SYMPOSIUM: NEONATOLOGY
Management of meconium
aspiration syndrome
Benjamin James Stenson
Claire Lindsay Smith
Abstract
Meconium aspiration syndrome (MAS) mainly affects term and post-term
infants. It ranges from mild respiratory distress to life-threatening cardio-
respiratory failure. Prevention and treatment strategies are evolving.
Amnioinfusion is no longer recommended for women with meconium
staining of the amniotic fluid (MSAF). Pharyngeal suction prior to delivery
of the fetal shoulders and tracheal suction of vigorous infants after birth
do not prevent MAS and may be harmful. Tracheal suction is recommen-
ded for non-vigorous infants with MSAF but has not been studied
prospectively. Bolus surfactant therapy, high frequency oscillatory ventila-
tion and inhaled nitric oxide may be beneficial in severe cases. Surfactant
lavage reduces the combined risk of death or requirement for extracorpo-
real membrane oxygenation (ECMO) when compared with no surfactant
treatment but its role in the routine management of MAS is uncertain
and it should be compared with bolus surfactant in prospective studies.
ECMO reduces the risk of mortality in severe cases so it is of paramount
importance to discuss the transfer of severely ill infants to an ECMO
centre.
Keywords extracorporeal membrane oxygenation; high frequency
ventilation; infant; labour, induced; meconium aspiration syndrome;
newborn; nitric oxide; persistent fetal circulation; pulmonary surfactant
Introduction
Meconium aspiration syndrome (MAS) mainly affects term or
post-term infants and can be defined as the presence of respira-
tory distress and chest X-ray changes, not explained by other
pathology, where there has been meconium stained amniotic
fluid prior to delivery.
Meconium staining of the amniotic fluid (MSAF) occurs in
around 4% of deliveries before 37 weeks, 10e20% of term
deliveries, and up to 30e40% of post-term deliveries. Around
5% of infants born through MSAF go on to develop meconium
aspiration syndrome. In the developed world, 0.43e2.1 per 1000
live-born infants receive mechanical ventilation for MAS.
Benjamin James Stenson MD FRCPCH is Consultant Neonatologist at the
Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh,
Little France Crescent, Edinburgh, UK.
Claire Lindsay Smith MD MRCPCH is a Higher Specialist Trainee in
Neonatal Medicine at the Simpson Centre for Reproductive Health,
Royal Infirmary of Edinburgh, Little France Crescent, Edinburgh, UK.
PAEDIATRICS AND CHILD HEALTH 22:12
What’s new?
C Amnioinfusion is no longer recommended for women with
MSAF.
C Surfactant lavage has been shown to reduce the risk of death or
requirement for ECMO. Larger trials, including comparison with
bolus surfactant treatment are required to define its role.
Mortality rates for infants with meconium aspiration syndrome
remain around 2.5e5%.
Pathophysiology
In most cases MSAF is not associated with identifiable fetal
compromise and may simply reflect fetal gut maturation.
However, meconium passage may follow fetal stress such as
hypoxia-ischaemia, and this may also be associated with fetal
gasping, leading meconium to be aspirated into the fetal airways.
It is unclear to what extent meconium enters the distal airways in
utero or after delivery with the onset of air breathing.
Meconium consists of gastrointestinal and pancreatic secre-
tions, bile and bile acids, mucous, swallowed vernix, lanugo
hair, blood and cellular debris. The pathophysiology of meco-
nium aspiration syndrome is multi-factorial and reflects the
direct effects of meconium in the airways, the resulting inflam-
matory response and any associated hypoxic-ischaemic insult.
There is mechanical obstruction, chemical pneumonitis, surfac-
tant dysfunction and pulmonary vasoconstriction. Mechanical
obstruction, particularly in expiration leads to gas trapping, local
or generalized hyperinflation and increased risk of air leaks.
