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CASE REPORT Table of Contents  
Ahead of print publication
Congenital cytomegalovirus infection-related diaphragmatic dysfunction: Acase study


 Department of Neonatology, Zulekha Hospital, Sharjah, United Arab Emirates

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  Abstract 


Congenital cytomegalovirus(CMV) infection is a common disorder that can lead to multiple developmental sequelae. This case study reports a newborn with respiratory distress syndrome(RDS) associated with diaphragmatic dysfunction due to congenital CMV infection. In newborns with unexplained RDS, CMV infection-related diaphragmatic dysfunction is a potential underlying pathological mechanism.

Keywords: Congenital cytomegalovirus, diaphragmatic dysfunction, respiratory distress syndrome


How to cite this URL:
Gad YA, Khalaf M N, Sujay N. Congenital cytomegalovirus infection-related diaphragmatic dysfunction: Acase study. Hamdan Med J [Epub ahead of print] [cited 2019 Mar 18]. Available from: http://www.hamdanjournal.org/preprintarticle.asp?id=239178





  Introduction Top


Cytomegalovirus(CMV) is the most common congenital infection worldwide, and it is diverse in its clinical manifestations.[1] Despite the rarity of persistent diaphragmatic dysfunction in newborns, it is the cause of respiratory insufficiency in a number of newborns with congenital CMV infection.[2] In the 1970s, two case reports described infants with congenital CMV infection, respiratory failure and diaphragmatic dysfunction; death occurred shortly after birth in both cases.[3],[4] In 2010, three case reports described the same condition with long-term survival.[2] We report a newborn with congenital CMV infection who presented with severe persistent respiratory distress syndrome(RDS) associated with diaphragmatic dysfunction.


  Case Report Top


Ababy girlwas delivered by emergency caesarean section at the 39thweek of gestation owing to foetal distress, as evidenced by passage of fresh meconium-stained amniotic fluid and non-reactive cardiotocography, after an uncomplicated pregnancy.

Birth weight was 2535g(below the 10thcentile), length was 51cm(50thcentile), head circumference was 33cm(10thcentile), chest circumference was 29cm and abdominal circumference was 26cm. Apgar scores of 4, 6 and 8 were recorded at 1, 5 and 10min, respectively. Endotracheal intubation was performed in the delivery room owing to respiratory failure. Physical examination revealed decreased breath sounds below the nipple line and a scaphoid abdomen. The baby was admitted to a Neonatal Intensive Care Unit(NICU) for conventional ventilation. Chest radiography revealed low lung volume with bilateral elevated hemidiaphragm[Figure1], which was initially attributed to pulmonary hypoplasia.
Figure 1: Chest radiograph showing low lung volume during ventilation

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On day 2, with normal blood gases and a stable condition with minimal mechanical ventilation, the baby was weaned to high-flow nasal cannula(HFNC) oxygen at 5L/min and 50% FiO2. On day 5, reintubation occurred owing to laboured breathing, a rising oxygen requirement and hypercarbia in arterial blood gas(PaCO2 = 64.3mmHg).

Focussed physical examination results were unremarkable for age, except for mild hypotonia and the same low lung volume[Figure2] as revealed by previous radiography. Echocardiography showed a structurally normal heart, and there was no evidence of pulmonary hypertension. On day 10, there was apparent improvement and the baby was again weaned to HFNC oxygen at 3L/min and 40% FiO2.
Figure 2: Chest radiograph showing low lung volume during high-flow nasal cannula oxygen therapy

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Three days later, on day 13, the baby's oxygen requirements increased and breathing was increasingly laboured; this improved with the aid of nasal(biphasic) continuous positive airway pressure for approximately 48h. The baby was then successfully weaned to HFNC oxygen and subsequently to room air over the next 10days.

Orogastric feeding then commenced, and oral intake (standard infant formula) was gradually introduced and increased until full oral feeding. However, weight gain was less than expected.

While stabilising the baby's condition, first-line intravenous antibiotics were administered. On day 18, suspected diaphragmatic dysfunction was confirmed by fluoroscopy. On day 23, suspected congenital CMV infection was confirmed by diagnostic laboratory investigation. On day 27, oral treatment with valganciclovir(at a dose of 16mg/kg/day) commenced after detailed counselling and discussion with parents.

Laboratory and imaging findings

Thrombocytopenia developed gradually with a nadir platelet count on day 6 of 87×109/L(normal range: 150–350×109/L). CMV-specific immunoglobulin M(IgM) was elevated on day 18 at 566mg/dl(normal range<180mg/dl) and CMV viral load, measured by real-time polymerase chain reaction(PCR) assay, was high on day 23 at 22,000 copies/ml (normal range<1000 copies/ml), confirming congenital CMV infection. Chest fluoroscopy revealed increased vascular marking and that both lungs were well aerated; both diaphragms were high in position with sluggish movement. Cranial ultrasound performed at birth showed possible periventricular flaring, which, reviewed on day 7, was no longer present. Ophthalmological examination showed no evidence of chorioretinitis. Hearing screening revealed automated auditory brainstem response to be normal.

Outcome

Supplemental oxygen was no longer required by day 22. Oral valganciclovir was administered from day 27. After 5days of treatment(at day 32), the baby was vitally stable, with normal blood counts, except for mild intermittent tachypnoea. On day 33, sudden unexplained infant death occurred.


