Fetal development is largely dependent on the mother. However, pregnancy maintenance and consequently fetal development are highly vulnerable and sensitive to disruption, triggered by the macro- or microenvironment. High stress perception is becoming the ‘epidemic’ of the 21st century, as identified by a recent study carried out by the World Health Organisation in Northern European countries. Also, women giving birth to their first child are now in average 10 years older than 3-4 decades ago. Higher maternal age or high maternal stress perception affects the maternal endocrine and immune adaptation required for an uncomplicated pregnancy. Both, maternal age and stress perception could be linked to low levels of progesterone during pregnancy, associated with a high risk for spontaneous abortion or negative repercussions on the child’s health later in life. It has been reported that prenatal stress also increases the risk for the child to develop chronic immune diseases, such allergies and asthma. The markers and mediators along which prenatal environmental challenges increase the offspring’s risk for chronic immune diseases remain largely elusive. In basic science models and prospectively designed birth cohorts, we observed that prenatal stress challenge, mirrored by e.g. a decrease of maternal progesterone, impairs fetal immune ontogeny. Such impaired immune ontogeny carried over into postnatal life, rendering the child more prone to develop chronic immune diseases. Further, the data arising from our research endeavours pursued to date revealed a pivotal role of maternal progesterone during pregnancy in preventing allergic diseases in the offspring later in life. We envision that identification of relevant stress-sensitive biomarkers may eventually allow detection of pregnant women at risk to give birth to immune disease-prone offspring. The creation of therapeutic interventions designed to prevent negative consequences of prenatal stress would then be within reach.