Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice.

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.

Predicting the likelihood of bronchopulmonary dysplasia in premature neonates.

Introduction: Bronchopulmonary dysplasia (BPD) is the most common serious pulmonary morbidity in premature infants. Despite ongoing advances in neonatal care, the incidence of BPD has not improved. A potential explanation for this phenomenon is the limited ability for accurate early prediction of the risk of BPD. BPD continues to represent a therapeutic challenge and no single effective therapy exists for this condition. Areas covered: Here, we review risk factors of BPD derived from clinical data, biological fluid biomarkers, respiratory management data, and scientific advancements using 'omics' technologies, and their ability to predict the pathogenesis of BPD in preterm neonates. Risk factors and biomarkers were identified via literature search with a focus on the last 5 years of data. Expert opinion: The most accurate predictive tools utilize risk factors that encompass a variety of categories. Numerous predictive models have been proposed but suffer from a lack of adequate validation. An ideal model should include multiple, easily measurable variables validated across a heterogeneous population. In addition to evaluating recent BPD prediction models, we suggest approaches to enhance future models.

An Outpatient Methadone Weaning Program by a Neonatal Intensive Care Unit for Neonatal Abstinence Syndrome.

Through retrospective chart review, this study described characteristics and length of stay for a cohort of newborns discharged on methadone following an inpatient weaning for neonatal abstinence syndrome (NAS). Data were assessed for all term infants born between January 1, 2010, and December 31, 2014, admitted to the hospital with a co-diagnosis of NAS at discharge, for gestational age, length of stay, days on treatment protocol before discharge, time to once-daily interval methadone dosing, and hospital charges, as well as for categorical characteristics. The 53 patients were predominantly male (58%), white (71%), and covered by Medicaid insurance (72%). Mean gestational age was 39.5 ± 1.1 weeks; length of hospital stay was 11.8 ± 5 days. Common co-diagnoses were newborn feeding problems (26%) and neonatal hypoglycemia (23%). In conclusion, use of the study site's methadone weaning protocol, which can be easily replicated, resulted in a relatively short length of stay and low readmission rates for these patients.