Meconium aspiration syndrome (MAS) is the aspiration of stained amniotic fluid, which can occur before, during, or immediately after birth. Meconium is the first intestinal discharge from newborns, a viscous, dark-green substance composed of intestinal epithelial cells, lanugo, mucus, and intestinal secretions (eg, bile. Water is the major liquid constituent, comprising 85-95% of meconium; the remaining 5-15% of ingredients consists of solid constituents, primarily intestinal secretions, mucosal cells, and solid elements of swallowed amniotic fluid, such as proteins and lipids.
Meconium is sterile and does not contain bacteria, which is the primary factor that differentiates it from stool. Intrauterine distress can cause passage of meconium into the amniotic fluid. Factors that promote the passage in utero include placental insufficiency, maternal hypertension, preeclampsia, oligohydramnios, infection, acidosis, and maternal drug abuse, especially use of tobacco and cocaine.
As noted above, meconium-stained amniotic fluid may be aspirated before or during labor and delivery. Because meconium is rarely found in the amniotic fluid prior to 34 weeks' gestation, meconium aspiration primarily affects infants born at term and postterm.
In utero meconium passage results from neural stimulation of a maturing gastrointestinal (GI) tract, usually due to fetal hypoxic stress. As the fetus approaches term, the GI tract matures, and vagal stimulation from head or spinal cord compression may cause peristalsis and relaxation of the rectal sphincter, leading to meconium passage.
The effects of meconium in amniotic fluid are well documented.[1] Meconium directly alters the amniotic fluid, reducing antibacterial activity and subsequently increasing the risk of perinatal bacterial infection. In addition, meconium is irritating to fetal skin, thus increasing the incidence of erythema toxicum. However, the most severe complication of meconium passage in utero is perinatal aspiration of stained amniotic fluid (before, during, or immediately after birth)—ie, meconium aspiration syndrome (MAS). Aspiration of meconium-stained amniotic fluid may occur if the fetus is in distress, leading to a gasping breathing pattern. This aspiration induces hypoxia via four major pulmonary effects: airway obstruction, surfactant dysfunction, chemical pneumonitis, and pulmonary hypertension.[1]
Airway obstruction
Complete obstruction of the airways by meconium results in atelectasis. Partial obstruction causes air trapping and hyperdistention of the alveoli, commonly termed the ball-valve effect. Hyperdistention of the alveoli occurs from airway expansion during inhalation and airway collapse around inspissated meconium in the airway, causing increased resistance during exhalation. The gas that is trapped (hyperinflating the lung) may rupture into the pleura (pneumothorax), mediastinum (pneumomediastinum), or pericardium (pneumopericardium).
Surfactant dysfunction
Meconium deactivates surfactant and may also inhibit surfactant synthesis.[2, 3] Several constituents of meconium, especially the free fatty acids (eg, palmitic, stearic, oleic), have a higher minimal surface tension than surfactant and strip it from the alveolar surface, resulting in diffuse atelectasis.[4]
Chemical pneumonitis
Enzymes, bile salts, and free fatty acids in meconium irritate the airways and parenchyma, causing a release of cytokines (including tumor necrosis factor (TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-13), which initiate a diffuse pneumonitis that may begin within a few hours of aspiration.
All of these pulmonary effects can produce a gross ventilation-perfusion (V/Q) mismatch.
Persistent pulmonary hypertension of the newborn
To complicate matters further, many infants with meconium aspiration syndrome (MAS) have primary or secondary persistent pulmonary hypertension of the newborn (PPHN) as a result of chronic in utero stress and thickening of the pulmonary vessels. PPHN further contributes to the hypoxemia caused by meconium aspiration syndrome.[5]
Finally, although meconium is sterile, its presence in the air passages can predispose the infant to pulmonary infection.
In the industrialized world, meconium in the amniotic fluid can be detected in 8-25% of all births after 34 weeks' gestation. Historically, approximately 10% of newborns born through meconium-stained amniotic fluid developed meconium aspiration syndrome (MAS). However, changes in obstetric and neonatal practices appear to be decreasing its incidence.[6] MAS was the admission diagnosis for 1.8% of term neonates in one large retrospective study from 1997-2007.[1]
International data
In developing countries with less availability of prenatal care and where home births are common, the incidence of MAS is thought to be higher and is associated with a greater mortality rate.
Age-, sex-, and race-related demographics
MAS is exclusively a disease of newborns, especially those delivered at or beyond the mother's estimated due date.[1] MAS affects both sexes equally.
