Gestational age-specific reference ranges from different laboratories misclassify pregnant women's thyroid status: comparison of two longitudinal prospective cohort studies

TY - JOUR

T1 - Gestational age-specific reference ranges from different laboratories misclassify pregnant women's thyroid status

T2 - comparison of two longitudinal prospective cohort studies

AU - Bliddal, Sofie

AU - Feldt-Rasmussen, Ulla

AU - Boas, Malene

AU - Faber, Jens

AU - Juul, Anders

AU - Larsen, Torben

AU - Precht, Dorthe Hansen

PY - 2014/2

Y1 - 2014/2

N2 - Abstract Objectives: Correct interpretation of thyroid status during pregnancy is vital to secure fetal development. Pregnancy-related changes in maternal thyroid status necessitate the use of gestational age-specific reference ranges. In this study, we investigated between-laboratory reproducibility of thyroid reference ranges in pregnant women. Design: Comparison of two longitudinal prospective cohort studies including 255 (cohort 1) and 101 (cohort 2) healthy antibody-negative Danish pregnant women attending prenatal care at Copenhagen University Hospital. Methods: Different immunoassays were used to measure thyroid hormone levels in the two cohorts. Thyroid hormone reference ranges were established for every 5 weeks of gestation. Differences between cohorts were explored through mixed-model repeated measures regression analyses. By applying reference ranges from one cohort to the other, the proportion of women who would be misclassified by doing so was investigated. Results: TSH increased and free thyroxine (FT4) decreased as pregnancy progressed. Results indicated highly significant differences between cohorts in free triiodothyronine (FZ21.3, P!0.001) and FT4 (FZ941, P!0.001). TSH levels were comparable (PZ0.09). Up to 90.3% of the women had FT4 levels outside their laboratory's nonpregnant reference range, and up to 100% outside the other cohort's gestational-Age-specific reference ranges. Z-score-based reference ranges markedly improved comparison between cohorts. Conclusion: Even in the same region, the use of gestational-Age-specific reference ranges from different laboratories led to misclassification. Up to 100% of maternal FT4 levels fell outside the other cohort's reference range despite similar TSH levels. In clinical practice, thyroid testing of pregnant women without adding method specificity to gestational age-dependent reference ranges will compromise patient safety.

AB - Abstract Objectives: Correct interpretation of thyroid status during pregnancy is vital to secure fetal development. Pregnancy-related changes in maternal thyroid status necessitate the use of gestational age-specific reference ranges. In this study, we investigated between-laboratory reproducibility of thyroid reference ranges in pregnant women. Design: Comparison of two longitudinal prospective cohort studies including 255 (cohort 1) and 101 (cohort 2) healthy antibody-negative Danish pregnant women attending prenatal care at Copenhagen University Hospital. Methods: Different immunoassays were used to measure thyroid hormone levels in the two cohorts. Thyroid hormone reference ranges were established for every 5 weeks of gestation. Differences between cohorts were explored through mixed-model repeated measures regression analyses. By applying reference ranges from one cohort to the other, the proportion of women who would be misclassified by doing so was investigated. Results: TSH increased and free thyroxine (FT4) decreased as pregnancy progressed. Results indicated highly significant differences between cohorts in free triiodothyronine (FZ21.3, P!0.001) and FT4 (FZ941, P!0.001). TSH levels were comparable (PZ0.09). Up to 90.3% of the women had FT4 levels outside their laboratory's nonpregnant reference range, and up to 100% outside the other cohort's gestational-Age-specific reference ranges. Z-score-based reference ranges markedly improved comparison between cohorts. Conclusion: Even in the same region, the use of gestational-Age-specific reference ranges from different laboratories led to misclassification. Up to 100% of maternal FT4 levels fell outside the other cohort's reference range despite similar TSH levels. In clinical practice, thyroid testing of pregnant women without adding method specificity to gestational age-dependent reference ranges will compromise patient safety.

KW - Adult

KW - Diagnostic Errors

KW - Female

KW - Fluoroimmunoassay

KW - Gestational Age

KW - Humans

KW - Longitudinal Studies

KW - Luminescent Measurements

KW - Pregnancy

KW - Prospective Studies

KW - Reference Values

KW - Reproducibility of Results

KW - Thyroid Diseases

KW - Thyroid Function Tests

KW - Thyroid Gland

KW - Thyrotropin

KW - Thyroxine

KW - Triiodothyronine

U2 - 10.1530/eje-13-0672

DO - 10.1530/eje-13-0672

M3 - Journal article

C2 - 24277773

SN - 0804-4643

VL - 170

SP - 329

EP - 339

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 2

ER -