不同实验室的妊娠期特异性参考范围会错误分类孕妇的甲状腺功能状态：两项纵向前瞻性队列研究的比较。

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

机构信息

Department of Endocrinology, Section 2132, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.

出版信息

Eur J Endocrinol. 2013 Dec 27;170(2):329-39. doi: 10.1530/EJE-13-0672. Print 2014 Feb.

DOI:10.1530/EJE-13-0672

PMID:24277773

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 (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.

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.

摘要

目的

正确解读妊娠期间的甲状腺功能对于保障胎儿发育至关重要。母体甲状腺功能在妊娠期间的变化需要使用特定于妊娠龄的参考范围。在这项研究中，我们研究了孕妇甲状腺参考范围在不同实验室间的重现性。

设计

比较了包括 255 名（队列 1）和 101 名（队列 2）健康、抗体阴性的丹麦孕妇的两项纵向前瞻性队列研究，这些孕妇在哥本哈根大学医院接受产前护理。

方法

使用不同的免疫分析法在两个队列中测量甲状腺激素水平。为每 5 周的妊娠建立甲状腺激素参考范围。通过混合模型重复测量回归分析探讨队列间的差异。通过将一个队列的参考范围应用于另一个队列，研究这样做会导致多少女性被错误分类。

结果

随着妊娠的进展，TSH 增加，游离甲状腺素（FT4）降低。结果表明，游离三碘甲状腺原氨酸（F=21.3，P<0.001）和 FT4（F=941，P<0.001）在两个队列之间存在显著差异。TSH 水平相当（P=0.09）。多达 90.3%的女性 FT4 水平超出了实验室的非妊娠参考范围，多达 100%的女性 FT4 水平超出了其他队列的特定于妊娠龄的参考范围。基于 Z 分数的参考范围显著改善了队列间的比较。