Symposium 4: Challenges in neonatal care

MECONIUM ASPIRATION
SYNDROME
Ismail Haron
Consultant Paediatrician & Neonatologist
Hospital Sungai Buloh

Challenges in neonatal care: Meconium Aspiration Syndrome

Introduction
Epidemiology
Pathogenesis of MAS
Clinical features
Management
General
Specific

Conclusion

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Introduction
Meconium aspiration syndrome (MAS) is not
an uncommon problem.
Important cause of respiratory distress in the term
newborn with high morbidity and mortality.
The pathophysiology is complex and is not well
defined.
Despite advances in neonatal intensive care over
the last 2 decades, MAS remains one the most
vexing clinical conditions to manage.

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Composition of meconium
Sterile compound made primary of water (75%),
with mucous glycoproteins, lipids and proteases.
Small dried amniotic fluid debris, vernix and lanugo.
Bile pigments.
The residue from intestinal secretions.

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Epidemiology

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Epidemiology
Approximately 10 15% of all live births are
complicated by meconium stained amniotic fluid (MSAF).
About 5% of neonates born through MSAF develop MAS.
MSAF and MAS related to advanced gestation.
Generally incidence of MSAF and MAS are in a declining
trend.

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Incidence of MAS according to gestation

Yoder BA et al. Obstet Gynecol 2002;99:731-9

Dargaville PA, Copnell B. Pediatrics 2006;117:1712-1721
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Incidence of MAS

Yoder BA et al. Obstet Gynecol 2002;99:731-9

Dargaville PA, Copnell B. Pediatrics 2006;117:1712-1721
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Pathogenesis of
MAS

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Causes of MSAF
Under normal circumstances, the passage of meconium from
the fetus into the amnion is prevented by;
Lack of intestinal peristalsis (low motilin level)
Tonic contraction of anal sphincter
Terminal cap of viscous meconium

Fetal maturation post-term.

Vagal stimulation produced by head or cord compression in
the absence of fetal distress.
In-utero stress (hypoxia and acidosis) producing relaxation
of anal sphincter
Presence of meconium in the amniotic fluid may increase the
risk of intraamniotic infection.
Piper HM et al. Obstet Gynecol 1998;91:741-5
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Risk factors
Maternal hypertension
Maternal diabetes mellitus
Maternal heavy cigarette smoking.
Maternal chronic respiratory or CVS disease.
Post-term pregnancy.
Pre-eclampsia / eclampsia
Oligohydramnios
Intrauterine growth retardation
Poor biophysical profile
Abnormal fetal heart rate patterns

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Causes of MAS
Reason why some infants born through MSAF develop
an aspiration syndrome whereas others do not unclear.

Aspiration of meconium may occur in-utero or after delivery

with the first few breaths.
Chronic fetal hypoxia and acidosis may lead to fetal gasping
and the subsequent in-utero aspiration of meconium.
Chronic in-utero insult may be responsible for most cases of
severe MAS as opposed to an acute peripartum event.
Blackwell SC et al. Am J Obstet Gynecol 2001;184:1422-6
Ghidini A, Spong CY. Am J Obstet Gynecol 2001;185:931-8
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Mechanisms of injury
Mechanical obstruction of airways.
Chemical pneumonitis.
Vasoconstriction of pulmonary vessels.
Inactivation of surfactant.
Activation of complement.
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Mechanism of injury cont

Mechanical obstruction of airways

Thick and viscous.
Complete or partial airway obstruction.
With onset of respiration meconium migrates
from central to peripheral airways.
Complete obstruction atelectasis
Partial obstruction
Ball-valve air trapping.
Risk of pneumothorax - 15 33%
Cleary GM, Wiswell TE. Pediatr Clin North Am. 1998;45:511-29

V/Q mismatch
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Mechanism of injury cont

Pneumonitis
Neutrophils & Macrophages

Cytokines

(alveoli, airway & parenchyma)

(TNF, IL-1, IL-8)

Pneumonitis
Vascular leakage

Haemorrhagic pulmonary oedema

Bodil S et al. Pediatrics 2008;121:e496-e505

Kaoru O et al. Pediatrics 2008;121:e748-e753
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Mechanism of injury cont

Vasoconstriction of pulmonary vessels

Severe MAS may be complicated by PPHN.
Pulmonary vasoconstriction is in part may
be a result of the underlying inutero stress.
The release of vasoactive mediators as a
result of injury from meconium;
Eicosanoids,
Endothelin-1
Prostaglandin E2

Hageman JR, Caplan MS. Clin Perinatol 1995;22:251-261

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Mechanism of injury cont

Inactivation of surfactant
In the early 1990s meconium inactivates surfactant.
Greenough A. Eur J Pediatr 1995;154:S2-4

Meconium displaces surfactant from the alveolar surface

inhibits surface tension-lowering ability.
Direct inhibitory effect of meconium on the function of
surfactant in vitro an in in vivo animal models.
Cleary GM et al. Pediatrics 1997;100:998-1003
Higgins ST et al. Pediatr Res 1996;39:443-7

