Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder among infants born extremely preterm. The pathogenesis of BPD involves multiple prenatal and postnatal mechanisms affecting the development of a very immature lung. Their combined effects alter the lung’s morphogenesis, disrupt capillary gas exchange in the alveoli, and lead to the pathological and clinical features of BPD. The disorder is ultimately the result of an aberrant repair response to antenatal and postnatal injuries to the developing lungs. Neonatology has made huge advances in dealing with conditions related to prematurity, but efforts to prevent and treat BPD have so far been only partially effective. Seeing that BPD appears to have a role in the early origin of chronic obstructive pulmonary disease, its prevention is pivotal also in long-term respiratory outcome of these patients. There is currently some evidence to support the use of antenatal glucocorticoids, surfactant therapy, protective noninvasive ventilation, targeted saturations, early caffeine treatment, vitamin A, and fluid restriction, but none of the existing strategies have had any significant impact in reducing the burden of BPD. New areas of research are raising novel therapeutic prospects, however. For instance, early topical (intratracheal or nebulized) steroids seem promising: they might help to limit BPD development without the side effects of systemic steroids. Evidence in favor of stem cell therapy has emerged from several preclinical trials, and from a couple of studies in humans. Mesenchymal stromal/stem cells (MSCs) have revealed a reparatory capability, preventing the progression of BPD in animal models. Administering MSC-conditioned media containing extracellular vesicles (EVs) have also demonstrated a preventive action, without the potential risks associated with unwanted engraftment or the adverse effects of administering cells. In this paper, we explore these emerging treatments and take a look at the revolutionary changes in BPD and neonatology on the horizon.

Bronchopulmonary dysplasia (BPD) still carries a heavy burden of morbidity and mortality in survivors of extreme prematurity. The disease is characterized by simplification of the alveolar structure, involving a smaller number of enlarged alveoli due to decreased septation and a dysmorphic pulmonary microvessel growth. These changes lead to persistent abnormalities mainly affecting the smaller airways, lung parenchyma, and pulmonary vasculature, which can be assessed with lung function tests and imaging techniques. Several longitudinal lung function studies have demonstrated that most preterm‐born subjects with BPD embark on a low lung function trajectory, never achieving their full airway growth potential. They are consequently at higher risk of developing a chronic obstructive pulmonary disease‐like phenotype later in life. Studies based on computer tomography and magnetic resonance imaging, have also shown that in these patients there is a persistence of lung abnormalities like emphysematous areas, bronchial wall thickening, interstitial opacities, and mosaic lung attenuation also in adult age. This review aims to outline the current knowledge of pulmonary and vascular growth in survivors of BPD and the evidence of their lung function and imaging up to adulthood.

Early therapeutic effect of intratracheally (IT)-administered extracellular vesicles secreted by mesenchymal stem cells (MSC-EVs) has been demonstrated in a rat model of bronchopulmonary dysplasia (BPD) involving hyperoxia exposure in the first 2 postnatal weeks. The aim of this study was to evaluate the protective effects of IT-administered MSC-EVs in the long term. EVs were produced from MSCs following GMP standards. At birth, rats were distributed in three groups: (a) animals raised in ambient air for 6 weeks ( n = 10); and animals exposed to 60% hyperoxia for 2 weeks and to room air for additional 4 weeks and treated with (b) IT-administered saline solution ( n = 10), or (c) MSC-EVs ( n = 10) on postnatal days 3, 7, 10, and 21. Hyperoxia exposure produced significant decreases in total number of alveoli, total surface area of alveolar air spaces, and proliferation index, together with increases in mean alveolar volume, mean linear intercept and fibrosis percentage; all these morphometric changes were prevented by MSC-EVs treatment. The medial thickness index for <100 µm vessels was higher for hyperoxia-exposed/sham-treated than for normoxia-exposed rats; MSC-EV treatment significantly reduced this index. There were no significant differences in interstitial/alveolar and perivascular F4/8-positive and CD86-positive macrophages. Conversely, hyperoxia exposure reduced CD163-positive macrophages both in interstitial/alveolar and perivascular populations and MSC-EV prevented these hyperoxia-induced reductions. These findings further support that IT-administered EVs could be an effective approach to prevent/treat BPD, ameliorating the impaired alveolarization and pulmonary artery remodeling also in a long-term model. M2 macrophage polarization could play a role through anti-inflammatory and proliferative mechanisms.

