Bronchopulmonary dysplasia (BPD) is a chronic lung disease of primarily premature infants that results from an imbalance between lung injury and repair in the developing lung. BPD is the most common respiratory morbidity in preterm infants, which affects nearly 10, 000 neonates each year in the United States. Over the last two decades, the incidence of BPD has largely been unchanged; however, the pathophysiology has changed with the substantial improvement in the respiratory management of extremely low birth weight (ELBW) infants. Here we have attempted to comprehensively review and summarize the current literature on the pathogenesis and pathophysiology of BPD. Our goal is to provide insight to help further progress in preventing and managing severe BPD in the ELBW infants.

Background The available data regarding morbidity and mortality associated with multiple gestation births is conflicting and contradicting. Objective To compare morbidity, mortality, and length of stay (LOS) outcomes between multiple gestation (twin, triplet and higher-order) and singleton births. Methods Data from the national multicenter Kids’ Inpatient Database of the Healthcare Cost and Utilization Project from the years 2000, 2003, 2006, 2009, 2012, and 2016 were analyzed using a complex survey design using Statistical Analysis System (SAS) 9.4 (SAS Institute, Cary NC). Neonates with ICD9 and ICD10 codes indicating singletons, twins or triplets, and higher-order multiples were included. Mortality was compared between these groups after excluding transfer outs to avoid duplicate inclusion. To analyze LOS, we included inborn neonates and excluded transfers; who died inpatient and any neonates who appear to have been discharged less than 33 weeks PMA. The LOS was compared by gestational age groups. Results A total of 22,853,125 neonates were analyzed for mortality after applying inclusion-exclusion criteria; 2.96% were twins, and 0.13% were triplets or more. A total of 22,690,082 neonates were analyzed for LOS. Mean GA, expressed as mean (SD), for singleton, twins and triplets, were 38.30 (2.21), 36.39 (4.21), and 32.72 (4.14), respectively. The adjusted odds for mortality were similar for twin births compared to singleton (aOR: 1.004, 95% CI:0.960–1.051, p = 0.8521). The adjusted odds of mortality for triplet or higher-order gestation births were higher (aOR: 1.33, 95% CI: 1.128–1.575, p = 0.0008) when compared to the singleton births. Median LOS (days) was significantly longer in multiple gestation compared to singleton births overall (singletons: 1.59 [1.13, 2.19] vs. twins 3.29 [2.17, 9.59] vs. triplets or higher-order multiples 19.15 [8.80, 36.38], p < .0001), and this difference remained significant within each GA category. Conclusion Multiple gestation births have higher mortality and longer LOS when compared to singleton births. This population data from multiple centers across the country could be useful in counseling parents when caring for multiple gestation pregnancies.

Supportive care with mechanical ventilation continues to be an essential strategy for managing severe neonatal respiratory failure; however, it is well known to cause and accentuate neonatal lung injury. The pathogenesis of ventilator-induced lung injury (VILI) is multifactorial and complex, resulting predominantly from interactions between ventilator-related factors and patient-related factors. Importantly, VILI is a significant risk factor for developing bronchopulmonary dysplasia (BPD), the most common chronic respiratory morbidity of preterm infants that lacks specific therapies, causes life-long morbidities, and imposes psychosocial and economic burdens. Studies of older children and adults suggest that understanding how and why VILI occurs is essential to developing strategies for mitigating VILI and its consequences. This article reviews the preclinical and clinical evidence on the pathogenesis and pathophysiology of VILI in neonates. We also highlight the evidence behind various lung-protective strategies to guide clinicians in preventing and attenuating VILI and, by extension, BPD in neonates. Further, we provide a snapshot of future directions that may help minimize neonatal VILI.

Diuretic therapy, commonly used in the newborn intensive care unit, is associated with a variety of electrolyte abnormalities such as hyponatremia, hypokalemia, and hypochloremia. Hypochloremia, often ignored, is associated with significant morbidities and increased mortality in infants and adults. Clinicians respond in a reflex manner to hyponatremia than to hypochloremia. Hypochloremia is associated with nephrocalcinosis, hypochloremic alkalosis, and poor growth. Besides, the diuretic resistance associated with hypochloremia makes maintaining chloride levels in the physiological range even more logical. Since sodium supplementation counters the renal absorption of calcium and lack of evidence for spironolactone role in diuretic therapy for bronchopulmonary dysplasia (BPD), alternate chloride supplements such as potassium or arginine chloride may need to be considered in the management of hypochloremia due to diuretic therapy. In this review, we have summarized the current literature on hypochloremia secondary to diuretics and suggested a pragmatic approach to hypochloremia in preterm infants.