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



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.


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.


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.


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.

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Fig. 1

Adapted from Lambertini et al. [66]; Perera and Herbstman [69]

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This work was supported by the NIMH Grants K01 MH080062, ARRA supplement K01 MH080062S and R01MH102729 (to YN), and MRC Grant MR/MD013960/1 (to AJ).

Author Contributions

Y Nomura: Protocol/project development, Manuscript writing/editing, Study Design; R John: Manuscript writing/editing, Placenta Biology, and Epigenetics; AB Janssen: Manuscript writing/editing, Translational Epigenetics; C Davey: Manuscript writing/editing, Critical Review; J Finik: Manuscript writing/editing, Literature Review, Literature Search; J Buthmann: Manuscript writing/editing, Literature Review, Literature Search; V Glover: Manuscript writing/editing, Critical Review; L Lambertini: Manuscript writing/editing, Translational Epigenetics.

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Correspondence to Yoko Nomura.

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Nomura, Y., John, R.M., Janssen, A.B. et al. Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes. Arch Gynecol Obstet 295, 1319–1329 (2017).

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  • Genomic imprinting
  • Placenta Epigenetics
  • Preeclampsia
  • Neurobehavioral development