Pulmonary Hemorrhage in Newborns

Etiology

Neonatal Pulmonary Hemorrhage Risk Factors

Pulmonary hemorrhage in newborns is associated with multiple risk factors, with extreme prematurity (<32 weeks gestation) and low birth weight (<1500 g) being the most significant.[4] Additional risk factors include intrauterine growth restriction, patent ductus arteriosus (PDA) with a left-to-right shunt, intrapartum asphyxia, sepsis-induced increased microvascular permeability, shock, chorioamnionitis, coagulopathy, disseminated intravascular coagulation, polycythemia, anemia, thrombocytopenia, and blood transfusion. Transfusion-related pulmonary hemorrhage may result from volume overload, leading to left ventricular failure and elevated pulmonary capillary pressure.[3] 

Other contributing factors that also contribute to the occurrence of pulmonary hemorrhage include respiratory distress syndrome (RDS), apnea of prematurity, lung hypoplasia, low Apgar scores, mechanical ventilation, congenital heart disease, erythroblastosis fetalis, hemorrhagic disease of the newborn, exogenous surfactant use, neonatal encephalopathy, intraventricular hemorrhage, congenital metabolic diseases, and hypothermia.[1][3][6][7][8] Among these, independent risk factors for pulmonary hemorrhage include lower gestational age, low birth weight, exogenous surfactant use, and hemodynamically significant PDA (hsPDA).[4][6] 

Preterm neonates born before 32 weeks of gestation face a higher incidence of pulmonary hemorrhage, with risk increasing as gestational age decreases, suggesting a causal relationship.[9] Premature neonates with underdeveloped pulmonary vasculature are particularly susceptible to injury from high inspiratory pressure, improperly regulated surface tension, and sudden lung overdistension caused by artificial ventilation, all of which contribute to pulmonary hemorrhage.[6] Apnea of prematurity further increases the risk, as it is often associated with upper airway obstruction or laryngospasm. These conditions generate high negative intrathoracic pressure during inspiratory effort, mechanically disrupting the alveolar-capillary barrier and leading to pulmonary hemorrhage.[3]

Factors Associated With Pulmonary Hemorrhage in Newborns

Surfactant dysfunction has been implicated in causing pulmonary hemorrhage, as indicated by the significant presence of pulmonary surfactant inhibitors in lung effluents. However, the use of surfactant in preterm ventilated newborns has also been shown to contribute to pulmonary hemorrhage.[10][11] Surfactant administration can impair coagulation pathways and worsen pulmonary hemorrhage, leading to clinical hesitation in its routine use to preterm infants despite recommendations from the American Academy of Pediatrics (AAP).[4][11]

An hsPDA is implicated in causing pulmonary hemorrhage due to high-volume ductal shunting (left to right) as pulmonary vascular resistance decreases after birth. This leads to excessive pulmonary blood flow, increased pulmonary capillary pressure, and hemorrhagic pulmonary edema.[7][9] Surfactant therapy induces a rapid decrease in pulmonary vascular resistance and intrapulmonary pressure, which facilitates left-to-right shunting through the PDA, further increasing pulmonary blood flow and vascular pressure. This can damage the pulmonary vasculature and result in massive pulmonary hemorrhage.[6][10][12]

Perinatal asphyxia can lead to left ventricular failure, resulting in increased pulmonary capillary pressure and subsequent leakage of hemorrhagic fluid into the air spaces.[4] Moreover, stress failure of pulmonary capillaries due to alveolar overdistention in perinatal asphyxia can contribute to pulmonary hemorrhage.[4] High pulmonary flow and asphyxia can also cause left ventricular dysfunction and failure, further increasing the risk of pulmonary hemorrhage.[7][8] However, when no identifiable risk factors or etiology for pulmonary hemorrhage are found, the condition is classified as acute idiopathic pulmonary hemorrhage.[2]

Contrary to other risk factors, an unrestricted foramen ovale is protective against pulmonary hemorrhage. Newborns with a restrictive foramen ovale or a significantly small PFO, in conjunction with hsPDA, are more likely to develop pulmonary hemorrhage. An unrestricted PFO helps offload the increased volume in the left atrium caused by hsPDA, distributing the excess volume to both ventricles. This prevents stress failure of the left atrium and left ventricle, as well as the rupture of fragile pulmonary capillaries due to pulmonary venous congestion. In contrast, in newborns with a restrictive foramen ovale and hsPDA, a rapid decrease in pulmonary vascular resistance after birth leads to high-volume left-to-right shunting, which results in left atrial volume overload, increased pulmonary venous congestion, and subsequent pulmonary hemorrhage.[5]

Epidemiology

The incidence of pulmonary hemorrhage ranges from 1 to 12 per 1000 live births in high-income countries, with significantly higher rates reported in low- and middle-income countries.[3][9] As a result, neonatal mortality rates due to pulmonary hemorrhage are notably higher in these regions compared to high-income countries.[3] Among at-risk newborns, such as those who are premature or critically ill, the incidence of pulmonary hemorrhage is significantly elevated, reaching approximately 50 per 1000 live births.[4] Additionally, a slight female predominance has been observed in the incidence of pulmonary hemorrhage.[4]

Pulmonary hemorrhage most commonly occurs within the first 72 hours of life, particularly in mechanically ventilated, premature, and low-birthweight newborns (<1500 g).[1][4][9] The condition tends to progress rapidly within the first week of life.[6] Affected newborns often have PDA with hemodynamically significant left-to-right shunting.[1][9] Pulmonary hemorrhage remains a major challenge in neonatal intensive care units (NICUs), emphasizing the urgent need for early identification and effective management strategies to improve neonatal outcomes.

History and Physical

Pulmonary hemorrhage should be suspected when blood is aspirated from the trachea during suctioning, accompanied by acute clinical deterioration. This deterioration often manifests as respiratory distress (eg, tachypnea, tachycardia, and dyspnea), hemodynamic instability, and an increased need for ventilatory support.[2][3] However, pediatricians should also recognize that pulmonary hemorrhage can present more indolently in some cases.[3]

The typical presentation involves a premature neonate with the sudden onset of frothy, pink-tinged secretions or frank bleeding from the upper respiratory tract (eg, hemoptysis and epistaxis), often in the context of RDS. In intubated newborns, this may appear as bleeding from the endotracheal tube, requiring increased ventilatory support.[1][2] If pulmonary hemorrhage persists, further signs may include hypotonia, bradycardia, apnea, pallor, cyanosis, and hypovolemic shock.[1][4] Prompt recognition of these signs is crucial for timely diagnosis and management, which can significantly improve neonatal outcomes.

Evaluation

Chest x-ray (CXR) findings in pulmonary hemorrhage are nonspecific and may reveal bilateral diffuse infiltration with ground-glass opacities, often resembling the CXR appearance of pneumonia. Other radiographic presentations include fluffy opacities with a focal ground-glass pattern or complete white-out lungs in cases of massive pulmonary hemorrhage.[2][4] Laboratory studies in these patients may reveal anemia and abnormal coagulation profiles.[2] Blood samples should be collected for a complete blood count, crossmatch, blood gas analysis, coagulation tests, comprehensive metabolic profile, blood culture, procalcitonin, and C-reactive protein. Cranial ultrasound should be performed to assess for intraventricular hemorrhage. 

Serial echocardiography, including subcostal views, is typically performed to identify left-to-right shunts through the PDA and is essential for evaluating the foramen ovale and the interatrial left-to-right shunt through the foramen ovale.[5] In cases of hsPDA, surgical closure is preferred over indomethacin due to the bleeding risk associated with the latter. Additionally, echocardiography is recommended within the first 12 hours of life for preterm newborns (<32 weeks gestation) to assess left ventricular diastolic dysfunction, which is associated with pulmonary hemorrhage and increased respiratory morbidity.[5] Prompt and accurate diagnosis using these imaging techniques is crucial for effective management and improved outcomes in newborns with pulmonary hemorrhage.

Treatment / Management

Pulmonary hemorrhage in newborns currently lacks a curative treatment, but various management strategies have been identified to improve survival rates.[1] The primary goal of managing pulmonary hemorrhage is to prevent exsanguination while ensuring adequate gas exchange. An interprofessional approach is essential, including ventilatory support (such as high-frequency oscillatory ventilation [HFOV]), pressor support with continuous monitoring to maintain normal mean arterial pressure, appropriate surfactant therapy, and management of coagulopathy.[1][3] Early placement of a peripherally inserted central catheter (PICC) line is recommended for optimal nutritional support via total parenteral nutrition, ensuring adequate calories, protein, and vasopressor administration. Enteral feeding should be introduced once the neonate is clinically stable. Please see StatPearls' companion resource, "Peripherally Inserted Central Catheter (PICC) Line Placement," for more information.

Emergent management involves standard resuscitation measures, including airway, breathing, and circulation support, as well as the administration of crystalloids, colloids, blood products, and necessary medications.[4] Endotracheal tubes should be suctioned to prevent blockage, but unnecessary and aggressive endotracheal suctioning should be avoided. The FiO₂ should be adjusted according to oxygen saturation levels.[4] Positive end-expiratory pressure (PEEP) should be maintained at 6 to 8 cm H₂O to tamponade the pulmonary capillaries and reduce lung hemorrhage. HFOV is preferred over conventional mechanical ventilation due to its ability to improve oxygenation index and mean airway pressure, especially in neonates with persistent hypoxia or respiratory acidosis, despite conventional mechanical ventilation.[1] Clinical improvement, indicated by a decrease in the oxygenation index, has been observed within 1 hour of initiating HFOV.[13]

