Neonatal Course and Long‐Term Outcome in Children With Congenital Chylothorax

ABSTRACT

Background

Congenital chylothorax is a rare pulmonary developmental disorder with high associated morbidity and mortality. A limited number of cases have been described, and clinical manifestations and outcomes vary.

Methods

This study aims to delineate the neonatal and long‐term outcome of patients with congenital chylothorax by retrospective and prospective data collection at Ghent University Hospital in Belgium between 1992 and 2022.

Results

Eighteen patients with congenital chylothorax were included, seven of whom had a pathology‐confirmed diagnosis of congenital pulmonary lymphangiectasia. Of 16 patients with prenatal diagnosis, four underwent an intra‐uterine intervention. Thirteen patients were born prematurely. The most common comorbidities were hydrops (8/18), pulmonary hypertension (3/18), and reflux disease (6/18). One patient was diagnosed with Noonan syndrome. The majority of patients (14/18) required mechanical ventilation. Treatment included pleural drainage (15/18), total parenteral nutrition (14/18), medium‐chain triglyceride diet (11/18), somatostatin (8/18), and surgical intervention (3/18), with a median hospital stay of 59 days. Three patients died during or after the neonatal period. Follow‐up ranged from 6 months to 30 years, with most patients reporting good general health but variable respiratory complaints. Five out of eight respiratory function tests showed mild abnormalities. Follow‐up chest CT showed persistent changes in all but two patients up to a maximum age of 16 years. Health‐related quality of life was similar to healthy controls.

Conclusion

Congenital chylothorax demonstrates a variable neonatal course. Long‐term outcomes are generally favorable in patients without comorbidities, although mild pulmonary function and chest CT abnormalities persist in the majority of patients.

1. Introduction

Congenital chylothorax is a rare disorder defined as an effusion of lymphatic fluid into the pleural cavity during the prenatal or neonatal period. Although rare, chylothorax is the most frequent cause of neonatal pleural effusions [1, 2]. A distinction is made between secondary chylothorax—resulting from functional obstructions such as post‐thoracic surgery or congenital heart disease‐related increased venous pressure—and congenital chylothorax, which may occur independently or in association with chromosomal anomalies, congenital malformations, or abnormalities of the lymphatic system [3, 4, 5]. Diagnosis of a pleural effusion is, in most cases, established prenatally by ultrasound. Postnatally, clinical presentation, imaging, and pleural fluid analysis can confirm the diagnosis of congenital chylothorax [1, 2]. One potential underlying cause is congenital pulmonary lymphangiectasia (CPL), a developmental disorder involving dilation of subpleural, interlobular, perivascular, and bronchial lymphatic vessels [6, 7]. CPL may present as an isolated pulmonary condition or as part of a systemic lymphatic disorder. Clinical presentation and imaging of CPL are nonspecific. Although lung biopsy is the gold standard for confirming the diagnosis, it is often deemed too invasive for neonates with respiratory compromise. Consequently, the term “congenital pulmonary lymphangiectasia” is frequently applied to cases of undifferentiated congenital chylothorax when no other identifiable cause is present [6].

The symptoms of congenital chylothorax can present within hours to days after birth and depend largely on the volume of chyle accumulation. Clinical manifestations range from asymptomatic to severe respiratory distress requiring urgent intervention [6].

Due to its rarity and clinical heterogeneity, no standardized or evidence‐based treatment protocols exist. Management is individualized and guided by gestational age, severity, and progression of the lymphatic leakage and associated complications such as hydrops, pulmonary hypoplasia, or mediastinal shift [1, 2, 4, 5]. Mild cases may be managed conservatively with close monitoring by serial ultrasound. In cases of larger or progressive fluid accumulation or hydrops, prenatal interventions—such as transthoracic thoracocentesis, in utero pleurodesis, thoraco‐amniotic shunting, or repeated amniotic drainages—are often indicated. Postnatal treatment includes respiratory support (noninvasive or mechanical ventilation), pleural drainage, fluid and nutritional management (e.g., medium‐chain triglyceride [MCT] diet or total parenteral nutrition [TPN]), and second‐line pharmacological therapy with somatostatin analogs. Alternative pharmaceutical options, including sirolimus, sildenafil, inhaled nitric oxide, and propranolol, have been reported anecdotally. Surgery is reserved for refractory cases where initial conservative management fails, and spontaneous resolution is unlikely, after exclusion of secondary causes [1, 2, 8].

Perinatal mortality remains high, ranging from 11% to 53%, but advances in fetal and neonatal care have improved outcomes. In CPL, morbidity and mortality seem to be even higher, but data on this specific subpopulation are scarce. For those surviving the neonatal period, long‐term outcomes are generally favorable and largely depend on the underlying etiology and comorbidities [9, 10]. However, data on the lung function trajectory throughout life, long‐term structural abnormalities, and adult respiratory morbidity remain scarce [11, 12].

This observational study aims to gain insights into both the neonatal course and long‐term outcome for children with congenital chylothorax in order to determine the need for structured long‐term respiratory follow‐up in this population.

2. Materials and Methods

2.1. Data Collection

A study was performed with retrospective and prospective data collection on patients treated for congenital chylothorax in Ghent University Hospital, Belgium, between 1992 and 2022. Patients were identified through multidisciplinary contacts and through searches in diagnostic lists. The number of cases in the area during the study period determined the sample size. Approval by the Ethics Committee of University Ghent and Ghent University Hospital was obtained (ethical approval number ONZ‐2022‐0444). All patients diagnosed with congenital chylothorax were included. All parents, guardians, or next of kin provided written informed consent for the minors to participate in this study. All adult participants provided written informed consent to participate in this study.

After patient identification, data were obtained regarding the perinatal period by searching the medical files on patient characteristics and neonatal course. Outcome data were gathered from medical records (routine follow‐up visits) and through one scheduled study visit. In patients aged 6 years and older, a pulmonary function test was performed using the Global Lung Function Initiative reference values, in which a z‐score below −1.64 (−2 standard deviations [SD]) was considered abnormal [13, 14]. Imaging was not conducted as part of this study; however, results from any imaging performed for standard care were obtained from medical records and interpreted as part of the follow‐up data. Chest CT scans were evaluated by experienced tertiary care pediatric radiologists, and lung abnormalities were collected from their study report. In the absence of a validated qualitative chest CT scoring system for this patient population, imaging characteristics were summarized based on the structural lung abnormalities described in bronchopulmonary dysplasia, defined in the PRAGMA‐BPD score, with the additional description of pleural effusion and interstitial abnormalities [15].

The health‐related quality of life (HRQOL) was measured using the Dutch version of the validated age‐specific PedsQL questionnaire covering physical, emotional, social, and school functioning by asking questions like how much of a problem the child had with “running,” “feeling sad,” “playing with other children,” or “paying attention in class” in the past month on a 5‐point scale. All domains were analyzed independently and standardized on a scale of 0−100, with a higher score indicating a better HRQoL in that domain. For the patients aged 1−24 months, the parent reported PedsQL infant scales were used. For children and adults, the age‐specific PedsQL TM 4.0 Generic Core Scales were used. This questionnaire was chosen for its brevity (23 questions, less than 5 min to complete), documented reliability, validity, sensitivity, and wide age range, making it well suited to measure pediatric population quality of life in a diverse population [16].

2.2. Statistical Analysis

Statistical analysis was mainly descriptive due to the limited population sample. Continuous data were summarized with median and interquartile range (IQR). Categorical data were summarized as absolute counts. The number of missing values is reported in the results for each variable of interest. No individuals were excluded because of missing data. All living patients attended the follow‐up consultation; no patients were lost to follow‐up.

