- Email: [email protected]
Respiratory Distress of the Term Newborn Infant
Paediatric Respiratory Reviews 14 (2013) 29–37
Contents lists available at SciVerse ScienceDirect
Paediatric Respiratory Reviews
CME article
Respiratory Distress of the Term Newborn Infant Martin O. Edwards, Sarah J. Kotecha, Sailesh Kotecha * Department of Child Health, School of Medicine, Cardiff University, Cardiff, United Kingdom
EDUCATIONAL AIMS The reader will be able to:
Recognise the importance of respiratory distress in term newborn infants. Discuss the differential diagnosis of respiratory distress in term newborn infants. Describe the more common causes of respiratory distress in term newborn infants. Initiate a management plan for the term newborn infant presenting with respiratory distress.
A R T I C L E I N F O
S U M M A R Y
Keywords: Respiratory distress syndrome Transient tachypnoea of the newborn Pneumonia Meconium aspiration syndrome Extracorporeal membrane oxygenation
Respiratory distress is recognised as any signs of breathing difficulties in neonates. In the early neonatal period respiratory distress is common, occurring in up to 7% of newborn infants, resulting in significant numbers of term-born infants being admitted to neonatal units. Many risk factors are involved; the increasing number of term infants delivered by elective caesarean section has also increased the incidence. Additionally the risk decreases with each advancing week of gestation. At 37 weeks, the chances are three times greater than at 39-40 weeks gestation. Multiple conditions can present with features of respiratory distress. Common causes in term newborn infants include transient tachypnoea of the newborn, respiratory distress syndrome, pneumonia, meconium aspiration syndrome, persistent pulmonary hypertension of the neonate and pneumothorax. Early recognition of respiratory distress and initiation of appropriate treatment is important to ensure optimal outcomes. This review will discuss these common causes of respiratory distress in term-born infants. ß 2012 Elsevier Ltd. All rights reserved.
INTRODUCTION Respiratory distress is common in the early neonatal period and occurs in up to 7% of newborn infants.1 Much of the focus has been on respiratory distress syndrome and chronic lung disease of prematurity in preterm infants (<37 weeks of gestation)2,3 but every year a significant number of term-born infants are admitted to neonatal units for management of their respiratory distress.4–6 Multiple conditions can cause respiratory distress in term newborn infants (Table 1). Conditions such as surfactant protein deficiency syndromes or alveolar capillary dysplasia are rare and the reader is referred to recent excellent reviews.7,8 In Switzerland, Ersch et al. reported an increasing incidence of respiratory distress of all neonates admitted to neonatal units
* Corresponding author. Department of Child Health, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XW, United Kingdom Tel.: +44 29 20 74 4187; fax: +44 29 20 74 4283. E-mail addresses: [email protected] (M.O. Edwards), [email protected] (S.J. Kotecha), [email protected] (S. Kotecha). 1526-0542/$ – see front matter ß 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2012.02.002
between 1974 and 2004 citing three possible explanations: an increase in extremely low birth weight infants, changes in admission policies and increasing numbers of infants delivered by caesarean section.9 The impact of elective caesarean sections has specifically increased the incidence of respiratory distress in term infants.10 This has been known for many years; in 1995 Morrison et al. estimated that 2,000 cases per year required neonatal admission for pulmonary diseases following caesarean section before onset of labour in the United Kingdom (UK).11 There were 706,248 live births in England and Wales in 2009 and approximately 94% of these were full term deliveries (37 weeks of gestation).12,13 Between 1990 and 2002, the admission rate to a busy neonatal unit in England was 8.6% of all live births.14 The commonest reason for admission was respiratory distress.6,9 There is a clear inverse relationship between gestational age and incidence of respiratory distress most notably by transient tachypnoea of the newborn (TTN) and respiratory distress syndrome (RDS).4,10 Gouyon et al. also noted that a major risk factor for severe respiratory distress in term infants was elective caesarean section at 37–38 weeks gestation but with meconium
30
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
Table 1 Differential diagnosis of respiratory distress in term-born infants. Less common conditions Pulmonary haemorrhage Pleural effusion (chylothorax) Neuromuscular disorders (e.g. congenital myotonic dystrophy) Metabolic acidosis (secondary to inborn error of metabolism) Congenital or surgical conditions Diaphragmatic hernia Tracheo-oesophageal fistula Choanal atresia Cystic congenital adenomatoid malformation (CCAM) Lobar emphysema Pulmonary sequestration Pulmonary hypoplasia Rare causes Surfactant protein deficiency syndromes Alveolar capillary dysplasia
Common conditions Transient tachypnoea of the newborn Respiratory distress syndrome Pneumonia Meconium aspiration syndrome Pneumothorax Primary or secondary pulmonary arterial hypertension Cardiac failure (due to congenital heart disease) Hypoxic-ischaemic encephalopathy Aspiration of milk or blood
stained liquor being most frequently noted at 39–41 weeks gestation.10 Thus, avoiding routine elective caesarean sections prior to 38 weeks of gestation would markedly decrease the incidence of respiratory problems in the term infant. ASSESSMENT Respiratory distress is recognised as any signs of breathing difficulties in the neonate (Figure 1). Useful questions to ask are shown in Figure 2. The initial assessment of any infant with respiratory distress should include blood tests (full blood count, Creactive protein, blood culture and blood gases), pulse oximetry and chest radiography. The initial treatment will aim to reverse the hypoxia, hypercapnia and acidosis that may have developed. TRANSIENT TACHYPNOEA OF THE NEWBORN TTN was first coined by Avery in 1966 and is now recognised as the commonest cause of respiratory distress in newborn term infants.15 It is caused by the delay in the absorption of fluid in the lungs after birth (i.e. excessive lung fluid).10 Thus, TTN is frequently seen in babies born following elective caesarean section. It usually presents with grunting and mild signs of respiratory distress, which persist for up to 48 hours and is generally a self-limiting disorder. However, some infants develop an oxygen requirement that necessitates admission to the neonatal unit for a few days accounting for approximately 10% of all newborn term admissions.16
Pathophysiology The lungs in utero are constantly secreting fluid to aid lung growth and development. However the rate of lung fluid production and volume of foetal lung lumen decreases before birth, most notably during labour.17 The mechanism for fluid absorption is triggered by neuroendocrine hormones, which cause lymphatic vessel dilatation. As the lung pulmonary circulation increases following the first breath, the fluid in the lungs is cleared thus interruption of this process of clearing fluid from the lungs may result in respiratory distress. Risk factors The main risk factor for TTN is delivery following elective caesarean section. The usual mechanisms to clear fluid, which occur after the onset of labour, are not activated after elective caesarean section thus there is often inadequate clearance of pulmonary fluid, which can result in TTN.18,19 Other risk factors include delivery prior to 38 weeks of gestation, male sex, low birth weight and macrosomia20,21 and maternal diseases such gestational diabetes and asthma.22–24 Prevention The Burgundy Perinatal Network has shown that the incidence of TTN requiring ventilation is significantly reduced for each extra week in utero decreasing from 34% at 37 weeks to 0.5% at 41 weeks gestation.10 A recent multicentre pragmatic randomised trial showed that administration of antenatal steroids prior to elective caesarean delivery at 37–39 weeks’ gestation reduces the incidence of TTN.25 As the long term effects are currently unknown, at present the best course is to avoid elective caesarean sections prior to 38 weeks wherever possible. Management
Figure 1. The common signs and symptoms of respiratory distress in term newborn infants.
It is important to establish the diagnosis by taking a thorough history and performing a physical examination. TTN commonly presents within the first few hours of life and is often managed conservatively i.e. a period of close observation on the postnatal ward or in the neonatal unit but must be weighed against other differential diagnoses (Table 1) including RDS and pneumonia which may progress rapidly in newborn infants. Chest radiographs often show ‘‘a wet silhouette’’ around the heart (Figure 3) with fluid in the horizontal fissures.26 Some infants may require oxygen therapy or other forms of respiratory support for several days to aid recovery. Antibiotics are often routinely used, as differentiation from an infective process is often difficult. Other forms of therapies
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
31
FAQ’s when assessing an infant with respiratory distress Is anything else causing the respiratory distress? Consider metabolic, renal, neurological causes.
Is it a cardiac or respiratory problem? Consider the need for Chest radiograph and Echocardiogram.
What is the gestaonal age of the baby? Preterms (<37weeks) are more likely to have RDS; Post term (>42 weeks) are more likely to have MAS; Late preterms and terms are more likely to have TTN.
Is it severe or mild respiratory distress? Severe distress more likely with RDS, MAS or PPHN. Mild distress more likely with TTN.
Are there any known congenital anomalies? Review antenatal scan reports for CDH, CCAM etc…
What was the delivery method? Pre-labour secon more likely to be TTN; Evidence of MSAF is more likely to be MAS.
Is there poor improvement with increasing oxygen flow? Persistent hypoxia and cyanosis despite 100% oxygen need to consider PPHN or CCHD.
Are there any risk factors for sepsis? PROM, GBS on HVS, maternal pyrexia or raised inflammatory markers in maternal bloods would suggest pneumonia.
Abbreviations: RDS - Respiratory Distress Syndrome; MAS - Meconium Aspiration Syndrome; TTN - Transient Tachypnoea of the Newborn; PPHN - Persistent Pulmonary Hypertension of the Neonate; CDH - Congenital Diaphragmatic Hernia; CCAM - Congenital Cystic Adenomatoid Malformation; MSAF - Meconium Stained Amniotic Fluid; CCHD - Congenital Cyanotic Heart Disease; GBS - Group B Streptococcus; HVS - High Vaginal Swab.
Figure 2. Useful questions to ask while assessing a term-born infant with respiratory distress.
such as diuretics have been tested but fail to change the course of TTN.27 Prognosis Infants who develop TTN generally recover fully and are nursed in air within a few days of delivery. However, TTN may be associated with development of asthma later in childhood, especially amongst males.28,29 Adams & Doull discuss the association of birth by caesarean section and asthma, and state that there is evidence for an association between these, but there is still no indication of causality.30 In a review of TTN, Yurdakok suggests a genetic link between TTN and later onset asthma.31 RESPIRATORY DISTRESS SYNDROME RDS is caused by a deficiency of surfactant and is often also called hyaline membrane disease, which strictly speaking is a
histological diagnosis.32 Newborn infants with RDS present during the first 4 to 6 hours of life. It is commonly seen in preterm infants; however, published data have shown that infants with a birth weight of >2500 g account for 9.9%20 to 11.5%9 of infants with RDS and those with gestational age of 37 weeks gestation account for 7.8%.20 The Near-Term Respiratory Failure Research Group, who studied 1011 infants (mean gestational age of 37 2 weeks gestation), who all required mechanical ventilation, identified 43% developed RDS.33 Pathophysiology It can be difficult to distinguish between RDS and TTN, especially in newborn term infants. It has been suggested that both these conditions are part of the same spectrum of respiratory disease occurring whilst adapting to postnatal life at birth.34 The production of surfactant by type 2 pneumocytes commences around 24–25 weeks gestation reaching adequate levels to support
32
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
Figure 4. Chest radiograph showing signs of RDS. The x-ray shows air bronchograms and reticulonodular shadowing throughout the lung fields (often termed ‘ground glass’ appearance).
