Management of large congenital chylous ascites in a preterm infant: fetal and neonatal interventions

Abstract

Congenital chylous ascites is a rare cause of ascites in newborn infants. Its aetiology varies from localised leaky lymphatic duct to genetic syndromes. Most of these cases have transient ascites resolving over time with conservative management but some may progress needing medical as well as surgical treatment. We describe a case of antenatally detected large fetal ascites necessitating abdominal paracentesis and amnioreduction. Marked respiratory distress at birth required urgent abdominal paracentesis to relieve symptoms. The infant initially showed a good response to medium chain triglyceride (MCT) based formula milk feeds. Feeds were discontinued for 3 weeks due to sepsis with ileus. On recovery, recommencement of feeds resulted in reaccumulation of ascites. As the response to MCT-based formula was inadequate, octreotide therapy was initiated. Ascites showed remarkable resolution over the next 2 weeks and was discharged home. Follow-up at 5 years of age revealed normal growth and neurodevelopment.

Background

Chylous ascites is the accumulation of chyle within the peritoneal cavity. It is characterised by the presence of an odourless, milky, triglyceride (TG)-rich peritoneal fluid within the abdomen. The causes of chylous ascites in the younger age group can be related to delayed maturation of lacteals or abnormal development of lymphatic vessels, or effects from destruction to lymphatic system secondary to neoplasm, infection or inflammation.¹ Developmental disorders of lymphatic vessels due to genetic factors contribute to the main cause of congenital chylous ascites (CCA) and it has been reported in genetic syndromes, such as Turner syndrome, Noonan syndrome, Down syndrome, Klippel-Trenaunay-Weber syndrome and also in twins.^{2 3} Often, these infants present with abdominal distension at birth but nowadays with antenatal screening, it is commonly detected and closely followed up in fetal life. Chylous ascites can have serious mechanical, nutritional and immunological consequences due to significant loss of protein, immunoglobulins and lymphocytes.⁴ Conservative measures aim at relieving the pressure on the diaphragm, maintaining an optimum nutritional balance and administering therapies in order to reduce the production and flow of lymph. They include paracentesis, total parenteral nutrition (TPN), medium chain triglyceride (MCT)-based milk formula and use of somatostatin analogue, octreotide. Surgical treatment such as glue embolisation of leaky lymphatic channels and surgical ligation is considered only when conservative treatment fails.⁵

Case presentation

A preterm female infant was born at 33 weeks with a birth weight of 3480 g. The couple was non-consanguineous. The antenatal screening using ultrasound (US) scan at 21 weeks of gestation showed ascites measuring 23.2 mm and an amniotic fluid index (AFI) of 12.4 (50th centile). There were no evidence of hydrops in fetal scan. Maternal serology for intrauterine infection (Toxoplasmosis, Rubella, Cytomegalovirus and Herpes (TORCH)) screen was negative and there was no ABO or Rh incompatibility. Progressive increase in fetal ascites was detected in serial US, measuring 60.6 mm by 28 weeks of gestation and AFI of 25.2 (>97th centile) (figure 1). Amnioreduction of 1600 mL and fetal abdominal paracentesis removing 625 mL of fluid were done. Amniotic fluid showed normal female karyotype (46XX) and was negative for cytomegalovirus and toxoplasmosis screen. Fetal ascitic fluid analysis was suggestive of an exudate (white cell count 0.82×10⁹/L and protein 22 g/L). Ascitic fluid continues to reaccumulate, measuring 89 mm at 31 weeks of gestation. The infant was delivered at 33⁺² weeks by emergency lower segment caesarean section, the indication being increasing maternal discomfort due to polyhydramnios, with an Apgar score of 9 at 1 and 5 min of life. She was born with marked generalised abdominal distension and respiratory distress, needing continuous positive airway pressure support and was transferred to neonatal intensive care unit for further care.

Figure 1.

