Hostname: page-component-f554764f5-rvxtl Total loading time: 0 Render date: 2025-04-13T05:33:08.894Z Has data issue: false hasContentIssue false
  • English
  • Français

THYROID FUNCTION IN PREGNANCY: MATERNAL AND FETAL OUTCOMES WITH HYPOTHYROIDISM AND SUBCLINICAL THYROID DYSFUNCTION

Published online by Cambridge University Press:  21 June 2011

NEIL K VANES ,
JOHN H LAZARUS  and
SHIAO-Y CHAN
NEIL K VANES
Affiliation:
The School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham.
JOHN H LAZARUS
Affiliation:
Centre for Endocrine and Diabetes Sciences, Cardiff School of Medicine, University Hospital of Wales, Cardiff.
SHIAO-Y CHAN*
Affiliation:
The School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham.
*
Shiao-Y Chan, Level 3, Academic Department, Birmingham Women's Hospital, Metchley Park Road, Edgbaston, Birmingham, West Midlands B15 2TG. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Extract

Thyroid hormones are important in the development of the fetus and the placenta as well as in maintaining maternal wellbeing. Thyroid disorders are common in the population as a whole, particularly in women, and therefore are common during pregnancy and the puerperium. Biochemical derangement of thyroid function tests are present in approximately 2.5–5% of pregnant women.

Type
Research Article
Information
Fetal and Maternal Medicine Review , Volume 22 , Issue 3 , August 2011 , pp. 169 - 187
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

1Cleary-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.CrossRefGoogle ScholarPubMed
2Yen, PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev 2001; 81: 1097–142.CrossRefGoogle ScholarPubMed
3de Escobar, GM, Ares, S, Berbel, P, Obregon, MJ, del Rey, FE. The changing role of maternal thyroid hormone in fetal brain development. Semin Perinatol 2008; 32: 380–86.CrossRefGoogle ScholarPubMed
4Calvo, RM, Jauniaux, E, Gulbis, B, Asuncion, M, Gervy, C, Contempre, B et al. Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. J Clin Endocrinol Metab 2002; 87: 1768–777.CrossRefGoogle ScholarPubMed
5Contempre, B, Jauniaux, E, Calvo, R, Jurkovic, D, Campbell, S, de Escobar, GM. Detection of thyroid hormones in human embryonic cavities during the first trimester of pregnancy. J Clin Endocrinol Metab 1993; 77: 1719–722.Google ScholarPubMed
6Sinha, AK, Prabakaran, D., Godbole, M, Chattopadhyay, N, Karmarkar, M, Pickard, MR et al. Hendrich, CE (ed.) Thyroid hormone and brain maturation. Recent research developments in neuroendocrinology Trivandrum: India, Research Signpost 1997; 1–14.Google Scholar
7Vulsma, T, Gons, MH, de Vijlder, JJ. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N Engl J Med 1989; 321: 13–16.CrossRefGoogle ScholarPubMed
8Delahunty, C, Falconer, S, Hume, R, Jackson, L, Midgley, P, Mirfield, M et al. Levels of neonatal thyroid hormone in preterm infants and neurodevelopmental outcome at 5 1/2 years: millennium cohort study. J Clin Endocrinol Metab 2010; 95: 4898–908.CrossRefGoogle ScholarPubMed
9Chan, SY, Vasilopoulou, E, Kilby, MD. The role of the placenta in thyroid hormone delivery to the fetus. Nat Clin Pract Endocrinol Metab 2009; 5: 45–54.CrossRefGoogle ScholarPubMed
10Hume, R, Simpson, J, Delahunty, C, van Toor, H, Wu, SY, Williams, FLR et al. Human fetal and cord serum thyroid hormones: Developmental trends and interrelationships. J Clin Endocrinol Metab 2004; 89: 4097–103.CrossRefGoogle ScholarPubMed
11Richard, K, Hume, R, Kaptein, E, Stanley, EL, Visser, TJ, Coughtrie, MW. Sulfation of thyroid hormone and dopamine during human development: ontogeny of phenol sulfotransferases and arylsulfatase in liver, lung, and brain. J Clin Endocrinol Metab 2001; 86: 2734–742.Google ScholarPubMed
12Farwell, AP, Dubord-Tomasetti, SA, Pietrzykowski, AZ, Leonard, JL. Dynamic nongenomic actions of thyroid hormone in the developing rat brain. Endocrinology 2006; 147: 2567–574.CrossRefGoogle ScholarPubMed
