Bilateral Congenital Chylothorax With Neonatal Ventilator-Associated Pneumonia and Sepsis: Diagnostic and Therapeutic Challenges: A Case Report

Introduction

Congenital chylothorax is a rare neonatal condition characterized by the accumulation of lymphatic fluid within the pleural space. It represents the most common cause of pleural effusion in the neonatal period and is associated with a reported mortality rate ranging from 20% to 60%, which can increase up to 98% when complicated by hydrops fetalis [1]. The estimated incidence varies between 1 in 10 000 and 1 in 24 000 live births, with a male predominance; bilateral involvement is considered exceptionally rare [2]. Congenital chylothorax can present antenatally or postnatally and often leads to respiratory distress, hemodynamic instability, and significant nutritional and immunological deficiencies due to the loss of proteins and lymphocytes [3].

The etiology can be congenital, acquired traumatic, or acquired non-traumatic. Congenital causes include fetal hydrops, genetic syndromes (Noonan, Down, Turner, Yellow Nail), and lymphatic malformations such as thoracic duct atresia or lymphangiomatosis. Acquired causes are usually surgical or perinatal trauma [4].

The diagnosis of congenital chylothorax is primarily established by pleural fluid analysis, which typically demonstrates a milky appearance, elevated triglyceride levels (>110 mg/dL, 1.24 mmol/L), and lymphocyte predominance, often exceeding 70% to 80%. Cholesterol levels are generally lower than triglyceride levels and often below 200 mg/dL, which, together with a triglyceride-predominant profile, helps differentiate chylothorax from pseudochylothorax. A pleural fluid-to-serum triglyceride ratio greater than 1 may provide additional supportive evidence for the diagnosis. The milky appearance may be more pronounced in breastfed or enterally fed neonates. Detection of chylomicrons confirms the diagnosis; when available, this can be assessed using lipoprotein electrophoresis of the pleural fluid sample. Chest radiography and ultrasound are used to detect and monitor pleural effusion, while computed tomography (CT) can help identify the underlying cause. In selected or refractory cases, lymphangiography or lymphoscintigraphy can be used to localize the site of lymphatic leakage [5,6].

The management of congenital chylothorax is initially focused on stabilization of respiratory function and drainage of pleural effusion, when clinically indicated. Following acute management, treatment is primarily conservative and aims to reduce chyle production while maintaining adequate nutrition. This includes dietary modification with medium-chain triglyceride–based formulas, fat-modified or skimmed breast milk, or total parenteral nutrition in more severe cases. Pharmacologic therapy, most commonly octreotide, may be used in persistent or high-output effusions, while somatostatin may be used as an alternative. Most cases respond to conservative measures; however, surgical or interventional approaches, such as thoracic duct ligation, pleurodesis, or thoracic duct embolization, are reserved for refractory cases or those with ongoing high-volume chylous drainage [2,6,7].

Previous studies, including a systematic analysis by Resch et al, have demonstrated considerable variability in clinical presentation, management strategies, and outcomes of congenital chylothorax, highlighting the rarity of bilateral cases and the absence of standardized treatment approaches [8,9].

This report describes a 3-day-old male neonate with respiratory distress due to bilateral congenital chylothorax with ventilator-associated pneumonia and neonatal sepsis.

Case Report

The male Kosovar neonate was transferred from the delivery room following a cesarean delivery for close monitoring and evaluation due to the mother’s significant obstetric history. He is the second child of the mother’s fourth pregnancy (G4P2) and was delivered at 40 weeks of gestation. At birth, he was a male neonate weighing 4230 g, measuring 53 cm in length, and having a head circumference of 37 cm. The Apgar score was 8–9, with heart rate 2, respiration 2, skin color 1–2, muscle tone 1, and reflexes 1. Maternal history is notable for a prior intrauterine fetal demise and 1 neonatal death in a twin pregnancy at 33 weeks of gestation; both previous pregnancies were complicated by non-immune fetal hydrops.

