Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy

Abstract

In-utero exposure to maternal psychological distress is increasingly linked with disrupted fetal and neonatal brain development and long-term neurobehavioral dysfunction in children and adults. Elevated maternal psychological distress is associated with changes in fetal brain structure and function, including reduced hippocampal and cerebellar volumes, increased cerebral cortical gyrification and sulcal depth, decreased brain metabolites (e.g., choline and creatine levels), and disrupted functional connectivity. After birth, reduced cerebral and cerebellar gray matter volumes, increased cerebral cortical gyrification, altered amygdala and hippocampal volumes, and disturbed brain microstructure and functional connectivity have been reported in the offspring months or even years after exposure to maternal distress during pregnancy. Additionally, adverse child neurodevelopment outcomes such as cognitive, language, learning, memory, social-emotional problems, and neuropsychiatric dysfunction are being increasingly reported after prenatal exposure to maternal distress. The mechanisms by which prenatal maternal psychological distress influences early brain development include but are not limited to impaired placental function, disrupted fetal epigenetic regulation, altered microbiome and inflammation, dysregulated hypothalamic pituitary adrenal axis, altered distribution of the fetal cardiac output to the brain, and disrupted maternal sleep and appetite. This review will appraise the available literature on the brain structural and functional outcomes and neurodevelopmental outcomes in the offspring of pregnant women experiencing elevated psychological distress. In addition, it will also provide an overview of the mechanistic underpinnings of brain development changes in stress response and discuss current treatments for elevated maternal psychological distress, including pharmacotherapy (e.g., selective serotonin reuptake inhibitors) and non-pharmacotherapy (e.g., cognitive-behavior therapy). Finally, it will end with a consideration of future directions in the field.

Fig. 1. Fetal brain segmentation.

Brain tissue segmentation of fetuses at 24, 29, and 35 gestational weeks (GW) (the first row); brain 3D surfaces of fetuses at 20, 23, 26, 29, 32 and 35 GW (the second row). The brain segmentation includes left (green) and right (blue) cortex, left (yellow) and right (light green) subplate, left (grass green) and right (light pink) intermediate zone, left (light purple) and right (light brown) germinal matrix, left (light orange) and right (orange) hippocampi, left (pink) and right (beige) white matter, left (light blue) and right (deep green) deep gray matter, corpus callosum (light grass green), lateral ventricle (cyan), left (purple) and right (red) cerebellum, and brainstem (brown).

Fig. 2. 2 Fetal functional connectivity.

Functional connectivity strength follows a medial to lateral developmental gradient [56, 62] (A). In brain regions (red dots in (B)) such as inferior frontal cortex (Brodmann areas, BA, 44), primary sensorimotor cortex (BA 2), middle temporal gyrus (BA 21), and inferior temporal gyrus (BA 20), connectivity strength between homologous areas increases with advancing gestational age [56]. In utero, overall brain connectivity showed a sigmoid, non-linear expansion curve, peaking between 26 and 29 weeks [adapted from [65]] (C). Connections arising from regions in (D) reliably predict biologic sex; BG basal ganglia, CRB cerebellum, and FRO frontal [68].

Fig. 3. Prenatal maternal distress and outcomes.

Brain and neurobehavior developmental outcomes of prenatal maternal psychological distress and possible mechanisms.