Due to the smaller gestational age, lower birth weight and immature lung development, very preterm infants are vulnerable to pulmonary hemorrhage. According to reports from different centers, the incidence in VLBWI vary from 0.5–11.0%, while the mortality is as high as 50–82% [19–21]. Our data showed that the incidence was 15.3% (42/275), and the mortality rate was 21.4% (9/42) in VLBWIs. Although the survival rate seems improved, longer mechanical ventilation is often needed after pulmonary hemorrhage.
Considering the lung injury caused by pulmonary hemorrhage and subsequent long-term invasive ventilation, it seems that pulmonary hemorrhage can increase the incidence of BPD. A retrospective study found that moderate to severe BPD was significantly higher in the group with massive pulmonary hemorrhage (647 VLBWIs, p < 0.05) [7]. In contrast, another study showed that no differences in moderate to severe BPD between pulmonary hemorrhage group and non-pulmonary hemorrhage group (7/17 and 40/107 ELBWIs respectively, p > 0.05) [6]. Tomaszewska M et al further performed a retrospective case-control study and found infants with oxygen dependence at 28 days in pulmonary hemorrhage group is not significantly more than infants in non-pulmonary hemorrhage group (24/29 and 17/29 VLBWIs respectively, p > 0.05) [8]. However, almost all the reports studying on the association between BPD and pulmonary hemorrhage are univariate analysis which limits the reliability of the results.
Previous study has definitely shown that severe RDS and hemodynamically significant PDA (hsPDA) are triggers of pulmonary hemorrhage [22]. And the mechanism of pulmonary hemorrhage is mainly related to pulmonary congestion, pulmonary edema and pulmonary small vessel embolism [23]. Moreover, newborns with severe RDS and hsPDA often need longer invasive ventilation, which may increase the possibility of BPD. Our univariate analysis showed that in the comparison of survival VLBWIs, pulmonary hemorrhage increased the risks of BPD (pulmonary hemorrhage group 26/33 vs non-pulmonary hemorrhage group 98/181, p = 0.008) and moderate to severe BPD (pulmonary hemorrhage group 16/33 vs non-pulmonary hemorrhage group 38/181, p = 0.037). In fact, the correlation between invasive ventilation and BPD has already been widely reported [24]. Pulmonary hemorrhage also could prolong and increase the duration and frequency of invasive ventilation (Table 3). However, through further multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD (aOR = 2.647, 95%CI0.879-7.968) and moderate to severe BPD (aOR = 2.096, 95%CI0.672-6.540). But, if the interference of invasive ventilation is excluded, pulmonary hemorrhage could increase the incidence of BPD (aOR = 3.295, 95%CI1.183-9.179), but did not increase the chance of moderate to severe BPD (aOR = 2.619, 95%CI 0.885–7.752).
Limitations
We should note that the sample size of this study is not large enough. In addition, some data including coagulation function, cardiac hemodynamics are not available because of respective study design. Consequently, better designed multicenter study is still necessary.