Surfactant deficiency due to inactivation leads to increased

surface tension;
Atelectasis
Decreased lung compliance
Decreased lung volumes
Findlay RD et al. Pediatrics 1996;97:48-52
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Mechanism of injury cont

Activation of complement
Meconium is a potent activator of the complement
Castellheim A et al. Pediatr Res 2004;55(2):310-318
system.
Castellheim A et al. Scand J Immunol 2005;61(3):217-225
Activation of complement system was correlated
with lung dysfunction and mortality.
Lindenskov PH et al. Pediatr Res 2004;56(5):810-817

Meconium-induced cytokines production is mediated

by complement and CD14.
Bodil S et al. Pediatrics 2008;121:e496-e505

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Physiologic meconium passage

(particularly if postdates)

Fetal compromise (hypoxia, cord

compression, etc) meconium passage

Meconium-stained amniotic fluid

Postpartum aspiration

Umbilical cord spasm

Inutero gasping

Continued compromise

Meconium aspiration
Peripheral airway
obstruction
Complete

Atelectasis

V/Q mismatch

Proximal airway
obstruction
Partial

Air trapping

Inactivation of surfactant

Pneumonitis
Decreased lung
compliance

Ball-valve
effect

Air leaks

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Cytokines activation

Acidosis
Acidosis
Hypoxemia
Hypoxemia
Hypercapnea
Hypercapnea

Remodeling of pulmonary
vasculature
(muscular hyperplasia)

Vasoactive mediators

PPHN

Clinical features

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Diagnosis
MAS must be considered in any infant born through MSAF
who develops symptoms of respiratory distress.

Various radiographic findings may be present.

Diffuse asymmetric patchy infiltrates

Areas of atelectasis
Hyperinflated areas

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Diagnosis
Severity of MAS

Mild
Requires < 40% oxygen for less than 48 hours

Moderate.
Requires > 40% oxygen for more than 48 hours
No air leak

Severe
Requires assisted ventilation for more than 48 hours
Often associated with PPHN

Cleary GM, Wiswell TE. Pediatr Clin North Am 1998;45:511-29

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Management

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Prevention
Prevention
Prevention
Prevention
Prevention
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Antepartum
Intrapartum
Postnatal
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Treatment
General
Temperature regulation
Haemodynamic status
Biochemistry
Haematology
Possible infection
Associated asphyxia
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Treatment
Respiratory management
Depends on the amount of respiratory distress.
Increasing oxygenation while minimising
barotrauma/volutrauma.
Hyperventilation did not proven beneficial.
No randomised trials have compared different
forms of ventilation in MAS.

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Treatment
Mode of ventilation
HFV claimed to be gentler.
Theoretically, HFV should reduce air leaks.
HFV may slow the progression of meconium
down the tracheobronchial tree and allow more
time for meconium removal.
Hachey WE et al. Crit Care Med 1998;26:556-61

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Treatment
Surfactant Therapy
Two randomised trials evaluate the efficacy of
exogenous surfactant therapy in MAS showed
promising results with decrease in the number of
infants requiring ECMO and possible reduction
of pneumothorax.
Findlay RD et al. Pediatrics 1996;97:48-52
Lotze A et al. J Pediatr 1998;132:40-7

Cochrane meta-analysis 4 randomised trials;

Reduce the use of ECMO (RR 0.64)
No effect on mortality
El Shahed A et al. Cochrane Database Syst Rev 2007

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Treatment
Surfactant Therapy
Surfactant inactivation property of meconium.
Herting E et a. Pediatr Res 2001;50:44-9

Search for new synthetic surfactant preparations;

highly resistant to inactivation by meconium.

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Treatment
Surfactant Lavage
Removal of noxious material from the lungs.
Minimised obstruction.
Offset the inactivation of surfactant by meconium
Increase oxygenation & reduction in duration of
mechanical ventilation
Lam BCC, Yeung CY. Pediatrics 1999;103:1014-8
Wiswell TE et al. Pediatrics 2002;109:1081-7

LessMAS Trial.

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Aetiology of PPHN

Clark RH et al. N Engl J Med. 2000;342:469-74

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Treatment
Inhaled nitric oxide
Selective pulmonary vasodilation.
Activate guanylate cyclase and increases cyclic GMP
and acting directly on the vascular smooth muscle.
Decreased need for ECMO (RR 0.61) but no difference
in mortality.

Finer NN, Barringtan KJ. Cochrane Database Syst Rev 2006

Pretreatment with surfactant improves in delivery of iNO

to the alveoli. Rais-Bahrami KRO et al. Crit Care Med 1997;25(10):1744-7
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Treatment
Inhaled nitric oxide
HFOV + iNO seems to work better, likely due to improve
lung inflation and better delivery of the drug.
Kinsella JP et al. J Pediatr 1997;131:55-62

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(RR:0.6)

(RR:0.6)

(RR:0.6)

(RR:0.6)

Clark RH et al. N Engl J Med. 2000;342:469-74

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Treatment
Steroid
Insufficient evidence to assess the effects of
steroid therapy in the management of MAS.
Ward M, Sinn J. Cochrane Database Syst Rev 2003

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Thank you for

your kind
attention
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