Chemical pneumonitis occurs, invoking a powerful inflammatory
response through cytokines such as IL-8, pro-inflammatory
enzymes such as phospholipase A2 and by activating comple-
ment. Surfactant dysfunction results from direct inhibition,
toxicity to type II pneumocytes, displacement of surfactant from
the surface of alveoli and reduction of surfactant proteins A and
B. Pulmonary vasoconstriction due to release of vasoconstrictors
such as endothelin and thromboxane, contributes to pulmonary
hypertension. Meconium may also induce non-inflammatory cell
death (apoptosis) in the lungs. Ventilation perfusion mismatch
and intrapulmonary shunting, lead to hypoxaemia, hypercarbia
and acidosis and in may progress to severe cardiorespiratory
failure.
Respiratory distress, cyanosis and chest hyperinflation may be
observed from soon after birth or develop over several hours.
Typical X-ray changes are of hyperinflation and patchy intersti-
tial shadowing (Figure 1). More uniform atelectasis is also seen
in some cases. The X-ray changes and clinical severity do not
always correlate.
Management
General supportive measures
Most infants born through MSAF do not require resuscitation at
birth and remain well. In the absence of other concerns or risk
factors they should receive routine postnatal care. Infants who
develop signs of respiratory distress require further management
532 Ó 2012 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: NEONATOLOGY
Figure 1 Chest X-ray of a ventilated infant with meconium aspiration
syndrome showing typical appearances of hyperinflation and patchy
interstitial shadowing.
and admission to a neonatal unit. Although there is little
objective evidence regarding the general management of infants
with MAS, monitoring and treatment should include the
following:
 Careful observation with monitoring of heart rate, respi-
ratory rate and oxygen saturation.
 Minimal handling.
 Treatment with intravenous fluids, rather than enteral
feeding, until respiratory signs subside.
 Oxygen therapy to maintain saturation in the upper 90s,
aiming to minimize pulmonary hypertension.
 Blood gas and blood glucose monitoring to detect wors-
ening respiratory acidosis or the development of
hypoglycaemia.
 For ventilated infants, assessment of the need for anal-
gesia, sedation and in some cases muscle relaxation to
facilitate optimal ventilation.
It is usual practice for infants with respiratory distress of
uncertain aetiology to be treated with antibiotics pending blood
culture results. Meconium would usually be sterile prior rupture
of the fetal membranes so its presence around delivery does not
make a strong argument for routine antibiotic therapy. One small
randomized controlled trial showed no evidence of reduction in
neonatal sepsis or neonatal intensive care admission following
maternal antibiotic prophylaxis in labour where there was MSAF
but power was limited by sample size. Passage of meconium may
be triggered by a fetal stress response and this could be due to
infection. Given the potential devastating effects of neonatal
sepsis, it is reasonable to perform blood cultures and give
empirical treatment with penicillin and gentamicin for possible
early onset sepsis until the results are available. Large studies
would be required to answer the question definitively.
PAEDIATRICS AND CHILD HEALTH 22:12
The clinical management of MAS can be considered in two
phases: perinatal and postnatal management.
Perinatal management
Management of “post dates” pregnancy
MAS is clearly associated with advancing gestation, especially
beyond 40 weeks. MAS is reduced after induction of labour post
dates in comparison with expectant management. The relative
risk of MAS at 41 weeks after induction compared with expectant
management is 0.29 (95% CI 0.12e0.68). The relative risk at 42
weeks is 0.66 (CI 0.24e1.81) but this is not statistically signifi-
cant. However, the absolute risk of MAS is small and this, in
isolation, is not considered to be an indication for post dates
induction of labour. Key goals of intrapartum care to minimize
the risk of MAS include early detection and prompt management
of fetal hypoxia.
Amnioinfusion
Transcervical infusion of fluid during labour with MSAF was
postulated potentially to reduce MAS by diluting thick meconium,
reversing oligohydramnios or by providing support to the umbil-
ical cord and thus reducing the risk of cord obstruction. A Cochrane
review by Xu et al. concluded that amnioinfusion was not benefi-
cial in terms of significant reduction of perinatal deaths or
morbidity in infants with meconium staining of the liquor, except
perhaps in resource poor settings with limited means of fetal
monitoring. Amnioinfusion is not without risks, including cord
prolapse and prolongation of labour. The UK National Institute of
Health and Clinical Excellence (NICE) Guidelines, currently
recommend against use of amnioinfusion in women with MSAF.