Necrotizing enterocolitis (NEC), the first cause of short bowel syndrome (SBS) in the neonate, is a serious neonatal gastrointestinal disease with an incidence of up to 11% in preterm newborns less than 1500 g of birth weight. The rate of severe NEC requiring surgery remains high, and it is estimated between 20–50%. Newborns who develop SBS need prolonged parenteral nutrition (PN), experience nutrient deficiency, failure to thrive and are at risk of neurodevelopmental impairment. Prevention of NEC is therefore mandatory to avoid SBS and its associated morbidities. In this regard, nutritional practices seem to play a key role in early life. Individualized medical and surgical therapies, as well as intestinal rehabilitation programs, are fundamental in the achievement of enteral autonomy in infants with acquired SBS. In this descriptive review, we describe the most recent evidence on nutritional practices to prevent NEC, the available tools to early detect it, the surgical management to limit bowel resection and the best nutrition to sustain growth and intestinal function.

More and more very low birth weight (VLBW) infants around the world survive nowadays, with consequently larger numbers of children developing prematurity-related morbidities, especially bronchopulmonary dysplasia (BPD). BPD is a multifactorial disease and its rising incidence in recent years means that general pediatricians are much more likely to encounter a child born extremely preterm, possibly with BPD, in their clinical practice. Short- and long-term sequelae in VLBW patients may affect not only pulmonary function (principally characterized by an obstructive pattern), but also other aspect including the neurological (neurodevelopmental and neuropsychiatric disorders), the sensorial (earing and visual impairment), the cardiological (systemic and pulmonary hypertension, reduced exercise tolerance and ischemic heart disease in adult age), nutritional (feeding difficulties and nutritional deficits), and auxological (extrauterine growth restriction). For the most premature infants at least, a multidisciplinary follow-up is warranted after discharge from the neonatal intensive care unit in order to optimize their respiratory and neurocognitive potential, and prevent respiratory infections, nutritional deficiencies or cardiovascular impairments. Conclusion: The aim of this review is to summarize the main characteristics of preterm and BPD infants, providing the general pediatrician with practical information regarding these patients’ multidisciplinary complex follow-up. We explore the current evidence on respiratory outcomes and their management that actually does not have a definitive available option. We also discuss the available investigations, treatments, and strategies for prevention and prophylaxis to improve the non-respiratory outcomes and the quality of life for these children and their families, a critical aspect not always considered. This comprehensive approach, added to the increased needs of a VLBW subjects, is obviously related to very high health-related costs that should be beared in mind. What is Known:• Every day, a general pediatrician is more likely to encounter a former very low birth weight infant.• Very low birth weight and prematurity are frequently related not only with worse respiratory outcomes, but also with neurological, sensorial, cardiovascular, renal, and nutritional issues. What is New:• This review provides to the general pediatrician a comprehensive approach for the follow-up of former premature very low birth weight children, with information to improve the quality of life of this special population.

There is growing evidence in medical literature to support an association between early-life respiratory syncytial virus lower respiratory tract-lower respiratory tract infection (RSV-LRTI) and recurrent wheezing/asthma-like symptoms. It has been estimated that children with a history of RSV-LRTI have a 2- to 12-fold higher risk of developing asthma. The connection between RSV infection and a developmental trajectory of reduced lung function remains throughout adolescence and early adulthood, suggesting a possible role for RSV even in the inception of chronic obstructive pulmonary disease. That is why the postnatal period appears to offer a specific window of opportunity for early intervention to prevent chronic obstructive lung diseases. The mechanisms by which RSV contributes to the onset of wheezing/asthma and lung function impairment are not fully understood but appear to relate to injury caused directly by the virus and/or to pre-existing predisposing factors. While awaiting a deeper understanding of the association between RSV and chronic lung diseases, the crucial role of pediatricians and physicians is to develop strategies to prevent RSV infections to try and protect children's lifelong respiratory health.Key Points