The Journal of Maternal-Fetal & Neonatal Medicine

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Meconium aspiration syndrome: risk factors and

predictors of severity

Cláudia Patrícia Lourenço Oliveira, Filipa Flôr-de-Lima, Gustavo Marcondes

Duarte Rocha, Ana Paula Machado & Maria Hercília Ferreira Guimarães
Pereira Areias

To cite this article: Cláudia Patrícia Lourenço Oliveira, Filipa Flôr-de-Lima, Gustavo Marcondes
Duarte Rocha, Ana Paula Machado & Maria Hercília Ferreira Guimarães Pereira Areias (2017):
Meconium aspiration syndrome: risk factors and predictors of severity, The Journal of Maternal-
Fetal & Neonatal Medicine, DOI: 10.1080/14767058.2017.1410700

To link to this article: https://doi.org/10.1080/14767058.2017.1410700

Published online: 08 Dec 2017.

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 THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE, 2017
https://doi.org/10.1080/14767058.2017.1410700

ORIGINAL ARTICLE

Meconium aspiration syndrome: risk factors and predictors of severity

Cl
audia Patr
ıcia Lourenço Oliveiraa , Filipa Flo
^r-de-Limab, Gustavo Marcondes Duarte Rochab,
Ana Paula Machado and Maria Herc
ılia Ferreira Guimar~aes Pereira Areiasa,b
c

a
Faculty of Medicine, Porto University, Porto, Portugal; bNeonatal Intensive Care Unit, Pediatrics Hospital, Centro Hospitalar S~ao Jo~ao.
Alameda Professor Hern^ani Monteiro, Porto, Portugal; cDepartment of Gynecology and Obstetrics, Centro Hospitalar S~ao Jo~ao.
Alameda Professor Hern^ani Monteiro, Porto, Portugal

ABSTRACT ARTICLE HISTORY

Purpose: To identify risk factors and predictors of severity associated with meconium aspiration Received 4 April 2017
syndrome (MAS) in the patients admitted to the neonatal intensive care unit (NICU). Revised 19 November 2017
Materials and methods: Retrospective study including newborns admitted, between 2005 and Accepted 25 November 2017
2015, with a diagnosis of MAS.
Downloaded by [University of Florida] at 02:56 09 December 2017

Results: Of the newborns admitted to the NICU, 0.66% were diagnosed with MAS. These had KEYWORDS
higher prevalence of caesarean delivery (p < .001), nonreassuring or abnormal cardiotocography Meconium aspiration
(CTG) (p < .001), intrapartum maternal fever (p ¼ .002), Apgar scores at the first minute <7 syndrome; neonatal
(p < .001) and need of endotracheal intubation at birth (p < .001). Newborns with severe MAS intensive care unit;
had higher median reactive C protein (86.9 versus 9.65, p ¼ .001) and 73.3% had pulmonary perinatal asphyxia;
hypertension (p ¼ .027). They required significantly more days of oxygen therapy, mechanical predictors of severity; risk
ventilation, nitric oxide, inotropic, and surfactant therapy, as well as longer hospital stay. factors
Conclusions: Nonreassuring or abnormal CTG and low Apgar score at the first minute were
established as risk factors for MAS and need of surfactant therapy as a predictor of severity.

