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BMJ Case Rep. 2010; 2010: bcr0120102689.
Published online Oct 12, 2010. doi:  10.1136/bcr.01.2010.2689
PMCID: PMC3028444
Findings that shed new light on the possible pathogenesis of a disease or an adverse effect
Auditory neuropathy associated with postnatally acquired cytomegalovirus infection in a very preterm infant
W Baerts1 and H L M (Irma) van Straaten2
1Department of Neonatology, Utrecht University Hospital/Wilhelmina Children's Hospital, Utrecht, The Netherlands
2Department of Neonatology, Isala Clinics, Zwolle, The Netherlands
Correspondence to H L M van Straaten, h.l.m.van.straaten/at/isala.nl
Neurosensory hearing loss is a well-known complication of antenatally acquired cytomegalovirus (CMV) infection. We here report an infant who developed auditory neuropathy after a postnatally acquired CMV infection. Infection probably occurred through ingestion of infected breast milk. Following a cochlear implant, there is normal language perception and a mildly delayed language expression at age 4. We speculate that the long-term effects of perinatal CMV infections are more dependent on the postconceptional age at which infection occurs than on whether the infection occurs antenatally or postnatally. An early acquired neonatal CMV infection in very preterm infants may therefore have long-term neurological sequelae, including auditory deficits.
Cytomegalovirus (CMV) is the most common viral infection of the newborn. It is estimated that 0.2–2.0% of all newborn infants are born with congenital CMV infection, transmitted through their mothers. Antenatal viraemia causes placental infection which is then followed by viral dissemination to the fetus. Only 10–15% of congenitally infected infants are symptomatic at birth. Chances of symptomatic neonatal disease are increased when CMV infection occurs earlier in pregnancy.1 2 The infection may involve multiple organs resulting in intrauterine growth retardation, hepatosplenomegaly, hyperbilirubinaemia or pneumonia. Neurological manifestations depend on the time of infection during intrauterine development.
Typical neurological sequelae include microcephaly, periventricular calcifications, chorioretinitis, cognitive developmental delay, visual problems and epilepsy.2 Also, progressive neurosensory hearing loss (NS-HL) may develop even after the age of 2 years.35 Asymptomatic congenital CMV infection may be associated with similar sequelae, especially NS-HL.6 7 The virus was recently shown to have mutagenical effects in chromosome areas associated with sensorineural hearing impairment.8 Perinatal or early neonatal infection is much less common than congenital infection. It usually presents with less severe clinical manifestations in term babies and may not have any serious sequelae.2 The course of the disease is less clear for the very preterm baby, particularly for those born before 28 weeks gestation. In this group, early onset of viral shedding has been shown to be a significant risk factor for later neurological impairment, and transient hearing loss was reported in one paper.9 Auditory neuropathy (AN), a more centrally located type of NS-HL, has, to our knowledge, not been reported in postnatally acquired CMV. We report a very preterm infant with early postnatally acquired CMV infection who was diagnosed with AN shortly after term.
Our patient was born prematurely at 26 4/7 weeks with a birth weight of 1050 g as the first of dichorionic diamniotic twins. The early neonatal course was complicated by respiratory insufficiency, due to hyaline membrane disease, treated with surfactant and mechanical ventilation for 7 days. In addition, as a bacterial infection could not be ruled out, antibiotics were routinely administered. A transient circulatory insufficiency was treated with volume expansion. Hyperglycaemia was treated with insulin and mild hyperbilirubinaemia (maximum bilirubin level 250 μmol/l) was treated with phototherapy. Brain ultrasound showed a bilateral grade II intraventricular haemorrhage in the first days of life; a mild posthaemorrhagic ventricular dilatation resolved spontaneously. Recurrent anaemia was treated with several CMV-free erythrocyte top-up transfusions.
At 3 weeks of age, when the child was already respiratory stable, increasing signs of a pulmonary disease became evident. The diagnostic programme included a virological work-up, and CMV was cultured from the urine. CMV PCR diagnostics in the Guthrie card at day 3 was negative. Breast milk culture was initially negative, but a second test 6 weeks after birth was positive for CMV. Maternal IgG antibodies 1 week after birth were positive; IgM antibodies were negative. The relationship between the timing and results of the CMV diagnostics and the clinical course are presented in figure 1. Lung problems were treated with nasal positive airway pressure, supplemental oxygen and diuretics (a thiazide and an aldosterone antagonist) for a period of 4 weeks. No antiviral medication was prescribed.
Figure 1
Figure 1
CMV diagnostics in relation to clinical signs and postconceptional age.
Routine, automated, auditory brain response hearing screening failed around term age. Further audiological diagnostics at the corrected age of 6 weeks showed negative responses on the classic auditory brainstem response (ABR) on both sides, slightly lowered oto-acoustic emissions (OAEs) on the left side and normal OAEs on the right side. A normal tympanogram was recorded. These results are consistent with a diagnosis of hearing loss due to AN. The hearing level during observational audiometry at 1 year of age was 90 dB. At 3.5 years of age, the hearing level was 35–40 dB until 3000 Hz. No reaction occurred above 3000 HZ. Initially the child communicated only through sign language. At 2 years follow-up no signs of a generalised neurological disease were present. Except for a delay in the speechlanguage domain, there was normal neurodevelopment. During the intake procedure for a cochlear implant procedure, the CT scan showed no congenital malformation of the inner ear and direct stimulation of the acoustic nerve showed no response. At 4 years of age, there is normal language perception and a mildly delayed language expression.
The twin sister did not develop any clinical or laboratory sign of acquired early CMV infection.
Retrocochlear AN is a recently recognised type of sensorineural hearing loss that constitutes a separate entity of functional hearing loss. This disorder is also known as auditory dys-synchrony. More recently, the term auditory dys-sychrony disorder spectrum has been proposed.10 The diagnosis of AN is based on electrophysiological testing in which ABRs are absent and OAEs are present, reflecting auditory nerve dysfunction in the presence of normal cochlear outer hair cell function. Clinically, a wide spectrum of manifestations may result. Hearing loss varies from a very mild hearing impairment to almost total hearing loss. Most striking are problems with understanding speech in noisy environments.10 11
While antenatally acquired CMV is a well-known cause of hearing loss,37 postnatally acquired CMV has until now not been considered to be a major cause of hearing loss, even in premature infants.12 13 This case report presents an unusual course of a postnally acquired CMV infection in a very premature infant that was associated with AN. Clinically, the infection presented with a pneumonitis at a postconceptional age of 30 weeks in an otherwise stable patient.
There were signs of severe hearing loss at term which later proved to be caused by AN. Additional diagnostics did not show any other likely explanation for the occurrence of AN in this child. The early neonatal course was relatively unremarkable, with only mild respiratory problems, moderate hyperbilirubinaemia and mild transient posthaemorrhagic ventricular dilatation problems which are not usually associated with AN. Although bilirubin toxicity generally may be a cause of AN, in this patient the serum bilirubin did not reach values presently considered to be a cause of central nervous system damage in similar very preterm infants.14 No known ototoxic medication like aminoglycosides, vancomycine or furosemide had been administered. Congenital malformations of the inner ear were ruled out by CT. Genetic causes associated with abnormal electromechanical signal function in the inner ear seemed very unlikely as the child was of Northern European origin and there was no profound hearing loss.15 16 Finally, besides functional problems due to this isolated AN, no signs of a separate neurological disorder were present at follow-up. All things considered, we find it very likely that the AN in this child was the result of a postnatally acquired CMV infection.
In conclusion, we report the first case of AN after a postnatally acquired CMV infection in a very preterm baby of 26 weeks gestation. As this infection occurred before a postconceptual age of 30 weeks, we speculate that the sequelae of perinatal CMV infections are more dependent on the postconceptional age at which infection occurs than on whether an infection occurs antenatally or postnatally. The very preterm infant with early acquired CMV infection may, therefore, be at risk of developing neurological deficits, including auditory. Our finding presents a further argument for research into the early diagnosis and therapeutic management of perinatal CMV infection.
Footnotes
Competing interests None.
Patient consent Obtained.
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