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Method-dependent variation in TSH and FT4 reference intervals in pregnancy: A systematic review
Onyebuchi E Okosieme1,2, Medha Agrawal1,2, Danyal Usman1,2
1Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, UK.
Thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference intervals in pregnancy vary significantly by assay method. These variations highlight the need for method-specific gestational reference intervals, not extrapolation from non-pregnant values.
Area of Science:
- Endocrinology
- Clinical Chemistry
- Reproductive Medicine
Background:
- Thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference intervals during pregnancy are crucial for diagnosing thyroid dysfunction.
- Existing reference intervals may differ based on assay methods, but systematic evaluations are lacking.
Purpose of the Study:
- To systematically review and quantify method-related differences in gestational TSH and FT4 reference intervals.
- To compare intervals across four common assay methods: Abbott, Beckman, Roche, and Siemens.
Main Methods:
- Systematic literature search for studies published between 2000 and 2020.
- Inclusion of studies on healthy pregnant women without thyroid antibodies or disease.
- Extraction of trimester-specific TSH and FT4 reference intervals (2.5-97.5 percentiles) and non-pregnant reference intervals.
Main Results:
- Significant study-to-study variation in TSH and FT4 reference intervals was observed.
- The Beckman method consistently showed lower FT4 reference intervals.
- First-trimester TSH upper limits were highly variable and often unpredictable from non-pregnant values.
Conclusions:
- Significant intra- and inter-method disparities exist in gestational thyroid hormone reference intervals.
- Extrapolating non-pregnant values for gestational references is unreliable.
- Laboratories should establish method-specific gestational reference intervals for their populations.
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