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.
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. 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.
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).
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.
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.
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. Changes in obstetrical and neonatal practices appear to be decreasing the incidence of meconium aspiration syndrome. Meconium aspiration syndrome was the admission diagnosis for 1.8% of term neonates in one large retrospective study from 1997-2007.
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.
A large retrospective analysis demonstrated the overall mortality rate for meconium aspiration syndrome to be 1.2% in the United States. 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.
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.
Meconium aspiration syndrome equally affects both sexes.
Meconium aspiration syndrome is exclusively a disease of newborns, especially those that are delivered at or beyond the mother's estimated due date.
Presence of meconium in amniotic fluid is required to cause meconium aspiration syndrome (MAS), but not all neonates with meconium-stained fluid develop meconium aspiration syndrome. The presence of thick particulate meconium in the amniotic fluid increases the likelihood of prenatal aspiration.
Inadequate removal of meconium from the airway prior to the first breath and use of positive pressure ventilation (PPV) prior to clearing the airway of meconium increase the likelihood of a neonate developing meconium aspiration syndrome.
Green urine may be observed in newborns with meconium aspiration syndrome less than 24 hours after birth. Meconium pigments can be absorbed by the lung and can be excreted in urine.
The diagnosis of meconium aspiration syndrome requires the presence of meconium stained amniotic fluid or neonatal respiratory distress, and characteristic radiographic abnormalities.
The following studies are indicated in suspected meconium aspiration syndrome (MAS):
Ventilation-perfusion (V/Q) mismatch and perinatal stress are prevalent and assessment of 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).
ABG measurement of pH, partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), and continuous measurement of oxygenation by pulse oximetry are necessary for appropriate management.
Serum electrolytes: Obtain sodium, potassium, and calcium concentrations at 24 hours of life in infants with meconium aspiration syndrome because the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and acute renal failure are frequent complications of perinatal stress.
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 meconium aspiration syndrome 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.
Chest radiography is essential in order to achieve the following:
Confirm the diagnosis of meconium aspiration syndrome and determine the extent of intrathoracic pathology (see images below)
Identify areas of atelectasis and air block syndromes (see images below)
Ensure appropriate positioning of the endotracheal tube and umbilical catheters
Air trapping and hyperexpansion from airway obstruction.
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.
Later in the course of meconium aspiration syndrome, when the infant is stable, imaging studies of the brain (eg, MRI, CT scanning, cranial ultrasonography) are indicated, if the infant's neurologic examination is abnormal.
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 notsupport routine amnioinfusion to prevent meconium aspiration syndrome.[10, 11, 12] One large, multicenter study determined that amnioinfusion did not reduce the risk of moderate or severe meconium aspiration syndrome or meconium aspiration syndrome–related death.
Current recommendations no longer advise routine intrapartum suctioning for infants born to mothers with meconium staining of the amniotic fluid.[14, 15]
When aspiration occurs, intubation and immediate suctioning of the airway can remove much of the aspirated meconium.
No clinical trials justify suctioning based on the consistency of meconium. 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 Neonatal Resuscitation Program Steering Committee and the American Heart Association have promulgated guidelines for management of the baby exposed to meconium. The guidelines are under continuous review and are revised as new evidence-based research becomes available. The current guidelines are as follows:
If the baby is not vigorous (defined as depressed respiratory effort, poor muscle tone, and/or heart rate < 100 beats/min): Use direct laryngoscopy, intubate, and suction the trachea immediately after delivery. Suction for no longer than 5 seconds. If no meconium is retrieved, do not repeat intubation and suction. If meconium is retrieved and no bradycardia is present, reintubate and suction. If the heart rate is low, administer positive pressure ventilation and consider suctioning again later.
If the baby is vigorous (defined as normal respiratory effort, normal muscle tone, and heart rate >100 beats/min): Do not electively intubate. Clear secretions and meconium from the mouth and nose with a bulb syringe or a large-bore suction catheter.
In both cases, the remainder of the initial resuscitation steps should ensue, including drying, stimulating, repositioning, and administering oxygen as necessary.
Continued care in the neonatal ICU (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 decrease agitation.
An umbilical artery catheter should be inserted to monitor blood pH and blood gases without agitating the infant.
Continue respiratory care. Oxygen therapy via hood or positive pressure is crucial in maintaining adequate arterial oxygenation. Mechanical ventilation is required by approximately 30% of infants with meconium aspiration syndrome. 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 now commonly used to replace displaced or inactivated surfactant and as a detergent to remove meconium.[17, 18, 19] Although surfactant use does not appear to affect mortality rates, it may reduce the severity of disease, progression to extracorporeal membrane oxygenation (ECMO) , and decrease length of hospital stay.
Although conventional ventilation commonly is initially used, 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 (PaCO2 < 30 mm Hg). Prolonged alkalosis has been shown to cause neuronal injury in animals and humans, providing another reason to avoid alkalosis in these patients.
Ventilator therapy aimed at minimizing mean airway pressure and tidal vlume 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. 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 meconium aspiration syndrome requiring vasopressor support.
Ensure adequate oxygen carrying capacity by maintaining the hemoglobin concentration of at least 13 g/dL.
Corticosteroids are not recommended. Evidence supporting the use of steroids in the management of meconium aspiration syndrome is insufficient.
Neonates with meconium aspiration syndrome 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.
Extracorporeal membrane oxygenation (ECMO) is used if all other therapeutic options have been exhausted. Although effective in treating meconium aspiration syndrome, ECMO is associated with a high incidence of poor neurologic outcomes.
Although primary management of air block 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.
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.
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.
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.
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.
In patients with meconium aspiration syndrome (MAS), thorough cardiac examination and echocardiography are necessary to evaluate for congenital heart disease and persistent pulmonary hypertension of the newborn (PPHN).
Confirming the degree of pulmonary hypertension, prior to instituting therapy, is extremely important.
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.
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]
Most infants with meconium aspiration syndrome (MAS) have complete recovery of pulmonary function. Severely affected infants have approximately a 50% risk of developing reactive airway disease in the first 6 months of life.
Prenatal and intrapartum events initiating the meconium passage may cause the infant to have long-term neurologic deficits, including CNS damage, seizures, mental retardation, and cerebral palsy.
Melinda B Clark, MD, Assistant Professor of Pediatrics, Department of Pediatrics, Albany Medical College
Disclosure: Nothing to disclose.
David A Clark, MD, Chairman, Professor, Department of Pediatrics, Albany Medical College
Disclosure: Nothing to disclose.
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.
Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine