Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors
Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded t...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | International Journal of Neonatal Screening |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2409-515X/8/4/58 |
| _version_ | 1797457185826930688 |
|---|---|
| author | Martin Kharrazi Charlene Sacramento Anne Marie Comeau Jaime E. Hale Michele Caggana Denise M. Kay Rachel Lee Brendan Reilly John D. Thompson Samya Z. Nasr Mary Kleyn Gary Hoffman Mei W. Baker Colleen Clarke Cheryl L. Harris M. Christine Dorley Hilary Fryman Ankit Sutaria Amy Hietala Holly Winslow Holly Richards Bradford L. Therrell |
| author_facet | Martin Kharrazi Charlene Sacramento Anne Marie Comeau Jaime E. Hale Michele Caggana Denise M. Kay Rachel Lee Brendan Reilly John D. Thompson Samya Z. Nasr Mary Kleyn Gary Hoffman Mei W. Baker Colleen Clarke Cheryl L. Harris M. Christine Dorley Hilary Fryman Ankit Sutaria Amy Hietala Holly Winslow Holly Richards Bradford L. Therrell |
| author_sort | Martin Kharrazi |
| collection | DOAJ |
| description | Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above (“high”) and below (“low”) the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with “high” CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with “low” CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce “high” IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce “low” IRT CFFNs. |
| first_indexed | 2024-03-09T16:17:30Z |
| format | Article |
| id | doaj.art-304dd445b57e49f2992e15dc0f65b32c |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-09T16:17:30Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-304dd445b57e49f2992e15dc0f65b32c2023-11-24T15:35:25ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2022-10-01845810.3390/ijns8040058Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk FactorsMartin Kharrazi0Charlene Sacramento1Anne Marie Comeau2Jaime E. Hale3Michele Caggana4Denise M. Kay5Rachel Lee6Brendan Reilly7John D. Thompson8Samya Z. Nasr9Mary Kleyn10Gary Hoffman11Mei W. Baker12Colleen Clarke13Cheryl L. Harris14M. Christine Dorley15Hilary Fryman16Ankit Sutaria17Amy Hietala18Holly Winslow19Holly Richards20Bradford L. Therrell21California Department of Public Health, Richmond, CA 94804, USASequoia Foundation, La Jolla, CA 92037, USANew England Newborn Screening Program, UMass Chan Medical School, Worcester, MA 01605, USANew England Newborn Screening Program, UMass Chan Medical School, Worcester, MA 01605, USANew York State Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USANew York State Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY 12208, USATexas Department of State Health Services, Austin, TX 78756, USATexas Department of State Health Services, Austin, TX 78756, USAWashington State Department of Health, Public Health Laboratories, Newborn Screening Program, Shoreline, WA 98155, USAMichigan Medicine, University of Michigan, Ann Arbor, MI 48109, USAMichigan Department of Health and Human Services, Lansing, MI 48913, USAWisconsin Newborn Screening Laboratory at Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USAWisconsin Newborn Screening Laboratory at Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USALouisiana Office of Public Health, Baton Rouge, LA 70802, USALouisiana Office of Public Health, Baton Rouge, LA 70802, USATennessee Department of Health, Newborn Screening Laboratory and Follow-Up Program, Nashville, TN 37216, USATennessee Department of Health, Newborn Screening Laboratory and Follow-Up Program, Nashville, TN 37216, USAGeorgia Department of Public Health, Atlanta, GA 30303, USAMinnesota Department of Health, Public Health Laboratory, Newborn Screening, St. Paul, MN 55164, USAMinnesota Department of Health, Public Health Laboratory, Newborn Screening, St. Paul, MN 55164, USAMaine Newborn Screening Program, Augusta, ME 04333, USANational Newborn Screening and Global Resource Center, Austin, TX 78759, USATesting immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above (“high”) and below (“low”) the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with “high” CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with “low” CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce “high” IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce “low” IRT CFFNs.https://www.mdpi.com/2409-515X/8/4/58cystic fibrosisCFnewborn screeningmissed casesimmunoreactive trypsinogenIRT |
| spellingShingle | Martin Kharrazi Charlene Sacramento Anne Marie Comeau Jaime E. Hale Michele Caggana Denise M. Kay Rachel Lee Brendan Reilly John D. Thompson Samya Z. Nasr Mary Kleyn Gary Hoffman Mei W. Baker Colleen Clarke Cheryl L. Harris M. Christine Dorley Hilary Fryman Ankit Sutaria Amy Hietala Holly Winslow Holly Richards Bradford L. Therrell Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors International Journal of Neonatal Screening cystic fibrosis CF newborn screening missed cases immunoreactive trypsinogen IRT |
| title | Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors |
| title_full | Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors |
| title_fullStr | Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors |
| title_full_unstemmed | Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors |
| title_short | Missed Cystic Fibrosis Newborn Screening Cases due to Immunoreactive Trypsinogen Levels below Program Cutoffs: A National Survey of Risk Factors |
| title_sort | missed cystic fibrosis newborn screening cases due to immunoreactive trypsinogen levels below program cutoffs a national survey of risk factors |
| topic | cystic fibrosis CF newborn screening missed cases immunoreactive trypsinogen IRT |
| url | https://www.mdpi.com/2409-515X/8/4/58 |
| work_keys_str_mv | AT martinkharrazi missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT charlenesacramento missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT annemariecomeau missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT jaimeehale missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT michelecaggana missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT denisemkay missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT rachellee missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT brendanreilly missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT johndthompson missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT samyaznasr missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT marykleyn missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT garyhoffman missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT meiwbaker missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT colleenclarke missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT cheryllharris missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT mchristinedorley missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT hilaryfryman missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT ankitsutaria missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT amyhietala missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT hollywinslow missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT hollyrichards missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors AT bradfordltherrell missedcysticfibrosisnewbornscreeningcasesduetoimmunoreactivetrypsinogenlevelsbelowprogramcutoffsanationalsurveyofriskfactors |