Hypertensive Disorders of Pregnancy: Risk Factor for Later Cognitive Impairment
-Association mainly driven by women with gestational hypertension
by Zeena Nackerdien PhD, CME Writer, MedPage Today 2021-01-11
Study Authors: Maria C. Adank, Rowina F. Hussainali, et al.; Lisa Leffert, Calin I. Prodan, Nils Peters
Target Audience and Goal Statement: Neurologists, obstetrician-gynecologists, primary care physicians
The goal of this study was to determine the association between hypertensive disorders of pregnancy and cognitive impairment 15 years after pregnancy.
- Did hypertensive disorders of pregnancy lead to future cognitive impairment?
Study Synopsis and Perspective:
Hypertensive disorders of pregnancy are estimated to occur in up to 8% of women worldwide and include new-onset hypertension diagnosed during pregnancy (gestational hypertension), preeclampsia, and chronic hypertension with superimposed preeclampsia.
There is a known association between hypertensive disorders of pregnancy and future renal, cardiovascular, and cerebrovascular disease. Women with these disorders are five times more likely to develop peripartum stroke and other short- and long-term cerebrovascular events compared with their normotensive counterparts.
- Women who developed a hypertensive disorder of pregnancy were more likely to show cognitive impairment 15 years later, according to a population-based prospective study from the Netherlands.
- Note that hypertensive disorders of pregnancy are estimated to occur in up to 8% of women worldwide.
According to a recent population-based prospective study, women who developed hypertension during pregnancy were more likely to show cognitive impairment 15 years later.
Compared with those who had normal blood pressure during pregnancy, women who developed gestational hypertension or preeclampsia performed worse on immediate and delayed recall testing a median of 14.7 years later, reported Maria Adank, MD, of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues.
“Women who have experienced [hypertensive disorders of pregnancy], in particular gestational hypertension or preeclampsia, are advised to make lifestyle changes to reduce their risk of later life disease,” they wrote in Neurology.
The study included a cohort of pregnant women in the ORACLE substudy with a delivery date from April 2002 to January 2006 who were part of the population-based prospective Generation R study in Rotterdam.
Of the 596 women who were pregnant at the start of the study, 115 developed high blood pressure during pregnancy (80 with gestational hypertension and 35 with preeclampsia) and 481 had a normotensive pregnancy. Most of the women with preeclampsia (94.3%) developed the condition at term, as defined as an onset at >34 weeks of gestation.
Women with hypertensive disorders of pregnancy were more often of non-European descent, had a lower level of education, a higher pre-pregnancy body mass index (BMI), and higher systolic and diastolic blood pressure at early pregnancy (13.3 weeks of gestation).
Cognitive assessments a median 14.7 years later included executive function, processing speed, verbal learning and memory, fine motor, and visuospatial tests, which were combined into a composite global cognition factor. Mean age at cognitive testing was 46. Of women with hypertensive disorders of pregnancy, 20% had depression at the time of cognitive testing.
About 6 months before cognitive testing, 68 women were classified as hypertensive. Women with a history of hypertensive disorders of pregnancy had a higher proportion of hypertension (30.4%) compared with those previously normotensive during pregnancy (6.9%).
Women were asked to remember a list of 15 words, first immediately and then after waiting 20 minutes. Participants with hypertensive disorders of pregnancy had worse immediate recall and delayed recall scores — measured by the number of correct answers in three trials of the 15-word learning test — compared with women who had a normotensive pregnancy. These associations remained significant after adjusting for confounders (immediate recall -0.25, 95% CI -0.44 to -0.06; delayed recall -0.30, 95% CI -0.50 to -0.10).
Sensitivity analysis excluding women with preeclampsia showed that women with gestational hypertension performed worse than women with a normotensive pregnancy on all parts of the 15-word learning test, even after accounting for confounders.
Hypertensive disorders of pregnancy were negatively associated with other cognitive assessments and the composite global factor, but these relationships were nonsignificant after adjustment.
The association with cognitive impairment was driven mainly by women with gestational hypertension and was independent of ethnicity, educational level, and pre-pregnancy BMI.
The study had several limitations, the researchers noted. No cognitive tests were performed before or during pregnancy, and effects within one woman could not be investigated. Selection bias may have occurred and unknown confounders may have influenced results.
Source References: Neurology 2020; DOI: 10.1212/WNL.0000000000011363
Editorial: Neurology 2020; DOI: 10.1212/WNL.0000000000011364
Study Highlights and Explanation of Findings:
This prospective study based in the Netherlands showed that hypertensive disorders of pregnancy were associated with impairment in working memory and verbal learning 15 years after a pregnancy compared with women with normotensive pregnancies. This association was largely driven by women with gestational hypertension.
“It’s important to consider gestational hypertension and preeclampsia as risk factors for cognitive impairment that are specific to women,” Adank said in a statement. “Many women may think of this as a temporary issue during pregnancy and not realize that it could potentially have long-lasting effects. Future studies are needed to determine whether early treatment of high blood pressure can prevent cognitive problems in women with a history of high blood pressure in pregnancy.”
“That hypertension during pregnancy, even in the absence of preeclampsia, is associated with such detrimental long-term effects should serve as a call to action for prevention,” noted Lisa Leffert, MD, of Massachusetts General Hospital in Boston, and colleagues in an accompanying editorial.
“Gestational hypertension differs from preeclampsia with severe features by the absence of proteinuria or evidence of other end-organ damage,” they wrote. “One might surmise that women with gestational hypertension are less impaired than those with preeclampsia and are therefore less likely to develop future related disease. Instead, the Adank et al. study and those of others have demonstrated long-term cognitive, cerebrovascular, and cardiac sequelae in women with gestational hypertension.”
Preeclampsia has been linked with subjective cognitive symptoms in earlier research, but showed no clear evidence of impairment on standard neurocognitive tests. Gestational hypertension has been tied to higher rates of chronic high blood pressure and other comorbidities, while gestational hypertension and preeclampsia have been associated with maternal atherosclerotic cardiovascular disease, independent of traditional risk factors.
How gestational hypertension or preeclampsia are linked with subsequent dysfunction is unclear. “What is clear is that once a woman has been diagnosed with one of the hypertensive disorders of pregnancy, it is of paramount importance that she be educated about her future vascular disease risk as well as the potential cognitive implications and receive close and comprehensive follow-up care,” the editorialists observed. “Increasing awareness among healthcare providers to the existence of a delayed cognitive component in women with hypertensive disorders of pregnancy may help identify those at risk for future decline.”
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College