Skip to main content

Isolated Hypothyroxinemia During Pregnancy

  • Chapter
  • First Online:
Thyroid Diseases in Pregnancy
  • 395 Accesses

Abstract

During pregnancy, multiple adaptative changes occur in physiology to maintain an adequate level of thyroid hormones; however, various factors can compromise the functionality of the thyroid insufficiency during pregnancy, among which is isolated maternal hypothyroxinemia (IMH). The objective of this chapter is to present a review of the information available to date on the main epidemiological aspects, the diagnosis and management of this entity, as well as some of the perinatal and offspring outcomes of women diagnosed with IMH.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Furnica RM, Lazarus JH, Gruson D, Daumerie C. Update on a new controversy in endocrinology: isolated maternal hypothyroxinemia. J Endocrinol Investig. 2015;38(2):117–23.

    Article  CAS  Google Scholar 

  2. 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(3):315–89.

    Article  PubMed  Google Scholar 

  3. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J. 2014;3(2):76–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pakkila F, Mannisto T, Surcel HM, Ruokonen A, Bloigu A, Pouta A, et al. Maternal thyroid dysfunction during pregnancy and thyroid function of her child in adolescence. J Clin Endocrinol Metab. 2013;98(3):965–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Etemadi A, Amouzegar A, Mehran L, Tohidi M, Azizi F, Moradi K, et al. Isolated hypothyroxinemia in iranian pregnant women, the role of iodine deficiency: a population-based cross-sectional study. Thyroid. 2020;30(2):262–9.

    Article  CAS  PubMed  Google Scholar 

  6. Zhou M, Wang M, Li J, Luo X, Lei M. Effects of thyroid diseases on pregnancy outcomes. Exp Ther Med. 2019;18(3):1807–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Teng W, Shan Z, Patil-Sisodia K, Cooper DS. Hypothyroidism in pregnancy. Lancet Diabetes Endocrinol. 2013;1(3):228–37.

    Article  CAS  PubMed  Google Scholar 

  8. Negro R, Mestman JH. Thyroid disease in pregnancy. Best Pract Res Clin Endocrinol Metab. 2011;25(6):927–43.

    Article  CAS  PubMed  Google Scholar 

  9. Casey 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(5):1129–35.

    Article  PubMed  Google Scholar 

  10. Zimmermann MB, Burgi H, Hurrell RF. Iron deficiency predicts poor maternal thyroid status during pregnancy. J Clin Endocrinol Metab. 2007;92(9):3436–40.

    Article  CAS  PubMed  Google Scholar 

  11. Vaidya 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(1):203–7.

    Article  CAS  PubMed  Google Scholar 

  12. 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(1):85–92.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Moleti M, Lo Presti VP, Campolo MC, Mattina F, Galletti M, Mandolfino M, et al. Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency. J Clin Endocrinol Metab. 2008;93(7):2616–21.

    Article  CAS  PubMed  Google Scholar 

  14. Berbel P, Mestre JL, Santamaria A, Palazon I, Franco A, Graells M, 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. 2009;19(5):511–9.

    Article  CAS  PubMed  Google Scholar 

  15. Hamm MP, Cherry NM, Martin JW, Bamforth F, Burstyn I. The impact of isolated maternal hypothyroxinemia on perinatal morbidity. J Obstet Gynaecol Can. 2009;31(11):1015–21.

    Article  PubMed  Google Scholar 

  16. Henrichs J, Bongers-Schokking JJ, Schenk JJ, Ghassabian A, Schmidt HG, Visser TJ, et al. Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab. 2010;95(9):4227–34.

    Article  CAS  PubMed  Google Scholar 

  17. Su PY, Huang K, Hao JH, Xu YQ, Yan SQ, Li T, 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(10):3234–41.

    Article  CAS  PubMed  Google Scholar 

  18. Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493–501.

    Article  CAS  PubMed  Google Scholar 

  19. Craig WY, Allan WC, Kloza EM, Pulkkinen AJ, Waisbren S, Spratt DI, et al. Mid-gestational maternal free thyroxine concentration and offspring neurocognitive development at age two years. J Clin Endocrinol Metab. 2012;97(1):E22–8.

    Article  CAS  PubMed  Google Scholar 

  20. Oguz Kutlu A, Kara C. Iodine deficiency in pregnant women in the apparently iodine-sufficient capital city of Turkey. Clin Endocrinol. 2012;77(4):615–20.

