Congenital Chylothorax with Cytomegalovirus Positivity: An Etiological Dilemma in a Neonate with Non-Immune Hydrops Fetalis

Yash Jain; Shivani Jain; Jenisha Jain; Minakshi Sharma

doi:10.4103/ipcares.ipcares_8_23

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CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 106-109

Congenital Chylothorax with Cytomegalovirus Positivity: An Etiological Dilemma in a Neonate with Non-Immune Hydrops Fetalis

Yash Jain¹, Shivani Jain¹, Jenisha Jain², Minakshi Sharma³
¹ Department of Neonatology and Pediatrics, Choithram Hospital and Research Centre, Indore, Madhya Pradesh, India
² Department of Neonatology, Choithram Hospital and Research Centre, Indore, Madhya Pradesh, India
³ Department of Obstetrics and Gynaecology, Choithram Hospital and Research Centre, Indore, Madhya Pradesh, India

Date of Submission	06-Jan-2023
Date of Decision	19-Mar-2023
Date of Acceptance	06-Apr-2023
Date of Web Publication	24-May-2023

Correspondence Address:
Dr. Jenisha Jain
297, Indrapuri, Indore, Madhya Pradesh
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_8_23

Abstract

Background: Nonimmune hydrops fetalis (NIHF) due to congenital chylothorax (CC) is rare and is usually associated with high mortality. Chylothorax complicated with congenital cytomegalovirus (CMV) infection is extremely rare and the management becomes challenging. We present a case of CC in a preterm infant with associated CMV positivity, which was managed successfully. Clinical Description: A 2.25 kg, 34-week female newborn, with antenatally diagnosed hydrops, delivered by emergency cesarean section, presented with pleural effusion and poor respiratory efforts. Management: The baby was provided mechanical ventilation and all supportive treatments. Pleural fluid testing was suggestive of high proteins with high white cell counts, predominantly lymphocytes. Baby was also positive for CMV immunoglobulin M with a high number of copies in the urine polymerase chain reaction. The baby initially responded well to oral valgancyclovir but returned with severe respiratory distress on day 20 of life, at which time, was again found to have right-sided chylothorax. This was managed successfully with octreotide at a dose of 8 μg/kg/hour and 90% medium chain triglyceride diet. Conclusions: CC should be considered in the differential diagnosis of NIHF. An incidental serological test positivity for CMV may be superimposed on underlying CC. If the latter is managed optimally with close monitoring, the outcome is usually favorable.

Keywords: Chylous, cytomegalovirus, congenital infection, neonate, pleural effusion

How to cite this article:
Jain Y, Jain S, Jain J, Sharma M. Congenital Chylothorax with Cytomegalovirus Positivity: An Etiological Dilemma in a Neonate with Non-Immune Hydrops Fetalis. Indian Pediatr Case Rep 2023;3:106-9

How to cite this URL:
Jain Y, Jain S, Jain J, Sharma M. Congenital Chylothorax with Cytomegalovirus Positivity: An Etiological Dilemma in a Neonate with Non-Immune Hydrops Fetalis. Indian Pediatr Case Rep [serial online] 2023 [cited 2023 Jun 3];3:106-9. Available from: http://www.ipcares.org/text.asp?2023/3/2/106/377521

Fetal hydrops is a serious condition characterized by the excessive accumulation of fluid in at least two of the extravascular compartments including ascites, pericardial effusion, pleural effusions, and generalized skin edema.^[1] The underlying etiology could be immune or nonimmune mediated. With the introduction of immunoglobulin (Ig) prophylaxis for Rhesus-D alloimmunization, the incidence of immune fetal hydrops has significantly decreased. Thus, majority of the cases encountered these days are nonimmune hydrops fetalis (NIHF). The causes for NIHF include congenital infections, cardiovascular disease, chromosomal abnormalities, twin-to-twin transfusion syndrome, hematological, lymphatic anomalies, and miscellaneous causes.^[1] NIHF due to congenital chylothorax (CC) is extremely rare and carries high mortality.^[2] We present a case of CC-induced NIHF with an associated cytomegalovirus (CMV) positivity.

