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

Brian M Casey; Lisa Mele; Alan M Peaceman; Michael W Varner; Uma M Reddy; Ronald J Wapner; John M Thorp Jr; George R Saade; Alan T N Tita; Dwight J Rouse; Baha M Sibai; Maged M Costantine; Brian M Mercer; Steve N Caritis; Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network, Bethesda, MD, USA

doi:10.1055/s-0043-1778037

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

Am J Perinatol. 2024 Jan 16. doi: 10.1055/s-0043-1778037. Online ahead of print.

Authors

Brian M Casey¹, Lisa Mele², Alan M Peaceman³, Michael W Varner⁴, Uma M Reddy⁵, Ronald J Wapner⁶, John M Thorp Jr⁷, George R Saade⁸, Alan T N Tita⁹, Dwight J Rouse¹⁰, Baha M Sibai¹¹, Maged M Costantine¹², Brian M Mercer¹³, Steve N Caritis¹⁴; Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units Network, Bethesda, MD, USA

Affiliations

¹ Departments of Obstetrics and Gynecology, University of Texas-Southwestern, Dallas, Texas.
² The George Washington University Biostatistics Center, Washington, District of Columbia.
³ Northwestern University, Chicago, Illinois.
⁴ University of Utah Health Sciences Center, Salt Lake City, Utah.
⁵ The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
⁶ Columbia University, New York, New York.
⁷ University of North Carolina, Chapel Hill, North Carolina.
⁸ University of Texas Medical Branch, Galveston, Texas.
⁹ University of Alabama at Birmingham, Birmingham, Alabama.
¹⁰ Brown University, Providence, Rhode Island.
¹¹ University of Texas-Houston, Houston, Texas.
¹² The Ohio State University, Columbus, Ohio.
¹³ Case Western Reserve University, Cleveland, Ohio.
¹⁴ University of Pittsburgh, Pittsburgh, Pennsylvania.

PMID: 38228158
DOI: 10.1055/s-0043-1778037

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], P_adj 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..