Newborn screening offers hope for early diagnosis

The ear­ly diag­no­sis of a rare dis­ease can help peo­ple with such con­di­tions to improve their qual­i­ty of life. When this hap­pens short­ly after birth, it can enable life-sav­ing inter­ven­tions and pre­vent severe dis­abil­i­ties from devel­op­ing.

All babies in the UK are offered new­born blood-spot screen­ing on the NHS, also known as the heel-prick test, which is ide­al­ly con­duct­ed when they’re five days old.

This test typ­i­cal­ly screens for nine rare but seri­ous con­di­tions: sick­le-cell dis­ease, cys­tic fibro­sis, con­gen­i­tal hypothy­roidism and six inher­it­ed meta­bol­ic dis­eases. (In some parts of Eng­land, it also cov­ers severe com­bined immun­od­e­fi­cien­cy.) But Pro­fes­sor Jim Bon­ham, pres­i­dent of the Inter­na­tion­al Soci­ety for Neona­tal Screen­ing, says that the “genet­ics rev­o­lu­tion” means that 300 to 400 more con­di­tions could be cov­ered.

“I think we should cer­tain­ly explore the poten­tial that genet­ics offers, but do so in a way that serves patients’ inter­ests,” he says. “We need clear evi­dence to demon­strate that, by inter­ven­ing ear­ly in life, we are going to offer real ben­e­fits for the child.”

Bon­ham adds that new­born screen­ing is best applied to treat­able dis­eases where ear­ly diag­noses would offer improved out­comes.  

“It is very impor­tant to main­tain pub­lic con­fi­dence,” he stress­es. “Some par­ents may not wish to know about a con­di­tion if no treat­ment for it is avail­able. Oth­ers may wish to know, even if there’s no treat­ment, to enable them to plan effec­tive­ly for the future of their fam­i­ly. But all would agree that the ear­ly diag­no­sis of a seri­ous dis­or­der that leads direct­ly to life-chang­ing treat­ment is to be wel­comed. This is the cen­tral remit of new­born screen­ing.”

A pilot pro­gramme backed by NHS Eng­land is set to explore the poten­tial for extend­ing the scope of the heel-prick test. With sup­port from UK Research and Innovation’s Sci­ence­wise pro­gramme, the UK Nation­al Screen­ing Com­mit­tee and Genomics Eng­land, the body estab­lished to deliv­er the 100,000 Genomes Project, have invit­ed the pub­lic to com­ment on their pro­posed use of whole-genome sequenc­ing in new­born screen­ing. The find­ings of the con­sul­ta­tion so far indi­cate wide­spread sup­port for the move, pro­vid­ing that the right safe­guards and resources are in place.

The UK Nation­al Screen­ing Com­mit­tee, which reviews its rec­om­men­da­tions on test­ing for dif­fer­ent con­di­tions as new research find­ings become avail­able, advis­es the NHS on which screen­ing pro­grammes to offer. When con­sid­er­ing whom to test and which con­di­tions to test for, the ben­e­fits of offer­ing such a pro­gramme are weighed against the poten­tial harms. The com­mit­tee rec­om­mends screen­ing only when it believes that the ben­e­fits to those being screened will out­weigh the harms.

The abil­i­ty to sequence and analyse a newborn’s entire genet­ic code could enable clin­i­cians to detect many more con­di­tions and trans­form the NHS into a more pre­ven­tion-focused health­care sys­tem. But the pro­pos­al rais­es eth­i­cal and soci­etal ques­tions, which is why the com­mit­tee and Genomics Eng­land are seek­ing the public’s input before con­sid­er­ing the use of whole-genome sequenc­ing in the NHS. There will also be exten­sive engage­ment with clin­i­cians and patients to shape the pro­gramme.

“The dif­fi­cult ques­tions con­cern how pre­dic­tive the results are; which con­di­tions it would be accept­able to look for; what infor­ma­tion to give to whom and when; and how to help par­ents make informed choic­es about tests that could have impor­tant impli­ca­tions for their child, them­selves and oth­ers,” explains Pro­fes­sor Bob Steele, chair of the UK Nation­al Screen­ing Com­mit­tee.

Pro­fes­sor Sir Mark Caulfield, who recent­ly stepped down from Genomics Eng­land after eight years as its chief sci­en­tist, adds: “This work is a fan­tas­tic foun­da­tion from which to take for­ward the explo­ration of a pilot new­born pro­gramme.”

The next step of this project will be to design and run an eth­i­cal­ly approved research pilot embed­ded in the NHS to explore whether and how to offer whole-genome sequenc­ing to all new­borns to accel­er­ate diag­no­sis and access to treat­ments for rare genet­ic con­di­tions. Up to 200,000 babies’ genomes will be sequenced and analysed for a set of action­able con­di­tions that may affect their health in infan­cy. 

With par­ents’ con­sent, babies’ genomes will be de-iden­ti­fied and added, along­side their health data, to the Nation­al Genom­ic Research Library that Genomics Eng­land man­ages. This infor­ma­tion will help vet­ted aca­d­e­m­ic, clin­i­cal and com­mer­cial health­care researchers to improve their knowl­edge; devel­op new tests and treat­ments; and under­stand how ther­a­pies can be improved or repur­posed.

Stor­ing babies’ genomes secure­ly, regard­less of their screen­ing out­come, could also enable these to be reanalysed as need­ed, poten­tial­ly enabling access to new devel­op­ments in genomics through­out their life­times.

The scale and deliv­ery qual­i­ty of new­born screen­ing pro­grammes can vary dras­ti­cal­ly from one coun­try to anoth­er. Test­ing for more than 50 dis­eases, Italy leads the way in Europe, with Aus­tria, Hun­gary and Spain test­ing for 20 or more.

Eurordis, an alliance of near­ly 1,000 patient organ­i­sa­tions in the UK and 73 oth­er nations, advo­cates a har­monised approach to new­born screen­ing as the only way to ensure that as many babies as pos­si­ble are cov­ered by the most com­pre­hen­sive tests avail­able.

This would “guar­an­tee the human right of achiev­ing the high­est stan­dard of health for all new­borns, regard­less of their coun­try of birth”, says Eurordis board direc­tor Simona Bel­lagam­bi, who has a teenage niece with tuber­ous scle­ro­sis, a rare and cur­rent­ly incur­able genet­ic con­di­tion. “If you could help your baby by reduc­ing the sever­i­ty of their dis­ease, or pos­si­bly even help them to be healthy, wouldn’t you try your best? Screen­ing is an effec­tive way to obtain a diag­no­sis – and all new­borns deserve it.”