Meconium Aspiration Syndrome

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Background

The first intestinal discharge from newborns is meconium, which is a viscous, dark-green substance composed of intestinal epithelial cells, lanugo, mucus, and intestinal secretions (eg, 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, comprising 85-95% of meconium. Meconium is sterile and does not contain bacteria, the primary factor that differentiates it from stool. Intrauterine distress can cause passage into the amniotic fluid. Factors that promote the passage in utero include placental insufficiency, maternal hypertension, preeclampsia, oligohydramnios, and maternal drug abuse, especially of tobacco and cocaine.

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 chiefly affects infants born at term and postterm.

Pathophysiology

In utero meconium passage results from neural stimulation of a maturing GI tract and usually results from fetal hypoxic stress. As the fetus approaches term, the GI tract matures, and vagal stimulation from head or 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. Additionally, meconium is irritating to fetal skin, thus increasing the incidence of erythema toxicum. However, the most severe complication of meconium passage in utero is aspiration of stained amniotic fluid before, during, and after birth. Aspiration induces hypoxia via four major pulmonary effects: airway obstruction, surfactant dysfunction, chemical pneumonitis, and pulmonary hypertension.

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)-1ß, I-L6, 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.

Epidemiology

Frequency

United States

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. Changes in obstetrical and neonatal practices appear to be decreasing the incidence of meconium aspiration syndrome.[6] Meconium aspiration syndrome was the admission diagnosis for 1.8% of term neonates in one large retrospective study from 1997-2007.[7]

International

In developing countries with less availability of prenatal care and where home births are common, incidence of meconium aspiration syndrome is thought to be higher and is associated with a greater mortality rate.

Mortality/Morbidity

A large retrospective analysis demonstrated the overall mortality rate for meconium aspiration syndrome to be 1.2% in the United States.[7] The mortality rate for meconium aspiration syndrome resulting from severe parenchymal pulmonary disease and pulmonary hypertension is as high as 20%. Other complications include air block syndromes (eg, pneumothorax, pneumomediastinum, pneumopericardium) and pulmonary interstitial emphysema, which occur in 10-30% of infants with meconium aspiration syndrome. 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.[8]

Race

A study of 499,096 singleton live births in London, England reported the rates of meconium-stained amniotic fluid varied by ethnicity: blacks (22.6%), south Asian (16.8%), and whites (15.7%). The study also demonstrated that later-gestational-age pregnancies and babies in the breach presentation more often had meconium-stained amniotic fluid.[9]

Sex

Meconium aspiration syndrome equally affects both sexes.

Age

Meconium aspiration syndrome is exclusively a disease of newborns, especially those that are delivered at or beyond the mother's estimated due date.[1]

History

Physical

Severe respiratory distress may be present. Symptoms include the following:

Yellow-green staining of fingernails, umbilical cord, and skin may be observed.

Causes

Laboratory Studies

The following studies are indicated in suspected meconium aspiration syndrome (MAS):

Imaging Studies

Other Tests

Medical Care

Surgical Care

Consultations

Diet

Medication Summary

In addition to the treatments listed below, surfactant replacement therapy is frequently used. 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 meconium aspiration syndrome (MAS); however, its efficacy, dosage regimen, and most effective product are not yet established.

Nitric oxide, inhaled (INOmax)

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.

Class Summary

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.

Dopamine (Intropin)

Clinical Context:  At lower doses, dopamine stimulates beta1-adrenergic and dopaminergic receptors (renal vasodilation, positive inotropism); at higher doses, it stimulates alpha-adrenergic receptors (renal vasoconstriction).

Dobutamine (Dobutrex)

Clinical Context:  Increases blood pressure primarily via stimulation of beta1-adrenergic receptors. Drug appears to have more prominent effect on cardiac output than on blood pressure.

Epinephrine

Clinical Context:  Used for severe bronchoconstriction, especially in patients with underlying reactive airways 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.

Class Summary

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.

Morphine

Clinical Context:  Used for analgesia and sedation.

Fentanyl (Sublimaze)

Clinical Context:  Potent opioid used for analgesia, sedation, and anesthesia. Has a shorter duration of action than morphine.

Phenobarbital (Luminal)

Clinical Context:  An anticonvulsant that may be used as a sedative. Suppresses the CNS from the reticular activating system (ie, presynaptic, postsynaptic).

Pentobarbital (Nembutal)

Clinical Context:  CNS sedative and hypnotic that acts primarily on the cerebral cortex and reticular formation through decreased neuronal synaptic activity.

Class Summary

These agents maximize efficiency of mechanical ventilation, minimize oxygen consumption, and treat the discomfort of invasive therapies.

Pancuronium (Pavulon)

Clinical Context:  Neuromuscular blocker whose effects are reversed by neostigmine and atropine.

Class Summary

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.

Further Inpatient Care

Further Outpatient Care

Transfer

Although initial stabilization is necessary at community hospitals, infants with meconium aspiration syndrome frequently require high-frequency ventilation, inhaled nitric oxide (NO), or extracorporeal membrane oxygenation (ECMO). Therefore, infants with a significant aspiration should be transferred to a regional neonatal ICU (NICU) as soon as possible.

Deterrence/Prevention

The American College of Obstetricians and Gynecologists continues to provide guidance regarding the appropriate indications for delivery to prevent neonatal complications of a prolonged pregnancy as well as avoiding the unnecessary delivery of a preterm baby.[25, 26]

Complications

Prognosis

Author

Melinda B Clark, MD, Assistant Professor of Pediatrics, Department of Pediatrics, Albany Medical College

Disclosure: Nothing to disclose.

Coauthor(s)

David A Clark, MD, Chairman, Professor, Department of Pediatrics, Albany Medical College

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.

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina

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.

References

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Air trapping and hyperexpansion from airway obstruction.

Acute atelectasis.

Pneumomediastinum from gas trapping and air leak.

Left pneumothorax with depressed diaphragm and minimal mediastinal shift because of noncompliant lungs.

Diffuse chemical pneumonitis from constituents of meconium.

Air trapping and hyperexpansion from airway obstruction.

Acute atelectasis.

Pneumomediastinum from gas trapping and air leak.

Left pneumothorax with depressed diaphragm and minimal mediastinal shift because of noncompliant lungs.

Diffuse chemical pneumonitis from constituents of meconium.