First- and second-trimester thyroid hormone reference data in pregnant women: a FaSTER (First- and Second-Trimester Evaluation of Risk for aneuploidy) Research Consortium study

Abstract

Objective: The purpose of this study was to calculate first and second trimester reference ranges and within-woman correlations for TSH, free T4, and thyroid antibodies.

Study design: TSH, free T4, and thyroid antibodies were measured in paired sera from 9562 women in the FaSTER trial of Down syndrome screening.

Results: The median first trimester TSH (1.05 mIU/L) is lower than the second (1.23 mIU/L); and 98th centile is higher (4.15 vs 3.77 mIU/L). Within-woman paired TSH correlations are moderately strong (r(2) = 0.64). Among women with first trimester TSH values above the 98th centile, second trimester values are over the 95th centile in 68%. Median first trimester free T4 values (1.10 ng/dL) are higher than second (1.01 ng/dL). Paired free T4 measurements correlate weakly (r(2) = 0.23). Among women with first trimester free T4 values below the 2nd centile, second trimester values are below the 5th centile in 32%. Antibody measurements correlate strongly between trimesters (thyroperoxidase r(2) = 0.79, thyroglobulin r(2) = 0.83).

Conclusion: TSH and free T4 measurements require gestation-specific reference ranges.

Figure 1. Selected TSH centiles for 9,562 women by gestational week in the first and second trimesters

The variance (spread) of TSH values is greater at weeks 10 through 13 than at weeks 15 through 18, at both the lower and upper extremes of the distribution.

Figure 2. TSH measurements in 9,562 women who provided a sample in the first trimester (horizontal axis) and in the second trimester (vertical axis)

In this Figure, 75 paired samples were excluded, because at least one of the TSH measurements was below 0.01 mIU/L. The shown measurements are highly correlated (r² = 0.64).

Figure 3. TSH measurements in 191 women with TSH values greater than the 98^th centile in the first trimester

Overall, 130 (68%) of the values remain above the 95^th centile, and only four are below the 50^th centile, in the second trimester. Open squares indicate TSH values associated with positive antibodies.

Figure 4. Free T4 measurements in 9,562 women who provided samples in both the first (horizontal axis) and second (vertical axis) trimesters

In this Figure, two paired samples were excluded because at least one of the free T4 measurements was below 0.3 or greater than 5 ng/dL. The shown measurements are less highly correlated (r² = 0.23) than TSH.

Figure 5. Free T4 measurements in 177 women with free T4 values less than the 2^nd centile in the first trimester

Overall, 56 of the values (32%) remain below the 5^th centile, in the second trimester. In addition, 28 of the values (16%) fall above the median in the second trimester.

Figure 6. Thyro-peroxidase (TPO) antibody measurements in women having at least one elevated result in the first or second trimester of pregnancy

An elevated TPO antibody level (defined as 35 IU/mL or greater) in the first trimester was found in 933 women in the cohort (9.8%). The two TPO antibody measurements in this subgroup are highly correlated (r²=0.79, after logarithmic transformation and trimming of fourteen women having one measurement under 10 IU/mL).