The Third Trimester Human Fetus may be Protected from Prenatal Stress and Programmed Adult Mental Illness - Abstract
There is evidence, primarily from animal models, that fetal exposure to drugs, endotoxins and infectious agents acting as physiological stressors lead to atypical adult behaviors. Maternal restraint and other “psychosocial” stressors also have been shown to induce aberrant behavioral phenotypes in the adult offspring. Translation to humans is supported by retrospective and prospective studies revealing increased risk of psychopathology in the adult children of women exposed to war, bereavement or other cognitively perceived stressors during their pregnancies, especially during the first and second trimesters. The presumed mechanism is the excess levels of corticosteroids from stressed mothers entering fetal circulation, binding the glucocorticoid receptor and promoting neural changes underlying psychiatric diseases. Collectively, the data support a fetal programming disease model that perinatal insults, including maternal stress, can predispose the individual to develop adult pathology, including mental illness. We propose that the animal findings of prenatal, psychosocial stress are best applied to the first and second trimester human fetus. Findings in the literature are highlighted to support our contention that the third trimester human fetus has evolved unique mechanisms that largely protect the fetus, rendering it resilient to maternal stress. The third trimester fetus is unlikely to experience later psychopathology from maternal exposure to psychosocial stress, thus limiting the reach of the fetal programming disease model.