Introduction Few studies have sought to determine predictors of

Cleary and Wiswell defined meconium aspiration syn-
drome (MAS) as the respiratory distress in a newborn
born through meconium-stained amniotic fluid (MSAF)
that cannot be explained by other pathologies [1]. It
has been estimated that MASF is present in 8–25% of
births [2,3] and, among these, 5% develop MAS [1,2].
Although we have seen a decline in the incidence
of MAS related with better obstetric practices, particu-
larly in consequence of a lower frequency of deliveries
past 41 weeks of gestation and better management in
cases of fetal distress [4–7], MAS still remains a signifi-
cant cause of neonatal mortality and morbidity, mainly
in developing countries [8].
Over the years, several studies have sought to
determine the risk factors for MAS, however, there
have been contradicting results. Risk factors such as
cesarean delivery [4,7,9], advanced gestation [4,7,9–11],
ethnicity [1,4,7,10,11], low Apgar score at birth, and
fetal heart rate abnormalities [1,3,4,7,9,10] have con-
sistently been associated with a higher frequency of
MAS, but variables such as nulliparity [9,10], birth-
weight [1,10,11], mean low umbilical cord pH [10], or
thick meconium [1,3,9,11,12] have been found to have
contradicting relations to the development of MAS.
severity of MAS. According to Hernandez C et al. [13]
these factors are low 5-minute Apgar score, fetal dis-
tress, umbilical arterial pH <7.20, birth weight >90th
percentile and nulliparity. In a population-based study,
moderate to thick meconium, fetal tachycardia, and
very low Apgar score at the first minute were associ-
ated with severe MAS [3]. A more recent study, evalu-
ating risk factors for nonsevere and for severe MAS
established an association between fetal heart rate
abnormalities (reduced variability and bradycardia)
and cesarean delivery and the development of severe
MAS [10].
In light of these studies, the aim of this study was
to identify risk factors for the development of meco-
nium aspiration syndrome and predictors of severity of
the disease and to evaluate the differences between
the newborns that developed severe MAS from those
that developed nonsevere disease, in the patients
admitted to the Neonatal Intensive Care Unit (NICU).
Materials and methods
This is a retrospective case-control study that included
all newborns admitted to the NICU of this institution,

CONTACT Cl
audia Patr
ıcia Lourenço Oliveira claudia92oliveira@gmail.com Faculty of Medicine, Porto University, Porto, Portugal
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
 2 C. P. L. OLIVEIRA ET AL.
between 1 January 2005 and 31 December 2015, born
through MSAF, with respiratory distress and changes
in thoracic radiography compatible with MAS diagno-
sis. We excluded the newborns with a diagnosis other
than MAS that explained the respiratory distress, those
with normal thoracic radiography or with no need of
oxygen therapy.
We followed the definition of MAS established by
Cleary and Wiswell and classified each case as severe,
when assisted ventilation was required for more than
48 h, and as nonsevere when there was no need of
assisted ventilation or this need was for less than
48 hours [1].
A control group was selected, in a ratio of two con-
trols for each case, among newborns of our hospital,
with the same gender, gestational age (more or less a
week), weight at birth (more or less 500 g), born 2
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weeks before or after the newborns with MAS and
with normal amniotic fluid, with no major congenital
malformations or known pathology.
All data were obtained from neonatal and obstetric
electronic databases (Obscare) of our hospital, as well
as from patients’ individual medical files. We collected
and analyzed data relative to mother (age, education,
employment status, previous gestations, habits, and
diseases), delivery (type of birth, complications during
labor, degree of meconium, Apgar score, and need for
resuscitation), and neonatal variables (gender, birth
weight, gestational age, vital signs, analytical results,
therapy, and outcomes during stay in the NICU).
MSAF was classified as grade 1, 2, or 3 when it was
fluid, viscous or thick, respectively [3]. We defined
obesity as a body mass index above or equal to 30 kg/
m2. Clinical chorioamnionitis was diagnosed in the
presence of maternal fever (temperature above 38  C)
and at least two of the following criteria: maternal
leukocytosis, maternal tachycardia, fetal tachycardia,
uterine tenderness, and malodorous amniotic fluid
[14]. Maternal infection was considered both when a
diagnosis of clinical chorioamnionitis was established
and in the presence of signs of other infections (intra-
partum maternal fever and antibiotic therapy during
labor). Cardiotocography (CTG) was classified as nor-
mal or as abnormal/nonreassuring according to data
obtained in the delivery records. CTG is routinely
assessed by obstetricians following department
protocols.
Neonatal sepsis was diagnosed in the presence of a
positive blood culture, along with clinical and labora-
torial parameters (white blood cell count, platelet
count, reactive C protein (PCR)) [15].
Perinatal asphyxia was defined by pH <7.00 and
base deficit over 12 mmol/L, in the first hour of life
[16]. Hypoxic–ischemic encephalopathy was diagnosed
in the presence of an abnormal pH at birth and
altered consciousness or seizures [17].
Respiratory acidosis was considered when blood pH
<7.25 and PCO2 > 60 mmHg, and metabolic acidosis
when pH <7.25 with normal PCO2 and base deficit
over 5 mmol/L.
Persistent pulmonary hypertension was diagnosed
based on 2D-echocardiograhic findings: elevated pul-
monary vascular resistance, right to left shunt at duc-
tus arteriosus or foramen ovale, orientation of the
ventricular septum (budging from right-to-left), and
decreased left ventricular ejection fraction [5,7].
In regards to clinical criteria in the newborns, hypo-
thermia was defined as skin temperature below 36  C,
tachycardia as heart frequency above 160 beats per
minute, hypotension as a median blood pressure
below gestational age in weeks, hypoxia as oxygen
saturation under 94%, anemia as hemoglobin under
13 g/dL at birth, leukopenia as leukocyte count under
5000 per mL and leukocytosis over 30 000 leukocytes
per mL and thrombocytopenia as platelet count below
150 000 per mL [18].
This study has been approved by the Ethics
Committee Centro Hospitalar S~ao Jo~ao/Faculty of
Medicine, University of Porto. The statistical analysis
was performed using SPSS for Windows, version 23.
Categorical variables were analyzed by absolute and
relative frequencies and continuous variables were
analyzed according to their distribution by mean (±
standard deviation) or median (minimum–maximum) if
there was symmetric or asymmetric distribution,
respectively. Chi-squared or Fisher’s exact test were
used to analyze categorical variables and Independent
T test or Mann–Whitney U test were used to analyze
continuous variables. Risk factors and predictors of
severity were evaluated by a multivariate analysis by
logistic regression. A p value below .05 was considered
as statistically significant.
Results
There were 4400 admissions to the NICU between 1
January 2005 and 31 December 2015. Of these, 29
(0.66%) newborns had a diagnosis of MAS: 14 (48.3%)
nonsevere and 15 (51.7%) severe cases. Seven (24.1%)
out of these patients were born in other hospitals and
transferred to ours for continued care. Two mothers of
newborns with MAS had no surveillance during preg-
nancy. There was no mortality among cases of MAS in
the period considered.
Demographic, maternal and delivery data of MAS
and controls (58 newborns) are presented in Table 1.
 THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 3