Despite its potential role in the pathophysiology of pulmonary hemorrhage, surfactant therapy is used to treat this condition.[10] Surfactant therapy has been shown to reduce mortality rates, improve lung compliance, and enhance the oxygenation index, without causing recurrence of pulmonary hemorrhage or long-term disability. A prospective randomized controlled trial demonstrated improved oxygenation and ventilation following surfactant therapy, suggesting that it may serve as a beneficial adjunctive treatment for newborns with pulmonary hemorrhage.[14] Exogenous surfactants (eg, poractant alfa and beractant) replenish the deficit of endogenous surfactants inactivated by hemorrhagic pulmonary edema, thereby improving pulmonary mechanics.[1][10] (A1)

The molecular components of hemorrhagic pulmonary edema that inactivate endogenous lung surfactants include hemoglobin, plasma proteins, and cell membrane lipids.[10][12][15] A favorable response, defined as a ventilatory index of less than 0.047, has been reported as early as 1 hour after surfactant administration.[1][10] Exogenous surfactants can also be administered to neonates who have previously received them for other indications.[4](A1)

Intermittent positive pressure ventilation helps correct acidosis and reduces the alveolar-arterial gradient, thereby improving oxygenation.[1] Increasing PEEP can also increase mean airway pressure.[1] Endotracheal epinephrine (0.5 mL of 1:10,000 adrenaline) is effective in halting pulmonary hemorrhage due to its vasoconstrictive properties, reducing the need for endotracheal suctioning.[1] Coagulopathy should be managed with treatments such as vitamin K, blood products, recombinant factor VIIa, and endotracheal haemocoagulase.[1][16][17] Hemoglobin levels should be maintained above 12 g/dL, and platelet counts should remain above 50,000/μL in neonates with active bleeding.[1] Please see StatPearls' companion resource, "Platelet Transfusion," for more information.

Activated factor VII is a potential adjunct therapy for life-threatening pulmonary hemorrhage, as it maximizes coagulation system activation by increasing thrombin activity, which facilitates fibrin clot formation.[4] Additional measures for managing pulmonary hemorrhage include administering tolazoline (a nonselective alpha-adrenergic antagonist and vasodilator) and using extracorporeal membrane oxygenation.[3][4]

Preventive measures are key to reducing the incidence and morbidity of pulmonary hemorrhage. Given the association between exogenous surfactant use and pulmonary hemorrhage, selective surfactant administration is recommended for neonates showing clinical signs of RDS, rather than its prophylactic use for every preterm, premature, or small gestational age newborn.[6][18] Managing hsPDA through pharmacological interventions (eg, indomethacin) or transcatheter closure is essential for extremely premature neonates prone to pulmonary hemorrhage, particularly those with a restrictive or significantly small-diameter foramen ovale.[5][6] A complete course of antenatal corticosteroids significantly reduces the risk of massive pulmonary hemorrhage and related mortality, making it an important consideration for women with anticipated preterm delivery. These corticosteroids promote fetal lung maturation, thereby decreasing overall neonatal morbidity and mortality in premature neonates.[6](B3)

Differential Diagnosis

The differential diagnoses of pulmonary hemorrhage in newborns include various conditions affecting the lungs, cardiovascular system, and coagulation pathways, as well as other contributing factors, such as:

• Foreign bodies
• Trauma
• Infections (eg, bacterial, viral, fungal, and parasitic)
• Cystic fibrosis
• Neoplasms
• Pulmonary hemosiderosis
• Congenital cardiovascular lesions [2]

Prognosis

Mortality rates for pulmonary hemorrhage in extremely premature neonates range from 50% to 68%, with most deaths occurring within the first week of life.[1][3][9] Survivors face an increased risk of bronchopulmonary dysplasia and neurosensory impairments, including cerebral palsy, cognitive delays, seizures, and periventricular leukomalacia. However, advancements in NICU management over the past decade have contributed to a decline in pulmonary hemorrhage-related mortality.[11]

Early screening and treatment of hsPDA in very preterm newborns are crucial for reducing the incidence of pulmonary hemorrhage. However, while early PDA intervention lowers the risk of pulmonary hemorrhage, it does not significantly improve overall survival rates.[7][9]

Complications

Neonates with pulmonary hemorrhage experience a higher incidence of RDS, pneumothorax, shock, and severe intraventricular hemorrhage.[9] The accumulation of blood cells and inflammatory mediators in the alveoli during pulmonary hemorrhage can result in lung tissue fibrosis, which contributes to the development of bronchopulmonary dysplasia, also referred to as chronic lung disease of prematurity.[7][11] Radiographic findings indicative of bronchopulmonary dysplasia include fine interstitial markings and diffuse haziness.[11]

Prolonged mechanical ventilation and extended hospitalization are common in neonates with pulmonary hemorrhage.[7] While oxygen therapy is essential for survival, its prolonged and excessive use may lead to increased production of reactive oxygen species and elevated expression of proinflammatory cytokines, potentially exacerbating lung injury.[7] Additional complications associated with pulmonary hemorrhage include cerebral palsy, cognitive delays, seizures, and periventricular leukomalacia.[6]