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Am J Perinatol 2024; 41(S 01): e3326-e3332
DOI: 10.1055/s-0043-1778037
Original Article

Association of Mild Iodine Insufficiency during Pregnancy with Child Neurodevelopment in Patients with Subclinical Hypothyroidism or Hypothyroxinemia

Brian M. Casey
1   Departments of Obstetrics and Gynecology, University of Texas—Southwestern, Dallas, Texas
,
Lisa Mele
2   The George Washington University Biostatistics Center, Washington, District of Columbia
,
Alan M. Peaceman
3   Northwestern University, Chicago, Illinois
,
Michael W. Varner 
4   University of Utah Health Sciences Center, Salt Lake City, Utah
,
Uma M. Reddy
5   The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
,
Ronald J. Wapner
6   Columbia University, New York, New York
,
John M. Thorp Jr.
7   University of North Carolina, Chapel Hill, North Carolina
,
George R. Saade
8   University of Texas Medical Branch, Galveston, Texas
,
Alan T.N. Tita
9   University of Alabama at Birmingham, Birmingham, Alabama
,
Dwight J. Rouse
10   Brown University, Providence, Rhode Island
,
Baha M. Sibai
11   University of Texas—Houston, Houston, Texas
,
Maged M. Costantine 
12   The Ohio State University, Columbus, Ohio
,
Brian M. Mercer
13   Case Western Reserve University, Cleveland, Ohio
,
Steve N. Caritis
14   University of Pittsburgh, Pittsburgh, Pennsylvania
,
for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network, Bethesda, MD› Institutsangaben
Funding The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS; HD34116, HD40512, HD27917, HD34208, HD40485, HD40560, HD53097, HD27869, HD40500, HD40545, HD27915, HD40544, HD53118, HD21410, and HD36801). Comments and views of the authors do not necessarily represent the views of the NIH.
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Abstract

Objective Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years.

Study Design This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 μg/L were considered iodine sufficient, and concentrations of 150 μg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years.

Results A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 μg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84–105] vs. 96 [87–109], P adj = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 – 102] and 91 [81 – 100], Padj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status (p > 0.05).

Conclusion Maternal urinary iodine concentrations ≤150 μg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia.

Key Points

  • Most pregnant patients with subclinical thyroid disease are iodine sufficient.

  • Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.

  • Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ.

Keywords

subclinical hypothyroidism - hypothyroxinemia - neurodevelopment - IQ - iodine sufficiency

* Other members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network are listed in Appendix A.


ClinicalTrials.gov number NCT00388297




Publikationsverlauf

Eingereicht: 12. September 2023

Angenommen: 05. Dezember 2023

Artikel online veröffentlicht:
16. Januar 2024

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