Evaluating the evidence for newborn screening of rare disorders

7 April 2010

Newborn screening involves the testing of blood samples from newborn babies for various different rare genetic disorders. In some cases, early identification can allow interventions to prevent or ameliorate disease; other potential benefits of early, pre-symptomatic diagnosis include avoiding the need for extensive medical investigations later in life and allowing prompt genetic counselling for families (including advice about the risk of recurrence in future children).

Technological developments have led to the possibility of screening for many rare disorders. However, prior to their inclusion in a newborn screening programme, careful consideration of the risks and benefits of screening must be undertaken. In the US, a wide panel of disorders are included in newborn screening programmes: 29 conditions are deemed mandatory and another 25 secondary conditions have been recommended for inclusion in screening (see previous news). However, expanded newborn screening has raised some concerns and a white paper published by the President’s Council of Bioethics discusses some of the ethical implications of newborn screening in the US (see previous news).

Evaluating rare conditions nominated for population-based newborn screening is made difficult by the scarcity of data, such as those from large-scale population screening studies and randomised clinical trials. In a recent issue of Genetics in Medicine dedicated to newborn screening, two articles describe the US approach to evaluating evidence in screening for rare conditions. Perrin et al. describe some of the challenges in the evidence review for rare diseases and the adaptation of standard evidence review processes to screening for rare diseases [Perrin et al. (2010) Genet Med 12 (3):131-134]. Calonge et al. describe the framework by which the US Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children evaluates conditions to be included in newborn screening programmes [Calonge et al. (2010) Genet Med 12(3):153-159]. The approach taken by the Committee involved the formation of an Evidence Work Group to review all the published evidence as well as unpublished data from experts relating to a particular disorder. The report it produces highlights the key findings, and indicates where key data are missing. This review is then evaluated by the Committee in three broad areas relating to the condition, the screening and diagnostic test, and the treatment. Recommendations are made based on the systematic evidence review and additional information that may be available from other sources.

Comment: With rapidly developing techniques for high-throughput analysis such as tandem mass spectroscopy (MS/MS), it has become increasingly feasible to test for multiple genetic diseases. However, the inherent difficulties of studying the epidemiology of conditions that are extremely heterogeneous and also very rare, in addition to the differing considerations of what constitutes the benefit of screening (see previous news) make assessment of what to include in a newborn screening panel a difficult decision. The PHG Foundation is currently undertaking a literature-based systematic review of the evidence to support expanded newborn screening for five conditions in the UK.

More from us

Genomics and policy news