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Defining Gestational Thyroid Dysfunction Through Modified Nonpregnancy Reference Intervals: An Individual Participant Meta-Analysis Publisher Pubmed



Osinga JAJ1, 2 ; Nelson SM3 ; Walsh JP4, 5 ; Ashoor G6 ; Palomaki GE7 ; Lopezbermejo A8, 9 ; Bassols J10 ; Aminorroaya A11 ; Broeren MAC12 ; Chen L13 ; Lu X13 ; Brown SJ4 ; Veltri F14 ; Huang K15 Show All Authors
Authors
  1. Osinga JAJ1, 2
  2. Nelson SM3
  3. Walsh JP4, 5
  4. Ashoor G6
  5. Palomaki GE7
  6. Lopezbermejo A8, 9
  7. Bassols J10
  8. Aminorroaya A11
  9. Broeren MAC12
  10. Chen L13
  11. Lu X13
  12. Brown SJ4
  13. Veltri F14
  14. Huang K15
  15. Mannisto T16
  16. Vafeiadi M17
  17. Taylor PN18
  18. Tao FB15
  19. Chatzi L19
  20. Kianpour M11
  21. Suvanto E20
  22. Grineva EN21
  23. Nicolaides KH22
  24. Dalton ME23
  25. Poppe KG21
  26. Alexander E24
  27. Feldtrasmussen U25, 26
  28. Bliddal S25, 26
  29. Popova PV21
  30. Chaker L1, 2, 27
  31. Visser WE1, 2
  32. Peeters RP1, 2
  33. Derakhshan A1, 2
  34. Vrijkotte TGM28
  35. Pop VJM29
  36. Korevaar TIM1, 2
Show Affiliations
Authors Affiliations
  1. 1. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3000 CA, Netherlands
  2. 2. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, 3000 CA, Netherlands
  3. 3. School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, G12 8QQ, United Kingdom
  4. 4. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, 6009, WA, Australia
  5. 5. Medical School, University of Western Australia, Crawley, 6009, WA, Australia
  6. 6. Harris Birthright Research Center for Fetal Medicine, King's College Hospital, London, SE5 9RS, United Kingdom
  7. 7. Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School at Brown University, Providence, 02903, RI, United States
  8. 8. Pediatric Endocrinology Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital, Girona, 17007, Spain
  9. 9. Departament de Ciencies Mediques, Universitat de Girona, Girona, 17003, Spain
  10. 10. Maternal-Fetal Metabolic Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital, Girona, 17007, Spain
  11. 11. Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, 81745-33871, Iran
  12. 12. Laboratory of Clinical Chemistry and Haematology, Maxima Medical Centre, Veldhoven, 5504 DB, Netherlands
  13. 13. Department of Endocrinology, Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China
  14. 14. Endocrine Unit, Centre Hospitalier Universitaire Saint-Pierre, UniversitCrossed D Sign© Libre de Bruxelles (ULB), Brussels, 1000, Belgium
  15. 15. Department of Maternal, Child and Adolescent Health, Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, Anhui, 230032, China
  16. 16. NordLab, Oulu and Translational Medicine Research Unit, University of Oulu, Oulu, 90570, Finland
  17. 17. Department of Social Medicine, School of Medicine, University of Crete, Heraklion, Crete, 710 03, Greece
  18. 18. Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, CF10 3EU, United Kingdom
  19. 19. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, 90089, CA, United States
  20. 20. Department of Obstetrics and Gynecology, Medical Research Center Oulu, University of Oulu, Oulu, 90570, Finland
  21. 21. Institute of Endocrinology, Almazov National Medical Research Centre, Saint Petersburg, 197341, Russian Federation
  22. 22. Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, SE5 9RS, United Kingdom
  23. 23. Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, 10032, NY, United States
  24. 24. Division of Endocrinology, Hypertension and Diabetes, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, MA, United States
  25. 25. Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Copenhagen, 2100, Denmark
  26. 26. Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, 2100, Denmark
  27. 27. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, Netherlands
  28. 28. Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, 1081 HV, Netherlands
  29. 29. Department of Medical and Clinical Psychology, Tilburg University, Tilburg, 5000 LE, Netherlands

Source: Journal of Clinical Endocrinology and Metabolism Published:2024


Abstract

Background: Establishing local trimester-specific reference intervals for gestational TSH and free T4 (FT4) is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific nonpregnancy reference intervals as compared to trimester-specific reference intervals. Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the nonpregnancy reference intervals included an absolute modification (per. 1 mU/L TSH or 1 pmol/L free T4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 and 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity, and positive predictive value (PPV) of these methodologies with population-based trimester-specific reference intervals. Results: The final study population comprised 52 496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity,. 70, CI, 0.47-0.86; PPV, 0.64, CI, 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity, 0.91; CI, 0.67-0.98; PPV, 0.71, CI, 0.58-0.80). Absolute and fixed modifications yielded similar results. CIs were wide, limiting generalizability. Conclusion: We could not identify modifications of nonpregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned toward studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits. © 2024 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
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