Bakken Kjersti S, Niraula Apeksha, Chandyo Ram K, Ulak Manjeswori, Shrestha Laxman, Sharma Vijay Kumar, Strand Tor A, Korevaar Tim I M
Center for International Health, University of Bergen, Bergen, Norway.
Women's Clinic, Innlandet Hospital Trust, Lillehammer, Norway.
Clin Endocrinol (Oxf). 2025 Mar;102(3):332-343. doi: 10.1111/cen.15175. Epub 2024 Dec 16.
Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population-based pregnancy-specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population-based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.
A total of 800 healthy pregnant women aged 20-40 years in the Bhaktapur municipality were included. Population-based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non-pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels.
Median gestational age was 11 weeks. The reference interval was 0.05-3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89-15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody-positive women. Compared with the current non-pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels.
We found meaningful changes using population-based pregnancy-specific TSH and fT4 reference intervals and encourage further studies in other low- and middle-income settings. Our findings suggest that population screening for TRAb is not clinically meaningful.
Clinical Trial Registration: U1111-1183-4093.
孕期甲状腺功能障碍的不同定义可能导致治疗不足或过度治疗。本研究的目的是：（1）确定尼泊尔孕早期基于人群的甲状腺功能障碍妊娠特异性参考范围，并评估抗体阳性的影响；（2）量化基于人群的参考范围与当前实践相比的诊断影响；（3）评估甲状腺功能和抗体阳性的决定因素。
纳入了巴克塔普尔市800名年龄在20 - 40岁的健康孕妇。采用竞争性免疫发光测定法，将甲状腺激素水平的基于人群的参考范围定义为第2.5百分位数和第97.5百分位数。使用当前非妊娠新参考范围计算甲状腺疾病病例和有推荐治疗指征的病例。进行多变量回归分析以确定甲状腺激素和抗体水平的决定因素。
中位孕周为11周。排除甲状腺过氧化物酶抗体阳性女性后，促甲状腺激素（TSH）的参考区间为0.05 - 3.69 μLU/mL，游离甲状腺素（fT4）的参考区间为8.89 - 15.28 pg/mL。与当前非妊娠参考范围相比，新的计算方法使需要治疗的女性人数从5人增加到12人（增加了0.9%）。我们确定了19名促甲状腺激素受体抗体（TRAb）阳性的女性（2.4%）。我们无法确定TRAb阳性的决定因素，且TRAb阳性与TSH或fT4水平无关。
我们发现使用基于人群的妊娠特异性TSH和fT4参考区间有显著变化，并鼓励在其他低收入和中等收入环境中进行进一步研究。我们的研究结果表明，对TRAb进行人群筛查在临床上没有意义。
临床试验注册：U1111 - 1183 - 4093。
