Effects of subclinical hypothyroidism on maternal and obstetric outcomes during pregnancy

Objectives: Subclinical hypothyroidism has been defined as normal free thyroxine (FT4) with elevated thyroid stimulating hormone (TSH) levels. The aim of this study is to examine the relationship between the first trimester subclinical hypothyroidism with adverse obstetric outcomes in pregnant women. Methods: This retrospective cohort study was conducted by examining the pregnant women who applied to the Gynecology Department of Okmeydani Training and Research Hospital at their 6th to 14th gestational weeks and had antenatal follow-ups between February 1, 2017 and December 31, 2020. Results: Fetal weight (OR: 1; 95% CI, 0.99-1.03, p = 0.023), gestational age at delivery (OR: 0.91; 95% CI, 0.83-0.99, p = 0.022), and preterm delivery (OR: 0.79; 95% CI, 0.48-1.06, p = 0.005) were found to be statistically significant parameters in univariate risk analyses performed in the group whith patients normal T4 levels and TSH levels ≥ 2.5-4 mIU/L. Lower gestational age at delivery (OR: 1; 95% CI, 0.93-1.88, p = 0.016), and higher preterm delivery rates (OR: 0.99; 95% CI, 0.96-1.01, p = 0.003) were found to be statistically significant in multivariate risk analysis. Conclusions: The rate of preterm delivery was statistically higher, and fetal weight and week of delivery were significantly lower in the group of pregnant women diagnosed with SCH having TSH values between 2.5 and 4 mIU/L.

Keywords:

Pregnancy Preterm birth, Subclinical hypothyroidism,

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1. Negro R, Mestman JH. Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab 2011;25:927-43.
2. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: co-sponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012;18:988-1028.
3. Derakhshan A, Peeters RP, Taylor PN, Bliddal S, Carty DM, Meems M, et al. Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis. Lancet Diabetes Endocrinol 2020;8:501-10.
4. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017;27:315-89.
5. Korevaar TIM, Medici M, Visser TJ, Peeters RP. Thyroid disease in pregnancy: new insights in diagnosis and clinical management. Nat Rev Endocrinol 2017;13:610-22.
6. Ausó E, Lavado-Autric R, Cuevas E, Del Rey FE, Morreale De Escobar G, Berbel P. A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. Endocrinology 2004;145:4037-47.
7. Soldin OP, Tractenberg RE, Hollowell JG, Jonklaas J, Janicic N, Soldin SJ. Trimester-specific changes in maternal thyroid hormone, thyrotropin, and thyroglobulin concentrations during gestation: trends and associations across trimesters in iodine sufficiency. Thyroid 2004;14:1084-90.
8. Moleti M, Trimarchi F, Vermiglio F. Thyroid physiology in pregnancy. Endocr Pract 2014;20:589-96.
9. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1081-125.
10. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF et al. Guidelines Committee, National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003;13:3-126.
11. Wang J, Gong XH, Peng T, Wu JN. Association of thyroid function during pregnancy with the risk of preeclampsia and gestational diabetes mellitus. Endocr Pract 2021;27:819-25.
12. León G, Murcia M, Rebagliato M, Álvarez-Pedrerol M, Castilla AM, Basterrechea M, et al. Maternal thyroid dysfunction during gestation, preterm delivery, and birthweight. The Infancia y Medio Ambiente Cohort, Spain. Paediatr Perinat Epidemiol 2015;29:113-22.
13. Almomin AMS, Mansour AA, Sharief M. Trimester-specific reference intervals of thyroid function testing in pregnant women from Basrah, Iraq using electrochemiluminescent immunoassay. Diseases 2016;4:20.
14. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131:e49-e64.
15. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hpertens Pregnancy 2001;20:IX-XIV.
16. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2543-65.
17. Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ, et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen 2000;7:127-30.
18. Benhadi N, Wiersinga WM, Reitsma JB, Vrijkotte TG, van der Wal MF, Bonsel GJ. Ethnic differences in TSH but not in free T4 concentrations or TPO antibodies during pregnancy. Clin Endocrinol (Oxf) 2007;66:765-70.
19. McNeil AR, Stanford PE. Reporting Thyroid Function Tests in Pregnancy. Clin Biochem Rev 2015;36:109-26.
20. Marwaha RK, Chopra S, Gopalakrishnan S, Sharma B, Kanwar RS, Sastry A, et al. Establishment of reference range for thyroid hormones in normal pregnant Indian women. BJOG 2008;115:602-6.
21. Kannan S, Mahadevan S, Sigamani A. A systematic review on normative values of trimester-specific thyroid function tests in Indian women. Indian J Endocrinol Metab 2018;22:7-12.
22. Kalra S, Agarwal S, Aggarwal R, Ranabir S. Trimester-specific thyroid-stimulating hormone: an Indian perspective. Indian J Endocrinol Metab 2018;22:1-4.
23. Chen LM, Du WJ, Dai J, Zhang Q, Si GX, Yang H, et al. Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population. PLoS One 2014;9:e109364.
24. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005;105:239-45.
25. Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab 2010;95:E44-8.
26. Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol 2012;119:315-20.
27. Monen L, Kuppens SM, Hasaart TH, Oosterbaan HP, Oei SG, Wijnen H, et al. Maternal thyrotropin is independently related to small for gestational age neonates at term. Clin Endocrinol (Oxf). 2015;82:254-9.
28. Ohashi M, Furukawa S, Michikata K, Kai K, Sameshima H, Ikenoue T. Risk-based screening for thyroid dysfunction during pregnancy. J Pregnancy 2013;2013:619718.
29. Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, et al. Maternal thyroid hypofunction and pregnancy outcome. Obstet Gynecol 2008;112:85-92.
30. Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012;119:983-8.
31. Nelson DB, Casey BM, McIntire DD, Cunningham FG. Subsequent pregnancy outcomes in women previously diagnosed with subclinical hypothyroidism. Am J Perinatol 2014;31:77-84.
32. Maraka S, Ospina NM, O'Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid 2016;26:580-90.