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Rita M. Ryan, MD
Chief, Division of Neonatology
Professor of Pediatrics, Pathology and Anatomical
Sciences, and Gynecology-Obstetrics
Meconium
first intestinal discharge from newborns is meconium
a viscous, dark green substance composed of intestinal epithelial cells,
lanugo, mucus, and intestinal secretions, such as bile.
Intestinal secretions, mucosal cells, and solid elements of swallowed
amniotic fluid are the 3 major solid constituents of meconium.
Water is the major liquid constituent, making up 85-95% of meconium.
MSAF
The passage of mec in utero accompanies 8% to 20%
(average 12-13%) of all deliveries
<37 weeks
2%
>42 weeks
44%
seen predominantly in infants who are SGA and postmature,
cord complications or other factors compromising the in
utero placental circulation
Prenatal Management
presence of MSAF is not always an
indication of fetal distress in all infants
Pathophysiology
passage of meconium in utero:
we think it is associated with asphyxia but data
actually are weak
? result of transient parasympathetic stimulation from
cord compression in a neurologically mature fetus
? natural phenomenon that reflects the maturity of
the GI tract
most agree that MSAF plus FHR abnormalities are a
marker for fetal distress and associated with
increased perinatal morbidity
Pathophysiology
Mec in the AF may stain the umb cord, placenta
and fetus
when fetal distress is present, gasping may be
initiated in utero AF and particulate matter
contained therein may be inhaled into the large
airways
mec aspiration may occur antenatally
mec inhaled by the fetus may be present in the
trachea or larger bronchi at delivery
after air
breathing has commenced
rapid distal
migration of mec within the lung
Pathophysiology
If aspiration of meconium stained
amniotic fluid before, during, and after
birth occurs, there can be 3 major
pulmonaryy effects:
p
airway obstruction
surfactant dysfunction
chemical pneumonitis
Ball--Valve Phenomenon
Ball
Pathophysiology
areas of atelectasis, resulting from total airway
obstruction, adjacent to
areas of overexpansion, from gas trapping in regions
with partial obstruction
salt and pepper appearance on CXR
air leaks
pneumomediastinum
pneumothorax
chemical inflammation
pneumonitis
in vitro: concentration-dependent inhibition of
surfactant
animal models: influx of inflammatory cells and protein,
inactivation of surfactant, decrease in surf proteins
Clinical Findings
postmaturity
mec staining nails, skin, umbilical cord
often perinatal depression
neurologic, resp depression secondary to hypoxia (which
precipitated the passage of mec in the first place)
Cyanosis
End-expiratory grunting
Alar flaring
Intercostal retractions
Tachypnea
Barrel chest in the presence of air trapping
Rales
Dave Clark emedicine 2004
Fanaroff and Martin 2002, Miller, Fanaroff and Martin
PPHN in MAS
Clinical Manifestations
clinical symptoms progress over 12-24
hours as mec migrates to the periphery
mec ultimately has to be removed by
phagocytosis
p
agocytos s
resp
esp distress
st ess and
a resp
esp
support may be persist for days or even
weeks
active vasoconstriction
directly or may cause plt aggregation
potent pulm vasoconstrictor
release of thromboxane, a
CXR
coarse, irregular densities with areas of
diminished aeration and consolidation
pneumomediastinum, PTX
hyperinflation
cardiomegaly at times, due to perinatal
asphyxia
salt and pepper
Meconium Aspiration
Treatment
let them breathe fast in hood oxygen
Diffuse chemical
pneumonitis
from constituents
of meconium
PPHN
Treatment
r/o sepsis but not automatic commitment
to a full course Abx
steroids are not recommended
textbook
te
tboo recommendation
eco
e at o but this
t s may
ay
be changing.
Surfactant
meconium may inhibit surf function
role for exogenous surf
multicenter RCT of term infants with
severee resp
seve
esp failure,
a u e, 50% of
o whom
w o had
a
MAS as primary dx
surf decr need for
ECMO
The need for ECMO therapy was significantly less in the surfactant group than in
the placebo group (p = 0.038)
this effect was greatest within the lowest oxygenation index stratum
(15 to 22; p = 0.013).
Sultantate of Oman
pilot study, case series, not RCT
all ventilated, all OI >25, all PPHN
average age starting dex 80hrs
dex 0.5/kg/day div q12h x3d, 0.3 x3d, 0.125 x3d
steroids started if not weaning on vent or OI worsening over
16h
RCT, 3 arms
placebo
0.5 mg/kg/d Methylprednisilone div q12h
50 ug q12h budesonide
blinded
not sure if ventilated population
2006
Steroids
Results
2 deaths, both in placebo group (one with
massive PTX, one with sepsis/DIC)
no baby in steroids group needed MV
Inflammation in MAS
11 neonatal patients with MAS, 16 neonates without
MAS, and 9 healthy children.
