Prenatal programming of stress responsiveness, depression, cognitive functioning and the moderating effect of mother-infant interaction: From birth to age 20

Exposure to adverse environmental cues during critical windows of time in the prenatal life period could predispose the individual for somatic and mental diseases. We tested this prenatal programming hypothesis in humans in two prospective longitudinal studies in which maternal emotional state was measured during each pregnancy trimester and after pregnancy. In a recent study a small, significant negative association was found between maternal cortisol awakening response (CAR) in the second trimester of pregnancy and infant cortisol response 15’ after inoculation. A moderating effect of infant’s affect during inoculation was seen: in anxious (crying) infants an association was found between a negative maternal CAR in the 2 trimester and a strong infant cortisol response during inoculation, while in less anxious (smiling) infants a small positive correlation between CAR and cortisol response, indicating an adaptive physiological regulation, was seen. A second study was set up in 1986. When the offspring was 14-15 years old, HPA-axis function was measured through establishing a saliva day-time cortisol profile. Severity of depressive symptoms was measured with the Children’s Depression Inventory. Maternal anxiety at 12-22 weeks of pregnancy was in female and male offspring associated with a diurnal cortisol profile that was attenuated due to elevated cortisol secretion in the evening. Moreover, in female adolescents this flattened cortisol curve was associated with depressive symptoms. At the age of 14-15 ADHD-related symptoms and impairments in endogenous cognitive control in children were associated with maternal anxiety during their pregnancy. At the age of 17, adolescents whose mother experienced high levels of anxiety during weeks 12-22 of their pregnancy performed significantly lower on a dual task and on a response shifting task. Results of event-related potentials (ERP)-EEG at age 17 and fMRI at age 20, confirmed less optimal endogenous cognitive control function. Our results indicate that maternal anxiety during pregnancy enhances neurobiological vulnerability to enhanced stress responsiveness, depressive symptoms and cognitive malfunctioning, possibly by altering (or programming) foetal physiology.