    Article  CAS  Google Scholar 

  21. Altomare M, La Vignera S, Asero P, Recupero D, Condorelli RA, Scollo P, et al. High prevalence of thyroid dysfunction in pregnant women. J Endocrinol Investig. 2013;36(6):407–11.

    CAS  Google Scholar 

  22. Finken MJ, van Eijsden M, Loomans EM, Vrijkotte TG, Rotteveel J. Maternal hypothyroxinemia in early pregnancy predicts reduced performance in reaction time tests in 5- to 6-year-old offspring. J Clin Endocrinol Metab. 2013;98(4):1417–26.

    Article  CAS  PubMed  Google Scholar 

  23. Breathnach FM, Donnelly J, Cooley SM, Geary M, Malone FD. Subclinical hypothyroidism as a risk factor for placental abruption: evidence from a low-risk primigravid population. Aust N Z J Obstet Gynaecol. 2013;53(6):553–60.

    Article  PubMed  Google Scholar 

  24. Gowachirapant S, Melse-Boonstra A, Winichagoon P, Zimmermann MB. Overweight increases risk of first trimester hypothyroxinaemia in iodine-deficient pregnant women. Matern Child Nutr. 2014;10(1):61–71.

    Article  PubMed  Google Scholar 

  25. Saki F, Dabbaghmanesh MH, Ghaemi SZ, Forouhari S, Ranjbar Omrani G, Bakhshayeshkaram M. Thyroid function in pregnancy and its influences on maternal and fetal outcomes. Int J Endocrinol Metab. 2014;12(4):e19378.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Habimana L, Twite KE, Daumerie C, Wallemacq P, Donnen P, Kalenga MK, et al. High prevalence of thyroid dysfunction among pregnant women in Lubumbashi, Democratic Republic of Congo. Thyroid. 2014;24(3):568–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yu X, Shan Z, Li C, Mao J, Wang W, Xie X, et al. Iron deficiency, an independent risk factor for isolated hypothyroxinemia in pregnant and nonpregnant women of childbearing age in China. J Clin Endocrinol Metab. 2015;100(4):1594–601.

    Article  CAS  PubMed  Google Scholar 

  28. Han C, Li C, Mao J, Wang W, Xie X, Zhou W, et al. High body mass index is an indicator of maternal hypothyroidism, hypothyroxinemia, and thyroid-peroxidase antibody positivity during early pregnancy. Biomed Res Int. 2015;2015:351831.

    PubMed  PubMed Central  Google Scholar 

  29. Knight BA, Shields BM, Hattersley AT, Vaidya B. Maternal hypothyroxinaemia in pregnancy is associated with obesity and adverse maternal metabolic parameters. Eur J Endocrinol. 2016;174(1):51–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Dieguez M, Herrero A, Avello N, Suarez P, Delgado E, Menendez E. Prevalence of thyroid dysfunction in women in early pregnancy: does it increase with maternal age? Clin Endocrinol. 2016;84(1):121–6.

    Article  CAS  Google Scholar 

  31. Furnica RM, Gruson D, Lazarus JH, Maiter D, Bernard P, Daumerie C. First trimester isolated maternal hypothyroxinaemia: adverse maternal metabolic profile and impact on the obstetrical outcome. Clin Endocrinol. 2017;86(4):576–83.

    Article  CAS  Google Scholar 

  32. Korevaar TI, de Rijke YB, Chaker L, Medici M, Jaddoe VW, Steegers EA, et al. Stimulation of thyroid function by human chorionic gonadotropin during pregnancy: a risk factor for thyroid disease and a mechanism for known risk factors. Thyroid. 2017;27(3):440–50.

    Article  CAS  PubMed  Google Scholar 

  33. Casey BM, Thom EA, Peaceman AM, Varner MW, Sorokin Y, Hirtz DG, et al. Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. N Engl J Med. 2017;376(9):815–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hernandez-Mariano JA, Torres-Sanchez L, Bassol-Mayagoitia S, Escamilla-Nunez MC, Cebrian ME, Villeda-Gutierrez EA, et al. Effect of exposure to p,p -DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area. Environ Res. 2017;156:597–604.

    Article  CAS  PubMed  Google Scholar 

  35. Nelson SM, Haig C, McConnachie A, Sattar N, Ring SM, Smith GD, et al. Maternal thyroid function and child educational attainment: prospective cohort study. BMJ. 2018;360:k452.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zhu YD, Han Y, Huang K, Zhu BB, Yan SQ, Ge X, et al. The impact of isolated maternal hypothyroxinaemia on the incidence of large-for-gestational-age infants: the Ma'anshan Birth Cohort study. BJOG. 2018;125(9):1118–25.

    Article  CAS  PubMed  Google Scholar 

  37. Yang J, Liu Y, Liu H, Zheng H, Li X, Zhu L, et al. Associations of maternal iodine status and thyroid function with adverse pregnancy outcomes in Henan Province of China. J Trace Elem Med Biol. 2018;47:104–10.

    Article  CAS  PubMed  Google Scholar 

  38. Dong AC, Stagnaro-Green A. Differences in diagnostic criteria mask the true prevalence of thyroid disease in pregnancy: a systematic review and meta-analysis. Thyroid. 2019;29(2):278–89.

    Article  PubMed  Google Scholar 

  39. Huang K, Xu Y, Yan S, Li T, Xu Y, Zhu P, et al. Isolated effect of maternal thyroid-stimulating hormone, free thyroxine and antithyroid peroxidase antibodies in early pregnancy on gestational diabetes mellitus: a birth cohort study in China. Endocr J. 2019;66(3):223–31.

    Article  CAS  PubMed  Google Scholar 

  40. Consortium on T, Pregnancy-Study Group on Preterm B, Korevaar TIM, Derakhshan A, Taylor PN, Meima M, et al. Association of thyroid function test abnormalities and thyroid autoimmunity with preterm birth: a systematic review and meta-analysis. JAMA. 2019;322(7):632–41.

    Article  CAS  Google Scholar 

  41. Su X, Zhao Y, Cao Z, Yang Y, Duan T, Hua J. Association between isolated hypothyroxinaemia in early pregnancy and perinatal outcomes. Endocr Connect. 2019;8(4):435–41.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chen Z, Yang X, Zhang C, Ding Z, Zhang Y, Korevaar TIM, et al. Thyroid function test abnormalities in twin pregnancies. Thyroid. 2020;

    Google Scholar 

  43. Chen L, Yang H, Ye E, Lin Z, Peng M, Lin H, et al. Insignificant effect of isolated hypothyroxinemia on pregnancy outcomes during the first and second trimester of pregnancy. Front Endocrinol (Lausanne). 2020;11:528146.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Refaat B, Azzeh F. Factors Associated with Thyroid Disorders and Iodine Adequacy in Pregnant Saudi Women. Biol Trace Elem Res. 2020;

    Google Scholar 

  45. Dosiou C, Medici M. Management of endocrine disease: isolated maternal hypothyroxinemia during pregnancy: knowns and unknowns. Eur J Endocrinol. 2017;176(1):R21–38.

    Article  CAS  PubMed  Google Scholar 

  46. Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update. 2003;9(2):149–61.

    Article  PubMed  Google Scholar 

  47. Ramezani Tehrani F, Nazarpour S, Behboudi-Gandevani S. Isolated maternal hypothyroxinemia and adverse pregnancy outcomes: a systematic review. J Gynecol Obstet Hum Reprod. 2021;50(7):102057.

    Article  PubMed  Google Scholar 

  48. Shan ZY, Chen YY, Teng WP, Yu XH, Li CY, Zhou WW, et al. A study for maternal thyroid hormone deficiency during the first half of pregnancy in China. Eur J Clin Investig. 2009;39(1):37–42.

    Article  CAS  Google Scholar 

  49. Krassas G, Karras SN, Pontikides N. Thyroid diseases during pregnancy: a number of important issues. Hormones (Athens). 2015;14(1):59–69.

    Article  Google Scholar 

  50. Lopez-Munoz E, Mateos-Sanchez L, Mejia-Terrazas GE, Bedwell-Cordero SE. Hypothyroidism and isolated hypothyroxinemia in pregnancy, from physiology to the clinic. Taiwan J Obstet Gynecol. 2019;58(6):757–63.

    Article  PubMed  Google Scholar 

  51. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18(3):404–33.

    Article  CAS  PubMed  Google Scholar 

  52. Vermiglio F, Lo Presti VP, Castagna MG, Violi MA, Moleti M, Finocchiaro MD, et al. Increased risk of maternal thyroid failure with pregnancy progression in an iodine deficient area with major iodine deficiency disorders. Thyroid. 1999;9(1):19–24.

    Article  CAS  PubMed  Google Scholar 

  53. Henrichs J, Ghassabian A, Peeters RP, Tiemeier H. Maternal hypothyroxinemia and effects on cognitive functioning in childhood: how and why? Clin Endocrinol. 2013;79(2):152–62.

    Article  Google Scholar 

  54. Dahiya B. ASEAN economic integration and sustainable urbanization. J Urban Cult Res. 2016;3(1):8–15. https://doi.org/10.14456/JUCR.2016.10.

    Article  Google Scholar 

  55. Veltri F, Decaillet S, Kleynen P, Grabczan L, Belhomme J, Rozenberg S, et al. Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered? Eur J Endocrinol. 2016;175(3):191–9.

    Article  CAS  PubMed  Google Scholar 

  56. Rosario PW, Oliveira LFF, Calsolari MR. Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study. Arch Endocrinol Metab. 2018;62(3):332–6.

    PubMed  Google Scholar 

  57. Korevaar TI, Steegers EA, de Rijke YB, Visser WE, Jaddoe VW, Visser TJ, et al. Placental angiogenic factors are associated with maternal thyroid function and modify hCG-mediated FT4 stimulation. J Clin Endocrinol Metab. 2015;100(10):E1328–34.

    Article  CAS  PubMed  Google Scholar 

  58. Clark DE, Smith SK, He Y, Day KA, Licence DR, Corps AN, et al. A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol Reprod. 1998;59(6):1540–8.

    Article  CAS  PubMed  Google Scholar 

  59. Kamba T, Tam BY, Hashizume H, Haskell A, Sennino B, Mancuso MR, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006;290(2):H560–76.

    Article  CAS  PubMed  Google Scholar 

  60. Korevaar TI, Steegers EA, Schalekamp-Timmermans S, Ligthart S, de Rijke YB, Visser WE, et al. Soluble Flt1 and placental growth factor are novel determinants of newborn thyroid (dys)function: the generation R study. J Clin Endocrinol Metab. 2014;99(9):E1627–34.

    Article  CAS  PubMed  Google Scholar 

  61. Fan J, Zhang Y, Zhang C, Barjaktarovic M, Yang X, Peeters RP, et al. Persistency of thyroid dysfunction from early to late pregnancy. Thyroid. 2019;29(10):1475–84.

    Article  CAS  PubMed  Google Scholar 

  62. Oostenbroek MHW, Kersten RHJ, Tros B, Kunst AE, Vrijkotte TGM, Finken MJJ. Maternal hypothyroxinaemia in early pregnancy and problem behavior in 5-year-old offspring. Psychoneuroendocrinology. 2017;81:29–35.

    Article  CAS  PubMed  Google Scholar 

  63. Yang X, Yu Y, Zhang C, Zhang Y, Chen Z, Dubois L, et al. The association between isolated maternal hypothyroxinemia in early pregnancy and preterm birth. Thyroid. 2020;30(12):1724–31.

    Article  CAS  PubMed  Google Scholar 

  64. Sheng Y, Huang D, Liu S, Guo X, Chen J, Shao Y, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Knudsen N, Bulow I, Laurberg P, Ovesen L, Perrild H, Jorgensen T. Parity is associated with increased thyroid volume solely among smokers in an area with moderate to mild iodine deficiency. Eur J Endocrinol. 2002;146(1):39–43.

    Article  CAS  PubMed  Google Scholar 

  66. Korevaar TI, Nieboer D, Bisschop PH, Goddijn M, Medici M, Chaker L, et al. Risk factors and a clinical prediction model for low maternal thyroid function during early pregnancy: two population-based prospective cohort studies. Clin Endocrinol. 2016;85(6):902–9.

    Article  CAS  Google Scholar 

  67. Rotondi M, Amato G, Biondi B, Mazziotti G, Del Buono A, Rotonda Nicchio M, et al. Parity as a thyroid size-determining factor in areas with moderate iodine deficiency. J Clin Endocrinol Metab. 2000;85(12):4534–7.

    Article  CAS  PubMed  Google Scholar 

  68. Moleti M, Lo Presti VP, Mattina F, Mancuso A, De Vivo A, Giorgianni G, et al. Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus continuous monitoring of maternal thyroid status. Eur J Endocrinol. 2009;160(4):611–7.

    Article  CAS  PubMed  Google Scholar 

  69. Koopman-Esseboom C, Morse DC, Weisglas-Kuperus N, Lutkeschipholt IJ, Van der Paauw CG, Tuinstra LG, et al. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res. 1994;36(4):468–73.

    Article  CAS  PubMed  Google Scholar 

  70. Ghassabian A, Pierotti L, Basterrechea M, Chatzi L, Estarlich M, Fernandez-Somoano A, et al. Association of exposure to ambient air pollution with thyroid function during pregnancy. JAMA Netw Open. 2019;2(10):e1912902.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Pearce EN, Oken E, Gillman MW, Lee SL, Magnani B, Platek D, et al. Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use. Endocr Pract. 2008;14(1):33–9.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Olivares EL, Silva-Almeida C, Pestana FM, Sonoda-Cortes R, Araujo IG, Rodrigues NC, et al. Social stress-induced hypothyroidism is attenuated by antidepressant treatment in rats. Neuropharmacology. 2012;62(1):446–56.

    Article  CAS  PubMed  Google Scholar 

  73. 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(8):2543–65.

    Article  PubMed  CAS  Google Scholar 

  74. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31(5):702–55.

    Article  CAS  PubMed  Google Scholar 

  75. Dong AC, Stephenson MD, Stagnaro-Green AS. The need for dynamic clinical guidelines: a systematic review of new research published after release of the 2017 ATA guidelines on thyroid disease during pregnancy and the postpartum. Front Endocrinol (Lausanne). 2020;11:193.

    Article  Google Scholar 

  76. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081–125.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Rotondi M, Capelli V, Chiovato L, Nappi RE. 2017 ATA guidelines on the management of thyroid dysfunctions in pregnancy: what do OB/GYNs need to know? Gynecol Endocrinol. 2019;35(4):276–9.

    Article  CAS  PubMed  Google Scholar 

  78. Yue B, Rockwood AL, Sandrock T, La'ulu SL, Kushnir MM, Meikle AW. Free thyroid hormones in serum by direct equilibrium dialysis and online solid-phase extraction--liquid chromatography/tandem mass spectrometry. Clin Chem. 2008;54(4):642–51.

    Article  CAS  PubMed  Google Scholar 

  79. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988–1028.

    Article  PubMed  Google Scholar 

  80. Azizi F, Mehran L, Amouzegar A, Delshad H, Tohidi M, Askari S, et al. Establishment of the trimester-specific reference range for free thyroxine index. Thyroid. 2013;23(3):354–9.

    Article  PubMed  CAS  Google Scholar 

  81. Korevaar TI, Chaker L, Medici M, de Rijke YB, Jaddoe VW, Steegers EA, et al. Maternal total T4 during the first half of pregnancy: physiologic aspects and the risk of adverse outcomes in comparison with free T4. Clin Endocrinol. 2016;85(5):757–63.

    Article  CAS  Google Scholar 

  82. Weeke J, Dybkjaer L, Granlie K, Eskjaer Jensen S, Kjaerulff E, Laurberg P, et al. A longitudinal study of serum TSH, and total and free iodothyronines during normal pregnancy. Acta Endocrinol. 1982;101(4):531–7.

    Article  CAS  Google Scholar 

  83. Pramanik S, Mukhopadhyay P, Ghosh S. Total T4 rise in pregnancy: a relook? Thyroid Res. 2020;13:14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pantalone KM, Hatipoglu B, Gupta MK, Kennedy L, Hamrahian AH. Measurement of serum free thyroxine index may provide additional case detection compared to free thyroxine in the diagnosis of central hypothyroidism. Case Rep Endocrinol. 2015;2015:965191.

    PubMed  PubMed Central  Google Scholar 

  85. Lee RH, Spencer CA, Mestman JH, Miller EA, Petrovic I, Braverman LE, et al. Free T4 immunoassays are flawed during pregnancy. Am J Obstet Gynecol 2009;200(3):260 e1–6.

    Google Scholar 

  86. Zoeller RT, Rovet J. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol. 2004;16(10):809–18.

    Article  CAS  PubMed  Google Scholar 

  87. Yazbeck CF, Sullivan SD. Thyroid disorders during pregnancy. Med Clin North Am. 2012;96(2):235–56.

    Article  CAS  PubMed  Google Scholar 

  88. Taylor PN, Muller I, Nana M, Velasco I, Lazarus JH. Indications for treatment of subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy. Best Pract Res Clin Endocrinol Metab. 2020;34(4):101436.

