Alissa Carver

Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model

Objective Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention. Materials and Methods For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra “experimental group”) or water (sFlt-1 “positive control”) until weaning. The mFc group (“negative control”) received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis. Results Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes. Conclusion Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.

The effect of maternal pravastatin therapy on adverse sensorimotor outcomes of the offspring in a murine model of preeclampsia

Animal and human studies show that in‐utero exposure to preeclampsia alters fetal programming and results in long‐term adverse cardiovascular outcomes in the offspring. Human epidemiologic data also suggest that offspring born to preeclamptic mothers are also at risk of adverse long term neurodevelopmental outcomes. Pravastatin, a hydrophilic lipid‐lowering drug with pleiotropic properties, was found to prevent the altered cardiovascular phenotype of preeclampsia and restore fetal growth in animal models, providing biological plausibility for its use as a preventive agent for preeclampsia. In this study, we used a murine model of preeclampsia based on adenovirus over‐expression of the anti‐angiogenic factor soluble Fms‐like tyrosine kinase 1, and demonstrated that adult offspring born to preeclamptic dams perform poorly on assays testing vestibular function, balance, and coordination, and that prenatal pravastatin treatment prevents impairment of fetal programming.

Prenatal diagnosis and postnatal course of a giant abdominal aortic aneurysm: a case report

Abstract Congenital abdominal aortic aneurysms are rare but have chronic and life-threatening sequelae including hypertension, thromboses, and death. A fetal ultrasound at 27 weeks’ gestation diagnosed a giant abdominal aortic aneurysm. The patient delivered at another tertiary care center where pediatric cardiovascular surgery care was available. Her term 3096-g female infant developed hypertension, biventricular hypertrophy, and right kidney ischemia. She underwent surgical repair at 2 months of life but subsequently lost all residual renal function and was not a candidate for dialysis. Support was withdrawn and she expired. Although isolated fetal AAA is rare, prenatal diagnosis is feasible and facilitates early referral for multi-disciplinary postnatal care. Outcome depends on the size and location of the aneurysm as well as on peri-operative complications.