ISNS General Guidelines for Neonatal Screening 2002

1. Neonatal screening, an accepted medical intervention
  1. Newborn screening to detect treatable metabolic and other disorders is now an accepted part of routine neonatal health care in almost all countries with well-developed medical services, and is becoming established in many countries in less well-developed regions.
  2. Detailed recommendations for screening policy will vary from country to country and region to region, depending on local economic, political and medical factors and public health organisation.
  3. Guidelines have been published for neonatal screening in general for many parts of the world as well as for specific disorders.
  4. Some guidelines for neonatal screening have stipulated the need for evidence derived from high-quality randomised controlled trials showing benefit from presymptomatic diagnosis. Such evidence may not always be obtainable. Either there is already so strong a perception of benefit that trials will not be ethical, (for example with phenylketonuria or hypothyroidism), or else the very large numbers required in each arm of the trial for relatively rare diseases and the prolonged follow-up required make formal trial virtually impossible.
  5. There are several general principles about genetic screening and testing that are widely accepted. These have been included in a World Health Organisation document “Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Service. The International Society for Neonatal Screening endorses in the main these principles and offers the following general guidance for the conduct of neonatal screening programs.
2. General Recommendations

For a range of disorders neonatal screening is recommended provided that:

i. There is considered to be a direct benefit to the neonate from early diagnosis;
ii. The benefit is reasonably balanced against financial and other costs;
iii. There is a reliable test suitable for neonatal screening;
iv. There is a satisfactory system in operation to deal with diagnostic testing, counselling, treatment and follow-up of patients identified by the test.

Organisation of Programmes
1. The screening programme comprises the sum of the operations necessary to ensure that as far as possible all neonates in the target population are tested, all necessary follow-up is done and all cases found are adequately treated with a minimum of delay and equitably.
2. Screening programmes should be organised and controlled by a body in which health professionals participate.. It is recommended that the body take advice about the general operation of the screening programme from multidisciplinary expert sources.
3. Screening tests should where possible be carried out in large centralised laboratories, so that costs can be kept low and expertise gained and kept.
4. Laboratories should have appropriate expertise, preferably combined with some form of accreditation. Where a system exists, external assessors should review programmes to ensure that suitable tests, quality assurance, cut-off points, follow-up procedures, and screening audit processes are in operation.
5. Regular assessments of screening programme performance should be undertaken and must include test sensitivity, specificity, positive predictive value, timeliness of reporting, and outcome of diagnosed patients. Outcome assessment should include short and long-term evaluation.
6. Health care authorities have a responsibility to ensure that tests are available to all neonates born in their region.
Legal and Ethical Considerations
1. The public should be kept well informed about screening programmes. As far as possible, written information should be provided to parents before testing.
2. Legal considerations will vary widely according to local laws.
3. Where neonatal screening is mandated, there should be provision for parents to refuse the test on behalf of their neonate, where there is some religious or other ground for objecting to participation. Parents refusing the test should be made aware of the possible consequences.
4. The privacy of the patient and the family should be carefully protected, and results not disclosed other than to appropriate health professionals without the consent of the parents. Specific attention must be paid to the possible future detrimental effects of such information.
5. Each programme should develop a policy for the storage and possible later use of neonatal sample cards, including provisions for the protection of the privacy of the individual and family.
Research
1. Continuing research into the natural history of disorders actually or potentially detectable by screening and into biochemical characteristics of particular disorders which might prove to be the basis for useful screening tests in the future is a valid part of any screening programme. Research into the effectiveness of early treatment is also vital, and such research should be facilitated be the screening programme.
Recommendations for screening for specific disorders
1. Screening should be recommended unequivocally for conditions where there is a demonstrated benefit from early diagnosis, the benefit is balanced against financial and other costs, there are suitable tests, and follow-up services are available for management. (As demonstration of benefit for most disorders relevant to neonatal screening has seldom been achieved by randomised control trials, see 1.4, lower orders of evidence should be taken into consideration).
2. Screening can be recommended, if resources permit, for conditions for which there is a demonstrated benefit from early diagnosis, suitable tests and follow-up services are available, but the benefit may or may not be balanced against financial and other costs depending on the available technology, the frequency of the disorder in the region and other local circumstances.
3. A pilot screening programme should be recommended for disorders where benefit to the neonate from early diagnosis appears probable, it is likely the benefit will be balanced against financial and other costs if suitable technology is available, there are tests available which are very likely to be suitable, and there are follow-up services available.
4. Screening tests should not be recommended if indications of advantage from early diagnosis are lacking or uncertain, or the test is unsuitable, or does not detect those cases in which there might be an advantage.
5. There are several disorders which may be detected as an incidental finding when screening for a recommended disorder. Properly constituted research programmes into the utility of screening for these conditions should be encouraged.