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

Area of Science:

• Reproductive endocrinology and metabolism.
• Clinical diagnostics and laboratory medicine.

Background:

• Thyroid physiology undergoes significant changes during pregnancy, necessitating pregnancy-specific reference intervals for accurate diagnosis.
• However, the clinical utility and superiority of these specialized intervals over standard non-pregnancy intervals remain unproven.
• Preconception data offer a valuable baseline for comparing diagnostic accuracy.

Purpose of the Study:

• To evaluate the prevalence of thyroid disease using both pregnancy-specific and non-pregnancy reference intervals during gestation.
• To compare these prevalence rates with preconception data.
• To assess the diagnostic contribution of free T3 (FT3) measurements in pregnant individuals.

Main Methods:

• A prospective, population-based cohort study (Generation R Next) in Rotterdam.
• Assessment of thyroid disease prevalence using pregnancy-specific and non-pregnancy reference intervals during pregnancy.
• Comparison with non-pregnancy reference intervals in the preconception period; FT3 levels analyzed in euthyroid and thyroid-affected participants.

Main Results:

• The study included 1,058 women preconceptionally and 2,084 during pregnancy.
• Pregnancy-specific intervals showed higher subclinical hypothyroidism (3.6%) vs. non-pregnancy (1.5%), and lower subclinical hyperthyroidism (1.5%) vs. non-pregnancy (11.1%).
• FT3 testing could reclassify 14.3% of pregnant subclinical hyperthyroidism cases.

Conclusions:

• This study is the first to compare pregnancy vs. non-pregnancy reference intervals for thyroid disease prevalence against preconception data.
• Pregnancy-specific reference intervals may lead to overdiagnosis of subclinical hypothyroidism.
• FT3 measurements appear to have limited added value for diagnosing thyroid dysfunction in pregnancy.