Table 1. Demographic, maternal and delivery data comparing cases of MAS and controls.
Total (n ¼ 87) Cases (n ¼ 29) Controls (n ¼ 58) p
Gender, n (%) .999a
Male 45 (51.7) 15 (51.7) 30 (51.7)
Female 42 (48.3) 14 (48.3) 28 (48.3)
Gestational age (weeks), mean ± SD 39.8 (± 0.9) 40 (± 0.9) 39.7 (± 0.9) .177b
Birth weight (g), mean ± SD 3383 (± 298) 3381 (± 288) 3384 (± 305) .972b
Outborn, n (%) 7 (8.0) 7 (24.1) 0 <.001c
Maternal age (years), mean ± SD 28.7 (± 5.9) 28.2 (± 6) 29 (± 5.9) .305b
Maternal education .156c
Higher Education, n (%) 22 (27.8) 3 (14.3) 19 (32.8)
Secondary Education or less, n (%) 57 (72.2) 18 (85.7) 39 (67.2)
Maternal employment .640a
Employed, n (%) 70 (81.4) 22 (78.6) 48 (82.8)
Unemployed, n (%) 16 (18.6) 6 (21.4) 10 (17.2)
Primipara, n (%) 61 (70.1) 23 (79.3) 38 (65.5) .185a
Maternal obesity, n (%) 37 (48.1) 13 (61.9) 24 (42.9) .136a
Smokers, n (%) 11 (12.6) 5 (17.2) 6 (10.4) .362a
Gestational diabetes, n (%) 19 (22.1) 5 (17.9) 14 (24.1) .511a
Type of delivery
C-section, n (%) 36 (41.4) 20 (69.0) 16 (27.6) <.001a
Complications during labor, n (%)
Failure to progress 12 (13.8) 7 (24.1) 5 (8.6) .048a
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Nonreassuring or abnormal CTG 21 (24.1) 15 (51.7) 6 (10.3) <.001a

