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Fetal intervention in congenital malformations of the respiratory system

Key points Congenital malformations of the respiratory system consist of a wide range of fetal anomalies that can affect the developing of the fetal lungs. Most congenital malformations of the respiratory system can be diagnosed prenatally by identifying hyperechoic lung masses on ultrasonography. Once the prenatal diagnosis of congenital malformations of the respiratory system is made, it is crucial to have these patients referred to a…

Genetic disorders of alveolar formation and homeostasis

Key points Lung morphogenesis begins with the formation of the tracheal and bronchial buds. Subsequent branching morphogenesis forms the respiratory tubules, the acini, and the alveolar regions of the lung required for gas exchange after birth. Lung morphogenesis is dependent upon precise paracrine signaling among pulmonary progenitor cells controlling gene transcription, which determines the precise numbers, positions, and functions of pulmonary cells. Interactions between the mesenchymal…

The neonatal lung: Lung imaging using ultrasound and electric impedance tomography

Key points Lung ultrasound and electrical impedance tomography are point-of-care imaging modalities that provide continuous, radiation-free bedside lung imaging. Lung ultrasound relies on the interpretation of reproducible ultrasound artifact patterns that correspond to the degree of lung aeration. It has an established role in the diagnosis of numerous neonatal respiratory disorders. Electrical impedance tomography analyzes variations in electrical bioimpedance to provide detailed information on total and…

Caffeine—respiratory stimulant or magic bullet?

Key points Caffeine is the respiratory stimulant of choice to prevent or treat apnea of prematurity. The standard loading is 20 mg/kg of caffeine citrate, and the daily maintenance dose is 5 to 10 mg Beneficial effects of this caffeine regimen include reduced risks of motor impairment, bronchopulmonary dysplasia, and severe retinopathy of prematurity. Lasting harmful effects have not been detected with standard doses of caffeine…

Perinatal nutrition and the lung

Key points Lung development is influenced by both prenatal and postnatal nutrient quality and quantity. The wide spectrum of maternal and preterm infant nutritional states has differing impacts on the trajectory of fetal-infant lung development. Specific nutrient supplements given during gestation or postnatally have been shown to affect pulmonary outcomes. Introduction The causes of altered fetal and neonatal lung development are numerous, but prematurity, which affects…

Long-term pulmonary outcome of preterm infants

Key points Preterm infants are vulnerable to adverse long-term sequelae including pulmonary outcomes. Respiratory morbidities, including hospitalizations for respiratory infections, asthma, and wheezing illnesses, are higher in those born preterm compared with term. These risks decrease as the children get older. Expiratory flow is lower in children born preterm compared with controls and worse in children who had bronchopulmonary dysplasia compared with those who did not.…

A physiology-based approach to the respiratory care of children with severe bronchopulmonary dysplasia

Key points Despite advances in perinatal care, including many innovations in cardiorespiratory management of extremely preterm infants, the incidence of bronchopulmonary dysplasia (BPD) and its severity has not decreased over time and remains a major public health problem. Severe BPD (sBPD) is characterized by abnormalities of large and small airways with reduced distal lung surface area with heterogeneous lung units, leading to marked regional variations in…

Definitions and diagnostic criteria of bronchopulmonary dysplasia: Clinical and research implications

Key points Bronchopulmonary dysplasia (BPD) is a common complication of prematurity that results from abnormal lung development and injury that leads to chronic impairment of lung function. Use of standardized diagnostic classifications of BPD and its severity is important in clinical trials that evaluate therapeutic strategies and in epidemiologic cohorts to benchmark respiratory outcomes in neonatal centers. Current criteria to diagnose BPD do not consistently predict…

Cell-based therapy for neonatal lung diseases

Key points The postnatal lung contains populations of stem cells that reconstitute the lung following injury. Prematurity and its antecedent factors alter endogenous stem cells leading to dysfunctional lung repair. Preterm infants who develop bronchopulmonary dysplasia (BPD) exhibit decreased and/or dysfunctional lung stem cells. Mesenchymal stem cells augment lung repair by supporting endogenous lung progenitors, promoting angiogenesis, and reducing inflammation, apoptosis, and fibrosis. Cell-free approaches such…

Prenatal and postnatal steroids and pulmonary outcomes

Key points Antenatal steroids (ANS) are one of the oldest and most effective therapies in perinatal medicine. The randomized controlled trials (RCTs) are dated and do not necessarily apply for current clinical populations in high-resource environments where treatments reduce mortality. In low-resource environments, there is potential for risk and unclear benefit of ANS. There are minimal RCT data to support ANS use for deliveries before 28…