The male neonate was eupneic, with normal cardiac findings, normal muscle tone, and intact reflexes. The skin was pink, with well-developed subcutaneous tissue. The head had a normal shape and configuration. The thorax was cylindrical and symmetrically mobile. Respiratory examination revealed bilateral bronchovesicular breath sounds. Cardiac auscultation demonstrated clear and rhythmic heart tones. The abdomen was soft on palpation, with liver and spleen palpable within normal limits. The urogenital system was consistent with age and sex. The central nervous system responded symmetrically to external stimuli, with preserved reflexes.

On day of life (DOL) 2, the newborn remained in stable condition on room air, with normal vital signs, and was breastfeeding successfully. However, on DOL 3, after midnight, his condition deteriorated, presenting with signs of respiratory distress, a respiratory rate of 93 breaths per minute, heart rate of 140 beats per minute, and peripheral oxygen saturation (SpO2) of 88%. He was transferred to the neonatal intensive care unit and placed on nasal continuous positive airway pressure (CPAP) with fraction of inspired oxygen (FiO2) of 40%, achieving SpO2 of 93% and a temperature of 37.1°C. Breastfeeding was discontinued, intravenous fluids were initiated, and empirical antibiotic therapy with imipenem and vancomycin was started. Due to a prolonged capillary refill time greater than 3 seconds and a mean arterial pressure of 32 mmHg, a 0.9% NaCl bolus of 10 mL/kg was administered, accompanied by inotropic support with dopamine at a dose of 5 mcg/kg/min.

On DOL 4, the newborn’s condition further deteriorated, with SpO2 dropping below 90%, and the patient exhibiting dyspnea with a respiratory rate exceeding 90 breaths per minute while on nasal CPAP with FiO2 50%. The mean arterial pressure was 46 mmHg, blood glucose 5.4 mmol/L, and temperature 37°C. Arterial blood gas analysis revealed respiratory acidosis with a pH of 7.23, PCO2 of 82 mmHg, and HCO3− of 29.4 mmol/L. He was intubated and connected to a mechanical ventilator (Figure 1) with the following settings: peak inspiratory pressure/positive end-expiratory pressure of 22/4 cmH2O, ventilator rate of 45 breaths per minute, inspiratory-to-expiratory ratio of 1: 2, FiO2 50%, achieving SpO2 of 96%, heart rate of 141 beats per minute, and mean arterial pressure of 49 mmHg.

Based on serum biochemistry and the presence of generalized edema, 20% human albumin was administered. Blood cultures were negative. Laboratory test results are summarized in Table 1. Serum biochemistry, including total cholesterol, triglycerides, total protein, and albumin, was performed and is presented in Table 2. Thyroid function tests were within the reference range (thyroxine 13.6 pmol/L, triiodothyronine 2.5 pmol/L, thyroid-stimulating hormone 0.68 mIU/L), thereby excluding congenital hypothyroidism. Serum biochemistry demonstrated hypoproteinemia and hypoalbuminemia, although albumin levels fluctuated due to intravenous supplementation. Triglyceride levels remained within the reference range, with episodic decreases in cholesterol down to 1.9 mmol/L. C-reactive protein and lactate dehydrogenase were elevated on several occasions, suggesting concomitant inflammatory processes. Urea levels were generally low, while total and direct bilirubin, alanine aminotransferase, and aspartate aminotransferase remained within the reference ranges

Planned further examinations included echocardiography, which revealed no pathological findings. Thoracoabdominal ultrasound demonstrated a right-sided pleural effusion with a considerable amount of fluid. The liver and spleen were of normal size and shape. Free intra-abdominal fluid was noted in the hepatorenal recess (Morrison’s pouch), while the Douglas pouch was free of fluid. The right kidney appeared normal, whereas the left kidney showed dilatation of the renal pelvis measuring 1.24 cm. A megaureter was observed on the left side, associated with grade III–IV vesicoureteral reflux. Abdominal and chest radiography revealed bilateral pleural effusions with obliteration of the bilateral costophrenic angles. No air-fluid levels were identified in the abdomen, and no free subdiaphragmatic air was present (Figure 2)

The patient was consulted by a thoracic surgeon for pleural effusion. A thoracic puncture was performed on the right side, evacuating 2 mL of pleural fluid, which was sent for cytological, bacteriological, and biochemical analysis, with results pending (Table 3).

