Congenital Isolated Pleural Effusion in Neonates -A Case Series

Pleural effusion is defined as fluid accumulation in the pleural space, which exists between the parietal pleura of the chest wall and the visceral pleura of the lung. Both pleural surfaces filter fluid into the pleural space, and the lymphatics are responsible for most of the fluid reabsorption. Any alteration of the pulmonary venous hydrostatic pressure, lymphatic pressure, blood oncotic pressure and inflammation will lead to pleural effusion [1]. Pleural effusions are rare in the neonate. The incidence of pleural effusion ranges from 5.5 per 10,000 to 2.2%. [2,3]. The well-known reported causes of neonatal pleural effusion  are parapneumonic effusion, empyema, chylothorax, hydrothorax, hemothorax, leakage of central-line fluid, or parenteral nutrition [2]. Pleural effusion may be detected antenatally, at birth or during the neonatal period. They may be asymptomatic and recover spontaneously, but some may present with respiratory distress. Diagnosis of pleural effusion in antenatal period is done by fetal ultrasound whereas postnatal diagnosis is done by clinical examination and chest radiography, confirmed by ultrasound chest. 

Congenital isolated pleural effusion is a rare condition with an incidence of about 1 in 12,000 to 1 in 15,000 pregnancies [4]. It is usually chylous [5,6]. Congenital chylothorax is the most frequent cause of neonatal pleural effusion [4],  Congenital chylothorax occurs more  in males than in females (2 : 1), and is more common  in the right side of the thorax, probably related to the anatomy of the thoracic duct [7,8]. Few cases of isolated nonchylous neonatal pleural effusion have been reported [9].

During the period of eight year (2012-2020), we had diagnosed and successfully treated four cases of congenital chylothorax and one case of isolated nonchylous pleural effusion in neonatal intensive care unit at tertiary care centre. Patient data was taken from medical records using a standardized case record form. Information was obtained about demographic, clinical, and laboratory characteristics of the neonates and their outcomes.

Baseline characteristics and clinical details of the cases have been described in Table 1. 

Table 1: Demographic data 

GA-gestational age, M-male, R-right, L-left, DBF-direct breast feeding 

Index case/ case 1 

A late preterm baby boy, weighing 3 kg, appropriate for gestation, was born by cesarean section done for previous LSCS to a 29-year-old gravida 2, para 1 without   respiratory distress. The initial Apgar scores were seven at 1 min and 8 at 5 min respectively.  Baby had normal transitional period, was started on DBF and was well for 5 days. From day of life 6, baby developed refusal of feeds and respiratory distress, for which she was admitted to the neonatal intensive care unit. Respiratory rate (RR) was 76/minute with subcostal and intercostal recessions and breath sounds were diminished over the right hemithorax. There were no dysmorphic features and the baby was not hydropic. Rest of the systemic examination was normal. An arterial blood gas analysis revealed respiratory acidosis with pH 7.20, HCO3 19 mmol, PaO2 80 mmHg, and PaCO2 52 mmHg. The baby was administrated oxygen via nasal continuous positive airway pressure (CPAP); IV fluids and antibiotics were Charted. An urgent bedside chest X-ray done which revealed white out of right side hemithorax with shifting of airway and heart to the left side. Ultrasonogram confirmed pleural effusion in the right hemithorax. A diagnostic tap was performed and 20 ml of milky white coloured fluid was aspirated and was sent for cell count, biochemical analysis and culture. A chest tube was inserted and which drained 150 ml. The pleural fluid analysis showed exudative fluid containing protein 3.3 g/l and sugar 96 mg/dl,  triglycerides 1123 mg/dl, cholesterol 45 mg/dl, lactate dehydrogenase 230 IU/l, with cell count of 20,80/mm3 (lymphocytes 90%/Polymorphs 10%);RBC 5/hpf no microorganisms were seen on gram staining and pleural fluid culture was sterile, indicative of chylothorax. In view of persistent pleural drainage, octreotide was commenced on day 18 of life, for a total of 12 days. The pleural fluid resolved over a period of 16 days, allowing discontinuation of chest tube drainage. Admission blood culture showed no growth, following which antibiotics were stopped. Follow-up chest radiograph showed clear resorption of pleural effusion. He was discharged home after 4 weeks with a formula containing a medium-chain triglyceride, without any respiratory symptoms. 

