682 [12] [13] [14] [15] [16] [17] [18] [19] [20] [2] [3] [23] [22] [21] [24] SPSS 12.0.1 for Windows software (SPSS, Chicago, Ill.) published over a range of 13 years. Other reported ranges and Excel (Microsoft, Redmond, Wash.). of covariates were 8.7 h average time on CMV before start of study, 5 weeks average gestational age, and 0.65 kg average birth weight. These ranges were used to calculate Results RRRs. Two studies dominated the analyses by virtue of the weight they received in the analyses: Johnson et al. [3] For the analyses 15 studies were available that speciﬁed ei- and Courtney et al. [2] (together 69% for CLD and 73% ther CLD in survivors or death or CLD as outcome meas- for death or CLD as outcome). ures [2, 3, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, A funnel plot of the inverse of the standard error against 24]. In 11 trials a high frequency oscillatory ventilator was the natural logarithm of the RR for CLD was indicative of used [2, 3, 12, 13, 16, 17, 19, 20, 22, 23, 24], in 7 of publication bias because of asymmetry round the line of these trials this was the SensorMedics ventilator [2, 12, 13, the pooled effect (Fig. 1). A rank test showed a p-value of 17, 22, 23]. Two studies used a high-frequency jet ventila- 0.112. A stratiﬁed analysis of publication bias is indicated tor [14, 15] and in two studies a high-frequency ﬂow in- by different colors in Fig. 1. To visually evaluate publica- terrupter ventilator was used [18, 21]. In the HFV group tion bias within subgroups of ventilation strategy, the dis- a total of 1141 patients were included for the outcome of tribution of trials round the corresponding colored lines CLD with 373 events and a total of 1457 patients with 671 (mean effect size within subgroup) was assessed. Strati- events for the outcome death or CLD. In the CMV group ﬁcation by ventilation strategy (HLVS and LPVS vs either a total 1159 patients were reported for the outcome of CLD no HLVS and/or no LPVS) showed p-values of 0.456 and with 428 events and a total of 1473 patients with 730 events 0.851, respectively, indicating less evidence of publication for the outcome death or CLD. A forest plot of these trials bias. The distribution of stratiﬁed studies round the lines can be found in the Electronic Supplement. of pooled estimates showed less asymmetry (Fig. 1). Pub- Table 1 summarizes the main characteristics of the lication bias for the composite outcome of death or CLD studies. The outcome of CLD was available in all studies was less likely with a p-value of 0.329. Stratiﬁed analysis but one [22]. Time on CMV to start of the study was not showed p-values of 0.677 and 1.000. reported by Plavka et al. [17] and Craft et al. [21]. In Figures 2, 3, 4 show the results of the linear meta- only one study was surfactant not used as concomitant regression analyses for continuous explanatory variables treatment [12]. A high lung volume strategy (HLVS) with relative risk of CLD as dependent variable. Two was used in all but two studies [14, 16]. A ventilation studies dominate these ﬁgures, designated by the weight strategy in the CMV-treated patients that could qualify as they received in the analyses [2, 3]. Over the years the lung protective (LPVS) was reported in the most recent reported beneﬁt of HFV over CMV seemed to diminish 9 studies [2, 3, 18, 19, 20, 21, 22, 23, 24]. Studies were (Fig. 2). A longer time on CMV prior to study initiation 1992 1996 1996 1997 1998 1999 1999 2001 2001 2002 2002 2003 2003 2003 2005 9.0 3.0 7.2 8.0 1.0 0.5 2.6 0.3 2.7 1.0 1.0 14.0 0.3 28 31 27 27 28 26 27 26 28 26 26 29 27 26 27 1.100 1.500 0.950 1.020 1.100 0.850 0.870 0.840 0.990 0.850 0.850 1.200 0.980 0.726 0.880 Y Y N N N Y N Y N Y N Y Y N N Y Y N Y N Y Y Y Y Y Y Y Y Y Y N N N N N N Y Y Y Y Y Y Y Y Y N Y Y Y Y Y Y Y Y Y Y Y Y Y Y -1.29 -0.67 0.02 -0.70 0.00 -1.03 0.09 -0.98 -0.20 -0.06 -0.01 0.32 0.10 -1.44 0.01 0.04 0.01 0.03 0.00 0.01 0.06 0.02 0.05 0.16 0.54 0.03 0.05 0.01 Year: year of publication; Time CMV: Mean time on CMV before start of the study in hours; Age: Mean gestational age (weeks); Birth 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; CLD: chronic lung disease, deﬁned as on oxygen at 30–36 weeks postmenstrual age; LnRR: natural log of the relative risk Table 1 Study characteristics Reference Year Time on CMV Age Birth weight CLD Surf lnRR SensorM HLVS LPVS Weight Weight Death or CLD lnRR -0.58 -0.55 -0.23 0.48 0.31 -0.74 0.01 -0.59 -0.06 -0.22 -0.02 0.27 -0.04 0.09 -1.20 0.01 0.02 0.10 0.03 0.00 0.01 0.04 0.02 0.05 0.13 0.60 0.04 0.05 0.03 0.00