Due to the small volume of pleural fluid, only the parameters listed in Table 3 could be measured, which indicated an exudative effusion. Other parameters were not available.

Initial cytological analysis demonstrated high cellularity, with a predominance of erythrocytes and lymphocytes. Large atypical cells with an increased nucleocytoplasmic ratio and hyperchromatic nuclei were observed, prompting a recommendation for further clinical evaluation to exclude a possible neoplastic process.

Three days after the initial puncture, a thoracoabdominal CT scan demonstrated bilateral pleural effusions, more pronounced on the right side, along with emphysematous bullae. On DOL 12, a right thoracocentesis was performed, and a chest drain was placed and connected to a Pleurovac, resulting in the evacuation of 100 mL of serous (yellow) pleural fluid. Fluid analysis revealed a total protein level of 39.7 g/L, albumin level of 35.1 g/L, triglyceride level of 1.7 mmol/L, and glucose level of 3.2 mmol/L.

On DOL 13, chest radiography showed pulmonary consolidation and obliteration of the bilateral costophrenic angles (Figure 3). Endotracheal aspirate culture yielded Acinetobacter spp., confirming ventilator-associated pneumonia. Consequently, the initial empirical antibiotic therapy with imipenem and vancomycin was discontinued and switched to cefepime and ampicillin-sulbactam, according to the antibiogram, while the pleural fluid culture remained sterile.

In the following days, the neonate received minimal enteral nutrition, consisting of 5 mL of breast milk. Upon resumption of full breastfeeding, an increased accumulation of pleural fluid and generalized edema were observed, raising suspicion for congenital chylothorax. Enteral feeding was therefore discontinued.

Two days after the placement of the right-sided chest drain, a left-sided thoracostomy with drain insertion was performed (Figure 4), evacuating approximately 60 mL of pleural fluid. Subsequently, the fluid from both drains developed a milky (white) appearance, consistent with chylous effusion. The results from the pleural fluid analysis were as follows (Table 4).

Elevated pleural fluid triglyceride levels (2.41 mmol/L), together with a pleural fluid-to-serum triglyceride ratio greater than 1, provided strong evidence for chylothorax. The triglyceride-to-cholesterol ratio of 1.52 further supported a chylous profile. These findings, combined with relatively low cholesterol levels (1.59 mmol/L, equivalent to 61.5 mg/dL) and a pleural fluid-to-serum cholesterol ratio less than 1, reinforced a chylous etiology and helped differentiate it from pseudochylothorax. Additional features, including elevated protein levels and a low serum-pleural albumin gradient, were consistent with an exudative profile. In combination with the characteristic milky appearance and negative Gram stain and culture results, these findings supported the diagnosis of congenital chylothorax.

Cytological analysis revealed a predominance of lymphocytes (>80%) with rare mesothelial cells without atypia. The examined material was consistent with lymph, and the cytological features corresponded to the clinical presentation, thereby confirming the diagnosis of chylothorax.

Following bilateral thoracocentesis, drain placement, pleural fluid analysis, and the cytological findings described above, treatment was initiated according to established protocols for congenital chylothorax. The patient received continuous intravenous octreotide (a somatostatin analogue) for 25 days, starting at 1 mcg/kg/h and gradually titrated to a maximum of 4 mcg/kg/h, in combination with feeding using a medium-chain triglyceride–based formula.

