Meconium aspiration syndrome: Management and outcome

INTRODUCTION — Meconium aspiration syndrome (MAS) is defined as respiratory distress in newborn infants born through meconium-stained amniotic fluid (MSAF) whose symptoms cannot be otherwise explained. MAS can present with varying degrees of severity from mild respiratory distress to life-threatening respiratory failure. Coordination of care between the obstetric and neonatal team is important to reduce the incidence of MAS and to identify and provide urgent therapy in those who develop MAS to reduce morbidity and mortality.

The management and outcome of MAS will be reviewed here. The pathophysiology, clinical features, and diagnosis of MAS are discussed separately. (See "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis".)

DELIVERY ROOM MANAGEMENT OF INFANTS WITH MSAF

Obstetrical care — We concur with the guidelines of the American Heart Association (AHA), the American Academy of Pediatrics (AAP), and the American College of Obstetricians and Gynecologists (ACOG), which recommend against routine intrapartum nasopharyngeal suctioning of newborns who are delivered through meconium-stained amniotic fluid (MSAF). Based on the available evidence, intrapartum oro/nasopharyngeal suctioning of newborns with MSAF does not appear to reduce the likelihood of developing MAS [1,2]. In a meta-analysis of two randomized trials involving 3032 newborns born through MSAF, mortality was slightly higher among infants assigned to intrapartum suctioning compared with no suctioning; however, the finding was not statistically significant and the low number of events precludes drawing a firm conclusion (1.1 versus 0.46 percent, relative risk [RR] 2.29, 95% CI 0.94-5.53) [2]. Rates of MAS were not reported in the meta-analysis, but in the larger of the two trials (n = 2514), the incidence of MAS was similarly low in both groups (4 percent in each arm, RR 0.9, 95% CI 0.6-1.3) [1]. The need for mechanical ventilation, duration of respiratory support, and hospital length of stay were also similar in both groups.

Neonatal care

●Initial care – Based on the available evidence, the care of infants delivered through MSAF should be guided by the general principles of neonatal resuscitation. The need for intervention, including positive pressure ventilation and endotracheal intubation, should be based upon the neonate's respiratory effort (gasping, labored breathing, or poor oxygenation), heart rate (<100 bpm), or signs of airway obstruction. The approach is summarized in the figure (algorithm 1) and discussed in detail separately.(See "Neonatal resuscitation in the delivery room".)

We do not endorse routine endotracheal suctioning for infants delivered through MSAF regardless of the neonate's clinical status (vigorous or nonvigorous). Endotracheal suctioning may delay resuscitation efforts without clear evidence of benefit. Intubation and tracheal suction may be beneficial in a very select subset of patients (ie, when there is evidence of airway obstruction in the nonvigorous neonate during attempted positive pressure ventilation) [3]. The risk of airway obstruction is likely higher in newborns delivered through MSAF and thus skilled caregivers who can address this possibility should be immediately available, if needed. (See "Neonatal resuscitation in the delivery room", section on 'Infants requiring delivery room resuscitation'.)

The practice of using standard neonatal resuscitation without routine endotracheal suctioning for both vigorous and nonvigorous infants is consistent with the guidelines from the International Liaison Committee on Resuscitation (ILCOR), AAP, and AHA [3,4]. This practice is supported by multiple randomized trials demonstrating that endotracheal suctioning does not reduce the incidence of MAS nor prevent associated morbidities [5-11]. The recommendation not to perform routine endotracheal suctioning in infants with MSAF is also based the principle of avoiding harm (ie, avoiding delays in providing assisted ventilation in nonvigorous neonates and avoid complications of endotracheal intubation in vigorous neonates) [3,4,7].

•Vigorous infants – In a meta-analysis of four rials including 2884 infants with MSAF who were randomly assigned to endotracheal suctioning versus no intubation, MAS occurred in a similarly small proportion of patients in both groups (2.5 versus 2 percent, respectively; relative risk [RR] 1.29, 95% CI 0.80-2.08) [6]. There were few deaths in either group (four in the endotracheal suctioning group, two in the control group).

