Pathophysiological mechanisms of sudden infant death syndrome

Abstract

AbstractThere is a consensus that sudden infant death syndrome, the leading cause of mortality in the first year of life, is multifactorial. Most of the cases are probably due to respiratory or cardiac disorders. It has been proposed that some cases of sudden infant death might result from ventricular fibrillation triggered by a sudden increase in sympathetic activity affecting the heart with reduced electrical stability. This impairment can be due to an insufficient or delayed development of cardiac vagal innervation, with the resultant lack of its protective effect that has been demonstrated to be present since the third week of life. Clinical studies suggest that some of the sudden infant death victims may have a reduced heart rate variability that could be interpreted as a decreased parasympathetic activity to the heart. On the other hand, a reduced cardiac electrical stability may be provoked by a developmental imbalance in sympathetic innervation such to create a dominance of left-sided nerves. We have demonstrated that an imbalance of this type experimentally induced in puppies increases the susceptibility to ventricular fibrillation and prolongs QT interval. In order to demonstrate a significant relationship between prolonged QT interval and sudden infant death, we performed a large prospective study on 18,832 neonates. QT interval corrected for heart rate (QTc) measured from an electrocardiogram on the fourth day of life, was within the normal limits in nine victims from known causes, while it was exceeding the mean by two standard deviations (>433 msec) in six of 12 sudden infant death victims. If these data are confirmed by a larger multicenter study started in Italy, it will be possible to identify some of the sudden infant death victims by the observation of a prolonged QT interval on the electrocardiogram. In this case a preventive strategy based on a time-limited administration of beta adrenergic blocking agents to the infants at risk, might reduce the incidence of sudden infant death.