Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring?

Abstract

The current study sought to determine whether hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) are associated with neurocognitive outcomes in middle childhood. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study. Data were available for 1389 children (675 females; mean age = 10.59 years; SD = 0.19). Twenty-five per cent of these participants were offspring of pregnancies complicated by either gestational hypertension (n = 279), or pre-eclampsia (n = 34). Verbal ability at age 10 years was assessed with the Peabody Picture Vocabulary Test - Revised (PPVT-R), and non-verbal ability with Ravens Colored Progressive Matrices (RCPM). Separate multivariable regression analyses, incorporating sociodemographic, antenatal, obstetric and postnatal covariates, investigated the effect of a two- (normotensive pregnancy vs. hypertensive pregnancy) and three-level (normotensive pregnancy vs. gestational hypertension vs. pre-eclampsia) predictor variable on PPVT-R and RCPM scores. Offspring of pregnancies complicated by maternal hypertension (gestational hypertension or pre-eclampsia) had a mean PPVT-R score that was 1.83 ([95% confidence interval (CI) -3.48, -0.17], P = 0.03) points lower than children from normotensive pregnancies. Multivariable regression analysis also identified a significant inverse association between the three-level predictor variable and offspring PPVT-R scores (P = 0.02). Gestational hypertension (without pre-eclampsia) reduced offspring PPVT-R scores by 1.71 points [95% CI -3.39, -0.03] and pre-eclampsia led to a reduction of 3.53 points [95% CI -8.41, 1.35], although this latter association did not achieve statistical significance. There was no effect of the two- (P = 0.99) or three-level (P = 0.92) predictor variable on RCPM scores. Maternal hypertensive diseases of pregnancy are a risk factor for a small reduction in offspring verbal ability.

Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model

“…In addition, we showed that pups born to “preeclamptic” dams are more susceptible to hypoxic ischemic injury, have altered candidate gene expression in the brain, and as adults perform worse on neuromotor assays testing vestibular function, balance, and locomotor coordination compared with pups born to control mothers, all in a gender-specific manner [7]–[8]. These findings are in accordance with various epidemiologic studies showing altered neuromotor fetal programming in infants born to preeclamptic mothers [9]–[14].…”

“…However, this is balanced by consistency across this model in phenotypic and mRNA expression patterns (unpublished data) [8] as well as support of existing epidemiologic data [9]–[14]. Fourth, in this work, we examined offspring brains at a single time-point of 6 months, which was designed to evaluate long-term adulthood outcomes.…”

“…The association between preeclampsia and adverse neurologic outcomes and other chronic adult diseases has been well documented [9]–[14], [28]–[29]. It is thought that hypoxia, oxidative stress, and abnormal vascular and endothelial activity that occur in the setting of preeclampsia [2] contribute to an adverse uterine environment which is associated with alterations in gene expression during critical periods of fetal development resulting in long-term adverse effects in adult offspring.…”

Diffusion Tensor Imaging of White Matter in Children Born from Preeclamptic Gestations

“…[5][6][7][8][9][10][11][12][13][14] The brain regions with statistically significant DTI differences were previously identified in an independent analysis as having anatomic variances in volume or global vessel width compared with children born from typical pregnancies.…”

“…For PE-F1s, lower cognitive function was the prominent, reliable association. 5 The deficits in cognitive functions reported for PE-F1s 5-7 include lower intelligence quotient scores, 8,9 reduced verbal and nonverbal abilities, 10,11 and reduced arithmetic reasoning. 12,13 Recently, we conducted a pilot study to determine whether clinical cognitive function test outcomes and brain MR imaging findings differed between PE-F1s and typical 7-to 10-year-old children.…”