Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

Chaochao Ma; Xiaoqi Li; Lixin Liu; Xinqi Cheng; Fang Xue; Jie Wu; Liangyu Xia; Yicong Yin; Danchen Wang; Yutong Zou; Ling Qiu; Juntao Liu

doi:10.1055/a-1402-0290

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2021; 53(04): 272-279
DOI: 10.1055/a-1402-0290

Endocrine Care

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

Chaochao Ma‡^*

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Xiaoqi Li‡^*

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Lixin Liu‡^*

²Department of Obstetrics and Gynecology, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Xinqi Cheng

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Fang Xue

³Department of Epidemiology and Biostatistics, School of Basic Medicine Peking Union Medical College, Beijing, P. R. China

,

Jie Wu

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Liangyu Xia

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Yicong Yin

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Danchen Wang

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Yutong Zou

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Ling Qiu

¹Department of Clinical Laboratory, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

,

Juntao Liu

²Department of Obstetrics and Gynecology, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, P. R. China

› Author Affiliations

Abstract

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052–3.393 μIU/ml, 1.01–1.54 ng/dl, and 2.51–3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

Key words

early pregnancy - thyroid hormones models - reference intervals - real world data

Full Text

References

References
1 Springer D, Jiskra J, Limanova Z. et al. Thyroid in pregnancy: From physiology to screening. Crit Rev Clin Lab Sci 2017; 54: 102-116
2 Su PY, Huang K, Hao JH. et al. Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: A prospective population-based cohort study in China. J Clin Endocrinol Metab 2011; 96: 3234-3241
3 Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev 2010; 31: 702-755
4 Korevaar TI, Muetzel R, Medici M. et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: A population-based prospective cohort study. Lancet Diabetes Endocrinol 2016; 4: 35-43
5 Casey BM, Dashe JS, Wells CE. et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005; 105: 239-245
6 Poon LC, McIntyre HD, Hyett JA. et al. The first-trimester of pregnancy - A window of opportunity for prediction and prevention of pregnancy complications and future life. Diabetes Res Clin Pract 2018; 145: 20-30
7 Tan MY, Poon LC, Rolnik DL. et al. Prediction and prevention of small-for-gestational-age neonates: Evidence from SPREE and ASPRE. Ultrasound Obstet Gynecol 2018; 52: 52-59
8 Sharp AN, Alfirevic Z. First trimester screening can predict adverse pregnancy outcomes. Prenat Diagn 2014; 34: 660-667
9 Wang W, Teng W, Shan Z. et al. The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy. Eur J Endocrinol 2011; 164: 263-268
10 Vaidya B, Anthony S, Bilous M. et al. Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high-risk case finding?. J Clin Endocrinol Metab 2007; 92: 203-207
11 Hirsch D, Levy S, Nadler V. et al. Pregnancy outcomes in women with severe hypothyroidism. Eur J Endocrinol 2013; 169: 313-320
12 Glinoer D. What happens to the normal thyroid during pregnancy?. Thyroid 1999; 9: 631-635
13 Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997; 18: 404-433
14 Boas M, Forman JL, Juul A. et al. Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women. Eur J Endocrinol 2009; 161: 903910
15 Männistö T, Surcel H-M, Ruokonen A. et al. Early Pregnancy reference intervals of thyroid hormone concentrations in a thyroid antibody-negative pregnant population. Thyroid 2011; 21: 291-298
16 Yuen LY, Chan MHM, Sahota DS. et al. Development of gestational age-specific thyroid function test reference intervals in four analytic platforms through multilevel modeling. Thyroid 2020;
17 Walker JA, Illions EH, Huddleston JF. et al. Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period. Obstet Gynecol 2005; 106: 1365-1371
18 Medici M, Korevaar TI, Visser WE. et al. Thyroid function in pregnancy: What is normal?. Clin Chem 2015; 61: 704-713
19 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017; 27: 315-389
20 CLSI. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory. Approved Guideline—Third Edition. CLSI document EP28-A3c. Wayne: PA: Clinical and Laboratory Standards Institute; 2008
21 Jones GRD, Haeckel R, Loh TP. et al. Indirect methods for reference interval determination - review and recommendations. Clin Chem Lab Med 2018; 57: 20-29
22 Ceriotti F. Prerequisites for use of common reference intervals. Clin Biochem Rev 2007; 28: 115-121
23 Baloch Z, Carayon P, Conte-Devolx B. et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003; 13: 3-126
24 Altman DG. Construction of age-related reference centiles using absolute residuals. Stat Med 1993; 12: 917-924
25 Ollero MD, Toni M, Pineda JJ. et al. Thyroid function reference values in healthy iodine-sufficient pregnant women and influence of thyroid nodules on thyrotropin and free thyroxine values. Thyroid 2019; 29: 421-429
26 Khalil AB, Salih BT, Chinengo O. et al. Trimester specific reference ranges for serum TSH and Free T4 among United Arab Emirates pregnant women. Pract Lab Med 2018; 12: e00098
27 Sheng Y, Huang D, Liu S. et al. Reference intervals of thyroid hormones and correlation of bmi with thyroid function in healthy zhuang ethnic pregnant women. Biomed Res Int 2018; 2018: 2032413
28 Kim HJ, Cho YY, Kim SW. et al. Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area. Korean J Intern Med 2018; 33: 552-560
29 Han L, Zheng W, Zhai Y. et al. Reference intervals of trimester-specific thyroid stimulating hormone and free thyroxine in Chinese women established by experimental and statistical methods. J Clin Lab Anal 2018; 32: e22344
30 Kostecka-Matyja M, Fedorowicz A, Bar-Andziak E. et al. Reference Values for TSH and Free Thyroid Hormones in Healthy Pregnant Women in Poland: A Prospective, Multicenter Study. Eur Thyroid J 2017; 6: 82-88
31 Liu J, Yu X, Xia M. et al. Development of gestation-specific reference intervals for thyroid hormones in normal pregnant Northeast Chinese women: What is the rational division of gestation stages for establishing reference intervals for pregnancy women?. Clin Biochem 2017; 50: 309-317
32 Xing J, Yuan E, Li J. et al. Trimester- and assay-specific thyroid reference intervals for pregnant women in China. Int J Endocrinol 2016; 3754213
33 Akarsu S, Akbiyik F, Karaismailoglu E. et al. Gestation specific reference intervals for thyroid function tests in pregnancy. Clin Chem Lab Med 2016; 54: 1377-1383
34 Zhang J, Li W, Chen QB. et al. Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel DxI 600. Clin Chem Lab Med 2015; 53: 1409-1414
35 Li C, Shan Z, Mao J. et al. Assessment of thyroid function during first-trimester pregnancy: What is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women?. J Clin Endocrinol Metab 2014; 99: 73-79
36 Quinn FA, Reyes-Mendez MA, Nicholson L. et al. Thyroid function and thyroid autoimmunity in apparently healthy pregnant and non-pregnant Mexican women. Clin Chem Lab Med 2014; 52: 1305-1311
37 Springer D, Bartos V, Zima T. Reference intervals for thyroid markers in early pregnancy determined by 7 different analytical systems. Scand J Clin Lab Invest 2014; 74
38 Shan Z, Chen L, Lian X. et al. Iodine status and prevalence of thyroid disorders after introduction of mandatory universal salt iodization for 16 years in China: A cross-sectional study in 10 cities. Thyroid 2016; 26: 1125-1130