Abstract
Background: Hypertensive disorders of pregnancy, such as Preeclampsia (PreE) and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome, affects approximately 5–10% of pregnancies and increases the risk of women developing disorders, such as anxiety or depression, in the postpartum period. Using preclinical rodent models, we set out to determine whether rats with a history of PreE or HELLP had evidence of anxiety, depression or cognitive impairment and whether immune suppression during pregnancy prevented these changes in mood and/or cognition. Methods: Timed-pregnant rats were infused with sFlt-1 and/or sEng to induce PreE or HELLP beginning on gestational day 12. After delivery, a battery of validated behavioral assays was used to assess post-partum depression, anxiety and learning. Results: There was no negative effect on maternal pup interaction due to PreE or HELLP; however, hypertensive dams spent more time immobile in the forced swim test (p < 0.0001). Hypertensive dams also spent less time in the open area of the open field (p = 0.001). There were no significant changes in recognition memory (p = 0.08); however, spatial learning was impaired in hypertensive dams (p = 0.003). Immobility time in the forced swim test was positively correlated with increased circulating S100B (p = 0.04), while increased time spent in the outer zones of the open field was negatively correlated with BDNF levels (p < 0.0001). Conclusion: The results from this study suggest that hypertensive pregnancy disorders are associated with depression, anxiety and learning impairments in the post-partum period.
Highlights
IntroductionHypertensive disorder of pregnancy (HDP) affects approximately 5–10% of all pregnancies [1,2]
Post hoc analysis indicated a significant increase in the frequency of this behavior in HELLP + Orencia dams vs. PreE + Orencia dams (p = 0.04, Figure 2B)
This study extends the current knowledge regarding Hypertensive disorder of pregnancy (HDP), mood disorders and cognition in preclinical animal models by demonstrating that hypertension and inflammation during pregnancy contributes to long-lasting changes in maternal mood and cognition
Summary
Hypertensive disorder of pregnancy (HDP) affects approximately 5–10% of all pregnancies [1,2]. Women with advanced HDPs, such as preeclampsia (PreE; new onset of high blood pressure after 20 weeks gestation) or HELLP (hemolysis, elevated liver enzyme, low platelet; considered to be a variant of PreE with more severe organ dysfunction and often life threatening) syndrome, are even more susceptible to these mood disorders and have been reported by some to have disturbances in cognitive function [6,7,8]. There have been several theories as to why women affected by HDPs are more susceptible to these changes, ranging from cerebral vascular dysfunction during pregnancy to long-term complications due to hypertension [9,10]; to date, none have been conclusive. What is more striking is that despite the similar etiology between PreE and HELLP, the few reports on maternal mood and cognition differ between the two conditions
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