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Respiratory problems in premature infants. Dr. Rozin Ilya Department of Neonatology Kaplan Medical Center . Respiratory problems. Respiratory Distress Syndrome (RDS) or Hyaline Membrane Diseases (HMD) Broncho-Pulmonary Dysplasia (BPD). Respiratory Distress Syndrome. Definition.
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Respiratory problems in premature infants Dr. Rozin Ilya Department of Neonatology Kaplan Medical Center
Respiratory problems • Respiratory Distress Syndrome (RDS) or Hyaline Membrane Diseases (HMD) • Broncho-Pulmonary Dysplasia (BPD)
Definition • Also known as hyaline membrane disease • Deficiency of pulmonary surfactant in an immature lung • Common respiratory disorder of premature infants • RDS can also be due to genetic problems with lung development
Epidemiology • Major cause of morbidity and mortality in preterm infants • 20,000-30,000 newborn infants each year ( in US) • Incidence and severity of RDS are related inversely to gestational age of newborn infant (most case before 37 weeks) • 26-28 weeks gestation : 50% • 30-31 weeks gestation : <30%
Epidemiology • Overall incidence in 501-1500 grams: 42% • 501-750 grams: 71% • 751-1000 grams: 54% • 1001-1250 grams: 36% • 1251-1500 grams: 22%
Other risk factors for RDS Increased Risk Decreased Risk Chronic intra-uterine stress Prolonged rupture of membranes Maternal hypertension or toxemia IUGR/SGA Antenatal glucocorticoids Maternal use of narcotics/cocaine Tocolytic agents Hemolytic disease of the newborn • Prematurity • Male gender • Familial predisposition • Cesarean section without labor • Perinatal asphyxia • Caucasian race • Infant of diabetic mother • Chorioamnionitis • Non-Immune hydrops fetalis • Multiple pregnancy (twins or more)
Surfactant • Complex lipoprotein • Composed of 6 phospholipids and 4 apoproteins • Surfactant contains • 70-80% phospholipids, • 8-10% protein, and • 10% neutral lipids
4 surfactant apoproteins • Surfactant protein B (SP-B) • Surfactant protein C (SP-C) for preventing atelectasis, and • Surfactant protein A (SP-A) - facilitates phagocytosis of pathogens by macrophages and their clearance from the airways • Surfactant protein D (SP-D) – if absent -increased surfactant lipid pools in the airspaces and emphysema in mice
Assessment of Fetal Lung Maturity • Lecithin / sphingomyelin (L/S) ratio • Lamellar body counts • Phosphatidylglycerol • After 35 weeks gestation
Etiology • Preterm delivery • Mutations in genes encoding surfactant proteins • SP-B • SP-C • ATP-binding cassette (ABC) transporter A3 (ABCA3) -is critical for proper formation of lamellar bodies and surfactant function and may also be important for lung function in other pulmonary diseases
Surfactant Inactivation • Meconium and blood can inactivate surfactant activity (Full-term > Preterm) • Proteinaceous edema and inflammatory products increase conversion rate of surfactant into its inactive vesicular form • Oxidant and mechanical stress associated with mechanical ventilation that uses large TV
Clinical Manifestations • Tachypnea • Nasal flaring • Grunting • Intercostal, sub xiphoid, and subcostal retractions • Cyanosis • Apnea
Differential Diagnosis • TTN • MAS • Pneumonia • Cyanotic Congenital Heart Disease • Pneumomediastinum, pneumothorax • Hypoglycemia • Metabolic problems • Hematologic problems • Anemia, polycythemia • Congenital anomalies of the lungs
Diagnosis • Onset of progressive respiratory failure shortly after birth • Characteristic chest radiograph • Laboratory tests – rule out infection • Analysis of blood gas: • Hypoxia • Hypercarbia
Chest X Ray “ground glass”
Prevention • Antenatal glucocorticoids • Enhances maturational changes in lung architecture and inducing enzymes • Stimulate phospholipid synthesis and release of surfactant • All pregnant mothers at risk for preterm delivery between 24 and 34 weeks gestation should receive ACS
Treatment • Surfactant Therapy • Assisted Ventilation Techniques and Oxygen therapy (be careful) • Supportive Care • Thermoregulation • Fluid Management • Nutrition • Antibiotic therapy • Gentle handling
Prognosis Acute complications of respiratory distress syndrome : • Alveolar rupture • Infection • Intracranial hemorrhage and periventricular leukomalacia • Patent Ductus Arteriosus (PDA) with increasing left-to-right shunt • Pulmonary hemorrhage • Necrotizing enterocolitis (NEC) and/or gastrointestinal (GI) perforation • Apnea of prematurity
Prognosis • Chronic complications of respiratory distress syndrome : • Broncho pulmonary dysplasia (BPD) • Retinopathy of prematurity (ROP) • Neurologic impairment
Bronchopulmonary dysplasia • Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in preterm neonates treated with oxygen and positive-pressure ventilation (PPV). • The pathogenesis of this condition remains complex and poorly understood.