13Mortimer, RH, Galligan, JP, Cannell, GR, Addison, RS, Roberts, MS. Maternal to fetal thyroxine transmission in the human term placenta is limited by inner ring deiodination. J Clin Endocrinol Metab 1996; 81: 2247–249.Google ScholarPubMed
14Chan, S, Kachilele, S, Hobbs, E, Bulmer, JN, Boelaert, K, McCabe, CJ et al. Placental iodothyronine deiodinase expression in normal and growth-restricted human pregnancies. J Clin Endocrinol Metab 2003; 88: 4488–495.CrossRefGoogle ScholarPubMed
15Loubiere, LS, Vasilopoulou, E, Bulmer, JN, Taylor, PM, Stieger, B, Verrey, F et al. Expression of thyroid hormone transporters in the human placenta and changes associated with intrauterine growth restriction. Placenta 2010; 31: 295–304.CrossRefGoogle ScholarPubMed
16Maruo, T, Matsuo, H, Mochizuki, M. Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy. Acta Endocrinol (Copenh) 1991; 125: 58–66.Google ScholarPubMed
17Laoag-Fernandez, JB, Matsuo, H, Murakoshi, H, Hamada, AL, Tsang, BK, Maruo, T. 3,5,3‘-triiodothyronine down-regulates Fas and Fas ligand expression and suppresses caspase-3 and poly (adenosine 5‘-diphosphate-ribose) polymerase cleavage and apoptosis in early placental extravillous trophoblasts in vitro. J Clin Endocrinol Metab 2004; 89: 4069–4077.CrossRefGoogle ScholarPubMed
18van der Deure, WM, Peeters, RP, Visser, TJ. Genetic variation in thyroid hormone transporters. Best Pract Res Clin Endocrinol Metab 2007; 21: 339–50.CrossRefGoogle ScholarPubMed
19Lazarus, JH. Thyroid function in pregnancy. Br Med Bull 2011; 97: 137–48.CrossRefGoogle ScholarPubMed
20Fantz, CR, gogo-Jack, S, Ladenson, JH, Gronowski, AM. Thyroid function during pregnancy. Clin Chem 1999; 45: 2250–258.CrossRefGoogle ScholarPubMed
21Hegde, UC. Immunomodulation of the mother during pregnancy. Med Hypotheses 1991; 35: 159–64.CrossRefGoogle ScholarPubMed
22Glinoer, D, De, NP, Robyn, C, Lejeune, B, Kinthaert, J, Meuris, S. Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy. J Endocrinol Invest 1993; 16: 881–88.CrossRefGoogle ScholarPubMed
23Dashe, JS, Casey, BM, Wells, CE, McIntire, DD, Byrd, EW, Leveno, KJ et al. Thyroid-stimulating hormone in singleton and twin pregnancy: importance of gestational age-specific reference ranges. Obstet Gynecol 2005; 106: 753–57.CrossRefGoogle ScholarPubMed
24Soldin, OP. Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals. Ther Drug Monit 2006; 28: 8–11.CrossRefGoogle ScholarPubMed
25Glinoer, D, Spencer, CA. Serum TSH determinations in pregnancy: how, when and why? Nat Rev Endocrinol 2010; 6: 526–29.CrossRefGoogle Scholar
26Lee, YL, Ng, HP, Lau, KS, Liu, WM, WS, O, Yeung, WS et al. Increased fetal abortion rate in autoimmune thyroid disease is related to circulating TPO autoantibodies in an autoimmune thyroiditis animal model. Fertil Steril 2009; 91 (5 Suppl): 2104–109.CrossRefGoogle Scholar
27Stagnaro-Green, A, Glinoer, D. Thyroid autoimmunity and the risk of miscarriage. Best Pract Res Clin Endocrinol Metab 2004; 18: 167–81.CrossRefGoogle ScholarPubMed
28Negro, R, Mangieri, T, Coppola, L, Presicce, G, Casavola, EC, Gismondi, R et al. Levothyroxine treatment in thyroid peroxidase antibody-positive women undergoing assisted reproduction technologies: a prospective study. Hum Reprod 2005; 20: 1529–533.CrossRefGoogle ScholarPubMed
29Negro, R, Formoso, G, Mangieri, T, Pezzarossa, A, Dazzi, D, Hassan, H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006; 91: 2587–591.CrossRefGoogle ScholarPubMed
30Thangaratinam, S, Tan, A, Knox, E, Kilby, MD, Franklyn, JA, Coomarasamy, A. Thyroid auto-antibodies are strongly associated with miscarriage and preterm birth: A meta-analysis of evidence. BMJ, In press. 2011.CrossRefGoogle Scholar
31Kaprara, A, Krassas, GE. Thyroid autoimmunity and miscarriage. Hormones (Athens) 2008; 7: 294–302.CrossRefGoogle ScholarPubMed
