Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy

Casey, Brian M.; Thom, Elizabeth A.; Peaceman, Alan M.; Varner, Michael W.; Sorokin, Yoram; Hirtz, Deborah G.; Reddy, Uma M.; Wapner, Ronald J.; Thorp, John M.; Saade, George; Tita, Alan T.N.; Rouse, Dwight J.; Sibai, Baha; Iams, Jay D.; Mercer, Brian M.; Tolosa, Jorge; Caritis, Steve N.; VanDorsten, J. Peter

doi:10.1056/nejmoa1606205

Cited by 462Thyroid Disorders and TreatmentsMaternal Mental Health During Pregnancy and PostpartumThyroid and Parathyroid Surgery

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy

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Casey, Brian M., Thom, Elizabeth A., Peaceman, Alan M., Varner, Michael W., Sorokin, Yoram, Hirtz, Deborah G., Reddy, Uma M., Wapner, Ronald J. +10 more·2017·New England Journal of Medicine

DOI 10.1056/nejmoa1606205PMC PMC5605129

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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: 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. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).

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There is no evidence to support a benefit to offspring IQ by levothyroxine treatment of subclinical hypothyroidism or hypothyroxinemia.
“Noteworthy, there is no evidence to support a benefit to offspring IQ by LT4 treatment of subclinical hypothyroidism or hypothyroxinemia [29, 30].”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [30]

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“Noteworthy, there is no evidence to support a benefit to offspring IQ by LT4 treatment of subclinical hypothyroidism or hypothyroxinemia [29, 30].”
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Authors: 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.
Affiliations: Northwestern University (US)
ORCID: Casey, Brian M.
Thom, Elizabeth A.
Peaceman, Alan M.
Varner, Michael W.
Hirtz, Deborah G.
Reddy, Uma M.
Wapner, Ronald J.
Thorp, John M.
Tita, Alan T.N.
Rouse, Dwight J.
Sibai, Baha
Iams, Jay D.
Tolosa, Jorge
Caritis, Steve N.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2017-03-02
Volume: 376
Issue: 9
Pages: 815-825
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1606205
PMC: PMC5605129
OpenAlex: W2591960209
Cited by: 462
References: 30
Citations by year: 2026: 22 · 2025: 25 · 2024: 41 · 2023: 54 · 2022: 63 · 2021: 43 · 2020: 54 · 2019: 52 · 2018: 71 · 2017: 34 · 2016: 2 · 2014: 1
FWCI: 45.64
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01HD036801, U10HD040544, U10HD034208, U10HD040512, UG1HD034116, UG1HD053097, U10HD027915, U10HD040545, U10HD040560, U10HD027917, U10HD036801, U10HD021410, U10HD053097, U10HD034116, U10HD040500, U10HD040485, U10HD053118, U10HD027869, UG1HD034208, U24HD036801, UG1HD040500, UG1HD040512, UG1HD027869, UG1HD087230, UG1HD040544, UG1HD040485, UG1HD027915, UG1HD040560, UG1HD040545)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords: subclinical hypothyroidism, hypothyroxinemia, pregnancy, levothyroxine, thyroid hormone replacement, child cognitive development, IQ, offspring neurodevelopment, pregnancy outcomes
MeSH terms: Adult, Developmental Disabilities, Child, Preschool, Female, Follow-Up Studies, Humans, Hypothyroidism, Infant, Intelligence, Intelligence Tests, Intellectual Disability, Pregnancy, Pregnancy Complications, Thyroxine, Treatment Failure

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Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy

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