Premature Rupture of Membranes 23 (27.4) 3 (11.5) 20 (34.5) .035c
Maternal fever, n (%) 11 (13.3) 8 (32.0) 3 (5.2) .002c
Antibiotics during labor, n (%) 9 (11.0) 5 (20.0) 4 (7.0) .123c
Clinical Chorioamnionitis, n (%) 2 (2.4) 2 (8.0) 0 .088c
Apgar Score, n (%)
First min <7 26 (30.2) 23 (79.3) 3 (5.3) <.001c
Fifth min <7 14 (16.3) 14 (48.3) 0 (0.0) <.001c
Resuscitation at birth, n (%)
Endotracheal Intubation 19 (21.8) 19 (65.5) 0 <.001c
a
Chi square test;
b
Independent t test;
c
Fisher’s exact test.
The bold values indicate the statistically significant results (p < .05).

Significant differences were found in frequency of cae-
sarean delivery (p < .001), complications during labor
(especially nonreassuring or abnormal cardiotocogra-
phy (CTG), p < .001), and intrapartum maternal fever
(p ¼ .002). In 79.3% of cases the Apgar scores at the
first minute were <7 (p < .001), 48.3% had Apgar
scores at the fifth minute <7 (p < .001), and 65.5%
needed endotracheal intubation at birth (p < .001).
According to severity, the two groups of MAS are
compared in Table 2. In 73.3% of severe MAS there
was nonreassuring or abnormal CTG (p ¼ 0.027) and all
mothers of newborns with nonsevere cases were pri-
miparas (100% versus 60.0%, p ¼ .017). We found no
other statistically significant differences between the
two groups.
In Table 3, we present clinical and analytical data
comparing severe and nonsevere cases of MAS; 73.3%
of newborns with severe MAS had pulmonary hyper-
tension (p ¼ .027). Although newborns with severe
MAS had higher median PCR (86.9 versus 9.65,
p ¼ .001), we found no significant differences in fre-
quencies of sepsis or perinatal asphyxia.
Concerning treatments (Table 3), newborns with
severe MAS required more days of oxygen therapy
(p < .001) and higher maximum fraction of inspired
oxygen (FiO2) (p ¼ .004), more days of mechanical ven-
tilation (p < .001) and higher need of inhaled nitric
oxide (iNO) (p ¼ .035), inotropic therapy (p ¼ .008), sur-
factant (p ¼ .003), and parenteral nutrition (p ¼ .014).
Three patients met criteria for hypothermia treatment
protocol [16], none requiring treatment with extracor-
poreal membrane oxygenation (ECMO) [19]. Patients
with severe MAS had also longer periods of hospital-
ization in the NICU, when compared with newborns of
nonsevere cases (median 6.5 versus 12 days, p ¼ .004).
We performed a multivariate analysis by logistic
regression for predictive factors for MAS development
and for predictors of severity of MAS. Nonreassuring
or abnormal CTG (OR 7.37, 95%CI 1.45–37.45, p ¼ .016)
and Apgar score at the first minute <7 (OR 34.9,
95%CI 7.53–161.70, p < .0001) were significantly associ-
ated with development of MAS. Of the possible predic-
tors of severity, only the need of surfactant therapy
was associated with the development of severe MAS
(OR 16.5, 95%CI 2.51–108.6, p ¼ .004).
Discussion
The pathophysiology of MAS is still not fully under-
stood. It is more likely a complex process starting in
 4 C. P. L. OLIVEIRA ET AL.

