Parechovirus infection as a cause of necrotising enterocolitis in a premature neonate

Abstract

Parechovirus is becoming increasingly recognised as a cause of morbidity in the neonatal population. It is widely known to cause sepsis, encephalitis and myocarditis. We report a case of parechovirus as a possible cause of necrotising enterocolitis in a premature neonate. The infant, who was born at 28 weeks’ gestation, deteriorated at 1 month of life with fever and abdominal distension and had evidence of intramural bowel gas on imaging. Parechovirus was subsequently isolated from naso-oropharyngeal and rectal swabs, and he was managed medically with antibiotics and cessation of enteral feeds.

Background

Clinical presentation of parechovirus in neonates can range from mild gastroenteritis to sepsis and meningoencephalitis. Necrotising enterocolitis (NEC) in premature neonates usually occurs in the context of an immature gastrointestinal tract and a disruption of the normal intestinal microbiome with increased growth of pathogenic bacteria, with a subsequent inflammatory response.¹ These infants typically present with abdominal signs initially, followed by temperature instability and cardiorespiratory compromise and mount an inflammatory response visible in biochemical markers.¹ Parechovirus infection has been reported to cause NEC in neonates, often with atypical presentations and laboratory findings. This case highlights parechovirus infection as a possible cause of abdominal distension and NEC in neonates. Identifying parechovirus as an aetiology for NEC has significant implications for hospital infection control, as it has the potential to spread rapidly within a neonatal intensive care unit (NICU).²

Case presentation

An infant, born at 28 weeks’ gestation, deteriorated on day 30 of life with fever, abdominal distension and increasing apnoeic episodes. He underwent a full septic workup, which showed parechovirus on a swab of the naso-oropharynx and rectum and had an abdominal X-ray concerning for NEC.

The mother received no antenatal care during the pregnancy, and he was estimated to be 28 weeks’ gestation, with a birth weight of 1112 g. His gestation was based on an ultrasound on the day of delivery. He had initially been intubated in the context of respiratory distress syndrome, receiving a dose of endotracheal surfactant and was extubated to continuous positive airway pressure support on day 4 of life. He had poor cardiac contractility initially that required inotropic support until day 3. From day 15, he had been stable on high flow nasal prong support. He was fed expressed breast milk, and the volume was graded up slowly by 20 mL/kg/day from day 13. Prior to this, he was receiving small volume trophic feeds while milk supply was established. Full enteral feeds were achieved on day 18, with fortifier introduced on day 19. His main issues had been feeding intolerance, with concerns about abdominal distension and vomiting. In the 24 hours prior to the development of fever, he had had more frequent episodes of apnoea with bradycardia and desaturation and larger volume nasogastric aspirates were noted.

On day 30 of life, he became febrile to 38.2°C with associated tachycardia and tachypnoea. He had a normal neurological examination. A septic workup was performed, including cerebrospinal fluid (CSF) culture and viral studies. A naso-oropharyngeal and rectal swab was taken for enterovirus and parechovirus PCR. An abdominal X-ray showed moderate gaseous distension (figure 1) and he was started on intravenous flucloxacillin and gentamicin. The following day he had worsening abdominal distension and developed left-sided abdominal tenderness, thus metronidazole was added for treatment of NEC. A repeat abdominal X-ray, reported by the paediatric radiologist, showed intramural bowel gas (figure 2) and the infant was medically managed with 7 days of antibiotics and bowel rest. The naso-oropharyngeal and rectal swab subsequently returned a positive result for parechovirus. Other cultures, including CSF and blood, were negative. In consultation with the hospital infection prevention team, he was isolated with droplet and contact precautions until 3 weeks after his deterioration. None of his family members were unwell at the time, and no other infants in the NICU displayed any symptoms suggestive of parechovirus infection.

Figure 1.

Chest and abdominal X-ray on day 1 of illness.

Figure 2.

Abdominal X-ray on day 2 of illness with arrows demonstrating areas of intramural bowel gas.

Investigations

Inflammatory markers were benign, with a normal immature-to-total neutrophil ratio and a C reactive protein of <1 mg/L initially, and 6 mg/L when repeated 24 hours later. Haemoglobin was 76 g/L and thus a transfusion of packed red blood cells was given on day 2 of the illness.

The blood culture had no growth. CSF had 2×10⁶/L white cells and bacterial culture was negative. Viral PCR of the CSF for herpes simplex virus, enterovirus and parechovirus were also negative. Naso-oropharyngeal and rectal swabs for parechovirus PCR were positive and negative for enterovirus.

Outcome and follow-up

Chest and abdominal X-ray initially showed moderate bowel distension (figure 1). Repeat abdominal X-ray the following day showed intramural bowel gas (figure 2).

The infant was medically treated for NEC, with 7 days of bowel rest and intravenous antibiotics. He clinically improved in the first 48 hours of treatment, with less frequent episodes of apnoea and desaturation, no further temperature instability and improved abdominal distension and tenderness. Following treatment, enteral feeds were reintroduced without issue.

Discussion

Parechovirus (HPeV) belongs to the Picornaviridae family, and is a non-enveloped single-stranded RNA virus.³ There are 16 different human subtypes, with HPeV 1–3 responsible for the majority of morbidity in the neonatal and paediatric populations.⁴ The spectrum of clinical presentations of parechovirus infection in the neonatal period can include gastroenteritis, sepsis, encephalitis and myocarditis.^4–7 HPeV encephalitis is associated with gliosis and white matter loss, with subsequent neurodevelopmental implications.⁸

This case highlights parechovirus infection as a possible aetiological agent in neonates with NEC. This infant had not had perinatal asphyxia, had been given probiotics and with a slow introduction of breast milk feeds, all of which lowered his risk of NEC.¹ He presented at a later age than is commonly expected for infants born at 28weeks’ gestation to develop NEC.⁹ In addition, abdominal signs are usually the presenting feature in these infants, yet fever and tachycardia preceded abdominal tenderness and the development of intramural bowel gas in this case. Also in keeping with parechovirus being the cause of this episode of NEC was the lack of biochemical rise in his inflammatory markers.

There are only a few isolated cases reported of neonates with HPeV infection presenting with abdominal distension and NEC. An outbreak of HPeV in a NICU resulted in 12 infants having diarrhoea, seven of whom developed bloody stools and radiographic signs of NEC.² Sainato et al discussed a 7-week-old infant presenting with severe parechovirus infection, requiring ventilatory and inotropic support. There was also significant abdominal distension, and the infant had an exploratory laparotomy that demonstrated thickened hyperaemic transverse colon consistent with NEC.¹⁰ Bangalore et al described eight infants with HPeV infection, five of whom were noted to have abdominal distension. One of these infants had an exploratory laparotomy due to concerns about NEC, although the intraoperative findings were normal.¹¹

Furthermore, a case report from Japan demonstrated that HPeV infection in neonates can also present in a similar fashion to Hirschprung’s enterocolitis. The infant in this report presented at 6 weeks of age with sepsis and abdominal distension, requiring ventilatory and inotropic support. Imaging showed significant colon dilatation without gas in the rectum, although a rectal mucosal biopsy was negative for Hirschprung’s disease and parechovirus was subsequently isolated from serum.¹²

Our case highlights that parechovirus infection is worth including as a differential in neonates presenting with a septic deterioration and abdominal distension. Consideration should be given to testing neonates as part of a septic workup, as the isolation of parechovirus can have significant implications for a NICU. Parechovirus infection is a cause of significant mortality and morbidity in the neonatal population, with sepsis, myocarditis and encephalitis all well-described presentations of the virus. Thus, there may be a benefit to identifying and isolating infants with parechovirus within a NICU to minimise transmission to other neonates. Further work to determine the role of parechovirus in NEC pathology could help NICUs design appropriate prevention strategies.

Learning points.

• Parechovirus infection can be associated with necrotising enterocolitis (NEC) in neonates.

• Consideration should be given to including parechovirus PCR swabs in the septic workup of febrile neonates.

• As parechovirus infections can spread within a neonatal intensive care unit causing significant mortality and morbidity, isolating HPeV as a cause of NEC has significant hospital infection control implications.