The thyroid gland is substantially challenged during pregnancy. Total T3 and T4 levels increase by 50% during pregnancy owing to a 50% increase in thyroxine-binding globulin levels. Serum TSH levels decrease in the first trimester and increase in the second and third trimesters; however, not to prepregnancy levels. Hypothyroidism is present in up to 3% of all pregnant women. Subclinical hypothyroidism during pregnancy is associated with an increased rate of miscarriage and preterm delivery, and a decrease in the IQ of the child. Overt hyperthyroidism is present in less than 1% of pregnant women but is linked to increased rates of miscarriage, preterm delivery and maternal congestive heart failure. In women who are euthyroid, thyroid autoantibodies are associated with an increased risk of spontaneous miscarriage and preterm delivery. Postpartum thyroiditis occurs in 5.4% of all women following pregnancy; moreover, 50% of women who are euthyroid in the first trimester of pregnancy but test positive for thyroid autoantibodies will develop postpartum thyroiditis. The need for the essential nutrient iodine increases during pregnancy and in women who are breastfeeding, and the effect of treatment of mild iodine deficiency on maternal and fetal outcomes is consequently being evaluated in a prospective study. The debate regarding the pros and cons of universal screening for thyroid disease during pregnancy is ongoing.
Nonpregnant reference ranges for thyroid function tests do not apply to pregnant women; laboratory-specific, trimester-specific normal ranges for T3, T4 and TSH should be used when available
Overt hypothyroidism has adverse fetal and obstetric effects and should always be treated, whereas treatment for subclinical hypothyroidism in pregnancy remains controversial
In overtly hyperthyroid pregnant women, Graves disease must be distinguished from gestational thyrotoxicosis
Although the presence of thyroid autoantibodies in euthyroid pregnant women is associated with adverse obstetric outcomes, treatment of these women is not currently recommended by obstetric or endocrine societies
Adequate iodine intake is essential in pregnancy and iodine supplementation is recommended in areas of the world where dietary iodine intake is not sufficient
Screening for thyroid dysfunction in pregnant women is controversial and current guidelines provide conflicting recommendations
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency
European Journal of Nutrition Open Access 19 December 2014
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Krassas, G. E., Poppe, K. & Glinoer, D. Thyroid function and human reproductive health. Endocr. Rev. 31, 702–755 (2010).
Smallridge, R. C. Postpartum thyroid diseases through the ages: a historical view. Thyroid 9, 671–673 (1999).
Hershman, J. M. Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid. Best Pract. Res. Clin. Endocrinol. Metab. 18, 249–265 (2004).
Stagnaro-Green, A. et al. A prospective study of lymphocyte-initiated immunosuppression in normal pregnancy: evidence of a T-cell etiology for postpartum thyroid dysfunction. J. Clin. Endocrinol. Metab. 74, 645–653 (1992).
Glinoer, D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr. Rev. 18, 404–433 (1997).
Lazarus, J. H. et al. Antenatal thyroid screening and childhood cognitive function. N. Engl. J. Med. 366, 493–501 (2012).
Haddow, J. E. et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N. Engl. J. Med. 341, 549–555 (1999).
Stagnaro-Green, A. et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 21, 1081–1125 (2011).
Lee, R. H. et al. Free T4 immunoassays are flawed during pregnancy. Am. J. Obstet. Gynecol. 200, 260.e1–260.e6 (2009).
Sapin, R., D'Herbomez, M. & Schlienger, J. L. Free thyroxine measured with equilibrium dialysis and nine immunoassays decreases in late pregnancy. Clin. Lab. 50, 581–584 (2004).
Anckaert, E. et al. FT4 immunoassays may display a pattern during pregnancy similar to the equilibrium dialysis ID–LC/tandem MS candidate reference measurement procedure in spite of susceptibility towards binding protein alterations. Clin. Chim. Acta. 411, 1348–1353 (2010).
Kahric-Janicic, N. et al. Tandem mass spectrometry improves the accuracy of free thyroxine measurements during pregnancy. Thyroid 17, 303–311 (2007).
Haddow, J. E. et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J. Med. Screen. 7, 127–130 (2000).
Klein, R. Z. et al. Prevalence of thyroid deficiency in pregnant women. Clin. Endocrinol. (Oxf.) 35, 41–46 (1991).
Casey, B. M. et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet. Gynecol. 105, 239–245 (2005).
Stagnaro-Green, A. Overt hyperthyroidism and hypothyroidism during pregnancy. Clin. Obstet.Gynecol. 54, 478–487 (2011).
Tudela, C. M., Casey, B. M., McIntire, D. D. & Cunningham, F. G. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet. Gynecol. 119, 983–988 (2012).
Negro, R. et al. 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. 95, E44–E48 (2010).
Benhadi, N., Wiersinga, W. M., Reitsma, J. B., Vrijkotte, T. G. & Bonsel, G. J. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur. J. Endocrinol. 160, 985–991 (2009).
Negro, R. et al. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J. Clin. Endocrinol. Metab. 95, 1699–1707 (2010).
American College of Obstetricians and Gynecology. ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 37, August 2002. (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy. Obstet. Gynecol. 100, 387–396 (2002).
De Groot, L. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 97, 2543–2565 (2012).
Brent, G. A. The debate over thyroid-function screening in pregnancy. N. Engl. J. Med. 366, 562–563 (2012).
Mandel, S. J., Larsen, P. R., Seely, E. W. & Brent, G. A. Increased need for thryoxine during pregnancy in women with primary hypothyroidism. N. Engl. J. Med. 323, 91–96 (1990).
Abalovich, M. et al. The relationship of preconception thyrotropin levels to requirements for increasing the levothyroxine dose during pregnancy in women with primary hypothyroidism. Thyroid 20, 1175–1178 (2010).
Yassa, L., Marqusee, E., Fawcett, R. & Alexander, E. K. Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. J. Clin. Endocrinol. Metab. 95, 3234–3241 (2010).
Casey, B. M. et al. Subclinical hyperthyroidism and pregnancy outcomes. Obstet. Gynecol. 107, 337–341 (2006).
Goodwin, T. M. & Hershman, J. M. Hyperthyroidism due to inappropriate production of human chorionic gonadotropin. Clin. Obstet. Gynecol. 40, 32–44 (1997).
Tan, J. Y., Loh, K. C., Yeo, G. S. & Chee, Y. C. Transient hyperthyroidism of hyperemesis gravidarum. BJOG 109, 683–688 (2002).
Hershman, J. M. Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Thyroid 9, 653–657 (1999).
Bouillon, R. et al. Thyroid function in patients with hyperemesis gravidarum. Am. J. Obstet. Gynecol. 143, 922–926 (1982).
Patil-Sisodia, K. & Mestman, J. H. Graves hyperthyroidism and pregnancy: a clinical update. Endocr. Pract. 16, 118–129 (2010).
Mandel, S. J. & Cooper, D. S. The use of antithyroid drugs in pregnancy and lactation. J. Clin. Endocrinol. Metab. 86, 2354–2359 (2001).
Van Dijke, C. P., Heydendael, R. J. & De Kleine, M. J. Methimazole, carbimazole, and congenital skin defects. Ann. Int. Med. 106, 60–61 (1987).
Di Gianantonio, E. et al. Adverse effects of prenatal methimazole exposure. Teratology 64, 262–266 (2001).
Barbero, P. et al. Choanal atresia associated with maternal hyperthyroidism treated with methimazole: a case–control study. Am. J. Med. Genet. A 146A, 2390–2395 (2008).
Clementi, M. et al. Treatment of hyperthyroidism in pregnancy and birth defects. J. Clin. Endocrinol. Metab. 95, E337–E341 (2010).
Rosenfeld, H., Ornoy, A., Shechtman, S. & Diav-Citrin, O. Pregnancy outcome, thyroid dysfunction and fetal goitre after in utero exposure to propylthiouracil: a controlled cohort study. Br. J. Clin. Pharmacol. 68, 609–617 (2008).
Bahn R. S. et al. The role of propylthiouracil in the management of Graves' disease in adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 19, 673–674 (2009).
Zwaveling-Soonawala, N., van Trotsenburg, P. & Vulsma, T. Central hypothyroidism in an infant born to an adequately treated mother with Graves' disease: an effect of maternally derived thyrotrophin receptor antibodies? Thyroid 19, 661–662 (2009).
Peleg, D., Cada, S., Peleg, A. & Ben-Ami, M. The relationship between maternal serum thyroid-stimulating immunoglobulin and fetal and neonatal thyrotoxicosis. Obstet. Gynecol. 99, 1040–1043 (2002).
Laurberg, P., Nygaard, B., Glinoer, D., Grussendorf, M. & Orgiazzi, J. Guidelines for TSH-receptor antibody measurements in pregnancy: results of an evidence-based symposium organized by the European Thyroid Association. Eur. J. Endocrinol. 139, 584–586 (1998).
Luton, D. et al. Management of Graves' disease during pregnancy: the key role of fetal thyroid gland monitoring. J. Clin. Endocrinol. Metab. 90, 6093–6098 (2005).
Polak, M. et al. Fetal and neonatal thyroid function in relation to maternal Graves' disease. Best Pract. Res. Clin. Endocrinol. Metab. 18, 289–302 (2004).
Huel, C. et al. Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet. Gynecol. 33, 412–420 (2009).
Thangaratinam, S. et al. Association between thyroid auto-antibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 342, d2616 (2011).
Stagnaro-Green, A. et al. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 264, 1422–1425 (1990).
Stagnaro-Green, A. Thyroid antibodies and miscarriage: where are we at a generation later? J. Thyroid Res. 2011, 841949 (2011).
Danza, A., Ruiz-Irastorza, G. & Khamashta, M. Antiphospholipid syndrome in obstetrics. Best Pract. Res. Clin. Obstet. Gynaecol. 26, 65–76 (2012).
Toulis, K. A. et al. Risk of spontaneous miscarriage in euthyroid women with thyroid autoimmunity undergoing IVF: a meta-analysis. Eur. J. Endocrinol. 162, 643–652 (2010).
Stagnaro-Green, A. Maternal thyroid disease and preterm delivery. J. Clin. Endocrinol. Metab. 94, 21–25 (2009).
Swamy, G. K., Ostbye, T. & Skjaerven, R. Association of preterm birth with long-term survival, reproduction, and next-generation preterm birth. JAMA 299, 1429–1436 (2008).
Glinoer, D. et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J. Clin. Endocrinol. Metab. 73, 421–427 (1991).
Haddow, J. E. et al. Thyroperoxidase and thyroglobulin antibodies in early pregnancy and preterm delivery. Obstet. Gynecol. 116, 58–62 (2010).
Negro, R. et al. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J. Clin. Endocrinol. Metab. 91, 2587–2591 (2006).
American College of Obstetricians and Gynecologists, Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 32, November 2001 (replaces Technical Bulletin Number 181, June 1993, and Committee Opinion Number 241, September 2000). Thyroid disease in pregnancy. Obstet. Gynecol. 98, 879–888 (2001).
Gharib, H., Cobin, R. H. & Dickey, R. A. Subclinical hypothyroidism during pregnancy: Position statement from the American Association of Clinical Endocrinologists. Endocr. Pract. 5, 367–368 (1999).
Reid, S. M., Middleton, P., Cossich, M. C. & Crowther, C. A. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database of Systematic Reviews, Issue7. Art. No.: CD007752. http://dx.doi.org/10.1002/14651858.CD007752.pub2.
Amino, N. et al. High prevalence of transient post-partum thyrotoxicosis and hypothyroidism. N. Engl. J. Med. 306, 849–852 (1982).
Stagnaro-Green, A. Approach to the patient with postpartum thyroiditis. J. Clin. Endocrinol. Metab. 97, 334–342 (2012).
Muller, A. F., Drexhage, H. A. & Berghout, A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr. Rev. 22, 605–630 (2001).
Mizukami, Y. et al. Postpartum thyroiditis. A clinical, histologic, and immunopathologic study of 15 cases. Am. J. Clin. Pathol. 100, 200–205 (1993).
Jansson, R., Safwenberg, J. & Dahlberg, P. A. Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis. J. Clin. Endocrinol. Metab. 60, 168–173 (1985).
Alvarez-Marfany, M., Roman, S. H., Drexler, A. J., Robertson, C. & Stagnaro-Green, A. Long-term prospective study of postpartum thyroid dysfunction in women with insulin dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 79, 10–16 (1994).
Elefsiniotis, I. S., Vezali, E., Pantazis, K. D. & Saroglou, G. Post-partum thyroiditis in women with chronic viral hepatitis. J. Clin. Virol. 41, 318–319 (2008).
Stagnaro-Green, A. et al. Thyroid disease in pregnant women with systemic lupus erythematosus: increased preterm delivery. Lupus 20, 690–699 (2011).
Tagami, T. et al. The incidence of gestational hyper-thyroidism and postpartum thyroiditis in treated patients with Graves disease. Thyroid 17, 767–772 (2007).
Stagnaro-Green, A. et al. High rate of persistent hypothyroidism in a large-scale prospective study of postpartum thyroiditis in southern Italy. J. Clin. Endocrinol. Metab. 96, 652–657 (2011).
Walfish, P. G., Meyerson, J., Provias, J. P., Vargas, M. T. & Papsin, F. R. Prevalence and characteristics of post-partum thyroid dysfunction: results of a survey from Toronto, Canada. J. Endocrinol. Invest. 15, 265–272 (1992).
Lazarus, J. H. Clinical manifestations of postpartum thyroid disease. Thyroid 9, 685–689 (1999).
Hayslip, C. C. et al. The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction. Am. J. Obstet. Gynecol. 159, 203–209 (1988).