•Nonvigorous infants – In a meta-analysis of four trials including 581 nonvigorous neonates born through MSAF who were randomly assigned to endotracheal suctioning versus no routine suctioning, the risk of MAS was the same in both groups (35 percent in each group; RR 1.00, 95% CI 0.80-1.25) [8]. All-cause mortality was also similar in both groups (11 versus 9 percent, respectively; RR 1.24, 95% CI 0.76-2.02).

Observational studies have reached variable conclusions regarding the relative efficacy of the two approaches. Support for the approach of not routinely performing endotracheal suctioning comes from a follow-up study from the California Perinatal Quality Care Collaborative and data from a single center, which found no increase in the incidence or severity of MAS after implementing this practice [12,13]. Another observational study reported that a higher proportion of nonvigorous infants were admitted to the neonatal intensive care unit (NICU) for respiratory problems following implementation of a no endotracheal suctioning approach compared with the previous year [14]. However, the inference of causal effect in this study is contradicted by the finding that there was no increase in the number of neonates diagnosed with MAS after implementing the no suctioning approach.

●Subsequent care and triage – Based upon the assessment in the delivery room, the neonatal provider should determine the appropriate setting for subsequent care. Infants who develop MAS generally exhibit signs of respiratory distress immediately after birth [15].

•Asymptomatic infants with Apgar scores ≥9 at five minutes can be admitted to the normal nursery for routine newborn care without additional monitoring or intervention. (See "Overview of the routine management of the healthy newborn infant".)

•In our practice, infants with MSAF with Apgar scores <9 at five minutes are admitted to the NICU or Special Care Nursery for further evaluation and management. Symptomatic neonates should be observed for a minimum of four to six hours to ensure they transition successfully to extrauterine life. Those with evidence of persistent respiratory distress remain in a more intensive care setting and are evaluated for adequate oxygenation by pulse oximetry (or in more severe infants, arterial blood gas) and chest radiography to diagnose MAS. The approach to the initial evaluation of infants with suspected MAS is discussed separately. (See "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis", section on 'Evaluation and initial management'.)

MANAGEMENT

Approach — Management of MAS is largely supportive (oxygen therapy, assisted ventilation, antibiotics until infection has been excluded, and additional interventions if needed based upon the severity of illness) [16]. Prompt identification and care of affected patients decreases morbidity and mortality, especially in patients with severe disease. Coordination of care between the obstetric and neonatal team is crucial to initiate effective management of infants who develop MAS [17]. (See 'Outcome' below.)

The general approach to care includes:

●Respiratory support to maintain adequate oxygenation and ventilation. (See 'Respiratory support' below.)

●Hemodynamic support to maintain of adequate blood pressure (BP) and perfusion. (See 'Hemodynamic support' below.)

●Correction of any metabolic abnormality including hypoglycemia and acidosis, which increase oxygen consumption. (See "Management and outcome of neonatal hypoglycemia".)

●Empiric antibiotic therapy until infection has been excluded. (See 'Antibiotics' below.)

●Care in a neutral thermal environment. The exception is the neonate with signs of hypoxemic ischemic encephalopathy immediately after delivery, for whom therapeutic hypothermia is recommended, as discussed separately. (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy", section on 'Therapeutic hypothermia'.)

●Minimal handling of the infant to avoid agitation, which exacerbates persistent pulmonary hypertension of the newborn (PPHN), if present. (See "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis".)

●Additional interventions may be used in severely affected neonates, including surfactant, inhaled nitric oxide (iNO), and extracorporeal membrane oxygenation (ECMO). (See 'Additional interventions for severe MAS' below.)

