Abstract
Although bronchopulmonary dysplasia (BPD) is the most frequent adverse outcome for infants born at < 30 weeks gestational age, there remain major gaps in understanding the pathophysiology, ...and thus there are few effective targeted therapies to prevent and treat BPD. This review will focus on the substantial problems and knowledge gaps for the clinician and investigator when considering lung injury and BPD. The epidemiology of BPD is clear: BPD is a lung injury syndrome predominantly in extremely low-birth-weight infants with an incidence that increases as gestation/birth weight decrease, with growth restriction, in males and with fetal exposures and with injury from postdelivery respiratory care. However, we do not have a good definition of BPD that identifies the infants that die of respiratory disease before 36 weeks or that predicts long-term outcomes as well. The injury resulting in BPD likely begins as altered lung development before delivery in many infants (small for gestational age, chorioamnionitis, tobacco exposure), can be initiated by resuscitating at birth, and then amplified by postnatal exposures (oxygen, mechanical ventilation, infection). Conceptually the events leading to BPD are the continued interplay of lung development that is altered progressively by injury and repair to result in poorly defined phenotypes of BPD. The injury pathways prominently cause inflammation, and as a proof of principle, corticosteroids can decrease the incidence and severity of BPD, as demonstrated by three recent trials of the early use of steroids. There are likely “adaptation” and “tolerance” responses that modulate the injury and repair to increase or decrease the damage, interactions that are not understood. BPD is a more complex disease.
Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth. A number of recent animal models and clinical studies provide new information about pathophysiology and ...treatment.
The epidemiology of BPD continues to demonstrate that birth weight and gestational age are most predictive of BPD. Correlations of BPD with chorioamnionitis are clouded by the complexity of the fetal exposures to inflammation. Excessive oxygen use in preterm infants can increase the risk of BPD but low saturation targets may increase death. Numerous recent trials demonstrate that many preterm infants can be initially stabilized after delivery with continuous positive airway response (CPAP) and then be selectively treated with surfactant for respiratory distress syndrome. The growth of the lungs of the infant with BPD through childhood remains poorly characterized.
Recent experiences in neonatology suggest that combining less invasive care strategies that avoid excessive oxygen and ventilation, decrease postnatal infections, and optimize nutrition may decrease the incidence and severity of BPD.
The transition from fetus to newborn is the most complex adaptation that occurs in human experience. Lung adaptation requires coordinated clearance of fetal lung fluid, surfactant secretion, and ...onset of consistent breathing. The cardiovascular response requires striking changes in blood flow, pressures, and pulmonary vasodilation. Energy metabolism and thermoregulation must be quickly controlled. The primary mediators that prepare the fetus for birth and support the multiorgan transition are cortisol and catecholamine. Abnormalities in adaptation are frequently found following preterm birth or cesarean delivery at term, and many of these infants need delivery room resuscitation to assist in this transition.
Can We Define Bronchopulmonary Dysplasia? Jobe, Alan H.; Steinhorn, Robin
The Journal of pediatrics,
September 2017, 2017-09-00, 20170901, Volume:
188
Journal Article
Peer reviewed
Full text
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Antenatal corticosteroids are standard of care for pregnancies at risk of preterm delivery between 24-34 weeks’ gestational age. Recent trials demonstrate modest benefits from antenatal ...corticosteroids for late preterm and elective cesarean deliveries, and antenatal corticosteroids for periviable deliveries should be considered with family discussion. However, many women with threatened preterm deliveries receive antenatal corticosteroids but do not deliver until >34 weeks or at term. The net effect is that a substantial fraction of the delivery population will be exposed to antenatal corticosteroids. There are gaps in accurate assessments of benefits of antenatal corticosteroids because the randomized controlled trials were performed prior to about 1990 in pregnancies generally >28 weeks. The care practices for the mother and infant survival were different than today. The randomized controlled trial data also do not strongly support the optimal interval from antenatal corticosteroid treatment to delivery of 1-7 days. Epidemiology-based studies using large cohorts with >85% of at-risk pregnancies treated with antenatal corticosteroids probably overestimate the benefits of antenatal corticosteroids. Although most of the prematurity-associated mortality is in low-resource environments, the efficacy and safety of antenatal corticosteroids in those environments remain to be evaluated. The short-term benefits of antenatal corticosteroids for high-risk pregnancies in high-resource environments certainly justify antenatal corticosteroids as few risks have been identified over many years. However, cardiovascular and metabolic abnormalities have been identified in large animal models and cohorts of children exposed to antenatal corticosteroids that are consistent with fetal programming for adult diseases. These late effects of antenatal corticosteroids suggest caution for the expanded use of antenatal corticosteroids beyond at-risk pregnancies at 24-34 weeks. A way forward is to develop noninvasive fetal assessments to identify pregnancies across a wider gestational age that could benefit from antenatal corticosteroids.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Very preterm infants are commonly exposed to a chronic, often asymptomatic, chorioamnionitis that is diagnosed by histologic evaluation of the placenta only after delivery. The reported effects of ...these exposures on fetal lungs are inconsistent because exposure to different organisms, durations of exposure, and fetal/maternal responses affect outcomes. In experimental models, chorioamnionitis can both injure and mature the fetal lung and cause immune nodulation. Postnatal care strategies also change how chorioamnionitis relates to clinical outcomes such as bronchopulmonary dysplasia.
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