Running head: MECONIUM ASPIRATION SYNDROME 1

Treatment Options of Meconium Aspiration Syndrome

Autumn Cooley

Baptist College of Health Sciences

MECONIUM ASPIRATION 2

Abstract

The pathophysiology of MAS is multi-factorial and reflects: the direct effects of meconium in

the airways, the resulting inflammatory response, and any associated hypoxic-ischemic insult.

The development of MAS initiates the occurrence of mechanical obstruction, chemical

pneumonitis, surfactant dysfunction, and pulmonary vasoconstriction. Obstruction of the

airways, particularly in expiration, results in: air trapping, generalized hyperinflation, and a

heightened risk of air leaks. Air trapping also predisposes the lungs to pulmonary interstitial

emphysema (PIE), pneumomediastinum, and pneumothorax.

MECONIUM ASPIRATION 3

Treatment Options of Meconium Aspiration

Meconium aspiration syndrome (MAS) occurs when a newborn inhales a mixture of

meconium and amniotic fluid before, during, or after labor and delivery. Meconium passage into

the amniotic fluid occurs in 9% to 20% of all births. Actual aspiration of meconium into the

trachea occurs in about half of the neonates born with meconium staining of the amniotic fluid

(Eberle, Trujillo, & Whitaker, 2015). The severity of MAS depends on the amount of meconium

aspirated by the infant, as larger quantities will increase the severity. The most severe cases of

MAS result in respiratory failure and are associated with high mortality and morbidity rates.

Several factors contribute to the severity of MAS leading to a complex multisystem disorder

requiring respiratory, cardiovascular, neurological and sepsis management (Emmerson, 2014,

p.610). Current methods of treatment have improved the survival rates of patients with MAS.

Therapies proven to be effective in the treatment of severe MAS include: surfactant replacement,

high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation.

Meconium is the name given to the sterile contents of the fetal bowel. It is a thick, tar-

like, dark green material in combination of swallowed amniotic fluid, bile salts and acids,

squamous cells, vernix, bile salts and acids, squamous cells, and intestinal enzymes (Eberle,

Trujillo, & Whitaker, 2015). Meconium is the first stool of the newborn that typically passes

within 48 hours postpartum. MAS occurs when the neonate aspirates a mixture of meconium and

amniotic fluid into the lungs before, during, or after delivery. Once aspirated, meconium

migrates down the tracheobronchial tree, causing a variable degree of airway obstruction as it

disperses into the distal airways (Hahn, Choi, Soll, & Dargaville, 2013). The Department of

Neonatology states: multiple life threatening complications are secondary to MAS including:

hypoxic ischemic encephalopathy (HIE) (46%), hypotensive shock (22%), pneumothorax

MECONIUM ASPIRATION 4

(11.4%), myocardial dysfunction (22%), and pulmonary hypertension (PHN) (17%). Meconium

staining of the amniotic fluid (MSAF) occurs in around 4% of deliveries before 37 weeks, 10-

20% of term deliveries, and up to 30-40% of post term deliveries. However, only about 5% of

infants born through MSAF go on to develop MAS (Stenson & Smith, 2012). Therefore, post

term infants are at a significantly higher risk of developing MAS than that of an infant delivered

before 37-weeks gestational age.

The sequence of events that results in the aspiration of meconium into the trachea

involves a complex series of asphyxia-induced occurrences. The asphyxial episode produces a

shift in blood distribution to the vital organs. The response to the fetal bowel and vagal

stimulation (subsequent from compression of the head or umbilical cord during labor), may

result in increased peristalsis and relaxation of the anal sphincter. This allows meconium to pass

into the amniotic fluid that envelopes the neonate (Eberle, Trujillo, & Whitaker, 2015). Next,

meconium is inhaled into the lungs as the neonate gasps for air while still in the womb or during

the initial gasping breaths after delivery. The gasping of breaths usually occurs in attempt to

compensate for hypoxia that is a secondary result of asphyxia or vagal stimulation. In proportion

to asphyxia, deep gasping movements enable the passage of meconium into the oropharynx and

upper levels of the tracheobronchial tree. According to Kids Health from Nemours, multiple

perinatal risk factors have been linked to MAS including: a prolonged or complicated delivery;

advanced gestational age; a mother who smokes cigarettes heavily or who has maternal diabetes

mellitus, preeclampsia, oligohydramnios, or chronic cardiopulmonary disease; placental

insufficiency, umbilical cord complications; the lack of prenatal care; and poor intrauterine

growth. Frey et al. (2014) states, multiple studies have reported that MAS is associated with
MECONIUM ASPIRATION 5

adverse neonatal outcomes to include fetal acidemia, low Apgar scores, and a need for neonatal

resuscitation.