Most neonates with MAS do not require all of these interventions. In a large multicenter retrospective study including 7518 infants with MAS, these interventions were used with the following frequencies [18]:

●Antibiotic therapy – 92 percent

●Respiratory support during first 48 hours after birth:

•Oxygen therapy only (via hood, low-flow nasal cannula [LFNC], or high-flow nasal cannula [HFNC]) – 43 percent

•Continuous positive airway pressure (CPAP) – 7 percent

•Intubation and mechanical ventilation (MV) – 36 percent, including conventional mechanical (CMV) in 28 percent and high frequency ventilation (HFV) in 8 percent

●Vasopressors and inotropes – 20 percent

●Surfactant – 16 percent

●iNO – 6 percent

●ECMO – 1.4 percent

Respiratory support — Respiratory support for neonates with MAS focuses on maintaining optimal oxygenation and ventilation. Hypoxemia and respiratory acidosis increase pulmonary vascular resistance and contribute to the development of PPHN. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome".)

Target oxygen saturation — Neonates with MAS should be monitored with continuous pulse oximetry and serial arterial blood gases. We suggest maintaining preductal peripheral oxygen saturation (SpO₂) in the range of 95 to 98 percent (arterial partial pressure of oxygen [PaO₂] between 55 and 90 mmHg) [19]. The goal is to provide adequate tissue oxygenation while avoiding prolonged exposure to high concentrations of oxygen [19]. Hypoxemia should be avoided because it contributes to pulmonary vasoconstriction and worsens PPHN.

Target oxygen levels in infants with MAS (nearly all of whom are born at term or postterm) are more liberal than for preterm infants who are at greater risk for toxicity from exposure to high oxygen concentrations. Target oxygen levels for preterm neonates are discussed separately. (See "Neonatal target oxygen levels for preterm infants".)

Mild to moderate disease (noninvasive support) — For patients with mild or moderate disease, supplemental oxygen therapy can be provided with oxygen hood, low-flow nasal cannula (LFNC), high-flow nasal cannula (HFNC), CPAP, or other noninvasive modality. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)

At our center, we typically provide supplemental oxygen therapy via oxygen hood initially. LFNC and HFNC are reasonable alternatives. One advantage of the oxygen hood is that it allows accurate determination of the fraction of inspired oxygen (FiO₂). For LFNC, the effective FiO2 delivered to the lungs is variable and depends on the liter flow, size of the newborn, and respiratory rate. When using unblended oxygen, LFNC is typically administered at flow rates of 1/8 to 1 L/min, which provides and effective FiO2 of approximately 0.25 to 0.4. However, this is a rough estimate and the exact FiO2 cannot accurately be measured with LFNC. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Low-flow nasal cannula'.)

When providing oxygen therapy, we generally limit the FiO2 to <0.5. If the neonate requires FiO2 ≥0.5 to maintain SpO2 in the target range, we initiate CPAP. In a randomized trial involving 135 neonates with MAS, CPAP reduced the need for mechanical ventilation (3 versus 17 percent; odds ratio [OR 0.09, 95% CI 0.02-0.43) [20]. Additional indirect support for CPAP comes from clinical trials in other neonatal populations (eg, preterm neonates with respiratory distress syndrome). These data are presented separately. (See "Respiratory distress syndrome (RDS) in preterm infants: Management", section on 'Nasal continuous positive airway pressure (nCPAP)'.)

CPAP should be used cautiously in infants with hyperinflation as it may exacerbate air trapping. If overinflation is noted on chest radiograph, blood gases should be monitored and follow-up chest radiographs obtained to ensure that overinflation does not worsen. Additional details of CPAP use in neonates are provided separately. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Continuous positive airway pressure'.)

Severe disease (mechanical ventilation) — Despite the use of CPAP, some infants with severe MAS develop worsening respiratory failure with severe hypoxemia requiring intubation and MV. In addition to MV, severely affected neonates generally warrant administration of exogenous surfactant, and, if there is associated severe PPHN, iNO. (See 'Surfactant' below and 'Inhaled nitric oxide' below.)

