Iodine Supplementation throughout Pregnancy Does Not Prevent the Drop in FT4 in the Second and Third Trimesters in Women with Normal Initial Thyroid Function

Abstract

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: Free T4; Iodine; Ioduria; Pregnancy; Thyroglobulin.

Fig. 1

Evolution of median FT4, TT4, TT4/TBG in 36 women followed at each trimester during pregnancy and 3 months postpartum (n = 18 in both groups): paired analysis. V1 = 1st trimester visit; V2 = 2nd trimester visit; V3 = 3rd trimester visit; V5 = postpartum visit. FT4 and T4/TBG have similar evolution in the iodine and control groups: V2 vs. V1, p < 0.001; V3 vs. V1, p < 0.01; V5 vs. V2, p < 0.05; V5 vs. V3, p < 0.05. TT4 has similar evolution in the iodine and control groups: V5 vs. V2, p < 0.001; V5 vs. V3, p < 0.001; V5 vs. V1 reaches significance only in the iodine group (p < 0.05). No difference was found between the two groups at each time interval.

Fig. 2

Evolution of median FT3, TSH, and Tg in 36 women followed at each trimester of pregnancy and 3 months postpartum (n = 18 in both groups): paired analysis. FT3 has similar evolution in the iodine and control groups: V2 vs. V1, p < 0.01; V3 vs. V1, p < 0.01; V5 vs. V2, p < 0.05; V5 vs. V3, p < 0.01. There is no difference in TSH over time and between the two groups. The rise in Tg is not significant in the control group, while Tg is lower in the 2nd trimester (p < 0.05) and postpartum (p < 0.01) in the iodine group. Tg was lower in the iodine group compared to the control group in the 2nd trimester (p < 0.05) and postpartum (p < 0.02).