Cognitive Change Seen Later in Life After Hypertensive Pregnancy

Cognitive changes were seen later in life in women who had hypertensive disorders of pregnancy compared with those who had normotensive pregnancy, a prospective cohort study found.

“A history of hypertensive disorders of pregnancy is independently associated with poorer working memory and verbal learning, 15 years after pregnancy,” wrote Maria Adank, MD, of the University Medical Center Rotterdam in the Netherlands, and co-authors in Neurology. “This association is mainly driven by women with gestational hypertension. Clinicians and women who experienced hypertensive disorders of pregnancy should be aware of this risk.”

Hypertensive disorders of pregnancy include new-onset hypertension during pregnancy (gestational hypertension), preeclampsia, and chronic hypertension with superimposed preeclampsia.

In the study, cognitive scores in women with hypertensive disorders of pregnancy (n=115; 80 with gestational hypertension and 35 with pre-eclampsia) were compared with 481 women with normotensive pregnancies. A median 14.7 years after index pregnancy, hypertensive disorders of pregnancy were negatively associated with poorer immediate and delayed recall on a 15-word learning test (−0.25 standard deviations, 95% CI −0.44 to −0.06, and −0.30 standard deviations, 95% CI −0.50 to −0.10, respectively).

A composite global cognition factor (g-factor) score was not significantly different between the groups after adjustment for ethnicity, educational level, and pre-pregnancy BMI.

“Not only women with a history of pre-eclampsia, but also gestational hypertension should be monitored closely after their pregnancy,” Adank and colleagues wrote. “Whether early treatment of hypertension prevents cognitive decline in women with a history of hypertensive disorders of pregnancy should be investigated in clinical trials. Both clinicians and women with a history of hypertensive disorders of pregnancy should be aware of these patients’ risk of cognitive impairment later in life.”

In an accompanying editorial, Lisa Leffert, MD, of Massachusetts General Hospital in Boston, and co-authors, noted that “gestational hypertension differs from preeclampsia with severe features by the absence of proteinuria or evidence of other end-organ damage.”

“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,” they wrote. “Instead, the Adank et al. study and those of others have demonstrated long-term cognitive, cerebrovascular and cardiac sequelae in women with gestational hypertension.”

Hypertensive disorders of pregnancy are thought to range between 2%-8% worldwide, and rates in the U.S. increased 25% between 1987 and 2004. Women giving birth in 2003 compared with 1980 had 6.7 times greater risk of preeclampsia. The etiology of preeclampsia is thought to involve endothelial dysfunction with increased tyrosine kinase 1 (sFlt-1), which binds and changes concentrations of placental and vascular endothelial growth factors, about 5 weeks prior to onset.

Hypertensive disorders of pregnancy is associated with development of known vascular risk factors including chronic hypertension, hypercholesterolemia, and type 2 diabetes. Other associated outcomes include short and longer term renal, cardiovascular and cerebrovascular disease, including stroke and vascular dementia.

A 2018 meta-analysis of cognitive consequences included 13 studies with preeclampsia as a diagnosis and cognitive-related outcomes. The authors found a higher rate of subjective deficits in perception, memory, and motor functioning for those with versus without any prior preeclamptic pregnancy, but not clear evidence of worse performance on specific cognitive tests.

Adank and colleagues analyzed data from an ongoing population-based prospective birth cohort study in Rotterdam (Generation R). They included women with a delivery date between April 2002 and January 2006 who also participated in a subsequent brain health study that included cognitive evaluations. Mean age was 46, and gestational age at birth was 40.3 months for the normotensive pregnancy group and 39.4 in the hypertensive disorders of pregnancy group.

Compared with those with normotensive pregnancy, those with hypertensive disorders of pregnancy were more often of non-European descent and had lower educational level, greater pre-pregnancy BMI, and higher systolic and diastolic blood pressures in early pregnancy.

Evaluations included verbal learning, working memory, visuospatial ability, executive function, and processing speed, and results were combined in a composite g-factor. Among the evaluations was a 15-word learning test in which immediate recall and 20-minute recall were assessed to evaluate verbal learning and retrieval from verbal memory.

“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,” the editorialists said. “However, the best course of action is not clear.”

“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,” they continued. “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.”

Limitations include absence of cognitive testing before or during pregnancy, precluding cognitive evaluation on an individual level. In addition, preeclampsia subtypes (such as early-onset, or severe features) were not evaluated, participants were relatively young, and high-resolution imaging studies were not used to confirm vascular involvement, the editorialists noted.

1. Cognitive changes were seen later in life in women who had hypertensive disorders of pregnancy compared with those who had normotensive pregnancy, a prospective cohort study found.

2. The association was mainly driven by women with gestational hypertension.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Cat ID: 41

Topic ID: 83,41,730,6,130,41,192,925