The baby born through meconium-stained amniotic fluid is at risk for acute respiratory distress, long-term sequelae, or even death. Early identification and treatment of sick infants limit complications.
Physicians attending a newborn who is born through meconium-stained amniotic fluid (MSAF) may well be confronted with an infant in distress. All obstetricians, especially those who do not have immediate access to a neonatologist, need to be able to identify meconium aspiration syndrome (MAS)a potentially fatal conditionand know how to manage it. Familiarity with strategies to prevent or minimize illness also is important.
MSAF is present in 8% to 19% of all term deliveries, and the risk increases with advancing gestational age.1-4 MSAF is one and one-half times as likely in births to African-American women than in those to Caucasian women.5 The presence of MSAF may be associated with adverse fetal and neonatal outcomes, including acute respiratory distress, long-term pulmonary and neurologic sequelae, and death. MAS develops in 5% to 33% of all infants born through MSAF, and more than one third of these infants require mechanical ventilation.3 Approximately one third of infants with MAS have persistent pulmonary hypertension of the newborn (PPHN).6 A large proportion of the disturbingly high mortality associated with MAS (4% to 19%) is probably attributable to PPHN. Although most infants with MAS survive, some have abnormal pulmonary function both during infancy and in later childhood, including increased functional residual capacity and airway reactivity.7,8
Infants born through MSAF of a moderate to thick consistency are seven times more likely than other infants to have neonatal seizures, presumably secondary to hypoxic events, and are five times more likely to have hypotonia.9 Babies born through MSAF who have a low 5-minute Apgar score also appear to be at increased risk of cerebral palsy.10
"How MAS develops," describes how meconium moves from the fetal GI tract to the mother's uterus and then is aspirated into the infant's lungs.11-16
Whether respiratory complications develop in an infant born through MSAF depends on the degree of hypoxia in utero and on the consistency of the meconium. Infants born through thick MSAF, as well as those whose respiration is depressed at birth, are at greatest risk for developing MAS. Neonates who are apparently vigorous at birth, particularly if born through thin MSAF, are at low risk for developing MAS. In a large multicenter clinical trial, 3% of apparently vigorous infants born through MSAF developed MAS.18 When the MSAF was thin, incidence of MAS was about 1% compared with 7% in infants born through thick MSAF. Incidence of all respiratory complications in the trial, including transient tachypnea of the newborn, sepsis and pneumonia, pulmonary edema, and pneumothorax, was significantly higher in infants born through thick MSAF (15%) than in those born through thin MSAF (2%). About half of the infants with MAS required mechanical ventilation.18
Infants with MAS are often postterm. In addition to showing signs of respiratory and neurologic depression at birth, they may have respiratory distress with tachypnea, grunting, flaring, retractions, and cyanosis. Although MAS can occur secondary to pulmonary hypertension, infants with MAS may in turn develop pulmonary hypertension, with significant hypoxemia, hypercapnia, and right-to-left shunting of blood at either the ductus arteriosus or the foramen ovale. Typical findings on chest radiography include diffuse patchy infiltrates, areas of consolidation, and hyperinflation (Figure 1).
Other radiographic findings may include pneumothorax and cardiomegaly, if perinatal hypoxia was significant.
Based on clinical presentation and chest radiography, it may be almost impossible to differentiate MAS from sepsis or pneumonia. Table 1 lists the differential diagnosis.
Differential diagnosis of MAS*
Respiratory distress syndrome in a term infant
Transient tachypnea of the newborn
Persistent pulmonary hypertension
Acute respiratory distress syndrome
Congenital cyanotic heart disease (needs to be ruled out in presence of significant hypoxemia)
*When meconium-stained amniotic fluid is present at delivery
The management of infants with severe MAS can be extremely difficult. Since avoiding morbidity and mortality depends in part on alleviation of hypoxemia, the rapid identification of sick infants and instigation of treatmentwhich is largely supportiveare crucial.
Umbilical arterial and venous catheter placement. This helps monitor arterial blood gases and cardiovascular function and provides central venous access for administration of drugs and nutrition. Serum electrolytes should be closely monitored and attention paid to fluid intake and urine output.
Antibiotic administration. Given the possible confusion of MAS with sepsis, all infants diagnosed with MAS should probably initially be treated for possible sepsis, at least until the blood culture is negative for 2 to 3 days.
Antibiotics should be started immediately after birth since it is hard to differentiate these infants from those with pneumonia. Obtain a blood culture prior to starting antibiotics.