Table 2. Demographic, maternal and delivery data comparing cases of severe and nonsevere MAS.
Total (n ¼ 29) Nonsevere (n ¼ 14) Severe (n ¼ 15) p
Gender, n (%) .096a
Male 15 (51.7) 5 (35.7) 10 (66.7)
Female 14 (48.3) 9 (64.3) 5 (33.3)
Gestational age (weeks), mean ± SD 40 (± 0.9) 39.9 (± 0.8) 40 (± 1) .683b
Birth weight (g), mean ± SD 3381 (± 288) 3322 (± 308) 3436 (± 265) .294b
Outborn, n (%) 7 (24.1) 1 (7.1) 6 (40.0) .080c
Maternal age (years), mean ± SD 28.2 (± 6) 26.6 (± 4.1) 29.7 (± 7.2) .158d
Maternal education .999c
Higher Education, n (%) 3 (14.3) 2 (16.7) 1 (11.1)
Secondary Education or less, n (%) 18 (85.7) 10 (83.3) 8 (88.9)
Maternal employment .999c
Employed, n (%) 22 (78.6) 11 (78.6) 11 (78.6)
Unemployed, n (%) 6 (21.4) 3 (21.4) 3 (21.4)
Primipara, n (%) 23 (79.3) 14 (100.0) 9 (60.0) .017c
Maternal obesity, n (%) 13 (61.9) 8 (66.7) 5 (55.6) .673c
Smokers, n (%) 5 (17.2) 1 (7.1) 4 (26.7) .330c
Gestational diabetes, n (%) 5 (17.9) 3 (21.4) 2 (14.3) .999c
Type of delivery
C-section, n (%) 20 (69.0) 8 (57.1) 12 (80.0) .245c
Complications during labor, n (%)
Failure to progress 7 (24.1) 4 (28.6) 3 (20.0) .682c
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Nonreassuring or abnormal CTG 15 (51.7) 4 (28.6) 11 (73.3) .027c

Premature Rupture of Membranes 3 (11.5) 1 (7.7) 2 (15.4) .999c
Maternal fever, n (%) 8 (32.0) 5 (35.7) 3 (27.3) .695c
Antibiotics during labor, n (%) 5 (20.0) 4 (28.6) 1 (9.1) .341c
Clinical Chorioamnionitis, n (%) 2 (8.0) 2 (14.3) 0 (0.0) .487c
Meconium Stained Amniotic Fluid, n (%)
Grade 3 11 (37.9) 4 (28.6) 7 (46.7) .450c
Apgar Score, n (%)
First min <7 23 (79.3) 11 (78.6) 12 (80.0) .598c
Fifth min <7 14 (48.3) 7 (50.0) 7 (46.7) .812c
Resuscitation at birth, n (%)
Endotracheal Intubation 19 (65.5) 9 (64.3) 10 (66.7) .999a
a
Chi square test;
b
Independent t test;
c
Fisher’s exact test;
d
Mann–Whitney U test; CTG: cardiotocography.
The bold values indicate the statistically significant results (p < .05).

utero, possibly a consequence of a chronic exposure [6]
with several mechanisms involved, from small airway
obstruction, to surfactant dysfunction and several path-
ways of inflammation activated [11,20]. Therefore, previ-
ous concepts that referred MAS as a direct consequence
of aspiration during delivery are now being dismissed
and a new outlook on this disease is being considered,
questioning the need for an aggressive airway manage-
ment in the presence of meconium [6,10–12,20].
In this regard, it is also considered that the more
severe cases of MAS do not represent necessarily a
continuum of the disease, but may have different
pathophysiological bases than the mild or moderate
cases, such as chronic asphyxia, infection or persistent
pulmonary hypertension [10,12]. Supporting this
hypothesis, is the lack of direct correlation between
severity of meconium aspiration (in duration of expos-
ition, thickness or even amount of meconium) and
severity of MAS [10,12] and a lack of correlation
between the radiological findings and the clinical man-
ifestations of the disease [1].
As a trend observed in studies published in recent
years [4–7], the prevalence of MAS in our population is
also decreasing compared to a previous study on MAS
performed in our NICU in 2009 [7] and it represented
only 0.66% of the admissions in the past decade.
Neonates that developed MAS had no significant
differences in gender (51.7% male), had a mean birth
weight of 3381 g and mean gestational age of 40
weeks. Their mothers had a mean age of 28.2 years
and when compared with mothers of healthy neo-
nates, we found no differences in education, employ-
ment status, previous gestations or deliveries,
smoking, obesity, or gestational diabetes.
We found that the MAS group had a higher fre-
quency of caesarean delivery (69%), complications dur-
ing labor (mostly nonreassuring or abnormal CTG,
51.7%) and intrapartum maternal fever (32%).
Neonates diagnosed with MAS were also more likely
to have Apgar scores at the first and fifth minute <7
and more often needed resuscitation maneuvers,
including endotracheal intubation (65.5%).
However, we found only two variables as predictive
factors for the development of MAS: nonreassuring or
abnormal CTG (OR 7.37) and Apgar score at the first
minute <7 (OR 34.9). Both reflect a depressed state of
 THE JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 5