The scores of the questionnaires were calculated into a physical score, a psychosocial score, and a total score. For the infant scales, a healthy control population sample was found in a 2010 article by Varni et al. on validation of the scales and consisted of 246 parents of infants [17]. For the children's PedsQL TM 4.0 Generic Core Scales, a control group was collected in a similar validation study by Varni with a sample size of 5972 patients for the self‐reported questionnaire and 10,070 parents for the proxy‐report [16]. In the pediatric study, cut‐off points were defined by identifying scores below 1 SD of the total population and were considered indicative of an “at‐risk” status for impaired HRQOL. Scores under 1 SD below the population sample were found to be similar to scores observed in children with severe chronic health conditions. Similarly, we defined cut‐off point scores for the infant population based on the PedsQL infant score validation study.

3. Results

3.1. Perinatal Data

3.1.1. Patient Characteristics

Eighteen patients with congenital chylothorax were identified. All patients and their parents agreed to participate in the study. Table 1 shows the demographic data, while Table 2 demonstrates the individual patient characteristics. Genes included in the genetic panels that were performed are listed in the Supporting Information Data.

Table 1.

Demographic data of 18 patients with congenital chylothorax.

Demographic data	Results in N or median (IQR)
Male gender	12
Birth weight (g)	2950 (2478−3345)
Gestational age (weeks)	36 (34−37)
Prematurity (< 37 weeks of gestation)	13
Cesarean section	13

Abbreviation: IQR = interquartile range.

Table 2.

Perinatal data of 18 patients with congenital chylothorax.

Case	Prenatal diagnosis	Prenatal thoraco‐amniotic shunting	Gestational age at birth (weeks)	Pleural effusion	Hydrops	Poly‐hydramnios	CPL	Genetic analysis
1	Yes	Yes	28	Bilateral	Present (ascites)	Present	No	Normal karyotype
2	Yes	No	37	Bilateral	Absent	Absent	Yes	Respiratory disorders panel negative,a missense variant in EPHB4
3	No	No	36 + 1/7	Bilateral	Absent	Absent	No	Normal karyotype
4	Yes	No	39 + 2/7	Left sided	Absent	Absent	Yes	Normal karyotype and array‐CGH. No variants in PIK3CA, FOXC2, FLT4, and VEGFR3. Heterozygous variant in PIEZO1
5	Yes	No	38	Bilateral	Absent	Absent	No	Normal karyotype
6	Yes	No	29 + 3/7	Bilateral	Present (ascites)	Present	No	Normal karyotype and array‐CGH, no variants in PTPN11, SOS1, and RAF1
7	Yes	No	34 + 1/7	Bilateral	Present (skin edema, ascites)	Present	No	Noonan syndrome (mutation c.182A>G(p.Asp61Gly) in PTPN11 gene)
8	Yes	No	36	Bilateral	Present (ascites)	Absent	No	Karyotype and array‐CGH negative, no variants in the PTEN gene
9	Yes	Yes	32 + 6/7	Bilateral	Present (ascites)	Present	No	Karyotype and array CGH normal
10	Yes	Yes	35 + 4/7	Bilateral	Absent	Absent	Yes	Karyotype normal, no variants in FOX2C, VEGFC, ITGA2, PIEZO1, Child interstital lung disease panel negativea
11	Yes	No	37 + 2/7	Right sided	Present (ascites)	Absent	No	/
12	Yes	No	33 + 2/7	Bilateral	Absent	Absent	Yes	Normal karyotype
13	Yes	No	35	Right sided	Absent	Present	Yes	/
14	Yes	Yes	31	Right sided	Absent	Present	Yes	/
15	Yes	No	36	Bilateral	Present (skin edema, ascites)	Absent	No	Normal karyotype, vascular gene panel negativea
16	No	No	36 + 1/7	Bilateral	Absent	Absent	No	/
17	Yes	No	37 + 1/7	Bilateral	Absent	Absent	No	Respiratory disorders panel negative, missense variant in EPHB4
18	Yes	No	35 + 2/7	Bilateral	Present (skin edema)	Present	Yes	Normal karyotype and array‐CGH, no variants in PTPN11, SOS1, and RAF1

Abbreviation: CPL = congenital pulmonary lymphangiectasia.

