Pregnancy, Preeclampsia, and Brain.

Preeclampsia is a pregnancy-specific hypertensive disorder that presents with systemic symptoms, and commonly proteinuria, after 20 weeks of gestation. It may occur either de novo or superimposed on chronic hypertension. Other hypertensive disorders of pregnancy (HDP) include chronic and gestational hypertension. Eclampsia is the convulsive form of preeclampsia that affects 0.1% of all pregnancies. First descriptions of preeclampsia/eclampsia date back to 400 BC and focused on headaches and convulsions, representing central nervous system signs and symptoms of preeclampsia and eclampsia, respectively. Critical clinical findings of preeclampsia, such as proteinuria and elevated blood pressure, were not described until the 1800s. Consequently, from ancient times through the 19th century, practicing physicians and scholars concentrated on understanding the underlying pathophysiology of eclamptic seizures and improving treatment. Bloodletting, use of opiates, warm baths, and hastening delivery were therapeutic options that developed over time. These efforts culminated in the introduction of magnesium sulfate for seizure prevention in the 20th century, the therapeutic approach which is currently accepted as standard of care. The immediate central nervous system involvement and complications of preeclampsia/ eclampsia have been recognized for years; however, recognition of the long-term consequences of preeclampsia/eclampsia, in the form of cardiovascular and cerebrovascular disease, and impaired cognition dates back only a few decades. In this issue, Dayan et al explore the relationship between preeclampsia and cognitive function after a long period of follow-up. They used data from the CARDIA cohort (Coronary Artery Risk Development in Young Adults), which included healthy individuals between the ages of 18 to 30 years who were followed for 25 years. Neurocognitive measurements were made at the conclusion of follow-up. They matched 193 women with preeclampsia to 375 women with normotensive pregnancies based on date of delivery within a range of 5 years. Women were included if they had at least 1 pregnancy and completed neurocognitive testing, and they were excluded if they had histories of prior major depression, neurodegenerative disease, epilepsy, multiple sclerosis, or cancer (including brain tumors). The authors used standardized testing of neurocognitive functions that have been used previously in similar studies. The mean age at cognitive measurement was 49.3 years. The authors found that women with preeclampsia had lower scores for psychomotor speed and executive function, but the relationship lost statistical significance after adjustments for age, body mass index, hypertension, depression, and level of education. There was no difference between the 2 groups for the learning and memory faculty. The strength of this study stems from the large number of subjects included from a diverse population in the United States. The authors accounted for cumulative duration of hypertension, used validated cognitive measurements, and had a long period of follow-up. The implications of the presented results need to be viewed/discussed in the context of the current state of knowledge about preeclampsia, cardiovascular risk, and future cognition. It has been increasingly recognized that HDP, in general, and preeclampsia, in particular, are sex-specific risk factors that are associated with an array of maternal morbidities that occur later in life. Indeed, the American Heart Association and the American Stroke Association released guidelines that focus on cardiovascular disease (CVD)4 and stroke prevention in women and recommend documenting preeclampsia as a risk factor for both conditions. One possible explanation for these associations (Figure) is that preeclampsia and CVD (including stroke) share common risk factors, including obesity, diabetes mellitus, and hyperlipidemia, that may lead to preeclampsia and CVD at different times during a woman’s life. Under those circumstances, pregnancy may serve as a stress test that women with underlying unfavorable cardiovascular profiles may fail by developing preeclampsia, which, in turn, heralds elevated CVD risk later in life. Alternatively, preeclampsia itself may induce metabolic and vascular changes that may increase the CVD risk in women years after their affected pregnancies. It has been increasingly recognized that CVD increases the risks for both Alzheimer disease (AD) and vascular dementia. Thus, it is possible that women with a history of HDP also have an increased risk of dementia through their increased risks for CVD later in life. In eclampsia, a direct injury to cerebral vasculature in the form of posterior reversible encephalopathy syndrome—characterized by neuroimaging findings of vasogenic edema in the posterior circulation of the brain—has been associated with persistent imaging findings of infarction in up to a fourth of eclamptic women. This The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. Correspondence to Vesna D. Garovic, Division of Nephrology and Hypertension, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email garovic.vesna@mayo.edu Pregnancy, Preeclampsia, and Brain Three Thousand Years of Progress