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.
Highlights
In intrauterine life, mild and transient changes in maternal hormone levels, even within the currently accepted physiologic levels, can directly affect target gene expression profiles, which are generally involved in normal brain growth and maturation (Brunton & Russell, 2011; Morreale de Escobar et al, 2004b)
Some fetal hormonal axes are susceptible to long-term programming effects that can persist throughout life and result in impaired brain growth, altered behavior, and increased susceptibility to chronic disease
We will provide an update of the research data on maternal hormonal impact on fetal neurodevelopment, giving particular emphasis to thyroid hormones and glucocorticoids, for which the relevance for fetal neurodevelopment is well established, the body of published scientific evidence is robust, and clinical guidelines are already available for hormonal replacement in particular circumstances
Summary
Mild and transient changes in maternal hormone levels, even within the currently accepted physiologic levels, can directly affect target gene expression profiles, which are generally involved in normal brain growth and maturation (Brunton & Russell, 2011; Morreale de Escobar et al, 2004b). Some observational studies have suggested the benefit of treatment (Li et al, 2010; Negro et al, 2006), but the larger Controlled Antenatal Thyroid Screening (CATS) randomized controlled trial demonstrated that thyroxine replacement in women with isolated high TSH or isolated low free T4 levels had no impact on cognitive function in children evaluated at 3 years old (Lazarus, 2010; Lazarus et al, 2012) Another multicenter randomized placebo- controlled clinical trial, the Randomized Trial of Thyroxine Therapy for Subclinical Hypothyroidism or Hypothyroxinemia Diagnosed During Pregnancy, selected 677 women with subclinical hypothyroidism and 526 women with isolated maternal hypothyroxinemia to T4 treatment or placebo, showing no significant effect of treatment on offspring IQ at the age of 5 years (Casey, 2016). AM provided substantial contribution to the conception and drafting of the review; NS had an important contribution in critically revising the work for important intellectual content and gave the final approval of the version to be published
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