Meconium-stained amniotic fluid (MSAF) Pediatrics point of view

1. Meconium-stained amniotic fluid (MSAF)Pediatrics point of view M&M Presentation Darinka Shaw MD Pediatrics Resident February 2009

2. Objectives • Definition • Epidemiology • Etiology • Pathophysiology • Clinical features • Management • Morbidity&Mortality

3. Definition Meconium aspiration syndrome (MAS) is a respiratory disorder in an infant born through Meconium stained amniotic fluid whose symptoms cannot be otherwise explained.

4. MAS Cleary&Wiswell proposed severity criteria to define MAS: • Mild: requires <40%O2 for <48hrs • Moderate: >40%O2 for >48hrs, no air leak. • Severe: assisted ventilation for >48hrs often with PPH.

5. Epidemiology • MSAF observed in 13% of all live births. • MAS occurs in 5% of newborns delivered through MSAF. • 25,000 to 30,000 cases and 1,000 deaths related to MAS annually in US.

6. Epidemiology • More frequently in infants who are postmature and small for gestational age. • Decline from 5.8% to 1.5% (1990–1997), attributed to a 33% reduction in the incidence of births >41 weeks gestation.

7. Physiology • The passage of meconium from the fetus into amnion is prevented by lack of peristalsis (low motilin level), tonic contraction of the anal sphincter, terminal cap of viscous meconium. • MSAF may be a natural phenomenon that doesn’t indicate fetal distress but mature GI tract in post term fetus with increased motilin level. • Vagal stimulation by cord or head compression may be associated with passage of meconium in the absence of fetal distress.

8. Risk factors for MSAF • Maternal HT • Maternal DM • Maternal heavy cigarette smoking • Maternal chronic respiratory or CV Dx • Post term pregnancy • Pre-eclampsia/eclampsia • Oligohydramnios • IUGR • Poor biophysical profile • Abnormal fetal HR pattern

9. Pathophysiology • The pathophysiology of MAS is complex. • Intrauterine fetal gasping, mechanical airway obstruction, pneumonitis, surfactant inactivation, and damage of umbilical vessels: all play roles in the pathophysiology of meconium aspiration. • There is also a strong association between MAS and persistent pulmonary hypertension of the newborn (PPHN).

10. Pathophysiology • Thetimingof the initial insult resulting in MAS remains controversial. • Chronic in-utero insult may be responsible for most cases of severe MAS. • In contrast to these severe cases, the vigorous infant who aspirates meconium-stained fluid from the nasopharynx at birth usually develops mild to moderate disease.

11. Pathophysiology • The traditional belief was that meconium aspiration occurs immediately after birth. • Aspirated particulate or thick meconium can be carried rapidly by the first breaths to the distal airways. • Studies of neonatal puppies with tantalum-labeled meconium instilled into the trachea before the first breath have confirmed that the distal migration of particulate matter can occur within 1 hour of birth.

12. Pathophysiology • Several investigators have suggested that most cases of meconium aspiration occur in utero when fetal gasping is initiated before delivery. • Meconium has been found distally as far as the alveoli in some stillborn infants and in some infants that die within hours of delivery. • There is currently no way to distinguish between the infant who has developed MAS by intrauterine respiration or gasping and the infant who has developed MAS by inhalation of meconium at the first breaths after delivery.

13. Mechanism of injury 1.Mechanical Obstruction of the Airway • It is commonly thought that the initial and most important problem of the infant with MAS is obstruction caused by meconium in the airways. • Complete obstruction of large airways by thick meconium is an uncommon occurrence. • The exact incidence of large-airway obstruction is unknown, though Thureen et al, in an autopsy study of infants who died of MAS, found no evidence of such obstruction.

14. Pathophysiology • Usually, small amounts of meconium migrate slowly to the peripheral airways. • This mechanism can create a ball valve phenomenon, in which air flows past the meconium during inspiration but is trapped distally during expiration, leading to increases in expiratory lung resistance, functional residual capacity, and anterior posterior diameter of the chest.

15. Pathophysiology • Regional atelectasis and V/P mismatches can be developed from total obstruction of the small airways. • Adjacent areas often are partially obstructed and over expanded, leading to pneumothorax and pneumomediastinum air leaks. • Pulmonary air leaks are 10x more likely to develop in infants with MAS than those without, and leaks often develop during resuscitation.

16. Pathophysiology 2. Pneumonitis • Pneumonitis is a usual feature of MAS, occurring in about ½ of the cases. • Meconium has a direct toxic effect mediated by inflammation. • An intense inflammatory response in the bronchi and alveoli can occur within hours of aspiration of meconium.

17. Pathophysiology • The airways and lung parenchyma become infiltrated with large numbers of polymorphonuclear leukocytes and macrophages. • Produce direct local injury by release of inflammatory mediators-cytokines (TNF-α, IL-1β, IL-8) and reactive oxygen species. • Lead to vascular leakage, which may cause toxic pneumonitis with hemorrhagic pulmonary edema.

18. Pathophysiology • Meconium contains substances such as bile acids that also can cause direct injury. • Clinicians should maintain a high index of suspicion for bacterial pneumonia in infants with MAS. • Presence of fever, an abnormal WBC or a decline in respiratory function are indications of bacterial pneumonia and/or sepsis and should prompt the clinician to obtain relevant cultures and initiate antimicrobial therapy.

19. Pathophysiology 3.Pulmonary vasoconstriction • The release of vasoactive mediators, such as eicosanoids, endothelin-1 and prostaglandin E2 as a result of injury from meconium seems to play role in the development of persistent PH. • The pulmonary vasoconstriction is, in part, the result of the underlying in utero stressors.

20. Pathophysiology 4. Surfactant inactivation • Recognized in the early 1990. • Meconium displaces surfactant from the alveolar surface and inhibits its surface tension lowering ability. • A full term baby born with a sufficient quantity of surfactant may develop surfactant deficiency by inactivation that leads to atelectasis, decreased lung compliance/volume and poor oxygenation.

21. Pathophysiology

22. CLINICAL FEATURESHistory • Infants with MAS have a history of MSAF. • They often are postmature or small for gestational age. • Many are depressed at birth.

23. CLINICAL FEATURES Physical examination • Evidence of postmaturity: peeling skin, long fingernails, and decreased vernix. • The vernix, umbilical cord, and nails may be meconium-stained, depending upon how long the infant has been exposed in utero. • In general, nails will become stained after 6 hours and vernix after 12 to 14 hours of exposure.

24. CLINICAL FEATURES Physical examination • Affected patients typically have respiratory distress with marked tachypnea and cyanosis. • Reduced pulmonary compliance and use of accessory muscles of respiration are evidenced by intercostal and subcostal retractions and abdominal (paradoxical) breathing, often with grunting and nasal flaring.

25. CLINICAL FEATURES Physical examination • The chest typically appears barrel-shaped, with an increased anterior-posterior diameter caused by overinflation. • Auscultation reveals rales and rhonchi -immediately after birth. • Some patients are asymptomatic at birth and develop worsening signs of respiratory distress as the meconium moves from the large airways into the lower tracheobronchial tree.

26. Diagnosis MAS must be considered in any infant born through MSAF who develops symptoms of RD.

27. Diagnosis • The diagnosis of MAS is confirmed by chest radiograph. • The initial CXR may show streaky, linear densities similar in appearance to transient tachypnea of the newborn (TTN). • As the disease progresses, the lungs typically appear hyperinflated with flattening of the diaphragms. • Diffuse patchy densities may alternate with areas of expansion.

28. Coarse focal consolidation with emphysema.

29. Hyperinflation and patchy asymmetric airspace disease that is typical of MAS.

30. Coarse interstitial infiltrates +L side pneumothorax

31. Areas of opacification due to atelectasis bilaterally.

32. Close up of left lung demonstrating the streaky lucencies of the air in the interstitium (red arrows) complicated by a pneumothorax(yellow arrow).

33. Diagnosis • In infants with severe disease who require high concentrations of supplemental oxygen and mechanical ventilation, the lungs may develop an appearance of homogeneous density similar to respiratory distress syndrome (RDS). • Radiographic changes resolve over the course of 7 to 10 days but sometimes persist for several weeks. • Air leak occurs in 10 to 30 percent of infants with MAS.

34. Homogeneous density similar to respiratory distress syndrome (RDS).

35. Diagnosis • Arterial blood gas measurements typically show hypoxemia and hypercarbia. • Infants with pulmonary hypertension and right-to-left shunting may have a gradient in oxygenation between preductal and postductal samples. • 2D Echocardiogram for evaluation of PPH.

36. Management

37. Management • Sept 2007 the ACOG revised recommendations and recommended that “all infants with MSAF should not longer receive intrapartum suctioning. If meconium present and the newborn depressed, the clinician should intubate the trachea and suction meconium from beneath the glottis”. • Intrapartum suctioning not effective in removing meconium aspirated by the fetus into the lungs prior delivery.

38. Management • Skilled resuscitation team should be present at all deliveries that involve MSAF. • Pediatric intervention depends on whether the infant is vigorous. • Vigorous infant is if has: • Strong resp. efforts • Good muscle tone • Heart rate >100b/m • When this is a case-no need for tracheal suctioning, only routine management.