A study of 499,096 singleton live births in London, England, reported the rates of meconium-stained amniotic fluid varied by ethnicity: It was 22.6% in the black population, 16.8% in south Asian groups, and 15.7% in the white population.[7] The study also demonstrated that meconium-stained amniotic fluid occurred more often in later-gestational-age pregnancies and in babies in the breech presentation.
Most infants with meconium aspiration syndrome (MAS) have complete recovery of pulmonary function; however, MAS infants have a slightly increased incidence of respiratory infections in the first year of life because the lungs are still in recovery. Severely affected infants have an increased risk of developing reactive airway disease (RAD) in the first 6 months of life.[8]
Children with MAS may develop chronic lung disease from intense pulmonary intervention.
Prenatal and intrapartum events that initiate the meconium passage may cause the infant to have long-term neurologic deficits, including central nervous system (CNS) damage, seizures, mental retardation, and cerebral palsy.
Morbidity/mortality
A large retrospective analysis demonstrated the overall mortality rate for MAS to be 1.2% in the United States.The mortality rate for MAS resulting from severe parenchymal pulmonary disease and pulmonary hypertension is as high as 20%. Other complications include air leak syndromes (eg, pneumothorax, pneumomediastinum, pneumopericardium), which occur in 10-30% of infants with MAS. The neurologic disabilities of survivors are not due primarily to the aspiration of meconium, but rather by in-utero pathophysiology, including chronic hypoxia and acidosis.
A large retrospective analysis demonstrated the overall mortality rate for MAS to be 1.2% in the United States.[1] The mortality for MAS resulting from severe parenchymal pulmonary disease and pulmonary hypertension is as high as 20%. Other complications include air-leak syndromes (eg, pneumothorax, pneumomediastinum, pneumopericardium) and pulmonary interstitial emphysema, which occur in 10-30% of infants who have MAS. The neurologic disabilities of survivors are not due primarily to the aspiration of meconium, but rather owing to in utero pathophysiology, including chronic hypoxia and acidosis.[9]
The presence of meconium in amniotic fluid is required to cause meconium aspiration syndrome (MAS), but not all neonates with meconium-stained fluid develop this condition. The diagnosis of MAS requires the presence of meconium-stained amniotic fluid or neonatal respiratory distress, as well as characteristic radiographic abnormalities.
Historically, efforts to reduce the development of MAS included oropharyngeal suctioning at the perineum, followed by intubation and tracheal suction of meconium immediately following delivery. This universal practice was abandoned over a decade ago when studies showed that infants who were vigorous at birth did not benefit from this intervention. Following this practice change, the Neonatal Resuscitation Program (NRP) recommended intubation and tracheal suctioning only for nonvigorous infants born through meconium-stained fluid.
However, in 2015, these recommendations changed again: It is no longer recommended to intubate and suction nonvigorous infants born through meconium-stained fluid due to a lack of evidence to support this practice.[10, 11] Instead, in this setting, the NRP now recommends having a practitioner skilled at endotracheal intubation be present at the time of birth, and they should begin with the initial steps of resuscitation (ie, provide warmth, position the head and neck to open the airway, clear secretions with a bulb syringe, dry, and stimulate the infant).[10, 11] The 2017 American College of Obstetricians and Gynecologists (ACOG) opinion number 689 indicates that, regardless of whether infants with meconium-stained amniotic fluid are vigorous or nonvigorous, do not routinely administer intrapartum suctioning.[11]
In a 2015 developing nation retrospective study (2008-2009) that evaluated the effect of intrapartum oropharyngeal suction on MAS in 509 meconium-stained, term singleton neonates without major congenital malformations, investigators found that outcomes in those who received suctioning were similar to those in the control group (who did not undergo suctioning).[12] The incidence and severity of MAS, as well as oxygen requirements longer than 48 hours, were comparable between the groups.
Severe respiratory distress may be present. Symptoms include the following:
Cyanosis
End-expiratory grunting
Alar (nasal) flaring
Intercostal retractions
Tachypnea
Barrel chest (increased anteroposterior diameter) due to the presence of air trapping
Auscultated rales and rhonchi (in some cases)
Yellow-green staining of fingernails, umbilical cord, and skin may be also observed.
Green urine may be noted in newborns with MAS less than 24 hours after birth. Meconium pigments can be absorbed by the lung and can be excreted in urine.
