Approach to the neonate with pleural effusions

INTRODUCTION — Pleural effusions are rare in neonates. They can cause significant respiratory distress. Acute management focuses on providing respiratory support, draining the fluid (if necessary), and identifying the underlying cause.

This topic will review the causes of pleural effusions in neonates and will provide an overview of initial management, including thoracocentesis. The management of chronic neonatal pleural effusions is discussed separately. (See "Management of chronic pleural effusions in the neonate".)

DEFINITIONS

●The pleural space is defined as the potential space bound by the visceral and parietal pleura mesothelial membranes that line the chest wall and lung surface (image 1).

●Pleural effusion is defined as an abnormal accumulation of fluid within the pleural space. It occurs when production exceeds absorption. Normally, there is a balance between the production of pleural fluid, thought to be produced by the visceral pleura, and absorption by the lymphatics of the parietal pleura. Pleural effusions occur when there is excessive pleural fluid production, reduced absorption, or a combination of the two.

The mechanisms of pleural fluid turnover under normal and abnormal (resulting in accumulation of pleural fluid) conditions are discussed separately. (See "Mechanisms of pleural liquid turnover in the normal state" and "Mechanisms of pleural liquid accumulation in disease".)

EPIDEMIOLOGY — Data are limited on the prevalence of neonatal pleural effusions. The reported prevalence ranges from <1 to 2.2 percent among neonates admitted to a neonatal intensive care unit [1,2]. The prevalence of pleural effusions is particularly high among infants who undergo surgery for congenital heart disease. (See 'Postnatally acquired' below.)

ETIOLOGY — Approximately 10 to 30 percent of neonatal pleural effusions are identified prenatally, while up to 90 percent are postnatally acquired [1,3,4].

Prenatally acquired — Causes of antenatal pleural effusion include congenital heart disease (CHD), infection, and chylothorax [1]. Many of these disorders present as hydrops fetalis or as a manifestation of a genetic, cardiac, or pulmonary abnormality.

Hydrops fetalis — Hydrops fetalis is defined as abnormal fetal fluid collection in a minimum of two anatomic locations. It results from many different in utero conditions in which there is dysregulation of the net fluid movement between the vascular and interstitial spaces. Most fetuses with hydrops fetalis have pleural effusions, which are usually bilateral. In some cases, the pleural effusions are large and can cause immediate respiratory distress at birth. (See "Nonimmune hydrops fetalis".)

Hydrops fetalis can be immune-mediated (caused by Rh incompatibility between the mother and fetus) or nonimmune. Conditions associated with nonimmune hydrops fetalis include genetic syndromes, structural abnormalities, especially CHD, metabolic disorders, hematologic disorders resulting in severe anemia (eg, alpha thalassemia), and infection. The causes of nonimmune hydrops fetalis are summarized in the table (table 1) and discussed in detail separately. (See "Nonimmune hydrops fetalis", section on 'Etiology and prenatal management of disorders associated with hydrops'.)

Immune-mediated hydrops fetalis is rare since the implementation of antenatal Rh(D) immune globulin prophylaxis. Immune-mediated hydrops fetalis is discussed separately. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management", section on 'Hydrops fetalis'.)

Congenital chylothorax — Neonatal chylothorax results from the accumulation of chyle in the pleural space. It may be either congenital or an acquired condition [1,5,6]. Congenital chylothorax is most likely due to abnormal development or obstruction of the lymphatic system and is often associated with hydrops fetalis [1,5-7]. It can be idiopathic or may be associated with various genetic syndromes [1,6,8-15].

In a systematic review of 753 cases of congenital chylothorax, genetic syndromes were identified in 16 percent [16]. The most common syndromes were trisomy 21, Noonan syndrome, and Turner syndrome. The same review reported congenital pulmonary lymphangiectasia (22 percent), pulmonary hypoplasia (20 percent), and extrapulmonary lymphatic dysplasia/malformation (seven percent) as the most common associated findings. Congenital chylothorax has also been associated with generalized lymphangiomatosis [17-19]. Several case reports indicate that congenital chylothorax can recur in subsequent offspring, suggesting a possible underlying genetic etiology [19-21].

