The Intersection of Maternal Inflammatory Stress and the Developmental Origins of Health and Disease

Abstract

The most important factor influencing the prenatal environment is the maternal environment. There is a growing body of evidence suggesting that the maternal and intrauterine milieu, through the action of inflammatory mediators may permanently change the health of the fetus. Gestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy and is associated with aberrant systemic inflammation and known to cause considerable morbidity, mortality, and long-term complications for both mother and child. Maternal immune activation (MIA), another prenatal insult, is common and occurs as the result of an infection during pregnancy. Several epidemiological as well as clinical studies have shown associations between infection and MIA during pregnancy and an increased risk for developing neurocognitive disorders such as autism and schizophrenia in offspring. The aberrant inflammation caused by GDM and maternal obesity is also gaining evidence as a possible cause for the same neurocognitive disorders. For progress to be made in the prevention and treatment of these disorders it is important to identify both the biological and environmental factors underlying disorder pathogenesis. Several transcriptional changes within the placenta and fetal brain were identified as a result of GDM, MIA, and the combination of the two. Within the placenta, many of these changes were dependent upon the sex of the fetus.