Sex differences in behavioral outcome following neonatal hypoxia ischemia: Insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic injury

摘要

Neonatal hypoxia-ischemia (HI) predisposes infants to developmental disabilities. Adverse perinatal events can complicate the clinical courses of both preterm and full term infants. The effects of HI events on the neurological injury and the consequent developmental outcomes can differ between preterm and full term infants (Gancia and Pomero, 2011). Perinatal complications such as hypoxia, ischemia, infections, metabolic disorders, and other perinatal insults increase the likelihood of brain injury both in preterm and in full term neonates. In addition, life saving measures including prolonged ventilation during treatment of neonatal respiratory disorders and untoward events such as sepsis and necrotizing enterocolitis can also contribute to adverse neurodevelopmental outcomes particularly in preterm infants (Adams-Chapman and Stoll, 2006; Albertine, 2012; O'Shea et al., 2013; Stoll et al., 2004; Walsh et al., 2005). The work by Smith et al. described in a recent issue of Experimental Neurology demonstrates that there are also sex differences with respect to developmental outcomes both in preterm and in full term subjects (Smith et al., 2014). Their metaanalysis of IQ. scores addresses long-term outcomes in former preterm infants and shows a female advantage for full scale IQ. and performance IQ, but not for verbal IQ (Smith et al., 2014). Their work also provides detailed neurodevelopmental analyses of male versus female rats exposed to HI on P7. This age in neonatal rats approximately corresponds to a neurodevelopmental stage similar to full term infants. Smith et aL showed task-dependent sex differences with HI exposed neonatal male rats exhibiting greater deficits than females in some tasks, but similar deficits in other tasks (Smith et al., 2014). Thus, the findings in the former preterm human infants and full term rodent model appear to support the contention that developmental outcomes are more favorable in females than males in most but not all outcome measures. These findings could be important when designing individualized early intervention programs for infants after untoward perinatal events.