There is only sparse knowledge available on the effects of the different prenatal stressors on brain structure and function during ageing. Stress sensitivity is programmed prenatally mainly due to maternal stress, stress hormone (glucocorticoid treatment) and nutrient restriction. Many questions on how timing, type, intensity, and duration of environmental disturbances are related to altered neurobehavioral development and early brain ageing still remain unanswered.
Maternal stress during pregnancy
Indications that maternal stress results in alteration of cognitive functioning, behavioral and emotional problems are to be had from human cohorts aged up to 20y from van den Bergh's group. Other studies focusing on offspring CNS structures or structure-functioning relationships following maternal stress during pregnancy have shown altered brain function at the neurophysiological level in the newborn and gray matter volume reductions in the 6-9y old offspring at the structural level. The fact that maternal anxiety and stress during human pregnancy is linked with behavior abnormalities during childhood and adolescence, even after controlling for effects of postnatal maternal mood and other relevant prenatal and post-natal confounders, suggests that, as in animal models, a programming effect on the fetal brain had taken place.
Glucocorticoid treatment during pregnancy
Almost 10% of all pregnant women threatening preterm delivery are treated with glucocorticoid to enhance fetal lung maturation. This treatment ensures that preterm babies can artificially be ventilated and leads to survival.
Numerous effects of prenatal glucocorticoid treatment at doses used clinically to enhance fetal lung maturation on brain development and brain function during later life were observed in rodents, sheep and non-human primates in the studies from Nathanielsz's and Schwab's groups. In contrast, the effects of prenatal glucocorticoid exposure are much less clear in humans. There is one exception which refers to the few studies that followed-up offspring until the age of 32y and who showed no behavior or neurocognitive abnormalities after one course of prenatal betamethasone. Multiple courses of betamethasone to enhance fetal lung maturation, however, induced abnormalities of functional brain development and behavior disorders between 3 and 6 years of age.
In addition to direct effects of increased stress sensitivity on neuronal activity complex, there is evidence that indirect effects may also play a role. For example, resistance of peripheral glucocorticoid receptors to immunosuppressive GC leads to a pro-inflammatory state that has negative effects on neuronal function.
Moderate undernutrition during pregnancy is common in both developing countries and in western societies such as the EU. In industrialized countries, a lifestyle comprising of dieting (including global food reduction) for cosmetic purposes is widespread and is a common cause of moderate undernutrition. A recent study showed that most women do not improve their dietary and lifestyle patterns during pregnancy. Finally, poor fetal nutrition is also present in teenage and in elderly primigravid pregnancies.
Roseboom's group has shown in the Dutch famine cohort and Nathanielsz's and Schwab's groups have shown in non-human primates that maternal malnutrition during pregnancy have effects on cognition that were independent of size and weight at birth. The evidence obtained recently by Roseboom's group from the mid-fifties suggests that cognitive function may also deteriorate faster in those prenatally exposed to the famine in early gestation, but not among those exposed in late gestation. In the British 1946 birth cohort, birth weight was positively associated with cognition in adult age.