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Gad, Khalaf, and Sujay: Congenital cytomegalovirus infection-related diaphragmatic dysfunction: a case study


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 presentation

A baby girl was delivered by emergency caesarean section at the 39th week of gestation owing to fetal distress, as evidenced by passage of fresh meconium-stained amniotic fluid and non-reactive cardiotocography, after an uncomplicated pregnancy.

Birth weight was 2535 g (below the 10th centile), length was 51 cm (50th centile), head circumference was 33 cm (10th centile), chest circumference was 29 cm and abdominal circumference was 26 cm. Apgar scores of 4, 6 and 8 were recorded at 1, 5 and 10 minutes 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 (Figure 1), which was initially attributed to pulmonary hypoplasia.


Chest radiograph showing low lung volume during ventilation.


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 5  l/min and 50% FiO2. On day 5, reintubation occurred owing to laboured breathing, a rising oxygen requirement and hypercarbia in arterial blood gas (PaCO2  =  64.3 mmHg).

Focused physical examination results were unremarkable for age, except for mild hypotonia and the same low lung volume (Figure 2) 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 3  l/min and 40% FiO2.


Chest radiograph showing low lung volume during HFNC oxygen therapy.


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 48 hours. The baby was then successfully weaned to HFNC oxygen and subsequently to room air over the next 10 days.

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 stabilizing 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 16 mg/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 566 mg/dl (normal range < 180 mg/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.


Supplemental oxygen was no longer required by day 22. Oral valganciclovir was administered from day 27. After 5 days 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.


Although CMV pneumonitis in newborns is a well-known respiratory manifestation of CMV infection,6 CMV infection presenting with respiratory insufficiency associated with diaphragmatic dysfunction has rarely been reported and the actual incidence of the condition is unknown.26

There are only five previous cases of such comorbid presentation in the literature.25 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 6 months 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 11 months 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.911


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.


The lead author wishes to send her gratitude to Dr Ehab 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.



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