Assessment of Risk of Bias
The overall risk of bias was low for most studies, except that the study
by Thome (2006) 16 had a high overall risk of bias for
BPD and NDI (Supplemental Table B). In the study by Thome (2006), the
mortality in the permissive hypercapnia group was higher than that in
the normocapnia group (36% vs. 19%). This can lead to a bias in the
rates of BPD and NDI because those who died before the assessment of BPD
or NDI could not have these outcomes. Owing to the characteristics of
the intervention (targeting PaCO2), care providers were
not blinded in any of the included trials. BPD diagnosis that was made
without an objective algorithm (e.g., oxygen reduction test) might be
influenced by the outcome assessors’ knowledge of the intervention
assignment.20 Therefore, the measurement outcome of
BPD was considered to be concerning, to some extent, except for that
reported in the study by Carlo (2002) 15, which used
an algorithm for BPD diagnosis (Supplemental Table B).
Of note, the study by Carlo (2002) was terminated early because the
infants treated with dexamethasone (another intervention of the RCT with
a 2 Ă— 2 factorial design) had high rates of NEC. Because the reason for
early termination was not related to the comparison between permissive
hypercapnia and normocapnia, we did not consider that it increased the
risk of bias. For the cohort study of Hagen (2008) 19,
the overall risk of bias was judged to be serious for IVH and NDI owing
to concerns about remaining confounding and measurement outcomes
(Supplemental Table C).