Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

Abstract

Purpose Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3–8% of all pregnancies in the US are complicated by preeclampsia and another 5–7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. Method Pub Med and Web of Science databases were searched using the terms “preeclampsia,” “gestational hypertension,” “imprinting genes,” “imprinting dysregulation,” and “epigenetic modification,” in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. Results The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. Conclusion Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

Maternal Exposure to Ambient Air Pollution and Risk of Preeclampsia: A Population-Based Cohort Study in Scania, Sweden

“…For example, an adjusted odds ratio (AOR) of 1.35 with a 95% confidence interval (CI) of 1.11-1.63 was found when comparing the lowest quartile of BC exposure to the highest quartile in the third trimester (Table 3). Results were very similar among the trimesters, and similar effects were also seen for NO x and locally emitted levels of PM 2.5 and PM 10 (Table 3). For total PM 2.5 and PM 10 , an effect of the exposures during the entire pregnancy period was found; however, this was only statistically significant in some trimester-specific exposure windows (Table 3).…”

“…Results were very similar among the trimesters, and similar effects were also seen for NO x and locally emitted levels of PM 2.5 and PM 10 (Table 3). For total PM 2.5 and PM 10 , an effect of the exposures during the entire pregnancy period was found; however, this was only statistically significant in some trimester-specific exposure windows (Table 3). Figure S5 (b-f) illustrates these effect estimates in graphic form.…”

“…Preeclampsia (PE) is a pregnancy-induced hypertensive disorder marked by a new-onset hypertension and one or more maternal manifestations including proteinuria, maternal organ dysfunction, or uteroplacental dysfunction presenting after 20 gestational weeks [8]. This condition is the second main cause of maternal death worldwide and one of the leading causes of adverse fetal outcomes, such as low birth weight and prematurity [9][10][11][12]. The widely used clinical subclassification for assessing the severity of preeclampsia includes early-and late-onset PE: diagnosed at their occurrence before and after 34 weeks of gestation, respectively [8].…”

Pathophysiology and Current Clinical Management of Preeclampsia

“…In addition to this, these children are more susceptible to neurodevelopmental and behavioral problems as well as cardiovascular diseases as they age [68•]. All of which suggest that we still need to further our understanding of the complex relationship between the ischemic placenta, maternal inflammation and fetal programming.…”

Association between preeclampsia and autism spectrum disorder: a population‐based study

“…Preeclampsia is one of the leading causes of maternal morbidity and mortality and has recently been redefined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) as newonset hypertension (blood pressure ≥140/90 mmHg on/after 20 weeks' gestation) accompanied by proteinuria and/or other maternal organ dysfunction and/or uteroplacental dysfunction (Brown et al, 2018). Preeclampsia is associated with maternal inflammation, poor placentation and oxidative stress, which may also represent some of the potential aetiological pathways in the development of ASD (Brown et al, 2014;Nomura et al, 2017;Yui, Kawasaki, Yamada, & Ogawa, 2016).…”