Perinatal Programming of Neurodevelopment

Glover V, Vivette Glover, Glover, Vivette

Marta C. Antonelli

Many prospective studies have shown that if a mother is depressed, anxious or stressed while pregnant, this increases the risk for her child having a wide range of adverse outcomes including emotional problems, symptoms of attention deficit hyperactivity disorder (ADHD) or impaired cognitive development. Although genetics and postnatal care clearly affect these outcomes, evidence for a prenatal causal component also is substantial. Prenatal anxiety/depression may contribute 10-15 % of the attributable load for emotional/behavioural outcomes.The mechanisms underlying these changes are just starting to be explored. One possible mediating factor is increased exposure of the fetus to cortisol, as has been shown in animal studies. However, the human hypothalamic-pituitary-adrenal (HPA) axis which makes cortisol functions differently in human pregnancy from in most animals. The maternal HPA axis becomes gradually less responsive to stress as pregnancy progresses. And there is only a weak, if any, association between a mother's prenatal mood and her cortisol level, especially later in pregnancy. Cytokines are alternative possible mediators. An additional explanation is that stress or anxiety causes increased transfer of maternal cortisol across the placenta to the fetus. The placenta plays a crucial role in moderating fetal exposure to maternal factors and presumably in preparing the fetus for the environment in which it is going to find itself. There is some evidence in both rat models and in humans that prenatal stress can reduce placental 11β-HSD2, the enzyme which metabolises cortisol to inactive cortisone. The level of cortisol in the amniotic fluid, surrounding the baby in the womb, has been shown to be inversely correlated with infant cognitive development. However, several other biological systems are likely to be involved. Serotonin is another possible mediator of prenatal stress induced programming effects on offspring neurocognitive and behavioural development. The role of epigenetic changes in mediating alterations in offspring outcome following prenatal stress is likely to be important and starting to be explored.