Congenital chylothorax is rare, with an estimated incidence of 4 cases per 100,000 live births [11]. The mortality rate among neonates with congenital chylothorax is approximately 30 percent [16]. Preterm delivery is a risk factor for mortality [6,22]. In the available reports, most cases were diagnosed prenatally and approximately 40 percent of fetuses underwent intrauterine interventions (eg, thoracentesis and thoracic-amniotic shunting) [6,16,22]. In one series, successful reversal of hydrops with thoracic-amniotic shunting was associated with improved survival [22]. (See "Nonimmune hydrops fetalis", section on 'Thoracic and lymphatic abnormalities'.)

Congenital heart disease/vascular malformations — Various congenital cardiac disorders (including structural CHD and cardiac arrhythmias), can result in fetal heart failure, which may be associated with pleural effusions and/or hydrops fetalis [1,6,23]. (See "Nonimmune hydrops fetalis", section on 'Cardiovascular abnormalities'.)

Other rare vascular abnormalities associated with pleural effusions include bilateral agenesis of the superior vena cava [24], glomuvenous malformations [25], and placental chorangioma [26].

Pulmonary malformations — Pulmonary malformations associated with fetal pleural effusions and hydrops fetalis include bronchopulmonary sequestration, pulmonary lymphangiectasia, pulmonary lymphatic hypoplasia, and congenital pulmonary airway malformation [17,27,28]. The effusions may be transudates or chylous depending on the underlying cause. (See "Bronchopulmonary sequestration" and "Congenital pulmonary airway malformation" and "Nonimmune hydrops fetalis", section on 'Thoracic and lymphatic abnormalities'.)

In utero infection — Various congenital infections can be associated with development of pleural effusions in utero. Examples include cytomegalovirus (CMV), parvovirus B19, syphilis, herpes simplex viral (HSV), toxoplasmosis, and coxsackievirus. (See "Nonimmune hydrops fetalis", section on 'Infection'.)

Other causes — Other rare causes of congenital pleural effusions include:

●Obstructive uropathy [29,30].

●Congenital malignancies and benign tumors as noted in case reports of diaphragmatic rhabdomyosarcoma [31], Langerhans cell histiocytosis [32], monoblastic leukemia [33], thoracic hamartomas [34,35], and intrapericardial teratomas [36].

Postnatally acquired — There are numerous causes for postnatally acquired pleural effusions in neonates. The most common causes include infection (eg, parapneumonic effusion) and iatrogenic causes (eg, as a complication of thoracic surgery or central venous catheter insertion) [1,3].

Iatrogenic — Pleural effusions can develop as a complication of various invasive procedures (eg, sternotomy or thoracotomy for surgical repair of CHD, surgical repair of congenital diaphragmatic hernia, central line placement).

●Traumatic chylothorax– Injury to the thoracic duct resulting in chylothorax is one of the most frequent causes of acquired neonatal pleural effusions [4,37].

•Congenital heart disease (CHD) – Chylothorax can occur as a complication of cardiothoracic surgery for repair or palliation of CHD. The reported incidence is 2 to 3 percent [38]. Risk factors include younger age and size at surgery, higher procedural complexity, longer cardiopulmonary bypass and crossclamp times, and delayed chest closure [38,39].

•Congenital diaphragmatic hernia – Chylothorax is a common complication in infants who undergo repair of a congenital diaphragmatic hernia, with a reported incidence of approximately 5 to 6 percent [40,41]. (See "Congenital diaphragmatic hernia in the neonate".)

•Esophageal atresia – Chylothorax has been reported following repair of esophageal atresia [42].

●Central catheter-related – Centrally placed catheters can result in pleural effusions by:

•Extravasation of intravenous fluids into the thoracic cavity [43-47]

•Venous hypertension from intravascular blood clots resulting in pleural effusions, which are often chylous [48,49]

•Esophageal perforation

Infections — Pleural effusions are commonly seen in neonates with bacterial pneumonia and sepsis. (See "Neonatal pneumonia", section on 'Diagnostic imaging'.)

