The COVID-19 pandemic affected many essential aspects of public health, including newborn screening programs (NBS). Centers reported missing cases of inherited metabolic disease as a consequence of decreased diagnostic process quality during the pandemic. A number of problems emerged at the start of the pandemic, but from the beginning, solutions began to be proposed and implemented. Contingency plans were arranged, and these are reviewed and described in this article. Staff shortage emerged as an important issue, and as a result, new work schedules had to be implemented. The importance of personal protective equipment and social distancing also helped avoid disruption. Staff became stressed, and this needed to be addressed. The timeframe for collecting bloodspot samples was adapted in some cases, requiring reference ranges to be modified. A shortage of essential supplies and protective equipment was evident, and laboratories described sharing resources in some situations. The courier system had to be adapted to make timely and safe transport possible. Telemedicine became an essential tool to enable communication with patients, parents, and medical staff. Despite these difficulties, with adaptations and modifications, some centers evaluated candidate conditions, continued developments, or began new NBS. The pandemic can be regarded as a stress test of the NBS under real-world conditions, highlighting critical aspects of this multidisciplinary system and the need for establishing local, national, and global strategies to improve its robustness and reliability in times of shortage and overloaded national healthcare systems.

Center for Inherited Metabolic Diseases Karolinska University Hospital 141 86 Stockholm Sweden

Clinical Institute for Special Laboratory Diagnostics University Children's Hospital UMC Ljubljana 1000 Ljubljana Slovenia

Department of Dermatovenerology General Hospital Novo Mesto 8000 Novo Mesto Slovenia

Department of Endocrinology Diabetes and Metabolic Diseases University Children's Hospital UMC Ljubljana Bohoričeva Ulica 20 1000 Ljubljana Slovenia

Department of Molecular Medicine and Surgery Karolinska Institutet 141 86 Stockholm Sweden

Department of Pediatrics and Inherited Metabolic Disorders Charles University 1st Faculty of Medicine and General University Hospital Prague Ke Karlovu 455 2 128 08 Praha Czech Republic

Division of Child Neurology and Metabolic Medicine Center for Child and Adolescent Medicine Heidelberg University Hospital Im Neuenheimer Feld 430 69120 Heidelberg Germany

Faculty of Medicine University of Ljubljana Vrazov Trg 2 1000 Ljubljana Slovenia

National Screening Centre Institute of Health Information and Statistics of the Czech Republic 128 01 Prague Czech Republic

Office of the International Society for Neonatal Screening Reigerskamp 273 3607 HP Maarssen The Netherlands

Regional Coordinating Center for Rare Diseases European Reference Network for Hereditary Metabolic Diseases Udine University Hospital Piazzale Santa Maria Della Misericordia 15 33100 Udine Italy

Sheffield Children's NHS Foundation Trust Western Bank Sheffield S10 2TH UK

See more in PubMed

Lanpher B., Brunetti-Pierri N., Lee B. Inborn errors of metabolism: The flux from Mendelian to complex diseases. Nat. Rev. Genet. 2006;7:449–459. doi: 10.1038/nrg1880. PubMed DOI

Wilcken B., Wiley V., Hammond J., Carpenter K. Screening Newborns for Inborn Errors of Metabolism by Tandem Mass Spectrometry. N. Engl. J. Med. 2003;348:2304–2312. doi: 10.1056/NEJMoa025225. PubMed DOI

Therrell B.L., Padilla C.D., Loeber J.G., Kneisser I., Saadallah A., Borrajo G.J.C., Adams J. Current status of newborn screening worldwide: 2015. Semin. Perinatol. 2015;39:171–187. doi: 10.1053/j.semperi.2015.03.002. PubMed DOI

Loeber J.G., Platis D., Zetterström R.H., Almashanu S., Boemer F., Bonham J.R., Borde P., Brincat I., Cheillan D., Dekkers E., et al. Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010. Int. J. Neonatal Screen. 2021;7:15. doi: 10.3390/ijns7010015. PubMed DOI PMC

Sikonja J., Groselj U., Scarpa M., la Marca G., Cheillan D., Kölker S., Zetterström R.H., Kožich V., Le Cam Y., Gumus G., et al. Towards Achieving Equity and Innovation in Newborn Screening across Europe. Int. J. Neonatal Screen. 2022;8:31. doi: 10.3390/ijns8020031. PubMed DOI PMC

Greaves R.F., Pitt J., McGregor C., Wall M., Christodoulou J. Newborn bloodspot screening in the time of COVID-19. Genet. Med. 2021;23:1143–1150. doi: 10.1038/s41436-020-01086-6. PubMed DOI PMC

COVID-19 NBLS Response: Continuity of Operations Plans (COOP)|NewSTEPs. [(accessed on 4 October 2022)]. Available online: https://www.newsteps.org/resources/covid-19-nbs-response-continuity-operations-plans-coop.

Tumiene B., Peters H., Melegh B., Peterlin B., Utkus A., Fatkulina N., Pfliegler G., Graessner H., Hermanns S., Scarpa M., et al. Rare disease education in Europe and beyond: Time to act. Orphanet J. Rare Dis. 2022;17:441. doi: 10.1186/s13023-022-02527-y. PubMed DOI PMC

Wynn J., Tavakoli N.P., Armstrong N., Gomez J., Koval C., Lai C., Tang S., Prince A.Q., Quevedo Y., Rufino K., et al. Improving Recruitment for a Newborn Screening Pilot Study with Adaptations in Response to the COVID-19 Pandemic. Int. J. Neonatal Screen. 2022;8:23. doi: 10.3390/ijns8020023. PubMed DOI PMC

Koracin V., Loeber J.G., Mlinaric M., Battelino T., Bonham J.R., Groselj U. COVID-NBS ISNS global network. Global impact of COVID-19 on newborn screening programmes. BMJ Glob. Health. 2022;7:e007780. doi: 10.1136/bmjgh-2021-007780. PubMed DOI PMC

Sebastião F.M., Michelin-Tirelli K., Bender F., Lopes F.F., Moraes I., Kubaski F., Giugliani R., Burin M. COVID-19 impact on the diagnosis of Inborn Errors of Metabolism: Data from a reference center in Brazil. Genet. Mol. Biol. 2021;45:e20210253. doi: 10.1590/1678-4685-gmb-2021-0253. PubMed DOI PMC

Paneghetti L., Bellettato C.M., Sechi A., Stepien K.M., Scarpa M. One year of COVID-19: Infection rates and symptoms in patients with inherited metabolic diseases followed by MetabERN. Orphanet J. Rare Dis. 2022;17:109. doi: 10.1186/s13023-022-02247-3. PubMed DOI PMC

Mütze U., Gleich F., Barić I., Baumgartner M., Burlina A., Chapman K.A., Chien Y., Cortès-Saladelafont E., De Laet C., Dobbelaere D., et al. Impact of the SARS-CoV-2 pandemic on the health of individuals with intoxication-type metabolic diseases—Data from the E-IMD consortium. J. Inherit. Metab. Dis. 2022;46:220–231. doi: 10.1002/jimd.12572. PubMed DOI PMC

Sechi A., Macor D., Valent S., Da Riol R.M., Zanatta M., Spinelli A., Bianchi K., Bertossi N., Dardis A., Valent F., et al. Impact of COVID-19 related healthcare crisis on treatments for patients with lysosomal storage disorders, the first Italian experience. Mol. Genet. Metab. 2020;130:170–171. doi: 10.1016/j.ymgme.2020.04.002. PubMed DOI PMC

Singh S., Caggana M., Johnson C., Lee R., Zarbalian G., Gaviglio A., Keehn A., Morrison M., Becker S.J., Ojodu J. COVID-19 Pandemic-Related Impacts on Newborn Screening Public Health Surveillance. Int. J. Neonatal Screen. 2022;8:28. doi: 10.3390/ijns8020028. PubMed DOI PMC

Simon D., Broadbridge E., Baker M., Gaviglio A., Gruber D., Piper K.N., Tavakoli N.P., Sullivan J., Kennedy A. Common Challenges and Identified Solutions for State Newborn Screening Programs during COVID-19 Pandemic. Int. J. Neonatal Screen. 2022;8:7. doi: 10.3390/ijns8010007. PubMed DOI PMC