Definition • 1967, Northway et al. : premature infants with RDS, resaved prolonged ventilation, with high concentration of oxygen and high peak inspiratory pressure • All require oxygen at 28 days after birth and progressive change on chest x-ray
Definition • 1979, Bancalari: same to Northway + tachypnea and crackles or retraction. • 1988, new criterion: oxygen supplementation at 36 weeks postmenstrual age (PMA) • - more accurately predicted abnormal pulmonary outcome at 2 years of age • - with medical care more infant with oxygen at 28 days
Definition 2000, National Institute of Child Health and Human Development (NICHD)
Definition • Because of absent specified in the consensus BPD definition, it was recommended that a physiologic test confirming the need for supplementation oxygen be performed
Epidemiology • Incidence: • 42-46% (BW-501-750g) • 25-33% (BW=751-1000g) • 11-14% (BW=1001=1250g) • 5-6% (BW=1251-1500g) • Risk factors: • Prematurity, low BW • White boys • Genetic heritability
Epidemiology • By the NICHD at 2010 from Neonatal Research Network • BW 401-1500 gr • GA 22 0/7 – 28 6/7 weeks • BPD of all diagnosis - 68% • Mild - 27% • Moderate – 23% • Severe – 18%
Pathology • “Old” BPD: • Airway inflammation • Fibrosis • Smooth muscle hypertrophy • “New” BPD: • Lung development arrests before alveolarization: lung have larger but fewer alveoli than normal lung • Pulmonary vasculature to be dysmorphic
Pathology • “Old BPD” (before surfactant and steroids) • Cystic changes, heterogeneous aeration • “New BPD” (after surfactant and steroids) • More uniform inflation and less fibrosis, absence of small and large airway epithelial metaplasia and smooth muscle hypertrophy • Some parenchymal opacities, but more homogenous aeration and less cystic areas • PATHOLOGIC HALLMARKS: larger simplified alveoli and dysmorphic pulmonary vasculature
Pathology • Old BPD: • Airway injury, inflammation and parenchymal fibrosis due to mechanical ventilation and oxygen toxicity • New BPD: • Decreased septation and alveolar hypoplasia leading to fewer and larger alveoli, so less surface area for gas exchange • Dysregulation of vascular development leading to abnormal distribution of alveolar capillaries and thickened muscular layer of pulmonary arterioles
Pathogenesis • Chorioamnionitis – caused by an ascending infection, as possible cause • But histologic chorioamnionitisto be protective ( same umbilical vasculitis) – potential role of transcription factor nuclear factor kB and inflammation • Ureaplasma colonization • Bacterial sepsis
Pathogenesis • Hemodynamic significantly PDA and surgery ligation • Mechanical ventilation (volutrauma and barotrauma) • Oxygen toxicity • High volume of fluids intake n the first few days after birth • Lower serum cortisol level (in VLBW) – early adrenal insufficiency
Outcomes • Higher rate recurrent hospitalization in the first year after birth • Lung disease in adulthood: airway obstruction, reactive airways, emphysema • Affect growth • Cardiovascular sequelae: pulmonary artery hypertension, corpulmonale, systemic hypertension • Poor neurodevelopmental outcomes: language delay, increased fine and gross motor impairment
Prevention and therapy • Antenatal: • corticosteroids administration • standard of care – 24 – 34 weeks • effect on the incidence of BPD controversial • in animals studies – arrest alveolarization and microvascular development
Prevention and therapy • Postnatal: • postnatal corticosteroids therapy • decreased time to extubation • early use – poor neurodevelopmental outcomes (CP) • adverse effects: hyperglycemia, hypertension, GI bleeding, hypertrophic cardiomyopathy, infection
Prevention and therapy • Azithromycin • macrolides antibiotic • anti-inflammatory effect • active against Ureaplasma infection • in a RCT no statistic significance (for 6 weeks of therapy)
Prevention and therapy • Vitamin A: • regulation of lung development • injury repair • low level – increased risk to BPD • Vitamin E and Selenium: • study result have been mixed • selenium works synergistically with Vit E to prevent peroxide formation – not show to reduce risk to BPD
Prevention and therapy • Caffeine: • significant reduce in BPD • Pentoxiphilline: • non specific phosphodiesterase inhibitor • decreased pulmonary inflammation • Cromolyn: • mast cell stabilizer • non protective effect