The most likely bacterial pathogens causing infections in neonates soon after birth include group B Streptococcus, Escherichia coli, Listeria monocytogenes, and Enterococcus species. These organisms are sensitive to a combination of ampicillin (100 mg/kg every 12 hours) and gentamicin (4 mg/kg every 24 to 36 hours).
Ventilatory support. Depending on the severity of respiratory distress, required ventilatory support ranges from supplemental oxygen, using an oxygen hood or nasal prongs, to mechanical ventilation, either conventional or high frequency.
Infants should initially be treated with conventional modes of ventilation. However, hypoxemic and hypercapneic infants should receive either continuous positive airway pressure or mechanical ventilation. In infants with substantial hypoxemia and/or hypercapnia, high-frequency ventilation may help improve gas exchange.
Surfactant therapy. This is not yet specifically approved by the Food and Drug Administration for use in MAS, exogenous surfactant (beractant) 6 mL/kg, may help improve oxygenation.19
Echocardiography. It is often necessary to do echocardiography to evaluate cardiac contractility and ventricular filling, as well as to look for evidence of pulmonary hypertension. Treatment of pulmonary hypertension can be frustrating because infants with MAS can be severely hypoxemic and hemodynamically unstable. Management includes correction of acidosis and maintenance of adequate blood pressure using ionotropic or chronotropic drugs. Reduced intravascular volume, as evidenced by hypotension and decreased ventricular filling on echocardiography, needs to be corrected.
In some instances, inhaled nitric oxide (iNO), an experimental selective pulmonary vasodilator, improves oxygenation. The FDA recently approved this therapy for treatment of term infants with hypoxic respiratory failure associated with clinical and echocardiographic evidence of pulmonary hypertension. Infants with severe hypoxemia not responsive to supportive management and iNO therapy and infants who are hemodynamically unstable may benefit from extracorporeal membrane oxygenation (ECMO). Table 2 lists suggested studies and monitoring techniques in infants with MAS.
Investigations and monitoring for MAS
Electrolytes including Ca++
Arterial blood gases
Poor cardiac contractility
Decreased ventricular filling
Structural cardiac anomalies
Placental/umbilical cord examination by a pathologist
Close monitoring of neurologic status
Urine output and monitoring of serial blood urea nitrogen and creatinine
Serial complete blood counts for platelet count, total lymphocyte count, and absolute neutrophil count
Monitor for hypoglycemia and hypocalcemia
Consider neuroimaging if abnormal neurologic findings are present
Continuous blood pressure measurement
Close monitoring of intake and urine output
Several strategies for preventing meconium aspiration or lessening its effects have been proposed, but only a few have undergone sufficient study to be proven effective.
Prenatal strategies. Several studies have evaluated amnioinfusion (AI) for preventing MAS. AI is based on the principle that increasing the volume of amniotic fluid will dilute meconium. Although one would think that diluting the meconium would make it easier for the fetus to aspirate the substance, as we previously mentioned, respiratory complications are more likely to occur in infants born through moderate and thick meconium, compared with infants born through thin meconium. Additionally, meconium dilution decreases its toxicity.
Furthermore, if oligohydramnios is present, an increase in fluid volume might relieve cord compression, which could prevent fetal hypoxia and acidosis, further meconium passage, gasping, and meconium aspiration. In the largest retrospective study evaluating the efficacy of AI, however, investigators were unable to show any difference in neonatal outcomes between infants born to women who had received AI for MSAF and those born to women who did not. Moreover, investigators noted a higher incidence of fetal heart rate abnormalities, instrument-assisted deliveries, and endometritis in women who received AI.20 Given these and other findings so far, AI must be considered an experimental therapy for preventing MAS.
Intrapartum strategies. Several options have demonstrated efficacy.
Although oropharyngeal suctioning at the perineum has not eliminated the occurrence of MAS when MSAF is present, it has been shown to decrease the incidence of MAS.21 This technique, which is recommended by the American College of Obstetricians and Gynecologists, American Academy of Pediatrics, and American Heart Association, is associated with improved Apgar scores at 1 and 5 minutes, fewer abnormalities on chest radiography, and less need for mechanical ventilation than in infants born through MSAF who were not suctioned.22,23 A bulb syringe and a suction catheter give similar results.
Some authors recommend cesarean sections for infants surrounded by MSAF. They speculate that preventing the stresses of vaginal delivery may decrease the risk of meconium aspiration. No data support this strategy and we do not recommend it.
