LAB Newbrn screening in sme Eurpean Cuntries Françis Macary : cchair f IHE Labratry Cmmittee 1. Intrductin This dcument prduced by the IHE Labratry Cmmittee studies the prcess f newbrn screening in France, and prvides a quick glance n this prcess in Germany and Austria. The bjective f the dcument and its attachments (varius frms and case statements) is t prvide input fr the crdinated wrk f the IHE QRPH and HITSP grups n the same subject based n the AHIC newbrn screening use case available at http://www.hhs.gv/healthit/usecases/nbs.html. 2. Overview f the newbrn screening activity in France France mandates and systematizes newbrn screening fr 5 cngenital diseases, serius and disabling. This activity is rganized and steered by a natinal nn-prfit assciatin l Assciatin Française pur le Dépistage et la Préventin des Handicaps de l Enfant (http://www.afdphe.ass.fr/), which is financed by the natinal public health insurance. This assciatin is subdivided per regin, and the newbrn screening wrkflw is managed at the reginal level. There are 22 regins in France. Each reginal assciatin cntracts with a fixed set f labratries t perfrm the tests. These labratries mst ften belng t reginal university hspitals. Three specialties are invlved: bichemistry, hematlgy and mlecular bilgy, hence three r mre labratries per regin. Newbrn screening tests are perfrmed n bld spts. The specimen is a filter paper frm with 7 t 9 bld spts, als carrying the newbrn administrative and clinic data, as well as the parents cnsent r nn-cnsent t genetic testing. All filter paper frms are sent t ne central pint: The reginal newbrn screening assciatin, wh enters the data, accessins each frm, and sticks the accessin number in bar cde frmat n it, and then dispatches the frms t the intended labratries. Newbrn screening cncerns 800,000 newbrns per year in France. A quarter f them (195 000) are brn in the biggest regin: Ile-de-France, which is arund Paris. The bld spts are cllected by the birth center staff at three days f age (72 hurs), frm the child s heel. The screening is a systematic prcedure applied by the staff f the birth center. There is n rder whatsever prduced fr bld spt testing, except fr genetic tests perfrmed after psitive chemistry results fr cystic fibrsis,. The results prduced by the labs n bld spts are integrated int the reginal database. There is n labratry reprt prduced except in sme specific cases. Hwever, psitive results are ntified in a cnditin ntificatin frm. 3. The diseases screened in France and the crrespnding analytes Disease Nature Incidence Analyte in France Cngenital varius frms, rarely 1 / 3500 TSH (Thyrid Stimulating Hrmne) Hypthyridism genetic Cngenital adrenal hyperplasia recessive autsmic 1 / 14000 a) 17 Alpha-Hydrxyprgesterne (17-OHP) b) Electrlyte Cystic fibrsis Phenylketnuria Sickle cell anemia recessive autsmic recessive autsmic recessive autsmic 1 / 4000 a) Immunreactive trypsingen (IRT) b) CFTR mutatin/variant panel c) Chlride n sweat 1 / 17000 Phenylalanine variable Hemglbine S (HbS) depending n ppulatin Page 1 / 6
4. The main actrs f newbrn screening in France The natinal assciatin AFDPHE : Defines the scpe and rientatin f the activity, defines the prcedures, cnslidates the results prduced by the regins and prduces natinal statistics and related utcme. Each reginal assciatin: Centralizes all bld spts specimens and assciated data, including parents cnsent t generic testing. Accessins and identifies each specimen with a barcde label. Dispatches the specimens t the appinted labs and prepares the wrklist f each lab. Centralizes all the results frm the labs f the regin. Sends psitive (i.e. abnrmal) results t the birth center as well as t the referent fr the pathlgy n the gegraphic sectr. Prepares cnvcatins f the parents (in case f psitive results) and mails them t the referent fr the pathlgy n the gegraphic sectr. In case f psitive chemistry results fr cystic fibrsis, checks the parents cnsent, then creates the rder fr genetic testing, and sends the rders t the mlecular bilgy lab, with a cpy f the parents cnsent attached, and at the same time requests the chemistry lab t frward the bld spt specimen t the bimlecular lab. This is the nly case where an explicit rder is made and placed t a lab. The rdering is the chairman f the reginal assciatin. Prvides educatin n newbrn screening n bld spts t the birth centers staff. Prvides educatin flyers t be handed t the parents. Prvides the prcedures and guidelines t all ther actrs f the prcess in the regin. Handles the prvisin f filter paper frms t each birth center f the regin. specimen cllectrs (nursery nurses, midwives ) The staff cllects bld spts frm the newbrn s heel at 72 hurs f age. The staff als fills