Sex, drugs and rock and roll: tales from preterm fetal life

Premature fetuses and babies are at greater risk of mortality and morbidity than their term counterparts. The underlying causes are multifactorial, but include exposure to hypoxia. Immaturity of organs and their functional controlmay impair the physiological defence responses to hypoxia and the pretermfetal responses, or lack thereof, to moderate hypoxia appear to support this concept. However, as this reviewdemonstrates, despite immaturity, the pretermfetus responds to asphyxia in a qualitatively similar manner to that seen at term. This highlights the importance in understanding metabolism versus homeostatic threat when assessing fetal responses to adverse challenges such as hypoxia. Data are presented to show that the preterm fetal adaptation to asphyxia is triphasic in nature. Phase one represents the rapid institution of maximal defences, designed to maintain blood pressure and central perfusion at the expense of peripheral organs. Phase two is one of adaptive compensation. Controlled reperfusion partially offsets peripheral tissue oxygen debt, while maintaining sufficient vasoconstriction to limit the fall in perfusion. Phase three is about decompensation. Strikingly, the preterm fetus generally performs better during phases two and three, and can survive for longer without injury. Paradoxically, however, the ability to survive can lead to longer exposure to hypotension and hypoperfusion and thus potentially greater injury. The effects of fetal sex, inflammation and drugs on the triphasic adaptations are reviewed. Finally, the review highlights the need for more comprehensive studies to understand the complexity of perinatal physiology if we are to develop effective strategies to improve preterm outcomes.