    Article  CAS  PubMed  Google Scholar 

  89. Vermiglio F, Lo Presti VP, Moleti M, Sidoti M, Tortorella G, Scaffidi G, et al. Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild-moderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab. 2004;89(12):6054–60.

    Article  CAS  PubMed  Google Scholar 

  90. Gyllenberg D, Sourander A, Surcel HM, Hinkka-Yli-Salomaki S, McKeague IW, Brown AS. hypothyroxinemia during gestation and offspring Schizophrenia in a National Birth Cohort. Biol Psychiatry. 2016;79(12):962–70.

    Article  CAS  PubMed  Google Scholar 

  91. Korevaar TI, Schalekamp-Timmermans S, de Rijke YB, Visser WE, Visser W, de Muinck Keizer-Schrama SM, et al. Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study. J Clin Endocrinol Metab. 2013;98(11):4382–90.

    Article  CAS  PubMed  Google Scholar 

  92. Zhang Y, Dai X, Yang S, Zhang C, Han M, Huang HF, et al. Maternal low thyroxin levels are associated with adverse pregnancy outcomes in a Chinese population. PLoS One. 2017;12(5):e0178100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Sheehan PM, Nankervis A, Araujo Junior E, Da Silva CF. Maternal thyroid disease and preterm birth: systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(11):4325–31.

    Article  CAS  PubMed  Google Scholar 

  94. Oguz A, Tuzun D, Sahin M, Usluogullari AC, Usluogullari B, Celik A, et al. Frequency of isolated maternal hypothyroxinemia in women with gestational diabetes mellitus in a moderately iodine-deficient area. Gynecol Endocrinol. 2015;31(10):792–5.

    Article  CAS  PubMed  Google Scholar 

  95. Ashoor G, Maiz N, Rotas M, Jawdat F, Nicolaides KH. Maternal thyroid function at 11–13 weeks of gestation and spontaneous preterm delivery. Obstet Gynecol. 2011;117(2 Pt 1):293–8.

    Article  CAS  PubMed  Google Scholar 

  96. 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(3):282–8.

    Article  Google Scholar 

  97. Levie D, Korevaar TIM, Bath SC, Dalmau-Bueno A, Murcia M, Espada M, et al. Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data. J Clin Endocrinol Metab. 2018;103(8):2967–79.

    Article  PubMed  Google Scholar 

  98. 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(6):501–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Grau G, Aguayo A, Vela A, Aniel-Quiroga A, Espada M, Miranda G, et al. Normal intellectual development in children born from women with hypothyroxinemia during their pregnancy. J Trace Elem Med Biol. 2015;31:18–24.

    Article  CAS  PubMed  Google Scholar 

  100. Li Y, Shan Z, Teng W, Yu X, Li Y, Fan C, et al. Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months. Clin Endocrinol. 2010;72(6):825–9.

    Article  CAS  Google Scholar 

  101. Korevaar TI, Muetzel R, Medici M, Chaker L, Jaddoe VW, de Rijke YB, 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(1):35–43.

    Article  CAS  PubMed  Google Scholar 

  102. Medici M, Timmermans S, Visser W, de Muinck Keizer-Schrama SM, Jaddoe VW, Hofman A, et al. Maternal thyroid hormone parameters during early pregnancy and birth weight: the Generation R Study. J Clin Endocrinol Metab. 2013;98(1):59–66.

    Article  CAS  PubMed  Google Scholar 

  103. Julvez J, Alvarez-Pedrerol M, Rebagliato M, Murcia M, Forns J, Garcia-Esteban R, et al. Thyroxine levels during pregnancy in healthy women and early child neurodevelopment. Epidemiology. 2013;24(1):150–7.

    Article  PubMed  Google Scholar 

  104. Roman GC, Ghassabian A, Bongers-Schokking JJ, Jaddoe VW, Hofman A, de Rijke YB, et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013;74(5):733–42.

    Article  CAS  PubMed  Google Scholar 

  105. Oken E, Braverman LE, Platek D, Mitchell ML, Lee SL, Pearce EN. Neonatal thyroxine, maternal thyroid function, and child cognition. J Clin Endocrinol Metab. 2009;94(2):497–503.