Transient tachypnea of the newborn (TTN) — Newborns with TTN sometimes have small pleural effusions noted on chest radiograph. (See "Transient tachypnea of the newborn", section on 'Radiographic features'.)

Hemothorax — Blood in the pleural space (hemothorax) appears similar to other types of pleural effusions on chest radiograph (image 2).

Other causes — Other acquired causes for neonatal pleural effusions include hypoalbuminemia, which may be due to congenital nephrotic syndrome, and initiation of peritoneal dialysis [1,2].

PRESENTATION

Antenatal presentation — Antenatal pleural effusions are usually detected by ultrasonography (image 3A-B) and are often a component of hydrops fetalis. (See "Nonimmune hydrops fetalis".)

Large bilateral pleural effusions may cause immediate respiratory distress at birth in the delivery room. In addition, long-standing effusions developed prior to 20 weeks of gestation may result in pulmonary hypoplasia, which may also present as severe respiratory distress at birth.

Postnatal presentation — Postnatal pleural effusions are typically detected by chest radiography (image 4A-C). Clinical findings vary depending on the size of the effusion:

●If the pleural effusion is small, the patient usually is asymptomatic and the pleural effusion may be noted as an incidental finding.

●Symptomatic infants with large effusions typically present with respiratory distress that is manifested by tachypnea, retractions, and cyanosis. Pleural effusion associated with intravenous fluid extravasation or hemothorax can be rapid and catastrophic (image 2), resulting in acute cardiovascular collapse.

Physical findings may include diminished breath sounds and dullness to percussion. These findings tend to be less apparent in neonates compared with older individuals with pleural effusions.

On chest radiography, pleural effusions are easily identifiable as a rim of fluid on the affected side (image 4A-C). On supine view, large effusions may appear as diffuse homogenous density superimposed over the lung field. If the clinical status of the infant permits, frontal, lateral, oblique, and decubitus radiographic views can be helpful to demonstrate the shift of pleural fluid as it layers in the most dependent part of the thoracic cavity. The use of bedside ultrasound may provide better delineation of the effusion with less radiation and avoids the need to position a severely ill neonate [50].

INITIAL ACUTE MANAGEMENT — The initial management and evaluation depend upon the timing of presentation (antenatal versus postnatal) and the degree of symptoms. Neonates with respiratory compromise due to significant pleural effusions generally require drainage of the fluid.

Antenatally diagnosed effusion

Prenatal management — Fetuses with antenatally detected large pleural effusions typically have hydrops fetalis with fluid collections in other locations (eg, ascites, skin edema, pericardial effusion). In severe cases, fetal intervention may be performed in an attempt to prevent pulmonary hypoplasia. This is discussed separately. (See "Nonimmune hydrops fetalis", section on 'Thoracic and lymphatic abnormalities' and "Bronchopulmonary sequestration: Prenatal diagnosis and management", section on 'Management of complicated cases'.)

Delivery room — Antenatally diagnosed pleural effusions that are moderate to large in size have the potential to cause significant symptoms at birth. In such cases, delivery should occur at a center with a level III neonatal intensive care unit where the required resources are available (eg, neonatal resuscitation team, advanced respiratory support, equipment and expertise for performing thoracocentesis [if needed]).

Resuscitation in the delivery room should proceed according to standard guidelines, as summarized in the figure (algorithm 1) and discussed in detail separately. (See "Neonatal resuscitation in the delivery room".)

Neonates requiring thoracocentesis in the delivery room usually can be successfully managed with simple needle aspiration of the fluid. Effusions resulting from hydrops fetalis often do not recur or do so slowly after needle aspiration and fluid removal, and further intervention is usually not required. (See 'Thoracocentesis' below.)

Postnatally diagnosed effusion — For neonates with pleural effusions that are detected postnatally, the initial management depends on whether the infant is symptomatic.

