A review on exploring link between maternal tsh levels during gestational hypothyroidism and foetal developmental mile stones
Abstract
Pregnancy is a complex state with many endocrinological challenges to a woman’s physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and foetal outcomes such as miscarriage, pre-eclampsia, placental abruption, foetal loss, premature delivery, and neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated.
Keywords:
Gestational hypothyroidism, subclinical hypothyroidism, pregnancy, thyroid disorders, placenta, oestrogen, iodine, levothyroxine
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References
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29. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol 2003; 59: 228-288.
30. Skjoldebrand L, Brundin J, Carlstrom A, Pettersson T. Thyroid associated components in serum during normal pregnancy. Acta Endocrinol 1982; 100: 504- 511.
31. Okosieme OE, Marx H, Lazarus JH. Medical management of thyroid dysfunction in pregnancy and the postpartum. Expert Opin Pharmacother 2008; 9: 2281-2293.
32. De Groot L, et al. Management of thyroid dysfunction during pregnancy and postpartum: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543–65. https://doi.org/10.1210/jc.2011-2803
33. American Academy of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002; 8: 457-469.
34. 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.
35. Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update 2003:9: 149-161.
36. Murcia M, Rebagliato M, Iniguez C, Lopez-Espinosa M, Estarlich M, Plaza B, et al. Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 Year of Age. Am J Epidemiol 2011; 173: 804-812.
37. Maraka S, Ospina NM, O’Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, Coddington CC 3rd, Stan MN, Murad MH, Montori VM. Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid 2016;26:580-590. Epub 2016 Mar 3
2. Taylor PN, Minassian C, Rehman A et al (2014) TSH levels and risk of miscarriage in women on long-term levothyroxine: a community-based study. J Clin Endocrinol Metab 99:3895–3902. https://doi.org/10.1210/JC.2014-1954
3. Obregon MJ, Calvo RM, Del Rey FE & de Escobar GM 2007 Ontogenesis of thyroid function and interactions with maternal function. Endocrine Development 10 86–98. (doi:10.1159/000106821)
4. Glinoer D 2001 Pregnancy and iodine. Thyroid 11 471–481. (doi:10.1089/ 105072501300176426)
5. S. Chunchaiah, N. Prasad, M. M, M. R, N. Rangaiah A prospective observational study of thyroid dysfunctions during pregnancy in a tertiary care hospital Int J Reprod Contracept Obstet Gynecol, 5 (11) (2016), pp. 3683-3689 View at publisherCrossrefGoogle Scholar
6. Nisha Nathan, Shannon D, Sullivan. Thyroid disorders during pregnancy. Endocrinol Metab. Clin North Am. 2014;43(2):573–97. https://doi.org/10.1016 /j.ecl.2014.02.008
7. Siobhan Deshauer MD, Ahraaz Wyne MD. Subclinical hypothyroidism in pregnancy. CMAJ 2017;17:189:E941. https://doi.org/10.1503/cmaj.161388
8. De Leo S, Pearce EN. Autoimmune thyroid disease during pregnancy. Lancet Diabetes Endocrinol. 2018;6(7):575–86. https://doi.org/10.1016/S2213-8587(1 7)30402-3
9. Riley Epp J, Malcolm K, Jolin-Dahel M, Clermont. Erin Keely. Postpartum thyroiditis. BMJ 2021;3:372. https://doi.org/10.1136/bmj.n495
10. Kilby MD. Thyroid hormones and fetal brain development. Clin Endocrinol 2003; 59: 280-281.
11. 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.
12. DeRuiter J. Thyroid hormone tutorial: thyroid pathology. Endocrine Module (PYPP 5260), Thyroid Section, spring. Available at: 61Thttp://www.book.xlibx61T. info/bo-other/3556700-1-endocrine-module-pypp-526 0-thyroid-section-spring-2002-thyroid-h.php.
13. Raymond J, Lafranchi SH. Fetal and neonatal thyroid function: review and summary of significant new findings. Curr Opin Endocrinol Diabetes Obes 2010; 17: 1-7.
