The new bronchopulmonary dysplasia.

Purpose Of Review: Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth. A number of recent animal models and clinical studies provide new information about pathophysiology and treatment.

Recent Findings: The epidemiology of BPD continues to demonstrate that birth weight and gestational age are most predictive of BPD.

Communities, birth attendants and health facilities: a continuum of emergency maternal and newborn care (the Global Network's EmONC trial).

Background: Maternal and newborn mortality rates remain unacceptably high, especially where the majority of births occur in home settings or in facilities with inadequate resources. The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes. However, the effectiveness of emergency obstetric and neonatal care services has never been proven.

Inflammation and lung maturation from stretch injury in preterm fetal sheep.

Mechanical ventilation is a risk factor for the development of bronchopulmonary dysplasia in premature infants. Fifteen minutes of high tidal volume (V(T)) ventilation induces inflammatory cytokine expression in small airways and lung parenchyma within 3 h. Our objective was to describe the temporal progression of cytokine and maturation responses to lung injury in fetal sheep exposed to a defined 15-min stretch injury.

Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep.

Background: Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation.

Objective: We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs.

"Miracle" extremely low birth weight neonates: examples of developmental plasticity.

Many extremely low birth weight (LBW) neonates now survive with intensive care. Their survival depends on fetal and neonatal adaptations of multiple organ systems, which represents a plasticity of development. Many extremely LBW neonates do not have severe lung immaturity, will breathe, and do not require surfactant treatment.

Inflammation in fetal sheep from intra-amniotic injection of Ureaplasma parvum.

Bronchopulmonary dysplasia is associated with chorioamnionitis and fetal lung inflammation. Ureaplasma species are the bacteria most frequently isolated from chorioamnionitis. Very chronic ureaplasma colonization of amniotic fluid causes low-grade lung inflammation and functional lung maturation in fetal sheep.

Exposure to in utero lipopolysaccharide induces inflammation in the fetal ovine skin.

Inflammation is a defensive process by which the body responds to both localized and systemic tissue damage by the induction of innate and adaptive immunity. Literature from human and animal studies links inappropriate in utero inflammation to preterm parturition and fetal injury. The pathways by which such inflammation may cause labor, however, are not fully understood.

Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis.

Monocyte chemoattractant proteins (MCP-1 and MCP-2) mediate monocyte and T-lymphocyte chemotaxis, and IL-1 contributes to the pathogenesis of chorioamnionitis-induced lung inflammation and fetal inflammatory responses. We tested the hypothesis that IL-1 mediates the systemic and pulmonary induction of MCP-1 and MCP-2 in response to lipopolysaccharide (LPS)-induced chorioamnionitis. MCP-1 mRNA, MCP-2 mRNA, and MCP-1 protein expression were measured in two models: 1) intra-amniotic LPS and 2) intra-amniotic recombinant sheep IL-1alpha given at varying intervals before preterm delivery at 124 d GA.

Maternal administration of erythromycin fails to eradicate intrauterine ureaplasma infection in an ovine model.

Erythromycin is the standard antibiotic used for treatment of infection with Ureaplasma spp. during pregnancy; however, maternally administered erythromycin may be ineffective at eliminating intra-amniotic ureaplasma infections. We examined whether erythromycin would eradicate intra-amniotic ureaplasma infections in pregnant sheep.

The severity of chorioamnionitis in pregnant sheep is associated with in vivo variation of the surface-exposed multiple-banded antigen/gene of Ureaplasma parvum.

Ureaplasma species are the bacteria most frequently isolated from human amniotic fluid in asymptomatic pregnancies and placental infections. Ureaplasma parvum serovars 3 and 6 are the most prevalent serovars isolated from men and women. We hypothesized that the effects on the fetus and chorioamnion of chronic ureaplasma infection in amniotic fluid are dependent on the serovar, dose, and variation of the ureaplasma multiple-banded antigen (MBA) and mba gene.

Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum.

Ureaplasma species, the most commonly isolated microorganisms in women with chorioamnionitis, are associated with preterm delivery. Chorioamnionitis increases the risk and severity of bronchopulmonary dysplasia and persistent pulmonary hypertension in newborns. It is not known whether the timing of exposure to inflammation in utero is an important contributor to the pathogenesis of bronchopulmonary dysplasia.

Long term consequences of oxygen therapy in the neonatal period.