Symptomatic infants — Infants with moderate to large pleural effusions associated with respiratory distress should receive respiratory support as needed. Noninvasive support (eg, continuous positive pressure airway pressure [CPAP]) is typically the initial modality used. However, severely affected neonates my require intubation and mechanical ventilation. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn" and "Overview of mechanical ventilation in neonates".)

Neonates with significant ongoing respiratory compromise despite positive pressure ventilation generally require drainage of the fluid, as discussed below. (See 'Thoracocentesis' below.)

If pleural fluid is obtained, it should be is sent for analysis and culture. (See 'Pleural fluid analysis' below.)

For most symptomatic patients, it is appropriate to treat empirically with antibiotic therapy pending culture results, unless a noninfectious cause of the pleural effusion has been identified. Empiric antibiotic therapy for neonates with suspected pneumonia is discussed separately. (See "Neonatal pneumonia", section on 'Initial empiric therapy'.)

Asymptomatic infants — Neonates with small effusions who lack respiratory or circulatory compromise can be managed conservatively with ongoing monitoring.

Monitoring includes:

●Ongoing cardiorespiratory assessments, including respiratory rate, heart rate, and oxygen saturation

●Periodic measurement of blood gasses to assess the infant's acid-base status

●Serial chest radiographs and/or bedside ultrasonography to follow effusion size and monitor for resolution

If the neonate develops significant respiratory distress, hypoxemia, and/or respiratory acidosis, drainage of the fluid may be warranted. (See 'Thoracocentesis' below.)

Diagnostic thoracentesis is rarely necessary in asymptomatic neonates, but may occasionally be performed (eg, in select cases of suspected infection wherein the results would alter management). However, in most cases, if the effusion is thought to be secondary to pneumonia, the neonate is treated empirically, and it is unnecessary to perform pleural fluid sampling solely for the purpose of obtaining a culture. (See "Neonatal pneumonia", section on 'Initial empiric therapy'.)

THORACOCENTESIS — Moderate or large pleural effusions associated with significant respiratory compromise generally require drainage. Chest ultrasonography should be performed prior to performing thoracocentesis to confirm the size and location of the effusion and to evaluate for loculations.

For most causes of neonatal effusions, simple needle thoracocentesis is sufficient for draining the fluid and relieving symptoms [1-3]. The likelihood of recurrence is generally low provided that the underlying cause is adequately addressed (eg, antibiotics if the cause is pneumonia). In patients who have persistent effusion with continued symptoms, needle aspiration can be repeated two or three times. If the effusion does not resolve despite serial needle aspirations, tube thoracostomy is generally warranted. This is discussed separately. (See "Management of chronic pleural effusions in the neonate", section on 'Tube thoracostomy'.)

Chylothorax in particular tends to be a chronic process that requires more long-term management. Nevertheless, needle thoracocentesis is still the first step in management since it confirms the diagnosis of chylothorax. Management of chylothorax is discussed separately.(See "Management of chronic pleural effusions in the neonate", section on 'Chylous effusions'.)

Procedure — Needle thoracocentesis should be performed under sterile conditions. It involves the following steps:

●The infant should be placed in a supine position allowing the fluid to layer in the posterior chest

●An 18- to 20-gauge intravascular catheter is introduced into the pleural space in the midaxillary line in the 5^th or 6^th intercostal space and directed posteriorly.

●The needle is removed from the catheter (leaving the catheter in place in the chest) and a three-way stopcock is placed on the catheter.

●With the stopcock open to the patient and the syringe, fluid is withdrawn into the syringe.

The volume of fluid removed depends upon the size of the effusion and infant. It should be enough to restore adequate ventilation and circulation, but not so much as to put the infant at risk of hypovolemia if the fluid reaccumulates rapidly.

If the infant has bilateral effusions, drainage is generally performed initially on the right side because it has a larger lung volume than the left.

Once the fluid has been removed and the neonate is stable, the catheter is removed. A follow-up chest radiograph should be obtained to ensure that drainage is adequate and that there is no pneumothorax.