The pathophysiology of MAS is multi-factorial and reflects: the direct effects of

meconium in the airways, the resulting inflammatory response, and any associated hypoxic-

ischemic insult. The development of MAS initiates the occurrence of mechanical obstruction,

chemical pneumonitis, surfactant dysfunction, and pulmonary vasoconstriction. Obstruction of

the airways, particularly in expiration, results in: air trapping, generalized hyperinflation, and a

heightened risk of air leaks. Air trapping also predisposes the lungs to pulmonary interstitial

emphysema (PIE), pneumomediastinum, and pneumothorax. Additionally, blockage of the

airway by way of meconium often creates atelectasis distal to the occlusion. Inflammation plays

an essential role in the pathogenesis of MAS. Meconium is a source of pro-inflammatory

cytokines, such as the tumor necrosis factor or interleukins (Mokra, Mokry, & Tonhajzerova,

2013). Activated neutrophils and macrophages may damage the lungs by different pathways.

Production of pro-inflammatory substances, activation of complement, activation of coagulation

cascade, production of platelet activating factor, and of vasoactive substances may result in the

destruction of capillary endothelium and basement membranes. An injury to alveolocapillary

membrane results in a leak of liquid, plasma proteins, and cells into the interstitial and alveolar

spaces (Mokra, Mokry, & Tonhajzerova, 2013). The liberation of vasoconstrictors, such as

endothelin and thromboxane, contribute to pulmonary hypertension. Surfactant dysfunction is

linked to: direct inhibition generated by the meconium, toxicity to type II pneumocytes,

displacement of surfactant from the alveolar surface, and a notable decrease of surfactant

proteins A and B. The progression of MAS may induce: non-inflammatory cell death in the
MECONIUM ASPIRATION 6

lungs, ventilation/perfusion mismatch, intrapulmonary shunting, hypoxemia, hypercarbia, and

acidosis ensuing severe cardiopulmonary failure (Stenson & Smith, 2012).

Research by Vora & Nair (2014) discuss a prospective study that was conducted at a

tertiary care hospital NICU. A total of 90 infants born of MSAF and admitted to the NICU were

studied. Detailed maternal history was taken and all infants underwent routine septic screen and

chest x-ray. Out of the total 90 infants born with MSAF, 41 were female and 49 were male.

Majority (95.6%) cases with MSAF occurred either in full term or post term infants. MAS was

found in 68 of the total 90 infants, of which 48 (70.5%) were vigorous and 20 (19.5%) were non-

vigorous. Abnormal x-ray was found in 39 (43.3%), 23.5% required ventilator care, and overall
MECONIUM ASPIRATION 7

mortality rate was 15.5% (Vora & Nair, 2014). The study continues to discuss that majority

Infants Born With MSAF

50

48

46

44

42

40

38

36
Female Male

*Information pulled from Vora & Nair, 2014.

(95.6%) of cases in MSAF occur in either full term or post term babies. Gupta et al study found

preterm 7.8%, full term 86.7%, and post term 5.3%. Out of the 90 infants in the study, mothers of

50% had one of the following risk factors: preeclampsia, heavy smoking, post-term pregnancy,

oligohydroamnios, and diabetes mellitus. 60% had PIH, 28% had oligohydroamnios, 8.8% had

hypertension, and 2.2% had diabetes mellitus. Out of the 90 infants studied, 73.3% had the
MECONIUM ASPIRATION 8

presence of thick meconium and the other 26.6% had thin meconium. Of the 73.3% of infants

born with thick meconium, 39.3% were non-vigorous, 77.9% developed MAS, and 21%

deceased. This depicts that thick meconium is associated with a higher incidence of MAS and

poorer health outcomes. A total of 14 of the 90 infants died, giving an overall mortality rate of

15.5%.