14. Adu-Gyamfi EA, Wang YX, Ding YB. The Interplay Between Thyroid Hormones and the Placenta: A Comprehensive Review. Biol Reprod (2020) 102(1):8–17. doi: 10.1093/biolre/ioz182
15. Delitala AP, Capobianco G, Cherchi PL, Dessole S, Delitala G. Thyroid Function and Thyroid Disorders During Pregnancy: A Review and Care Pathway. Arch Gynecol Obstetr (2019) 299(2):327–38. doi: 10.1007/s00404-018-5018-8
16. Rebagliato M, Murcia M, Espada M, Á lvarez-Pedrerol M, Bolúmar F, Vioque J, et al. Iodine Intake and Maternal Thyroid Function During Pregnancy. Epidemiology (2010) 21(3):62–9. doi: 10.1097/EDE.0b013e3181c1592b
17. Xiao Y, Sun H, Li C, Li Y, Peng S, Fan C, et al. Effect of Iodine Nutrition on Pregnancy Outcomes in an Iodine-Sufficient Area in China. Biol Trace Element Res (2018) 182(2):231–7. doi: 10.1007/s12011-017-1101-4
18. De Geyter C, Steimann S, Müller B, Kränzlin ME, Meier C. Pattern of Thyroid Function During Early Pregnancy in Women Diagnosed With Subclinical Hypothyroidism and Treated With L-Thyroxine is Similar to That in Euthyroid Controls. Thyroid (2009) 19(1):53–9. doi: 10.1089/thy.2007.0355
19. Calvo RM, Jauniaux E, Gulbis B, Asuncion M, Gervy C, Contempre B & Morreale de Escobar G 2002 Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. Journal of Clinical Endocrinology and Metabolism 87 1768–1777. (doi:10.1210/ jc.87.4.1768)
20. Bernal J 2007 Thyroid hormone receptors in brain development and function. Nature Clinical Practice. Endocrinology & Metabolism 3 249–259. (doi:10.1038/ ncpendmet0424)
21. Dorizzi RM, et al. Trimester-specific reference intervals for thyroid function parameters in pregnant caucasian women using Roche platforms: a prospective study. J Endocrinol Invest. 2023;46(12):2459–69. https://doi.org/10.1007/s 40618-023-02098-0
22. Dong AC, et al. Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2020;113(3):587–e6001. https://doi.org/10.1016/j.fertnstert.2019.11.003
23. Maraka S, et al. Subclinical hypothyroidism in pregnancy: a systematic review and Meta-analysis. Thyroid. 2016;26(4):580–90. https://doi.org/10.1089/thy.20 15.0418. Epub 2016 Mar 3.
24. Mitchell ML, Larsen PR, Levy HL, Bennett AJ, Madoff MA. Screening for congenital hypothyroidism. Results in the newborn population of new England. JAMA, 239(22), 2348–51. https://doi.org/10.1001/jama.239.22.2348
25. Tuija Männistö P, Mendola U, Reddy. Katherine Laughon. Neonatal outcomes and Birth Weight in pregnancies complicated by maternal thyroid disease. Am J Epidemiol. 2013;178(5):731–40
26. Nguyen BT, Chang EJ, Bendikson KA: Advanced paternal age and the risk of spontaneous abortion: an analysis of the combined 2011-2013 and 2013-2015 National Survey of Family Growth. Am J Obstet Gynecol. 2019, 221:476.e1. 10.1016/j.ajog.2019.05.028
27. Franco B, Laura F, Sara N, Salvatore G: Thyroid function in small for gestational age newborns: a review . J Clin Res Pediatr Endocrinol. 2013, 5:2-7. 10.4274/jcrpe.846
28. Haddow JE, Palomaki GE, All an WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid deficincy during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341: 549-555.
29. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol 2003; 59: 228-288.
30. Skjoldebrand L, Brundin J, Carlstrom A, Pettersson T. Thyroid associated components in serum during normal pregnancy. Acta Endocrinol 1982; 100: 504- 511.
31. Okosieme OE, Marx H, Lazarus JH. Medical management of thyroid dysfunction in pregnancy and the postpartum. Expert Opin Pharmacother 2008; 9: 2281-2293.
32. De Groot L, et al. Management of thyroid dysfunction during pregnancy and postpartum: an endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543–65. https://doi.org/10.1210/jc.2011-2803
33. American Academy of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002; 8: 457-469.
34. 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.
35. Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update 2003:9: 149-161.
36. Murcia M, Rebagliato M, Iniguez C, Lopez-Espinosa M, Estarlich M, Plaza B, et al. Effect of iodine supplementation during pregnancy on infant neurodevelopment at 1 Year of Age. Am J Epidemiol 2011; 173: 804-812.
37. Maraka S, Ospina NM, O’Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, Coddington CC 3rd, Stan MN, Murad MH, Montori VM. Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid 2016;26:580-590. Epub 2016 Mar 3
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12/10/2025
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R, V. S., S. M, P. C. Y, V. Penabaka, and A. Patan. “A Review on Exploring Link Between Maternal Tsh Levels During Gestational Hypothyroidism and Foetal Developmental Mile Stones”. International Journal of Health Care and Biological Sciences, Vol. 6, no. 4, Oct. 2025, pp. 7-12, doi:10.46795/ijhcbs.v6i4.747.
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