Loh T.P., Greaves R.F., Mak C.M., Salomons G.S., Bonham J.R., Lang T., IFCC Committee on Emerging Technologies in Paediatric Laboratory Medicine. Impact of COVID-19 on Pediatric Laboratory Medicine: An IFCC C-ETPLM, SSIEM, ISNS Global Survey. EJIFCC. 2022;33:194–208. PubMed PMC

Loh T.P., Horvath A.R., Wang C.-B., Koch D., Lippi G., Mancini N., Ferrari M., Hawkins R., Sethi S., Adeli K. The International Federation of Clinical Chemistry and Laboratory Medicine Taskforce on COVID-19. Laboratory practices to mitigate biohazard risks during the COVID-19 outbreak: An IFCC global survey. Clin. Chem. Lab. Med. 2020;58:1433–1440. doi: 10.1515/cclm-2020-0711. PubMed DOI

Ramgoolam T. The impact of COVID-19 on the GOSH newborn screening service. Arch. Dis. Child. 2020;105:A35.

Cheng R.J., Fisher A.C., Nicholson S.C. Interest in Home Birth during the COVID-19 Pandemic: Analysis of Google Trends Data. J. Midwifery Women’s Health. 2022;67:427–434. doi: 10.1111/jmwh.13341. PubMed DOI PMC

Verhoeven C.J.M., Boer J., Kok M., Nieuwenhuijze M., de Jonge A., Peters L.L. More home births during the COVID-19 pandemic in the Netherlands. Birth. 2022;49:792–804. doi: 10.1111/birt.12646. PubMed DOI PMC

Maceda E.B.G., Abadingo M.E., Panol K.A.R., Beltran F.D.E., Valdez-Acosta I.R.C., Taquiqui G.D., Gawigawen S.B., Macalino M.V.L., Aguirre-Aguinaldo L.M.S.M., Flores-Declaro M.A., et al. Newborn Screening Long-Term Follow-Up Clinics (Continuity Clinics) in the Philippines during the COVID-19 Pandemic: Continuing Quality Patient Care. Int. J. Neonatal Screen. 2022;9:2. doi: 10.3390/ijns9010002. PubMed DOI PMC

Aragona E., West D., Loyal J. Well-Newborn Unit Director Experiences During the COVID-19 Pandemic: A BORN Study. Hosp. Pediatr. 2021;11:e170–e181. doi: 10.1542/hpeds.2021-005862. PubMed DOI

Elmonem M.A., Belanger-Quintana A., Bordugo A., Boruah R., Cortès-Saladelafont E., Endrakanti M., Giraldo P., Grünert S.C., Gupta N., Kabra M., et al. The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective. Mol. Genet. Metab. 2020;131:285–288. doi: 10.1016/j.ymgme.2020.09.004. PubMed DOI PMC

Lippi G., Adeli K., Ferrari M., Horvath A.R., Koch D., Sethi S., Wang C.-B. Biosafety measures for preventing infection from COVID-19 in clinical laboratories: IFCC Taskforce Recommendations. Clin. Chem. Lab. Med. CCLM. 2020;58:1053–1062. doi: 10.1515/cclm-2020-0633. PubMed DOI

Guidance for General Laboratory Safety Practices during the COVID-19 Pandemic. [(accessed on 4 October 2022)]; Available online: https://www.cdc.gov/coronavirus/2019-ncov/lab/lab-safety-practices.html.

EPA Cleaning and Disinfecting: Best Practices during the COVID-19 Pandemic. [(accessed on 4 October 2022)]; Available online: https://www.epa.gov/coronavirus/cleaning-and-disinfecting-best-practices-during-covid-19-pandemic.

Colorado Newborn Screening State Emergency Plan for Time Critical Testing Limited Staff. [(accessed on 4 October 2022)]. Available online: https://www.newsteps.org/sites/default/files/covid-19_newborn_screening_state_emergency_plan_for_time_critical_testing_limited_staff_colorado_4.2.20.pdf.

