Bronchopulmonary Dysplasia: Pathogenesis and Pathophysiology.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease, is the most common respiratory morbidity in preterm infants. "Old" or "classic" BPD, as per the original description, is less common now. "New BPD", which presents with distinct clinical and pathological features, is more frequently observed in the current era of advanced neonatal care, where extremely premature infants are surviving because of medical advancements. The pathogenesis of BPD is complex and multifactorial and involves both genetic and environmental factors. This review provides an overview of the pathology of BPD and discusses the influence of several prenatal and postnatal factors on its pathogenesis, such as maternal factors, genetic susceptibility, ventilator-associated lung injury, oxygen toxicity, sepsis, patent ductus arteriosus (PDA), and nutritional deficiencies. This in-depth review draws on existing literature to explore these factors and their potential contribution to the development of BPD.

Association of Infantile Hemangiomas and Retinopathy of Prematurity: Analysis of the Multicenter KID.

INTRODUCTION: Retinopathy of prematurity (ROP) and infantile hemangiomas (IHs) both have similar proposed pathophysiological mechanisms. IH is more common in preterm than term infants. Hypoxia-induced mediators like vascular endothelial growth factor have been found elevated in children with hemangiomas. The aim of our study was to determine if there is an association between ROP and IH in preterm infants and to investigate racial/ethnic and gender differences of ROP and IHs in this cohort. METHODS: We accessed the national multicenter Kids' Inpatient Database (KID) Healthcare Cost and Utilization Project (HCUP) including admissions at age ≤28 days. Eligible infants were identified by using ICD-9 codes of ROP and IH in infants with gestational age (GA) ≤32 weeks and/or birth weight ≤1,500 g during the years 2003, 2006, 2009, and 2012. A weight-based analysis was performed using SAS Enterprise Guide 7.1 for complex sample design. RESULTS: In the cohort of 1,068,502 eligible infants, the prevalence of IH was 4.7 per 1,000 preterm admissions (<32 weeks). ROP prevalence was 16% for GA ≤26 weeks, 12.5% for GA 27-30 weeks, and 2.7% for GA 31-32 weeks. IH was significantly higher in infants with ROP; this relationship was consistent among all stages of ROP. Regression analysis showed that females are at increased risk of IH with ROP compared to males (adjusted odds ratio [aOR]: 2.00 [1.85-2.56]). White non-Hispanic premature infants had an increased risk of IH with concomitant ROP compared to both African American (aOR: 3.9 [2.63-4.76]) and Hispanic (aOR: 1.2 [1.14-1.38]) infants. However, African American infants had an increased risk of ROP compared to white non-Hispanic infants (aOR: 1.16 [1.07-1.14]). These genders and racial/ethnic disparities were consistent among GA categories. CONCLUSIONS: To our knowledge, this is the largest cohort based on a national multicenter database comparing an association between ROP and IH. A strong association between ROP and IH may suggest similar risk factors and/or pathophysiology. A further role of genetic factors could explain racial/ethnic differences in both conditions despite similar pathogenesis. These findings may open up new bases of research for management and prevention strategies.

Ventilation-Induced Lung Injury (VILI) in Neonates: Evidence-Based Concepts and Lung-Protective Strategies.

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.

Hypochloremia Secondary to Diuretics in Preterm Infants: Should Clinicians Pay Close Attention?

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.

Outcomes of multiple gestation births compared to singleton: analysis of multicenter KID database.

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.

Calorie intake is associated with weight gain during transition phase of nutrition in female extremely low birth weight infants.

We sought to determine whether there are sex-based differences in the requirements for calories or protein for optimal growth during the transition phase (TP) when an extremely low birth weight (ELBW) infant, defined as a preterm infant with a birth weight of < 1000 g, is progressing from parenteral to enteral feeds. A retrospective review of ELBW infants born from 2014 to 2016 was performed at a tertiary NICU. Infants with necrotizing enterocolitis, short bowel syndrome, or chromosomal anomalies were excluded. TP was defined as the period when the infant's enteral feeds were increased from 30 up to 120 ml/kg/day while weaning parenteral nutrition (PN). Effects of sex and protein-calorie intake on the change in growth parameters from the beginning to the end of TP were analyzed. Pre-TP growth percentiles and calorie and protein intake were similar in both sexes. There was a significant (r = 0.22, p = 0.026) correlation of total calorie intake with a change in weight percentiles (wt.pc) for the whole group, but on sex-specific analysis, this correlation was more robust and significant only in girls (r = 0.28, p = 0.015). Protein intake did not correlate with the changes in wt.pc in either sex. Despite a similar intake of calories and protein during the TP, we found a significant decrease in wt.pc only in girls. More extensive studies are needed to understand the sex-based differences in caloric needs and metabolic rate in ELBW infants.

Bronchopulmonary dysplasia: A review of pathogenesis and pathophysiology.

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.