No abstract

Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy.

The consensus BPD definition identifies a spectrum of risk for adverse pulmonary and neurodevelopmental outcomes in early infancy more accurately than other definitions.

The strongest risk factors for BPD are prematurity and low birth weight 19-25. Almost 80% of infants who are born at 22-24 weeks of gestation are diagnosed with BPD 26 , whereas only 20% of infants born at 28 weeks of gestation develop BPD. Among infants with BPD, 95% are VLBW 27. Other perinatal risk factors include intrauterine growth restriction (IUGR) 13 , male sex 13,20,23 and, inconsistently, chorioamnionitis 28 , race or ethnicity 13,20,23 , and smoking 29,30. Genetic risk factors may also contribute to the development of BPD, as indicated by twin studies 31,32 , and there is an ongoing search for genetic markers for BPD 33-37. Early respiratory patterns of premature infants provide insight into risk factors for BPD. An early study suggested that peak inspiratory ventilator pressure and requirement for assisted ventilation on day 4 of life are early predictors of BPD 38. Subsequent studies found that three patterns of lung disease generally emerge in the first 2 weeks of life 39-45 (FIG. 2). In the first pattern, infants have fairly minimal lung disease and progressively recover. In the second pattern, early persistent pulmonary deterioration (EPPD), substantial and prolonged respiratory support is required from birth. In the third pattern, an initial improvement in lung disease in the first week of life is followed by a respiratory decompensation termed pulmonary deterioration, which often requires mechanical ventilation and an increase in supplemental oxygen. Risk factors that may be associated with pulmonary deterioration include late surfactant deficiency 46 , sepsis, increased levels of inflammatory proteins (such as RANTES) 47 and patent ductus arteriosus 40,43. Almost 50% of infants with pulmonary deterioration and almost 70% of infants with EPPD develop BPD 48. The National Institute of Child Health and Human Development (NICHD) Neonatal Research Network developed an online, publicly available risk estimator (https:// neonatal.rti.org/index.cfm) that accurately estimates the risk of developing BPD by postnatal day 49. Investigators identified risk factors for BPD, and the competing outcome of death, among gestational age, birth weight, ethnicity and sex, ventilatory support (ranging from no support (breathing room air without positive airway pressure) to high frequency ventilation) and fraction of inspired oxygen (FiO 2), on postnatal days 1, 3, 7, 14, 21 and 28 in 3,636 infants born at 23-30 weeks of gestation. The BPD prediction tool is internally and externally validated. The models predict the correct level of BPD or the occurrence of death in >80% of cases and have the highest area under the curve (AUC) among current BPD risk predictors 50. This tool is used to provide counselling to families and to quantify risk for determining patient inclusion in early phase therapeutic trials. Interestingly, systemic inflammation occurs early in the neonatal period and precedes clinical symptoms in infants with BPD 51. This finding suggests that a therapeutic window of opportunity exists during the early p...

No abstract

Summary The transition from a fetus to a newborn is the most complex adaptation that occurs in human experience. Lung adaptation requires the coordinated clearance of fetal lung fluid, surfactant secretion, and the onset of consistent breathing. With the removal of the low-pressure placenta, the cardiovascular response requires striking changes in blood flow, pressures and pulmonary vasodilation. The newborn must also quickly control its energy metabolism and thermoregulation. The primary mediators that both prepare the fetus for birth and support the multi-organ transition are cortisol and catecholamine. Abnormalities in adaptation are frequently found following preterm birth or delivery by cesarean section at term, and many of these infants will need delivery room resuscitation to assist in this transition.

Purpose of Review 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. Recent Findings The epidemiology of BPD continues to demonstrate that birth weight or 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 CPAP and then be selectively treated with surfactant for RDS. The growth of the lungs of the infant with BPD through childhood remains poorly characterized. Summary 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 surfactant protein A (SP-A) gene was disrupted by homologous recombination in embryonic stem cells that were used to generate homozygous SP-A-deficient mice. SP-A mRNA and protein were not detectable in the lungs