Harris, B. et al. Randomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women. Br. J. Psychiatry 180, 327–330 (2002).
Younes-Rapozo, V., Berendonk, J., Savignon, T., Manhães, A. C & Barradas, P. C. Thyroid hormone deficiency changes the distribution of oligodendrocyte/myelin markers during oligodendroglial differentiation in vitro. Int. J. Dev. Neurosci. 24, 445–453 (2006).
[No authors listed] Assessment of iodine deficiency disorders and monitoring their elimination. A guide for programme managers, 3rd edn (World Health Organization, Geneva, 2007).
Qian, M. et al. The effects of iodine on intelligence in children: a meta-anaylsis of studies conducted in China. Asia Pac. J. Clin. Nutr. 14, 32–42 (2005).
Glinoer, D. et al. Regulation of maternal thyroid during pregnancy. J. Clin. Endocrinol. Metab. 71, 276–287 (1990).
de Escobar, G. M., Obregón, M. J. & del Rey, F. E. Iodine deficiency and brain development in the first half of pregnancy. Publ. Health Nutr. 10, 1554–1570 (2007).
Velasco, I. et al. Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life. J. Clin. Endocrinol. Metab. 94, 3234–3241 (2009).
Berbel, P. et al. Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation: the importance of early iodine supplementation. Thyroid 19, 511–519 (2009).
Glinoer, D. The importance of iodine nutrition during pregnancy. Publ. Health Nutr. 10, 1542–1546 (2007).
Food and Nutrition Board, Institute of Medicine of the National Academies. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements (eds Otten, J. J., Hellwig, J. P. & Meyers, L. D.) 320–327 (National Academy Press, Washington, D. C., 2006).
WHO Secretariat, Andersson, M., de Benoist, B., Delange, F. & Zupan, J. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2 years old: conclusions and recommendations of the Technical Consultation. Pub. Health Nutr. 10, 1606–1611 (2007).
Andersen, S., Karmisholt, J., Pedersen, K. M. & Laurberg, P. Reliability of studies of iodine intake and recommendations for number of samples in groups and in individuals. Br. J. Nutr. 99, 813–818 (2008).
Leung, A. M., Pearce, E. N. & Braverman, L. E. Iodine content of prenatal multivitamins in the United States. N. Engl. J. Med. 360, 939–940 (2009).
Allan, W. C. et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J. Med. Screen. 7, 127–130 (2000).
Glinoer, D. Thyroid hyperfunction during pregnancy. Thyroid 8, 859–864 (2008).
Vaidya, B. et al. Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding? J. Clin. Endocrinol. Metab. 92, 203–207 (2007).
Horacek, J. et al. Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case finding. Eur. J. Endocrinol. 163, 645–650 (2010).
Chang, D., Leung, A. M., Braverman, L. E. & Pearce, E. N. Thyroid testing during pregnancy at an academic Boston area medical center. J. Clin. Endocrinol. Metab. 96, E1452–E1456 (2011).
Haddow, J. E., McClain, M. R., Palomaki, G. E., Kloza, E. M. & Williams, J. Screening for thyroid disorders during pregnancy: results of a survey in Maine. Am. J. Obstet. Gynecol. 194, 471–474 (2006).
Haymart, M. R. The role of clinical guidelines in patient care: thyroid hormone replacement in women of reproductive age. Thyroid 20, 301–307 (2010).
Blatt, A. J., Nakamoto, J. M. & Kaufman, H. W. National status of testing for hypothyroidism during pregnancy and postpartum. J. Clin. Endocrinol. Metab. 97, 777–784 (2012).
Vaidya B. et al. Treatment and screening of hypothyroidism in pregnancy: results of a European survey. Eur. J. Endocrinol. 166, 49–54 (2012).
Andersson, M., Karumbunathan, V. & Zimmermann, M. B. Global iodine status in 2011 and trends over the past decade. J. Nutr. 142, 744–750 (2012).
The authors declare no competing financial interests.
About this article
Cite this article
Stagnaro-Green, A., Pearce, E. Thyroid disorders in pregnancy. Nat Rev Endocrinol 8, 650–658 (2012). https://doi.org/10.1038/nrendo.2012.171
This article is cited by
Profiling of selenium absorption and accumulation in healthy subjects after prolonged l-selenomethionine supplementation
Journal of Endocrinological Investigation (2017)
Nature Reviews Endocrinology (2016)
Low-dose spinal–epidural anesthesia for Cesarean section in a parturient with uncontrolled hyperthyroidism and thyrotoxic heart disease
Journal of Anesthesia (2016)
Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency
European Journal of Nutrition (2016)