Maternal hormonal milieu influence on fetal brain development

Abstract

An adverse maternal hormonal environment during pregnancy can be associated with abnormal brain growth. Subtle changes in fetal brain development have been observed even for maternal hormone levels within the currently accepted physiologic ranges. In this review, we provide an update of the research data on maternal hormonal impact on fetal neurodevelopment, giving particular emphasis to thyroid hormones and glucocorticoids. Thyroid hormones are required for normal brain development. Despite serum TSH appearing to be the most accurate indicator of thyroid function in pregnancy, maternal serum free T4 levels in the first trimester of pregnancy are the major determinant of postnatal psychomotor development. Even a transient period of maternal hypothyroxinemia at the beginning of neurogenesis can confer a higher risk of expressive language and nonverbal cognitive delays in offspring. Nevertheless, most recent clinical guidelines advocate for targeted high‐risk case finding during first trimester of pregnancy despite universal thyroid function screening. Corticosteroids are determinant in suppressing cell proliferation and stimulating terminal differentiation, a fundamental switch for the maturation of fetal organs. Not surprisingly, intrauterine exposure to stress or high levels of glucocorticoids, endogenous or synthetic, has a molecular and structural impact on brain development and appears to impair cognition and increase anxiety and reactivity to stress. Limbic regions, such as hippocampus and amygdala, are particularly sensitive. Repeated doses of prenatal corticosteroids seem to have short‐term benefits of less respiratory distress and fewer serious health problems in offspring. Nevertheless, neurodevelopmental growth in later childhood and adulthood needs further clarification. Future studies should address the relevance of monitoring the level of thyroid hormones and corticosteroids during pregnancy in the risk stratification for impaired postnatal neurodevelopment.

The placenta as a window to the brain: A review on the role of placental markers in prenatal programming of neurodevelopment

“…foetal brain is mainly dependent on circulating T4 levels, with 80% of T3 in the cerebral cortex being produced by local deiodination of free T4 in astrocytes. DIO, deiodinase; BBB, blood– brain barrier (Adapted from Miranda and Sausa, 2018).…”

How early media exposure may affect cognitive function: A review of results from observations in humans and experiments in mice

“…The infant brain is very responsive to environmental changes. Many factors, such as early-life adverse events, pubertal and maternal stress (52)(53)(54), toxins (55)(56)(57), nutrition (58)(59)(60), geographic environment (61,62), and epigenetic factors (63,64), can have adverse consequences on neurodevelopment. Indeed, there is increasing evidence that most neurological and psychiatric disorders have a developmental origin that is the result of prenatal and early postnatal disturbances in this complex process (65)(66)(67)(68)(69).…”

Iodine Status, Thyroid Function, and Birthweight: A Complex Relationship in High-Risk Pregnancies

“…Even after the onset of fetal thyroid secretion, human data show that maternal transfer still represents about 30-60% of fetal serum T4 and continues to have an important protective role in fetal neurodevelopment until birth [24]. Our results attempt to demonstrate how the maternal-fetal communication network for TH in the late stages of pregnancy should be taken into account for decision making in cases of adverse antenatal or perinatal circumstances.…”