Preterm and term infants are frequently exposed to high concentrations of oxygen for prolonged periods. In experimental models, high and prolonged oxygen exposures cause delayed alveolar septation and a bronchopulmonary dysplasia phenotype. Often, however, the oxygen exposure is tolerated in that the infants recover without severe lung or systemic injury.

Thymic changes after chorioamnionitis induced by intraamniotic lipopolysaccharide in fetal sheep.

Objective: Regulatory T lymphocytes mediate homeostasis of the immune system and differentiate under the control of the transcription factor FoxP3 in the fetal thymus. We asked whether fetal inflammation caused by chorioamnionitis would modulate thymus development.

Study Design: Fetal sheep were exposed to an intraamniotic injection of 10 mg lipopolysaccharide at 5 hours, 1 day, 2 days, or 5 days before delivery at 123 gestation days.

Body temperature effects on lung injury in ventilated preterm lambs.

Aims: Mechanical ventilation causes lung injury in premature infants. Hypothermia may protect against and hyperthermia may augment lung injury. We tested the effects of hypo- and hyperthermia on ventilation induced acute lung injury in preterm lambs.

Lung maturation: the survival miracle of very low birth weight infants.

The increased survival of very preterm infants is generally attributed to improved care strategies. This review develops the thesis that the features of abnormal pregnancies responsible for very preterm deliveries also provide an explanation of why very preterm infants often survive. A normal fetus born at 24 weeks is very unlikely to survive.

Ventilation-mediated injury after preterm delivery of Ureaplasma parvum colonized fetal lambs.

Ureaplasma species are the microorganisms most frequently isolated from women with preterm birth and are associated with an increased risk of bronchopulmonary dysplasia. Initiation of ventilation with high tidal volumes (VT) causes lung injury and inflammation. We investigated whether antenatal colonization with Ureaplasma parvum serovar 3 (UP) would alter the inflammatory response to mechanical ventilation of preterm lambs.

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep.

Background: Initiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.

Objective: To test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.

Airway injury from initiating ventilation in preterm sheep.

Premature infants exposed to ventilation are at risk of developing bronchopulmonary dysplasia and persistent lung disease in childhood. We report where injury occurred within the lung after brief ventilation at birth. Preterm sheep (129 d gestation) were ventilated with an escalating tidal volume to 15 mL/kg by 15 min to injure the lungs, with the placental circulation intact (fetal) or after delivery (newborn).

Modulation of fetal inflammatory response on exposure to lipopolysaccharide by chorioamnion, lung, or gut in sheep.

Objective: We hypothesized that fetal lipopolysaccharide exposures to the chorioamnion, lung, or gut would induce distinct systemic inflammatory responses.

Study Design: Groups of 5-7 time-mated ewes were used to surgically isolate the fetal respiratory and the gastrointestinal systems from the amniotic compartment. Outcomes were assessed at 124 days gestational age, 2 days and 7 days after lipopolysaccharide (10 mg, Escherichia coli 055:B5) or saline solution infusions into the fetal airways or amniotic fluid.

Betamethasone dose and formulation for induced lung maturation in fetal sheep.

Objective: We hypothesized that maternal treatments with betamethasone acetate induce fetal lung maturation comparably to the betamethasone phosphate+betamethasone acetate used clinically.

Study Design: Ewes with singleton pregnancies were treated with single doses of 0.25-mg/kg or 0.

Oxygen, temperature and humidity of inspired gases and their influences on airway and lung tissue in near-term lambs.

Purpose: The relative contributions of factors influencing lung injury immediately after birth are poorly understood. We hypothesized that oxygen content and humidity of inspired air would influence markers of pulmonary inflammation in ventilated lambs.

Methods: Lambs delivered at 140 days gestation (term = 150 days) were assigned to one of five groups (n = 5-6/group): unventilated controls, or ventilation with 21 or 100% O(2) that was either heated and humidified or cold and dry.

IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung.

Preterm infants exposed to chorioamnionitis and preterm sheep fetuses exposed to intra-amniotic (IA) LPS have lung inflammation, increased IL-8 levels, and lung maturation. We tested the hypothesis that IL-8 signaling mediates IA LPS-induced lung inflammation and lung maturation. Two strategies were used: 1) we tested if IA injection of recombinant sheep IL-8 (rsIL-8) induced fetal inflammation and 2) if IL-8 signaling was blocked by a novel CXCR2 receptor blocker, nicotinanilide thioglycolate methyl ester (NTME).