Initially, pleural fluid drainage was 50 mL per 24 hours (12.5 mL/kg/day), which gradually decreased to 5 mL per 24 hours. The thoracic drains remained in situ for 14 days, until DOL 36. Gradual reduction of pleural effusion was also confirmed by ultrasound evaluation (Figure 5).

During octreotide therapy, the neonate did not experience bradycardia or hypotension. Blood glucose levels remained within reference ranges: on the first day after the initial octreotide dose, the 24-hour average was 5.53 mmol/L; on day 4, 4.5 mmol/L; day 7, 6.0 mmol/L; day 13, 4.3 mmol/L; and day 23, 4.4 mmol/L.

The patient required mechanical ventilation for 20 days, from DOL 4 to 25 (Table 5). Following clinical improvement, he was extubated and transitioned to nasal CPAP for 4 days. From DOL 25 onward, oxygen therapy via O2-hood at 3 L/min was continued for an additional 14 days.

The patient was also anemic (Table 1) and received packed red blood cell transfusions according to protocol (10 mL/kg/day), receiving 45 mL of concentrated red blood cells (A+) on DOLs 29, 31, 34, and 39.

During the neonatal period, the patient developed ventilator-associated pneumonia. Endotracheal aspirate cultures obtained on DOL 13, 19, and 24 isolated different bacteria: Acinetobacter spp. on DOL 13, Escherichia coli on DOL 19, and Enterobacter spp. on DOL 24 (Table 6). On DOL 31, blood culture grew Enterobacter spp., confirming neonatal sepsis. Laboratory findings showed a white blood cell count of 25.6×109/L, granulocytes 86.8%, and a C-reactive protein level of 125 mg/L. Based on the antibiogram (Table 6), targeted antimicrobial therapy was initiated. Vancomycin was administered at a dose of 15 mg/kg every 12 hours for 12 days, in combination with meropenem at a dose of 20 mg/kg every 12 hours for 7 days. Following completion of vancomycin therapy, treatment was continued with piperacillin-tazobactam at a dose of 100 mg/kg every 8 hours for 7 days, according to antimicrobial susceptibility results.

With follow-up results within reference ranges, antibiotic therapy was discontinued. After 25 days of octreotide therapy, the treatment was stopped. Following independence from supplemental oxygen and clinical stabilization, the infant was transferred to the room with the mother. Feeding was continued with a medium-chain triglyceride–based formula, and he began to gain weight.

On DOL 56, he was discharged home in good health (Figure 6), weighing 4485 g, with a head circumference of 36.5 cm. Guidance was provided to the mother regarding care and feeding.

A 5-year follow-up revealed no recurrence of the chylothorax, with normal growth and psychomotor development (Figure 7).

Discussion

This case highlights important diagnostic and therapeutic challenges in the management of congenital chylothorax, particularly in the presence of severe complications such as ventilator-associated pneumonia and neonatal sepsis.

Congenital chylothorax is the most common cause of pleural effusion in neonates; however, its diagnosis and management remain challenging because of variable clinical presentation and overlap with infectious and inflammatory conditions [6,7]. As outlined by De Angelis et al, early diagnosis may be particularly difficult when pleural fluid analysis is performed before the initiation of enteral feeding or during periods when enteral nutrition is temporarily withheld, as the biochemical characteristics of chyle may be absent at these stages [10]. Similarly, Tutor emphasized that initial pleural fluid samples in neonates frequently fail to meet diagnostic criteria for chylothorax in the absence of enteral fat intake, either prior to initiation or following temporary cessation of feeding [11]. In our patient, the initial pleural fluid analysis was non-diagnostic, which is consistent with previous reports describing false-negative results in the absence of enteral fat intake.

