ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 S16.3 | DOI: 10.1530/endoabs.63.S16.3

Mild maternal thyroid dysfunction during pregnancy and offspring neurodevelopment

Deborah Levie

The Netherlands.

In humans, brain developmental processes start already around week 5 of gestation and continue throughout pregnancy and postnatal life. The migration, differentiation, proliferation, and myelination of neurons are thyroid hormone dependent processes, as shown in animal studies. The fetal thyroid gland is not functionally mature before week 18–20 of gestation. During this period the fetus acquires thyroid hormone for the most part via placental transfer from the mother. This implies that there is an important time frame during which thyroid hormone dependent processes of brain development are completely dependent on the placental transfer of maternal thyroid hormones. A lack of thyroid hormone exposure to the fetal brain during its developmental stages in utero can lead to severe neurological phenotypes, such as cretinism, which is caused by iodine deficiency. While there is abundant evidence for an association of low maternal FT4 (hypothyroidism and/or hypothyroxinemia) during gestation with poorer fetal neurocognitive outcomes, evidence for an association of maternal subclinical hypothyroidism (elevated TSH but normal FT4) during pregnancy with offspring neurodevelopmental outcomes is scarce. In this talk the latest clinical studies on mild thyroid dysfunction and offspring neurodevelopmental outcomes will be discussed, including studies that have investigated critical time windows for exposure to inadequate thyroid hormone availability. Identifying critical time windows are important for improved understanding of thyroid physiology, translation of animal studies to human physiology, to facilitate the design of future randomized controlled studies on the benefits of treatment (i.e. subclinical hypothyroidism or hypothyroxinema) and aid clinicians in optimizing risk assessment strategies. In this talk I will also go over some of the challenges and next steps in these type of studies.

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