Clinical Description

A 2.25 kg female baby was born out of nonconsanguineous marriage, to a 34-year-old primigravida, delivered by emergency cesarean section in view of antenatal ultrasound showing polyhydramnios and hydrops fetalis at 34 weeks of gestation. The present pregnancy, conceived naturally, was not complicated by any maternal fever, rash, lymphadenopathy, hypertension, or gestational diabetes. The antenatal ultrasounds were done at 31 weeks and 32 + 6 weeks which showed largest amniotic pocket sizes of 22.8 cm and 25 cm at 31 weeks and 32 + 6 weeks, respectively. Bilateral moderate pleural effusion (right > left) was observed on ultrasonography at 31 weeks, while the scan at 32 + 6 weeks was suggestive of polyhydramanios with bilateral pleural effusion with mild pericardial effusion suggestive of fetal hydrops. In view of the decision to deliver the baby at 34 weeks, mother was given two doses of betamethasone with first dose administered 24 h prior to delivery.

At birth, the child had poor respiratory efforts and required resuscitation with positive pressure ventilation with oxygen, along with drainage of 40 ml fluid from the right pleural cavity in the operation theater. However, she did not require chest compressions nor adrenaline at the time of delivery. Baby had an APGAR score of 3 and 6 at 1 and 5 min, respectively and was transferred to neonatal intensive care unit for providing mechanical ventilation.

Management and Outcome

The baby received in the intensive care unit was found to be normothermic (36.5°C), poor spontaneous respiratory efforts and cyanosis, with a heart rate of 150/min and capillary filling time of 3 s. The length of the baby was 43 cm and the head circumference was 32 cm. Shape of the head was normal, with no obvious features of dysmorphism. There was edema present over eyes, abdomen and genitalia, with pitting edema over both lower limbs and sacrum. There was no rash. The baby was ventilated using pressure control ventilation with FiO₂ 50%, peak inspiratory pressure 12 and positive end-expiratory pressure 7, and respiratory rate 40/min. She was started on injection dobutamine at 10 μg/kg/min along with intravenous amikacin and maintenance intravenous fluid at the rate of 40 ml/kg/day in view of anasarca.

Investigations showed hemoglobin 17.6 g/dl, Total Leukocyte Count (TLC) 17,880/cu mm L – 22% P – 68%, platelets 3.71 lac/cu mm, C-reactive protein 0.5 mg/dl, urea, creatinine 0.5 mg/dl, total bilirubin 13.6 mg/dl, serum glutamic-oxaloacetic transaminase/serum glutamic pyruvic transaminase 5/47 IU/ml, and serum albumin 3.1 g/dl. Urine output was adequate and urine dipstick did not show proteinuria. Chest X-ray revealed right massive pleural effusion [Figure 1]. The two-dimensional echocardiography revealed structurally normal heart, with mild pericardial effusion with normal cardiac function with ejection fraction of 65%. Right-sided intercostal tube drainage (ICD) was placed in the 6^th intercostal space and 150 ml of clear fluid drained. Pleural fluid examination showed slightly turbid, pale yellow fluid with proteins 2.9 g%, albumin 2.2 g%, glucose 75 mg%, total white cell count (WBC) of 1800 cells/cu mm, with 100% lymphocytes. Pleural fluid culture was sterile. Karyotyping was normal. Serology for congenital infections such as toxoplasma, rubella, CMV, and herpes was sent and CMV Ig M was found to be positive. Urine polymerase chain reaction (PCR) for CMV was also positive showing 33,175 copies/ml. Mother's serological test for IgG CMV was positive; however, IgM antibodies were negative.

Figure 1: Chest X-ray suggestive of right-sided pleural effusion. AP: Anteroposterior

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Baby was started on oral valganciclovir at a dose of 16 mg/kg/dose 12 hourly. She was extubated on day 3 of life. The ICD was removed on day 4 of life. The baby had spontaneous respirations maintaining saturation and was discharged home on day 6 of life, on full feeds and oral valganciclovir. Repeat chest X-ray on day 5 of life showed no re-accumulation of fluid.

On Day 20 of life, baby was readmitted for severe respiratory distress. On examination, air entry on the right side was decreased. Chest X-ray again revealed massive right-sided pleural effusion. Again, ICD insertion was done and 150 ml of chylous fluid was drained [Figure 2]. Pleural fluid was turbid with proteins 3 g%, albumin 1.4 g%, cell count of 2500/cu mm with 95% lymphocytes. Pleural fluid triglyceride levels were very high (1332 mg/dl). The possibilities considered at this time were: Primary CMV infection (lymphangitis) with hydrops at birth including pleural effusion and appearance of chylothorax later or probable CC with an incidental detection of CMV infection. At this point of time, pleural fluid CMV PCR was sent, which turned out to be negative. Lymphoscintigraphy could identified anatomical abnormalities if any, shedding light on the pathogenesis of this chylothorax. However, due to unavailability at our center, this study could not be done.

Figure 2: Intercostal tube in the right chest wall, showing draining of chylous fluid

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The baby was provided oxygen by hood with venturimeter of 24% and given supportive therapy with maintenance fluids. Oral valganciclovir was stopped and intravenous ganciclovir was started at a dose of 6 mg/kg/dose twice a day. The child was kept nil by mouth for 24 h. In view of chylous fluid output of more than 20 ml/kg/day, she was started on injection octreotide infusion at 1 μg/kg/hour and was gradually increased to 8 μg/kg/hour. The dose was not escalated further as baby developed hyperglycemia with blood sugar of 320 mg/dl. She was started on 90% medium chain triglyceride (MCT) feeds (Metanutrition, Pristine Labs, Bangalore) which was tolerated well. Gradually, chyle output reduced to <10 ml/kg/day. Octreotide was gradually tapered and feeds were increased slowly. The ICD was removed on day 10 of admission. Serial chest X-ray monitoring revealed no re-accumulation of pleural fluid. She was continued on MCT feeds for next 4 weeks along with oral valgancyclovir at a dose of 16 mg/kg/dose twice a day. The magnetic resonance imaging (MRI) of brain was normal. Hearing evaluation by Brainstem Evoked Response Audiometry (BERA), done at 42 weeks of life, was reported as normal. Liver functions remained within normal limits. The MCT feeds were gradually tapered and breast milk was introduced after 4 weeks. Currently, at 4 months of age, the baby is on breast feeding as well as formula feeds. She is growing well with a current weight of 6.5 kg and is developmentally normal. She is receiving oral valgancyclovir with weekly monitoring of white blood cell count.

In view of the course of the disease, absence of other stigmata of congenital CMV infection and negative pleural fluid CMV PCR, it was considered as a case of NIHF due to CC with an incidental finding of CMV infection.

Discussion

The newborn presented above, is a case of NIHF, possibly due to CC associated with CMV infection. As the hydrops had been diagnosed antenatally, the baby was provided optimal care right from the time of delivery, and despite a tough course, was managed successfully and is now thriving well.

As per literature, NIHF is a rare condition with an incidence of 1 in 1700–3000 pregnancies in Western countries, with high morbidity and mortality.^[2] CC, which is one of the causes of NIHF, is estimated to affect 1 in 10,000 births with a male to female ratio of 2:1. The NIHF associated with CC has a mortality rate as high as 98%.^[3] The causes of NIHF have been depicted in [Box 1].