Figure 3. Chest radiograph showing TTN. The x-ray shows ‘‘a wet silhouette’’ around the heart with fluid in the horizontal fissure.
breathing after birth by 36–37 weeks gestation.35 Therefore, when infants are born 36 weeks gestation, the relatively immature lungs are unable to produce sufficient surfactant to maintain adequate breathing. The lack of surfactant results in poorly compliant lungs due to widespread alveolar collapse.32 The infant will show signs of respiratory distress and in many cases will require respiratory support with oxygen or mechanical ventilation. Risk factors The risk of RDS increases inversely with decreasing gestational age thus the commonest at-risk group are preterm infants. Dani et al. demonstrated that gestational age, low birthweight, maternal age, elective and emergency caesarean section and male sex are all risk factors for RDS.20
shows air bronchograms (Figure 4) and reticulonodular shadowing throughout the lung fields (often termed ‘ground glass’ appearance). In many neonatal units there are well-established guidelines for the management of RDS in newborn infants, including the use of exogenous surfactant.40,41 Newborn infants quickly produce their own surfactant thus the respiratory distress often resolves in untreated infants after 72 – 96 hours of age. The management of infants with RDS is largely supportive until adequate surfactant synthesis occurs. The occasional unresponsive infant should be investigated further to exclude rare conditions such as alveolar capillary dysplasia and genetic abnormalities of the surfactant system.7,8 Prognosis Engle et al. have reviewed the literature on the outcome of infants given surfactant for RDS and conclude that ‘the risk of respiratory abnormalities later in infancy (recurrent wheezing, asthma, respiratory infection, pulmonary function test abnormalities) and early childhood remains high for preterm infants with respiratory distress syndrome’.42 The long term effects of respiratory disease in the newborn however require further study.43
Prevention PNEUMONIA The Consortium on Safe Labour in the United States of America (USA) recently reported that the risk of RDS decreases with each advancing week of gestation until 38 weeks, even at the relatively mature age of 37 weeks gestation, the chances of developing RDS were three-fold greater than at 39–40 weeks gestation.4 The use of antenatal corticosteroids to boost foetal lung surfactant and antioxidant enzyme production is now routine in threatened preterm labour between 24 and 34 weeks gestation and is sometimes considered at 35–36 weeks gestation.36,37 Reducing elective caesarean sections may help, although RDS secondary to caesarean section accounts for only a small number of the total incidence.38,39
A lower respiratory tract infection, particularly bacterial pneumonia can cause severe respiratory distress in the newborn infant. This can be acquired congenitally, through the birth passages especially after prolonged rupture of membranes or postnatally. Pneumonia in newborn infants is often difficult to diagnose and often difficult to distinguish from other causes of respiratory distress including RDS and TTN. Although many investigations including blood white cell counts, blood cultures, C-reactive protein, etc. are performed, they lack the necessary sensitivity and specificity to accurately diagnose pneumonia. Pathophysiology
Management The initial management will follow the standard approach of obtaining a history and examination. The need for respiratory support will need to be assessed from clinical observations, chest radiographs and blood gas results. The chest radiograph in RDS
Pneumonia may be acquired due to ascending infection especially when chorioamnionitis is present or postnatally from nosocomial acquired infections.44 The most likely cause for the former is inhalation of infected amniotic fluid and crosscontamination for the latter, which can be prevented by strict
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
anti-septic measures including hand-washing. Common pathogens include bacteria, such as group B Streptococci (GBS), Streptococcus pneumonia, Staphylococcus aureus, Listeria and gram-negative enteric rods (e.g. E.Coli); and viruses, such as Herpes simplex virus, Respiratory syncytial virus and Influenza A & B viruses; atypical organisms such as chlamydia; and fungi such as Candida albicans. Risk factors The main risk factors for congenital pneumonia are prolonged rupture of membranes (PROM), prematurity and maternal infection (maternal fever or raised white cell count), particularly with GBS.44 Birth weight and age of onset are both strongly associated with the mortality risk from pneumonia.45 Pneumonia can occur secondary to invasive mechanical ventilation but is largely confined to preterm infants who receive prolonged ventilation.46 Prevention The most important and easiest method of preventing nosocomial pneumonia is hand washing to prevent cross-infection between vulnerable infants.47,48 Other methods of prevention include following local guidelines for the management of premature rupture of membranes49 and encouraging early and exclusive breast feeding.50,51 Screening for Group B Streptococcus (GBS) In the U.S.A, it is mandatory to screen all pregnant women in the third trimester for GBS and to treat those with vaginal GBS colonisation with intrapartum antibiotics, at least four hours prior to delivery.52 Universal screening and antepartum treatment can reduce the rate of early-onset disease by 89%.53,54 In the UK and other countries, however, screening is more targeted but those at risk are treated with intrapartum antibiotics.55 Management Pneumonia may present early or late. A thorough history and examination may help establish a suspected diagnosis. A chest radiograph may show bilateral patchy shadowing with or without pleural effusion (Figure 5). But these findings are often similar to other conditions such as RDS, TTN or meconium aspiration syndrome (MAS). Investigations such as blood cultures may identify
33
the causative organisms, and blood gases and pulse oximetry monitoring will guide the respiratory support required by the infant. There have only been a few randomized treatment trials for neonatal pneumonia and so the advice is to use local microbiology guidelines on use of antibiotics.45 The World Health Organisation recommend using ampicillin and gentamicin particularly to cover GBS and E.Coli but a wide range of antibiotics are often used guided by local policies, local flora and often local preferences.56 Supportive care such as oxygen, thermoregulation, prevention of hypoglycaemia and parenteral nutrition or nasogastric tube feeding are often required.45 MECONIUM ASPIRATION SYNDROME The passage of meconium in utero results in meconium-stained amniotic fluid (MSAF), which may be inhaled by the foetus especially if already compromised. If the infant has symptoms from the inhalation the condition is often referred to as meconium aspiration syndrome (MAS). MAS is essentially a disease of termand post-term born infants but an infective aetiology especially from Listeria should be suspected in preterm deliveries associated with MSAF. MAS results in respiratory distress of varying severity immediately after birth. MSAF is found in 5 to 30% of term and post-term deliveries of which 2 to 10% will progress to develop MAS. Pulmonary hypertension commonly develops in severe cases and should be aggressively treated. The reported mortality for MAS is between 4% and 40% although with modern techniques and interventions including the use of high frequency oscillatory ventilation, inhaled nitric oxide with extra-corporeal membrane oxygenation (ECMO) reserved for the most severe cases, survival has markedly improved in the last decade.57 Furthermore, the incidence of MAS in developed countries is on the decline possibly due to improved obstetric care.58,59 Pathophysiology MSAF appears to occur in utero due to foetal hypoxia from foetal distress. The passage of meconium prior to 37 weeks is uncommon thus MAS is largely confined to term and post-term deliveries.60 The inhaled meconium can cause mechanical obstruction of the airways leading to mismatched ventilation/ perfusion; chemical pneumonitis and infection which inhibit surfactant function and leads to inflammation and swelling, which also can block small airways.61 The respiratory distress observed at birth from inhaled meconium is likely to be due to the mechanical obstruction; however the distress that develops after a few hours of life is likely to be secondary to chemical pneumonitis and infection. The combination of ventilation/perfusion mismatch and pulmonary inflammatory can trigger vasoconstriction of the pulmonary vasculature leading to pulmonary hypertension. Risk factors Risk factors include greater MSAF density, post-term gestational age, foetal distress, male sex, Apgar score of less than 7 and oligohydramnios.57 The Australian and New Zealand Neonatal Network have shown that foetal distress and low Apgar scores can increase the risk of MAS.58 There is also an apparent relationship between maternal ethnicity and the risk of developing MAS with black Americans and Africans being at greatest risk.62,63 Prevention
Figure 5. Chest radiograph showing congenital pneumonia.
Duran et al. have reported a significant reduction in the incidence of perinatal asphyxia and improved Apgar scores at one
34
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
minute following the introduction of neonatal resuscitation programs for labour ward staff.64 Reducing post-term deliveries has also been shown to reduce the incidence of MAS.59 The practise of oropharyngeal suctioning is no longer recommended and has been shown to be of no benefit and may even cause harm.65 Management It is common practise to carry out ‘meconium observations’ for between 12 to 24 hours on all babies born following MSAF.66 Any signs of respiratory distress in these infants may indicate the early development of MAS and needs urgent further assessment. Most cases of MAS will recover within 2–3 days and only require supportive therapy. However, some infants will progress to develop severe MAS requiring intubation and ventilation.67,68 The initial chest radiograph is often similar to findings associated with pneumonia with bilateral patchy infiltrates and possible pleural effusion. Distinguishing MAS from pneumonia can be difficult thus antibiotics are usually prescribed either as treatment or as prophylaxis to prevent progression to infection. Treatment options for MAS, depending upon the severity, include conventional or high frequency oscillatory ventilation, surfactant (which is controversial),69 inhaled nitric oxide, and inotropic support as required and extracorporeal membrane oxygenation58 (which is discussed below). Prognosis The incidence of MAS continues to decrease largely due to improved obstetric care. Furthermore, mortality has decreased markedly but few studies have reported long term outcomes although there is some evidence of lasting neurodevelopmental abnormalities and persisting respiratory abnormalities.70 PERSISTENT PULMONARY HYPERTENSION OF THE NEONATE Pulmonary arterial hypertension is relatively common in newborn infants and can be either primary (often termed persistent pulmonary hypertension of the newborn, PPHN) or secondary due to conditions such as RDS, congenital diaphragmatic hernia (CDH), MAS and pneumonia. Pulmonary hypertension needs to be considered in any infants with respiratory distress either as a primary or secondary cause. It is often challenging to manage and usually presents in the first few hours of life but may present later especially when secondary to other conditions. It is also associated with significant mortality especially if associated with CDH.71 Pathophysiology There is failure of the pulmonary vascular resistance to decrease following delivery. In utero the pulmonary vascular resistance is high but rapidly decreases after birth following the infant’s first breath. The falls in pulmonary vasculature pressures continue rapidly over the first 24 hours of life and more gradually thereafter.72 Factors affecting the oxygenation of the pulmonary arteries will prevent the decreases of the pulmonary vascular leading to persistently increased pulmonary arterial pressures often resulting in right-to-left shunting of blood across the foramen ovale and ductus arteriosus. Ventilation perfusion mismatching is also likely to be present compounded by conditions such as MAS.
