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Respiratory problems in premature infants
Dr. Rozin IlyaDepartment of Neonatology Kaplan Medical Center
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Respiratory problems
• Respiratory Distress Syndrome (RDS) or Hyaline Membrane Diseases (HMD)
• Broncho-Pulmonary Dysplasia (BPD)
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Respiratory Distress Syndrome
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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
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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%
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Epidemiology
• Overall incidence in 501-1500 grams: 42%
• 501-750 grams: 71%• 751-1000 grams: 54%• 1001-1250 grams: 36%• 1251-1500 grams: 22%
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Other risk factors for RDS
Increased Risk• 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)
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
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Phases of Lung Development
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Lung Development
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Surfactant
• Complex lipoprotein • Composed of 6
phospholipids and 4 apoproteins
• Surfactant contains• 70-80%
phospholipids, • 8-10% protein, and• 10% neutral lipids
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Surfactant Metabolism
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Surfactant Metabolism
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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
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Assessment of Fetal Lung Maturity
• Lecithin / sphingomyelin (L/S) ratio
• Lamellar body counts
• Phosphatidylglycerol• After 35 weeks gestation
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L/S Ratio
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Pathophysiology
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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
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Lung Compliance
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Hyaline Membranes
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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
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Clinical Manifestations
• Tachypnea• Nasal flaring• Grunting• Intercostal, sub xiphoid, and
subcostal retractions • Cyanosis • Apnea
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Differential Diagnosis
• TTN• MAS• Pneumonia• Cyanotic Congenital Heart Disease• Pneumomediastinum, pneumothorax• Hypoglycemia• Metabolic problems• Hematologic problems
• Anemia, polycythemia• Congenital anomalies of the lungs
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Diagnosis
• Onset of progressive respiratory failure shortly after birth
• Characteristic chest radiograph• Laboratory tests – rule out infection • Analysis of blood gas:
• Hypoxia• Hypercarbia
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Chest X Ray
“ground glass”
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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
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Treatment
• Surfactant Therapy• Assisted Ventilation Techniques and Oxygen
therapy (be careful) • Supportive Care
• Thermoregulation• Fluid Management• Nutrition• Antibiotic therapy• Gentle handling
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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
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Prognosis
• Chronic complications of respiratory distress syndrome :
• Broncho pulmonary dysplasia (BPD)
• Retinopathy of prematurity (ROP)
• Neurologic impairment
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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.
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Pathogenesis
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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
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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
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Definition
2000 ,National Institute of Child Health and Human Development (NICHD)
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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
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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
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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%
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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
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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
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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
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Pathogenesis
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Pathogenesis
• Chorioamnionitis – caused by an ascending infection, as possible cause
• But histologic chorioamnionitis to be protective ( same umbilical vasculitis) – potential role of transcription factor nuclear factor kB and inflammation
• Ureaplasma colonization • Bacterial sepsis
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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
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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, cor pulmonale, systemic hypertension
• Poor neurodevelopmental outcomes: language delay, increased fine and gross motor impairment
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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
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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
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Prevention and therapy
Azithromycin• macrolides antibiotic• anti-inflammatory effect • active against Ureaplasma infection• in a RCT no statistic significance (for
6 weeks of therapy)
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Prevention and therapy
Vitamin A:• regulation of lung development • injury repair • low level – increased risk to BPDVitamin 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
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Prevention and therapy
Caffeine: • significant reduce in BPDPentoxiphilline:• non specific phosphodiesterase inhibitor • decreased pulmonary inflammation Cromolyn:• mast cell stabilizer
• non protective effect
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Prevention and therapy
Nitric Oxide:• benefit on oxidative stress and lung
development – in animal studies• not support the use in routine careSurfactant:• not decreased incidence of BPD• improving respiratory care • prophylactic therapy is associated with
lower risk of BPD
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Prevention and therapy
Ventilatory strategies:• permissive hypercapnia (pH>7.20 and
pCO2 from 45 to 55 mmHg)• gentle ventilation ( SIMV, HFV, Volume-
targeted ventilation, NSIMV (NIPPV) or NCPAP)• INSURE used • adequate oxygenation – difficult
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Prevention and therapy
Nutrition:• excessive fluids intake – more risk
for BPD• if BPD – infant may need up to 20%-
40% more kilocalories
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Prevention and therapy
• Therapy of established BPD:
Inhaled steroids:• evidence supporting is mixt• RCT for early therapy – no support Diuretics:• for decreased pulmonary alveolar and interstitial edema• routine used loop diuretics not recommended• Thiazide + Spironolactone Bronchodilators:• most commonly β adrenergic agonist• short term improvement • for acute exacerbation care only
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Thank you