684 CLD Year SensorM (no to yes) TimeCMV Age Weight HLVS LPVS Surf CMV Death or CLD Year SensorM TimeCMV Age Weight HLVS LPVS Surf CMV CLD Year TimeCMV Age Weight Death or CLD Year TimeCMV Age Weight Year of publication was not related to change in rela- and RRR = 0.44 for CLD and 0.92 for death or CLD in the tive risk of CLD in the subgroup of studies with HLVS, adjusted and crude analyses, respectively (Fig. 3; Table 2). LPVS and concomitant use of surfactant (RRR = 0.96). Multivariable linear regression analyses were con- There was only a small increase in relative risk for death ducted to assess the independent contributions to change or CLD (RRR = 1.20; Fig. 2; Table 2). Opposite effects of in RR by explanatory variables (Table 3). The RRRs gestational age (RRR = 1.22 for CLD and 1.38 for death in Table 3 have the same meaning as in Table 2, only or CLD vs RRR = 0.66 for CLD and 0.91 for death or they represented adjusted RRRs. Year of publication CLD, respectively) and birth weight were detected in the was not considered as an independent explanatory vari- subgroup analysis (Fig. 4; Table 2). Prior time on CMV able but rather as proxy for changes in treatment and exerted less effect on outcome compared with the crude patient population. Gestational age and birth weight analysis, RRR = 0.66 for CLD and 0.96 for death or CLD were collinearly related by nature; only gestational age Table 2 Univariable linear regression analysis 95% conﬁdence interval Lower Upper boundary boundary 95% conﬁdence interval Lower Upper boundary boundary 0.01 -0.55 -0.19 -0.23 -1.87 -1.74 0.19 -0.59 -1.53 -0.01 -0.39 -0.05 -0.13 -1.16 -2.44 -0.18 -0.51 -0.91 -0.23 -0.34 -0.22 -1.99 -0.15 -0.05 -0.10 -0.89 0.16 0.21 0.00 0.06 0.35 1.52 1.10 3.00 1.17 0.12 0.06 0.03 0.10 0.71 1.69 0.56 1.56 0.87 0.22 0.25 0.30 2.81 0.17 0.04 0.21 1.99 Simple linear regression analyses were calculated for chronic lung disease (CLD), deﬁned as on oxygen at 30–36 weeks postgesta- tional age, and death or CLD. The following co-variates were evaluated: Year: Number of years after the ﬁrst included study; Sen- sorM: Whether or not a Sensormedics type of HFV was used; TimeCMV : Mean time on CMV before start of the study in hours; Age: Mean gestational age (weeks); Weight: mean birth weight (kg); HLVS: high lung volume strategy in the HFV group; LPVS: lung protective ventilation strategy in the CMV group; Surf : use of surfactant in the study; B was the estimated crude coefﬁcient; RRR: relative risk ratio = RRcovariate=1 /RRcovariate=0 , for binary variables (SensorM, HLVS and LPVS), for continues variables the extreme values reported in the studies were used to calculate the ranges, 13 for years, 8.7 for Time on CMV, 5 for Age, 0.8 for Weight and 0.65 for CMV (RRRyears = RRyear=2005/RRyear=1992,RRRtimeonCMV = RRtime=9 h /RRtime=0.3 h , RRRage = RRage=31 weeks /RRyear=26 weeks , RRRweight = RRweight=1.5 kg/RRyear=0.7 kg , RRRincidenceo fCL DinCMV=0.75 /RRincidence=0.08 ) Crude B All studies 0.09 -0.17 -0.09 -0.08 -0.76 -0.11 0.64 1.21 -0.18 0.05 -0.17 -0.01 -0.02 -0.22 -0.37 0.19 0.52 -0.02 0.00 -0.05 0.04 0.41 0.01 0.00 0.06 0.55 Sig. 0.025 0.351 0.055 0.237 0.163 0.883 0.009 0.168 0.774 0.096 0.132 0.590 0.733 0.611 0.698 0.275 0.289 0.963 0.971 0.698 0.727 0.693 0.846 0.819 0.406 0.396 Studies with surfactant, HLVS, and LPVS RRR 3.13 0.84 0.44 0.66 0.54 0.89 1.91 3.34 0.90 2.01 0.85 0.92 0.91 0.84 0.69 1.21 1.69 0.99 0.96 0.66 1.22 1.38 1.20 0.96 1.34 1.55 1.18 0.58 0.19 0.32 0.22 0.17 1.21 0.56 0.42 0.86 0.67 0.65 0.52 0.40 0.09 0.84 0.60 0.60 0.05 0.05 0.33 0.20 0.15 0.65 0.61 0.49 8.27 1.24 1.02 1.36 1.33 4.57 3.00 20.03 1.92 4.65 1.06 1.29 1.61 1.77 5.45 1.76 4.75 1.63 17.34 8.75 4.49 9.44 9.72 1.43 2.92 4.90