Case 2 

A newborn, from 24-year-old gravida 2 abortion 1 mother, at 39 weeks gestational age was delivered by caesarean section, done for fetal distress and meconium stained liquor with no significant antenatal history. Baby required resuscitation with scores of 3 and 5 at 1 and 5 minutes, respectively. Baby had to be ventilated [synchronized intermittent mandatory ventilation (SIM V) mode] in view of impending respiratory failure. Chest radiograph initially showed increased opacity of the right hemithorax. Initial arterial blood gas analysis revealed respiratory acidosis with pH 7.02, HCO3 17 mmol, PaO2 79 mmHg, and PaCO2 62 mmHg. Baby was started on IV antibiotics and anticonvulsants. Baby received inotrophic support for 2 days. Ultrasonogram confirmed pleural effusion in the right hemithorax. A chest tube was inserted for continuous drainage of the effusion and drained 200ml of straw yellow coloured fluid and sent for cell count, biochemical analysis and culture. The pleural fluid analysis showed exudative fluid containing protein 4.4 g/dl and sugar 40 mg/dl,  triglycerides 140 mg/dl, cholesterol 39 mg/dl, lactate dehydrogenase 270 IU/l, with cell count of 1100/mm3 (lymphocytes 85%/Polymorphs 15%) RBC of 15/hpf, no microorganisms were seen on gram staining and pleural fluid culture was sterile, indicative of chylothorax. Baby required invasive ventilation for 10 days, intra venous fluid was given for 14 days, and following which skimmed milk were started with MCT oil .Octreotide was initiated on day 11 of life and given for a total of 10 days. The pleural fluid resolved over a period of two week, allowing discontinuation of chest tube drainage. Blood culture was sterile. She recovered fully with no recurrence of pleural effusion and was discharged on day 30 of life with fat free formula and MCT oil. 

Case 3 

A 2980 gms male neonate delivered at 40 weeks gestation via normal vaginal delivery to a 20 year old primigravida mother. There was no significant antenatal history. Apgar scores were eight at 1 min and nine at 5 min respectively, without hydropic or dysmorphic features at birth. Baby had normal transitional period, was started on DBF and was well for 2 days on day 3, the neonate developed tachypnea and mild subcostal retractions. Baby was admitted in NICU in view of respiratory distress with vitals of HR- 144/min, RR- 68/min, and BP- 96/55 mm of hg with Saturation of 95 % in room air. Physical examination on admission revealed respiratory distress quoted at 2/10 on the DOWNE score and decreased breath sounds on the left side, with normal other systemic examination. Chest x ray revealed complete opacification of the left hemithorax. Ultrasonogram thorax confirmed  pleural effusion  in the left  hemithorax Therapeutic thoracentesis removed 20 ml of an orange coloured fluid  with the following characteristics: protein 3.4 g/dl, glucose 54 mg/dl ,triglycerides 49 mg/dl ml, cholesterol 25.4 mg/dl, lactate dehydrogenase 250 IU/l with cells, showing 20-22   RBCs Polymorphs- 0 1/hpf,Lymphocytes-1-2/hpf. Gram stain showed no bacteria and the culture was sterile. Computed tomography (CT) of chest findings were suggestive of gross left sided pleural effusion with underlying collapse.in view of worsening distress on day 7 0f life, an intercostal drainage tube was inserted. And 150 ml of orange colored pleural fluid was drained. Following which the infant improved remarkably, X-ray chest showed expanded lung. Repeat pleural fluid analysis showed protein 3.2 g/dL, glucose 90 mg/dL, triglycerides 46 mg/dL, cholesterol 31mg/dL, and leukocyte 1-2; no microorganisms were seen on gram staining and pleural fluid culture was sterile. The pleural fluid resolved over a period of 4 days, allowing discontinuation of chest tube drainage the sepsis screen was normal. USG abdomen and Echocardiogram were normal and baseline renal and liver function tests were within normal limits. The karyotyping of the infant was normal, i.e. 46, XY. Hence, a diagnosis of idiopathic unilateral nonchylous pleural effusion was made. He was on breast feeds during the course of hospital stay. He recovered fully with no recurrence of pleural effusion and was discharged on day 14 of life. 

