A newborn boy with fever and seizures

The mother of a six-day-old boy contacted the postnatal ward. The infant had been lethargic and uninterested in feeding since discharge, with a rectal temperature of 38.4 °C over the past 24 hours. He was therefore referred to the paediatric department. He was born at 39 weeks gestational age following induction due to reduced fetal activity on cardiotocography. The pregnancy had otherwise been uncomplicated. The infant's Apgar scores were 9, 9 and 9, with a birth weight of 3710 g, length 49.5 cm and head circumference 34.5 cm. His stay in the postnatal ward had been unremarkable, and the findings from the paediatric examination on the second day of life had been normal.

On admission, the infant appeared irritable and difficult to soothe. He woke with high-pitched crying. Rectal temperature was 38.4 °C, with other vital signs within the normal range. His skin was cool and peripherally cyanosed, with a capillary refill time of two seconds. The pharynx was erythematous with mildly enlarged tonsils, without exudate. His weight was 10 % below birth weight. The findings were normal for the rest of the clinical examination.

Further history revealed that the mother had experienced fever, headache and body aches in the days before and after childbirth. Urine and nasopharyngeal tests performed for respiratory viruses at the maternity ward were negative. The infant's older brother had been home from nursery with mild fever, cough and nasal discharge in the days immediately before and after mother and baby returned from the maternity ward.

Biochemical tests in the infant showed a CRP of 3.8 mg/L (reference < 5), white blood cell count 15.9 × 10⁹/L (9–30 × 10⁹/L), neutrophils 8.7 × 10⁹/L (3–25 × 10⁹/L) and monocytes 2.7 × 10⁹/L (0.1–2.0 × 10⁹/L). Blood cultures, serum, urine, nasopharyngeal and stool samples were sent for microbiological analysis. Lumbar puncture was attempted but unsuccessful.

Given the infant's age and the absence of a clear infectious focus, intravenous antibiotic therapy was initiated with ampicillin 50 mg/kg three times daily and gentamicin 6 mg/kg once daily. The infant was admitted to hospital for further investigation and observation while awaiting test results. During the hospital stay, he developed a fever, with a rectal temperature of 38.6 °C, which responded to paracetamol. He gradually became more lethargic, protested less and showed reduced responsiveness to needle pricks. The infant was exclusively breastfed and did not receive any additional fluid therapy.

After two days in the paediatric ward, the results of the nasopharyngeal, serum and stool samples were ready. PCR analysis of the nasopharyngeal specimen was negative for respiratory syncytial virus, influenza virus, SARS-CoV-2, metapneumovirus, rhinovirus, adenovirus, parainfluenza virus, enterovirus D68, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serum and stool samples were analysed using an in-house PCR method targeting enteroviruses and parechoviruses, and enterovirus was found in both specimens. The infant began to feed better, gained weight and his temperature decreased. As biochemical markers were consistent with a viral infection and there were no clear signs of meningitis, no further attempts at lumbar puncture were made, and antibiotic therapy was discontinued. The infant, now eight days old, was discharged with an open return arrangement to the paediatric emergency department should his general condition deteriorate or in the event of fever.

Two days later, the mother and her now ten-day-old son returned to the paediatric emergency department due to increasing fever and irritability. The infant had slept little, and rectal temperature was 39.0 °C. On examination, he was crying vigorously and exhibited motor agitation. Blood tests showed monocyte counts at the upper end of the reference range, with all other values unremarkable. Blood and urine cultures from the previous admission showed no bacterial growth. The infant was admitted without initiation of antibiotics, as the infection was still considered viral. The following morning, his fever had decreased to 36.6 °C, and the family was discharged with an open return if symptoms worsened.

The following evening, the mother and son returned to the paediatric emergency department. The infant had experienced repeated episodes of brief, symmetrical jerking of the arms and legs. He was admitted to the paediatric ward, where nurses observed multiple seizures. Initially, he had a series of seizures lasting 2–3 minutes each, with a few seconds in between. These later evolved into jerking episodes of 1–2 minutes' duration occurring approximately once per hour. The seizures were rapid, jerky and occurred while awake, with affected body parts varying from the head to one or more limbs. Transient drops in oxygen saturation were observed during the episodes, reaching a low of 74 % with central cyanosis. Clinical examination and vital signs, including temperature, were otherwise unremarkable.

Blood tests showed Hb 16.3 g/dL (14.0–22.0), leukocytes 12.8 × 10⁹/L, monocytes 2.3 × 10⁹/L, CRP 1.0 mg/L and glucose 3.8 mmol/L (2.8–4.5). A neurologist recommended lumbar puncture and amplitude-integrated electroencephalography (aEEG), which were performed in the paediatric intensive care unit. Analysis of the cerebrospinal fluid showed leukocytes 180 × 10⁶/L (0–30 × 10⁶/L), of which 99 % were mononuclear cells, total protein 3.37 g/L (0.20–0.80) and glucose 1.9 mmol/L. The cerebrospinal fluid was also sent for bacterial culture and PCR-based viral testing. In addition, a panel of tests was requested to evaluate for congenital metabolic, autoimmune and genetic conditions. Antiepileptic therapy with intravenous phenobarbital was initiated, first as a loading dose of 20 mg/kg, followed by 2.5 mg/kg twice daily. Intravenous treatment with ampicillin 50 mg/kg three times daily, gentamicin 6 mg/kg once daily and aciclovir 20 mg/kg three times daily was started simultaneously pending microbiological results.

Over the following days, the infant remained in hospital for observation and further investigation. aEEG showed series of epileptic activity, corresponding to the clinical seizures. The clinical seizure activity ceased after initiation of phenobarbital. Microbiological analysis of the cerebrospinal fluid showed enterovirus, but not herpes simplex virus, varicella zoster virus or parechovirus, and there was no bacterial growth. Antibiotic and antiviral therapy were discontinued. MRI of the head showed no pathology.

After five days in hospital, the now three-week-old infant was considered stable and was discharged. At discharge, the phenobarbital dose was adjusted to 4.6 mg/kg/day as a liquid formulation. At follow-up one month later, he had experienced no further seizures. Clinical examination and EEG were unremarkable, and the phenobarbital dose was reduced to 3.5 mg/kg/day. At the three-month follow-up, the infant was considered completely healthy, and phenobarbital was gradually tapered and discontinued. In the meantime, results from the reference laboratory for polio and enterovirus at the Norwegian Institute of Public Health confirmed that the enterovirus found in the infant was coxsackievirus B5. At the two-year follow-up, the child had experienced no further seizures and, based on history and clinical examination, demonstrated normal motor, language and social development.