Table 3. Neonatal clinical and analytical data comparing cases of severe and nonsevere MAS.
Total (n ¼ 29) Nonsevere (n ¼ 14) Severe (n ¼ 15) p
Pulmonary hypertension, n (%) 15 (51.7) 4 (28.6) 11 (73.3) .027b
Moderate or severe, n (%) 8 (27.6) 0 8 (53.3) .085b
Perinatal asphyxia, n (%) 7 (24.1) 4 (28.6) 3 (20.0) .682a
Sepsis, n (%) 3 (10.3) 1 (7.1) 2 (13.3) .999b
Temperature ( C), median (min–max) 36.5 (33.5–37.7) 36.6 (34.1–37.7) 36.4 (33.5–37.6) .533c
Hypothermia (<36  C), n (%) 6 (20.7) 3 (21.4) 3 (20.0) .999b
Heart frequency (bpm), median (min–max) 150 (113–185) 151 (130–182) 149 (113–185) .561c
Tachycardia (>160 bpm), n (%) 9 (31.0) 4 (28.6) 5 (33.3) .999b
Hypotension at admission, n (%) 7 (24.1) 1 (7.1) 6 (40.0) .080b
White blood cells
Leukopenia, n (%) 0 0 0 –
Leukocytosis, n (%) 4 (13.8) 3 (21.4) 1 (6.67) .598b
Platelet count
Thrombocytopenia, n (%) 10 (35.7) 5 (38.5) 5 (33.3) .778a
PCR, median (min–max) 45.3 (0–250) 9.65 (0–250) 86.9 (4.4–244) .001c
Oxygen therapy, n (%) 29 (100.0) 14 (100.0) 15 (100.0) .999a
Days of oxygen, median (min–max) 3 (1–24) 2 (1–13) 9 (2–24) <.001c
Maximum FiO2, median (min–max) 0.5 (0.21–1) 0.4 (0.21–1) 1 (0.25–1) .004c
FiO2  0.4, n (%) 20 (69.0) 8 (57.1) 12 (80.0) .245b
Invasive mechanical ventilation, n (%) 20 (69.0) 5 (35.7) 15 (100.0) <.001b
Days, median (min–max) 4.5 (1–18) 1 (1–2) 6 (1–18) <.001c
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iNO, n (%) 8 (27.6) 1 (7.1) 7 (46.7) .035b

Dosage (ppm), median (min–max) 20 (20–40) 20 (20–20) 20 (20–40) .083c
Days, median (min–max) 4 (1–14) 1 (1–1) 4 (2–14) .051c
Inotropic therapy, n (%) 12 (41.4) 2 (14.3) 10 (66.7) .008b
Days, median (min–max) 4 (1–12) 1.5 (1–2) 5 (2–12) .012c
Surfactant, n (%) 13 (44.8) 2 (14.3) 11 (73.3) .003b
Doses, median (min–max) 3 (1–10) 2 (1–3) 3 (1–10) .003c
Hours after delivery, median (min–max) 5 (1–16) 3.75 (1.5–6) 5 (1–16) .006c
Hypothermia therapy, n (%) 3 (10.3) 0 (0.0) 3 (20.0) .224
Parenteral nutrition, n (%) 21 (72.4) 7 (50.0) 14 (93.3) .014b
Days, median (min–max) 6 (1–19) 3 (1–5) 3 (8.5–19) <.001c
Hospitalization
Days, median (min–max) 8 (2–29) 6.5 (2–11) 12 (5–29) .004c
a
Chi square test;
b
Fisher’s exact test;
c
Mann–Whitney U test.
The bold values indicate the statistically significant results (p < .05).