ductus arteriosus or foramen ovale. Chest radiograph may show an enlarged cardiac silhouette with findings of the underlying disease process or may show decreased vascular markings in the lung field especially in PPHN. Initial therapy is based on maintaining high oxygen saturations as oxygen is a potent vasodilator for pulmonary arteries.72 If adequate oxygenation cannot be maintained despite oxygen therapy, tracheal intubation and mechanical ventilation (including high frequency oscillatory ventilation) then therapies such as inhaled nitric oxide and inotropic support may be necessary. The use of inhaled nitric oxide has been shown to improve oxygen saturation levels in term infants with PPHN and to reduce the need for ECMO.73–75 Prognosis There has been marked improvement in mortality for infants developing PPHN but the prognosis for secondary pulmonary hypertension often depends on the underlying condition with prognosis being generally good for those with MAS but poor for those with CDH.76 There is some evidence that pulmonary hypertension may persist into adulthood for survivors of PPHN.77 Extracorporeal membrane oxygenation ECMO is generally reserved for the most severe cases usually instituted when the oxygenation index reaches 40. It is an option for PPHN and other related conditions such as MAS and pneumonia but its efficacy for CDH not responding to maximal medical management remains uncertain.71 The UK collaborative randomized trial of neonatal ECMO showed significant survival but neurodevelopmental deficits remain significant.78–80 ECMO can support either the lungs alone (veno-veno) or in combination with the cardiac function (veno-arterial). ECMO provides an opportunity for the underlying disease process to recover by providing the vital oxygenation to the body. ECMO centres sometimes differ in their acceptance criteria especially for conditions such as CDH but most agree that early referral is essential to plan transfer to these specialised units.81 By 2004, the ELSO registry reported that 19,061 neonates had been treated with ECMO for respiratory failure with a reported survival to discharge of 77%. The highest survival rate was observed for MAS at 94% and lowest for CDH at 53%.82
PNEUMOTHORAX Pneumothorax usually develops secondary to an underlying disease process but can occur spontaneously in 1% of newborns around the perinatal period, although only about 10% of these are symptomatic.83 The clinical presentation may vary from mild or severe signs of respiratory distress to a gradual decline in respiratory function. Pathophysiology Pneumothorax can be simply defined as air in the pleural space. It can occur spontaneously or secondary to conditions such as pneumonia, meconium aspiration, ventilation or congenital abnormalities of the lungs and is often seen in infants receiving respiratory support especially with invasive mechanical ventilation. Risk factors
Management Echocardiography is mandatory and is likely to confirm raised pulmonary arterial pressures and any shunting across the patent
There is an increased risk of spontaneous pneumothorax in preterm infants but any infant with an underlying respiratory illness is at risk of developing pneumothoraces as are infants
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
exposed to mechanical ventilation or vigorous resuscitation attempts.84 Management The initial diagnosis can be made using a fibre-optic light to trans-illuminate air in the pleural space although a chest x-ray is usually required to confirm the diagnosis and to search for any underlying causes. The treatment depends upon the clinical condition of the infant and the size of the pneumothorax. Small pneumothoraces are often treated conservatively especially if asymptomatic but larger ones associated with symptoms are usually drained with an in situ chest drain or tube. Pneumothoraces under tension require urgent decompression with needle thoracocentesis followed by chest drain insertion. The chest drain can be removed as the infant’s respiratory status improves. CONGENITAL THORACIC MALFORMATIONS AND SURGICAL CONDITIONS There are several congenital thoracic malformations or surgical conditions that can present in the early neonatal period with respiratory distress. These include CDH, congenital cystic adenomatoid malformation, pulmonary hypoplasia, trachea-oesophageal atresia, congenital emphysema, choanal atresia, Pierre Robin syndrome and any cause of mediastinal masses such as a teratoma. These are predominantly managed with surgical intervention and have been reviewed in detail elsewhere.71,85 CONCLUSION We have reviewed common causes of respiratory distress in term infants. TTN and RDS are common especially in infants delivered after elective caesarean sections but generally have excellent prognosis. Even delivery at 37 weeks gestation, considered term, is associated with increased respiratory morbidity thus should be avoided wherever possible. Conditions such as pulmonary arterial hypertension that may be primary or secondary to RDS, MAS or CDH will respond in most cases to oxygen therapy, mechanical ventilation including high frequency ventilation, inhaled nitric oxide or inotropes but ECMO should be considered if the respiratory failure does not respond to maximum medical therapy. The early recognition and initiation of appropriate management is important to ensure the optimal outcome for all infants presenting with respiratory distress. CONFLICT OF INTEREST STATEMENT No conflict of interest of any of the authors.
PRACTICE POINTS FOR RESPIRATORY DISTRESS IN THE TERM INFANT A common presenting feature of newborn infants. Early assessment and management are important to reduce complications. There are multiple risk factors, which may contribute to the development of respiratory distress and many of these are difficult to minimise. Often there is difficulty in differentiating between the various diseases that cause respiratory distress. Advances in medical treatment of infants with respiratory distress have improved the morbidity and mortality.
35
References 1. Kumar A, Bhat B. Epidemiology of respiratory distress of newborns. Indian Journal of Pediatrics 1996;63:93–8. 2. Kotecha S, Allen J. Oxygen therapy for infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2002;87:F11–4. 3. Shaw NJ, Kotecha S. Management of infants with chronic lung disease of prematurity in the United Kingdom. Early Hum Dev 2005;81:165–70. 4. Hibbard J, Wilkins I, Sun L, Gregory K, Haberman S, Hoffman M, et al. Respiratory morbidity in late preterm births. JAMA Journal of the American Medical Association 2010;304:419–25. 5. Qandalji B. Full term neonatal admissions. Early Human Development Conference: 2nd Union of European Neonatal and Perinatal Societies, UENPS Congress Academic Olympics Istanbul Turkey Conference Start 2010; 86(pp S133):S133. 6. QIAN Li-ling, LIU Cui-qing, GUO Yun-xia, JIANG Ye-jun, NI Li-ming, XIA Shi-wen, et al., Current status of neonatal acute respiratory disorders: a one-year prospective survey from a Chinese neonatal network. Chinese Medical Journal 2010; 123:2769–75. 7. Abdel-Latif ME, Oei J, Ward M, Wills EJ, Tobias V, Lui K. Galvanised by a respiratory distress diagnosis. Arch Dis Child Educ Pract Ed 2008;93:112–9. 8. Bishop NB, Stankiewicz P, Steinhorn RH. Alveolar capillary dysplasia. American Journal of Respiratory and Critical Care Medicine 2011;184:172–9. 9. Ersch J, Roth-Kleiner M, Baeckert P, Bucher HU. Increasing incidence of respiratory distress in neonates. Acta Paediatr 2007;96:1577–81. 10. Gouyon J, Ribakovsky C, Ferdynus C, Quantin C, Sagot P, Gouyon B. Severe respiratory disorders in term neonates. Paediatric and Perinatal Epidemiology 2007;22:22–30. 11. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol 1995;102:101–6. 12. Births and Deaths in England and Wales. In: Statistics OfN, editor. Newport, 2010:7. 13. Kotecha S, Adappa R, Paranjothy S, Hopkins J, Rolfe K, Watkins J. All Wales Perinatal Survey - Annual Report 2009. Cardiff: Cardiff University, 2011. 14. Manning D, Brewster B, Bundred P. Social deprivation and admission for neonatal care. Archives of Disease in Childhood - Fetal and Neonatal Edition 2005;90:F337–8. 15. Avery ME, Gatewood OB, Brumley G. Transient Tachypnea of Newborn: Possible Delayed Resorption of Fluid at Birth. Am J Dis Child 1966;111:380–5. 16. Tutdibi E, Gries K, Bucheler M, Misselwitz B, Schlosser RL, Gortner L. Impact of labor on outcomes in transient tachypnea of the newborn: population-based study. Pediatrics 2010;125:e577–83. 17. Bland R, Bressack M, McMillan D. Labor decreases the lung water content of newborn rabbits. American Journal of Obstetrics and Gynecology 1979;135:364–7. 18. Dehdashtian M, Riazi E, Aletayeb M. Influence of mode of delivery at term on the neonatal respiratory morbidity. Pakistan Journal of Medical Sciences 2008; 24:556–9. 19. Milner A, Saunders R, Hopkins I. Effects of delivery by caesarean section on lung mechanics and lung volume in the human neonate. Archives of Disease in Childhood 1978;53:545–8. 20. Dani C, Reali MF, Bertini G, Wiechmann L, Spagnolo A, Tangucci M, et al. Risk factors for the development of respiratory distress syndrome and transient tachypnoea in newborn infants. Italian Group of Neonatal Pneumology. Eur Respir J 1999;14:155–9. 21. Al-Agha R, Kinsley B, Finucane F, Murray S, Daly S, Foley M, et al. Caesarean section and macrosomia increase transient tachypnoea of the newborn in type 1 diabetes pregnancies. Diabetes Research and Clinical Practice 2010;89:e46–8. 22. Demissie K, Marcella SW, Breckenridge MB, Rhoads GG. Maternal asthma and transient tachypnea of the newborn. Pediatrics 1998;102(1 Pt 1):84–90. 23. Clark JM, Hulme E, Devendrakumar V, Turner MA, Baker PN, Sibley CP, et al. Effect of maternal asthma on birthweight and neonatal outcome in a British inner-city population. Paediatric and Perinatal Epidemiology 2007;21:154–62. 24. Persson B, Hanson U. Neonatal morbidities in gestational diabetes mellitus. Diabetes Care 1998;21(Suppl 2):B79–84. 25. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. Bmj 2005;331:662. 26. Kurl S, Heinonen KM, Kiekara O. The first chest radiograph in neonates exhibiting respiratory distress at birth. Clin Pediatr (Phila) 1997;36:285–9. 27. Wiswell TE, Rawlings JS, Smith FR, Goo ED. Effect of furosemide on the clinical course of transient tachypnea of the newborn. Pediatrics 1985;75:908–10. 28. Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A metaanalysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy 2008;38:629–33. 29. Liem JJ, Huq SI, Ekuma O, Becker AB, Kozyrskyj AL. Transient tachypnea of the newborn may be an early clinical manifestation of wheezing symptoms. J Pediatr 2007;151:29–33. 30. Adams M, Doull I. Birth by caesarean section and asthma. Clin Exp Allergy 2008;38:554–6. 31. Yurdakok M. Transient tachypnea of the newborn: what is new? J Matern Fetal Neona 2010;23(Suppl 3):24–6. 32. Pickerd N, Kotecha S. The Pathophysiology of Respiratory Distress Syndrome. Child Health and Paediatrics 2009;19:153–7. 33. Clark R. The epidemiology of respiratory failure in neonates born at an estimated gestational age of 34 weeks or more. Journal of Perinatology 2005; 25:251–7.
36
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
34. Barker PM, Olver RE. Invited review: Clearance of lung liquid during the perinatal period. J Appl Physiol 2002;93:1542–8. 35. Joshi S, Kotecha S. Lung growth and development. Early Hum Dev 2007;83: 789–94. 36. Vyas J, Kotecha S. Effects of antenatal and postnatal corticosteroids on the preterm lung. Arch Dis Child Fetal Neonatal Ed 1997;77:F147–50. 37. Antenatal Corticosteroids to Prevent Respiratory Distress Syndrome: Royal College of Obstetricians and Gynaecologists, 2004:RCOG. 38. Levine EM, Ghai V, Barton JJ, Strom CM. Mode of delivery and risk of respiratory diseases in newborns. Obstetrics and Gynecology 2001;97:439–42. 39. Madar J, Richmond S, Hey E. Surfactant-deficient respiratory distress after elective delivery at ‘term’. Acta Paediatr 1999;88:1244–8. 40. Sweet D, Bevilacqua G, Carnielli V, Greisen G, Plavka R, Saugstad OD, et al. European consensus guidelines on the management of neonatal respiratory distress syndrome. Journal of Perinatal Medicine 2007;35:175–86. 41. Wilkinson AR, Ahluwalia J, Cole A, Crawford D, Fyle J, Gordon A, et al. Management of babies born extremely preterm at less than 26 weeks of gestation: a framework for clinical practice at the time of birth. Arch Dis Child Fetal Neonatal Ed 2009;94:F2–5. 42. Engle W, Stark A, Adamkin D, Batton D, Bell E, Bhutani V, et al. Surfactantreplacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;121:419–32. 43. Stick S. Pediatric origins of adult lung disease. 1. The contribution of airway development to paediatric and adult lung disease. Thorax 2000;55:587–94. 44. Nissen MD. Congenital and neonatal pneumonia. Paediatric Respiratory Reviews 2007;8:195–203. 45. Duke T. Neonatal pneumonia in developing countries. Arch Dis Child Fetal Neonatal Ed 2005;90:F211–9. 46. Beeton ML, Maxwell NC, Davies PL, Nuttall D, McGreal E, Chakraborty M, et al. Role of pulmonary infection in the development of chronic lung disease of prematurity. Eur Respir J 2011;37:1424–30. 47. Webster J, Faoagali JL, Cartwright D. Elimination of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit after hand washing with triclosan. J Paediatr Child Health 1994;30:59–64. 48. Sharek PJ, Benitz WE, Abel NJ, Freeburn MJ, Mayer ML, Bergman DA. Effect of an evidence-based hand washing policy on hand washing rates and false-positive coagulase negative staphylococcus blood and cerebrospinal fluid culture rates in a level III NICU. J Perinatol 2002;22:137–43. 49. Kenyan S, Boulvain M, Neilson J. Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic Reviews 2001;4. CD001058. 50. Cesar JA, Victora CG, Barros FC, Santos IS, Flores JA. Impact of breast feeding on admission for pneumonia during postneonatal period in Brazil: nested casecontrol study. Bmj 1999;318:1316–20. 51. Kirkwood BR, Gove S, Rogers S, Lob-Levyt J, Arthur P, Campbell H. Potential interventions for the prevention of childhood pneumonia in developing countries: a systematic review. Bull World Health Organ 1995;73:793–8. 52. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. MMWR Recomm Rep 2010;59(RR10):1–36. 53. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al. A populationbased comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002;347:233–9. 54. Lin FY, Brenner RA, Johnson YR, Azimi PH, Philips 3rd JB, Regan JA, et al. The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease. American Journal of Obstetrics and Gynecology 2001;184:1204–10. 55. Antenatal care: routine care for the healthy pregnant woman. In: Excellence NIfHaC, editor. 2nd ed. London: RCOG Press, 2008. 56. Management of the Child with a serious infection or severe malnutrition: Guidelines for care at First-referral level in developing countries. In: WHO, editor. Geneva: World Health Organization, 2000. 57. Meritano J, Abraham S, Di Pietro S, Gerez G, Fernndez V. Respiratory distress syndrome associated with meconiumstained amniotic fluid in term and postterm newborns: Incidence, risk factors, morbidity, and mortality. Pediatric Research Conference: 47th Annual Meeting of the Latin American Society for Paediatric Research, LASPR Asuncion Paraguay Conference Start 2010;67:446. 58. Dargaville PA, Copnell B. The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome. Pediatrics 2006;117:1712–21.
CME SECTION This article has been accredited for CME learning by the European Board for Accreditation in Pneumology (EBAP). You can receive 1 CME credit by successfully answering these questions online. (A) Visit the journal CME site at http:// www.prrjournal.com/ (B) Complete the answers online, and receive your final score upon completion of the test. (C) Should you successfully complete the test, you may download your accreditation certificate (subject to an administrative charge).
59. Yoder BA, Kirsch EA, Barth WH, Gordon MC. Changing obstetric practices associated with decreasing incidence of meconium aspiration syndrome. Obstetrics and Gynecology 2002;99(5 Pt 1):731–9. 60. Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues. Pediatric Clinics of North America 1993;40:955–81. 61. Ross MG. Meconium Aspiration Syndrome - More Than Intrapartum Meconium. New England Journal of Medicine September 2005;353:946–8. 62. Sriram S, Wall SN, Khoshnood B, Singh JK, Hsieh HL, Lee KS. Racial disparity in meconium-stained amniotic fluid and meconium aspiration syndrome in the United States, 1989–2000. Obstetrics and Gynecology 2003;102:1262–8. 63. Sedaghatian MR, Othman L, Hossain MM, Vidyasagar D. Risk of meconiumstained amniotic fluid in different ethnic groups. J Perinatol 2000;20:257–61. 64. Duran R, Aladag N, Vatansever U, Sut N, Acunas B. The impact of Neonatal Resuscitation Program courses on mortality and morbidity of newborn infants with perinatal asphyxia. Brain Dev 2008;30:43–6. 65. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet 2004;364:597–602. 66. Intrapartum care: Care of healthy women and their babies during childbirth. In: Excellence NifHaC, editor. London: NICE, 2007. 67. Coltart TM, Byrne DL, Bates SA. Meconium aspiration syndrome: a 6-year retrospective study. Br J Obstet Gynaecol 1989;96:411–4. 68. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made a difference? Pediatrics 1990;85:715–21. 69. El Shahed A, Dargaville P, Ohlsson A, Soll R. Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane database of systematic reviews 2007;3:CD002054. 70. Ka¨a¨pa¨ PO. Meconium aspiration syndrome (MAS) - Where do we go? Research perspectives. Early Hum Dev 2009;85:627–9. 71. Kotecha S, Barbato A, Bush A, Claus F, Davenport M, Delacourt C, et al. European respiratory society task force on congenital diaphragmatic hernia. Eur Respir J 2012;39(4). 72. Spitzer AR, Davis J, Clarke WT, Bernbaum J, Fox WW. Pulmonary hypertension and persistent fetal circulation in the newborn. Clinics in Perinatology 1988;15:389–413. 73. Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818–9. 74. Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:819–20. 75. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database of Systematic Reviews 2006;4. CD000399. 76. Sartori C, Allemann Y, Trueb L, Delabays A, Nicod P, Scherrer U. Augmented vasoreactivity in adult life associated with perinatal vascular insult. Lancet 1999;353:2205–7. 77. Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatric Clinics of North America 2009;56:579–600. 78. Bennett CC, Johnson A, Field DJ, Elbourne D. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation: follow-up to age 4 years. Lancet 2001;357:1094–6. 79. The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up to 1 year of age. Pediatrics 1998;101:E1. 80. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. UK Collaborative ECMO Trail Group. Lancet 1996;348: 75–82. 81. Bahrami KR, Van Meurs KP. ECMO for neonatal respiratory failure. Seminars in Perinatology 2005;29:15–23. 82. Arbor A. ECLS Registry Report International Summary. Extracorporeal Life Support Organization 2004. 83. Greenough A, Morley C, Roberton N. Acute respiratory diseases in the newborn. In: Roberton N, editor. Textbook of Neonatology. 2nd ed., London: Churchill Livingstone; 1992. p. 385–504. 84. Horbar JD, Badger GJ, Carpenter JH, Fanaroff AA, Kilpatrick S, LaCorte M, et al. Trends in mortality and morbidity for very low birth weight infants, 1991– 1999. Pediatrics 2002;110(1 Pt 1):143–51. 85. Kotecha S, Barbato A, Bush A, Claus F, Davenport M, Delacourt C, et al. Antenatal and postnatal management of congenital cystic adenomatoid malformation. Paediatric Respiratory Reviews 2012. doi: 10.1016/j.prrv.2012.01.002. In Press.
1. a. b. c. d. e.
Which of the following is NOT a sign of respiratory distress: Tachypnoea Grunting Tachycardia Apnoea Abdominal distension
2. Which of the following is the commonest cause of respiratory distress in the term infant? a. Respiratory distress syndrome
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
b. c. d. e.
Pneumonia Pneumothorax Transient tachypnoea of the newborn Meconium aspiration syndrome
3. a. b. c. d. e.
With regards to congenital pneumonia: The pathogen is always bacterial. Is often preceded by chorioamnionitis. Broad-spectrum antibiotics should be used as treatment. Group B Strep on lower vaginal swabs is a risk factor. Can be secondary to invasive mechanical ventilation.
4. ECMO is indicated in the following circumstances: a. A term infant with severe MAS, not responding to high frequency oscillatory ventilation.
b. A term infant with a spontaneous pneumothorax. c. A term infant with persistent pulmonary hypertension of the newborn not responding to maximal medical therapy. d. A term infant with severe congenital diaphragmatic hernia. e. A preterm infant (30 weeks gestation) with respiratory distress syndrome. 5. a. b. c. d. e.
Antenatal steroids are licensed to be used to prevent: Congenital pneumonia Respiratory distress syndrome in the preterm infant Meconium aspiration syndrome Persistent pulmonary hypertension of the newborn Pneumothorax
37
Contents lists available at SciVerse ScienceDirect
Paediatric Respiratory Reviews
CME article
Respiratory Distress of the Term Newborn Infant Martin O. Edwards, Sarah J. Kotecha, Sailesh Kotecha * Department of Child Health, School of Medicine, Cardiff University, Cardiff, United Kingdom
EDUCATIONAL AIMS The reader will be able to:
Recognise the importance of respiratory distress in term newborn infants. Discuss the differential diagnosis of respiratory distress in term newborn infants. Describe the more common causes of respiratory distress in term newborn infants. Initiate a management plan for the term newborn infant presenting with respiratory distress.
A R T I C L E I N F O
S U M M A R Y
Keywords: Respiratory distress syndrome Transient tachypnoea of the newborn Pneumonia Meconium aspiration syndrome Extracorporeal membrane oxygenation
Respiratory distress is recognised as any signs of breathing difficulties in neonates. In the early neonatal period respiratory distress is common, occurring in up to 7% of newborn infants, resulting in significant numbers of term-born infants being admitted to neonatal units. Many risk factors are involved; the increasing number of term infants delivered by elective caesarean section has also increased the incidence. Additionally the risk decreases with each advancing week of gestation. At 37 weeks, the chances are three times greater than at 39-40 weeks gestation. Multiple conditions can present with features of respiratory distress. Common causes in term newborn infants include transient tachypnoea of the newborn, respiratory distress syndrome, pneumonia, meconium aspiration syndrome, persistent pulmonary hypertension of the neonate and pneumothorax. Early recognition of respiratory distress and initiation of appropriate treatment is important to ensure optimal outcomes. This review will discuss these common causes of respiratory distress in term-born infants. ß 2012 Elsevier Ltd. All rights reserved.
INTRODUCTION Respiratory distress is common in the early neonatal period and occurs in up to 7% of newborn infants.1 Much of the focus has been on respiratory distress syndrome and chronic lung disease of prematurity in preterm infants (<37 weeks of gestation)2,3 but every year a significant number of term-born infants are admitted to neonatal units for management of their respiratory distress.4–6 Multiple conditions can cause respiratory distress in term newborn infants (Table 1). Conditions such as surfactant protein deficiency syndromes or alveolar capillary dysplasia are rare and the reader is referred to recent excellent reviews.7,8 In Switzerland, Ersch et al. reported an increasing incidence of respiratory distress of all neonates admitted to neonatal units
* Corresponding author. Department of Child Health, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XW, United Kingdom Tel.: +44 29 20 74 4187; fax: +44 29 20 74 4283. E-mail addresses: [email protected] (M.O. Edwards), [email protected] (S.J. Kotecha), [email protected] (S. Kotecha). 1526-0542/$ – see front matter ß 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2012.02.002
between 1974 and 2004 citing three possible explanations: an increase in extremely low birth weight infants, changes in admission policies and increasing numbers of infants delivered by caesarean section.9 The impact of elective caesarean sections has specifically increased the incidence of respiratory distress in term infants.10 This has been known for many years; in 1995 Morrison et al. estimated that 2,000 cases per year required neonatal admission for pulmonary diseases following caesarean section before onset of labour in the United Kingdom (UK).11 There were 706,248 live births in England and Wales in 2009 and approximately 94% of these were full term deliveries (37 weeks of gestation).12,13 Between 1990 and 2002, the admission rate to a busy neonatal unit in England was 8.6% of all live births.14 The commonest reason for admission was respiratory distress.6,9 There is a clear inverse relationship between gestational age and incidence of respiratory distress most notably by transient tachypnoea of the newborn (TTN) and respiratory distress syndrome (RDS).4,10 Gouyon et al. also noted that a major risk factor for severe respiratory distress in term infants was elective caesarean section at 37–38 weeks gestation but with meconium
30
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
Table 1 Differential diagnosis of respiratory distress in term-born infants. Less common conditions Pulmonary haemorrhage Pleural effusion (chylothorax) Neuromuscular disorders (e.g. congenital myotonic dystrophy) Metabolic acidosis (secondary to inborn error of metabolism) Congenital or surgical conditions Diaphragmatic hernia Tracheo-oesophageal fistula Choanal atresia Cystic congenital adenomatoid malformation (CCAM) Lobar emphysema Pulmonary sequestration Pulmonary hypoplasia Rare causes Surfactant protein deficiency syndromes Alveolar capillary dysplasia
Common conditions Transient tachypnoea of the newborn Respiratory distress syndrome Pneumonia Meconium aspiration syndrome Pneumothorax Primary or secondary pulmonary arterial hypertension Cardiac failure (due to congenital heart disease) Hypoxic-ischaemic encephalopathy Aspiration of milk or blood
stained liquor being most frequently noted at 39–41 weeks gestation.10 Thus, avoiding routine elective caesarean sections prior to 38 weeks of gestation would markedly decrease the incidence of respiratory problems in the term infant. ASSESSMENT Respiratory distress is recognised as any signs of breathing difficulties in the neonate (Figure 1). Useful questions to ask are shown in Figure 2. The initial assessment of any infant with respiratory distress should include blood tests (full blood count, Creactive protein, blood culture and blood gases), pulse oximetry and chest radiography. The initial treatment will aim to reverse the hypoxia, hypercapnia and acidosis that may have developed. TRANSIENT TACHYPNOEA OF THE NEWBORN TTN was first coined by Avery in 1966 and is now recognised as the commonest cause of respiratory distress in newborn term infants.15 It is caused by the delay in the absorption of fluid in the lungs after birth (i.e. excessive lung fluid).10 Thus, TTN is frequently seen in babies born following elective caesarean section. It usually presents with grunting and mild signs of respiratory distress, which persist for up to 48 hours and is generally a self-limiting disorder. However, some infants develop an oxygen requirement that necessitates admission to the neonatal unit for a few days accounting for approximately 10% of all newborn term admissions.16
Pathophysiology The lungs in utero are constantly secreting fluid to aid lung growth and development. However the rate of lung fluid production and volume of foetal lung lumen decreases before birth, most notably during labour.17 The mechanism for fluid absorption is triggered by neuroendocrine hormones, which cause lymphatic vessel dilatation. As the lung pulmonary circulation increases following the first breath, the fluid in the lungs is cleared thus interruption of this process of clearing fluid from the lungs may result in respiratory distress. Risk factors The main risk factor for TTN is delivery following elective caesarean section. The usual mechanisms to clear fluid, which occur after the onset of labour, are not activated after elective caesarean section thus there is often inadequate clearance of pulmonary fluid, which can result in TTN.18,19 Other risk factors include delivery prior to 38 weeks of gestation, male sex, low birth weight and macrosomia20,21 and maternal diseases such gestational diabetes and asthma.22–24 Prevention The Burgundy Perinatal Network has shown that the incidence of TTN requiring ventilation is significantly reduced for each extra week in utero decreasing from 34% at 37 weeks to 0.5% at 41 weeks gestation.10 A recent multicentre pragmatic randomised trial showed that administration of antenatal steroids prior to elective caesarean delivery at 37–39 weeks’ gestation reduces the incidence of TTN.25 As the long term effects are currently unknown, at present the best course is to avoid elective caesarean sections prior to 38 weeks wherever possible. Management
Figure 1. The common signs and symptoms of respiratory distress in term newborn infants.
It is important to establish the diagnosis by taking a thorough history and performing a physical examination. TTN commonly presents within the first few hours of life and is often managed conservatively i.e. a period of close observation on the postnatal ward or in the neonatal unit but must be weighed against other differential diagnoses (Table 1) including RDS and pneumonia which may progress rapidly in newborn infants. Chest radiographs often show ‘‘a wet silhouette’’ around the heart (Figure 3) with fluid in the horizontal fissures.26 Some infants may require oxygen therapy or other forms of respiratory support for several days to aid recovery. Antibiotics are often routinely used, as differentiation from an infective process is often difficult. Other forms of therapies
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
31
FAQ’s when assessing an infant with respiratory distress Is anything else causing the respiratory distress? Consider metabolic, renal, neurological causes.
Is it a cardiac or respiratory problem? Consider the need for Chest radiograph and Echocardiogram.
What is the gestaonal age of the baby? Preterms (<37weeks) are more likely to have RDS; Post term (>42 weeks) are more likely to have MAS; Late preterms and terms are more likely to have TTN.
Is it severe or mild respiratory distress? Severe distress more likely with RDS, MAS or PPHN. Mild distress more likely with TTN.
Are there any known congenital anomalies? Review antenatal scan reports for CDH, CCAM etc…
What was the delivery method? Pre-labour secon more likely to be TTN; Evidence of MSAF is more likely to be MAS.
Is there poor improvement with increasing oxygen flow? Persistent hypoxia and cyanosis despite 100% oxygen need to consider PPHN or CCHD.
Are there any risk factors for sepsis? PROM, GBS on HVS, maternal pyrexia or raised inflammatory markers in maternal bloods would suggest pneumonia.
Abbreviations: RDS - Respiratory Distress Syndrome; MAS - Meconium Aspiration Syndrome; TTN - Transient Tachypnoea of the Newborn; PPHN - Persistent Pulmonary Hypertension of the Neonate; CDH - Congenital Diaphragmatic Hernia; CCAM - Congenital Cystic Adenomatoid Malformation; MSAF - Meconium Stained Amniotic Fluid; CCHD - Congenital Cyanotic Heart Disease; GBS - Group B Streptococcus; HVS - High Vaginal Swab.
Figure 2. Useful questions to ask while assessing a term-born infant with respiratory distress.
such as diuretics have been tested but fail to change the course of TTN.27 Prognosis Infants who develop TTN generally recover fully and are nursed in air within a few days of delivery. However, TTN may be associated with development of asthma later in childhood, especially amongst males.28,29 Adams & Doull discuss the association of birth by caesarean section and asthma, and state that there is evidence for an association between these, but there is still no indication of causality.30 In a review of TTN, Yurdakok suggests a genetic link between TTN and later onset asthma.31 RESPIRATORY DISTRESS SYNDROME RDS is caused by a deficiency of surfactant and is often also called hyaline membrane disease, which strictly speaking is a
histological diagnosis.32 Newborn infants with RDS present during the first 4 to 6 hours of life. It is commonly seen in preterm infants; however, published data have shown that infants with a birth weight of >2500 g account for 9.9%20 to 11.5%9 of infants with RDS and those with gestational age of 37 weeks gestation account for 7.8%.20 The Near-Term Respiratory Failure Research Group, who studied 1011 infants (mean gestational age of 37 2 weeks gestation), who all required mechanical ventilation, identified 43% developed RDS.33 Pathophysiology It can be difficult to distinguish between RDS and TTN, especially in newborn term infants. It has been suggested that both these conditions are part of the same spectrum of respiratory disease occurring whilst adapting to postnatal life at birth.34 The production of surfactant by type 2 pneumocytes commences around 24–25 weeks gestation reaching adequate levels to support
32
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
Figure 4. Chest radiograph showing signs of RDS. The x-ray shows air bronchograms and reticulonodular shadowing throughout the lung fields (often termed ‘ground glass’ appearance).
Figure 3. Chest radiograph showing TTN. The x-ray shows ‘‘a wet silhouette’’ around the heart with fluid in the horizontal fissure.
breathing after birth by 36–37 weeks gestation.35 Therefore, when infants are born 36 weeks gestation, the relatively immature lungs are unable to produce sufficient surfactant to maintain adequate breathing. The lack of surfactant results in poorly compliant lungs due to widespread alveolar collapse.32 The infant will show signs of respiratory distress and in many cases will require respiratory support with oxygen or mechanical ventilation. Risk factors The risk of RDS increases inversely with decreasing gestational age thus the commonest at-risk group are preterm infants. Dani et al. demonstrated that gestational age, low birthweight, maternal age, elective and emergency caesarean section and male sex are all risk factors for RDS.20
shows air bronchograms (Figure 4) and reticulonodular shadowing throughout the lung fields (often termed ‘ground glass’ appearance). In many neonatal units there are well-established guidelines for the management of RDS in newborn infants, including the use of exogenous surfactant.40,41 Newborn infants quickly produce their own surfactant thus the respiratory distress often resolves in untreated infants after 72 – 96 hours of age. The management of infants with RDS is largely supportive until adequate surfactant synthesis occurs. The occasional unresponsive infant should be investigated further to exclude rare conditions such as alveolar capillary dysplasia and genetic abnormalities of the surfactant system.7,8 Prognosis Engle et al. have reviewed the literature on the outcome of infants given surfactant for RDS and conclude that ‘the risk of respiratory abnormalities later in infancy (recurrent wheezing, asthma, respiratory infection, pulmonary function test abnormalities) and early childhood remains high for preterm infants with respiratory distress syndrome’.42 The long term effects of respiratory disease in the newborn however require further study.43
Prevention PNEUMONIA The Consortium on Safe Labour in the United States of America (USA) recently reported that the risk of RDS decreases with each advancing week of gestation until 38 weeks, even at the relatively mature age of 37 weeks gestation, the chances of developing RDS were three-fold greater than at 39–40 weeks gestation.4 The use of antenatal corticosteroids to boost foetal lung surfactant and antioxidant enzyme production is now routine in threatened preterm labour between 24 and 34 weeks gestation and is sometimes considered at 35–36 weeks gestation.36,37 Reducing elective caesarean sections may help, although RDS secondary to caesarean section accounts for only a small number of the total incidence.38,39
A lower respiratory tract infection, particularly bacterial pneumonia can cause severe respiratory distress in the newborn infant. This can be acquired congenitally, through the birth passages especially after prolonged rupture of membranes or postnatally. Pneumonia in newborn infants is often difficult to diagnose and often difficult to distinguish from other causes of respiratory distress including RDS and TTN. Although many investigations including blood white cell counts, blood cultures, C-reactive protein, etc. are performed, they lack the necessary sensitivity and specificity to accurately diagnose pneumonia. Pathophysiology
Management The initial management will follow the standard approach of obtaining a history and examination. The need for respiratory support will need to be assessed from clinical observations, chest radiographs and blood gas results. The chest radiograph in RDS
Pneumonia may be acquired due to ascending infection especially when chorioamnionitis is present or postnatally from nosocomial acquired infections.44 The most likely cause for the former is inhalation of infected amniotic fluid and crosscontamination for the latter, which can be prevented by strict
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
anti-septic measures including hand-washing. Common pathogens include bacteria, such as group B Streptococci (GBS), Streptococcus pneumonia, Staphylococcus aureus, Listeria and gram-negative enteric rods (e.g. E.Coli); and viruses, such as Herpes simplex virus, Respiratory syncytial virus and Influenza A & B viruses; atypical organisms such as chlamydia; and fungi such as Candida albicans. Risk factors The main risk factors for congenital pneumonia are prolonged rupture of membranes (PROM), prematurity and maternal infection (maternal fever or raised white cell count), particularly with GBS.44 Birth weight and age of onset are both strongly associated with the mortality risk from pneumonia.45 Pneumonia can occur secondary to invasive mechanical ventilation but is largely confined to preterm infants who receive prolonged ventilation.46 Prevention The most important and easiest method of preventing nosocomial pneumonia is hand washing to prevent cross-infection between vulnerable infants.47,48 Other methods of prevention include following local guidelines for the management of premature rupture of membranes49 and encouraging early and exclusive breast feeding.50,51 Screening for Group B Streptococcus (GBS) In the U.S.A, it is mandatory to screen all pregnant women in the third trimester for GBS and to treat those with vaginal GBS colonisation with intrapartum antibiotics, at least four hours prior to delivery.52 Universal screening and antepartum treatment can reduce the rate of early-onset disease by 89%.53,54 In the UK and other countries, however, screening is more targeted but those at risk are treated with intrapartum antibiotics.55 Management Pneumonia may present early or late. A thorough history and examination may help establish a suspected diagnosis. A chest radiograph may show bilateral patchy shadowing with or without pleural effusion (Figure 5). But these findings are often similar to other conditions such as RDS, TTN or meconium aspiration syndrome (MAS). Investigations such as blood cultures may identify
33
the causative organisms, and blood gases and pulse oximetry monitoring will guide the respiratory support required by the infant. There have only been a few randomized treatment trials for neonatal pneumonia and so the advice is to use local microbiology guidelines on use of antibiotics.45 The World Health Organisation recommend using ampicillin and gentamicin particularly to cover GBS and E.Coli but a wide range of antibiotics are often used guided by local policies, local flora and often local preferences.56 Supportive care such as oxygen, thermoregulation, prevention of hypoglycaemia and parenteral nutrition or nasogastric tube feeding are often required.45 MECONIUM ASPIRATION SYNDROME The passage of meconium in utero results in meconium-stained amniotic fluid (MSAF), which may be inhaled by the foetus especially if already compromised. If the infant has symptoms from the inhalation the condition is often referred to as meconium aspiration syndrome (MAS). MAS is essentially a disease of termand post-term born infants but an infective aetiology especially from Listeria should be suspected in preterm deliveries associated with MSAF. MAS results in respiratory distress of varying severity immediately after birth. MSAF is found in 5 to 30% of term and post-term deliveries of which 2 to 10% will progress to develop MAS. Pulmonary hypertension commonly develops in severe cases and should be aggressively treated. The reported mortality for MAS is between 4% and 40% although with modern techniques and interventions including the use of high frequency oscillatory ventilation, inhaled nitric oxide with extra-corporeal membrane oxygenation (ECMO) reserved for the most severe cases, survival has markedly improved in the last decade.57 Furthermore, the incidence of MAS in developed countries is on the decline possibly due to improved obstetric care.58,59 Pathophysiology MSAF appears to occur in utero due to foetal hypoxia from foetal distress. The passage of meconium prior to 37 weeks is uncommon thus MAS is largely confined to term and post-term deliveries.60 The inhaled meconium can cause mechanical obstruction of the airways leading to mismatched ventilation/ perfusion; chemical pneumonitis and infection which inhibit surfactant function and leads to inflammation and swelling, which also can block small airways.61 The respiratory distress observed at birth from inhaled meconium is likely to be due to the mechanical obstruction; however the distress that develops after a few hours of life is likely to be secondary to chemical pneumonitis and infection. The combination of ventilation/perfusion mismatch and pulmonary inflammatory can trigger vasoconstriction of the pulmonary vasculature leading to pulmonary hypertension. Risk factors Risk factors include greater MSAF density, post-term gestational age, foetal distress, male sex, Apgar score of less than 7 and oligohydramnios.57 The Australian and New Zealand Neonatal Network have shown that foetal distress and low Apgar scores can increase the risk of MAS.58 There is also an apparent relationship between maternal ethnicity and the risk of developing MAS with black Americans and Africans being at greatest risk.62,63 Prevention
Figure 5. Chest radiograph showing congenital pneumonia.
Duran et al. have reported a significant reduction in the incidence of perinatal asphyxia and improved Apgar scores at one
34
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
minute following the introduction of neonatal resuscitation programs for labour ward staff.64 Reducing post-term deliveries has also been shown to reduce the incidence of MAS.59 The practise of oropharyngeal suctioning is no longer recommended and has been shown to be of no benefit and may even cause harm.65 Management It is common practise to carry out ‘meconium observations’ for between 12 to 24 hours on all babies born following MSAF.66 Any signs of respiratory distress in these infants may indicate the early development of MAS and needs urgent further assessment. Most cases of MAS will recover within 2–3 days and only require supportive therapy. However, some infants will progress to develop severe MAS requiring intubation and ventilation.67,68 The initial chest radiograph is often similar to findings associated with pneumonia with bilateral patchy infiltrates and possible pleural effusion. Distinguishing MAS from pneumonia can be difficult thus antibiotics are usually prescribed either as treatment or as prophylaxis to prevent progression to infection. Treatment options for MAS, depending upon the severity, include conventional or high frequency oscillatory ventilation, surfactant (which is controversial),69 inhaled nitric oxide, and inotropic support as required and extracorporeal membrane oxygenation58 (which is discussed below). Prognosis The incidence of MAS continues to decrease largely due to improved obstetric care. Furthermore, mortality has decreased markedly but few studies have reported long term outcomes although there is some evidence of lasting neurodevelopmental abnormalities and persisting respiratory abnormalities.70 PERSISTENT PULMONARY HYPERTENSION OF THE NEONATE Pulmonary arterial hypertension is relatively common in newborn infants and can be either primary (often termed persistent pulmonary hypertension of the newborn, PPHN) or secondary due to conditions such as RDS, congenital diaphragmatic hernia (CDH), MAS and pneumonia. Pulmonary hypertension needs to be considered in any infants with respiratory distress either as a primary or secondary cause. It is often challenging to manage and usually presents in the first few hours of life but may present later especially when secondary to other conditions. It is also associated with significant mortality especially if associated with CDH.71 Pathophysiology There is failure of the pulmonary vascular resistance to decrease following delivery. In utero the pulmonary vascular resistance is high but rapidly decreases after birth following the infant’s first breath. The falls in pulmonary vasculature pressures continue rapidly over the first 24 hours of life and more gradually thereafter.72 Factors affecting the oxygenation of the pulmonary arteries will prevent the decreases of the pulmonary vascular leading to persistently increased pulmonary arterial pressures often resulting in right-to-left shunting of blood across the foramen ovale and ductus arteriosus. Ventilation perfusion mismatching is also likely to be present compounded by conditions such as MAS.
ductus arteriosus or foramen ovale. Chest radiograph may show an enlarged cardiac silhouette with findings of the underlying disease process or may show decreased vascular markings in the lung field especially in PPHN. Initial therapy is based on maintaining high oxygen saturations as oxygen is a potent vasodilator for pulmonary arteries.72 If adequate oxygenation cannot be maintained despite oxygen therapy, tracheal intubation and mechanical ventilation (including high frequency oscillatory ventilation) then therapies such as inhaled nitric oxide and inotropic support may be necessary. The use of inhaled nitric oxide has been shown to improve oxygen saturation levels in term infants with PPHN and to reduce the need for ECMO.73–75 Prognosis There has been marked improvement in mortality for infants developing PPHN but the prognosis for secondary pulmonary hypertension often depends on the underlying condition with prognosis being generally good for those with MAS but poor for those with CDH.76 There is some evidence that pulmonary hypertension may persist into adulthood for survivors of PPHN.77 Extracorporeal membrane oxygenation ECMO is generally reserved for the most severe cases usually instituted when the oxygenation index reaches 40. It is an option for PPHN and other related conditions such as MAS and pneumonia but its efficacy for CDH not responding to maximal medical management remains uncertain.71 The UK collaborative randomized trial of neonatal ECMO showed significant survival but neurodevelopmental deficits remain significant.78–80 ECMO can support either the lungs alone (veno-veno) or in combination with the cardiac function (veno-arterial). ECMO provides an opportunity for the underlying disease process to recover by providing the vital oxygenation to the body. ECMO centres sometimes differ in their acceptance criteria especially for conditions such as CDH but most agree that early referral is essential to plan transfer to these specialised units.81 By 2004, the ELSO registry reported that 19,061 neonates had been treated with ECMO for respiratory failure with a reported survival to discharge of 77%. The highest survival rate was observed for MAS at 94% and lowest for CDH at 53%.82
PNEUMOTHORAX Pneumothorax usually develops secondary to an underlying disease process but can occur spontaneously in 1% of newborns around the perinatal period, although only about 10% of these are symptomatic.83 The clinical presentation may vary from mild or severe signs of respiratory distress to a gradual decline in respiratory function. Pathophysiology Pneumothorax can be simply defined as air in the pleural space. It can occur spontaneously or secondary to conditions such as pneumonia, meconium aspiration, ventilation or congenital abnormalities of the lungs and is often seen in infants receiving respiratory support especially with invasive mechanical ventilation. Risk factors
Management Echocardiography is mandatory and is likely to confirm raised pulmonary arterial pressures and any shunting across the patent
There is an increased risk of spontaneous pneumothorax in preterm infants but any infant with an underlying respiratory illness is at risk of developing pneumothoraces as are infants
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
exposed to mechanical ventilation or vigorous resuscitation attempts.84 Management The initial diagnosis can be made using a fibre-optic light to trans-illuminate air in the pleural space although a chest x-ray is usually required to confirm the diagnosis and to search for any underlying causes. The treatment depends upon the clinical condition of the infant and the size of the pneumothorax. Small pneumothoraces are often treated conservatively especially if asymptomatic but larger ones associated with symptoms are usually drained with an in situ chest drain or tube. Pneumothoraces under tension require urgent decompression with needle thoracocentesis followed by chest drain insertion. The chest drain can be removed as the infant’s respiratory status improves. CONGENITAL THORACIC MALFORMATIONS AND SURGICAL CONDITIONS There are several congenital thoracic malformations or surgical conditions that can present in the early neonatal period with respiratory distress. These include CDH, congenital cystic adenomatoid malformation, pulmonary hypoplasia, trachea-oesophageal atresia, congenital emphysema, choanal atresia, Pierre Robin syndrome and any cause of mediastinal masses such as a teratoma. These are predominantly managed with surgical intervention and have been reviewed in detail elsewhere.71,85 CONCLUSION We have reviewed common causes of respiratory distress in term infants. TTN and RDS are common especially in infants delivered after elective caesarean sections but generally have excellent prognosis. Even delivery at 37 weeks gestation, considered term, is associated with increased respiratory morbidity thus should be avoided wherever possible. Conditions such as pulmonary arterial hypertension that may be primary or secondary to RDS, MAS or CDH will respond in most cases to oxygen therapy, mechanical ventilation including high frequency ventilation, inhaled nitric oxide or inotropes but ECMO should be considered if the respiratory failure does not respond to maximum medical therapy. The early recognition and initiation of appropriate management is important to ensure the optimal outcome for all infants presenting with respiratory distress. CONFLICT OF INTEREST STATEMENT No conflict of interest of any of the authors.
PRACTICE POINTS FOR RESPIRATORY DISTRESS IN THE TERM INFANT A common presenting feature of newborn infants. Early assessment and management are important to reduce complications. There are multiple risk factors, which may contribute to the development of respiratory distress and many of these are difficult to minimise. Often there is difficulty in differentiating between the various diseases that cause respiratory distress. Advances in medical treatment of infants with respiratory distress have improved the morbidity and mortality.
35
References 1. Kumar A, Bhat B. Epidemiology of respiratory distress of newborns. Indian Journal of Pediatrics 1996;63:93–8. 2. Kotecha S, Allen J. Oxygen therapy for infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2002;87:F11–4. 3. Shaw NJ, Kotecha S. Management of infants with chronic lung disease of prematurity in the United Kingdom. Early Hum Dev 2005;81:165–70. 4. Hibbard J, Wilkins I, Sun L, Gregory K, Haberman S, Hoffman M, et al. Respiratory morbidity in late preterm births. JAMA Journal of the American Medical Association 2010;304:419–25. 5. Qandalji B. Full term neonatal admissions. Early Human Development Conference: 2nd Union of European Neonatal and Perinatal Societies, UENPS Congress Academic Olympics Istanbul Turkey Conference Start 2010; 86(pp S133):S133. 6. QIAN Li-ling, LIU Cui-qing, GUO Yun-xia, JIANG Ye-jun, NI Li-ming, XIA Shi-wen, et al., Current status of neonatal acute respiratory disorders: a one-year prospective survey from a Chinese neonatal network. Chinese Medical Journal 2010; 123:2769–75. 7. Abdel-Latif ME, Oei J, Ward M, Wills EJ, Tobias V, Lui K. Galvanised by a respiratory distress diagnosis. Arch Dis Child Educ Pract Ed 2008;93:112–9. 8. Bishop NB, Stankiewicz P, Steinhorn RH. Alveolar capillary dysplasia. American Journal of Respiratory and Critical Care Medicine 2011;184:172–9. 9. Ersch J, Roth-Kleiner M, Baeckert P, Bucher HU. Increasing incidence of respiratory distress in neonates. Acta Paediatr 2007;96:1577–81. 10. Gouyon J, Ribakovsky C, Ferdynus C, Quantin C, Sagot P, Gouyon B. Severe respiratory disorders in term neonates. Paediatric and Perinatal Epidemiology 2007;22:22–30. 11. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. Br J Obstet Gynaecol 1995;102:101–6. 12. Births and Deaths in England and Wales. In: Statistics OfN, editor. Newport, 2010:7. 13. Kotecha S, Adappa R, Paranjothy S, Hopkins J, Rolfe K, Watkins J. All Wales Perinatal Survey - Annual Report 2009. Cardiff: Cardiff University, 2011. 14. Manning D, Brewster B, Bundred P. Social deprivation and admission for neonatal care. Archives of Disease in Childhood - Fetal and Neonatal Edition 2005;90:F337–8. 15. Avery ME, Gatewood OB, Brumley G. Transient Tachypnea of Newborn: Possible Delayed Resorption of Fluid at Birth. Am J Dis Child 1966;111:380–5. 16. Tutdibi E, Gries K, Bucheler M, Misselwitz B, Schlosser RL, Gortner L. Impact of labor on outcomes in transient tachypnea of the newborn: population-based study. Pediatrics 2010;125:e577–83. 17. Bland R, Bressack M, McMillan D. Labor decreases the lung water content of newborn rabbits. American Journal of Obstetrics and Gynecology 1979;135:364–7. 18. Dehdashtian M, Riazi E, Aletayeb M. Influence of mode of delivery at term on the neonatal respiratory morbidity. Pakistan Journal of Medical Sciences 2008; 24:556–9. 19. Milner A, Saunders R, Hopkins I. Effects of delivery by caesarean section on lung mechanics and lung volume in the human neonate. Archives of Disease in Childhood 1978;53:545–8. 20. Dani C, Reali MF, Bertini G, Wiechmann L, Spagnolo A, Tangucci M, et al. Risk factors for the development of respiratory distress syndrome and transient tachypnoea in newborn infants. Italian Group of Neonatal Pneumology. Eur Respir J 1999;14:155–9. 21. Al-Agha R, Kinsley B, Finucane F, Murray S, Daly S, Foley M, et al. Caesarean section and macrosomia increase transient tachypnoea of the newborn in type 1 diabetes pregnancies. Diabetes Research and Clinical Practice 2010;89:e46–8. 22. Demissie K, Marcella SW, Breckenridge MB, Rhoads GG. Maternal asthma and transient tachypnea of the newborn. Pediatrics 1998;102(1 Pt 1):84–90. 23. Clark JM, Hulme E, Devendrakumar V, Turner MA, Baker PN, Sibley CP, et al. Effect of maternal asthma on birthweight and neonatal outcome in a British inner-city population. Paediatric and Perinatal Epidemiology 2007;21:154–62. 24. Persson B, Hanson U. Neonatal morbidities in gestational diabetes mellitus. Diabetes Care 1998;21(Suppl 2):B79–84. 25. Stutchfield P, Whitaker R, Russell I. Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial. Bmj 2005;331:662. 26. Kurl S, Heinonen KM, Kiekara O. The first chest radiograph in neonates exhibiting respiratory distress at birth. Clin Pediatr (Phila) 1997;36:285–9. 27. Wiswell TE, Rawlings JS, Smith FR, Goo ED. Effect of furosemide on the clinical course of transient tachypnea of the newborn. Pediatrics 1985;75:908–10. 28. Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A metaanalysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy 2008;38:629–33. 29. Liem JJ, Huq SI, Ekuma O, Becker AB, Kozyrskyj AL. Transient tachypnea of the newborn may be an early clinical manifestation of wheezing symptoms. J Pediatr 2007;151:29–33. 30. Adams M, Doull I. Birth by caesarean section and asthma. Clin Exp Allergy 2008;38:554–6. 31. Yurdakok M. Transient tachypnea of the newborn: what is new? J Matern Fetal Neona 2010;23(Suppl 3):24–6. 32. Pickerd N, Kotecha S. The Pathophysiology of Respiratory Distress Syndrome. Child Health and Paediatrics 2009;19:153–7. 33. Clark R. The epidemiology of respiratory failure in neonates born at an estimated gestational age of 34 weeks or more. Journal of Perinatology 2005; 25:251–7.