Ventilation-perfusion (V/Q) mismatch and perinatal stress are prevalent in meconium aspiration syndrome (MAS); therefore, assessment of the infant's acid-base status is crucial.
Metabolic acidosis from perinatal stress is complicated by respiratory acidosis from parenchymal disease and persistent pulmonary hypertension of the newborn (PPHN).
Measurement of arterial blood gas (ABG) pH, partial pressure of carbon dioxide (pCO2), and partial pressure of oxygen (pO2), as well as continuous monitoring of oxygenation by pulse oximetry are necessary for appropriate management. The calculation of an oxygenation index (OI) can be helpful when considering advanced treatment modalities, such as extracorporeal membrane oxygenation (ECMO).
Serum electrolytes
Obtain sodium, potassium, and calcium concentrations at 24 hours of life in infants with MAS, because syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and acute renal failure are frequent complications of perinatal stress.
Complete blood cell (CBC) count
Note the following:
In utero or perinatal blood loss, as well as infection, contributes to postnatal stress.
Hemoglobin and hematocrit levels must be sufficient to ensure adequate oxygen-carrying capacity.
Thrombocytopenia increases the risk for neonatal hemorrhage.
Neutropenia or neutrophilia with left shift of the differential may indicate perinatal bacterial infection.
Polycythemia may be present secondary to chronic fetal hypoxia; polycythemia is associated with decreased pulmonary blood flow and may exacerbate the hypoxia associated with MAS and PPHN.
There is little evidence that empiric antibiotic therapy after obtaining a blood culture is beneficial, except in the case of prolonged rupture of the membranes and maternal fever.
Fetal scalp blood lactate sampling has not been shown to reduce the risk of respiratory distress syndrome in infants with meconium-stained amniotic fluid.[13]
Chest radiography is essential in order to achieve the following:
Confirm the diagnosis of meconium aspiration syndrome (MAS) and determine the extent of the intrathoracic pathology
Identify areas of atelectasis and air leak syndromes
Ensure appropriate positioning of the endotracheal tube and umbilical catheters
See the images below.
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Air trapping and hyperexpansion from airway obstruction.
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Acute atelectasis.
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Pneumomediastinum from gas trapping and air leak.
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Left pneumothorax with depressed diaphragm and minimal mediastinal shift because of noncompliant lungs.
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Diffuse chemical pneumonitis from constituents of meconium.
Ultrasonography
Echocardiography is necessary to ensure normal cardiac structure and for assessment of cardiac function, as well as to determine the severity of pulmonary hypertension and right-to-left shunting.
A prospective observational study of 117 newborns with MAS (and 100 controls) demonstrated that pulmonary ultrasonography may be a convenient, noninvasive, and accurate imaging modality for the diagnosis of MAS.[14] The primary features of MAS noted on sonograms included the following[14] :
Pulmonary consolidation with air bronchograms (all patients)
Pleural line anomalies and absence of the A-line (all patients)
Alveolar-interstitial syndrome or B-lines in nonconsolidated regions (all patients)
Atelectasis in severe MAS (16.2% of severe cases)
Pleural effusion (13.7% of patients)
Brain imaging studings
Later in the course of MAS, when the infant is stable and if the infant's neurologic examination is abnormal, imaging studies of the brain (eg, magnetic resonance imaging [MRI], computed tomography [CT] scanning, cranial ultrasonography) are indicated.
The American College of Obstetricians and Gynecologists (ACOG) continues to provide guidance regarding the appropriate indications for delivery to prevent neonatal complications of a prolonged pregnancy, as well as for avoiding the unnecessary delivery of a preterm baby.[15, 16]
In patients with meconium aspiration syndrome (MAS), a thorough cardiac examination and echocardiography are necessary to evaluate for congenital heart disease and persistent pulmonary hypertension of the newborn (PPHN).
Quantifying the degree of pulmonary hypertension, prior to instituting therapy, is essential.
Prevention of MAS
Prevention of MAS is paramount. Obstetricians should closely monitor fetal status in an attempt to identify fetal distress.
