DOI:10.1542/pir.31-12-487 2010;31;487-496Pediatr. Rev.Jamie B. Warren and JoDee M. Anderson Newborn Respiratory Disordershttp://pedsinreview.aappublications.org/cgi/content/full/31/12/487located on the World Wide Web at: The online version of this article, along with updated information and services, isPediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347. Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2010 by the American Academy of published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1979. Pediatrics in Review is owned, Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from Newborn Respiratory DisordersJamie B. Warren, MD,*JoDee M. Anderson, MD,MEd*Author DisclosureDrs Warren andAnderson havedisclosed no nancialrelationships relevantto this article. Thiscommentary does notcontain a discussionof an unapproved/investigative use of acommercial product/device.Objectives After completing this article, readers should be able to:1. Evaluate and diagnose the most common causes of respiratory distress in the newbornperiod.2. Differentiate between the normal results of a newborn chest radiograph and theradiographic patterns that reect neonatal respiratory distress syndrome, meconiumaspiration syndrome, retained fetal lung liquid syndrome, and neonatal pneumonia.3. Recognize subglottic stenosis as a complication of endotracheal intubation.4. Distinguish between pulmonary disease and cyanotic congenital heart disease as acause of hypoxemia and acidosis in the neonate.5. Discuss common complications of various respiratory disorders (such as meconium as-piration syndrome) and the untoward effects of specic therapies (intubation and me-chanical ventilation).6. Describe how chronic lung disease may result from meconium aspiration.IntroductionNeonatal respiratory disorders account for most admissions to intensive care units in theimmediate newborn period. Newborns in respiratory distress must be evaluated promptlyand accurately; occasionally, neonatal respiratory distress is life-threatening and requiresimmediate intervention. The causes of respiratory distress in the newborn are numerousandareduetopulmonaryornonpulmonaryprocesses. (1)Initial stabilizationof theneonate, through management of the airway, breathing, and circulation, takes precedenceover determiningthe cause. Athoroughinitial assessment, includingmaternal andneonatal history, physical examination, and appropriate use of diagnostic tests, is essentialto diagnosing the cause of respiratory distress.DenitionRespiratory distress in the neonate most commonly presents asone or all of the following physical signs: tachypnea, grunting,nasal aring, retractions, and cyanosis. (2) Anormal respiratoryrate in a newborn is between 30 and 60 breaths/min; tachy-pnea is classied as respiratory rates greater than 60 breaths/min. Patients born with surfactant deciency and poorly com-pliant lungs have rapid, shallowbreathing. Infants experiencingincreased airway resistance, such as those who have subglotticstenosis, usuallyexhibitslowerdeepbreathing(hyperpnea).Isolated tachypnea may be seen in congenital heart disease, butwhen accompanied by other signs of respiratory distress, tachy-pnea must be evaluated carefully to discern pulmonary fromcardiacandmetaboliccauses. Grunting, asoundmadeonexpiration against a partially closed glottis, produces elevatedtranspulmonary pressures and facilitates maintenance of func-tional residual capacity by stinting of the alveoli in a mannersimilartoappliedcontinuousdistendingpressure. Gruntingoften is seen in disease states in which the alveoli are prone tocollapse, such as surfactant deciency. Nasal aring results in a*Oregon Health & Science University, Portland, Ore.AbbreviationsABG: arterial blood gasBPD: bronchopulmonary dysplasiaCBC: complete blood countCLD: chronic lung diseaseCPAP: continuous positive airway pressureECMO: extracorporeal membrane oxygenationFiO2: fraction of inspired oxygenGBS: group B StreptococcusiNO: inhaled nitric oxideMAS: meconium aspiration syndromeNRP: Neonatal Resuscitation ProgramPaCO2: partial pressure of arterial carbon dioxidePaO2: partial pressure of arterial oxygenRDS: respiratory distress syndromeRFLLS: retained fetal lung liquid syndromeArticle fetus and newbornPediatrics in Review Vol.31 No.12 December 2010 487. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from marked reduction in nasal resistance, which can reducetotal lung resistance and decrease the work of breathing.Retractions indicate a disturbance in lung and chestwall mechanics and are commonly observed in the inter-costal, subcostal, and suprasternal muscles. Retractionsbecome more apparent as the lung becomes less compli-ant,suchasinsurfactantdeciency.Severeretractionsalso can indicate airway obstruction.Finally, cyanosis may be an advanced sign of respira-tory distress. (3) Central cyanosis is dened as cyanosis ofthemucousmembranesandismoreconcerningthanacrocyanosis, which can be a normal nding in a newlyborn infant. (3) Central cyanosis becomes clinically ap-parentwhenatleast5g/100mLofhemoglobinbe-comesunsaturated. (3)Clinical detectiondependsonthe amount