^a Genes included in genetic panels are listed in the Supporting Information Data.

3.1.2. Neonatal Course

Mechanical ventilation was reported in 14 out of 18 cases for a median of 9.5 days (IQR 5−27 days), and five patients were administered surfactant because of prematurity. Fifteen patients required supplementary oxygen, with a median of 15 days (IQR 12−47 days). Three patients showed no need for any kind of respiratory support. Fourteen patients were started on TPN. Treatment consisted of the implementation of the MCT diet in 11 patients (median duration of 21 days), somatostatin analog in eight (median duration of 14 days), corticosteroids in four (median duration of 13 days), and immunoglobulins in five. Diuretics and antibiotics were administered to 6 and 15 patients, respectively.

Pleural drainage was performed in 15 patients. Three patients underwent surgery because of insufficient response to non‐surgical treatment (Table 3): one received pleurectomy at the age of 6 weeks, another underwent ligation of the thoracic duct (TD) and pericardial fenestration at the age of 3 months, and the third had pleurodesis at the age of 6 months during a second hospitalization due to the recurrence of chylothorax. Median hospital stay was 59 days, with an IQR of 23−84 days.

Table 3.

Treatment and complications during the neonatal course of 18 patients with congenital chylothorax.

Case	Mechanical ventilation (days)	Pleural drainage	MCT diet	Somato‐statin	Surgical intervention	Comorbidity	Complications
1	30	Yes	Yes	No	No	Ichthyosis vulgaris	Recurrence chylothorax, thrombosis portal vein
2	1	No	No	No	No	Reflux disease	/
3	3	Yes	No	No	No	/	/
4	0	Yes	Yes	Yes	Pleurodesis	Pre‐auricular fistula	Recurrence chylothorax, pneumothorax
5	0	No	No	No	No	/	/
6	7	Yes	No	No	No	Ascites, reflux disease	Sepsis
7	34	Yes	Yes	Yes	No	Pulmonary hypertension, pulmonary hypoplasia, generalized edema, pulmonary stenosis, chronic myelomonocytic leukemia, cryptorchidy, reflux disease, failure to thrive, developmental delay	Sepsis, secondary hypogammaglobulinemia
8	5	Yes	Yes	Yes	No	Reflux disease, poly‐/syndactyly, fractured humerus, hypothyroidism	Secondary hypogammaglobulinemia
9	8	Yes	No	No	No	Ascites, reflux disease	Sepsis, pneumothorax
10	37	Yes	Yes	No	No	Pulmonary hypertension, pericardial fluid, horseshoe kidney, inguinal hernia, hydrocoele	Sepsis, prenatal shunt obstruction
11	11	Yes	Yes	No	No	/	/
12	55	Yes	Yes	Yes	No	/	Recurrence chylothorax, deceased at the age of 55 days due to respiratory failure
13	3	Yes	No	No	No	Pulmonary hypertension, subgaleal hemorrhage, polydactyly	Deceased at the age of 3 days due to respiratory failure
14	0	Yes	Yes	Yes	Ligation TD, pericardial fenestration	Pericardial fluid, reflux disease	Recurrence chylothorax, pericardial effusion, and post‐pericardiotomy syndrome
15	12	Yes	Yes	Yes	No	Partial syndactyly	Pneumothorax, secondary hypogammaglobulinemia, NEC
16	5	Yes	Yes	Yes	No	/	Recurrence chylothorax, secondary hypogammaglobulinemia
17	0	No	No	No	No	Congenital cytomegalovirus infection	/
18	19	Yes	Yes	Yes	Pleurectomy	Cholestasis	Recurrence chylothorax, sepsis

Abbreviations: MCT = medium chain triglyceride, NEC = necrotizing enterocolitis, TD = thoracic duct.