Pharyngeal suction before delivery of the fetal shoulders
A large randomized multi-centre study by Vain et al., showed
that the incidence of MAS, the need for mechanical ventilation
and mortality rates were similar for infants whether or not they
received intrapartum pharyngeal suction. Following this trial,
intrapartum pharyngeal suction is no longer recommended.
Postpartum management
Tracheal suction
The value of attempting to suction meconium from the trachea
remains unclear. Meta-analysis of four randomized controlled
trials of tracheal suction of vigorous infants (good tone, sponta-
neous respirations and heart rate of over 100 beats per minute)
does not support routine endotracheal suction of such infants.
Laryngoscopy and tracheal suction are still recommended prior
to commencement of positive pressure ventilation in infants who
are not vigorous at delivery. The benefits and risks of this
approach have not been evaluated in a prospective randomized
study. Such a trial would be a valuable addition to the literature.
Nasal continuous positive airway pressure (nCPAP)
Many neonatologist use nCPAP to support infants with respira-
tory dysfunction and its use in infants with MAS has been
described. Others avoid using nCPAP in this condition because of
the association between MAS, gas trapping and air leaks. There is
no clear evidence of benefit or harm for nCPAP in this patient
group as trials are lacking.
533 Ó 2012 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: NEONATOLOGY
Conventional ventilation
Ventilation of infants with MAS can be challenging and there
are no evidenced criteria for commencing ventilation or for
ventilatory strategies. Differing patterns of disease in MAS, with
some infants having homogenous lung changes and others the
more common patchy disease, mean that ventilation has to be
tailored to the individual clinical picture. It is common to aim
for a long expiratory time to avoid exacerbation of any air
trapping. It may be helpful to use pulmonary flow graphics to
ensure that the selected expiratory time allows complete
expiration.
In infants with severe MAS, there is often a requirement for
high airway pressures and high FiO2. It is common for sedation
and muscle relaxants to be used in order to optimize ventilation
and minimize the risk of pneumothorax associated with dys-
synchronous breathing.
High frequency oscillatory ventilation (HFOV)
In view of the high pressures often required with conventional
ventilation and poor lung aeration in MAS, HFOV is commonly
used in MAS. HFOV, as a component of treatment in trials has
been seen to lead to short-term improvements in gas exchange
but trials to define the role of HFOV in infants with MAS more
clearly have not yet been undertaken.
Surfactant replacement
Most neonatologists now consider surfactant treatment to be an
integral component of the management of MAS. Because of
surfactant inhibition, several doses of surfactant may be required
before the desired response is achieved. Meta-analysis of clinical
trials of surfactant replacement has not shown any statistically
significant reduction in mortality, duration of ventilation or air
leak when surfactant replacement is instituted. However, in two
randomized controlled trials, the severity of the respiratory
illness was reduced as there was a significant reduction in the
number of infants requiring treatment with extracorporeal
membrane oxygenation (ECMO). Relative risk was 0.64 (95% CI
0.46e0.91) and number needed to treat was 6 (95% CI 3e25).
Surfactant lavage
Surfactant lavage aims to use relatively large volumes of diluted
surfactant to facilitate removal of meconium from the lungs,
while at the same time maintaining adequate surfactant function.
A recent randomized controlled trial of 66 infants compared
lavage using two 15 ml/kg aliquots of dilute surfactant (in 0.9%
saline) with standard care (high frequency ventilation, inhaled
nitric oxide and ECMO as indicated). There was no benefit shown
for the primary outcome in this study e duration of ventilatory
support. There was a reduced risk of the combined outcome of
death or ECMO with surfactant lavage: OR 0.24 (95% CI 0.06e
0.9). Transient desaturations were observed during lavage in this
study but significant alterations in blood pressure and heart rate
were not noted. Meta-analysis that included this, another small
randomized trial and eight non-randomized series concurred
with these findings. Despite this, there is still concern that the
procedure is technically demanding and that complications are
not uncommon. Larger trials are still required to determine the
place of this treatment in clinical practice and this should include
comparison with bolus surfactant treatment.
