The first 1000 days of life are crucial for a child’s development and long-term health. External factors like infection or stress of the mother and child during this period can cause lasting changes in tissues and organs. This is known as developmental programming. These early life influences can predispose to long-term health consequences such as cardiovascular, metabolic, allergic, and autoimmune diseases. A common early life exposure during the fetal period, maternal immune activation (MIA), has gained attention due to the COVID-19 pandemic. MIA occurs when a mother’s immune system responds to an infection during pregnancy. MIA is linked to a higher risk of neurodevelopmental disorders, such as autism. Research also suggests that MIA is associated with various immune-related disorders.
This dissertation of Naomi Hofsink explores the fetal programming effect of MIA caused by maternal infections or systemic inflammation in preeclampsia. We observed transcriptional changes in the offspring’s T cells in a preclinical MIA model and in the offspring’s liver and brain in a preeclampsia model. In the Dutch GECKO birth cohort, maternal infection during the pregnancy induced small DNA methylation changes in umbilical cord white blood cells. Overall, a fetal programming effect of MIA was observed in preclinical animal models and in human population. While the link between MIA and neurodevelopmental disorders is the most studied, MIA can also affect the immune response and metabolism. Studies in both preclinical models and human population are valuable for understanding the fetal programming effect of MIA and their potential health consequences.