When meconium is detected, amnioinfusion with warm, sterile saline is theoretically beneficial to dilute the meconium in the amniotic fluid, thereby minimizing the severity of the aspiration. However, current evidence does not support routine amnioinfusion to prevent MAS.[17, 18, 19] One large, multicenter study determined that amnioinfusion did not reduce the risk of moderate or severe MAS or MAS-related death.[20]
As noted earlier under Presentation, current recommendations no longer advise routine intrapartum suctioning for infants born to mothers with meconium staining of the amniotic fluid.[10, 11, 21, 22, 23]
No clinical trials justify suctioning on the basis of the meconium consistency. Do NOT perform the following harmful techniques in an attempt to prevent aspiration of meconium-stained amniotic fluid:
Squeezing the chest of the baby
Inserting a finger into the mouth of the baby
The American Academy of Pediatrics (AAP) Neonatal Resuscitation Program Steering Committee and the American Heart Association (AHA) have promulgated guidelines for management of babies exposed to meconium.[10] The guidelines are under continuous review and are revised as new evidence-based research becomes available. The seventh edition of the Neonatal Resuscitation Program modified its previous recommendations regarding endotracheal suctioning for the nonvigorous infant. The most recent guidelines are as follows[10, 11] :
If the baby is vigorous (defined as havin a normal respiratory effort and normal muscle tone), the baby may stay with the mother to receive the initial steps of newborn care. A bulb syringe can be used to gently clear secretions from the nose and mouth.
If the baby is not vigorous (defined as having a depressed respiratory effort or poor muscle tone), place the baby on a radiant warmer, clear the secretions with a bulb syringe, and proceed with the normal steps of newborn resuscitation (ie, warming, repositioning the head, drying, and stimulating). If, after these initial steps are taken, the baby is still not breathing or the heart rate is below 100 beats per minute (bpm), administer positive pressure ventilation.
Resuscitation should follow the same principles for infants with meconium-stained fluid as for those with clear fluid.
Continued care in the neonatal intensive care unit (NICU)
Maintain an optimal thermal environment to minimize oxygen consumption.
Minimal handling is essential because these infants are easily agitated. Agitation can increase pulmonary hypertension and right-to-left shunting, leading to additional hypoxia and acidosis. Sedation may be necessary to reduce agitation.
An umbilical artery catheter should be inserted to monitor blood pH and blood gases without agitating the infant.
Continue respiratory care includes oxygen therapy via hood or positive pressure, and it is crucial in maintaining adequate arterial oxygenation. Mechanical ventilation is required by approximately 30% of infants with MAS.[5] Make concerted efforts to minimize the mean airway pressure and to use as short an inspiratory time as possible. Oxygen saturations should be maintained at 90-95%.
Surfactant therapy is commonly used to replace displaced or inactivated surfactant and as a detergent to remove meconium.[24, 25, 26] Although surfactant use does not appear to affect mortality rates, it may reduce the severity of disease, progression to extracorporeal membrane oxygenation (ECMO) utilization,[27] and decrease the length of hospital stay.
Although conventional ventilation is commonly used as initial management, high-frequency oscillation and jet ventilation are alternative effective therapies. Hyperventilation to induce hypocapnia and compensate for metabolic acidosis is no longer a primary therapy for pulmonary hypertension, because hypocarbia often results in decreased cerebral perfusion (partial pressure of carbon dioxide [PaCO2] 28</ref>
Jet ventilator therapy aimed at minimizing mean airway pressure and tidal volume should be used if pulmonary interstitial emphysema or a pneumothorax is present.
For treatment of persistent pulmonary hypertension of the newborn (PPHN), inhaled nitric oxide is the pulmonary vasodilator of choice.[29] Oxygen is also a potent pulmonary vasculature vasodilator. Phosphodiesterase inhibitors, including sildenafil and milrinone, are being increasingly used as adjunctive therapies for PPHN.
Pay careful attention to systemic blood volume and blood pressure. Volume expansion, transfusion therapy, and systemic vasopressors are critical in maintaining systemic blood pressure greater than pulmonary blood pressure, thereby decreasing the right-to-left shunt through the patent ductus arteriosus. Dopamine is often the first-line vasopressor for neonates with MAS requiring vasopressor support.
Ensure adequate oxygen carrying capacity by maintaining the hemoglobin concentration at a minimum of 13 g/dL.
Corticosteroids are not recommended. Evidence supporting the use of steroids in the management of MAS is insufficient.[30]
Neonates with MAS have historically been routinely treated with empiric broad-spectrum antibiotics, but this practice is being increasingly called into question. No studies have shown prophylactic antibiotics to reduce the incidence of sepsis in neonates born through meconium-stained amniotic fluid; thus, antibiotic use may be reserved for suspected or documented infections.
ECMO is used if all other therapeutic options have been exhausted. Although it is effective in treating MAS, note that ECMO is associated with a high incidence of poor neurologic outcomes.