6 cytokines higher in MAS compared with non-MAS
neonates:
IL-6, IL-8, GM-CSF, G-CSF, interferon, MIP-1, and TNF
Steroids in MAS
Tripathi et al, Ind J Med Microbiology (2007) 25
(2):103-7
RCT, blinded, 3 groups
Placebo, methylprednisilone, inhaled budesonide
Steroids given for 7 days
Amnioinfusion
intrapartum suctioning
tracheal suctioning
Amnioinfusion
dilutes meconium
relieves cord compression
relieving
hypoxia
decreasing gasping
does it reduce MAS? meta-analysis of
13 studies suggests that both fetal
distress and MAS are decreased:
Hofmeyr, GJ et al, Cochrane review, 2001, 2004
update
Table 3 continued
Amnioinfusion Fraser WD et al
N Engl J Med 2005;353: 909909-17
Intrapartum suctioning
considered standard for 25 years
Carson et al Am J Ob Gyn 1976;126:712-5
Fanaroff
and Martin
2002,
Miller,
Fanaroff
and Martin
Circulation 2005
Intrapartum suctioning
Infants were randomly allocated to either suctioning
of the oropharynx and nasopharynx (including the
hypopharynx) before delivery of the shoulders
(suction group), or no suctioning (no-suction group).
10-Fr to 13-Fr connected to a negative pressure of
150 mm Hg.
Hg
Oropharyngeal suctioning was done first, followed by
bilateral nasopharyngeal suctioning, when possible.
Thereafter, care was given according to NRP
tracheal suctioning for non-vigorous infants
Intrapartum suctioning
The primary outcome was incidence of MAS.
Diagnosis of the syndrome was defined by
(1) respiratory distress (tachypnea, retractions, or
grunting) in a neonate born through MSAF;
(2) need
d ffor supplemental
l
l oxygen to maintain
i i oxygen
saturation levels at 92% or greater;
(3) oxygen requirements starting during the first 2 h of
life and lasting for 12 h or longer; and
(4) absence of congenital malformation of the airway,
lung, or heart.
Vain et al, Lancet 2004;364;597-602
Vain et al, Lancet 2004;364;597-602
10
Circulation 2005
Circulation 2005
Tracheal suctioning
Linder et al Israel J Peds 1988 n>500
commentary
method to enhance removal of particulate meconium
from the airway using bronchoalveolar lavage with a
dilute bovine surfactant preparation.
2 week old piglets
They found that a 30-ml/kg lavage volume of dilute
surfactant was associated with increased meconium
removal, improved post-lavage lung function, and less
lung injury as compared with perflourocarbon emulsion
or multiple, smaller aliquots of dilute surfactant.
controls
perfluorocarbon
11
perfluorocarbon
Surfactant lavage
8 babies enrolled
median age of 23 h (range 883 h)
88% nitric oxide, 3 on adrenalin infusion
lavage was associated with significant
desaturation but not bradycardia or hypotension
No lavage
all lavaged infants
Tx lavage
Surfactant lavage
ECMO usage
iNO
HFOV
surfactant
less post-term pregnancies
less ECMO
12
1993-4
1996-7
Pre-ECMO surfactant
iNO
3 (6.1%)
0
18 (44.7%)
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14
Results
MASINT
1061of 2,490,862 live births (0.43 of 1000)
decrease in incidence from 1995 to 2002
Pediatrics 2006;117;1712-1721
May 2006
Data were gathered on all of the infants in Australia and New Zealand who
were intubated and mechanically ventilated with a primary diagnosis of
MAS between 1995 and 2002, inclusive. Information on all of the live births
during the same time period was obtained from perinatal data registries.
MASINT
34% > 40 weeks gestation
6.5% > 41 weeks gestation
g
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Is there a trade-off?
Logistic regression
5 factors
independently related
to resp morbidity:
GA, C/S, male, FHR,
low 5 min Apgar
Summary
MSAF is often associated with in utero fetal distress and
hypoxia.
The pathophysiology of MAS includes airway obstruction,
surfactant inactivation and a chemical pneumonitis leading to
air trapping, atelectasis and PPHN.
Standard therapy for MAS includes supplemental oxygen,
mechanical ventilation, surfactant, nitric oxide and ECMO.
The use of ECMO for MAS-PPHN patients is decreasing due
to the increased use of other therapies such as HFV,
surfactant and iNO.
Preventive measures such as amnioinfusion, intrapartum oroand naso-phayngeal suctioning, and tracheal suctioning are
now controversial and no longer recommended as routine.
The incidence of MAS is decreasing, primarily related to
fewer post-mature infants and less intrapartum fetal distress.
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