Regulation of fetal breathing

Traditionally, the idea of transient asphyxia plus some degree of cold stimulation has been used to explain the establishment of continuous breathing at birth. This idea was nurtured by observations made in the acute fetal preparation at a time when fetal breathing was considered absent. Experimental observations made in the past two decades have challenged this traditional view. First, complete peripheral chemodenervation, essential to the hypoxic stimulus theory, did not affect fetal breathing or the establishment of continuous breathing at birth. Second, occlusion of the umbilical cord in utero, as long as some oxygenation is provided to the fetus in order to avoid fetal hypoxaemia, establishes continuous breathing in utero, in the absence of all sensorial input thought to be important for the establishment of continuous breathing. These observations led us to hypothesize the presence of a placental factor responsible for the inhibition of breathing in utero. This placental factor appears to be a peptide with a molecular mass between 3.5 and 10 kDa. This review will also explore some new observations regarding the generation of central respiratory activity in the fetus, and suggests that the rhythm generator is a neuronal network in which the unit is a pacemaker-like cell uniquely responsive to CO2.