Consultations
Evaluation by a pediatric cardiologist is necessary for echocardiographic assessment of the cardiac structures and to assess the severity of pulmonary hypertension and right-to-left shunting.
Evaluation by a pediatric neurologist is helpful in the presence of neonatal encephalopathy or seizure activity.
Transfer
Although initial stabilization is necessary at community hospitals, infants with MAS frequently require high-frequency ventilation, inhaled nitric oxide (NO), or ECMO. Therefore, infants with a significant aspiration should be transferred to a regional NICU as soon as possible.
Diet
Perinatal distress and severe respiratory distress preclude feeding at the early stages of the disease.
Intravenous fluid therapy begins with adequate dextrose infusion to prevent hypoglycemia. Intravenous fluids should be provided at mildly restricted rates (60-70 mL/kg/day).
Progressively add electrolytes, protein, lipids, and vitamins to ensure adequate nutrition and to prevent deficiencies of essential amino acids and essential fatty acids.
Outpatient care
Infants with MAS are at increased risk for adverse developmental outcomes and should be referred for developmental assessment as an outpatient.
Although primary management of air leak syndromes (pneumothorax or pneumopericardium) is achieved by thoracic drainage tubes inserted by a neonatologist, a pediatric surgical consultation may be necessary in severe cases. Therapy with fibrin glue has been shown to be effective in patients with a persistent air leak.[31]
In addition to the treatments discussed earlier and the medications listed below, surfactant replacement therapy is frequently used in infants with meconium aspiration syndrome (MAS). Natural lung extract is administered to replace the surfactant that has been stripped. Surfactant also acts as a detergent to break up residual meconium, thereby decreasing the severity of lung disease. Surfactant is used in patients with MAS; however, its efficacy, dosage regimen, and most effective product are not yet established.
Clinical Context:
Endogenously produced from the action of the enzyme NO synthetase on arginine. Exogenously inhaled NO is used in an attempt to decrease pulmonary vascular resistance and improve lung blood flow. It relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cGMP, which then leads to vasodilation.
Inhaled nitric oxide (NO) has the direct effect of pulmonary vasodilatation without the adverse effect of systemic hypotension. It is approved for use, if concomitant hypoxemic respiratory failure occurs.
Clinical Context:
Increases blood pressure primarily via stimulation of beta1-adrenergic receptors. This drug appears to have a more prominent effect on cardiac output than on blood pressure.
Clinical Context:
Used for severe bronchoconstriction, especially in patients with underlying reactive airway disease. Alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
These agents are used to prevent right-to-left shunting by raising systemic pressure above pulmonary pressure. Systemic vasoconstrictors include dopamine, dobutamine, and epinephrine. Dopamine is the most commonly used.
Clinical Context:
An anticonvulsant that may be used as a sedative. Suppresses the CNS from the reticular activating system (ie, presynaptic, postsynaptic).
Phenobarbital remains a first-line therapy for neonatal seizures, which may occur in the setting of perinatal depression.
These agents maximize efficiency of mechanical ventilation, minimize oxygen consumption, and treat the discomfort of invasive therapies. However, some controversy exists around the unknown long-term effect(s) of analgesics and sedatives on the developing brain.
These agents are used for skeletal muscle paralysis to maximize ventilation by improving oxygenation and ventilation. They are also used to reduce barotrauma and minimize oxygen consumption.
The use of paralytics remains controversial and should be considered in newborns whose management with sedatives alone is failing.
Gina M Geis, MD, Attending Neonatologist, Associate Director, Neonatal-Perinatal Medicine Fellowship Program, Albany Medical Center; Assistant Professor, Department of Pediatrics, Albany Medical College
Disclosure: Nothing to disclose.
Coauthor(s)
David A Clark, MD, Professor and Martha Lepow Chairman of Pediatrics, Professor of Obstetrics and Gynecology, Albany Medical College; Director, Children's Hospital at Albany Medical Center
Disclosure: Nothing to disclose.
Specialty Editors
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Brian S Carter, MD, FAAP, Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Neonatology, Children's Mercy Hospital and Clinics; Faculty, Children's Mercy Bioethics Center
Disclosure: Nothing to disclose.
Chief Editor
Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Melinda B Clark, MD, Associate Professor of Pediatrics, Department of Pediatrics, Albany Medical College
Ranzini AC, Chan L. Meconium and fetal-neonatal compromise. In: Spitzer AR, ed. Intensive Care of the Fetus and Neonate. St Louis, Mo: Mosby; 1996. 297-303.
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