Gestational Age and MSAF

Maturity Present Study Gupta et al

Preterm 4.4% 7.8%

Full Term 87.7% 86.7%

Post Term 7.7% 5.3%

* Information gathered from Vora & Nair, 2014.

Shaikh et al. (2016) conducted a study to determine the impact of chemical pneumonitis,

pulmonary hypertension, and air leak as an outcome of infants with MAS. This cross sectional

descriptive study was conducted in a tertiary care Neonatology unit. A total of 96 cases of MAS

were initially included in the study. Out of those, 4 cases found to have congenital lung

anomalies, 12 had congenital heart diseases, and 8 had respiratory distress due to other causes.

Therefore, a total of those 24 infants were excluded from the study and the remaining 72 were

subjected to further analysis. Of the 72 babies, 44 were males and 28 were females. The

deliveries through caesarean were carried out in 33 cases while 39 were born through

spontaneous vaginal delivery. Out of the 72 infants with MAS, 21 did not develop any studied

complication while 51 were found to have one or more complication. Chemical pneumonitis was

found in 17, PHN in 15, and chemical pneumonitis with PHN was observed in 19 neonates. The
MECONIUM ASPIRATION 9

mean duration of stay among those who survived was 87.41+54.60 hours while the mean

duration of the hospital stay among those who deceased was 122.28+88.89 hours. Out of the 72

patients, 14 died, while 58 were discharged. The mortality was highest in infants having

chemical pneumonitis along with PHN (6/19,p-value=0.013) followed by chemical pneumonitis

(3/17, p-value=0.02) and PHN alone (5/15, p-value=0.032) (Shaikh et al., 2016).

The clinical management of MAS can be considered in two phases: perinatal and

postnatal management. Research by Stenson and Smith (2012) states the key goals of

intrapartum care to minimize the risk of MAS include early detection and prompt management of

fetal hypoxia. Amniofusion is the infusion of sterile, warm saline into the uterus when meconium

is detected in the amniotic fluid. This may help dilute the meconium and reduce the chance of

problems with aspiration. Recommendations by the American Congress of Obstetricians and

Gynecologists do not advise for the routine suctioning of infants with meconium staining

because the consistency of meconium is to viscous for routine suctioning. The American

Academy of Pediatrics has developed guidelines to manage infants exposed to meconium and are

summarized here. Upon delivery of the head, before the delivery of the thorax, the moth and

oropharynx are thoroughly suctioned and cleared of any meconium that is present using at least a

10 Fr. oral suction catheter. Once delivered, the infant is dried and placed under an open radiant

warmer. If respiratory effort is depressed, bradycardia, and poor muscle tone is described,

intubation and suctioning should immediately be performed. Furthermore, the guidelines state

that the largest endotracheal tube possible should be used to suction the meconium. Throughout

the procedure, 100% oxygen should be blown by the patients face, but positive pressure

ventilation should be administered if the patient becomes bradycardic. Stenson and Smith (2012)

state that postpartum management include: nasal continuous positive airway pressure (nCPAP),
MECONIUM ASPIRATION 10

conventional ventilation, high frequency oscillatory ventilation, surfactant replacement and

surfactant lavage, nitric oxide, corticosteroids, and extracorporeal membrane oxygenation.

Current methods of treatment have improved the survival rates of patients with MAS.

Therapies proven to be effective in the treatment of severe MAS include: surfactant replacement,

high-frequency oscillatory ventilation, extracorporeal membrane oxygenation. One study

systematically reviewed the efficacy of the commonly used intervention surfactant

administration. Surfactant is administered intratracheally as either a bolus dose or in dilute form

to lavage the lungs in neonates with MAS. Although bolus administration is thought to replenish

the endogenous surfactant inactivated by fatty acids present in the meconium, lung lavage with

surfactant is believed to wash the residual meconium from the airways (Natarajan, Sankar, Jain,

Agarwal, & Paul, 2015). Outcomes of the study included the following: in-hospital mortality

defined as all-cause death during the birth hospitalization, sepsis defined as clinical features of

sepsis with or without isolation of organisms from blood/cerebrospinal fluid/urine and laboratory

parameters suggestive of sepsis, duration of mechanical ventilation defined as number of days-

either invasive or non-invasive, duration of oxygen requirement defined as the number of days of

oxygen supplementation required during the initial hospital stay, duration of hospital stay defined

as number of days as inpatient, proportion of neonates who required ECMO therapy, and the

incidence of air leaks such as: PIE, pneumothorax, pneumomediastinum, or pneumopericardium.

