title: Gestational age-specific reference ranges from different laboratories misclassify pregnant women's thyroid status: comparison of two longitudinal prospective cohort studies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 (F=21.3, P<0.001) and FT4 (F=941, P<0.001). TSH levels were comparable (P=0.09). 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, Section 2132, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Sofie
authors.initials: S
authors.lastname: Bliddal
authors.forename: Ulla
authors.initials: U
authors.lastname: Feldt-Rasmussen
authors.forename: Malene
authors.initials: M
authors.lastname: Boas
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.forename: Torben
authors.initials: T
authors.lastname: Larsen
authors.forename: Dorthe Hansen
authors.initials: DH
authors.lastname: Precht
mesh_terms: D000328:Adult; D003951:Diagnostic Errors / Q000517:prevention & control*; D005260:Female; D015200:Fluoroimmunoassay; D005865:Gestational Age; D006801:Humans; D008137:Longitudinal Studies; D008163:Luminescent Measurements; D011247:Pregnancy / Q000502:physiology*; D011446:Prospective Studies; D012016:Reference Values; D015203:Reproducibility of Results; D013959:Thyroid Diseases / Q000175:diagnosis*; D013960:Thyroid Function Tests / Q000592:standards*; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine