Impacts of Preeclampsia on the Brain of the Offspring

Abstract

Preeclampsia (PE) is a significant gestational disorder that causes complications in 3-5% of all human pregnancies. Apart from the immediate risks and complications for mother and fetus, both additionally carry elevated lifelong risks for specific complications. Offspring of PE pregnancies (PE-F1) have higher risks for hypertension, stroke and cognitive impairment compared with well-matched offspring (F1) from uncomplicated pregnancies. Prior to the clinical onset of PE, placental angiokines secreted into the maternal plasma are deviated. In many PE patients this includes deficits in placental growth factor (PGF). Our laboratory found that mice genetically-deleted for PGF (PGF À / À ) have altered cerebrovascular and brain neurological development detectable from midgestation to adulthood. We hypothesized that the PGF deficits seen in human PE, deviate fetal cerebrovascular and neurological development in a manner that impairs cognitive functions and elevates stroke risk. Here we summarize the initial analytical outcomes from a pilot study of 8-10 year old male and female PE-F1s and matched controls. Our studies were the first to report magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) and functional brain region assessment by eye movement control and clinical psychometric testing in PE-F1s. Further studies in larger cohorts are essential to define whether there are image-based biomarkers that describe unique anatomical features in PE-F1 brains. ResumoA pré-eclampsia (PE) é importante doença gravídica complicando 3-5% de todas as gestações humanas. Além dos riscos imediatos e complicações para a mãe e o feto, a PE associa-se a outros riscos materno-fetais elevados em longo prazo. Nascituros de gestações complicadas por PE (PE-F1) apresentam maiores riscos de desenvolver hipertensão, acidente vascular cerebral e disfunção cognitiva em comparação com prole (F1) de gestações sem complicações. Antes do aparecimento clínico da PE, angiocitocinas placentárias secretadas no plasma materno apresentam-se alteradas. Em muitos pacientes com PE, isso inclui valores plasmáticos reduzidos de Fator de Crescimento Placentário (PGF). Nosso laboratório identificou que camundongos

Vascular Dysfunction in Mother and Offspring During Preeclampsia: Contributions from Latin-American Countries

“…Interestingly, they also found that children born to preeclamptic pregnancies exhibited reduced cerebral vessel radio in the occipital and parietal lobes, suggesting an intriguing hypothesis that vascular anatomic alterations in the population of offspring of preeclamptic pregnancies might be the underling mechanism for alteration in the brain function of those children. This fact may also contribute to increased stroke risk to this young population in later life [127,128]. Other studies have described an increased risk for metabolic and endocrine disease [118,119], depression [130], cerebral palsy [131], poor cognitive outcome [132], or intellectual disabilities [133] in children born from preeclamptic pregnancies compared to non-exposed children.…”

Placental growth factor and pre-eclampsia

“…The preliminary data in the children of pre-eclamptic women suggest subtle differences in brain vascular development, which is thought to be related to intrauterine events. 9 Therefore, while PlGF may not be essential to reproduction it is still likely to be an important influence on pregnancy and vascular development.…”

Sildenafil for the treatment of preeclampsia, an update: should we still be enthusiastic?

“…Longer term, preeclampsia (especially early-onset preeclampsia and recurring preeclampsia) is also associated with an increased risk of cardiovascular events, including fatal ones [5][6][7][8][9]. Beyond this, preeclampsia also increases the cardiovascular risk profile in the offspring [10], while hypertension, stroke and cognitive impairment are more frequent [11][12][13]. However, this issue is complex since lifestyle and genes overlap here.…”