the newborn before or immediately after birth, which
supports the hypothesis that the pathological changes
that lead to the respiratory distress seen in these new-
borns probably occur in utero and not, as it was
believed previously, only as a consequence of aspir-
ation of meconium during or after birth [12]. We can
hypothesize that fetal distress, reflected by both non-
reassuring or abnormal CTG and low Apgar score at
the first and fifth minute, is an indicator for the devel-
opment of MAS.
It is also important to take into account that mater-
nal infection was not found as a predictive factor for
MAS and only 10.3% of newborns with MAS also had
a concomitant diagnosis of sepsis, both findings that
are consistent with other studies that have found no
relation between MAS or MSAF and sepsis. This appar-
ent lack of evidence raised the question of the need
for the usual antibiotic administration for all neonates
born through MSAF [21,22].
In newborns with MAS classified as severe, there was
a higher prevalence of intrapartum nonreassuring or
abnormal CTG when compared with newborns having
nonsevere cases of MAS (73.3 versus 28.6%), which was
one of the risk factors that Choi et al. [10] have recently
established. However, we found no significant associ-
ation between caesarean delivery and severe MAS.
No significant differences were found between both
severity groups in clinical parameters upon admission
to the NICU. We did found, however, that the severe
MAS group had higher mean PCR values in the first
72 hours (median PCR 86.9), which is consistent with
the findings of Hofer et al. [22] that established a sig-
nificant correlation between inflammatory indices and
disease severity, and also higher prevalence of pul-
monary hypertension (73.3%), also previously associ-
ated with disease severity [2,20]. Surprisingly, no
significant association between severe MAS and peri-
natal asphyxia or sepsis was found.
As expected, neonates with severe cases of MAS
were more likely to require more days of treatment,
higher maximum FiO2 (median 0.4 versus 1) and more
often requiring iNO (46.7%), surfactant (73.3%), and
inotropic therapy (66.7%), as longer periods of hospi-
talization (median 12 versus 6.5).
The only variable associated with the development
of severe MAS was the need of surfactant therapy
 6 C. P. L. OLIVEIRA ET AL.
(OR 16.5). This therapy was provided in bolus and gen-
erally, the first dose was administrated within the first
12 hours of life. Surfactant therapy has been shown to
improve oxygenation, decrease the need for ventila-
tory support, reduce the severity of illness, reduce
requirement of ECMO, and improve clinical outcome
[6,23]. It is widely accepted that, as part of the physio-
pathology of MAS, there is an inhibition or alteration
of normal surfactant function or composition, although
it remains in question the process that leads to this
loss of normal function. It appears that inflammation
plays an important role and that hypoxia may also be
a key factor for this dysfunction, but further studies
are required [1,11,12].
Our study had three main limitations: its retro-
spective nature, the low number of cases that
reduced our statistical power and possibly limited our
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results and it represents only the reality of our
center.
Despite these limitations, we considered that evalu-
ating the risk factors for severity by comparing nonse-
vere with severe cases instead of healthy controls was
a better way to establish a correlation between varia-
bles and outcome. We have also determined severity
according to the most consensual classification,
although some of the results found in other studies
have different criteria for severity such as, duration of
respiratory support or the need for mechanical ventila-
tion [4].
Very few studies have evaluated the differences
between severe and nonsevere MAS. Despite of its low
incidence, MAS can present high morbidity and mor-
tality rates and the newborns affected often require
invasive and prolonged treatments, especially those
with severe cases. The decline in incidence of MAS is a
proven result of better obstetric and neonatal practi-
ces. The prediction of these cases are more likely to
present as severe disease, and therefore, more likely to
require mechanical ventilation would be a great
advantage to the clinical care. In our opinion more
studies are needed in this area, mainly population-
based studies, to a better understanding of the physio-
pathology of severe MAS and to optimize the interven-
tions and resources.
Acknowledgements
The authors would like to thank the ObsCare team for their
help in collecting maternal data.
Disclosure statement
The authors report no conflicts of interest.
ORCID
Cl
audia Patr
ıcia Lourenço Oliveira http://orcid.org/0000-
0002-8342-6298
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