Pregnancy-specific Reference Intervals for TSH and FT4: Novel Insights From Preconception-gestation Longitudinal Data

Pregnancy-specific changes in thyroid physiology have prompted the use of pregnancy-specific reference intervals to diagnose thyroid disease. However, such reference intervals are not widely available, and there is no evidence of their superiority over nonpregnancy reference intervals. Preconception data are understudied benchmarks to compare pregnancy-specific and nonpregnancy reference intervals. Moreover, the added value of free T3 (FT3) measurements, for example in cases of (subclinical) hyperthyroidism, remains to be quantified.

This study was embedded within Generation R Next, a population-based prospective cohort from preconception through postpartum in Rotterdam. Prevalence of thyroid disease entities was assessed using both pregnancy-specific and nonpregnancy reference intervals during pregnancy and using nonpregnancy reference intervals in the preconception period. FT3 concentrations of both euthyroid participants and those with thyroid disease entities were compared in the preconception period and during pregnancy.

The study population included 1058 women during preconception and 2084 women during pregnancy. The prevalence of subclinical hypothyroidism during pregnancy was 1.5% with the use of nonpregnancy reference intervals and 3.6% with pregnancy-specific reference intervals vs 2.2% during preconception. The prevalence of subclinical hyperthyroidism during pregnancy was 11.1% with the use of nonpregnancy reference intervals and 1.5% with pregnancy-specific reference intervals vs 2.0% during preconception. Additional FT3 measurements reclassified 5.6% of subclinical hyperthyroidism cases to hyperthyroidism during preconception and 14.3% during pregnancy.

This is the first study to assess the prevalence of (sub)clinical thyroid disease during pregnancy comparing nonpregnancy and pregnancy-specific reference intervals, while also comparing these prevalences to preconception data from the same source population. We show that pregnancy-specific reference intervals likely result in overdiagnosis of subclinical hypothyroidism and that FT3 has limited value in diagnosing (sub)clinical thyroid disease during pregnancy.