Pulmonary diseases in the newborn periodOla Didrik SaugstadDepartment of PediatricsThe National Hospital, University of Oslo

Student lecture at 9 th Semester Medical Faculty, University of Oslo

Pulmonary diseases in the newborn period1/13 have breathing problems at birth (7.5%)1/6 with breathing problems have infectionsGA< 31 uker: 1/2 have infectionsBoys 9.3%, Girls 5.9 %Mortality 0.4% (5% < 36 weeks GA)

Pulmonary diseases in the newborn period - Incidense

2,9% (Sweden 1976-77)2,1% (UK 1983-84)

Pulmonary diseases in the newborn period % Sweden UKRDS 0,33 0,96Trans Tachypnoe 0,93 0,36Pneumonia 0,17 0,05Mekonium Asp 0,09 0,05Total 2,9 2,1

Pulmonary diseases in the newborn periodSymptoms and signsTachypne (frequency > 60 per min)Cyanosis in room airFlare of the nostrilsChest retractionsGrunting

Pulmonary diseases in the newborn period Respiratory Distress Syndrome(RDS)Transitoric TachypnoePneumonia/InfectionMeconium AspirationAir LeaksPulmonary hypertensionChronic Lung Disease (CLD)

Pulmonary diseases in the newborn period Pulmonary causesCommon RareRDS Lung hypoplasiaTrans tachypne Obstr upper airwaysMeconium asp TumoursPneumonia Pulm hemorrhagePneumothorax Malformations Cong diaprhagmatic hernia

Pulmonary diseases in the newborn period Extra-pulmonale causesCommon RarePersist Fetal Circulat Cerebral edemaCong Card Malfor DrugsCerebral Hemorrhage Neuromuscular Polycythemia Asph, spinal cord Hypoglycemia Metabolic DiseasesHypothermiaAcidosis

Pulmonary diseases in the newborn period Work - UpExtra- pulmonary or pulmonary?If General condition is good and no cyanosis: Observe in incubator, ctr respiration and pulse frequencyIf Cyanosis: Observe in incubator, give O2, X ray of chestUmbilical/periperhal artery line if FiO2 > 0,40Infection work-up(R --> L Shunt calculation)

Pulmonary diseases in the newborn period Respiratory Distress Syndrome (RDS)Surfactant deficiency and immature surfactantLunge compliance reduced to 10-20% Reduced lung perfusion (50-60%)Increased R-> L shunting (30-60%)Reduced lungvolumIncreased work of breathing

Properties of surfactantRapid adsorptionEfficient spreadingLower surface tension

Alveoli as bubbles

Surface tensionAir

liquid

SURFACEPolar H2O molecules attract

Laplaces law where:P = pressureT = surface tensionR = radius of the bubbleP = 2t

r

P = 2x1= 0.2

10

P = 2x1= 0.4

5

10

5

Connected bubbles

PhospholipidsPolar headsInsoluble tailsNegative tails

Monolayer HypophaseSurfactant actionAlveolar gas

Composition1234567DPPC - dipalmitoylphosphatidylcholine 50%* Reduces alveolar surface tension PG - phosphatidylglycerol 7%* Promotes the spreading ofsurfactant throughout the lungsApoproteins or surfactantspecific proteins 2%*1. Serum proteins 8%*2. Other lipids 5%*3. Other phospholipids 3%*4. Phosphatidylinositol 2%*5. Sphingomyelin 2%*6. Phosphatidylethanolamine 4%*7. UnsaturatedPhosphatidylcholine 17%*

* By molecular weight

DPPCDipalmitoyl phosphatidylcholineWater solubleInsoluble fatty acid chains

Surfactant proteinsSpA Host defence, tubular myelin

SpD Immune activity

SpB & SpC Spreading and adsorption

Stimulus for releaseGas entering lungsAlveolar stretch (inspiration)Adrenergic innervationProstaglandins

Production and releaseType ll cellAlveolar air spaceHypophaseType I cellBasal laminaCapillaryendotheliumMonolayer HypophaseAlveolar gas LMVBGolgiRERDMVBType I cellTubular myelinLamellar bodies

Surfactant cycleTYPE II CELLLoss from lungsCholine fatty acidsLysosomesMVBDegradationEndoplasmic reticulumGolgiSynthesis and secretionLamellar bodiesRecyclingPrecursorsReuptakeCatabolicAnabolicAlveolar transformationsALVEOLUSOther losses- Macrophages- Airways- Other lung cells

Surfactant therapyInstillation of surfactant into the lungs

Synthetic surfactant ( almost not in use anymore)

Natural Surfactant (porcine, bovine)

Prophylactic vs Rescue

Before Surfactant 1 hr after Surfactant

Survival without, with one, and multiple doses of surfactantSurvivalWithout 1 dose multiple doses of surfactant

Median duration > 40% OxygenWithout one dose multiple doses Surfactantdays

Pulmonary diseases in the newborn period Respiratory Distress Syndrome0.5 (-1.0) % of all birthsIncreases with decreasing gestational age (GA < 28 weeks 60%)Most important neonatal morbidity and mortality factor

Pulmonary diseases in the newborn period Respiratory Distress Syndrome Symptoms and SignsTachypnoe > 60 breaths per minExpiratory gruntingRetractions (sternal, inter- and subcostal)Cyanosis in room airDuration > 24 hrs

Pulmonary diseases in the newborn period The natural course of Respiratory Distress Syndrome: Maximum after 24 -36 hrsSpontaneous breathing in room air in uncomplicated casesDeterioration at 3-5 days due to an open ductus arteriosus

