Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy

B. M. Casey, E. A. Thom, A. M. Peaceman, M. W. Varner, Y. Sorokin, D. G. Hirtz, U. M. Reddy, R. J. Wapner, J. M. Thorp, G. Saade, A. T N Tita, D. J. Rouse, B. Sibai, J. D. Iams, B. M. Mercer, J. Tolosa, S. N. Caritis, J. P. VanDorsten

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P = 0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P = 0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions.

Original languageEnglish (US)
Pages (from-to)815-825
Number of pages11
JournalNew England Journal of Medicine
Volume376
Issue number9
DOIs
StatePublished - Mar 2 2017

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Hypothyroidism
Thyroxine
Pregnancy
Thyrotropin
Placebos
Confidence Intervals
Therapeutics
Thyroid Diseases
Pregnancy Outcome
Random Allocation
Cognition
Thyroid Gland
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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Casey, B. M., Thom, E. A., Peaceman, A. M., Varner, M. W., Sorokin, Y., Hirtz, D. G., ... VanDorsten, J. P. (2017). Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. New England Journal of Medicine, 376(9), 815-825. https://doi.org/10.1056/NEJMoa1606205

Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. / Casey, B. M.; Thom, E. A.; Peaceman, A. M.; Varner, M. W.; Sorokin, Y.; Hirtz, D. G.; Reddy, U. M.; Wapner, R. J.; Thorp, J. M.; Saade, G.; Tita, A. T N; Rouse, D. J.; Sibai, B.; Iams, J. D.; Mercer, B. M.; Tolosa, J.; Caritis, S. N.; VanDorsten, J. P.

In: New England Journal of Medicine, Vol. 376, No. 9, 02.03.2017, p. 815-825.

Research output: Contribution to journalArticle

Casey, BM, Thom, EA, Peaceman, AM, Varner, MW, Sorokin, Y, Hirtz, DG, Reddy, UM, Wapner, RJ, Thorp, JM, Saade, G, Tita, ATN, Rouse, DJ, Sibai, B, Iams, JD, Mercer, BM, Tolosa, J, Caritis, SN & VanDorsten, JP 2017, 'Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy', New England Journal of Medicine, vol. 376, no. 9, pp. 815-825. https://doi.org/10.1056/NEJMoa1606205
Casey, B. M. ; Thom, E. A. ; Peaceman, A. M. ; Varner, M. W. ; Sorokin, Y. ; Hirtz, D. G. ; Reddy, U. M. ; Wapner, R. J. ; Thorp, J. M. ; Saade, G. ; Tita, A. T N ; Rouse, D. J. ; Sibai, B. ; Iams, J. D. ; Mercer, B. M. ; Tolosa, J. ; Caritis, S. N. ; VanDorsten, J. P. / Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy. In: New England Journal of Medicine. 2017 ; Vol. 376, No. 9. pp. 815-825.
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abstract = "BACKGROUND Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95{\%} confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95{\%} CI, 92 to 96) in the placebo group (P = 0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95{\%} CI, 91 to 95) in the levothyroxine group and 91 (95{\%} CI, 89 to 93) in the placebo group (P = 0.30). In each trial, IQ scores were missing for 4{\%} of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions.",
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T1 - Treatment of subclinical hypothyroidism or hypothyroxinemia in pregnancy

AU - Casey, B. M.

AU - Thom, E. A.

AU - Peaceman, A. M.

AU - Varner, M. W.

AU - Sorokin, Y.

AU - Hirtz, D. G.

AU - Reddy, U. M.

AU - Wapner, R. J.

AU - Thorp, J. M.

AU - Saade, G.

AU - Tita, A. T N

AU - Rouse, D. J.

AU - Sibai, B.

AU - Iams, J. D.

AU - Mercer, B. M.

AU - Tolosa, J.

AU - Caritis, S. N.

AU - VanDorsten, J. P.

PY - 2017/3/2

Y1 - 2017/3/2

N2 - BACKGROUND Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P = 0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P = 0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions.

AB - BACKGROUND Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P = 0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P = 0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions.

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