of desaturated hemoglobin present; in pa-tients who have anemia or those who have largeramounts of fetal hemoglobin, cyanosis may not be de-tectable until the partial pressure of arterial oxygen(PaO2) is very low. (4)AssessmentConsidering the complex series of cardiopulmonarychangesthatmustoccurforsuccessful transitionfromintrauterine to extrauterine life, it is not surprising thatnewborns frequently present withrespiratory distresssoonafterbirth. Approximately10%ofbabiesrequirerespiratory assistance immediately after delivery. Up to1% require intensive resuscitation, which underlines theimportance of having a person certied in the NeonatalResuscitation Program (NRP) available for all deliveriesand resuscitation equipment available in all deliveryrooms. (2) Because there may be little time to gather thenecessary history before stabilizing an infant in distress,initial assessment begins with a physical examination andassessment to identify any life-threatening conditions. Inthe immediate period following delivery, respiratory dis-tress often is a consequence of the laboring process andresultant neonatal acidemia. Per NRP guidelines, effec-tive ventilation with positive-pressure ventilation is indi-catedfor all newborns whoshowevidenceof apnea,gasping, ineffective respiratory effort, or heart rate of lessthan 100 beats/min. After stabilization per NRP guide-lines, a number of diagnostic studies can be helpful indetermining the cause of respiratory distress.Initial diagnostic studies, especially a chest radiograph,should be ordered in newborns presenting with respiratorydistress. Other helpful laboratorystudies includeserumglucoseassessment,arterialbloodgas(ABG)concentra-tions, complete blood count (CBC) with differential count,and blood culture. (3) After stabilization or assurance thatthe infant is stable from a respiratory standpoint, and onceinitial diagnosticstudieshavebeenordered, athoroughhistory, both maternal and neonatal, should be taken.Maternal history of medical disorders can be helpful indiagnosing the cause of neonatal respiratory distress. Forexample, a mother who has poorly controlled diabetes mayhave an infant susceptible to hypoglycemia, polycythemia,or relative surfactant deciency, all of which can be respon-sibleforneonatalrespiratorydistress.Thehistoryofthepregnancy also can be important. The estimated date ofconnement can allowapproximation of the infants gesta-tional age. A history of polyhydramnios can be concerningfortracheoesophageal stula; oligohydramnioscanbeasignofhypoplasticlungs.(3)Otherhelpfulstudiesper-formed during pregnancy include the triple screen (mater-nal alpha-fetoprotein, human chorionic gonadotropin, andestriol), whoseresultscanhelpassesstheoccurrenceofgenetic and developmental defects; prenatal ultrasonogra-phy; and a biophysical prole (measurement of fetal heartrate, muscle tone, movement, breathing, and amniotic uidindex). (2)Informationfromfetal monitoringduringlaboranddelivery as well as the presence of complications such asplacenta previa or abruption, which can result in fetal ane-mia or hypovolemia, may indicate the underlying cause ofrespiratory distress. (3) Meconium in the amniotic uid ortrauma sustained during the birthing process may lead torespiratory distress. (3) The need for resuscitation in theimmediate neonatal periodandthe circumstances sur-rounding the resuscitation also may provide clues to thediagnosis.Finally, the history of the presentation can yield clues.For example, aninfant whohas initial respiratorydis-tressthat graduallyimproveswithminimal interventionlikely is suffering from retained fetal lung liquid syndrome(RFLLS). If theinfant deterioratesgradually, themorelikelydiagnoses includepneumonia, respiratorydistresssyndrome (RDS), and sepsis. (2)Repeated thorough physical examinations of the infantshould follow stabilization and assessment. Vital signs arenecessary in any objective examination and should be as-sessed frequently. (3) Temperature instability can be a signof infection, and tachycardia may be a sign of hypovolemia.(3) It also is important simply to inspect the infant. Many ofthe signs of respiratory distress are seen rather than heard,includingnasal aring, retractions, andcyanosis. Ascaphoidabdomen may be a sign of congenital diaphragmatic hernia.(2) Asymmetric chest movement might be a visual sign oftensionpneumothorax.(3)Finally,theexaminershouldlisten to the infant. Asymmetric breath sounds can be diag-nosticof tensionpneumothorax. Stridor, anexpiratoryfetus and newborn newborn respiratory disorders488Pediatrics in Review Vol.31 No.12 December 2010. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from sound heard with upper airway obstruction, may representsubglottic stenosis in the previously intubated infant. (2)Assembling the information from the history, physical ex-amination, and diagnostic studies should narrowthe differ-ential diagnosis considerably.Differential DiagnosisThe differential diagnosis of respiratory distress in the new-bornincludesbothpulmonaryandnonpulmonarypro-cesses (Table 1). Common pulmonary causes includeRFLLS, RDS, meconiumaspiration syndrome (MAS), andpneumonia. (1) Nonpulmonary causes include cardiac dis-ease, infection, metabolic disorders, central nervous systemdisorders, and several other miscellaneous disorders. (1)Cardiac Disease Presenting asNewborn Respiratory DistressCyanotic congenital heart disease is a concerning non-pulmonary cause of respiratory distress that deservespromptrecognition.Heartdiseasecommonlypresentswithcentral cyanosis, buttheinfantalsomaypresentwithsigns of heart failure. (2) Very fewvarieties ofcongenital heart disease present immediately after birth;often, they present several hours to days after delivery asthe ductus arteriosus closes. The following ve forms ofcongenital heart disease result in early respiratory distresson separation from the placental circulation: hypoplasticleft heart syndrome with intact atrial septum, transposi-tion of the great arteries with an intact ventricular septumandrestrictiveatrial septum, Ebsteinanomalyof thetricuspidvalve,tetralogyofFallotwithsignicantpul-monary stenosis or atresia, and obstructed total anoma-lous pulmonary venous return. It can be extremely dif-cult to differentiate between pulmonary disease andcardiac disease in a newborn who has respiratory distress,and it is important to remember that the two can coexist.(2) A cardiovascular examination revealing a hyperactiveprecordial impulse, gallop rhythm, poor capillary rell,weakpulses, decreasedordelayedpulsesinthelowerextremities, or single second heart sound without split-ting is more consistent with congenital heart disease. (2)The absence of a murmur does not distinguish betweencardiac and pulmonary disease because murmurs are notpresent in many forms of congenital heart diseases. (5)The denitive diagnostic test to rule in or out congen-ital heart disease is echocardiography, but this technol-ogy may not be readily available in all centers at all times.(5) It is important for the practitioner to use other toolsto aid in diagnosis. A chest radiograph of the infant bornwith congenital heart disease may demonstrate abnormalpulmonary vasculature and a heart that is either enlargedTable 1. Differential Diagnosis ofRespiratory Distress in theNewborn(2)(3)Upper Airway ObstructionChoanal atresia, nasal stenosis, Pierre Robin syndrome,laryngeal stenosis or atresia, hemangioma, vocal cordparalysis, vascular rings, tracheobronchial stenosis,masses, cleft palate, nasal stufnessPulmonary DiseasesRespiratory distress syndrome*, retained fetal lungliquid syndrome*, aspiration (including meconiumaspiration syndrome)*, pneumonia*, pneumothorax,pneumomediastinum, primary pulmonaryhypertension, tracheoesophageal stula, pulmonaryhemorrhage, pulmonary hypoplasia, pulmonaryagenesis, cystic disease, pleural effusion, chylothorax,neoplasm, bronchopulmonary sequestration,pulmonary arteriovenous malformation, pulmonaryinterstitial emphysema, pulmonary edema, congenitalalveolar proteinosis, congenital lobar emphysemaCardiac DiseasesCyanotic congenital heart disease*, acyanotic congenitalheart disease*, arrhythmia, increased intravascularvolume, high-output cardiac failure,pneumopericardium, cardiomyopathyThoracic ConditionsChest wall deformity, massMetabolic DisordersHypoglycemia*, infant of a diabetic mother, inbornerrors of metabolism, hypermagnesemiaDiaphragmatic ConditionsHernia, paralysisNeuromuscular DiseasesCentral nervous system damage (birth trauma,hemorrhage), medication (maternal sedation, narcoticwithdrawal), muscular disease (myasthenia gravis),intraventricular hemorrhage, meningitis, hypoxic-ischemic encephalopathy, seizure disorder, obstructedhydrocephalus, infantile botulism, spinal cord injuryInfectious ConditionsSepsis*, pneumonia (especially group B Streptococcus)*Hemolytic/Vascular ConditionsAnemia, polycythemia, abnormal hemoglobinMiscellaneousAsphyxia, acidosis*, hypo/hyperthermia, hypo/hypernatremia*Common causes of respiratory distress in the newbornfetus and newborn newborn respiratory disordersPediatrics in Review Vol.31 No.12 December 2010 489. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from or abnormally shaped. (3) ABGs of the newborn who hascongenital heart disease typically reveal a normal partialpressureof arterial carbondioxide(PaCO2)andade-creased PaO2, and lung disease shows an increased PaCO2and a decreased PaO2. (3) Metabolic acidosis also may bepresentinresponsetolowcardiacoutputandismorecommon in heart disease than in pulmonary disease. (2)Pulseoximetrycanbeusedtoattempttodifferentiatebetween cardiac and lung disease. If oxygen saturationsare less than 85% in room air and remain less than 85% in100%fractionof inspiredoxygen(FiO2), most likelythere is an intracardiac shunt. (1) If saturations increaseto more than 85% in 100% FiO2, a hyperoxia test shouldbe performed to aid in the diagnosis. (1) In the hyperoxiatest, abaselineright radial arteryABG(preductal) isobtained while the newborn is breathing room air and asecond ABG is obtained from the same artery after theinfant has been breathing 100% FiO2. A PaO2 of greaterthan 300 mm Hg is a normal result, a PaO2 of greaterthan150mmHglikelyrepresentspulmonarydisease,and a PaO2 between 50 and 150 mm Hg represents car-diac disease or severe pulmonary hypertension. (1) Stepsto help differentiate between cardiac disease and pulmo-nary disease are summarized in Table 2.Retained Fetal Lung Liquid SyndromeRFLLSgenerallyis believedtobetransient pulmonaryedema that results fromdelayedclearance of fetal lung uid.