Traditionally, periodic breathing in preterm infants has been considered benign, yet we have seen it frequently associated with more prolonged respiratory pauses. To examine the profile of periodic breathing during development we studied preterm and term infants at postconceptional ages 30±2 wk (weight 1.2±0.2 kg; n=9), 34±2 wk (weight 1.9±0.3 kg; n=8), 38±2 wk (weight 3.0±0.3 kg; n=8), and 42±2 wk (weight 4.2±0.4 kg; n=10). We hypothesized that the presence of periodic breathing is an ominous sign which correlates closely with increased prematurity, low oxygenation and prevalence of significant apnea (≥20 s). Respiratory pattern was measured using a flow-through system. Sleep state was monitored. We found 1) the prevalence of periodic breathing decreased from 25% to 22%, 21%, and 10% at 30, 34, 38, and 42 wk respectively; 2) this trend correlated closely with an increase in TcPO2 from 53±2 Torr at 30 wk to 70±2 Torr at 42 wk(p=0.01); the lowest saturation observed increased from 82% at 30 wk to 92% at 42 wk (p=0.02); 3) these changes were similar in quiet and REM sleep although the proportion of quiet sleep increased with age at the expense of REM sleep; 4) prevalence of apneas ≥20 s decreased from 28% at 30 wk to 12% at 34 wk, and to 0% thereafter (p=0.005); the longest apnea decreased from 42 to 35, 14, and 11 seconds at 30, 34, 38, and 42 wk of postconceptional age, respectively, and 5) the breathing cycle decreased from 17±1 seconds at 30 wk to 15±1 seconds at 42 wk of gestation (p=0.01); this was due primarily to a decrease in the breathing interval, apnea length remaining unchanged. The findings indicate a very significant link between prematurity, low oxygenation, periodic breathing and significant apnea, which appears to be independent of sleep state. We conclude that periodic breathing of prematurity is indeed an ominous sign and represents the initial instability of the respiratory control system necessary to generate pathologic apneas.Supported by the Children's Hospital of Winnipeg Research Foundation.