Case 4 

A 3000gm boy baby, from 21-year-old primigravida woman, at 38 weeks gestational age was delivered by normal vaginal delivery without respiratory distress. He had been antenatally diagnosed to have pleural effusion on the right side by fetal ultra-sonogram at 32 weeks of gestational age. The initial Apgar scores were 7 at 1 min and 8 at 5 min respectively. Baby had normal transitional period, was started on DBF and was well for 3 days. He developed minimal tachypnea (66/min) and subcostal retractions without obvious respiratory

Insufficiency. On examination, breath sounds were diminished over the right hemithorax. There were no dysmorphic features and the baby was not hydropic. Rest of the systemic examination was normal. Chest radiograph initially showed increased opacity of the right hemithorax. USG Thorax confirmed right pleural effusion with no evidence of ascites or pericardial effusion. Diagnostic thoracentesis was performed on the right side.

Approximately 20 ml of milky fluid was recovered. Fluid analysis had characteristic findings of chylothorax with protein 11.4 g/dl, glucose 49 mg/dl , Triglycerides 750 mg/dl , Cholesterol 150 mg/dl, Lactate  dehydrogenase 200 IU with 4900/mm3 cells, showing 5-6 /HPF RBCs, Polymorphs 5% Lymphocytes 95%, with negative bacterial cultures . A diagnosis of congenital chylothorax was confirmed. Chest tube was placed on right side in view of worsening respiratory status, which drained100 ml of milky fluid. The intercostal tube was removed on day 4, as there was no pleural fluid drain. Repeat X-ray chest showed full expansion of lungs. Sepsis screen was negative and blood culture was sterile. He was discharged home after 7 days on fat free diet with MCT oil. 

Case 5 

A 3140 gm male baby born to 29-year-old primigravida mother was delivered by emergency LSCS in view of antepartum hemorrhage at 40 weeks of gestation. There was no significant antenatal history. Apgar scores were 8 at 1 min and 9 at 5 min respectively, at birth. He was well and on direct breast feeds till 8 days of life. He developed respiratory distress on day 9 of life and was admitted in neonatal intensive care unit. On examination he had tachypnea with respiratory rate of 66/min with subcostal retractions. Air entry was decreased on left hemithorax. Other systemic examinations were normal with no features of Hydrops.  Arterial blood gas analysis showed pH 7.35, HCO3 22 mmol, PaO2 82 mmHg, and PaCO2 41 mmHg. X ray chest showed increased opacity on left hemithorax with mediatinal shift to opposite side. USG thorax confirmed left sided gross pleural effusion. CT chest showed Left sided large pleural effusion with underlying compressed lung. Diagnostic thoracocentesis was done and 10 ml of milky white fluid was sent for analysis. The pleural fluid analysis showed exudative fluid containing protein 3.9 g/dl and sugar 51 mg/dl,  triglycerides 400 mg/dl, cholesterol 165 mg/dl, lactate dehydrogenase 270 IU/l, with cell count of 2000/mm3 (lymphocytes 92%/Polymorphs 8%); no microorganisms were seen on gram staining and pleural fluid culture was sterile, indicative of chylothorax. A diagnosis of congenital chylothorax was confirmed. Sepsis screen was negative and blood culture was sterile. Octreotide was initiated on day 7 of life and given for a total of 7 days. He was on breast feeds during the course of hospital stay. Follow-up chest radiograph showed clear resorption of pleural effusion. He was discharged home on day 15 of life, with fat free feeds and MCT oil.

