Non-heritable risk factors for autism spectrum disorder (ASD) and developmental delay (DD) include maternalconditions associated with metabolic dysregulation, most notably pre-pregnancy obesity, excessive gestationalweight gain, and complications associated with poor metabolic health, including chronic and gestational formsof hypertension, diabetes and dyslipidemia. Obesity has reached epidemic proportions in the U.S., with morethan half of pregnant women overweight or obese. Racial and socioeconomic disparities are profound. Theproposed research plan will explore physiological characteristics of maternal obesity that may be involved inneurodevelopmental compromise in a non-human primate model. We will compare inflammatory andmetabolic changes to the gestational milieu in obese and normal-weighted mothers, as well as histologic andepigenetic modifications to the placenta and infant brain. Additionally, we will evaluate the effectiveness of twomaternal intervention strategies, gestational weight maintenance and daily administration of the pharmacologicagent pravastatin through pregnancy, in reversing the effects of maternal obesity on the maternal and placentalenvironments. Weight management has been recommended by both the Institute of Medicine and theAmerican Congress of Obstetricians and Gynecologists for management of obesity in pregnancy, and thepharmacological properties of pravastatin provide biological plausibility for its use in preventing the systemic,placental and fetal consequences of maternal obesity. This proposal strives to utilize fully the uniqueresources inherent in the third trimester rhesus monkey model to address this serious clinical problem withsubstantial public health impact. Our interdisciplinary team weaves the expertise of investigators withextensive collaborative experience in maternal health and fetal development, reproductive physiology, nutrition,immunology, epigenetics, metabolomics, lipomics, biostatistics and neurodevelopment in both humans andnon-human primates. The specific aims of the project will: 1) explore the physiologic effects of maternalobesity that underlie neurodevelopmental impairment and 2) determine whether two interventional strategieswill prevent the effects of maternal obesity. The outcome of these studies will have direct translational value byinforming women and their health providers of the risks of maternal obesity to the developing brain and willprovide information on preventive options to help obese women and their health care providers lessen risk fortheir babies.
|Effective start/end date||8/1/16 → 4/30/20|
- National Institutes of Health: $512,608.00
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