  Discussion Top


Although CMV pneumonitis in newborns is a well-known respiratory manifestation of CMV infection–,[5] CMV infection presenting with respiratory insufficiency associated with diaphragmatic dysfunction has rarely been reported and the actual incidence of the condition is unknown.[2],[3],[4],[5],[6]

There are only five previous cases of such comorbid presentation in the literature.[2],[3],[4],[6] Two cases were reported in the 1970s, but both babies died relatively soon after birth.[3] In 2010, three cases were described: two babies needed tracheostomy at around 6months to facilitate long-term ventilatory support and both survived beyond infancy, with persistent hypotonia and mechanical ventilatory support only during sleep. The third baby died at 11months with unexplained fatal cardiac arrest, which occurred following symptoms of upper respiratory infection.[2]

The pathogenesis of this condition is not clearly understood, with diaphragmatic hypoplasia a possible mechanism rather than phrenic nerve affection.[2],[3]

In this case, several factors contributed to our suspicion of diaphragmatic dysfunction as the underlying pathological mechanism: first, ongoing respiratory impairment, which responded markedly to positive pressure ventilation; and second, the radiological finding of persistently elevated bilateral hemidiaphragm, in addition to small lung volume. While the radiological findings were initially attributed to pulmonary hypoplasia, this explanation was negated as the lungs were well aerated with normal vascularity. Therefore, the possibility of diaphragmatic dysfunction was raised and confirmed by fluoroscopy.

Taking into consideration perinatal history and clinical findings–intrauterine growth restriction and thrombocytopenia–the aetiology was proposed to be a congenital infection rather than birth trauma and neuromuscular disorder.[7],[8] Thus, screening for congenital infection, particularly CMV and toxoplasma, revealed congenital CMV infection. In this case, CMV infection triggered RDS secondary to diaphragmatic dysfunction.

The collaborative work of the NICU team, including the cooperation of parents and specialists in radiology and paediatric infectious diseases, was essential to the diagnosis and management of this case.

The optimal therapeutic approach was considered. Given the available international evidence-based guidelines for congenital CMV infection, oral valganciclovir was administered.[9],[10],[11]


  Conclusion Top


This case report describes challenges in the diagnosis of congenital CMV infection and diaphragmatic dysfunction. In this case, there was a discernible relationship between CMV infection and diaphragmatic dysfunction.

Diagnostic investigation for a newborn presenting with unexplained RDS is recommended to include diaphragmatic fluoroscopy, CMV IgM assay and real-time PCR assay (based on history, clinical symptoms and laboratory findings), which should help to diagnose similar cases.

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.

Acknowledgement

The lead author wishes to send her gratitude to DrEhab Elzawawy, consultant paediatrician, Alexandria University, Egypt, and Dr.Yasser Amer, paediatrician and clinical practice guidelines methodologist, Quality Management Department, Research Chair for Evidence-Based Health Care and Knowledge Translation, King Saud University, Saudi Arabia, for their suggestions for this manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
DreherAM, AroraN, FowlerKB, NovakZ, BrittWJ, BoppanaSB, etal. Spectrum of disease and outcome in children with symptomatic congenital cytomegalovirus infection. JPediatr 2014;164:855-9.  Back to cited text no. 1
[PUBMED]    
2.
IzumiK, HokutoI, YamaguchiS, UezonoA, IkedaK, RiceL, etal. Diaphragm dysfunction with congenital cytomegalovirus infection. JPerinatol 2010;30:691-4.  Back to cited text no. 2
[PUBMED]    
3.
Garcia-PratsJA. Eventration of the Diaphragm in Infants; 2016. Available from: http://www.uptodate.com/contents/eventration-of-the-diaphragm-in-infants.[Last accessed on 2017Mar30].  Back to cited text no. 3
    
4.
WayneER, BurringtonJD, MyersDN, CottonE, BlockW. Letter: Bilateral eventration of the diaphragm in a neonate with congenital cytomegalic inclusion disease. JPediatr 1973;83:164-5.  Back to cited text no. 4
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5.
CocliteE, Di NataleC, NigroG. Congenital and perinatal cytomegalovirus lung infection. JMatern Fetal Neonatal Med 2013;26:1671-5.  Back to cited text no. 5
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6.
BecroftDM. Prenatal cytomegalovirus infection and muscular deficiency(eventration) of the diaphragm. JPediatr 1979;94:74-5.  Back to cited text no. 6
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7.
WuS, ZangN, ZhuJ, PanZ, WuC. Congenital diaphragmatic eventration in children: 12years' experience with 177cases in a single institution. JPediatr Surg 2015;50:1088-92.  Back to cited text no. 7
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8.
GriffinIJ. Diaphragmatic Paralysis in the Newborn; 2016. Available from: http://www.uptodate.com/contents/diaphragmatic-paralysis-in-the-newborn.[Last accessed on 2017Mar30].  Back to cited text no. 8
    
9.
KimberlinDW, BradyMT, JacksonMA, LongSS. Red Book: 2015 Report of the Committee on Infectious Diseases. 30thed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.  Back to cited text no. 9
    
10.
BuonsensoD, SerrantiD, GargiulloL, CeccarelliM, RannoO, ValentiniP, etal. Congenital cytomegalovirus infection: Current strategies and future perspectives. Eur Rev Med Pharmacol Sci 2012;16:919-35.  Back to cited text no. 10
    
11.
Demmler-HarrisonGJ. Congenital Cytomegalovirus Infection: Management and Outcome; 2016. Available from: http://www.uptodate.com/contents/congenital-cytomegalovirus-infection-management-and-outcome.[Last accessed on 2017Mar30].  Back to cited text no. 11
    

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Correspondence Address:
Yasmin A Gad,
Department of Neonatology, Zulekha Hospital, Sharjah
United Arab Emirates
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2227-2437.239178



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