Neurodevelopmental Disruptions in Children of Preeclamptic Mothers: Pathophysiological Mechanisms and Consequences

Abstract

Preeclampsia (PE) is a multisystem disorder characterized by elevated blood pressure in the mother, typically occurring after 20 weeks of gestation and posing risks to both maternal and fetal health. PE causes placental changes that can affect the fetus, particularly neurodevelopment. Its key pathophysiological mechanisms encompass hypoxia, vascular and angiogenic dysregulation, inflammation, neuronal and glial alterations, and disruptions in neuronal signaling. Animal models indicate that PE is correlated with neurodevelopmental alterations and cognitive dysfunctions in offspring and in humans, an association between PE and conditions such as cerebral palsy, autism spectrum disorder, attention deficit hyperactivity disorder, and sexual dimorphism has been observed. Considering the relevance for mothers and children, we conducted a narrative literature review to describe the relationships between the pathophysiological mechanisms behind neurodevelopmental alterations in the offspring of PE mothers, along with their potential consequences. Furthermore, we emphasize aspects pertinent to the prevention/treatment of PE in pregnant mothers and alterations observed in their offspring. The present narrative review offers a current, complete, and exhaustive analysis of (i) the pathophysiological mechanisms that can affect neurodevelopment in the children of PE mothers, (ii) the relationship between PE and neurological alterations in offspring, and (iii) the prevention/treatment of PE.

Keywords: attention deficit hyperactivity disorder; autism; cerebral palsy; neurodevelopment; offspring; pathophysiological mechanisms; preeclampsia; spectrum disorder.

Figure 1

Physiopathological mechanisms that may affect neurodevelopment in children of preeclamptic mothers. Placental alterations caused by PE promote increased inflammation and cortisol, conditions of hypoxia, vascular dysregulation, and alterations in pro- and anti-angiogenic factors. These conditions induce an unfavorable intrauterine environment for the fetus. This adverse environment is associated with neuroanatomical changes; cerebrovascular alterations; connectivity disruptions; changes in the permeability of the BBB; and disruptions in neurons, glia, and neuronal signaling. Ultimately, these alterations impact the neurodevelopment of the child. Abbreviations: PE, preeclampsia; IUGR, intrauterine growth restriction; BBB, blood–brain barrier; ↑, increase; ↓, decrease.

Figure 2

Neurological alterations in the offspring of mothers with PE and potential tools for prevention and treatment for pregnant mothers and their children. The figure shows potential neurological alterations in children associated with PE in mothers, such as cerebral palsy, autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and mood disorders, schizophrenia, and emotional dysregulation. Additionally, it is noted that these alterations may vary depending on the gender of the child. Possible preventive interventions for PE in mothers include diet, exercise, pharmacological treatment, and vitamin use. For children, an effective treatment tool could be stimulation in the first years of life. Abbreviations: PE, preeclampsia; ↑, increase.