The neonate should then be monitored for possible reaccumulation of the effusion and for potential adverse effects of the procedure (eg, hemodynamic instability due to fluid shifts). If the neonate develops signs of hypovolemia (tachycardia, poor peripheral perfusion, hypotension), a normal saline fluid bolus should be administered.

Pleural fluid analysis — Analysis of pleural fluid samples helps to differentiate pleural effusions according to the etiologic category (transudative, exudative, or chylous effusion).

Analysis includes:

●Gross appearance – Diagnostic clues can be obtained during the gross inspection of the fluid:

•Red appearance is suggestive of active bleeding.

•Brown appearance is suggestive of old blood.

•White appearance is suggestive of chylothorax if feeding has been initiated. If the infant has had no enteral feeds, the fluid is typically straw colored.

•Pale yellow clear appearance is suggestive of transudate due to heart failure, hypoalbuminemia, or extravasation of intravenous fluid.

•Cloudy appearance and/or pus is suggestive of infection due to bacterial or fungal pneumonia/empyema.

●Cell counts and differential.

●Biochemical analysis (total protein, lactate dehydrogenase [LDH], glucose, cholesterol, and triglycerides). Serum protein, albumin, LDH, cholesterol, and triglycerides should also be obtained simultaneously for comparison with the pleural fluid sample. This analysis is used to differentiate between a transudative or exudative process. (See 'Interpreting pleural fluid findings' below.)

●In patients with a suspected underlying infection, microbiologic analysis including Gram stain and bacterial culture should be performed.

Interpreting pleural fluid findings

●Transudate – Transudates are largely due to imbalances in hydrostatic and oncotic pressures in the chest. Fluid moves through an intact vascular wall into the pleural space due to an elevated vascular hydrostatic and/or oncotic pressure. The transudative fluid has a low protein concentration (<3 g/dL) and LDH levels and few or no cellular elements. In the neonate, transudative effusions are usually the result of venous hypertension or obstruction due to congenital heart disease, or pulmonary malformations. Other less common causes of neonatal transudative pleural effusions include hypoalbuminemia (eg, congenial nephrotic syndrome), and extravasation of crystalloid fluid from venous lines. In the latter setting, the glucose and electrolyte composition in the pleural fluid is similar to that of the infused fluid.

●Exudate – An exudative effusion results primarily from pleural and lung inflammation or from impaired lymphatic drainage of the pleural space. Exudative fluid compared with transudate typically have higher protein and LDH concentration, and cellular elements. The most common cause of neonatal exudative pleural effusion is chylothorax. Other neonatal causes of exudative pleural effusions include pneumonia (empyema) and rare malignancies and autoimmune disorders.

●Chylothorax – When evaluating pleural fluid in a neonate with suspected chylothorax, it is important to interpret the findings in the context of the infant’s feeding. In the unfed state, the fluid is typically clear/yellow to slightly cloudy. In infants who have fed recently, the fluid appears milky due to chylomicrons in the fluid. In infants with chylothorax who are receiving fat-containing feedings, triglyceride levels in the pleural fluid are elevated (>110 mg/dL) and chylomicrons can be detected by lipoprotein electrophoresis. Lymphocytes predominate in the differential cell count [5].

The approach to interpreting pleural fluid analysis in neonates is generally similar to that in older children and adults. The approach is discussed in greater detail separately. (See "Pleural fluid analysis in adults with a pleural effusion", section on 'Interpreting pleural fluid findings' and "Epidemiology, clinical presentation, and evaluation of parapneumonic effusion and empyema in children", section on 'Pleural fluid analysis'.)

Empiric antibiotics — When there is concern for infection, fluid should be sent for diagnostic evaluation including culture. If the fluid appears purulent, fluid analysis suggests an infectious process, and/or if there are other clinical concerns in the neonate, empiric antibiotics should be provided pending culture results. Empiric antibiotic therapy for neonates with suspected pneumonia is discussed separately. (See "Neonatal pneumonia", section on 'Initial empiric therapy'.)

