Neurologic Sequelae Associated with Hypertensive Disorders of Pregnancy

Abstract

Hypertensive disorders of pregnancy (HDP) contribute to adverse gene-environment interactions prior to conception and continue throughout pregnancy. Embryonic/fetal brain disorders occur from interactions between genetic susceptibilities interacting with acquired diseases or conditions affecting the maternal/placental fetal (MPF) triad. Trimester-specific pathophysiological mechanisms, such as maternal immune activation and ischemic placental syndrome, contribute to adverse peripartum, neonatal and childhood outcomes. Two diagnostic approaches provide timelier diagnoses over the first 1000 days from conception until two years of age. Horizontal analyses assess the maturation of the triad, neonate and child. Vertical analyses consider systems-biology from genetic, molecular, cellular, tissue through organ networks during each developmental niche. Disease expressions associated with HDP have cumulative adverse effects across the lifespan when subjected to subsequent adverse events. Critical/sensitive periods of developmental neuroplasticity over the first 1000 days are more likely to result in permanent sequelae. Novel diagnostic approaches, beginning during pre-conception, will facilitate the development of effective preventive, rescue and reparative neurotherapeutic strategies in response to HDP-related trimester-specific disease pathways. Public health policies require the inclusion of women’s health advocacy during and beyond their reproductive years to reduce sequelae experienced by mothers and their offspring. A lower global burden of neurologic disease from HDP will benefit future generations.

Keywords

• hypertensive disorders of pregnancy
• maternal immune activation
• the great obstetrical syndromes
• developmental neuroplasticity
• fetal/neonatal neurology
• developmental origins/life-course theories