●Mechanical ventilation – Approximately one-third of neonates with MAS require MV [18,21]. The goal of MV is to achieve adequate gas exchange while minimizing ventilator-induced lung injury (VILI). We generally start with conventional mechanical ventilation (CMV) using a patient-triggered volume-targeted mode. We consider transitioning to high-frequency ventilation (HFV) if attempts to optimize CMV setting fail to achieve adequate gas exchange. For infants with refractory hypoxemia and/or hypercapnia despite optimal MV (including a trial of HFV) and pharmacologic treatment (ie, surfactant, iNO), ECMO should be considered. (See 'Extracorporeal membrane oxygenation (ECMO)' below.)

MV in neonates is discussed in greater detail separately. (See "Overview of mechanical ventilation in neonates".)

●Gas exchange targets – We suggest the following targets for gas exchange targets when providing MV in infants with MAS:

•Oxygenation – We aim for SpO2 between 95 to 98 percent (PaO₂ between 55 and 90 mmHg) (See 'Target oxygen saturation' above.)

•Carbon dioxide (CO₂) – We use a strategy of mild permissive hypercapnia, targeting a partial pressure of carbon dioxide (PaCO₂) 50 to 55 mmHg as long as pH remains in the range of pH 7.3 to 7.4.

●Analgesia and sedation – In our practice, we provide analgesia and sedation for mechanically ventilated neonates who experience significant agitation and/or dyssynchronous breathing. Agitation may be associated with catecholamine release, increased pulmonary vascular resistance, right-to-left shunting, and worsening hypoxemia. The goal of sedative therapy is to maintain effective and safe sedation to facilitate optimal gas exchange during the acute phase of the illness and allow for controlled weaning from assisted ventilation. In these patients, we typically provide a continuous infusion of opioid analgesic using morphine of fentanyl. (See "Management and prevention of pain in neonates".)

•Intravenous morphine sulfate (loading dose of 100 to 150 mcg/kg over one hour, followed by a continuous infusion of 10 to 20 mcg/kg per hour)

•Intravenous (IV) fentanyl (1 to 5 mcg/kg per hour)

If agitation and/or dyssynchronous breathing persists, we add a benzodiazepine (eg, midazolam). We reserve use of neuromuscular blocking agents (eg, vecuronium, pancuronium) for neonates with dyssynchronous breathing associated with persistent severe hypoxemia without another identified cause (eg, airway obstruction or air leak). However, we limit this intervention as much as possible because of potential adverse effects, which can include hypotension, prolonged blockade, and post-extubation muscle weakness [22].

Other supportive care

Hemodynamic support — Therapeutic measures that ensure adequate cardiac output and tissue perfusion include:

●Maintaining intravascular volume – Volume expansion using intravenous (IV) normal saline may be needed in infants with low BP (defined as a mean BP below the 5^th percentile (figure 1)) and/or inadequate peripheral tissue perfusion (eg, cold extremities, acrocyanosis, poor capillary refill, lactic acidosis). (See "Neonatal shock: Management".)

Once adequate intravascular volume has been restored, IV maintenance fluids during the first 24 hours of life are restricted to a volume of 65 mL/kg using a solution that consists of 5 percent dextrose without additional electrolytes. Subsequently, the volume is adjusted based on the needs of the infant, and sodium intake is limited to minimize peripheral and pulmonary edema. Enteral feeds are not provided until the neonate is on an improving clinical trajectory. (See "Fluid and electrolyte therapy in newborns", section on 'Fluid and electrolyte management'.)

●Vasoactive infusions – Approximately 20 percent of neonates with MAS require vasopressor and/or inotropic support to maintain perfusion and adequate BP [18]. We typically use dopamine (2.5 to 10 mcg/kg per min IV; titrated as necessary to maintain normal mean arterial BP). A high BP target may be warranted in infants with PPHN to minimize right-to-left shunting. (See "Neonatal shock: Management", section on 'Vasoactive agents' and "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Hemodynamic targets'.)

Antibiotics

●Symptomatic neonates with MAS – Although it is uncertain whether antibiotic therapy is beneficial in infants with MAS [23-25], broad-spectrum antibiotics (ampicillin and gentamicin/amikacin) are administered while awaiting the results of blood cultures because of the difficulty of distinguishing MAS from serious bacterial infection (eg, early-onset sepsis [EOS] or bacterial pneumonia). In symptomatic infants, the presence of meconium-stained amniotic fluid (MSAF) may reflect intrauterine stress, as can occur with intraamniotic infection. The choice of empiric antibiotics in neonates with suspected EOS is discussed in detail separately. (See "Management and outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy'.)

●Well-appearing neonates born through MSAF – Empiric antibiotic therapy is not necessary for asymptomatic infants born through MSAF who otherwise appear healthy and have no other risk factors for EOS. The approach to degerming the need for antibiotics in asymptomatic, well-appearing neonates born through MSAF is the same as for the general neonatal population, as discussed separately. (See "Management of neonates at risk for early-onset group B streptococcal infection", section on 'Management of the neonate'.)

Transfusion — For neonates with MAS who have severe hypoxemia and PPHN, the threshold we use to trigger red blood cell (RBC) transfusion is hemoglobin level <15 g/dL (hematocrit <40 percent). (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Transfusion'.)

For neonates without severe hypoxemia, RBC transfusion is usually not necessary; standard neonatal transfusion thresholds are used for such patients. (See "Red blood cell (RBC) transfusions in the neonate", section on 'Transfusion thresholds'.)

Other details of RBC transfusions in neonates, including selection of RBC products, risks associated with transfusion, and details of administration are discussed separately. (See "Red blood cell (RBC) transfusions in the neonate".)

Additional interventions for severe MAS

Surfactant — Use of surfactant for treatment of MAS is limited to infants with severe disease (ie, those requiring intubation and MV) [16,23,26-28].

Meconium is thought to inactivate endogenous surfactant, and it is thought that administration of exogenous may improve pulmonary mechanics and oxygenation in infants with severe MAS. In a meta-analysis of two randomized trials that included 208 neonates with MAS, surfactant reduced the need for ECMO (relative risk [RR] 0.64, 95% CI 0.46-0.91), with no apparent impact on mortality (RR 0.98, 95% CI 0.41-2.39) [27].

Surfactant may also be helpful in infants whose chest radiograph appearance suggests respiratory distress syndrome (eg, low lung volumes and homogeneous pulmonary parenchymal disease). (See "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis", section on 'Chest imaging'.)

Inhaled nitric oxide — For patients with severe MAS who have associated severe PPHN, iNO is a standard component of therapy that improves oxygenation and reduces the need for ECMO. This is discussed in detail separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Inhaled nitric oxide (iNO)'.)

Extracorporeal membrane oxygenation (ECMO) — For the most severely affected neonates who are refractory to mechanical ventilation (including HFV) and other medical therapies (eg, surfactant, iNO), ECMO can be life saving [29-31]. ECMO provides cardiopulmonary support while awaiting resolution of the underlying pulmonary disease process without exposing the lungs to further VILI. Criteria for ECMO in patients with PPHN are presented separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Extracorporeal membrane oxygenation (ECMO)'.)

OUTCOME — The overall outcome of MAS has improved with advances in neonatal care.

●Mortality – In the available reports, mortality rates for newborns with MAS ranged from 1 to 4 percent [18,21]. Risk factors for mortality include low five minute Apgar score, need for mechanical ventilation within the first 48 hours after birth, need for vasopressor therapy, and presence of a major congenital anomaly [18].

●Neurodevelopmental outcome — There are limited data on long-term neurodevelopmental outcomes for infants with MAS. Small observational case series report that approximately 20 percent have significant neurodevelopmental impairment [32]. This likely reflects that fact that a substantial subset of patients born through meconium-stained amniotic fluid (approximately 20 to 30 percent) have neurologic depression at birth, suggesting an underlying intrauterine process (primarily chronic asphyxia and/or infection) contributing to both MAS and poor neurodevelopmental outcome. (See "Perinatal asphyxia in term and late preterm infants" and "Clinical features, diagnosis, and treatment of neonatal encephalopathy", section on 'Prognosis'.)

