Sex differences in adult social, cognitive, and affective behavioral deficits following neonatal phlebotomy‐induced anemia in mice

INTRODUCTION: Anemia is common in prematurely born infants due to blood loss resulting from frequent phlebotomies and may contribute to their neurobehavioral deficits. Preclinical models of phlebotomy‐induced anemia (PIA) have revealed metabolic and genomic changes in multiple brain structures of young mice, yet the impact of neonatal PIA on early‐life and adult behavior has not been assessed. METHODS: The present study employed a range of behavioral measures in phlebotomized anemic neonatal mice to investigate short‐ and long‐term neurodevelopmental effects. PIA from postnatal (P) days 3 to 14 caused sex‐specific changes in social behavior, novelty preference, and anxiety at P17 that persisted into adulthood. RESULTS: Our preclinical model suggests that PIA may contribute to acute and long‐term behavioral and affective deficits and warrants further substantiation of the observed behavioral phenomena in larger samples. CONCLUSIONS: We conclude that this model is a useful tool for beginning to better understand the lasting effect that early‐life PIA might have on the developing brain. The differential impact of PIA on male and female subjects warrants further exploration for the development of appropriately targeted interventions.