in the bld spt filter paper frm and has the parents write and sign their cnsent r nn-cnsent t genetic testing at the back f the card. The staff als assesses the risks f the newbrn fr sickle cell anemia, and in case f such risk, ntifies it n the specimen frm and cllects tw mre bld spts n the frm. The specimen frms are sent t the newbrn screening reginal assciatin. The staff reprts the date f bld spt cllectin fr screening n the child s paper health recrd, that will be taken hme by the parents. attending The is ntified by the reginal assciatin f every abnrmal result. Perfrming nn-bimlecular labratry Generally a lab belnging t a reginal university hspital. Receives frm the reginal assciatin the specimen cards with their barcde id. Receives/dwnlads the crrespnding wrklist delivering patient demgraphics fr each specimen card. Perfrms the tests, with pssible rerun depending n first results, fllwing the defined prcedures. Validates the results. Sends/uplads the results t the reginal assciatin. In case f psitive results n IRT, is requested by the reginal assciatin t frward the specimen card t the bimlecular labratry, and des s. In case f psitive results n 17-OHP, prduces a reprt and sends it t the birth center: Cngenital adrenal hyperplasia needs very quick attentin frm the care prviders. This is almst the nly case where a nn-bimlecular labratry prduces a reprt fr newbrn screening. Page 2 / 6
Perfrming bimlecular labratry Receives by mail frm the reginal assciatin an explicit rder t perfrm CFTR mutatin/variant panel n the specimen card frwarded by the chemistry lab. The cpy f the parents cnsent t genetic testing is attached t the rder. Perfrms the panel, and validates the results. Prduces a reprt and mails it t the reginal assciatin. This is the nly labratry whse wrk is based n incming rders and systematically prduces reprts. The referent fr a pathlgy n a gegraphic sectr Is ntified by the reginal assciatin f every psitive result regarding the pathlgy. Receives the cnvcatin letter and frwards it t the family pediatric r pediatric center r t the parents themselves. The parents will be infrmed during a cnsultatin with the pediatric specialist. The pediatric (fr the family r frm the pediatric center chsen by the family): Cnvkes the parents in case f a suspected cnditin, and settles the apprpriate actins (additinal exams, treatment, fasten, admissin t a specialized center ) In case new specimens are needed, cllects the specimens and sends them t the reginal assciatin. 5. Wrkflws f French newbrn screening 5.1. Screening with apprpriate specimens and nrmal results Nrmal prcess, nrmal results (negative) Reginal assciatin 3) Accessining, printing barcde labels, archiving the frm (bttm f the specimen card, including patient cnsent at the back) 2) Specimen card including patient demgrathics and birth data, and patient cnsent at the back 4) Dispatches specimens and wrklists t the appinted labratries 7) Mnitrs the results, triggers cnvcatins, requests new specimens if needed 1) Bld spt cllectin 6) Uplads results t the reginal assciatin system 5) Perfrms the tests, and validates them 0) Cllects parents cnsent/nncnsent and fills in the specimen card Nn-bimlecular labs Page 3 / 6
5.2. Inapprpriate specimens The labratry discvers that the bld spts are inapprpriate (verlad, dilutin, stain). The labratry requests frm the reginal assciatin wh frwards this request. 4) New specimen identified and bar cded 3) New specimen cllected Reginal assciatin 1) Ntifies specimen unusable 2) Requests new specimen 5.3. Undecidable result, request fr new specimen Depending n the results psitin twards reference ranges, the birth data (prematured r nt ) and ther data, and accrding t the prcedure the perfrming labratry may decide Internal actin: rerun, nrmalizatin f the result Request a new specimen card frm the reginal assciatin 5) New specimen bar cded 4) New specimen card with fresh bld spts 1) dubtful result Fédératin réginale 2) - child back hme Request mailed t the parents, with letter attached fr the pediatric 2) - child admitted t an hspital Request sent t the attending ward Parents Hspital ward 3) cllects Pediatric 3) cllects the new specimen 5.4. Psitive chemistry results with need fr cnfirmatin by bimlecular test A psitive IRT result (suspicin f cystic fibrsis) has t be cnfirmed by a CFTR mutatin/variant panel. This genetic test can be perfrmed nly with the parents cnsent. 5) Genetic testing Reprt 1) psitive IRT Reginal assciatin 3) rders genetic testing Chemistry hrmnlgy labratry 3) requests specimen frwarding 4) Frwards specimen card 2) checks patient cnsent Bimlecular lab Page 4 / 6
5.5. Psitive result : Cnvcatin f parents 1 Specific flw with abnrmal 17-OHP : Lab reprt addressed directly t birth center and referent Referent 3) Frwards cnvcatin Fédératin réginale Pediatric 1) Psitive results 2) Request fr parents cnvcatin 4) Cnvcatin t cnsultatin Parents 6. Data f French wrkflw 6.1. Specimen filter paper card Data grup Item Values Newbrn Last name 1 st name Sex M F Date f birth Risk f sickle cell anemia Yes N Term r prematured Number f weeks f amenrrhea Birth weight g Transfused Yes N Parents Cnsent t genetic tests Chsen pediatric Mther s name Address Telephne father s cnsent Yes N + signature mther s cnsent Yes N + signature Name address telephne Birth Name, address, telephne birth lcatin ID a unique cde Number f birth in this lcatin a number Specimen Specimen cllectin lcatin Name, address, telephne lcatin ID a unique cde Specimen cllectin date & time bar cded ID prduced by reginal assciatin 6.2. Test results Bimlecular labratries prduce reprts f their genetic tests fr newbrn screening. Other labratries usually dn t, except in specific cases as shwn abve. These labs directly uplad their results int the reginal assciatin infrmatin system. Case identificatin Identificatin Screening Cnfirmatin Cnclusin Care plan Results are mnitred by the reginal assciatin. Cnfirmed psitive results are reprted int a case identificatin frm. Such frms are initialized by the reginal assciatin, and then cmpleted by each party (lab,, referent, pediatric specialist) invlved in the case. These case identificatin frms are sent bth t the birth center and t the natinal assciatin. See attached dcument. Page 5 / 6
7. Hearing screening in France Hearing screening is dne in parallel in sme birth centers, experimentally. This activity is als mnitred by the reginal assciatin, separated frm bld spt screening. This activity is nt generalized due t its cst, much higher than the bld spt screening. 8. Temprary cnclusin n the French newbrn screening wrkflw As f tday, the infrmatin systems f the varius rganizatins invlved in the wrkflw, have very little data exchange between ne anther, if any exchange at all. The glbal cherence and relative efficiency f this wrkflw is relying n the central system f the reginal assciatin, remtely used by the perfrming labs fr dwnlading their wrklists and uplading their results, als cmpleting the case identificatin frms. Any prject f a better integratin by IHE shall be submitted t a prir apprval by the chair f the natinal assciatin. AFDPHE (http://www.afdphe.ass.fr/) 9. Glance n newbrn screening activities in sme ther Eurpean cuntries 9.1. Austria The activity is centralized at the natinal level. Only ne rganizatin and ne lab perfrming the tests fr the whle cuntry. See attached dcuments. N labratry reprt frm this wrkflw. 9.2. Germany Newbrn screening is centralized. 99% f newbrns are tested. The tests are dispatched between 10 labs ver the cuntry: 3 cmmercial labs and 7 university hspital labs. Specimen cards may vary frm land t land. Sme f them are designed fr OCR and can then be integrated autmatically int the public health infrmatin system in charge f this activity. N labratry reprt frm this wrkflw. See attached dcuments. 10. Temprary cnclusin fr newbrn screening in Eurpe The shrt investigatin cnducted, shws that in mst cases in Eurpe, the newbrn bld spt screening wrkflw implies neither labratry rder nr labratry reprt. The screening being systematized is part f the birth center prcedures, and the labs appinted t perfrm the test d nt need any rder (with the exceptin f genetic testing). The results are cnslidated in the public health database and in mst cases d nt trigger any labratry reprt. Very little integratin between infrmatin systems exist, which induces in many cases manual entry f data, with the inherent risks f errrs. In sme cases, at least in France, the wkflw includes cperative fulfillment f sme dcuments. The wrkflw als needs a direct interactin between the LIS f the appinted labratries and the public health system mnitring this activity. Hearing screening, when it exists, is nt cnnected t bld spt screening. 11. Attached dcuments File name Cntent Origin France_specimen_card.ppt French specimen card Martine Marchand case_identificatin_fr.pdf rder_genetic_tests_fr.png hearing_screening_fr.pdf Austria_Germany_specimen.xls Case identificatin frm fr cystic fibrsis in France Order f genetic tests in France (CFTR mutatin) Hearing screening bservatins frm in France Cmparisn f specimen card cntent between Austria and Germany Valérie Gauthereau Valérie Gauthereau Valérie Gauthereau Filip Migm, Stefan Sabutsch Neugebrenen_screening_wien.pdf Austrian specimen card Filip Migm Germany_Cttbus.pdf Germany specimen card frm Cttbus Filip Migm Germany_Erfurt.pdf Germany specimen card frm Erfurt Filip Migm Page 6 / 6