(2) At birth, the infant is presented with the challenge ofrapidly clearing uid that has lled the alveoli during gesta-tion. During pregnancy, the lung epithelium is predomi-nantlyasecretorymembrane; chloridepumps causeaninux of chloride and water from the interstitium into thealveolar space. (6) It is believed that uid begins to clear thealveolar spaces about 2 to 3 days before the onset of labor,whenthepulmonaryepitheliumbecomes anabsorbingmembrane. (2) At that time, sodiumbecomes the predom-inant iontransportedacross thepulmonaryepithelium,thereby reversing the direction of ion and water movementfromthe airspace to the interstitium. (7) Fluid in the inter-stitium subsequently is absorbed by the pulmonary lym-phatics and vasculature. (6) About 40% of the fetal lunguidisclearedbeforespontaneousvaginal delivery. Forsuccessful transition from intrauterine to extrauterine life,the rest of the uid must clear within hours after birth. (7)Disruption of uid clearance is implicated in the pathogen-esis of RFLLS. (7)RFLLS, initially described in 1966 by Avery and col-leagues, presents withtachypnea, grunting, andnasalaringimmediatelyafterbirth.(2)Itcanoccurinthetermorpreterminfant,affecting3.6to5.7per1,000term infants and up to 10 per 1,000 preterm infants. (6)Infantfactorsthatincreasetheriskof RFLLSincludemale sex, delivery by cesarean section, perinatal asphyxia,and umbilical cord prolapse. (1) Maternal complicationsTable 2. Differentiation of Cyanotic Heart Disease from Pulmonary Diseasein Respiratory Distress*Cyanotic Heart Disease (CHD) Pulmonary DiseaseHistory Previous sibling having CHD CHD diagnosed on prenatalultrasonography Cesarean section without labor Preterm birth Meconium-stained amniotic uid Maternal feverPhysical Examination Cyanosis Single second heart sound Gallop rhythm Weak lower extremity pulses Quiet tachypnea Cyanosis Split second heart sound Retractions Temperature instability Crackles (rales), rhonchiChest Radiograph Increased heart size Abnormal heart shape Abnormal pulmonary vasculature Normal heart size Abnormal pulmonary parenchymaArterial Blood Gases Normal or decreased PaCO2 Decreased PaO2 Increased PaCO2 Decreased PaO2Hyperoxia Test PaO2 50 to 150 mm Hg PaO2>150 mm HgEchocardiography Abnormal heart and vessels Normal heart and vesselsPaCO2partial pressure of arterial carbon dioxide, PaO2partial pressure of arterial oxygen*Adapted from Aly (2).fetus and newborn newborn respiratory disorders490Pediatrics in Review Vol.31 No.12 December 2010. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from that can increase risk include asthma, diabetes, and needfor analgesia or anesthesia during labor. (1)The denitive diagnosis of RFLLS is basedonresolutionof symptoms within 1 to 5 days after minimal therapeuticintervention. (6) Chest radiographs can support the diag-nosis andclassically are characterizedby prominent perihilarstreaking, increased interstitial markings, and uid in theinterlobar ssures (Fig. 1). (6) There may be a wet silhou-ette around the heart as well as signs of alveolar edema.(1)(2) Usually, there is diffuse involvement in the lungs,which can make RFLLS difcult to distinguish radiograph-ically from RDS, and a coarse interstitial pattern that mayresemble pulmonary edema or irregular opacications maycause RFLLS toappear as MAS or neonatal pneumonia. (1)Blood gas analysis in RFLLS reveals a respiratory acidosiswith mild-to-moderate hypoxemia. (2)Treatment of RFLLS is supportive. The disorder usu-ally responds to oxygen therapy, but maintaining appro-priate oxygen saturation may require continuous positiveairway pressure (CPAP). (2) CPAP can aid in increasingthe distending pressure of the alveoli and the absorptionof the extra lung uid. (2) Supplemental oxygen shouldbeadministeredtokeepoxygensaturationsinnormalranges; at times, high concentrations of oxygen are nec-essary. (6) Very rarely is mechanical ventilation necessary.(2) RFLLS usually is a benign and self-limited disease,and typically there are no long-term sequelae. (2)Respiratory Distress SyndromeRDS is caused by surfactant deciency and, therefore, isprimarily a disease of prematurity. (1) In fact, the risk ofRDS decreases with increasing gestational age, with at least60%of babies born at less than 28 weeks gestation, approx-imately 30%of babies born at less than 30 weeks gestation,and fewer than 5% of babies born at termdeveloping RDS.