Several patients had significant comorbidities, mainly respiratory, such as pulmonary hypertension (3/18) or pulmonary hypoplasia (1/18), and gastrointestinal, such as gastroesophageal reflux disease (6/18), ascites (4/18), nutritional problems (2/18), and cholestasis (1/18). Cardiac comorbidities were pulmonary stenosis in one patient and concomitant pericardial fluid in two patients. Congenital CMV infection was diagnosed in one patient. Three patients showed nephro‐urological comorbidities. The patient with Noonan syndrome was diagnosed with juvenile myelomonocytic leukemia at the age of 3 months. Poly‐ or syndactyly was seen in three patients. Neonatal recurrence of chylothorax (6/18), sepsis (5/18), and secondary hypogammaglobulinemia were the most frequent complications encountered (Table 3).

3.2. Outcome Data

Fifteen patients were alive and attended the study visit at a median age of 7 years (IQR 1−10 years, min 1, max 30). Two patients (cases 12 and 13) with a confirmed diagnosis of CPL died due to respiratory failure during the neonatal phase. One patient (case 1) died beyond the neonatal period at age 3 years due to acute respiratory failure with a respiratory syncytial virus (RSV) infection. All deceased patients were born prematurely, and 2/3 showed bilateral pleural effusions at birth (Table 4).

Table 4.

Three‐way table indicating relation between mortality, prematurity, and extent of pleural effusion.

		Prematurely born	Not prematurely born
Mortality	Unilateral effusion	1	0
	Bilateral effusion	2	0
No mortality	Unilateral effusion	1	2
	Bilateral effusion	9	3

3.2.1. Clinical Status at Follow‐Up

All patients reported a good general well‐being. Five patients reported respiratory complaints including frequent coughing, exercise intolerance, and recurrent respiratory infections. Three younger patients had experienced bronchial hyperreactivity, while four received the diagnosis of asthma (one with dust mite allergy). Six of these patients were still on inhalation therapy. Clinical examination showed normal oxygen saturation (range 96%−100%), normal auscultation (except for wheezing in one patient) and a median normal growth and weight development (z‐scores for both weight and length around −0.2 [IQR −1.3 to 0.6 for weight and −1.1 to 0.6 for length], with a median z‐score for BMI/weight for length for age of 0.4 [IQR −0.9 to 1.2]).

3.2.2. Pulmonary Function

Pulmonary function tests were performed by the eight patients who were over 6 years old (Table 5). Three patients showed a mild obstructive spirometry pattern (forced expiratory volume in 1 second [FEV1] and/or Tiffeneau index [FEV1/FVC] z‐score < −1.64). Two patients had restrictive lung function based on their total lung capacity (TLC).

Table 5.

Lung function outcome data of eight patients with congenital chylothorax.

Lung function parameters	Median percent predicted (IQR)	Number of abnormal results (z‐score < −1.64)
FVC	99 (97−104)	0
FEV1	88 (81−95)	2
FEV1/FVC	80 (71−87)	3
TLC	95 (90−102)	2

Abbreviations: FEV1 = forced expiratory volume in 1 second; FEV1/FVC = Tiffeneau index, FVC = forced vital capacity, IQR = interquartile range, TLC = total lung capacity.

3.2.3. Imaging

Thirteen patients underwent diagnostic thoracic CT imaging during the neonatal period at a median age of 1 month (IQR 1−2, min 1, max 3). All 15 surviving patients got a CT scan at a later stage (median 16 months, IQR 11−40, min 7, max 192). A descriptive overview of the CT findings is presented in Table 6 and shows only one normal imaging on follow‐up conducted at the age of 9 months. Neonatal chest CTs mainly demonstrated pleural effusion, consolidations/atelectasis, ground glass opacities, and interlobular thickening. At follow‐up, atelectasis and bronchial wall thickening were the predominant persisting abnormalities.

Table 6.

Imaging characteristics at neonatal and follow‐up CT scan.