32Pop, VJ, de Vries, E, van Baar, AL, Waelkens, JJ, de Rooy, HA, Horsten, M et al. Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development? J Clin Endocrinol Metab 1995; 80: 3561–566.CrossRefGoogle ScholarPubMed
33Stagnaro-Green, A. Recognizing, understanding, and treating postpartum thyroiditis. Endocrinol Metab Clin North Am 2000; 29: 417–30, ix.CrossRefGoogle ScholarPubMed
34Kilby, MD, Gittoes, N, McCabe, C, Verhaeg, J, Franklyn, JA. Expression of thyroid receptor isoforms in the human fetal central nervous system and the effects of intrauterine growth restriction. Clin Endocrinol (Oxf) 2000; 53: 469–77.CrossRefGoogle ScholarPubMed
35Chan, S, Kachilele, S, McCabe, C, Tannahill, L, Boelaert, K, Gittoes, N et al. Early expression of thyroid hormone deiodinases and receptors in human fetal cerebral cortex. Brain Res Dev Brain Res 2002; 138: 109–16.CrossRefGoogle ScholarPubMed
36Kester, MHA, de Mena, RM, Obregon, MJ, Marinkovic, D, Howatson, A, Visser, TJ et al. Iodothyronine levels in the human developing brain: Major regulatory roles of iodothyronine deiodinases in different areas. J Clin Endocrinol Metab 2004; 89: 3117–128.CrossRefGoogle ScholarPubMed
37Bernal, J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab 2007; 3: 249–59.CrossRefGoogle Scholar
38Pop, 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 (Oxf) 2003; 59: 282–88.CrossRefGoogle ScholarPubMed
39Haddow, JE, Palomaki, GE, Allan, WC, Williams, JR, Knight, GJ, Gagnon, J et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med 1999; 341: 549–55.CrossRefGoogle ScholarPubMed
40Casey, BM, Dashe, JS, Wells, CE, McIntire, DD, Byrd, W, Leveno, KJ et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005; 105: 239–45.CrossRefGoogle ScholarPubMed
41Klein, RZ, Haddow, JE, Faix, JD, Brown, RS, Hermos, RJ, Pulkkinen, A et al. Prevalence of thyroid deficiency in pregnant women. Clin Endocrinol (Oxf) 1991; 35: 41–46.CrossRefGoogle ScholarPubMed
42Canaris, GJ, Manowitz, NR, Mayor, G, Ridgway, EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000; 160: 526–34.CrossRefGoogle ScholarPubMed
43LaFranchi, SH, Haddow, JE, Hollowell, JG. Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes? Thyroid 2005; 15: 60–71.CrossRefGoogle ScholarPubMed
44Davis, LE, Leveno, KJ, Cunningham, FG. Hypothyroidism complicating pregnancy. Obstet Gynecol 1988; 72: 108–12.Google ScholarPubMed
45Leung, AS, Millar, LK, Koonings, PP, Montoro, M, Mestman, JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol 1993; 81: 349–53.Google ScholarPubMed
46de Escobar, GM, Obregon, MJ, del Rey, FE. Maternal thyroid hormones early in pregnancy and fetal brain development. Best Pract Res Clin Endocrinol Metab 2004; 18: 225–48.CrossRefGoogle ScholarPubMed
47Abalovich, M, Gutierrez, S, Alcaraz, G, Maccallini, G, Garcia, A, Levalle, O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002; 12: 63–68.CrossRefGoogle ScholarPubMed
48Wolfberg, AJ, Lee-Parritz, A, Peller, AJ, Lieberman, ES. Obstetric and neonatal outcomes associated with maternal hypothyroid disease. J Matern Fetal Neonatal Med 2005; 17: 35–38.CrossRefGoogle ScholarPubMed
49Matalon, S, Sheiner, E, Levy, A, Mazor, M, Wiznitzer, A. Relationship of treated maternal hypothyroidism and perinatal outcome. J Reprod Med 2006; 51: 59–63.Google ScholarPubMed
50Idris, I, Srinivasan, R, Simm, A, Page, RC. Maternal hypothyroidism in early and late gestation: effects on neonatal and obstetric outcome. Clin Endocrinol (Oxf) 2005; 63: 560–65.CrossRefGoogle ScholarPubMed
51Casey, BM, Dashe, JS, Spong, CY, McIntire, DD, Leveno, KJ, Cunningham, GF. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol 2007; 109: 1129–135.CrossRefGoogle ScholarPubMed
52Abalovich, M, Amino, N, Barbour, LA, Cobin, RH, De Groot, LJ, Glinoer, D et al. Management of thyroid dysfunction during pregnancy and postpartum: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2007; 92: S1–S7.CrossRefGoogle ScholarPubMed