(8) Surfactant is a mixture of lipids and proteins pro-duced by type II pneumocytes in the lung epithelium. (9)The absence of surfactant in the liquid lm lining of thealveoli causesanincreaseinsurfacetensionandalveolarcollapse. (9) If not treated, such atelectasis leads to increasedwork of breathing, intrapulmonary shunting, ventilation-perfusion mismatch, hypoxia, and eventual respiratoryfailure. (10)In addition to prematurity, other factors that increasethe risk of RDS include male sex, maternal gestationaldiabetes, perinatal asphyxia, hypothermia, and multiplegestations. (11) Infants who develop RDS present withsigns of respiratory distress at the time of or soon afterbirth that worsen over time. (9)Along with the history and physical examination, a chestradiographisconsiderednecessaryfordiagnosingRDS.Diffuse microatelectasis is present on the chest lm, givingthe classic ground glass appearance of the lungs, (9) withresultant diminishedoverall lungvolume. Air broncho-grams,whichareair-lledbronchisuperimposedontherelatively airless parenchyma of the lung tissue, also are seencommonly on chest radiograph (Fig. 2). (9) ABGmeasure-Figure 1. Retained fetal lung liquid syndrome. Note theincreased interstitial markings and uid in the interlobarssure on the right (arrow).Figure 2. Respiratorydistress syndrome. Notethegroundglass appearance, which represents diffuse microatelectasis,and air bronchograms (arrows).fetus and newborn newborn respiratory disordersPediatrics in Review Vol.31 No.12 December 2010 491. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from ments demonstrate hypercarbia and hypoxia and eventu-ally, in the unsupported infant, metabolic acidosis. (9)Treatment of RDS begins antenatally with the adminis-trationof corticosteroidstowomenat riskforpretermdelivery before 34 weeks gestation, therapy that has con-stitutedstandardpractice since the 1994National Institutesof Health Consensus Conference. (12) Antenatal cortico-steroids decreasetheriskof RDSbyacceleratingfetallung maturation. (12) Postnatally, surfactant replacementtherapyhasbeenapprovedforusesince1990andpro-vides almost immediate improvement in oxygenation forsurfactant-decient infants. (8) Surfactant replacementtherapy continues to be an area of active research, includingthe use of natural versus synthetic surfactants, prophylacticversus selective administration, and single versus multipledoses.Mechanical ventilationoftenisnecessaryininfantsaffected by RDS; nasal CPAP also has been shown to beeffective in maintaining lung volumes in surfactant-decient lungs. Many centers now have begun to use astrategy of intubation and surfactant administration, fol-lowed by extubation and minimally invasive respiratorysupport (such as nasal CPAP), a regimen that has provento be safe and effective. (13)The major complications and long-term sequelae ofRDS are associated principally with the treatments.Bronchopulmonarydysplasia(BPD), characterizedbythe need for oxygen supplementation at 36 weeks cor-rected gestational age, likely results from high levels ofoxygen administration and mechanical ventilation. (14)Meconium Aspiration SyndromeMASisdenedasrespiratorydistressinaninfantbornthroughmeconium-stainedamnioticuidwhosesymp-tomscannototherwisebeexplained.(1)Amongalllivebirths, 13%are complicated by meconium-stained amnioticuid, and of these infants, 4%to 5%develop MAS. (1) Mostinfants affected by MAS are term or postterm because theynaturally pass meconiumbefore birth due to maturation ofthe gastrointestinal tract. (15) Afetus passing meconiuminutero usually is a sign of fetal stress and hypoxemia that ledto relaxation of the anal sphincter. (15)(16) Any factor thatresults in fetal stress can be a risk factor for passing meco-nium in utero, including maternal hypertension, maternaldiabetes, eclampsia, and many others. (15) Chronic fetalhypoxiaandacidosis canleadtogaspinginuteroandaspiration of meconium. (15) Evidence suggests thatchronic in utero meconiumaspiration is probably the causeof the most severe cases of MAS. (15)Severe MAS is associated with alterations in the pul-monary vasculature, including remodeling and thicken-ingof themuscularwalls. Thisprocessresultsinpul-monaryvascular hyperreactivity, vasoconstriction, andhypertension. Those more vigorous infants who aspiratemeconium through the nasopharynx at the time of birthare more likely to develop mild-to-moderate MAS. (15)Meconiumisdirectlytoxictothelungs. Meconiumconsists of water, desquamated cells from the gastrointes-tinal tract, skin, lanugo hair, vernix, bile salts, pancreaticenzymes, lipids, andmucopolysaccharides. (2) The bile saltsandpancreaticenzymes, alongwithsomeof theothercomponents, can cause a chemical pneumonitis, one aspectof MAS. (3) Meconium also inactivates surfactant by dis-placing it fromthe alveolar surface and inhibiting its surfacetension-loweringability. (15) Meconiumactivates the com-plement cascade, which leads to inammation and vaso-constriction of the pulmonary veins. (1) Finally, the thick,particulate meconium itself can cause partial-to-completeairway obstruction. (1)Infants who develop MAS typically present in the rst12hoursafterbirthwithvaryingdegreesof respiratorydistress. (15)Oninspection, manyaffectedinfantshavebarrel chests, and crackles (rales) and rhonchi often canbe heard on auscultation. (2) The chest radiograph of aninfant who has MAS varies with the severity of meconiumaspiration. (1) Typically, radiographs demonstrate areas ofpatchy atelectasis due to complete airway obstruction, withother areas of overination due to the air trapping seen withpartial obstruction and subsequent development of a one-way valve phenomenon (Fig. 3). (1) Widespread involve-ment of all lung elds is seen, and in the most severe cases,Figure3. Meconium aspiration syndrome. Note the areas ofpatchyatelectasiscombinedwiththeareasofoverinationdue to air trapping.fetus and newborn newborn respiratory disorders492Pediatrics in Review Vol.31 No.12 December 2010. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from there may be an almost total whiteout of the lungs, withonly large bronchi distinguishable. (1)Due to the extreme overination, secondary pulmo-nary air leaks on chest radiograph also are common. (15)Suchairleaksincludepneumothorax, seenin10%to20%of affectedinfants; pulmonaryinterstitial emphy-sema; andpneumomediastinum. (1)(2)Normalizationof chest radiographs after resolution of MAS may takedays to weeks. (15)Thetreatmentof MAShasevolvedovertheyears.Amnioinfusion, whichistheinfusionof isotonicuidinto the amniotic cavity via catheter before delivery, wasbelievedtobeareasonabletreatment formeconium-stainedamniotic uidat one time totry topreventaspirationof meconiuminthe birthingprocess. (1)However, subsequent randomized, controlled trialshavefoundthatamnioinfusionprovidesnosignicantbenet. (16) Similarly, suctioning of the mouth, nose,andnasopharynxafterdeliveryoftheheadandbeforedelivery of the shoulders previously was undertaken oneveryinfantbornthroughmeconium-stainedamnioticuid. (16) NRP guidelines now state that no interven-tion should be undertaken during delivery in the pres-ence of meconium-stained uid. If the infant is vigorous,as dened by strong respiratory effort, heart rate greaterthan 100 beats/min, and good muscle tone, bulb syringesuctioning of the mouth should be performed after de-livery, followedby standardNRPprocedures. If the infant isnot vigorous, the mouth and trachea should be suctionedbefore proceeding with NRP recommendations. (16)For thoseinfants whodevelopmoresevereMAS,transfer to a center capable of providing surfactant, in-haled nitric oxide (iNO), and extracorporeal membraneoxygenation(ECMO)isnecessary. Surfactantreplace-ment therapy has become more standardfor infantssuffering from MAS because surfactant inactivation is aknown result of acquiring intra-alveolar meconium. Ran-domized, controlled trials have shown a decreased needfor ECMO therapy and, perhaps, a lower rate of pneu-mothorax in infants treated with surfactant. (1)Approved for use by the United States Food and DrugAssociation in 2001, iNO has become a standard treat-ment for MAS. (1) Because meconium also causes vaso-constriction of the pulmonary vessels, iNO can amelio-rate the pulmonary hypertension that accompanies MASby its ability to vasodilate the pulmonary capillaries selec-tively. (15) Treatment withiNOresults ina betterventilation-perfusion match and decreases the need forECMO in infants who have MAS. (15)High-frequencyventilationstrategies havebecomepopularforuseininfantswhohaveMASbecausethismethod inicts less barotrauma to the lungs. (15) How-ever, no randomized, controlled trials have compared theuse of conventional ventilation to high-frequency venti-lation in this population. (15) Finally, ECMO is used ininfants who have MAS and who fail iNO therapy. Up to40% of infants who require iNO also need ECMO. (15)Of note, infants who have MAS and require ECMOtendto have survival rates of up to 93% to 100%. (15)A major condition associated with MAS is pulmonaryhypertension. The chemical pneumonitis and surfactantinactivation that result frommeconiuminjury lead to inad-equate ventilation after birth and impaired pulmonary tran-sition. (11) This situation, in combination with the releaseof pulmonary vasoconstrictors, leads to the pulmonary hy-pertension seen in MAS. (17) Treating infants who haveMAS often requires harsh ventilator therapy that can resultin chronic lung disease (CLD). However, improving oxy-genationshouldbeemphasizedbecausehypoxemiain-creases pulmonary vascular resistance that, in turn, worsenspulmonary hypertension. (17)PneumoniaPneumonia is the most common infection in the neonateand is a signicant cause of respiratory distress in newborns.(2) Pneumonia may develop in the antenatal, perinatal, orpostnatal period, and the cause varies according to whenthe infection develops. (1) Rubella, herpes simplex virus,cytomegalovirus, adenovirus, Toxoplasma gondii, varicella-zoster virus, and several other pathogens contracted in theintrauterineperiodcancausepneumonia.(1)Perinatallyacquired bacteria that cause pneumonia include group BStreptococcus (GBS), Escherichia coli, Klebsiella, and Chla-mydia trachomatis. (1) Pneumonia acquired in the post-Figure4. Neonatal pneumonia. Notetheright upper lobarconsolidation (arrow).fetus and newborn newborn respiratory disordersPediatrics in Review Vol.31 No.12 December 2010 493. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from natal period may be caused by respiratory viruses, gram-positive bacteria (groups A, B, andGstreptococci orStaphylococcus aureus), and gram-negative bacteria (Kleb-siella, Proteus, Pseudomonas aeruginosa, Serratiamarc-escens, and E coli). (1)Signsexhibitedbyinfantswhohavepneumoniain-clude any of the signs of respiratory distress, thus some-times makingpneumoniaverydifcult todistinguishfrom RFLLS, RDS, or MAS. (3) Signs typically presentin the rst several hours after birth unless the pneumoniaisacquiredpostnatally.(3)Othersignsandsymptomsmay include lethargy, poor feeding, jaundice, apnea, andtemperature instability. (2)If pneumonia is suspected, initial screening tests, includ-ing CBC with differential count and blood culture, shouldbe obtained before beginning antibiotic therapy. (3) Am-picillin and gentamicin are the antibiotics used most fre-quently in the neonatal period for treating infection. (18)Thechestradiographoftheinfantwhohaspneumoniavaries, depending on the cause. In utero infection typicallySummaryRespiratory distress presents with any or all of thefollowing ndings: tachypnea, grunting, nasalaring, retractions, and cyanosis.Respiratory distress can be pulmonary ornonpulmonary, stabilization is paramount, anddiagnosis is aided by history and physical examinationas well as diagnostic tests.Cyanotic congenital heart disease, an important causeof neonatal respiratory distress, must be recognizedpromptly.RFLLS probably is caused by a delay in the clearance offetal lung uid and is usually a benign, self-limitedillness.RDS occurs primarily in preterm infants as a resultof surfactant deciency; based on strong researchevidence, the use of antenatal corticosteroidsreduces the incidence of RDS (12) and use ofpostnatal surfactant is an effective treatment. (8)Severe MAS may require harsh ventilatory supportthat can result in CLD; strong research evidenceshows that surfactant administration (1) and iNOuse (15) both decrease the need for ECMO in infantswho have pulmonary hypertension related to MAS.Neonatal pneumonia can be acquired antenatally,perinatally, or postnatally, and causes vary,depending on the timing of disease acquisition.Table 3. Comparative Chest Radiograph Findings in Neonatal RespiratoryDistressRFLLS RDS MAS PneumoniaDiffuse parenchymal inltrates X X XAir bronchograms X XLobar consolidation XPatchy areas alternating with emphysema XPleural effusion XReticular granular pattern X XLoss of lung volume X XFluid accumulation in interlobar spaces XHyperination X XAtelectasis X XPneumothorax/Pneumomediastinum X X XMASmeconium aspiration syndrome, RDSrespiratory distress syndrome, RFLLSretained fetal lung liquid syndrome*Adapted from Flidel-Rimon & Shinwell, 2005.Table 4. When to Call aNeonatologist for RespiratoryDistress in an Infant Stabilization of the infant in respiratory distress ischallenging Heart disease is suspected and echocardiography ormedications (such as prostaglandins) are notavailable Need for respiratory support, supplemental oxygen, ormedications beyond what is available at the institution Concerns for evolving pulmonary hypertension,especially in an infant who has meconium aspirationsyndrome Concerns for evolving sepsis in an infant who haspneumonia Inability to ventilate Pulmonary hemorrhage Persistent or progressing pneumothoraxfetus and newborn newborn respiratory disorders494Pediatrics in Review Vol.31 No.12 December 2010. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from manifests as bilateral consolidation or whiteout. (2) Otherpneumonias can manifest as lobar consolidations on chestradiograph (Fig. 4). (2) GBS pneumonia is easy to confusewith other causes of respiratory distress when looking at thechest radiograph. For example, 50% of infants who haveGBS pneumonia have radiographic ndings indistinguish-able from those of RDS or RFLLS. (18) When present,pleural effusion or mild heart enlargement in the absence ofcardiac anomalies suggests the diagnosis of pneumonia. (1)Treatment of pneumonia focuses on supportive careof the infant and administration of antibiotic medicationsthat target the causative organism. (1) Oxygen therapy,mechanical ventilation, andvasopressoradministrationmay be necessary. (1) Oxygen should be used to maintainsaturations in the normal ranges for gestational age.Table 3 compares chest radiograph ndings inRFLLS, RDS, MAS, and pneumonia, and Table 4 listsrecommended reasons for consulting a neonatologist.References1. Flidel-Rimon O, Shinwell ES. Respiratory distress in the termand near-term infant. NeoReviews. 2005;6:e289e2972. Aly H. Respiratory disorders in the newborn: identication anddiagnosis. Pediatr Rev. 2004;25:2012083. Schreiner RL, Bradburn NC. Newborns with acute respiratorydistress: diagnosis and management. Pediatr Rev. 1988;9:2792854. LeesMH, KingDH. Cyanosisinthenewborn. PediatrRev.1987;9:36425. TingelstadJ. Consultationwiththespecialist: nonrespiratorycyanosis. Pediatr Rev. 1999;20:3503526. Guglani L, Lakshminrusimha S, Ryan RM. Transient tachypneaof the newborn. Pediatr Rev. 2008;29:e59e657. Jain L, Eaton DC. Physiology of fetal lung uid clearance andthe effect of labor. Semin Perinatol. 2006;30:34438. Stevens TP, Sinkin RA. Surfactant replacement therapy. Chest.2007;131:157715829. Kopelman AE, Mathew OP. Common respiratory disorders ofthe newborn. Pediatr Rev. 1995;16:20921710. Roberts D, Dalziel S. Antenatal corticosteroids for acceleratingfetal lung maturation for women at risk of preterm birth. CochraneDatabase Syst Rev. 2006;3:CD00445411. Fraser J, Walls M, McGuire W. ABC of preterm birth: respira-tory complications of preterm birth. Br Med J. 2004;329:96296512. Jobe AH. Prenatal corticosteroids: a neonatologists perspec-tive. NeoReviews. 2006;7:e259e26813. Stevens TP, Blennow M, Myers EH, Soll R. Early surfactantadministrationwithbrief ventilationvs. selectivesurfactant andcontinued mechanical ventilation for preterm infants with or at riskfor respiratory distress syndrome. Cochrane Database Syst Rev.2007;4:CD00306314. Jobe AH. The new BPD. NeoReviews. 2006;7:e531e54515. Walsh MC, Fanaroff JM. Meconium stained uid: approach tothe mother and the baby. Clin Perinatol. 2007;34:65366516. Escobedo M. Moving from experience to evidence: changes inUS Neonatal Resuscitation Programbased on International LiaisonCommittee on Resuscitation review. J Perinatol. 2008;28:S35S4017. SteinhornRH, FarrowKN. Pulmonaryhypertensionintheneonate. NeoReviews. 2007;8:e14e2118. TumbagaPF, PhilipAGS. Perinatal groupBstreptococcalinfections: past, present, and future. NeoReviews. 2003;4:e65e72fetus and newborn newborn respiratory disordersPediatrics in Review Vol.31 No.12 December 2010 495. Provided by Health Internetwork on December 10, 2010http://pedsinreview.aappublications.org Downloaded from PIR QuizQuiz also available online at http://pedsinreview.aappublications.org.1. A newborn male develops respiratory difculty 4 hours after birth. His estimated gestational age is30 weeks. Respirations are 65 breaths/min and shallow, heart rate is 130 beats/min, and blood pressure is60/30 mm Hg. He exhibits nasal aring, intercostal and subcostal retractions, and grunting. His nail bedsand lips appear dusky. A pulse oximetry reading shows an oxyhemoglobin saturation of 78% in room airand 92% in 60% oxygen hood. A chest radiograph shows a diffuse reticulogranular pattern, airbronchograms, and decreased lung volume. Which of the following is the most likely explanation for hisrespiratory distress?A. Decreased chest wall complianceB. Delayed clearance of amniotic uid.C. Increased airway resistance.D. Increased alveolar surface tension.E. Persistent pulmonary hypertension.2. A 12-hour-old girl appears cyanotic and is breathing rapidly. She was born after a term spontaneousvaginal delivery. Amniotic uid was stained with meconium. Physical examination reveals a respiratory rateof 66 breaths/min, heart rate of 130 beats/min, and blood pressure of 72/42 mm Hg. Mild intercostal andsubcostal retractions are noted. Pulses are equal in all extremities. Lips and nail beds are cyanotic. Chestauscultation reveals clear breath sounds, a single second heart sound, and no heart murmur. Chestradiograph shows clear lung elds. Pulse oximetry reveals an oxyhemoglobin saturation of 70% in room airand 75% in 100% FiO2. Which of the following is the most likely diagnosis?A. Hypoplastic left heart syndrome.B. Meconium aspiration syndrome.C. Persistent pulmonary hypertension of the newborn.D. Pulmonary atresia.E. Retained fetal lung liquid syndrome.3. A 1-hour-old boy develops rapid respirations. He was born after 39 weeks gestation and delivered byelective cesarean section. His mother had two other children delivered by cesarean sections forcephalopelvic disproportion. Apgar scores were 8 and 9 after 1 and 5 minutes, respectively. The infant isvigorous and responds appropriately to stimulation. The respiratory rate is 70 breaths/min, heart rate is120 beats/min, and blood pressure is 72/40 mm Hg. Pulses are equal in all extremities. Nasal aring,grunting, and intercostal retractions are noted. Chest auscultation reveals normal breath sounds and a splitsecond heart sound. Pulse oximetry monitoring shows an oxyhemoglobin saturation of 88% in room air and96% in 40% oxygen hood. Chest radiography shows prominent perihilar streaking and uid in theinterlobar ssures. Which of the following is the most appropriate management at this time?A. Continuation of current therapy and observation.B. Echocardiography evaluation.C. Hyperoxia test with radial artery blood gas determination.D. Intubation and inhaled nitric oxide therapy.E. Intubation and instillation of surfactant.4. You are called to attend the delivery of a term baby. The membranes ruptured 1 hour ago, and the amnioticuid is meconium-stained. The head is fully engaged. Which of the following is the most appropriatestrategy in managing this situation?A. If the infant remains vigorous after delivery, suction the mouth only with bulb syringe.B. Infuse isotonic saline in the amniotic cavity via a catheter before delivery.C. Recommend that cesarean section be performed immediately.D. Suction the mouth, nose, and nasopharynx as soon as the head is delivered.E. View the glottis and suction the trachea after delivery regardless of how the infant appears.fetus and newborn newborn respiratory disorders496Pediatrics in Review Vol.31 No.12 December 2010. 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