PAEDIATRICS AND CHILD HEALTH 22:12
Nitric oxide
Many infants with MAS have significant persistent pulmonary
hypertension of the newborn (PPHN). General measures to
maintain homeostasis including maintenance of adequate
systemic blood pressure, normalization of acid base balance and
avoidance of hypercarbia are important. Inhaled nitric oxide
(iNO) reduces the need for ECMO in infants with PPHN and has
been widely used in the management of MAS-related PPHN. In
cases of severe lung disease, iNO may be more effective if used in
combination with HFOV in order to maximize alveolar recruit-
ment. Infants with MAS have not been studied in isolation with
respect to iNO therapy but have been included in subgroups
within larger studies of iNO in term infants with PPHN and
severe respiratory failure. Definitive conclusions about the effi-
cacy of iNO in MAS are therefore not possible on current
evidence.
Corticosteroids
Chemical pneumonitis is part of the pathophysiology of MAS.
Corticosteroids have been thought to be potentially beneficial by
virtue of their anti-inflammatory properties. However,
a Cochrane review of two relatively small studies did not show
any benefit from steroid use in terms of mortality, duration of
ventilation or development of air leak. Infants who received
steroids were seen to have a small but significant increase in
duration of oxygen therapy. More recent studies have contra-
dicted this particular finding with reduced oxygen dependence
and improved X-ray appearances seen in infants treated with
steroids. Further, definitive studies would be beneficial to
determine the role of this treatment. Given concerns of the effects
of corticosteroids on infant growth and neurodevelopment,
treatment with steroids should not be considered standard
practice in the meantime.
Extracorporeal membrane oxygenation (ECMO)/
extracorporeal life support (ECLS)
As the pulmonary effects of meconium aspiration syndrome are
largely reversible, infants with severe disease are ideal candi-
dates for rescue therapy with ECMO. Outcome data from ECLS
registries and from the UK collaborative ECMO trial have shown
mortality rates of severe MAS to be reduced by ECLS and the
overall mortality rate of infants treated with ECLS for MAS is
extremely low. While implementing therapies such as HFOV,
iNO and surfactant is important in infants with severe disease,
delay in considering ECLS for the sickest infants must be avoi-
ded. It is vital that infants who are developing severe disease be
discussed with an ECLS centre so that the timing of transfer is
optimized and death prior to ECLS being instituted is avoided
wherever possible.
Outcome
Most infants with MAS recover to good health but there are
potential long term sequelae both in terms of pulmonary function
and neurological outcome. Increased incidence of wheeze and
bronchial reactivity in infancy and of asthma in later childhood
have been observed in infants who had MAS. In addition, MAS is
closely associated with perinatal hypoxia-ischaemia which
carries with it an increased risk of adverse neurodevelopmental
outcome. The risk is compounded by exposure to postnatal
534 Ó 2012 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: NEONATOLOGY
cardiorespiratory compromise and exposure to therapies which
may in themselves be associated with adverse outcomes. By
provoking a systemic inflammatory response with release of
inflammatory mediators into the systemic circulation it is
possible that MAS may cause injury remote from the lungs. More
research is needed to elucidate this.
Conclusions
The management of MAS continues to evolve. There is still
a need for further clinical studies to determine the optimal
overall treatment strategies. With good treatment, survival to
normal health should be the expected outcome for most infants.
Those with severe disease should be discussed promptly with an
ECMO centre to ensure that risk of mortality is minimized. A
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Practice points
C MAS occurs more commonly in post dates pregnancies and
incidence is reduced when labour is induced, in comparison
with continued expectant management
C Amnioinfusion is no longer recommended for women with
MSAF
C Routine pharyngeal suction prior to delivery of the shoulders
and routine tracheal suction in vigorous infants are no longer
recommended as they do not reduce the incidence of MAS
C Non-vigorous infants should have tracheal suction performed
at birth prior to positive pressure ventilation
C Surfactant replacement, HFOV and iNO are effective strategies
in ventilated infants with severe respiratory failure
C Surfactant lavage has been shown to reduce to risk the of
death or requirement for ECMO but its role remains uncertain
C ECMO reduces mortality in infants with the most severe
disease and early discussions with an ECMO centre should be
undertaken
535 Ó 2012 Elsevier Ltd. All rights reserved.