Does fetal growth restriction induce neuropathology within the developing brainstem?

Fetal growth restriction (FGR) is a complex obstetric issue describing a fetus that does not reach its genetic growth potential. The primary cause of FGR is placental dysfunction resulting in chronic fetal hypoxaemia, which in turn causes altered neurological, cardiovascular and respiratory development, some of which may be pathophysiological, particularly for neonatal life. The brainstem is the critical site of cardiovascular, respiratory and autonomic control, but there is little information describing how chronic hypoxaemia and the resulting FGR may affect brainstem neurodevelopment. This review provides an overview of the brainstem-specific consequences of acute and chronic hypoxia, and what is known in FGR. In addition, we discuss how brainstem structural alterations may impair functional control of the cardiovascular and respiratory systems. Finally, we highlight the clinical and translational findings of the potential roles of the brainstem in maintaining cardiorespiratory adaptation in the transition from fetal to neonatal life under normal conditions and in response to the pathological environment that arises during development in growth-restricted infants. This review emphasises the crucial role that the brainstem plays in mediating cardiovascular and respiratory responses during fetal and neonatal life. We assess whether chronic fetal hypoxaemia might alter structure and function of the brainstem, but this also serves to highlight knowledge gaps regarding FGR and brainstem development.