OBJECTIVE. The goal was to test the hypothesis that extremes of PaCO 2 during the first 4 days after birth are associated with severe intraventricular hemorrhage (grades 3 and 4). METHODS. A single-center retrospective review of clinical and blood gas data in the first 4 postnatal days for 849 infants with birth weights of 401 to 1250 g was performed. The univariate and multivariate relationships of severe intraventricular hemorrhage with maximal and minimal PaCO2, PaCO2 averaged over time (time-weighted PaCO2), and measures of PaCO2 fluctuation (SD of PaCO2 and difference in PaCO2 [maximum minus minimum]) were assessed. RESULTS. Birth weight (mean ± SD) was 848 ± 212 g, and the median gestational age was 26 weeks. Infants with severe intraventricular hemorrhage had higher maximal PaCO2 (median: 72 vs 59 mm Hg) and time-weighted PaCO2 (mean: 49 vs 47 mmHg) values but lower minimal PaCO2 values (32 vs 37mmHg). High PaCO2, low PaCO2, SD of PaCO2, and difference in PaCO2 predicted severe intraventricular hemorrhage, but time-weighted average PaCO2 was not as predictive. CONCLUSIONS. Both extremes and fluctuations of PaCO2 are associated with severe intraventricular hemorrhage. It may be prudent to avoid extreme hypocapnia and hypercapnia during the period of risk for intraventricular hemorrhage. Copyright © 2007 by the American Academy of Pediatrics.