Neonatal Catch Up Growth Increases Diabetes Susceptibility But Improves Behavioral and Cardiovascular Outcomes of Low Birth Weight Male Mice

Abstract

Premature infants are at increased risk for persistent growth failure, neurodevelopmental impairment, hypertension, and diabetes. Rapid neonatal growth has been linked to the increasing prevalence of diabetes and obesity. Nutritional goals for the premature infant with incipient growth failure have thus become a source of controversy. We used isogenic mice with natural variation in perinatal growth to test the hypothesis that neonatal catch up growth improves the neurobehavioral and cardiovascular outcomes of low-birth weight mice, despite an increase in diabetes susceptibility. Adult mice that experienced prenatal and neonatal growth restriction had persistent growth failure, hypertension, and neurobehavioral alterations. When switched from standard rodent chow to a hypercaloric diet, growth restricted mice were protected from diet-induced obesity. Among low-birth weight male mice, neonatal catch up growth normalized neurobehavioral and cardiovascular phenotypes, but led to insulin resistance and high fat diet-induced diabetes. Among low-birth weight female mice, neonatal catch up growth did not prevent the development of adult hypertension and significantly increased measures of anxiety, including self-injury and the avoidance of open spaces. These studies support the importance of the perinatal environment in the resetting of adult disease susceptibility and suggest an earlier window of vulnerability among growth restricted female mice.