Imaging characteristics	Neonatal CT (n = 13)	Follow‐up CT (n = 15)
Age at CT scan (months)	1 (min 1, max 3)	16 (min 7, max 192)
Normal lung	0	1
Pleural effusions	10	1
Decreased pulmonary attenuation	2	4
Mosaic perfusion	0	4
Emphysema	0	0
Bullae	2	1
Increased pulmonary attenuation	11	13
Consolidation	6	3
Atelectasis	5	11
Ground glass opacities	5	2
Bronchial wall thickening	5	7
Interlobular thickening/interstitial pattern	9	2

3.2.4. HRQOL

All 15 patients and/or their parents completed the age‐specific questionnaires. Twelve patients exhibited mean scores similar to (historical) normative data. Three patients were at risk for impaired HRQOL, including case 10 with an additional diagnosis of intrathoracic hemangiomatosis and pulmonary interstitial glycogenosis (follow‐up at the age of 1 year) and case 7 with Noonan syndrome (follow‐up at the age of 7 years). The third patient (case 11, follow‐up at the age of 1 year) scored lower than −1 SD on the psychosocial scale, after a prolonged neonatal course with above‐average length of hospital stay but good clinical follow‐up. Radar charts with a visual representation of the scores per category and per patient compared to healthy control groups can be found in the Supporting Information Data.

4. Discussion

This study presents an analysis of 18 patients diagnosed with congenital chylothorax, focusing on patient characteristics, neonatal course, and long‐term outcomes, including clinical status, pulmonary function, imaging, and HRQOL. It is the first study to provide data on long‐term CT changes and HRQOL related to congenital chylothorax.

A recent review by Resch et al. analyzed 753 previously published cases of congenital chylothorax between 1990 and 2018 [1]. Comparing our data with theirs, similarities in patient characteristics emerge regarding gender distribution (male predominance at a ratio of 2:1), prevalence of prematurity (70% with a mean gestational age of 34 weeks), predominance of bilateral chylothorax (75%), occurrence of hydrops (40%), and association with genetic syndromes. Differences include higher confirmed CPL cases (7/18 vs. 47/735, though without data on the number of biopsies) and more prenatal diagnoses in this study. In cases of prenatal diagnosis, a similar proportion of around 25% underwent placement of thoraco‐amniotic shunts, but none of this sample underwent intra‐uterine pleurodesis, given the irreversible nature of this procedure and the possibility of postnatal spontaneous resolution of the chylothorax.

In our study population, two patients were related (mother and son). Whole exome analysis revealed a missense variant in EPHB4 in the mother and son, but it was classified as a class 3 genetic variant based on prediction models. We found seven case reports documenting a total of 16 patients describing familial CPL in pairs of siblings [18, 19, 20, 21, 22], suggesting potential autosomal recessive inheritance, though no genetic defects were identified.

Primary treatment included respiratory support, pleural drainage, TPN, MCT diet, and somatostatin analog use. This cohort showed more advanced therapies used with a higher proportion of complications and longer hospital stay compared to previous literature on congenital chylothorax. This may be linked to the higher proportion of CPL cases and the more recent timeframe of the study, during which more advanced therapies have become standard practice. Surgical interventions were limited (3/18) and performed cautiously due to the inherent risks and the potential for spontaneous resolution [23].

The mortality rate observed in this study aligns with findings in the literature and is primarily attributed to respiratory failure [1, 2, 9, 24]. This study adds to the paucity of data on the long‐term outcome of congenital chylothorax. Most patients perceived their overall condition as satisfactory with no major respiratory compromise. However, one‐third of the patients reported persistent respiratory symptoms, along with a higher incidence of asthma and inhalation therapy use. This high asthma incidence has been previously noted in follow‐up studies by Caserio et al. (four out of 15 patients at a mean follow‐up of 7 years) and Resch et al. (two out of six patients at a mean follow‐up of 5 years) and might be explained by the higher rate of prematurity and recurrent infections, both of which are known risk factors for the development of asthma later in life [9, 12]. Pulmonary function testing was in line with these findings, showing mild obstructive patterns in three and borderline restrictive patterns in two. Another follow‐up study in six patients focusing on pulmonary function yielded similar results with one mildly restrictive and one obstructive pulmonary function [12].

