Neonatal Meningitis David HarveyProfessor of Paediatrics and Neonatal MedicineFaculty of Medicine, Imperial CollegeHammersmith Hospital CampusLondon

Neonatal meningitis This lecture is based on the studies conducted and published by the team in the Karim Centre at Queen Charlotte's and Chelsea Hospital in London.

We are grateful for financial support provided by the Al-Fayed Charitable Foundation.

Causative organisms The organisms causing meningitis in young infants are different from those seen in older patients.

Escherichia coli was the leading cause but this has now been overtaken by the Group B beta-haemolytic streptococcus, particularly in industrialised countries.

A small number of cases of viral meningitis are also reported.

Incidence of neonatal meningitis Meningitis is most common in infants under one year age.

The incidence is even higher in the first month of postnatal life, in preterm babies, and in those of low birth weight.

Incidence (continued) In a two-year national study conducted in the UK in the middle 1980s, the incidence of meningitis from all causes was 0.32/1000 live births (bacterial meningitis 0.22/1000)1.

Our other study in the middle 1990s showed a similar incidence of 0.39/1000 (bacterial meningitis 0.21/1000)2.

Clinical features The signs of meningitis in very young infants may be very difficult to detect.

Characteristic features found in older patients, such as neck stiffness, do not occur.

General signs of illness, including apnoeic attacks, vomiting and lethargy are common and significant.

Clinical features (continued) Some features will indicate that there is an illness affecting the brain.

Thus convulsions, which may result from an illness of the brain, such as meningitis, or a metabolic disturbance, such as hypoglycaemia or hypocalcaemia, are an indication for lumbar puncture.

Studies The Karim Centre has studied two cohorts of babies with neonatal meningitis who were born in England and Wales in 1985 to 19871 and 1995 to 19962.

The first cohort was identified prospectively using a monthly reporting card sent by the Karim Centre to all consultant paediatricians.

Studies (continued) The second cohort (1995-96) was identified using the system set up by the British Paediatric Surveillance Unit (BPSU) at the Royal College of Paediatrics and Child Health.

All members and fellows of the College are sent a card monthly on which they can report uncommon conditions.

Survey details (1985-87) 566 consultant paediatricians were sent a reporting card every month for two years.

They were asked to notify the researchers if they had seen a case of neonatal or postnatal meningitis in the previous month. Clinical details were obtained from those who reported a case.

Survey details (1995-96) During an 18 month period from July 1995 to December 1996 monthly cards were sent by the BPSU to 1800 paediatricians, compliance rates for return of cards during the period were 94%.

Survey details In both studies further cases were identified from the Communicable Diseases Surveillance Centre (CDSC) and the Meningococcal Reference Laboratory in Manchester.

Death certificates were also obtained.

Cases of Neonatal Meningitis (1985-87) 423 cases were identified.

Of these 118 (28%) were caused by group B beta-haemolytic streptococci and 78 (18%) by E coli. Listeria monocytogenes was identified as the cause in 23 cases (5%).

Viral meningitis was reported in 16 cases (4%).

Cases of Neonatal Bacterial Meningitis (1996-97) 274 cases of neonatal meningitis were reported.

This revealed that again the Group B beta-haemolytic streptococcus (42%) and Escherichia coli (16%) were the commonest organisms. 7% of cases were caused by enteroviruses.

Mortality in 1980s Survey The overall mortality from meningitis was 19.8%, and it was 24% in bacterial meningitis.

Mortality in 1990s The mortality in the 1996-7 survey was lower than in 1985-87.

It was 6.6% compared with 19.8% in the earlier survey.

Eight of 69 babies with Group B streptococcal infection died (12%) and 4 of 26 babies infected with Escherichia coli (15%).

Antibiotic usage in 1980s To our surprise, in 1980s chloramphenicol was a commonly used antibiotic for neonatal meningitis.

It was reported in 48% of cases. Cefotaxime was used in 26% and gentimicin in 40% of cases in combination with ampicillin or penicillin.

Antibiotics in 1990s The pattern of antibiotics used has changed dramatically.

Chloramphenicol was used in only 1% of cases, whereas third-generation cephalosporins, notably cefotaxime, were used in 84%.

This may account for the improvement in mortality.

Additional Therapy Neonatal intensive care will be needed for these fragile infants.

Ultrasound examination of the brain is needed to detect the beginning of hydrocephalus.

The place of steroids needs further study.

The length of antibiotic therapy is usually 2 weeks, but 3 weeks for E coli.

Follow-up A five-year follow-up has been conducted by postal survey of the parents and family doctors of the 1985-87 cohort3.

This study showed that there was a ten-fold increase in the risk of severe or moderate disability in the children who suffered meningitis.

Hearing Loss The overall relative risk of sensorineural hearing loss in meningitis under one year was 22.8 (95% confidence intervals 7.22 to 72.1).

Although children with neonatal meningitis had an overall increase in hearing problems, sensorineural hearing loss was not increased in the neonatal group compared with meningitis later in infancy.

Conclusions Neonatal meningitis in industrialised countries is now usually caused by Group B streptococci.

It is difficult to detect early.

The incidence has not changed, but the mortality has decreased recently.

Developmental studies show that it is followed by an increase in disability.

Bibliography 1. de Louvois J, Blackbourn J, Hurley R, Harvey D. Infantile meningitis in England and Wales: a two year study. Arch Dis Childhood 1991; 66: 603-607.

2. Holt DE, Halket S, de Louvois J, Harvey D. Neonatal meningitis in England and Wales: 10 years on. Arch Dis Child Fetal Neonatal Ed 2001; 84: F85-F89.

3. Bedford H, de Louvois J, Halket S, Peckham C, Hurley R, Harvey D. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 2001; 323: 533-6

Acknowledgements Daphne Holt John de Louvois Sue Halket Helen Bedford Catherine Peckham Rosalinde Hurley