    Article  CAS  PubMed  Google Scholar 

  106. Ghassabian A, Bongers-Schokking JJ, Henrichs J, Jaddoe VW, Visser TJ, Visser W, et al. Maternal thyroid function during pregnancy and behavioral problems in the offspring: the generation R study. Pediatr Res. 2011;69(5 Pt 1):454–9.

    Article  CAS  PubMed  Google Scholar 

  107. Morreale de Escobar G, Obregon MJ, Escobar del Rey F. Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab. 2000;85(11):3975–87.

    CAS  PubMed  Google Scholar 

  108. Modesto T, Tiemeier H, Peeters RP, Jaddoe VW, Hofman A, Verhulst FC, et al. Maternal mild thyroid hormone insufficiency in early pregnancy and attention-deficit/hyperactivity disorder symptoms in children. JAMA Pediatr. 2015;169(9):838–45.

    Article  PubMed  Google Scholar 

  109. Chang K, Shin JI. Association of gestational maternal hypothyroxinemia and increased autism risk: the role of brain-derived neurotrophic factor. Ann Neurol. 2014;75(6):971.

    Article  CAS  PubMed  Google Scholar 

  110. Negro R, Soldin OP, Obregon MJ, Stagnaro-Green A. Hypothyroxinemia and pregnancy. Endocr Pract. 2011;17(3):422–9.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Moleti M, Vermiglio F, Trimarchi F. Maternal isolated hypothyroxinemia: to treat or not to treat? J Endocrinol Investig. 2009;32(9):780–2.

    Article  CAS  Google Scholar 

  112. Auso 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(9):4037–47.

    Article  CAS  PubMed  Google Scholar 

  113. Lavado-Autric R, Auso E, Garcia-Velasco JV, Arufe Mdel C, Escobar del Rey F, Berbel P, et al. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J Clin Invest. 2003;111(7):1073–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Goodman JH, Gilbert ME. Modest thyroid hormone insufficiency during development induces a cellular malformation in the corpus callosum: a model of cortical dysplasia. Endocrinology. 2007;148(6):2593–7.

    Article  CAS  PubMed  Google Scholar 

  115. Lazarus JH, Taylor PN. Hypothyroxinaemia and brain development. Acta Endocrinol (Buchar). 2016;12(1):1–6.

    Article  CAS  Google Scholar 

  116. Koyuncu K, Turgay B, Soylemez F. Iodine deficiency in pregnant women at first trimester in Ankara. J Turk Ger Gynecol Assoc. 2019;20(1):37–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Harding KB, Pena-Rosas JP, Webster AC, Yap CM, Payne BA, Ota E, et al. Iodine supplementation for women during the preconception, pregnancy and postpartum period. Cochrane Database Syst Rev 2017;3:CD011761.

    Google Scholar 

  118. Shi X, Han C, Li C, Mao J, Wang W, Xie X, et al. Optimal and safe upper limits of iodine intake for early pregnancy in iodine-sufficient regions: a cross-sectional study of 7190 pregnant women in China. J Clin Endocrinol Metab. 2015;100(4):1630–8.

    Article  CAS  PubMed  Google Scholar 

  119. Chang DL, Pearce EN. Screening for maternal thyroid dysfunction in pregnancy: a review of the clinical evidence and current guidelines. J Thyroid Res. 2013;2013:851326.

    Article  PubMed  PubMed Central  Google Scholar 

  120. Taylor PN, Okosieme OE, Premawardhana L, Lazarus JH. Should all women be screened for thyroid dysfunction in pregnancy? Womens Health (Lond). 2015;11(3):295–307.

    Article  CAS  Google Scholar 

  121. Gong X, Liu A, Li Y, Sun H, Li Y, Li C, et al. The impact of isolated maternal hypothyroxinemia during the first and second trimester of gestation on pregnancy outcomes: an intervention and prospective cohort study in China. J Endocrinol Investig. 2019;42(5):599–607.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

López-Muñoz, E. (2022). Isolated Hypothyroxinemia During Pregnancy. In: Azizi, F., Ramezani Tehrani, F. (eds) Thyroid Diseases in Pregnancy. Springer, Cham. https://doi.org/10.1007/978-3-030-98777-0_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-98777-0_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-98776-3

  • Online ISBN: 978-3-030-98777-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics