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
Respiratory distress is common in the early neonatal period and
occurs in up to 7% of newborn infants.
Much of the focus has been
on respiratory distress syndrome and chronic lung disease of
prematurity in preterm infants (<37 weeks of gestation)
every year a significant number of term-born infants are admitted
to neonatal units for management of their respiratory distress.
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.
In Switzerland, Ersch et al. reported an increasing incidence of
respiratory distress of all neonates admitted to neonatal units
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.
The impact of elective caesarean sections
has specifically increased the incidence of respiratory distress in
term infants.
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).
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).
Between 1990 and 2002, the admission
rate to a busy neonatal unit in England was 8.6% of all live births.
The commonest reason for admission was respiratory distress.
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).
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
Paediatric Respiratory Reviews 14 (2013) 29–37
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.
Respiratory distress syndrome
Transient tachypnoea of the newborn
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, meconiumaspiration 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.
* 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: (M.O. Edwards), (S.J. Kotecha), (S. Kotecha).
Contents lists available at SciVerse ScienceDirect
Paediatric Respiratory Reviews
1526-0542/$ – see front matter ß 2012 Elsevier Ltd. All rights reserved.
stained liquor being most frequently noted at 39–41 weeks
Thus, avoiding routine elective caesarean sections
prior to 38 weeks of gestation would markedly decrease the
incidence of respiratory problems in the term infant.
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, C-
reactive 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.
TTN was first coined by Avery in 1966 and is now recognised as
the commonest cause of respiratory distress in newborn term
It is caused by the delay in the absorption of fluid in the
lungs after birth (i.e. excessive lung fluid).
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 tothe neonatal unit for a fewdays accounting
for approximately 10% of all newborn term admissions.
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.
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.
Other risk factors
include delivery prior to 38 weeks of gestation, male sex, low birth
weight and macrosomia
and maternal diseases such gesta-
tional diabetes and asthma.
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
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.
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.
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.
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
Table 1
Differential diagnosis of respiratory distress in term-born infants.
Common conditions
Transient tachypnoea of the newborn
Respiratory distress syndrome
Meconium aspiration syndrome
Primary or secondary pulmonary arterial hypertension
Cardiac failure (due to congenital heart disease)
Hypoxic-ischaemic encephalopathy
Aspiration of milk or blood
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
Figure 1. The common signs and symptoms of respiratory distress in term newborn
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37 30
such as diuretics have been tested but fail to change the course of
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.
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.
In a review of TTN, Yurdakok
suggests a genetic link between TTN and later onset asthma.
RDS is caused by a deficiency of surfactant and is often also
called hyaline membrane disease, which strictly speaking is a
histological diagnosis.
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%
to 11.5%
of infants with RDS
and those with gestational age of 37 weeks gestation account for
The Near-Term Respiratory Failure Research Group, who
studied 1011 infants (mean gestational age of 37 Æ 2 weeks
gestation), who all required mechanical ventilation, identified 43%
developed RDS.
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.
production of surfactant by type 2 pneumocytes commences
around 24–25 weeks gestation reaching adequate levels to support
Is it a cardiac or respiratory problem?
Consider the need for Chest
radiograph and Echocardiogram.
FAQ’s when assessing an infant
with respiratory distress
What is the gestaƟonal 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 anything else causing
the respiratory distress?
Consider metabolic, renal,
neurological causes.
Is there poor improvement with increasing oxygen flow?
Persistent hypoxia and cyanosis despite 100% oxygen
need to consider PPHN or CCHD.
What was the delivery method?
Pre-labour secƟon more likely to
be TTN; Evidence of MSAF is
more likely to be MAS.
Are there any risk factors for
PROM, GBS on HVS, maternal
pyrexia or raised inflammatory
markers in maternal bloods
would suggest pneumonia.
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
Review antenatal scan reports
for CDH, CCAM etc…
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.
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37 31
breathing after birth by 36–37 weeks gestation.
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.
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.
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.
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.
elective caesarean sections may help, although RDS secondary to
caesarean section accounts for only a small number of the total
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
shows air bronchograms (Figure 4) and reticulonodular shadowing
throughout the lung fields (often termed ‘ground glass’ appear-
ance). In many neonatal units there are well-established guidelines
for the management of RDS in newborn infants, including the use
of exogenous surfactant.
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
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 abnormal-
ities) and early childhood remains high for preterm infants with
respiratory distress syndrome’.
The long term effects of
respiratory disease in the newborn however require further
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.
Pneumonia may be acquired due to ascending infection
especially when chorioamnionitis is present or postnatally from
nosocomial acquired infections.
The most likely cause for the
former is inhalation of infected amniotic fluid and cross-
contamination for the latter, which can be prevented by strict
Figure 3. Chest radiograph showing TTN. The x-ray shows ‘‘a wet silhouette’’
around the heart with fluid in the horizontal fissure.
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).
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37 32
anti-septic measures including hand-washing. Common patho-
gens 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 infec-
tion (maternal fever or raised white cell count), particularly with
Birth weight and age of onset are both strongly associated
with the mortality risk from pneumonia.
Pneumonia can occur
secondary to invasive mechanical ventilation but is largely
confined to preterm infants who receive prolonged ventilation.
The most important and easiest method of preventing
nosocomial pneumonia is hand washing to prevent cross-infection
between vulnerable infants.
Other methods of prevention
include following local guidelines for the management of
premature rupture of membranes
and encouraging early and
exclusive breast feeding.
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.
Universal screening and antepartum treatment can
reduce the rate of early-onset disease by 89%.
In the UK and
other countries, however, screening is more targeted but those at
risk are treated with intrapartum antibiotics.
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
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.
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.
Supportive care such as oxygen, thermoregulation, prevention of
hypoglycaemia and parenteral nutrition or nasogastric tube
feeding are often required.
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 term-
and 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.
Furthermore, the
incidence of MAS in developed countries is on the decline possibly
due to improved obstetric care.
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
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.
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 gesta-
tional age, foetal distress, male sex, Apgar score of less than 7 and
The Australian and New Zealand Neonatal
Network have shown that foetal distress and low Apgar scores can
increase the risk of MAS.
There is also an apparent relationship
between maternal ethnicity and the risk of developing MAS with
black Americans and Africans being at greatest risk.
Duran et al. have reported a significant reduction in the
incidence of perinatal asphyxia and improved Apgar scores at one Figure 5. Chest radiograph showing congenital pneumonia.
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37 33
minute following the introduction of neonatal resuscitation
programs for labour ward staff.
Reducing post-term deliveries
has also been shown to reduce the incidence of MAS.
The practise
of oropharyngeal suctioning is no longer recommended and has
been shown to be of no benefit and may even cause harm.
It is common practise to carry out ‘meconium observations’ for
between 12 to 24 hours on all babies born following MSAF.
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.
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),
inhaled nitric oxide, and
inotropic support as required and extracorporeal membrane
(which is discussed below).
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.
Pulmonary arterial hypertension is relatively common in new-
born 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.
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
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.
Echocardiography is mandatory and is likely to confirm raised
pulmonary arterial pressures and any shunting across the patent
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
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.
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.
There is some evidence that pulmonary
hypertension may persist into adulthood for survivors of PPHN.
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.
The UK collaborative rando-
mized trial of neonatal ECMO showed significant survival but
neurodevelopmental deficits remain significant.
ECMO can
support either the lungs alone (veno-veno) or in combination with
the cardiac function (veno-arterial). ECMO provides an opportu-
nity 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.
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%.
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
The clinical presentation may vary from mild or
severe signs of respiratory distress to a gradual decline in
respiratory function.
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 ventila-
Risk factors
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 34
exposed to mechanical ventilation or vigorous resuscitation
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. Pneu-
mothoraces 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.
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 adeno-
matoid malformation, pulmonary hypoplasia, trachea-oesopha-
geal 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.
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 morbid-
ity 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 appro-
priate management is important to ensure the optimal outcome for
all infants presenting with respiratory distress.
No conflict of interest of any of the authors.
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 Associa-
tion 2010;304:419–25.
5. Qandalji B. Full term neonatal admissions. Early Human Development Confer-
ence: 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 pro-
spective survey from a Chinese neonatal network. Chinese Medical Journal 2010;
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 respira-
tory 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
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,
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;
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 ran-
domised trial. Bmj 2005;331:662.
26. Kurl S, Heinonen KM, Kiekara O. The first chest radiograph in neonates exhibit-
ing 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 meta-
analysis 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
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 esti-
mated gestational age of 34 weeks or more. Journal of Perinatology 2005;
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.
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37 35
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:
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. Manage-
ment 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. Surfactant-
replacement 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
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 Sta-
phylococcus 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 case-
control 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 coun-
tries: 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(RR-
53. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al. A population-
based 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 post-
term 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.
59. Yoder BA, Kirsch EA, Barth WH, Gordon MC. Changing obstetric practices
associated with decreasing incidence of meconium aspiration syndrome. Obste-
trics and Gynecology 2002;99(5 Pt 1):731–9.
60. Wiswell TE, Bent RC. Meconium staining and the meconium aspiration syn-
drome. 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 meconium-
stained 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. Orophar-
yngeal and nasopharyngeal suctioning of meconium-stained neonates before
delivery of their shoulders: multicentre, randomised controlled trial. Lancet
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
72. Spitzer AR, Davis J, Clarke WT, Bernbaum J, Fox WW. Pulmonary hypertension
and persistent fetal circulation in the newborn. Clinics in Perinatology
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
77. Konduri GG, Kim UO. Advances in the diagnosis and management of persistent
pulmonary hypertension of the newborn. Pediatric Clinics of North America
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 oxy-
genation. 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 Sup-
port 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.
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1. Which of the following is NOT a sign of respiratory distress:
a. Tachypnoea
b. Grunting
c. Tachycardia
d. Apnoea
e. 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 36
b. Pneumonia
c. Pneumothorax
d. Transient tachypnoea of the newborn
e. Meconium aspiration syndrome
3. With regards to congenital pneumonia:
a. The pathogen is always bacterial.
b. Is often preceded by chorioamnionitis.
c. Broad-spectrum antibiotics should be used as treatment.
d. Group B Strep on lower vaginal swabs is a risk factor.
e. 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
d. A term infant with severe congenital diaphragmatic hernia.
e. A preterm infant (30 weeks gestation) with respiratory
distress syndrome.
5. Antenatal steroids are licensed to be used to prevent:
a. Congenital pneumonia
b. Respiratory distress syndrome in the preterm infant
c. Meconium aspiration syndrome
d. Persistent pulmonary hypertension of the newborn
e. Pneumothorax
M.O. Edwards et al. / Paediatric Respiratory Reviews 14 (2013) 29–37 37