Male and female offspring from HELLP, but not PreE, experimental dams experience greater delays in neurodevelopment

Abstract

Objective Women with pregnancies complicated by hypertensive disorders of pregnancy such as Preeclampsia (PreE) and HELLP (Hemolysis, Elevated Liver Enzyme, and Low Platelets) Syndrome often have an angiogenic imbalance which is seen in increased levels of soluble fms-like tyrosine kinase-1 (sflt-1) and soluble endoglin (sEng). Offspring of these pregnancies are pre-disposed to neurodevelopmental delays. Many of these pregnancies are also affected by pre-term delivery, which is a risk factor for neurodevelopmental disorders in the offspring. Since pre-term-birth and hypertensive pregnancies have the same neurodevelopmental effects on offspring, research is needed to separate the impact each have on the offspring. Using two animal models of hypertensive pregnancy we evaluated sensorimotor development among offspring from PreE (hypertension and mild inflammation) and HELLP (hypertension and severe inflammation) dams compared with those from normal pregnant dams. Methods On gestational day (GD) 12, rats were infused with sFlt-1 (PreE) or sFlt-1 and sEng (HELLP). Following delivery pups were cross-fostered to NP SHAM dams and subjected to a series of developmental sensorimotor tests from beginning on postnatal day (PND) 3. For all behavioral tasks (surface righting, cliff avoidance and negative geotaxis) pups had 60seconds to complete. Their weights recorded daily. N's for the groups of pups were as followed: NP (36), PreE (35), and HELLP (29). Results Significant differences in weight began on PND10 and by the end of the study HELLP male pups were significantly smaller relative to PreE (p<0.01) and NP (p<0.01) male and female pups (p<0.05). HELLP males and females had a significant latency in completing surface righting relative to NP and PreE pups on PND3, however these differences were corrected on following days. Regarding cliff avoidance, there were sex differences among HELLP pups with HELLP males performing worse throughout on PND3-5 (p<0.05). Overall HELLP pups had longer latencies completing cliff avoidance from PND3-6 compared to both PreE (p<0.05) and NP (p<0.05) offspring. For the Negative Geotaxis behavior there was no significant differences. Conclusion Hypertension during pregnancy has negative effects on early sensorimotor behavior in offspring. Offspring from moms experiencing more severe inflammation (i.e. HELLP) had more evidence of sensorimotor delays and intrauterine growth restriction compared to PreE offspring. This data indicates that the degree of maternal inflammation and hypertension has direct effects on offspring sensorimotor development with males demonstrating a greater sensitivity relative to females.