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Review
. 2018 Jan 24;8(2):e00920.
doi: 10.1002/brb3.920. eCollection 2018 Feb.

Maternal hormonal milieu influence on fetal brain development

Alexandra Miranda  1   2   3 , Nuno Sousa  1   2   4
Affiliations
Review

Maternal hormonal milieu influence on fetal brain development

Alexandra Miranda et al. Brain Behav. .

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.

Keywords: fetal neurodevelopment; fetal programming; glucocorticoids; maternal hormones; melatonin; oxytocin; sex steroids; thyroid hormones.

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Figures

Figure 1
Figure 1
(a) The relative concentrations of maternal cortisol and free thyroid hormones during pregnancy; (b) important time points in the ontogeny of fetal cortisol and thyroid hormone function and metabolism; (c) time‐specific actions of HPA and HPT axes on fetal brain development. Figure adapted from Patel et al., 2011
Figure 2
Figure 2
Thyroid hormone transport and metabolism between placenta and fetal brain in humans. DIO3 activity in placenta is up to 400 times greater than that of DIO2, and the most relevant thyroid hormone membrane transporter in humans is MCT8 transporter. Thyroid hormones are delivered to the brain mainly through the blood–brain barrier (BBB) with a smaller fraction (about 20%) being transported through the choroid plexus. Fetal 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
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