53ACOG Committee Opinion No. 381: Subclinical hypothyroidism in pregnancy. Obstet Gynecol 2007; 110: 959–60.CrossRefGoogle Scholar
54ACOG practice bulletin. Thyroid disease in pregnancy. Number 37, August 2002. American College of Obstetrics and Gynecology. Int J Gynaecol Obstet 2002; 79: 171–80.Google Scholar
55Negro, R, Schwartz, A, Gismondi, R, Tinelli, A, Mangieri, T, Stagnaro-Green, A. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab 2010; 95: 1699–707.CrossRefGoogle ScholarPubMed
56Vaidya, B, Anthony, S, Bilous, M, Shields, B, Drury, J, Hutchison, S 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.CrossRefGoogle ScholarPubMed
57Wang, W, Teng, W, Shan, Z, Wang, S, Li, J, Zhu, L 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: 263–68.CrossRefGoogle Scholar
58Baskin, HJ, Cobin, RH, Duick, DS, Gharib, H, Guttler, RB, Kaplan, MM et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002; 8: 457–69.CrossRefGoogle Scholar
59Pharoah, PO, Connolly, KJ. Iodine and brain development. Dev Med Child Neurol 1995; 37: 744–48.CrossRefGoogle ScholarPubMed
60Lazarus, JH. Outcome of the CATS Study in Pregnant Women. 15-9-2010. 14th International Thyroid Congress, Paris. Ref Type UnpublishedGoogle Scholar
61Kuppens, SM, Kooistra, L, Wijnen, HA, Crawford, S, Vader, HL, Hasaart, TH et al. Maternal thyroid function during gestation is related to breech presentation at term. Clin Endocrinol (Oxf) 2010; 72: 820–24.CrossRefGoogle ScholarPubMed
62Wijnen, HA, Kooistra, L, Vader, HL, Essed, GG, Mol, BW, Pop, VJ. Maternal thyroid hormone concentration during late gestation is associated with foetal position at birth. Clin Endocrinol (Oxf) 2009; 71: 746–51.CrossRefGoogle ScholarPubMed
63Ashoor, G, Maiz, N, Rotas, M, Kametas, NA, Nicolaides, KH. Maternal thyroid function at 11 to 13 weeks of gestation and subsequent development of preeclampsia. Prenat Diagn 2010; 30: 1032–1038.CrossRefGoogle ScholarPubMed
64Benhadi, N, Wiersinga, WM, Reitsma, JB, Vrijkotte, TG, Bonsel, GJ. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol 2009; 160: 985–91.CrossRefGoogle ScholarPubMed
65Ashoor, G, Maiz, N, Rotas, M, Jawdat, F, Nicolaides, KH. Maternal thyroid function at 11 to 13 weeks of gestation and subsequent fetal death. Thyroid 2010; 20: 989–93.CrossRefGoogle ScholarPubMed
66Negro, 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–E48.CrossRefGoogle ScholarPubMed
67Association of Clinical Biochemists (ACB), British Thyroid Association (BTA), British Thyroid Foundation (BTF). UK guidelines for the use of thyroid function tests (http://www.acb.org.uk/docs/TFTguidelinefinal.pdf). 2006; 39–43.Google Scholar
68Casey, BM, Dashe, JS, Wells, CE, McIntire, DD, Leveno, KJ, Cunningham, FG. Subclinical hyperthyroidism and pregnancy outcomes. Obstet Gynecol 2006; 107: 337–41.CrossRefGoogle ScholarPubMed
69Alexander, EK, Marqusee, E, Lawrence, J, Jarolim, P, Fischer, GA, Larsen, PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. New Eng J Med 2004; 351: 241–49.CrossRefGoogle ScholarPubMed
70Mandel, SJ. Hypothyroidism and chronic autoimmune thyroiditis in the pregnant state: maternal aspects. Best Pract Res Clin Endocrinol Metab 2004; 18: 213–24.CrossRefGoogle ScholarPubMed
71Verga, U, Bergamaschi, S, Cortelazzi, D, Ronzoni, S, Marconi, AM, Beck-Peccoz, P. Adjustment of L-T4 substitutive therapy in pregnant women with subclinical, overt or post-ablative hypothyroidism. Clin Endocrinol (Oxf) 2009; 70: 798–802.CrossRefGoogle ScholarPubMed
72Yassa, L, Marqusee, E, Fawcett, R, Alexander, EK. Thyroid Hormone Early Adjustment in Pregnancy (The THERAPY) Trial. J Clin Endocrinol Metab 2010; 95: 3234–241.CrossRefGoogle ScholarPubMed
73Jansen, J, Friesema, EC, Milici, C, Visser, TJ. Thyroid hormone transporters in health and disease. Thyroid 2005; 15: 757–68.CrossRefGoogle ScholarPubMed
74Glinoer, D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997; 18: 404–33.CrossRefGoogle ScholarPubMed