All the studies were randomized trials that used accepted methods of randomization. Out of the

eight studies on surfactant for MAS, two used surfactant lung lavage (SLL) and the remaining

six used bolus surfactant (BS) (Natarajan et al., 2015). The studies conclude that the use of

surfactant as either SLL (RR 0.38;95% CI 0.09 to 1.57) or BS (RR 0.08; 95% CI 0.39 to 1.66)

did not reduce mortality in neonates with established MAS. Both SLL and BS reduced the
MECONIUM ASPIRATION 11

duration of hospital stay by 2 days (95% CI -3.7 to -0.3) and 4.7 days (95% CI -7.1 to -2.2).

Similarly, neonates who received surfactant by either SLL or BS had shorter days of mechanical

ventilation. Neonates who received BS (RR 0.64; 95% CI 0.46 to 0.91) but not SLL (RR 0.26;

95% CI 0.04 to 1.82) needed ECMO less often than those in the control group (Natarajan et al.,

2015). Neither method of surfactant administration reduced the duration of oxygen therapy or the

incidence of air leaks. The lack of benefits in key outcomes such as mortality and air leaks

following either mode of surfactant therapy could be related to: the degree of neonatal illness and

the timing of the lavage therapy.

Lung lavage followed by surfactant bolus versus only surfactant bolus.

Outcome or No. of Studies No. of Statistical Effect size

subgroup title participants method

1 Death 1 13 Risk ratio (M-H, 0.18 (0.01, 3.06)

Fixed, 95%, CI)

2 Pneumothorax 1 13 Risk ratio (M-H, 0.18 (0.01, 3.06)

Fixed, 95% CI)

The study conducted by Chen, Wu, and Wang (2015) is aimed to investigate the clinical

efficiency in the use of high-frequency oscillatory ventilation (HFOV) combined with pulmonary

surfactant (PS) for the treatment of MAS. Clinical data of 53 MAS patients admitted to the

NICU was collected and the patients were divided into 3 groups according to the different

treatment approach: group 1 conventional mechanical ventilation (CMV); group 2 HVOV; group

3 HFOV+ PS. The study performed by Chen et al., (2015) suggests that CMV can easily cause

barotrauma or volutrauma. Therefore, the clinical application of HFOV is the current preferred

method of ventilation which is characterized by an effective gas exchange using tidal volumes

equal to or less than the dead space volume. The HFOV produces biphasic pressure changes,
MECONIUM ASPIRATION 12

hence achieving efficient prevention and treatment of neonatal respiratory destress syndrome.

The defaults parameters set for HFOV in this study were: FiO2 50-80%; the frequency at 9-11

HZ; mean airway pressure (MAP) 10-17 cmH2O, amplitude of 40-60 cmH2O was gradually

adjusted in each patient to optimize chest wiggle (Chen et al.,). The analysis of the results reveal

that when compared with group 1, the difference in the various oxygenation indicators at

different points in time after treatment of group 2 and group 3 was statistically significant (P <

0.05); the ventilation time, duration of oxygen therapy, and hospitalization time of group 2 and

group 3 were significantly shorter, and the difference was statistically significant (P < 0.05);

indicating that HFOV has significant therapeutic effect in treating MAS (Chen et al., 2015).