Pulmonary diseases in the newborn period Respiratory distress syndrome differentialsPneumonia/sepsisTransitoric tachypnoeCongenital cardiac malformationPneumothorax/airleakPrimary pulmonary hypertension

Pulmonary diseases in the newborn period Respiratory Distress Syndrome - TherapyReduce prematurity rateAntenatal steroids 24 - 168 hrs before birth gives a 50% reduction in the incidens and 40% reduction in mortalitySurfactant therapy reduces mortality/Chronic lung disease 30-40%General therapy: Oxygen, respirator, fluid- electrolytes, nutrition, antibiotics

Pulmonary diseases in the newborn period Classification of neonatal pneumoniaeCongenitalEarly onset(< 48 hrs)Late onset (> 48 hrs)

Pulmonary diseases in the newborn period PneumoniaNeonatal pneumonia may be an isolated focal infection but usually is a part of a general infection - sepsis.Incidence of bacterial pneumonia:3,7 per 1000 live born (Oxford)

Neonatal pneumoniaAcquired by the fetus (ascending, transplacental passage, PPROM, through intact membranes?Gr B Streptococci (sepsis develops in 1% of colonized from maternal genital tract (1-4/1000 (USA).Intrapartum antibiotics as prophylaxis of group B pos mothers recommended AAP 1992-1997 . Incidence more than halved from 93-98

Pulmonary diseases in the newborn period Pneumonia - symptomsRespiratory distress (tachypnoe, apnoe, cyanosis, retractions)Vomiting, hypotensionPoor weigth gain, icterus, hypo/hyperthermiaPulmonary hypertensjon and hypoxemia R-->L shuntingReduced lungfunction (respirator patients)Increased tracheal aspirate

Pulmonary diseases in the newborn period Congenital pneumoniaRare - high mortalitySecondary to ascending infections (after PROM) through intact membranes? ChorioamnionitisIntrauterine asfyxia

Pulmonary diseases in the newborn period Early onset pneumonia1,8 per 1000 live newbornGr B streptococci (70% in UK)H. InfluenzaS. PneumoniaeListeria MonocytogenesGram negative enterobakterier(Fungi)Virus ( RS, Adeno, CMV, Coxsacki)

Pulmonary diseases in the newborn period Late onset pneumoniaUsual in preterm on artificial ventilation10-35% of all on ventilator

Gram positive Gram negativeStaph areus EnterobakterEnterocokker E. ColiGr B streptokokker Klebsiella FungiCandida

Pulmonary diseases in the newborn period Pneumonia -other agentsUreaplasma urealyticum (in vagina, -> pneumonia and lung fibrosis)RS virus (epidemics), more serious if chronic lung diseaseChlamydia (early onset - may cross intact membranes). In term infants typical debut 3-4 weeks of age. Slow onset. Treated with erythromycin

Pulmonary diseases in the newborn period Pneumonia - TherapyAntibioticsGeneral supportive therapy

Pulmonary diseases in the newborn period Transitoric tachypn (wet lung)A mild respiratory disturbancy in newborn infants occasionally seen after birthUnknown etiology increased lung waterDuration max 5-6 days

Pulmonary diseases in the newborn period Transitoric tachypnoeboys > girlsGA 32-42 weeks (average 38 weeks)BW (average) 3200 grResp rate at 6 hrs age: 80 per minOxygen in 60% of casesIncidens 0.37%Atle Moen Student thesis Oslo 1990

Pulmonary diseases in the newborn period Transitoric tachypnoeClinic Differential diagnosisTachypnoe RDSCyanosis in room air PneumoniaGrunting Mekonium aspirationRetractions Cong Heart malformationDuration > 3 hrsOxygen need not increasing

Pulmonary diseases in the newborn period Transitory tachypnoea - X ray findingsX ray: perihilar streaking, patchy infiltrates Reduced air and/or reticular pattern

TherapyObservation in incubatorOxygen if neededAntibiotics until infection is excluded

Pulmonary diseases in the newborn period Air leaksPneumothorax/mediastinum1% of all newborn but only 1/10 are symptomaticIncreased risk in positive pressure ventilation

Pulmonary diseases in the newborn period Primary pulmonary hypertension

Severe hypoxemiaR-L shuntingNormal heartArtificial ventilation NO inhalation

Pulmonary diseases in the newborn period Meconium Aspiration Syndrome (MAS)1:10 - 1:5 meconium stained amniotic fluid1:1000 - 1:5000 birth develop MASTerm-post term childrenInhalation before and during birthPlugging the airways (acute effects)Inflammation (later effects)Inactivates surfactant

Pulmonary diseases in the newborn period Symptoms in Meconium Aspiration Syndrom (MAS)Respiratory distressInfectionPulmonary hypertensionPulmonary failure and hypoxia/HIE

Pulmonary diseases in the newborn period Chronic Lung Disease (Bronchopulmonary Dysplasia)Preterm with RDS and artificial ventilation develop lung fibrosis and increased oxygen demand Typical chest X-ray (round woolen densities (fibrosis, emphysema, atelectasis), enlarged heart The incidence has not changed after surfactant therapy was introduced but the course is milder. More immature infants survive but have to pay the prize with CLD

Pulmonary diseases in the newborn period Chronic Lung DiseaseInitially the child is better of its acute lung disease but then gradually needs more oxygen. Some are oxygen- and respirator dependent for months (years).1/5 of children with RDS develop CLDEtiologyInflammation (also prenatally)Oxygen toxicity /Free oxygen radicalsBarotrauma- VolutraumaChorioamnionitis reduces RDS but increases CLD(The Watterberg paradox)

Pulmonary dseases in then newborn period