Control of breathing activity in the fetus and newborn.

Breathing movements have been demonstrated in the fetuses of every mammalian species investigated and are a critical component of normal fetal development. The classic sheep preparations instrumented for chronic fetal monitoring determined that fetal breathing movements (FBMs) occur in aggregates interspersed with long periods of quiescence that are strongly associated with neurophysiological state. The fetal sheep model also provided data regarding the neurochemical modulation of behavioral state and FBMs under a variety of in utero conditions. Subsequently, in vitro rodent models have been developed to advance our understanding of cellular, synaptic, network, and more detailed neuropharmacological aspects of perinatal respiratory neural control. This includes the ontogeny of the inspiratory rhythm generating center, the preBötzinger complex (preBötC), and the anatomical and functional development of phrenic motoneurons (PMNs) and diaphragm during the perinatal period. A variety of newborn animal models and studies of human infants have provided insights into age-dependent changes in state-dependent respiratory control, responses to hypoxia/hypercapnia and respiratory pathologies.