During the study period 2012-2020, five babies were diagnosed to have idiopathic neonatal pleural effusion.  Out of five cases four were male (80%) and one was female baby(20%), with gestational age between 36 to 40 weeks (mean gestational age 39weeks) and birth weight ranging between 2500g to 4000g,(mean birth weight of 3144g) mean age of presentation was 5 day of life. Most babies (80%) presented with respiratory distress and one baby had birth asphyxia with respiratory failure. Pleural effusion was suspected by clinical examination and chest roentgenogram and was confirmed by ultrasound of thorax .Three cases had right sided pleural effusion (60%), with two cases involving the left hemithorax (40%) 

In this case series four cases were congenital chylothorax (80%) and one case was non chylous pleural effusion (20%) which was confirmed by pleural fluid cytology (table 2) and biochemical examination by using buttiker criteria. Intercostal drainage was done for four of five cases, whereas octreotide was given for three cases. 

Table 2: Pleural fluid analysis

The production and absorption of pleural fluid depends on various factors, which includes pulmonary venous hydrostatic pressure, blood oncotic pressure, lymphatic pressure, and local tissue factors, such as trauma or inflammation. Spontaneous or idiopathic neonatal pleural effusion is defined as any effusion in a newborn of age less than 30 days, without any obvious explanation [10,11] very few case series have been reported which have included congenital and acquired cause of pleural effusion. Ours is the largest case series including review of literature reported to the best of our knowledge in our case series we had five cases of idiopathic congenital pleural effusion out which four were congenital chylothorax and one case was non-chylous pleural effusion.

 Chylothorax is the accumulation of lymphatic fluid within the pleural space. It has been first reported by Asellius in 1627–1628 [12]. Pisek, and Stewart and Linner, were the first to recognize spontaneous chylothorax in newborns in 1917 and 1926, respectively [13]. In our case series male sex is predominantly affected (80%) which was in similarity with literature [2,14], In 50% of the cases, symptoms of congenital chylothorax were present at birth, but some may develop later, usually when starting enteral feeding [8], as in our case series, where mean age of presentation was 5 days, with four cases were symptomatic after breast feeds and one case was symptomatic at birth(case 2). Congenital chylothorax is more frequent in the right side of the thorax, in our study three of five cases had right sided effusion, probably related to the anatomy of the thoracic duct [7,8]. Pleural effusion was suspected by clinical examination and chest roentgenogram and was confirmed by ultrasound of thorax, in our case series, four cases were congenital chylothorax (80%) and one case was non-chylous pleural effusion (25%), which was confirmed by pleural fluid cytology and biochemical examination in table 2. 

Chylothorax may respond to a single thoracentesis as this expands the lung and tamponades the duct or lymphatic defect, preventing further formation of pleural fluid. If fluid reaccumulates a chest drain should be inserted. In this study one case (case 2) required resuscitation at birth and mechanical ventilation, chest tube drain was done for four cases, none of the cases required reinsertion of chest tube drain. Management of chylothorax includes the use of medium-chain triglyceride oil, fat-free baby formula, or enteric rest with total parenteral nutrition (TPN) [15].in this study one case was managed with parenteral nutrition for 10 days and later,  all four cases of chylothorax were managed with fat free diet and medium chain triglycerides and responded well. During the last several years, octreotide, a somatostatin analogue, has become another option for conservative management of chylothorax [16,17,18]. In this study, a total of three cases received octreotide, two cases for persistent chylous effusion and one case (case 5) was conservatively managed with octreotide. 

Idiopathic neonatal pleural effusion is frequently chylous in nature. Simple effusions are known to turn chylous after establishment of external fat feeds. Few non chylous pleural effusion cases have been reported [10,19] In this study ,one case(case 3) had non chylous effusion even after establishment of full enteral feeds, which was managed with chest tube drainage for 3 days and enteral feeds . In this case series, all five cases survived and were discharged home. None of the cases required surgical intervention.

Congenital pleural effusion in neonate is a rare entity, which causes respiratory distress in neonate. Most cases respond well with Conservative management. Octreotide yields good results in the management of chylothorax, it decreases surgical intervention, as well as the duration of hospitalization and it should be considered in persistent chylous effusion. Prognosis of chylothorax is excellent  Non chylous pleural effusion is very rare with very good prognosis.

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