Altered trajectory of neurodevelopment associated with fetal growth restriction

Fetal growth restriction (FGR) is principally caused by suboptimal placental function. Poor placental function causes an under supply of nutrients and oxygen to the developing fetus, restricting development of individual organs and overall growth. Estimated fetal weight below the 10th or 3rd percentile with uteroplacental dysfunction, and knowledge regarding the onset of growth restriction (early or late), provide diagnostic criteria for fetuses at greatest risk for adverse outcome. Brain development and function is altered with FGR, with ongoing clinical and preclinical studies elucidating neuropathological etiology. During the third trimester of pregnancy, from ~28 weeks gestation, neurogenesis is complete and neuronal complexity is expanding, through axonal and dendritic outgrowth, dendritic branching and synaptogenesis, accompanied by myelin production. Fetal compromise over this period, as occurs in FGR, has detrimental effects on these processes. Total brain volume and grey matter volume is reduced in infants with FGR, first evident in utero, with cortical volume particularly vulnerable. Imaging studies show that cerebral morphology is disturbed in FGR, with altered cerebral cortex, volume and organization of brain networks, and reduced connectivity of long- and short-range circuits. Thus, FGR induces a deviation in brain development trajectory affecting both grey and white matter, however grey matter volume is preferentially reduced, contributed by cell loss, and reduced neurite outgrowth of surviving neurons. In turn, cell-to-cell local networks are adversely affected in FGR, and whole brain left and right intrahemispheric connections and interhemispheric connections are altered. Importantly, disruptions to region-specific brain networks are linked to cognitive and behavioral impairments.

Automated summary

Fetal growth restriction (FGR) is mainly caused by suboptimal placental function, leading to limited nutrient and oxygen supply to the developing fetus, particularly affecting brain development. FGR results in altered brain morphology, disrupted connectivity, and region-specific brain network disturbances, which are associated with cognitive and behavioral impairments.