In our patient, the initial pleural fluid analysis revealed high cellularity with erythrocyte and lymphocyte predominance and atypical cytological features, raising concern for alternative diagnoses such as infection or neoplasia. Such misleading cytological findings have been described in neonatal chylothorax and are thought to reflect inflammatory activation and lymphatic disruption rather than malignancy [12]. Diagnostic clarification was achieved after the reintroduction of breast milk, when the pleural effusion increased in volume, developed a milky appearance, and fulfilled biochemical criteria for chylothorax. This diagnostic evolution underscores the importance of repeated pleural fluid analysis and reassessment, as recommended by Tutor [11] and Jackson and Jnah [13].

Management of congenital chylothorax aims to reduce lymphatic flow while ensuring adequate respiratory support and nutritional balance. Conservative treatment remains the cornerstone of therapy and includes pleural drainage, ventilatory support, and dietary modification using medium-chain triglyceride–based nutrition, as described by Soto-Martinez and Massie [14] and further supported by Neumann et al [15]. In the present case, bilateral thoracic drainage was required due to progressive effusions. Although bilateral involvement is uncommon, it has been associated with increased disease severity and prolonged hospitalization [7,16].

Octreotide has increasingly been used as an adjunctive therapy in refractory or severe cases of congenital chylothorax. Bellini et al reported favorable outcomes with octreotide therapy in neonatal chylothorax, although standardized dosing regimens are lacking [17]. Similar results were described by Yin et al, who demonstrated effective reduction of chylous effusions with somatostatin or octreotide treatment [18]. In our patient, continuous octreotide infusion was administered for 25 days with careful titration from 1 to 4 mcg/kg/h, resulting in complete resolution of pleural effusions without cardiovascular or metabolic adverse effects. This supports the concept that individualized, lower-dose regimens may be sufficient in selected neonates. Other pharmacologic approaches have been described only in isolated case reports, including propranolol [1], sildenafil [19], sirolimus [20], and midodrine [21], and are generally reserved for refractory cases or specific underlying conditions.

The clinical course of our patient characterized by prolonged mechanical ventilation, ventilator-associated pneumonia, neonatal sepsis, and transfusion-dependent anemia reflects the high morbidity associated with severe congenital chylothorax. Resch et al reported similar infectious complications and prolonged ventilatory support in children with congenital chylothorax during long-term follow-up [8]. In a subsequent systematic review, Resch et al documented frequent use of octreotide, high rates of sepsis, and prolonged hospitalization, findings that closely parallel our patient’s course [9].

Despite these complications, our patient responded favorably to conservative management and avoided surgical intervention, which is generally reserved for cases refractory to medical therapy [14]. Long-term follow-up over 5 years revealed no recurrence of pleural effusions and normal growth and psychomotor development, consistent with outcomes reported by Resch et al and Roehr et al [8,9,22].

This case suggests that even severe bilateral congenital chylothorax complicated by infection, respiratory failure, and anemia can be successfully managed conservatively through meticulous respiratory care, nutritional support, pleural drainage, and octreotide therapy. Early diagnosis, repeated reassessment, close monitoring, and structured long-term follow-up remain essential. As the first reported case of bilateral congenital chylothorax in our country, this report adds valuable data to the existing literature.

This case report has some limitations. Since this is a single-case study, the findings may not be generalizable to all neonates with congenital chylothorax. Early pleural fluid sampling was limited, which may have influenced the initial diagnostic assessment. Genetic testing was not performed; however, the maternal history suggests a potential hereditary predisposition that could not be confirmed.

Conclusions

This case illustrates a rare presentation of bilateral congenital chylothorax complicated by ventilator-associated pneumonia and neonatal sepsis, highlighting the challenges of early diagnosis in the presence of coexisting neonatal conditions. Our findings illustrate that timely diagnosis and individualized conservative management, including pleural drainage, nutritional support, and octreotide therapy, can lead to successful outcomes. A multidisciplinary approach, along with careful monitoring and repeated diagnostic assessment, remains essential for optimal management and long-term recovery.