Antenatal ultrasound image at 22 weeks showing grossly distended abdomen with ascites. Bowel loops are situated together in central location.

Investigations

Postnatal abdominal radiograph (figure 2) and US confirmed the presence of a large ascites. Paracentesis was performed and drained 80–100 mL/day of ascitic fluid for the first 7 days of life and was replaced with equal volume of albumin. Analysis of the peritoneal fluid on day 1, while only on TPN, showed white cell count of 50/µL, with 87% lymphocytes, protein of 22 g/L, TG of 0.32 mmol/L and lactate dehydrogenase (LDH) of 150 IU/L (serum LDH 590 IU/L). On initiation of breast milk feeds on day 5 of life, ascitic fluid showed TG of 1.08 mmol/L rising to 8.96 mmol/L (serum TG, 1.3 mmol/L; ratio of ascitic to serum TG of 6.9) with increasing feeds on day 7. Ascitic fluid white cell count was 8190/µL with predominant lymphocytes (85%). Total ascitic fluid cholesterol was 1.24 mmol/L when serum was 3.6 mmol/L, a ratio of 0.34. Ascitic fluid analysis was consistent with a diagnosis of chylous effusion. Hence breast milk feeds were discontinued on day 7 even though paracentesis showed a downward trend in fluid volume. Peritoneal drain was removed. MCT-based formula feed (Monogen, Nutricia Medical, Ireland) was initiated and graded up to full feeds by day 10 of life with static abdominal girth. On day 11, she developed increasing liability needing escalation of respiratory support. X-ray of the abdomen showed moderate ascites and dilated loops of bowel. US of the abdomen revealed ascites and was negative for intramural gas. Haemogram and septic workup were suggestive of sepsis and antibiotics (cloxacillin and amikacin) were initiated. Blood culture grew Elizabethkingia meningoseptica (EKM). Cerebrospinal fluid analysis confirmed meningitis with white cell count, 2750/µL; protein, 4 g/L; glucose, <0.3 mmol/L (plasma glucose, 4.3 mmol/L) and EKM on culture. Cranial US, liver and renal function tests were unremarkable.

Figure 2.

Chest and abdominal radiograph on the first day of life shows a markedly distended abdomen due to congenital ascites. The bowel loops are situated in a central location due to the ascites. The lungs are poorly inflated.

Differential diagnosis

Differential diagnosis of isolated neonatal chylous ascites includes congenital lymphatic obstruction (45%–60% of cases) due to atresia or stenosis of the major lacteals, mesenteric cysts and lymphangiomatosis. In more than 50% cases no cause can be identified and is termed as ‘leaky lymphatics’. This is thought to be due to delayed maturation of the lacteals or hypoplasia of a portion of lymph vessels leading to chyle leakage. Postnatally, with time collaterals develop or lacteals mature, resulting in resolution chyle leakage. Diagnosis of chyle is based on ascitic fluid analysis following paracentesis while on milk feeds. Chyle is characterised by high white cell count with predominant lymphocytes and raised TGs. Resolution of ascites with MCT-based formula feeds also indicate leaky lymphatics. With worsening ascites, US and MRI or CT scan of the abdomen can help to rule out conditions such as meconium peritonitis that demand urgent surgical intervention. Lymphangiography and lymphoscintigraphy are indicated to identify the site of leakage if surgical intervention is planned.

