Trimester-Specific Reference Intervals for Thyroid Function Tests in Pregnancy
First Trimester Reference Intervals
TSH reference intervals in the first trimester range from 0.04-0.34 mIU/L (lower limit) to 2.53-3.81 mIU/L (upper limit) across different populations and assay platforms. 1, 2, 3, 4
- TSH: The most robust US data using Roche analyzers shows a first trimester range of 0.16-2.82 mIU/L 1
- Free T4 (FT4): 12.0-18.5 pmol/L (or 0.8-1.53 ng/dL when converted) 1, 4
- Total T4 (tT4): 62.8-177.9 nmol/L (or 7.31-15.00 μg/dL) 1, 4
- Free T3 (FT3): 1.5-3.4 nmol/L (or 0.90-2.51 ng/mL) 1, 4
Second Trimester Reference Intervals
TSH increases slightly in the second trimester, with upper limits ranging from 2.73-4.07 mIU/L, while free T4 progressively decreases throughout pregnancy. 1, 2, 3
- TSH: 0.18-0.68 mIU/L (lower) to 2.73-4.07 mIU/L (upper) across populations 1, 2, 3
- Free T4 (FT4): 10.2-16.6 pmol/L (or 0.7-1.20 ng/dL), representing a decline from first trimester 1, 4
- Total T4 (tT4): 66.6-176.0 nmol/L (or 8.92-17.38 μg/dL) 1, 4
- Free T3 (FT3): 1.56-3.6 nmol/L (or 1.99-2.87 ng/mL) 1, 4
Third Trimester Reference Intervals
By the third trimester, free T4 decreases by approximately 14.8% and free T3 by 13.2% compared to first trimester values, while TSH stabilizes at slightly higher levels than early pregnancy. 3
- TSH: 0.60-0.63 mIU/L (lower) to 4.00-4.50 mIU/L (upper) 3, 4
- Free T4 (FT4): Median values are 14.8% lower than first trimester, with ranges of 0.7-1.20 ng/dL 3, 4
- Total T4 (tT4): 7.98-17.70 μg/dL 4
- Free T3 (FT3): Median values are 13.2% lower than first trimester, with ranges of 1.20-2.70 ng/mL 3, 4
Critical Implementation Considerations
Institutions must calculate their own pregnancy-specific reference intervals rather than relying on universal cutoffs, as substantial variation exists between populations, assay platforms, and geographic regions. 5
- Population-specific factors including ethnicity, body mass index, and iodine status significantly affect thyroid function reference intervals during pregnancy 5
- The US data using Roche analyzers represents the most directly applicable reference for American laboratories using this platform 1
- Mediterranean populations (Greece) show slightly different ranges (TSH 0.05-2.53 first trimester, 0.18-2.73 second trimester) 2
- Iraqi populations demonstrate even wider variation (TSH 0.04-3.77 first trimester), highlighting the critical importance of population-specific ranges 4
Clinical Significance of Accurate Reference Intervals
Even small subclinical variations in thyroid function have been associated with detrimental pregnancy outcomes including low birth weight, pregnancy loss, preeclampsia, and neurodevelopmental effects in offspring. 5
- Using incorrect reference intervals leads to misclassification of thyroid disorders and inappropriate treatment decisions 5, 2
- Between 5.9-6.8% of pregnant women have TSH values exceeding population-specific upper limits when appropriate trimester-specific ranges are applied 2
- Standard non-pregnant reference intervals are completely unsuitable for pregnancy and result in both under-diagnosis and over-treatment 5, 3
Assay-Specific Recommendations
For laboratories using Roche platforms (Modular e170 or cobas e801), the US-derived reference intervals provide the most appropriate starting point for American populations. 1, 3
- Roche platform data from Caucasian populations shows consistent patterns across studies, with TSH 0.34-3.81 mIU/L in first trimester 3
- Electrochemiluminescence techniques may yield different absolute values requiring platform-specific validation 4
- The progressive decline in free T4 and free T3 throughout pregnancy is consistent across all assay platforms and populations 1, 3, 4