Extracorporeal membrane oxygenation (ECMO) has been used in treatment of neonates

with a variety of cardio-respiratory problems including meconium aspiration syndrome (MAS),

persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia

(CDH), sepsis/pneumonia, respiratory distress syndrome (RDS), air leak syndrome, and cardiac

anomalies (Bahrami & Meurs, 2012). The American College of Cardiology states criteria for

neonates in the use of ECMO include: gestational age of 34 weeks or more, birth weight of

2000g or more, no significant coagulopathy or uncontrolled bleeding, no major coagulopathy or

uncontrolled bleeding, no major intracranial hemorrhage, mechanical ventilation for 10-14 days,

reversible lung injury, no lethal malformations, and failure of maximal medical therapy. For one

group of high-risk neonates with an anticipated mortality rate of 80% to 85%, ECMO has an

overall survival rate of 84%, with recent data showing nearly 100% survival in many diagnostic

groups (Bahrami & Meurs, 2012). Extracorporeal membrane oxygenation (ECMO) is defined as

the use of a modified heartlung machine combined with a membrane oxygenator to provide

cardiopulmonary support for patients with reversible pulmonary and/or cardiac failure in whom
MECONIUM ASPIRATION 13

maximal conventional therapies have failed. ECMO is now well accepted as a standard treatment

for neonatal respiratory failure unresponsive to conventional therapies. This table summarizes

the differences between venoarterial and venovenous ECMO.

Venoarterial ECMO Venovenous ECMO

Higher PaO2 is achieved.
Lower perfusion rates needed.
Bypasses pulmonary circulation.
Decreases pulmonary artery pressures.
Provides cardiac support to assist systemic
Lower PaO2 achieved.
Higher perfusion rates needed.
Maintains pulmonary blood flow.
Elevates mixed venous PO2.
Does not provide cardiac support to assist

circulation. systemic circulation.

Requires arterial cannulation. Requires only venous cannulation.
*Information gathered from Cruz & Berger, 2016.

The incidence of MSAF occurs in 10-15% of all live births and about 2-9% of infants

born through MSAF will develop MAS. Due to the heightened severity of MAS, health care

providers must promptly recognize signs and symptoms and immediately begin the appropriate

treatment plan according to the patients clinical presentation. Mothers should become educated

on the importance of receiving adequate prenatal care to ensure that if MSAF or any other

complication does occur, it can be detected in time to improve patient health outcomes. Current

methods of treatment have improved the survival rates of patients with MAS. Therapies proven

to be effective in the treatment of severe MAS include: surfactant replacement, high-frequency

oscillatory ventilation, and extracorporeal membrane oxygenation. Present studies have shown

that certain treatment options will decrease: the length of hospital stay, duration of mechanical

ventilation, and reduce the need for ECMO. Further research should be done to find effective

therapies in decreasing mortality and morbidity rates associated with MAS.

MECONIUM ASPIRATION 14

References

Shaikh, M., Waheed, K. A., Javaid, S., Gul, R., Hashmi, M. A., & Fatima, S. T. (2016).

Detrimental complications of meconium aspiration syndrome and their impact on

outcome. Department of Neonatology. 28(3). 506-508.

Smith, C. L., & Stenson, B. J. (2012). Management of meconium aspiration syndrome.

Pediatrics and Child Health. 532-535.

Vora, H., & Nair, S. (2014). Study of meconium aspiration Syndrome in neonates. 3(1). 64-66.

Chen, D. M., Wu, L. Q., & Wang, R. Q. (2015). Efficiency of high-frequency oscillatory

ventilation combined with pulmonary surfactant in the treatment of neonatal meconium

aspiration syndrome. International Journal of Clinical and Experimental Medicine. 8(8),

14490-14496. PMCID: PMC4613124.

Natarajan, C. K., Sankar, M. J., Jain, K., Agarwal, R., & Paul, V. K. (2016). Surfactant therapy

and antibiotics in neonates with meconium aspiration syndrome: a systemic review and

meta-analysis. Journal of Perinatology. S49-S54. Doi:10.1038/jp.2016.32

Hahn, S., Choi, H. J., Soll, R., & Dargaville, P. A. (2013). Lung lavage for meconium aspiration

syndrome in newborn infants. Cochrane Database of Systemic Reviews. Issue 4. Art. No.:

CDOO3486. Doi:10.1002/14651858.

Eberle, P., Trujillo, L., & Whitaker, K. (2015). Comprehensive perinatal & pediatric respiratory

care. 4th ed. Stamford, CT.