Ventilator strategies to reduce lung injury and duration of mechanical ventilation

Key points The immature lungs of extremely preterm infants are susceptible to damage from a variety of factors that are potentially modifiable by the use of lung-protective strategies of respiratory support. Avoidance of mechanical ventilation (MV), optimal delivery room stabilization, and early use of noninvasive respiratory support are important elements in minimizing lung injury. When MV is needed, it should be employed with care and attention…

Pulmonary-cardiovascular interaction

Key points The respiratory and cardiac systems are integrally related both anatomically and functionally, and as a result there are significant interactions, particularly in the newborn period. Inappropriately high airway pressure during mechanical ventilation leads to adverse hemodynamic effects including a reduction in left and right ventricular output, a decrease in venous return, and an increase in pulmonary vascular resistance (PVR). Inappropriately low airway pressure can…

Respiratory control and oxygen instability in premature infants

Key points Understanding the physiology of neonatal respiratory control has served as an effective guide to common therapeutic approaches. Both the acute and longer-term consequences of intermittent hypoxemia and apnea of prematurity are subjects of intense interest. Intermittent hypoxemia may contribute to an inflammatory stress response. Although caffeine is the mainstay of apnea therapy, there remains considerable controversy regarding optimal treatment regimens. Innovative newer approaches to…

Newer strategies for surfactant delivery

Key points As fewer preterm infants are managed with an endotracheal tube (ETT) in early life, the usual conduit for surfactant delivery is lacking. With this approach has come a dilemma regarding how and when to deliver surfactant to those showing features of surfactant-deficient respiratory distress syndrome (RDS). Brief intubation solely for surfactant delivery has been widely practiced, but has disadvantages, not the least of which…

Noninvasive respiratory support for preterm infants: An alternative to mechanical ventilation

Key points Continuous positive airway pressure (CPAP) provides effective respiratory support for preterm infants for a range of indications, especially when delivered via binasal prongs or nasal masks at set pressures equal to or greater than 5 cm H 2 O. Extremely preterm infants may be managed with CPAP from the delivery room onward as an alternative to routine intubation and mechanical ventilation. Nasal intermittent positive-pressure…

Ventilator-associated pneumonia

Key points Invasive mechanical ventilation of neonates increases their risk of developing bacterial infection of the lower airways and lung parenchyma, which is termed “ventilator-associated pneumonia” (VAP). VAP is diagnosed on the basis of defined clinical, radiographic, and laboratory criteria. Unlike other neonatal bacterial infections, culture isolation of a single, causative organism is unusual in VAP. Suspected VAP should initially be treated with broad-spectrum antibiotics covering…

Airway microbiome and lung injury

Key points Contrary to conventional teaching, culture-independent molecular techniques have confirmed that the healthy lung is not sterile and the lung microbiome is likely established in early life, influences development of immune responses and pulmonary function, and is altered in disease states. Although the major pathway that microorganisms colonize the uterine cavity is vertical ascension from the vagina, there is emerging evidence suggesting transplacental transfer of…

Vascular development and pulmonary hypertension

Key points Lung vascular development occurs as highly choreographed sequence, regulated by hypoxia inducible factors, vascular endothelial growth factor, nitric oxide, and other transcription factors and mediators. In addition to arterial vessels, pulmonary veins are highly reactive vessels that contribute to the overall regulation of pulmonary vascular resistance in the fetus and newborn. Antenatal pulmonary vascular development can be disrupted by events such as placental insufficiency,…

Respiratory and cardiovascular support in the delivery room

Key points After birth, lung aeration and an increase in pulmonary blood flow are closely linked. Although it is possible to identify deliveries of infants at increased risk of requiring resuscitation, appropriately trained personnel should be present at every birth. Establishing effective ventilation is the key to successful neonatal resuscitation. A very small number of newborns require chest compressions or emergency medications. Routine tracheal suction for…

Perinatal events and their influence on lung development and injury

Key points Multiple antenatal exposures exert effects on the fetal lung—some adverse and other beneficial for postnatal survival. Antenatal exposures can alter lung development and interact with postnatal exposures. Early gestational lung maturation is common and promoted by both antenatal steroids and fetal exposure to inflammation. Antenatal steroid is a common exposure that may interact with postnatal care practices in presently unknown ways. Sepsis with chorioamnionitis…