Bronchopulmonary Dysplasia Is Not Associated with Ultrasound-Defined Cerebral White Matter Damage in Preterm Newborns

Abstract

Bronchopulmonary dysplasia (BPD) and cerebral white matter damage (WMD) are neonatal disorders that occur most commonly in those who are born much before term. In a large multicenter database, we sought to determine whether the two disorders occur together more frequently than expected and whether BPD and other neonatal respiratory characteristics are more common among infants who develop ultrasound-defined WMD than among those who do not. In a sample of 904 infants who were born before the 30th week of gestation and survived until 36 wk postmenstrual age, we did not find a co-occurrence of BPD and WMD above what would be expected by chance. Confounding does not seem to account for this lack of association between WMD and BPD. In conclusion, our findings do not support the hypothesis that BPD contributes to the occurrence of sonographically defined WMD. Preterm infants are exposed to a number of antenatal and postnatal challenges that, in concert with their immaturity, render them susceptible to a wide range of neonatal disorders. Among these, bronchopulmonary dysplasia (BPD) and cerebral white matter damage (WMD) are prominent entities.BPD was initially identified as a chronic neonatal lung disease that occurred in preterm infants who were exposed to prolonged ventilation with high airway pressure and high inspired oxygen concentrations (1). More recently, a "new" BPD was defined as a form of neonatal chronic lung disease, characterized by aberrational lung alveolarization and vascular development (2). Changes in neonatal practice, including the introduction of exogenous surfactant, increased use of antenatal glucocorticoids, and sophisticated ventilatory support strategies, might play a role in this changing clinical phenomenology of BPD. Antenatal effects apparently gain pathogenetic importance (3), and major research emphasis is being placed on inflammatory pathomechanisms (4). The current terminology has now returned from "chronic lung disease" to BPD (5). The new definition of BPD-"receiving O 2 at 36 wk postconceptional age"-has been shown to be a better predictor of abnormal pulmonary signs and symptoms at age 2 (83%) (6) than the 38% achieved by previously suggested definition of BPD-"receiving O 2 at 28 d of life" (7).

Lung and Brain Damage in Preterm Newborns

“…In light of these issues, we recently analyzed a large database of 904 infants born before the 30th week of gestation [29]. In support of the previous findings [20][21][22], we did not find that BPD (defined as oxygen dependence at 36 postmenstrual weeks) and WMD (defined as echolucency on neonatal ultrasound scans) occur together more frequently than expected by chance.…”

“…Any failure to find that WMD and BPD occur together might be due to chance, bias or confounding, the three classic sources of error in observational research. One way to reduce the likelihood of chance is calculating p values and 95%-confidence intervals for all effect estimates [29]. Nevertheless, a residual likelihood of erroneously rejecting the null hypothesis always remains present, even when smaller than 5%.…”

“…Moreover, only control infants who survived until 36 weeks' post-menstrual age (the time of BPD diagnosis in our study), and long enough to have a late cranial ultrasound scan to ascertain WMD, should be included. Finally, to reduce the likelihood of confounding, adjustment is needed for multiple factors that are associated with both WMD and BPD [29].…”

“…Another important methodological source of error might be the definitions used. We define WMD as a single echolucency [29], whereas some others are less than explicit about their criteria or else require bilateral echolucencies for their definition of 'periventricular leukomalacia'. Although definitions differ widely, all studies have failed to find an association between BPD and WMD [20][21][22]29].…”

“…On the other hand, multiple studies have confirmed that CAM [4], prolonged ventilation [29], and neonatal sepsis [56][57][58] are risk factors for WMD. Thus, one explanation for the absence of an association between BPD and WMD might be differential organ-specific effects of multiple inflammatory hits, which might be at least partially beneficial for the neonatal lung (in the absence of prolonged ventilation), while being harmful for the developing brain.…”