39. Management • When the infant is not vigorous: • Clear airways as quickly as possible. • Free flow 02. • Radiant warmer but drying and stimulation should be delayed. • Direct laryngoscopy with suction of the mouth and hypopharynx under direct visualization, followed by intubation and then suction directly to the ET tube as it slowly withdrawn. • The process is repeated until either ‘‘little additional meconium is recovered, or until the baby’s heart rate indicates that resuscitation must proceed without delay’’.

40. Postnatal Management Apparently well child born through MSAF • Most of them do not require any interventions besides close monitoring for RD. • Most infants who develop symptoms will do so in the first 12 hours of life.

41. Postnatal Management Approach to the ill newborns: • Transfer to NICU. • Monitor closely. • Full range of respiratory support should be available. • Sepsis w/up and ABx indicated. • Transfer to ECMO center may be necessary.

42. Treatment in NICU Goals: • Increased oxygenation while minimizing the barotrauma (may lead to air leak) by minimal MAP and as short IT as possible. • Prevent pulmonary hypertension. • Successful transition from intrauterine to extrauterine life with a drop in pulmonary arterial resistance and an increase in pulmonary blood flow.

43. Treatment in NICU • Severe MAS can spiral into vicious cycle of hypoxemia that leads to acidosis, which together cause pulmonary vein constriction. • May lead to persistent pulmonary hypertension. • The resultant right-to-left shunting at the level of the ductus arteriosus, the atrial level, or both causes further cyanosis and hypoxemia, which perpetuate the cycle.

44. Treatment in NICU Ventilatory support depends on the amount of respiratory distress: • O2 hood • Mechanical ventilation (40%). • CPAP (10%). • Observational study showed worse outcome for infants treated with hyperventilation. • High-frequency ventilators should reduce air leak syndromes in MAS, but animal and clinical models have yielded conflicting results. • High-frequency ventilators may slow the progression of meconium down the tracheobronchial tree and allow more time for meconium removal.

45. Treatment in NICU Surfactant • Two randomized controlled studies have evaluated the efficacy of exogenous surfactant administration. Results showed decreased number of infants requiring ECMO and possible reduction of pneumothorax, but no difference in mortality. • A Cochrane meta-analysis of 4 randomized trials confirmed that surfactant replacement showed no effect on mortality but reduce the use of ECMO (RR 0.64, 95% CI, 0.46-0.91). • Lavage with dilute surfactant-increases oxygenation and decrease the need of MV (need additional trials).

46. Treatment in NICU Inhaled NO • NO causes selective pulmonary vasodilation by acting directly on the vascular smooth muscle-activates guanylate cyclase and increases cGMP. • By dilating blood vessels in well ventilated areas of lung, NO decreases the V/P mismatch and improved oxygenation in infants with PPH. • Decreases need for ECMO (RR 0.61, 95%CI 0.51, 0.72) but no difference in mortality. • In a large randomized multicenter trial infants with MAS responded well to the combination of inhaled nitric oxide and HFOV, likely because of improved lung inflation and better delivery of the drug.

47. ECMO • 40% of infants with MAS treated with inhaled NO fail to respond and require bypass. • 35% of ECMO patients are with MAS. • Survival rate after ECMO 93-100%.

48. Morbidity & Mortality Pulmonary morbidity • Pulmonary outcome evaluated in 35 infants with MAS and 70 controls. • During the first 6mo after birth, the infants with MAS were significantly more likely to have one or more episodes of wheezing and/or coughing lasting ≥3 days (49% vs. 20%) and receive bronchodilator therapy (23% vs. 3%) compared to controls.

49. Morbidity & Mortality • Pulmonary function testing was performed at 8y of age in 11 children who had MAS and 9 controls. • The MAS group had evidence of mild airway obstruction, hyperinflation, and increased closing volumes compared to controls, and had more exercise-induced bronchospasm (4 vs. 0 children). • However, during graded exercise stress tests, MAS children had normal maximal oxygen consumption and anaerobic threshold without significant hypoxemia or hypercarbia.

50. Morbidity & Mortality • Respiratory symptoms, pulmonary function tests, and chest radiographs evaluated in 18 children age 6-11y who had MAS. • 7 children had recurrent cough and wheezing consistent with asthma, and 5 of these had exercise-induced bronchospasm that responded to bronchodilators. • Of the 11 asymptomatic children, 2 had mild expiratory airflow limitation, 1-exercise-induced bronchospasm, and 8 had normal pulmonary function. Chest radiographs were normal in all the children.