●Other morbidities – Short-term morbidities reported during the initial hospitalization include seizures (5 percent), intraventricular hemorrhage (<1 percent), and necrotizing enterocolitis (<1 percent) [18]. Small follow-up studies suggest that respiratory morbidity (eg, reactive airway disease or asthma) is common among surviving infants [33-35].

PREVENTION — Because of the potential for poor outcome, the best approach for managing MAS is prevention. The following obstetric practices may reduce the incidence of MAS. These issues are discussed in detail separately.

●Intrapartum fetal heart (FHR) monitoring – Continuous or periodic FHR monitoring has become a standard of care in the United States, particularly in pregnancies thought to be at higher risk for intrapartum fetal hypoxemia (eg, postterm pregnancy, intrauterine growth restriction, preeclampsia). The primary goal of FHR monitoring is to assess the adequacy of fetal oxygenation during labor. Evaluation and interventions are implemented in cases with abnormal tracings indicative of fetal stress to reduce the likelihood of perinatal asphyxia. Although the combination of a nonreassuring FHR tracing and thick meconium in amniotic fluid has been associated with an increased risk of MAS, the value of intrapartum fetal monitoring in preventing MAS has not been proven. Nevertheless, we agree that FHR monitoring identifies signs of hypoxemia and allows the caregivers to initiate prompt interventions in order to reduce the risk of MAS. (See "Intrapartum fetal heart rate monitoring: Overview" and "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis", section on 'Pathophysiology'.)

●Amnioinfusion – Amnioinfusion is a second-line intervention for persistent variable decelerations seen on FHR tracings during labor and appears to decrease the risk of MAS in the setting of moderate to thick amniotic-stained fluid [36]. This is discussed in greater detail separately. (See "Amnioinfusion" and "Intrapartum category I, II, and III fetal heart rate tracings: Management".)

●Prevention of postterm delivery – The risk of MAS is greatest in postterm deliveries (ie, >41 weeks). Thus, preventing postterm delivery likely reduces the risk of MAS. Induction of labor at ≥39 weeks is a reasonable option in low-risk patients who have well-dated pregnancies. Based on the available clinical trial data, this appears to reduce neonatal respiratory morbidity and other neonatal complications. These data are presented separately. (See "Induction of labor with oxytocin", section on 'At 39 weeks'.)

For pregnant individuals who opt for expectant management, induction is suggested if they have not delivered by 41 weeks, as discussed separately. (See "Postterm pregnancy", section on 'Our approach: Induction at 41+0 weeks'.)

SUMMARY AND RECOMMENDATIONS

●Definition – Meconium aspiration syndrome (MAS) is defined as respiratory distress in newborn infants born through meconium-stained amniotic fluid (MSAF) whose symptoms cannot be otherwise explained. In severe cases, MAS can be life threatening. (See "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis".)

●Delivery room care of newborns with MSAF

•Apply general principles of neonatal resuscitation – The care of newborns born through MSAF, regardless of whether they are vigorous or nonvigorous, is guided by the general principles of neonatal resuscitation. The need for intervention, including positive pressure ventilation and endotracheal intubation, is based upon the neonate's respiratory effort (gasping, labored breathing, or poor oxygenation), heart rate (<100 bpm), or evidence of airway obstruction. The approach is summarize in the figure (algorithm 1) and discussed in detail separately. (See "Neonatal resuscitation in the delivery room".)

•No role for routine nasopharyngeal or endotracheal suctioning – At delivery, we suggest against performing intrapartum nasopharyngeal suction for any newborn with MSAF (Grade 2C). The available evidence suggests that intrapartum suctioning does not reduce the risk of MAS. After delivery, we recommend against performing endotracheal suctioning for vigorous newborns with MSAF (Grade 1B) and we suggest against performing endotracheal suctioning for nonvigorous newborns (Grade 2B). (See 'Obstetrical care' above and 'Neonatal care' above.)