Heather N., Morgan L., Knoll D., Shore K., de Hora M., Webster D. Introduction of a Protocol for Structured Follow-Up and Texting of Inadequate and Borderline-Positive Newborn Metabolic Screening Results. Int. J. Neonatal Screen. 2022;8:30. doi: 10.3390/ijns8020030. PubMed DOI PMC

Chudleigh J., Shakespeare L., Holder P., Chinnery H., Hack G., Gill T., Gould R., Southern K.W., Olander E.K., Morris S., et al. Co-designing improved communication of newborn bloodspot screening results to Parents: Mixed Methods Study. J. Particip. Med. 2022;14:e33485. doi: 10.2196/33485. PubMed DOI PMC

Gold J.I., Campbell I.M., Ficicioglu C. Provider Perspectives on the Impact of the COVID-19 Pandemic on Newborn Screening. Int. J. Neonatal Screen. 2021;7:38. doi: 10.3390/ijns7030038. PubMed DOI PMC

CMS Telehealth Services MLN Fact Sheet. [(accessed on 4 October 2022)]; Available online: https://www.cms.gov/Outreach-and-Education/Medicare-Learning-Network-MLN/MLNProducts/MLN-Publications-Items/CMS1243327.

Lampe C., MetabERN collaboration group, Dionisi-Vici C., Bellettato C.M., Paneghetti L., van Lingen C., Bond S., Brown C., Finglas A., Francisco R., et al. The impact of COVID-19 on rare metabolic patients and healthcare providers: Results from two MetabERN surveys. Orphanet J. Rare Dis. 2020;15:341. doi: 10.1186/s13023-020-01619-x. PubMed DOI PMC

Galle A., Semaan A., Huysmans E., Audet C., Asefa A., Delvaux T., Afolabi B.B., El Ayadi A.M., Benova L. A double-edged sword—Telemedicine for maternal care during COVID-19: Findings from a global mixed-methods study of healthcare providers. BMJ Glob. Health. 2021;6:e004575. doi: 10.1136/bmjgh-2020-004575. PubMed DOI PMC

Shur N., Atabaki S.M., Kisling M.S., Tabarani A., Williams C., Fraser J.L.S., Regier D.S., Summar M., Rare Disease Institute. Rapid deployment of a telemedicine care model for genetics and metabolism during COVID-19. Am. J. Med. Genet. Part A. 2021;185:68–72. doi: 10.1002/ajmg.a.61911. PubMed DOI PMC

Mak D., Akinseye L., Lahoti A., Diaz-Thomas A. Abnormal Newborn Screen during a Pandemic. Neoreviews. 2022;23:e212–e215. doi: 10.1542/neo.23-3-e212. PubMed DOI

Ramanan A.V., Modi N., de Wildt S.N., c4c Learning from COVID-19 Group Improving clinical paediatric research and learning from COVID-19: Recommendations by the Conect4Children expert advice group. Pediatr. Res. 2022;91:1069–1077. doi: 10.1038/s41390-021-01587-3. PubMed DOI PMC

Osterrieder A., Cuman G., Pan-Ngum W., Cheah P.K., Cheah P.K., Peerawaranun P., Silan M., Orazem M., Perkovic K., Groselj U., et al. Economic and social impacts of COVID-19 and public health measures: Results from an anonymous online survey in Thailand, Malaysia, the UK, Italy and Slovenia. BMJ Open. 2021;11:e046863. doi: 10.1136/bmjopen-2020-046863. PubMed DOI PMC

Gemeinsamer Bundesausschuss Richtlinie des Gemeinsamen Bundesausschusses über die Früher-kennung von Krankheiten bei Kindern (Kinder-Richtlinie) 2022. [(accessed on 17 February 2023)]. Available online: https://www.g-ba.de/downloads/62-492-3038/Kinder-RL_2022-12-15_iK-2022-12-15.pdf.

Abhyankar S., Goodwin R.M., Sontag M., Yusuf C., Ojodu J., McDonald C.J. An update on the use of health information technology in newborn screening. Semin. Perinatol. 2015;39:188–193. doi: 10.1053/j.semperi.2015.03.003. PubMed DOI PMC

Malvagia S., Forni G., Ombrone D., la Marca G. Development of Strategies to Decrease False Positive Results in Newborn Screening. Int. J. Neonatal Screen. 2020;6:84. doi: 10.3390/ijns6040084. PubMed DOI PMC

Department of Health and Human Services Newborn Screening Contingency Plan (CONPLAN) [(accessed on 17 February 2023)]; Available online: https://www.cdc.gov/ncbddd/documents/screening-contingency-plan-version-ii.pdf.