Guidance

Overview and conditions

Published 24 November 2021

Applies to England

This guidance describes the requirements for laboratories involved in newborn screening.

Laboratories must check this Information frequently. The guidance and requirements described relate to a screening programme, not a diagnostic service.

The workload of the newborn screening laboratory should ideally be 50,000 specimens per year but must be at least 20,000 specimens per year. This ensures appropriate economies of scale and confidence in the interpretation of abnormal results.

Providers must comply with the national guidance for the management of safety concerns and incidents in screening programmes and NHS England guidance for managing serious incidents.

The British committee for standards in haematology (BCSH) has published guidance about screening.

1. Haemoglobinopathies

The haemoglobinopathies are a heterogeneous group of more than 1,000 mutations, which are categorised into 2 main groups:

• the haemoglobin variants
• the thalassaemias

The haemoglobin (Hb) variants arise from an alteration in the globin protein structure. The thalassaemias arise from inadequate production of structurally normal globin protein. There are also thalassaemic haemoglobinopathies that are produced when a structurally abnormal haemoglobin is synthesised at a reduced rate, for example HbE.

The frequency of different haemoglobinopathies varies in different ethnic groups and certain haemoglobinopathies are often associated with a family history. It is important to remember that no haemoglobinopathy is exclusive to any single ethnic group so all individuals are theoretically at risk of carrying an abnormal gene. It is not unusual for people to inherit more than one haemoglobin mutation and many populations are at risk of a range of affected genes. Many haemoglobin mutations have no associated clinical significance, whereas others are associated with severe morbidity and mortality, most notably sickle cell disease and beta (β) thalassaemia major (transfusion dependent thalassaemia). Carriers of a haemoglobin mutation are usually asymptomatic.

2. Sickle cell disease

Sickle haemoglobin (HbS) is a haemoglobin variant in which glutamic acid, the sixth amino acid in the β globin chain, is replaced by valine. Other much rarer haemoglobins have been reported that have this same glutamic acid to valine substitution, but also an additional substitution elsewhere in the β chain. All of these variants will cause sickle cell disease in the situations described below for HbS.

Sickle cell disease results from the inheritance of certain genotypes, including:

• homozygosity for HbS (sickle cell anaemia)
• compound heterozygosity for HbS and an interacting gene, such as HbC (Hb SC disease)
• β thalassaemia (Hb S/β thalassaemia)

See table of newborn screening results for sickle cell disease.

The sickling disorders are associated with severe life-threatening vaso-occlusive crises, overwhelming sepsis, splenic sequestration, aplastic crises, stroke, priapism, pulmonary hypertension, proliferative retinopathy and chronic organ damage, such as avascular necrosis of the hips and shoulders. There is substantial evidence that early administration of prophylactic penicillin markedly reduces the incidence of pneumococcal sepsis. There is also evidence that pneumococcal vaccines can increase immunity to pneumococcal infections in children with sickle cell disease.

Clinical monitoring to detect acute splenic sequestration reduces morbidity and mortality from homozygous sickle cell anaemia (Hb SS) in infancy and early childhood. Studies have demonstrated the benefits of early diagnosis by newborn screening programmes, parental education, and comprehensive care for patients with sickle cell disease and β thalassaemia major.

3. Screening helpline

Laboratories may have questions about screening policy or interpretation of results that cannot be answered easily by reference to this handbook or textbooks. Oxford University Hospitals NHS Trust provides, on behalf of the screening programme, a support service for screening laboratories via designated telephone helplines and secure email.

Telephone: 01865 572 767

Email: [email protected]