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Obesity and Weight Gain during Pregnancy Associate Independently with Behavior of Infant Rhesus Monkeys (Macaca mulatta)
Objectives: We explored relationships between maternal obesity, gestational weight gain (GWG) and neurobehavioral impairment in the indoor colony of rhesus (Macaca mulatta) monkeys at the California National Primate Research Center (CNPRC).
Methods: This retrospective cohort analysis examined whether maternal prepregnancy obesity and gestational weight gain were associated with behavioral outcomes in 172 rhesus macaque infants at the California National Primate Research Center. The rhesus macaque model is highly relevant to the study of gestational obesity, fetal programming and neurobehavioral outcomes with strong generalizability to humans. Dams conceived indoors, had uncomplicated pregnancies, delivered vaginally and reared infants indoors. Measures of maternal adiposity included prepregnancy Body Condition Score (BCS), a subjective semi-quantitative anatomic assessment that reliably identifies obese monkeys, and GWG measured as steepness of weight change over the interval from the last weight prior to pregnancy to the first weight after birth of the infant. Infants underwent standardized bio-behavioral analysis (BBA) at 90-120 days of age between March 2001 and May 2015. Outcomes were a series of measurements recorded in a standardized 25-hour program designed to characterize behavioral and physiological responsiveness.
Results:: Our exploration of rhesus macaque maternal adiposity measures revealed a pattern of greater behavioral disturbance during the BBA testing for infants of dams that had higher prepregnancy adiposity and / or that gained excess weight. Importantly, these effects were not evident immediately upon relocation to the testing area when all animals responded similarly to the separation and relocation. Rather, the pattern for the infants of obese mothers reflected poor adaptability, as indicated by a number of results from the later assessments, during which infants exhibited enhanced holding-cage Emotionality, substantial disturbance during the human intruder test, and completion of fewer problems and less interest in novel stimuli during the test for visual recognition memory compared with control infants. They also had significantly lower cortisol levels in response to dexamethasone suppression, indicating that the cortisol feedback loop in these animals was more sensitive to negative regulation by glucocorticoids.
Conclusions: These results amplify growing public health concerns implicating maternal adiposity in impaired fetal neurobehavioral programming. Further, this study highlights the translational potential of the nonhuman primate model for the study of developmental programming in humans. Children with ASD and ADHD often exhibit similar variation in temperament traits, including decreased adaptability, increased activity level and unusual approach behaviors. The nonhuman primate cohorts identified in this study would be excellent models for elucidation of fetal programming mechanisms that link maternal obesity and high GWG with adverse offspring behaviors often identified in individuals with ASD and / or ADHD.