Other authors recommend administering strong sedatives, such as morphine or paralytics, to the mother. They suggest that since these agents cross the placenta, they prevent the fetus from gasping and inhaling MSAF. No clinical investigations have shown this strategy to be beneficial, and we do not recommend it.
Postnatal strategies. In the infant born through MSAF, these include several that appear promising but require more study as well as some that are dangerous to the newborn and should not be used.
In contrast to intrapartum oropharyngeal suctioning, postnatal tracheal suctioning has generated considerable controversy. Based on existing data, 1992 AAP/AHA guidelines recommended tracheal suctioning of infants with depressed respiration and those born through thick, particulate meconium.23 A recent multicenter clinical trial was unable to demonstrate any difference in the incidence of MAS or other respiratory complications in apparently vigorous infants who underwent intubation and tracheal suctioning compared with those who received routine delivery room care (expectant management). Only a few children (3.8%) experienced complications of intubation, and all the complications were transient.18 Based on these findings, routine tracheal suctioning seems to be unnecessary. We do recommend intubation and tracheal suctioning of infants born through MSAF whose respiration is depressed and who require positive pressure ventilation soon after birth, or who develop respiratory distress after the initial assessment. The intubation should be performed rapidly since prolonged attempts could be damaging.
Surfactant replacement therapy with high concentrations of surfactant overcomes the inhibition of surfactant activity associated with meconium.15,16 In a randomized clinical trial, infants with MAS treated with 6 mL/kg of beractant within 6 hours of birth showed improved oxygenation, decreased incidence of air leaks, and reduced likelihood of requiring ECMO. Of particular significance, respiratory status improved only after the second dose of surfactant, suggesting inadequate initial dosing.19 Further research is needed to establish the optimal dose(s), timing of administration, type of surfactant, and mode of delivery. Based on results of the trial cited above, we currently recommend administering beractant at 6 mL/kg every 6 hours for four doses. A newer synthetic surfactant (Surfaxin) contains a mixture of phospholipids and KL4 peptide, a synthetic peptide with physicochemical properties of surfactant protein B (SP-B). Since increasing concentrations of SP-B in surfactant have been shown to confer enhanced resistance to inactivation by protein, this new product may prove to be beneficial.
Lung lavage with exogenous surfactant replacement is a promising therapy for infants who have aspirated meconium. Ideally, the surfactant dose for infants with MAS should be based on the amount of meconium aspirated and the degree of surfactant inactivation. This is possible only with a bronchoalveolar lavage, followed by evaluation of surfactant function in the lavage fluid.
Bronchoalveolar lavage is thought to remove meconium and inflammatory mediators, decreasing pulmonary symptoms caused by airway obstruction and inflammation. Improved aeration of the lungs also permits delivery of more homogenous surfactant and decreases ventilation-perfusion mismatch. In animal models, lavage of the airways with surfactant improves oxygenation.24 A pilot clinical trial demonstrated improved oxygenation and decreased duration of mechanical ventilation after lung lavage with a synthetic surfactant.25 Until other randomized clinical trials are completed, surfactant lavage for the management of infants with MAS should be considered an experimental therapy.
Glucocorticoids might decrease the inflammation in the lungs associated with meconium aspiration. A randomized clinical trial showed improved oxygenation and ventilation and decreased duration of mechanical ventilation in infants with MAS who were treated early with dexamethasone.26 Although these results are promising, the role of steroids in the treatment of MAS needs to be investigated further.
The FDA recently approved iNO, a selective pulmonary vasodilator, for treatment of term infants with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension. It is believed that NO decreases extrapulmonary right-to-left shunting and ventilation-perfusion mismatch by dilating the blood vessels in well-aerated lung fields. Its efficacy depends on adequate delivery of the agent to the target resistance vessels within the lung. Some clinical trials have indicated that the response to NO is disease-specific, with more consistent improvement in oxygenation in infants with extrapulmonary right-to-left shunting than in other infants. The drug should be tried in the presence of significant unremitting hypoxemia.
Liquid ventilation with perfluorocarbons appears promising but remains an experimental therapy. Meconium-stained lambs with respiratory distress improve rapidly after treatment with partial or total liquid ventilation.27 It may be that the unique ability of perflubron to dissolve large quantities of oxygen and carbon dioxide at atmospheric pressure can be useful for ventilating neonates with MAS, providing much-needed time for the lungs to recuperate from the insult.28
Three therapies are potentially dangerous and should not be used: (1) thoracic compression performed by encircling the child's chest with one's hands and applying pressure so as to prevent meconium aspiration before tracheal suctioning; (2) application of cricoid pressure to block the passage of MSAF into the thorax; and (3) manual epiglottal pressure in which one inserts one to three fingers into the hypopharynx and pushes the epiglottis over the glottis to prevent fluid entering the trachea. None of these maneuvers has undergone the scrutiny of clinical trials. Figure 2 suggests a management plan for minimizing meconium aspiration and its effects.
MSAF and MAS are often associated with suspected perinatal asphyxia, whose effects include central nervous system dysfunction, congestive heart failure and cardiogenic shock, and persistent pulmonary hypertension. The neurologic status of neonates suspected of having perinatal asphyxia should be closely monitored. According to the 1997 AAP/ACOG Guidelines for Perinatal Care, the term asphyxia applies only to an infant who meets all these criteria:
A pathologist should examine the placenta and umbilical cord of any infant with perinatal asphyxia to identify any placental or cord-related cause for fetal hypoxemia. Urine output as well as serial blood urea nitrogen and creatinine should be closely followed. In addition, serial liver function tests and complete blood counts (platelet, total lymphocyte, and absolute nucleated red cell count) should be performed. Asphyxiated infants are at risk for early hypoglycemia and hypocalcemia. Finally, if neurologic findings are abnormal, neuroimaging (computed tomography or MRI) should be performed within 2 to 7 days of birth.
MAS is a complex disorder resulting in a spectrum of clinical findings from mild respiratory distress to pulmonary hypertension and death. Although our limited understanding of the syndrome's pathophysiology hampers development of new treatment strategies, oropharyngeal suctioning at the perineum helps prevent problems in infants born through MSAF. Intubation and tracheal suctioning are required only if the infant is not vigorous or develops respiratory distress after the initial evaluation.
Management of infants with MAS is mainly supportive. Exogenous surfactant improves oxygenation, although optimal dose, timing, and route of administration need further evaluation. The role of other therapies, including surfactant lavage, steroid use, NO inhalation, and liquid ventilation also merits more investigation.
1. Fuloria M, Wiswell TE. Resuscitation of the meconium-stained infant and prevention of meconium aspiration syndrome. J Perinatol. 1999;19:234-241.
2. Gregory GA, Gooding CA, Phibbs RH, et al. Meconium aspiration in infantsa prospective study. J Pediatr. 1974;85:848-852.
3. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndromehave we made a difference? Pediatrics. 1990;85:715-721.
4. Nathan L, Leveno KJ, Carmody TJ, et al. Meconium: a 1990s perspective on an old obstetric hazard. Obstet Gynecol. 1994;83:329-332.
5. Alexander GR, Hulsey TC, Robillard PY, et al. Determinants of meconium-stained amniotic fluid in term pregnancies. J Perinatol. 1994;14:259-263.
6. Fleischer A, Anyaegbunam A, Guidette D, et al. A persistent clinical problem: profile of the term infant with significant respiratory complications. Obstet Gynecol. 1992;79:185-190.
7. Yuksel B, Greenough A, Gamsu HR. Neonatal meconium aspiration syndrome and respiratory morbidity during infancy. Pediatr Pulmonol. 1993;16:358-361.
8. Swaminathan S, Quinn J, Stabile MW, et al. Long-term pulmonary sequelae of meconium aspiration syndrome. J Pediatr. 1989;114:356-361.
9. Berkus MD, Langer O, Samueloff A, et al. Meconium-stained amniotic fluid: increased risk for adverse neonatal outcomes. Obstet Gynecol. 1994;84:115-120.
10. Nelson KB, Ellenberg JH. Obstetric complications as risk factors for cerebral palsy or seizure disorder. JAMA. 1984;251:1843-1848.
11. Lucas A, Adrian TE, Christofides N, et al. Plasma motilin, gastrin, and enteroglucagon and feeding in the human newborn. Arch Dis Child. 1980;55:673-677.
12. Rubin BK, Tomkiewicz RP, Patrinos ME, et al. The surface and transport properties of meconium and reconstituted meconium solutions. Pediatr Res. 1996;40:834-838.
13. Tyler DC, Murphy J, Cheney FW. Mechanical and chemical damage to lung tissue caused by meconium aspiration. Pediatrics. 1978;62:454-459.
14. Tran N, Lowe C, Sivieri EM, et al. Sequential effects of acute meconium aspiration on pulmonary function. Pediatr Res. 1980;14:34-38.
15. Moses D, Holm BA, Spitale P, et al. Inhibition of pulmonary surfactant function by meconium. Am J Obstet Gynecol. 1991;164:477-481.
