently recommended by UK National Screening Committee, but available in some countries.
The 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 1:40,000^10,11
• Galactosaemia (incidence 1:44,000) although neonatal mortality can be reduced with screening and early detection; long term outcome is still poor¹²
• Biliary atresia - population screening using heel prick blood tests not discriminatory enough.

Others include:

• Biotinidase deficiency:
  • Incidence approximately 1:110,000-160,000¹³
  • 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 1:17,000¹⁴
  • 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 disease¹⁵
• Familial hypercholesterolaemia
• Other metabolic disorders e.g. peroxisomal, lysosomal, purine or pyrimidine, urea cycle or trace metal disorders¹