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Tsh and Ft4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis Publisher Pubmed



Osinga JAJ1, 2 ; Derakhshan A1, 2 ; Palomaki GE3 ; Ashoor G4 ; Mannisto T5 ; Maraka S6, 7, 8 ; Chen L9 ; Bliddal S10 ; Lu X9 ; Taylor PN11 ; Vrijkotte TGM12 ; Tao FB13 ; Brown SJ14 ; Ghafoor F15 Show All Authors
Authors
  1. Osinga JAJ1, 2
  2. Derakhshan A1, 2
  3. Palomaki GE3
  4. Ashoor G4
  5. Mannisto T5
  6. Maraka S6, 7, 8
  7. Chen L9
  8. Bliddal S10
  9. Lu X9
  10. Taylor PN11
  11. Vrijkotte TGM12
  12. Tao FB13
  13. Brown SJ14
  14. Ghafoor F15
  15. Poppe K16
  16. Veltri F16
  17. Chatzi L17
  18. Vaidya B18
  19. Broeren MAC19
  20. Shields BM20
  21. Itoh S21
  22. Mosso L22
  23. Popova PV23, 24, 25
  24. Anopova AD23
  25. Kishi R21
  26. Aminorroaya A26
  27. Kianpour M26
  28. Lopezbermejo A27, 28
  29. Oken E29
  30. Pirzada A30
  31. Vafeiadi M31
  32. Bramer WM32
  33. Suvanto E33
  34. Yoshinaga J34
  35. Huang K35
  36. Bassols J36
  37. Boucai L37
  38. Feldtrasmussen U10
  39. Grineva EN23
  40. Pearce EN38
  41. Alexander EK39
  42. Pop VJM40
  43. Nelson SM41
  44. Walsh JP14, 42
  45. Peeters RP1, 2
  46. Chaker L1, 2, 43
  47. Nicolaides KH44
  48. Dalton ME45
  49. Korevaar TIM1, 2
Show Affiliations
Authors Affiliations
  1. 1. Department of Internal Medicine, Erasmus University Medical Center, Wytemaweg 80, Rotterdam, 3015, Netherlands
  2. 2. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, Netherlands
  3. 3. Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School, Brown University, Providence, 02905, RI, United States
  4. 4. Harris Birthright Research Center for Fetal Medicine, King's College Hospital, London, United Kingdom
  5. 5. Northern Finland Laboratory Center Nordlab and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
  6. 6. Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, 72205, AR, United States
  7. 7. Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, 55902, MN, United States
  8. 8. Central Arkansas Veterans Healthcare System, Little Rock, 72205, AR, United States
  9. 9. Department of Endocrinology, Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  10. 10. Department of Medical Endocrinology and Metabolism, Copenhagen University Hospital, Rigshospitalet, Department of Clinical Medicine, Faculty of Health and clinical Sciences, Copenhagen University, Copenhagen, Denmark
  11. 11. Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, United Kingdom
  12. 12. Department of Public and Occupational Health, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, Netherlands
  13. 13. Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui, Hefei, China
  14. 14. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  15. 15. Department of Research and Innovation, Shalamar Institute of Health Sciences, Lahore, Pakistan
  16. 16. Endocrine Unit, Centre Hospitalier Universitaire Saint-Pierre, Universite Libre de Bruxelles (ULB), Brussels, Belgium
  17. 17. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 90089, CA, United States
  18. 18. Department of Endocrinology, Royal Devon and Exeter Hospital NHS Foundation Trust, University of Exeter Medical School, Exeter, United Kingdom
  19. 19. Laboratory of Clinical Chemistry and Haematology, M xima Medical Centre, Veldhoven, Netherlands
  20. 20. Department of Medical Statistics, University of Exeter Medical School, Exeter, United Kingdom
  21. 21. Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan
  22. 22. Departments of Endocrinology, Pontificia Universidad Catolica de Chile, Santiago, Chile
  23. 23. Institute of Endocrinology, Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
  24. 24. Department of Internal Diseases and Endocrinology, St. Petersburg Pavlov State Medical University, Saint Petersburg, Russian Federation
  25. 25. World-Class Research Center for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
  26. 26. Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  27. 27. Pediatric Endocrinology Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital, Girona, Spain
  28. 28. Departament de Ci ncies M diques, Universitat de Girona, Spain
  29. 29. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School, Boston, 02115, MA, United States
  30. 30. Shifa Institute of Medical Technology, Shifa International Hospital, Islamabad, Pakistan
  31. 31. Department of Social Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece
  32. 32. Medical Library, Erasmus University Medical Centre, Rotterdam, Netherlands
  33. 33. Department of Obstetrics and Gynecology and Medical Research Center Oulu, University of Oulu, Oulu, Finland
  34. 34. Faculty of Life Sciences, Toyo University, Gunma, Japan
  35. 35. Department of Maternal, Child and Adolescent Health, Scientific Research Center in Preventive Medicine, School of Public Health, Anhui Medical University, China
  36. 36. Maternal-Fetal Metabolic Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta Hospital, Girona, Spain
  37. 37. Department of Medicine, Division of Endocrinology, Memorial Sloan-Kettering Cancer Center, Weill Cornell University, New York, 10065, NY, United States
  38. 38. Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, 02118, MA, United States
  39. 39. Division of Endocrinology, Hypertension and Diabetes, Brigham and Women's Hospital, Harvard Medical School, Boston, 0211, MA, United States
  40. 40. Department of Medical and Clinical Psychology, Tilburg University, Tilburg, Netherlands
  41. 41. School of Medicine, University of Glasgow, Glasgow, United Kingdom
  42. 42. Medical School, University of Western Australia, Crawley, WA, Australia
  43. 43. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands
  44. 44. Department of Women and Children's Health, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
  45. 45. Department of Obstetrics and Gynecology, Columbia University, Irving Medical Center, New York, 10032, United States

Source: Journal of Clinical Endocrinology and Metabolism Published:2022


Abstract

Context: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. Conclusion: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria. © 2022 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
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