•Subsequent care and triage – Based upon the assessment in the delivery room, the neonatal provider should determine the appropriate setting for subsequent care. Patients who develop MAS typically exhibit signs of respiratory distress immediately after birth. (See 'Neonatal care' above.)

-Infants with MSAF who exhibit signs of respiratory distress in the delivery room should be admitted to a neonatal intensive care unit (NICU) or Special Care Nursery for further evaluation and management. Symptomatic neonates should be observed for a minimum of four to six hours.

-Asymptomatic infants with five-minute Apgar score ≥9 can be admitted to the normal nursery for routine newborn care without additional monitoring or intervention. (See "Overview of the routine management of the healthy newborn infant".)

●Management of MAS

•Respiratory support – Respiratory support focuses on maintaining adequate oxygenation and ventilation. Hypoxemia and respiratory acidosis increase pulmonary vascular resistance and contribute to the development of persistent pulmonary hypertension of the newborn (PPHN). The goal is to maintain preductal peripheral oxygen saturation (SpO₂) in the range of 95 to 98 percent while avoiding prolonged exposure to high oxygen concentration. (See 'Respiratory support' above and 'Target oxygen saturation' above.)

-For patients with mild to moderate disease, supplemental oxygen can be administered via an oxygen hood or nasal cannula. For neonates who require a fraction of inspired oxygen (FiO2) ≥0.5 to maintain SpO2 in the target range, we suggest continuous positive airway pressure CPAP (Grade 2B). CPAP appears to reduce the need for invasive mechanical ventilation. (See 'Mild to moderate disease (noninvasive support)' above and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)

-Patients with severe disease generally require intubation and mechanical ventilation. The goal of MV is to achieve adequate gas exchange while minimizing ventilator-induced lung injury. (See 'Severe disease (mechanical ventilation)' above and "Overview of mechanical ventilation in neonates".)

•Other supportive care measures – Newborns with MAS should be cared for in a neutral thermal environment (unless receiving therapeutic hypothermia for management of neonatal encephalopathy). Care should be taken to avoid excessive agitation, which can exacerbate PPHN, if present. Additional supportive care measures include (see 'Other supportive care' above):

-Hemodynamic support – Hemodynamic support includes maintaining intravascular volume with intravenous fluids as needed. In addition, approximately 20 percent of patients with MAS have associated shock requiring vasopressor and/or inotropic support. (See 'Hemodynamic support' above and "Neonatal shock: Management".)

-Antibiotic therapy – Because MAS cannot be distinguished from bacterial pneumonia and sepsis initially, empiric antibiotic therapy is provided until sepsis is excluded based upon culture results. (See 'Antibiotics' above and "Management and outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy'.)

-Transfusion – For neonates with MAS who have severe hypoxemia and PPHN, the threshold used to trigger red blood cell (RBC) transfusion is hemoglobin level <15 g/dL (hematocrit <40 percent). For neonates without severe hypoxemia, RBC transfusion is usually not necessary; standard neonatal transfusion thresholds are used for such patients. These issues are discussed in greater detail separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Transfusion' and "Red blood cell (RBC) transfusions in the neonate", section on 'Transfusion thresholds'.)

•Additional interventions for severely affected neonates

-For patients with severe MAS who require intubation and mechanical ventilation, we suggest surfactant therapy (Grade 2B). Surfactant appears to reduce the need for extracorporeal membrane oxygenation (ECMO). (See 'Surfactant' above.)

-For patients with associated severe PPHN, inhaled nitric oxide is a standard component of therapy that improves oxygenation and reduces the need for ECMO. This is discussed in detail separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Inhaled nitric oxide (iNO)'.)

-For the most severely affected neonates who are refractory to other interventions, ECMO can be lifesaving. Criteria for ECMO in patients with PPHN are presented separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome", section on 'Extracorporeal membrane oxygenation (ECMO)'.)

●Outcome – The risk of mortality for neonates with MAS is approximately 1 to 4 percent. Survivors are at risk for long-term morbidity including reactive airway disease and neurodevelopmental impairment. (See 'Outcome' above.)