36
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
34. Barker PM, Olver RE. Invited review: Clearance of lung liquid during the perinatal period. J Appl Physiol 2002;93:1542–8. 35. Joshi S, Kotecha S. Lung growth and development. Early Hum Dev 2007;83: 789–94. 36. Vyas J, Kotecha S. Effects of antenatal and postnatal corticosteroids on the preterm lung. Arch Dis Child Fetal Neonatal Ed 1997;77:F147–50. 37. Antenatal Corticosteroids to Prevent Respiratory Distress Syndrome: Royal College of Obstetricians and Gynaecologists, 2004:RCOG. 38. Levine EM, Ghai V, Barton JJ, Strom CM. Mode of delivery and risk of respiratory diseases in newborns. Obstetrics and Gynecology 2001;97:439–42. 39. Madar J, Richmond S, Hey E. Surfactant-deficient respiratory distress after elective delivery at ‘term’. Acta Paediatr 1999;88:1244–8. 40. Sweet D, Bevilacqua G, Carnielli V, Greisen G, Plavka R, Saugstad OD, et al. European consensus guidelines on the management of neonatal respiratory distress syndrome. Journal of Perinatal Medicine 2007;35:175–86. 41. Wilkinson AR, Ahluwalia J, Cole A, Crawford D, Fyle J, Gordon A, et al. Management of babies born extremely preterm at less than 26 weeks of gestation: a framework for clinical practice at the time of birth. Arch Dis Child Fetal Neonatal Ed 2009;94:F2–5. 42. Engle W, Stark A, Adamkin D, Batton D, Bell E, Bhutani V, et al. Surfactantreplacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008;121:419–32. 43. Stick S. Pediatric origins of adult lung disease. 1. The contribution of airway development to paediatric and adult lung disease. Thorax 2000;55:587–94. 44. Nissen MD. Congenital and neonatal pneumonia. Paediatric Respiratory Reviews 2007;8:195–203. 45. Duke T. Neonatal pneumonia in developing countries. Arch Dis Child Fetal Neonatal Ed 2005;90:F211–9. 46. Beeton ML, Maxwell NC, Davies PL, Nuttall D, McGreal E, Chakraborty M, et al. Role of pulmonary infection in the development of chronic lung disease of prematurity. Eur Respir J 2011;37:1424–30. 47. Webster J, Faoagali JL, Cartwright D. Elimination of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit after hand washing with triclosan. J Paediatr Child Health 1994;30:59–64. 48. Sharek PJ, Benitz WE, Abel NJ, Freeburn MJ, Mayer ML, Bergman DA. Effect of an evidence-based hand washing policy on hand washing rates and false-positive coagulase negative staphylococcus blood and cerebrospinal fluid culture rates in a level III NICU. J Perinatol 2002;22:137–43. 49. Kenyan S, Boulvain M, Neilson J. Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic Reviews 2001;4. CD001058. 50. Cesar JA, Victora CG, Barros FC, Santos IS, Flores JA. Impact of breast feeding on admission for pneumonia during postneonatal period in Brazil: nested casecontrol study. Bmj 1999;318:1316–20. 51. Kirkwood BR, Gove S, Rogers S, Lob-Levyt J, Arthur P, Campbell H. Potential interventions for the prevention of childhood pneumonia in developing countries: a systematic review. Bull World Health Organ 1995;73:793–8. 52. Verani JR, McGee L, Schrag SJ. Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. MMWR Recomm Rep 2010;59(RR10):1–36. 53. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al. A populationbased comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002;347:233–9. 54. Lin FY, Brenner RA, Johnson YR, Azimi PH, Philips 3rd JB, Regan JA, et al. The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease. American Journal of Obstetrics and Gynecology 2001;184:1204–10. 55. Antenatal care: routine care for the healthy pregnant woman. In: Excellence NIfHaC, editor. 2nd ed. London: RCOG Press, 2008. 56. Management of the Child with a serious infection or severe malnutrition: Guidelines for care at First-referral level in developing countries. In: WHO, editor. Geneva: World Health Organization, 2000. 57. Meritano J, Abraham S, Di Pietro S, Gerez G, Fernndez V. Respiratory distress syndrome associated with meconiumstained amniotic fluid in term and postterm newborns: Incidence, risk factors, morbidity, and mortality. Pediatric Research Conference: 47th Annual Meeting of the Latin American Society for Paediatric Research, LASPR Asuncion Paraguay Conference Start 2010;67:446. 58. Dargaville PA, Copnell B. The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome. Pediatrics 2006;117:1712–21.
CME SECTION This article has been accredited for CME learning by the European Board for Accreditation in Pneumology (EBAP). You can receive 1 CME credit by successfully answering these questions online. (A) Visit the journal CME site at http:// www.prrjournal.com/ (B) Complete the answers online, and receive your final score upon completion of the test. (C) Should you successfully complete the test, you may download your accreditation certificate (subject to an administrative charge).
59. Yoder BA, Kirsch EA, Barth WH, Gordon MC. Changing obstetric practices associated with decreasing incidence of meconium aspiration syndrome. Obstetrics and Gynecology 2002;99(5 Pt 1):731–9. 60. Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syndrome. Unresolved issues. Pediatric Clinics of North America 1993;40:955–81. 61. Ross MG. Meconium Aspiration Syndrome - More Than Intrapartum Meconium. New England Journal of Medicine September 2005;353:946–8. 62. Sriram S, Wall SN, Khoshnood B, Singh JK, Hsieh HL, Lee KS. Racial disparity in meconium-stained amniotic fluid and meconium aspiration syndrome in the United States, 1989–2000. Obstetrics and Gynecology 2003;102:1262–8. 63. Sedaghatian MR, Othman L, Hossain MM, Vidyasagar D. Risk of meconiumstained amniotic fluid in different ethnic groups. J Perinatol 2000;20:257–61. 64. Duran R, Aladag N, Vatansever U, Sut N, Acunas B. The impact of Neonatal Resuscitation Program courses on mortality and morbidity of newborn infants with perinatal asphyxia. Brain Dev 2008;30:43–6. 65. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet 2004;364:597–602. 66. Intrapartum care: Care of healthy women and their babies during childbirth. In: Excellence NifHaC, editor. London: NICE, 2007. 67. Coltart TM, Byrne DL, Bates SA. Meconium aspiration syndrome: a 6-year retrospective study. Br J Obstet Gynaecol 1989;96:411–4. 68. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made a difference? Pediatrics 1990;85:715–21. 69. El Shahed A, Dargaville P, Ohlsson A, Soll R. Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane database of systematic reviews 2007;3:CD002054. 70. Ka¨a¨pa¨ PO. Meconium aspiration syndrome (MAS) - Where do we go? Research perspectives. Early Hum Dev 2009;85:627–9. 71. Kotecha S, Barbato A, Bush A, Claus F, Davenport M, Delacourt C, et al. European respiratory society task force on congenital diaphragmatic hernia. Eur Respir J 2012;39(4). 72. Spitzer AR, Davis J, Clarke WT, Bernbaum J, Fox WW. Pulmonary hypertension and persistent fetal circulation in the newborn. Clinics in Perinatology 1988;15:389–413. 73. Roberts JD, Polaner DM, Lang P, Zapol WM. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:818–9. 74. Kinsella JP, Neish SR, Shaffer E, Abman SH. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 1992;340:819–20. 75. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database of Systematic Reviews 2006;4. CD000399. 76. Sartori C, Allemann Y, Trueb L, Delabays A, Nicod P, Scherrer U. Augmented vasoreactivity in adult life associated with perinatal vascular insult. Lancet 1999;353:2205–7. 77. Konduri GG, Kim UO. Advances in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatric Clinics of North America 2009;56:579–600. 78. Bennett CC, Johnson A, Field DJ, Elbourne D. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation: follow-up to age 4 years. Lancet 2001;357:1094–6. 79. The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up to 1 year of age. Pediatrics 1998;101:E1. 80. UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. UK Collaborative ECMO Trail Group. Lancet 1996;348: 75–82. 81. Bahrami KR, Van Meurs KP. ECMO for neonatal respiratory failure. Seminars in Perinatology 2005;29:15–23. 82. Arbor A. ECLS Registry Report International Summary. Extracorporeal Life Support Organization 2004. 83. Greenough A, Morley C, Roberton N. Acute respiratory diseases in the newborn. In: Roberton N, editor. Textbook of Neonatology. 2nd ed., London: Churchill Livingstone; 1992. p. 385–504. 84. Horbar JD, Badger GJ, Carpenter JH, Fanaroff AA, Kilpatrick S, LaCorte M, et al. Trends in mortality and morbidity for very low birth weight infants, 1991– 1999. Pediatrics 2002;110(1 Pt 1):143–51. 85. Kotecha S, Barbato A, Bush A, Claus F, Davenport M, Delacourt C, et al. Antenatal and postnatal management of congenital cystic adenomatoid malformation. Paediatric Respiratory Reviews 2012. doi: 10.1016/j.prrv.2012.01.002. In Press.
1. a. b. c. d. e.
Which of the following is NOT a sign of respiratory distress: Tachypnoea Grunting Tachycardia Apnoea Abdominal distension
2. Which of the following is the commonest cause of respiratory distress in the term infant? a. Respiratory distress syndrome
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37
b. c. d. e.
Pneumonia Pneumothorax Transient tachypnoea of the newborn Meconium aspiration syndrome
3. a. b. c. d. e.
With regards to congenital pneumonia: The pathogen is always bacterial. Is often preceded by chorioamnionitis. Broad-spectrum antibiotics should be used as treatment. Group B Strep on lower vaginal swabs is a risk factor. Can be secondary to invasive mechanical ventilation.
4. ECMO is indicated in the following circumstances: a. A term infant with severe MAS, not responding to high frequency oscillatory ventilation.
b. A term infant with a spontaneous pneumothorax. c. A term infant with persistent pulmonary hypertension of the newborn not responding to maximal medical therapy. d. A term infant with severe congenital diaphragmatic hernia. e. A preterm infant (30 weeks gestation) with respiratory distress syndrome. 5. a. b. c. d. e.
Antenatal steroids are licensed to be used to prevent: Congenital pneumonia Respiratory distress syndrome in the preterm infant Meconium aspiration syndrome Persistent pulmonary hypertension of the newborn Pneumothorax
37