Treatment

Antibiotics were escalated to rifampicin and piperacillin/tazobactam and continued for a total period of 4 weeks. Due to increasing gastric aspirates she was kept nil orally for 3 weeks and feeds were reintroduced with monogen, which was well tolerated. Serial US of the abdomen was done to monitor the progress of ascites while child was on feeds. Serum immunoglobulin level done on day 15 of life showed borderline low level of 1.15 (1.10–7 g/L), hence intravenous immunoglobulin was given on 2 consecutive days. Serial of lymphocyte counts showed lymphopenia ranging from 0.40 to 1.28×10⁹/L from day 1 to 20 of life followed by a gradual normalisation of lymphocyte counts over 2 weeks. At 8 weeks of life, the US abdomen showed worsening of ascites. MRI of the chest and abdomen was requested by the surgical team to rule out any space-occupying lesions, such as lymphangioma. MRI images confirmed the presence of ascites but otherwise unremarkable (figure 3). On day 56 of life, octreotide was started at 1 µg/kg of intravenous infusion 6 hourly and graded up to 6 µg/kg/dose subcutaneously at 8 hourly intervals for a total of 18 days. Monogen feed was continued as main nutrition. Clinically and serial imaging of the abdomen revealed remarkable resolution of ascites before discharge (figure 4).

Figure 3.

This fat-saturated axial T2 weighted MRI obtained on day 59 of life still shows the presence of ascites (arrows) situated between the bowel loops (X).

Figure 4.

An ultrasound of the abdomen image obtained on day 77 of life. In this image, the probe is placed transversely just above the level of the umbilicus. It shows the resolution of ascites. The air-filled bowel loops are now situated just beneath the abdominal wall.

Outcome and follow-up

Her follow-up US showed complete resolution of ascites by 5 months of age (figure 5). She was weaned off gradually from monogen to normal infant formula feeds and semisolid diet by 6 months of age without any recurrence of ascites. Her follow-up growth and neurodevelopmental assessments were appropriate for age and when last reviewed at 5 years of age, she was attending mainstream school.

Figure 5.

Timeline depicting the management given from birth to 5 months of age. BM, breast milk; NBM, nil by mouth; TPN, total parenteral nutrition; Octr, octreotide.

Discussion

Chyle is a milky fluid formed in the lacteal system of the intestines, rich in long-chain TGs, which combine with phospholipids, cholesterol and its esters to form chylomicrons. Chyle is stored within cisterna chyli located at the level of lumbar 2 vertebrae. Chylous ascites results from the extravasation of thoracic or intestinal lymph, giving rise to a creamy or milky appearing peritoneal fluid.^{1 5} Chyle is characterised by T-lymphocyte predominance (>80%), rich with protein of >20 g/L, high TG levels (>110 mg/dL) and lower cholesterol levels than serum.^{1 5 6}

Fetal ascites is often diagnosed as early as 14 weeks of gestation during antenatal US screening and follow-up US will identify its progress and if any evidence of hydrops fetalis. If signs of hydrops such as pleural or pericardial effusion or fetal subcutaneous oedema are detected along with ascites in US scan, further urgent investigations including maternal serologies for TORCH infection, Rhesus factor and blood group antibodies, amniocentesis for karyotyping and fetal echocardiography need to be carried out to detect the underlying aetiology.^{7 8} On the other hand, in the presence of isolated fetal ascites, associated anomalies of gut, urogenital and the heart should be looked for during antenatal imaging. Fetal cordocentesis can add on to identifying the aetiology of ascites in 92% cases as reported by Schmider et al.⁸ If the ascites were to increase significantly, fetal paracentesis may need to be carried out as this will improve the lung growth, prevent pulmonary hypoplasia and the neonatal respiratory outcome. Moreover, it would avoid abdominal dystocia if vaginal delivery of the baby is planned.⁹ As noted in our case, fetal paracentesis allowed to carry the pregnancy to 33 weeks.

Evaluation of chylous ascites in newborn infants involve history taking, physical examination, laboratory parameters and radiological findings. The most common presentation is marked abdominal distension and respiratory distress at birth as noted in our case. US of the abdomen to confirm ascites and to rule out intestinal and urological abnormalities need to be performed as a bedside procedure. The most useful diagnostic method is paracentesis and fluid analysis. The rise in TG and the characteristic milky appearance noted in chylous fluid are often observed only after milk feeds are initiated as observed in our case.¹⁰ As a routine, chylous fluid will be subjected to cell count, typing and culture to rule out other infections. The gold standard of investigation for chylous ascites unresponsive to conservative measures would be lymphangiography and lymphoscintigraphy to identify the leaky lymphatics; however, the technical difficulty and limited access, particularly in newborn infants, limit its use.^{1 5}

Conservative management of chylous ascites includes TPN, and/or MCT-based formula such as monogen feeds aiming to reduce chyle volume. Intermittent symptomatic relief with therapeutic paracentesis would be an alternative treatment to relieve respiratory distress and abdominal discomfort. TPN allows gut resting and monogen being MCT-based formula gets absorbed directly into the portal system rather than through lymphatics. Dietary management should be continued for at least 10 weeks before labelling as ineffective.¹¹ In a report of 103 case studies with chylous ascites, there were 63.9% of cure rate after conservative treatment, with an average treatment period to be 63.5 days. Almost all responders had an acute response to conservative management. Surgical treatment was suggested by the authors only if inadequate or absent response is observed after 2 months of conservative care.^{12 13} MRI/CT of the abdomen and upper/lower gastrointestinal tract imaging studies are indicated if surgical cause, such as meconium peritonitis or malrotation of the gut is suspected.

While on conservative measures, the infant’s susceptibility to infection increases due to loss of fluid, lymphocytes, proteins and immunoglobulins in addition to the risk related to paracentesis. In addition to volume replacement with colloids such as albumin to prevent haemodynamic imbalance of drainage of chyle, one should consider periodic immunoglobulin replacement therapy to prevent the occurrence of infection.^{14 15} As noted in our case, by second week of life the infant developed severe gram-negative sepsis and meningitis. We have to cease the monogen feeds even though it showed improvement initially because of paralytic ileus due to sepsis.

Somatostatin, or its synthetic analogue octreotide, has been used in the treatment of chylous ascites. Octreotide reduces the splanchnic blood flow and thereby portal pressure and inhibits intestinal fat absorption. Octreotide is used in 0.3–10 µg/kg/hour as a continuous intravenous infusion or 10–70 µg/kg/day subcutaneously in four divided doses.⁶ Use of higher doses of octreotide can increase the risk of necrotising enterocolitis (NEC) in newborn infants.¹⁶ Use of octreotide was delayed in our case because of prematurity and concerns about NEC when she had EKM sepsis with paralytic ileus. A Cochrane Systematic Review based on multiple case reports has suggested the need for multicentre randomised controlled trial to assess efficacy of octreotide in chylothorax.¹⁷ Zaki et al suggested larger prospective controlled trials to establish optimal initial dosing, time of initiation, duration, safety and efficacy of octreotide treatment in newborn infants.¹⁸

Kassem et al reported that in 58% cases with intractable chylous ascites, surgery is an option as they have lesions amenable to aciurgy. Fibrin glue has been successfully used to seal the lymphatic leaks in CCA.^{19 20}

In summary, our case responded well to conservative treatment without surgical intervention. The infant developed fulminant gram-negative sepsis due to EKM possibly due to hypogammaglobulinaemia secondary to loss of proteins, immunoglobulins and lymphocyte rich lymph into the peritoneal space. Response to octreotide at a moderate dose for 18 days was optimal with no adverse events. Her follow-up over the last 5 years has shown normal growth and neurodevelopment.

Learning points.

• Congenital chylous ascites is rare and more than 50% cases are due to malformation of the lymphatic vessels.

• Often fetal diagnosis is made by ultrasound scan, facilitating close monitoring and if required fetal abdominal paracentesis and amnioreduction to prolong pregnancy.

• Diagnostic evaluation of chylous ascites is complex and its treatment is often prolonged.

• Most of the infants respond to conservative measures which include abdominal paracentesis, medium chain triglyceride-based formula feeds, total parenteral alimentation and medical treatment using somatostatin analogue, octreotide.