This is the first study reporting on CT changes observed in the long‐term follow‐up of congenital chylothorax. If not clinically indicated, control imaging on the long term after congenital chylothorax was not routinely advised. Given the availability of low‐dose radiation protocols and the remaining uncertainty about long‐term sequelae, all patients at Ghent University Hospital had a follow‐up CT scan at a median age of 16 months. Importantly, all but one CT scan revealed persistent changes up to a maximum age of 16 years. This indicates the presence of structural pulmonary changes that last into childhood and potentially adulthood. Together with the growing knowledge about impact of prenatal events on lung function trajectory throughout life, these findings strongly advocate for further studies on long‐term outcome of congenital chylothorax [25, 26].

This is also the first study to investigate the long‐term HRQOL in children born with congenital chylothorax. The results are reassuring, revealing predominantly lower scores during early follow‐up stages and highlighting primarily the impact of comorbidities on long‐term HRQOL.

The strength of this study lies in its provision of a valuable data set on a rare disease. Particularly noteworthy is the inclusion of long‐term data, CT chest results, and emphasis on HRQOL of patients with this condition. Additionally, seven patients had CPL confirmed on lung biopsy, which is a rare entity with scarce specific data due to challenges in diagnosis. This study has several limitations. Its monocentric, retrospective design and small sample size limit statistical power and preclude meaningful comparisons with healthy controls. The cohort was assembled over a 30‐year period, during which substantial advances in pre‐ and perinatal care, treatment strategies, and follow‐up practices occurred, introducing temporal heterogeneity that may have influenced management and outcomes and thus limits generalizability. This prolonged inclusion period also implies that follow‐up data are limited in duration for more recently included patients, thereby restricting the strength of conclusions regarding long‐term prognosis. Nevertheless, with this study, we aimed to provide an initial overview of potential long‐term sequelae in this rare patient population. Future studies specifically designed to evaluate imaging through quantitative imaging techniques and studies focusing on HRQOL in larger patient cohorts at fixed follow‐up time points would be of significant added value. Further investigation into the pathophysiology of congenital chylothorax is essential to enhance diagnostic methods and treatment options. Patient registers and long‐term follow‐up can yield insights into the disease course and outcome, aiding the development of better treatments.

In conclusion, this cohort study confirms the complexity and high variability of the neonatal course observed in patients with congenital chylothorax, ranging from mild to life‐threatening disease. The study reveals a high morbidity and mortality rate in this population during the neonatal period, partly due to multiple comorbidities and complications, highlighting the critical need for an individualized approach to patient management. Considering the diverse clinical presentations and outcomes, a tailored treatment strategy is essential to optimize outcomes.

After the neonatal period, an overall good outcome can be expected. However, this study shows that patients with congenital chylothorax are at higher risk of lingering mild respiratory complaints and persistent pulmonary function and imaging abnormalities. Therefore, we suggest regular follow‐up examinations and assessments throughout childhood. Furthermore, prospective collection of long‐term follow‐up data in patient registries should be instituted.

Author Contributions

Study conception and design: N. Beullens, K. Smets, H. Schaballie. Data collection: N. Beullens, K. Smets, M. De Lausnay, P. Schelstraete, S. Van Daele, J. Willekens, J. Van Dorpe, H. Schaballie. Analysis and interpretation of results: N. Beullens, K. Smets, H. Schaballie. Draft manuscript preparation: N. Beullens, H. Schaballie. All authors reviewed the results and approved the final version of the manuscript.

Funding

The authors have nothing to report.

Ethics Statement

This study was performed in accordance with the Declaration of Helsinki. This human study was approved by the Ethics Committee of Ghent University and Ghent University Hospital (ethical approval number ONZ‐2022‐0444). All parents, guardians, or next of kin provided written informed consent for the minors to participate in this study. All adult participants provided written informed consent to participate in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File 1

Beullens N., Smets K., De Lausnay M., et al., “Neonatal Course and Long‐Term Outcome in Children With Congenital Chylothorax,” Pediatric Pulmonology 61 (2026): e71820. 10.1002/ppul.71820.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.