16. Bae CW, Takahashi A, Chida S, et al. Morphology and function of pulmonary surfactant inhibited by meconium. Pediatr Res. 1998;44:187-191.
17. Higgins ST, Wu AM, Sen N, et al. Meconium increases surfactant secretion in isolated rat alveolar type II cell. Pediatr Res. 1996;39:443-447.
18. Wiswell TE, Gannon CM, Jacob J, et al. Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial. Pediatrics. 2000;105:1-7.
19. Findlay RD, Taeusch HW, Walther FJ. Surfactant replacement therapy for meconium aspiration syndrome. Pediatrics. 1996;97:48-52.
20. Usta IM, Mercer BM, Aswad NJ, et al. The impact of a policy of amnioinfusion for meconium-stained fluid. Obstet Gynecol. 1995;85:237-241.
21. Carson B, Losey RW, Bowes WA Jr, et al. Combined obstetric and pediatric approach to prevent meconium aspiration syndrome. Am J Obstet Gynecol. 1976;126:712-715.
22. Rossi C, Nascimento SD, Fernanda M, et al. Should obstetricians clear the airways of newborn infants with meconium stained amniotic fluid. Pediatr Res. 1997; 41:173A.
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24. Paranka MS, Walsh WF, Stancombe BB. Surfactant lavage in a piglet model of meconium aspiration syndrome. Pediatr Res. 1992;31:625-628.
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28. Fuloria M, Ying W, Brandt ML, et al. Effect of meconium- saline suspensions on the surface properties of perflubron. J Appl Physiol. in review 1999.
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Meconium is primarily water (72% to 80%) and also contains GI secretions, bile, mucus, pancreatic juice, cellular debris, swallowed amniotic fluid, vernix caseosa, and lanugo. In the infant with MAS, meconium moves from the infant's GI tract to the mother's uterus, where it is aspirated into the infant's lungs. Although meconium may be present in the GI tract as early as 10 to 16 weeks' gestation, the substance rarely is passed into the mother's uterus before 37 weeks' gestation. Passage initially is inhibited by the fetus's lack of strong intestinal peristalsis, along with the presence of a tonically contracted anal sphincter and a terminal cap of viscous meconium. Levels of motilin, a promotility hormone, are lower in preterm neonates than in those who are born at or after term, suggesting that maturation of the GI tract plays a role in the passage of meconium.11 Other research indicates that the amniotic fluid swallowed in early gestation contains small amounts of surfactant and is therefore very viscous. This may help inhibit meconium passage in utero.12
Meconium passage may also be associated with antenatal or intrapartum stresses such as hypoxemia or acidemia.4 Some observers believe that fetal hypoxia may cause the anal sphincter to relax, allowing passage of meconium. A distressed, gasping fetus is most apt to aspirate meconium, and this phenomenon is more likely in term and postterm neonates than in those who are preterm. Because of their maturity, term and postterm neonates are more likely to gasp than preterm babies. In addition, preterm infants are not likely to pass meconium in utero.
Respiratory symptoms can be caused by aspiration of meconium in utero or at the time of birth, or by alterations in the pulmonary vasculature secondary to asphyxia or the meconium itself. Aspiration of meconium can lead to partial or complete airway obstruction, followed by atelectasis with ventilation-perfusion mismatch, air trapping with increased functional residual capacity, and air leaks.13,14 Meconium in the airways induces an inflammatory response characterized by microvascular endothelial damage, which results in pulmonary edema, cellular necrosis, and chemical pneumonitis.13 In vitro studies show dysfunction of both alveolar macrophages and cord blood neutrophils.
Meconium can directly inhibit surfactant's ability to reduce the surface tension of pulmonary fluids, a dose-dependent effect.15,16 One study shows that meconium mixed with a cow-derived surfactant alters the surfactant's structure, so that spherical lamellar and folded linear structures replace the loosely stacked layers. When this happens, the surface tension of the mixture increases significantly.16 High concentrations of meconium are also toxic to rat type II alveolar cells, and studies with rats suggest that the presence of meconium either decreases production of surfactant proteins or increases their degradation.17
In about one third of infants with MAS, the syndrome is accompanied by persistent pulmonary hypertension (PPHN). But by the same token, between 40% and 66% of all infants with PPHN have an underlying diagnosis of MAS. The figure above depicts the pathophysiology of meconium aspiration and MAS.
Mamta Fuloria. Managing meconium aspiration.