In CC, fetal hydrops is due to an imbalance of interstitial fluid production and lymphatic return. Due to fact that fetus has a greater capillary permeability, compliant interstitial compartments, and vulnerability to venous pressure on lymphatic return, the fetus is at a high risk for CC.^[3] The condition can have a mass effect on fetal lungs leading to pulmonary hypoplasia, compromised pulmonary functions and cardiac failure. Furthermore, loss of proteins, lymphocytes, antibodies as well as nutrients and fluid result in malnutrition, dehydration and increased risk of infections.^[4] The etiology of CC could be thoracic malformations such as congenital pulmonary malformations, congenital diaphragmatic hernia or lymphatic anomalies such as lymphangioma, lymphangiectasia, and congenital lymphatic dysplasia syndrome.

The diagnosis of CC is based on – (a) Identification of chylous fluid (color of the fluid is clear if baby is not being fed and milky after feeding; protein content similar to plasma, pleural fluid showing high WBC count with more than 70% as lymphocytes and high triglyceride concentration [>1000 mg/dl] in a feeding child). This was observed in our case, as at birth the fluid was clear but had high proteins and WBC count with predominant lymphocytes, while, later, it turned milky with all the criteria satisfying that of a chylous fluid; (b) Identification of etiology for CC − this is the gold standard for the diagnosis. Appropriate investigations to identify the anatomy of lymphatic vessels include lymphangiography including magnetic resonance lymphangiography, lymphoscintigraphy, and nonionising lymphography.^[4]

Antenatal resolution of chylothorax and hydrops fetalis can be attained by fetal thoracocentesis and thoracoamniotic shunting.^[5] Postnatal treatment goals are delivery room stabilization, preventing and managing nutritional deficits, infections, treating chylothorax with medication and surgical methods. Thoracocentesis helps in alleviating respiratory difficulty. Measures to decrease lymph flow include keeping the child nil per oral, parenteral nutrition, MCT formula.^[6] Surgical interventions such as pleurodesis, ligation/embolization of lymphatic vessels, and pleuro-peritoneal shunts are used to treat CC, if medical management fails.^[7],[8],[9] Our patient responded well to diet modification and octreotide.

The interesting part of our case was an incidental CMV positivity. CMV can be transmitted to fetus as a result of primary infection in the mother, reactivation of the infection, or reinfection with a different strain of the virus. Transplacental transfer is the highest with primary maternal infection (15%–50%) decreasing to 0.5%–1% with recurrent maternal infection. Newborns with congenital CMV are mostly asymptomatic, with some showing certain features such as microcephaly, intra-uterine growth restriction, neonatal jaundice, hepato-splenomegaly, petechiae, chorioretinitis, and intracranial calcifications, with high incidence of neurodevelopmental disabilities on follow-up and sensorineural hearing loss even in asymptomatic neonates.^[10] The newborn described by us did not have any of the stigmata of CMV infection. There are reports describing congenital CMV as a rare but life-threatening cause of NIHF.^[11]

The serological tests for the diagnosis of CMV lack adequate sensitivity and specificity, the gold standard being virus isolation from urine or saliva, by rapid viral detection in culture immunohistochemistry.^[12] Apart from serological tests, brain imaging findings such as periventricular calcification, cerebellar hemorrhage, hyperechogenic bowel, pericardial effusion, and cardiomegaly provide useful diagnostic clues. These were not seen in our case, as per brain MRI. Symptomatic newborns need treatment with oral valganciclovir and monitoring for audiologic, visual, and neurodevelopment. Close monitoring of adverse effects including neutropenia is needed. In view of CMV serology positivity treatment was started. Our child is now on oral valganciclovir at 4 months of age, has no neutropenia, complete blood count being monitored weekly, and is developmentally appropriate for age.

CC is a rare cause of NIHF. When compounded with evidence of another etiology of NIHF like congenital CMV positivity, the management becomes tricky. Careful clinical examination and thorough investigations for associated findings help in decision-making for appropriate treatment strategy for a successful outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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