MANAGEMENT OF RECURRENCE — Neonates with symptomatic pleural effusions that persist or recur despite serial needle aspirations generally require tube thoracostomy. This is discussed separately. (See "Management of chronic pleural effusions in the neonate", section on 'Tube thoracostomy'.)

SUMMARY AND RECOMMENDATIONS

●Etiology – Approximately 10 to 30 percent of neonatal pleural effusions are identified prenatally and up to 90 percent are acquired postnatally. (See 'Etiology' above.)

•Prenatally acquired – Pleural effusions that develop in utero are usually detected by prenatal ultrasonography (image 3A-B) and may be associated with pulmonary hypoplasia. Causes of pleural effusions in the fetus include (see 'Prenatally acquired' above):

-Hydrops fetalis, which in turn has many different causes (table 1) (see "Nonimmune hydrops fetalis")

-Obstruction or maldevelopment of the lymphatic system (ie, congenital chylothorax)

-Congenital heart disease (CHD)

-Pulmonary malformations

-Infection

-Genetic syndromes

•Postnatally acquired – Postnatally acquired pleural effusions are typically detected by chest radiography (image 4A-C). Causes include (see 'Postnatally acquired' above):

-Iatrogenic causes (eg, as a complication of thoracic surgery or central venous catheter insertion)

-Pneumonia

-Transient tachypnea of the newborn

-Hemothorax (due to traumatic injury or coagulopathy)

-Hypoalbuminemia (eg, congenital nephrotic syndrome)

●Initial acute management:

•For asymptomatic infants – Neonates with small effusions who lack respiratory or circulatory compromise can be managed conservatively with ongoing monitoring. (See 'Asymptomatic infants' above.)

•For symptomatic infants

-Respiratory support – Infants with moderate to large pleural effusions associated with respiratory distress should receive respiratory support as needed. Noninvasive support (eg, continuous positive pressure airway pressure [CPAP]) is typically the initial modality used. However, severely affected neonates my require intubation and mechanical ventilation. Respiratory support for neonatal respiratory distress is discussed separately. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn" and "Overview of mechanical ventilation in neonates".)

-Fluid drainage – Neonates with significant ongoing respiratory compromise despite positive pressure ventilation generally require drainage of the fluid. In most cases, we suggest simple needle thoracocentesis as the initial intervention rather than tube thoracostomy (Grade 2C). Needle thoracocentesis is sufficient for draining the fluid and relieving symptoms in most cases. The exception is chylothorax, which tends to be a chronic process. Nevertheless, needle thoracocentesis is still the first step in management since it confirms the diagnosis of chylothorax. (See 'Thoracocentesis' above.)

-Empiric antibiotics – For most symptomatic patients, it is appropriate to treat empirically with antibiotic therapy pending culture results, unless a noninfectious cause of the pleural effusion has been identified. Empiric antibiotic therapy for neonates with suspected pneumonia is discussed separately. (See "Neonatal pneumonia", section on 'Initial empiric therapy'.)

●Pleural fluid analysis – For neonates who undergo thoracocentesis, the following tests should be performed on the pleural fluid (See 'Pleural fluid analysis' above.):

•Cell counts and differential.

•Biochemical analysis (total protein, lactate dehydrogenase [LDH], glucose, cholesterol, and triglycerides). Serum protein, albumin, LDH, cholesterol, and triglycerides should also be obtained simultaneously for comparison with the pleural fluid sample.

•Gram stain and bacterial culture.

Results of these tests can differentiate between a transudative, exudative, or chylous effusion. (See 'Interpreting pleural fluid findings' above.)

●Management of recurrence – The likelihood of recurrence is generally low provided that the underlying cause is adequately addressed (eg, antibiotics if the cause is pneumonia). In patients who have persistent effusion with continued symptoms, needle aspiration can be repeated two or three times. If the effusion persists or recurs despite serial needle aspirations, tube thoracostomy is generally warranted. This is discussed separately. (See "Management of chronic pleural effusions in the neonate", section on 'Tube thoracostomy'.)