Objectives: The aim of the study was to determine the evolution of thyroid tests throughout pregnancy and postpartum in healthy women with and without iodine supplementation. Methods: This was a prospective, randomized, interventional study of iodine supplementation (150 μg/day) from the first trimester until 3 months postpartum versus controls. 111 pregnant women with normal initial thyroid tests were enrolled, undergoing comprehensive thyroid assessment at each trimester. We present results of longitudinal and cross-sectional analyses. Results: Initial ioduria suggested mild iodine deficiency in both groups, while third-trimester ioduria rose to levels of iodine sufficiency in the iodine-supplemented group. In the longitudinal study, free T4 (FT4) levels decreased in the second and third trimesters compared to the first trimester in both groups, with no change in TSH, and rose postpartum, though lower than the first trimester. FT3 levels and the total T4 (TT4)/thyroxine-binding globulin (TBG) ratio followed the same evolution as FT4. TT4 levels rose due to TBG increase. Thyroglobulin (Tg) of iodine group remained stable, contrasting with the rise in the control group. In the cross-sectional study, there was no difference between the two groups in thyroid tests at any time-point, except for lower Tg in the second trimester and postpartum visits in the iodine group. Conclusions: In healthy, mildly iodine-deficient pregnant women, a ‘drop' of FT4 and TT4/TBG without TSH increase occurs between the first and second trimesters, and is not prevented by iodine supplementation, suggesting physiology. Therefore, FT4 is valuable to assess thyroid function in pregnancy in clinical practice with appropriate trimester-specific reference range. It brings up reflection on threshold for diagnosis and treatment of hypothyroxinemia.

Keywords:
Iodine, Pregnancy, Free T4, Thyroglobulin, Ioduria
1.
Glinoer D: The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-433.
2.
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;85:3975-3987.
3.
De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, Eastman CJ, Lazarus JH, Luton D, Mandel SJ, Mestman J, Rovet J, Sullivan S: Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2543-2535.
4.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin O, Sullivan S, Wiersinga W: Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1-45.
5.
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 prospective study. Clin Endocrinol 2003;59:282-288.
6.
Henrichs J, Bongers-Schokking JJ, Schenk JJ, Ghassabian A, Schmidt HG, Visser TJ, Hooijkaas H, de Muinck Keizer-Schrama SMPF, Hofman A, Jaddoe VVW, Visser W, Steegers EAP, Verhulst FC, de Rijke YB, Tiemeier H: Maternal thyroid function during early pregnancy and cognitive functioning in early childhood: the generation R study. J Clin Endocrinol Metab 2010;95:4227-4234.
7.
Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, Chiusano E, John R, Guaraldo V, George LM, Perona M, Dall'Amico D, Parkes AB, Joomun M, Wald NJ: Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012;366:493-501.
8.
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 of age: conclusions and recommendations of the Technical Consultation. Public Health Nutr 2007;10:1606-1611.
9.
Zimmermann MB: Iodine deficiency. Endocr Rev 2009;30:376-408.
10.
Glinoer D, De Nayer P, Delange F, Lemone M, Toppet V, Spehl M, Grün JP, Kinthaert J, Lejeune B: A randomized trial for the treatment of mild iodine deficiency during pregnancy: maternal and neonatal effects. J Clin Endocrinol Metab 1995;80:258-269.
11.
Delange F: Iodine deficiency as a cause of brain damage Postgrad Med J 2011;77:217-220.
12.
Pearce EN: What do we know about iodine supplementation in pregnancy? J Clin Endocrinol Metab 2009;94:3188-3190.
13.
Petrovic I, Savin S, Spasic S, Cvejic D, Paunkovic N, Paunkovic J: The T4/TBG ratio in healthy subjects and in patients with disorders of thyroid function: correlation with T4 concentrations. Jugoslov Med Biohem 2005;24:241-246.
14.
Nohr SB, Jorgensen A, Pedersen KM, Laurberg P: Postpartum dysfunction in pregnant thyroid peroxidase antibody-positive women iodine deficiency: is iodine supplementation safe? J Clin Endocrinol Metab 2000;85:3191-3198.
15.
Romano R, Jannini EA, Pepe M, Grimaldi A, Olivieri M, Spennati P, Cappa F, D'armiento M: The effects of iodoprophylaxis on thyroid size during pregnancy. Am J Obstet Gynecol 1991;164:482-485.
16.
Antonangeli L, Maccehini D, Cavaliere R, Di Giulio C, Reinhardt B, Pinchera A, Aghini-Lombardi F: Comparison of two different doses of iodide in the prevention of gestational goiter in marginal iodine deficiency: a longitudinal study. Eur J Endocrinol 2002;147:29-34.
17.
Pedersen KM, Laurberg P, Iversen E, Knudsen PR, Gregersen HE, Rasmussen OS, Larsen KR, Eriksen GM, Johannesen PL: Amelioration of some pregnancy-associated variations in thyroid function by iodine supplementation. J Clin Endocrinol Metab 1993;77:1078-1083.
18.
Liesenkötter KP, Göpel W, Bogner U, Stach B, Grüters A: Earliest prevention of endemic goiter by iodine supplementation during pregnancy. Eur J Endocrinol 1996;134:443-448.
19.
Velasco I, Carreira M, Santiago P, Muela JA, Garcia-Fuentes E, Sanchez-Munoz B, Gonzalez-Fernadez MC, Rodriguez A, Caballero F, Machado A, Gonzalez-Romero S, Anarte MT, Soriguer F: Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life. J Clin Endocrinol Metab 2009;94:3234-3241.
20.
Santiago P, Velasco I, Muela JA, Sanchez B, Martinez J, Rodriguez A, Berrio M, Gutierrez-Repiso C, Carreira M, Moreno A, Garcia-Fuentes E, Soriguer F: Infant neurocognitive development is independent of the use of iodised salt or iodine supplements given during pregnancy. Br J Nutr 2013;4:1-9.
21.
Stilwell G, Reynolds PJ, Parameswaran V, Blizzard L, Greenaway TM, Burgess JR: The influence of gestational stage on urine iodine excretion in pregnancy. J Clin Metab Endocrinol 2008;93:1737-1742.
22.
Hiéronimus S, Bec-Roche M, Ferrari P, Chevalier N, Fénichel P, Brucker-Davis F: Iodine status and thyroid function of 330 pregnant women from Nice area assessed during the second part of pregnancy. Ann Endocrinol 2009;70:218-224.
23.
Lee RH, Spencer CA, Mestman JH, Miller EA, Petrovic I, Braverman LE, Goodwin TM: Free T4 immunoassays are flawed during pregnancy. Am J Obstet Gynecol 2009;200:260.e1-260.e6.
24.
Anckaert E, Poppe K, Van Uytfanghe K, Schiettecatte J, Foulon W, Thienpont LM: FT4 immunoassays may display a pattern during pregnancy similar to the dialysis ID-LC/tandem MS candidate reference measurement procedure in spite of susceptibility towards binding protein alterations. Clin Chem Acta 2010;411:1348-1353.
25.
Zimmermann MB: The effects of iodine deficiency in pregnancy and infancy. Paed Perinatal Epidemiol 2012;26(suppl 1):108-117.
26.
Moleti M, Pio Lo Presti V, Campolo MC, Mattina F, Galletti M, Mandofilno M, Violi MA, Giorgianni G, De Domenico D, Trimarchi F, Vermiglio F: Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency. J Clin Endocrinol Metab 2008;93:2616-2621.
27.
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;14:1084-1090.
28.
Ball R, Freedman DB, Holmes JC, Midgley JEM, Sheehan CP: Low-normal concentrations of free thyroxin in serum in late pregnancy: physiological fact, not technical artefact. Clin Chem 1989;35:1891-1896.
29.
Migdley JE, Christofides ND: Free thyroxine assays: no going back! Am J Obstet Gynecol 2010;202:e6.
30.
Hiéronimus S, Ferrari P, Gal J, Berthier F, Azoulay S, Bongain A, Fenichel P, Brucker-Davis F: Relative impact of iodine supplementation and maternal smoking on cord blood thyroglobulin in pregnant women with normal thyroid function. Eur Thyr J 2012;1:264-273.
31.
Burns R, O'Herlihy C, Smyth PP: The placenta as a compensatory iodine storage organ. Thyroid 2011;21:541-546.
© 2013 European Thyroid Association Published by S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.