Meningitis in infancy in England and Wales: follow up at age 5 years

Introduction

Children are most likely to get meningitis during their first year. Although it is widely acknowledged that the consequences of meningitis in infancy may be severe, there are few reliable data from large prospective studies that focus on the outcome of infection in infancy. None of these have been based on a national population.

In a meta-analysis of 19 prospective studies of the outcome of bacterial meningitis in 1602 children1 and a review of follow up reports of neonatal meningitis2 there were wide variations in the rates of adverse sequelae associated with infection by different organisms and also variations within groups of organisms. This variation could be explained partly by methodological factors including the retrospective identification of cases, small numbers of participants, the inclusion of children from a wide range of ages, differing lengths of follow up, differences in the proportion of infections caused by different organisms, and either the lack of a control group or the inclusion of inappropriate controls. Few studies have investigated the full range of sequelae associated with meningitis 3 4; most have focused on specific outcomes, notably cognitive function and hearing loss.5^–9

A prospective study of the incidence of meningitis in infancy in England and Wales was carried out between 1985 and 1987.10 In that study 1880 children with meningitis were identified; we present the results of a follow up investigation at 5 years of age of the children who survived the initial illness.

Participants and methods

This follow up study is based on data from the 1717 children who survived an acute attack of meningitis between 1985 and 1987. With the permission of the notifying paediatrician, each child's general practitioner was contacted to confirm that the child was alive and still registered with the practice. If the child was no longer registered at the same practice, the child's current general practitioner was traced. Information on children who had died was sought from hospital records and death certificates. Approval for the study was obtained from the research ethics committees of the collaborating centres.

Permission was sought from the child's general practitioner to approach the family health services authority for the name of another child on the general practitioner's list to act as a control; controls were matched by sex and age to the index child. For both cases and controls general practitioners were asked to complete a questionnaire detailing any health or developmental problems in the areas of neuromotor development, learning, vision, hearing, speech and language, or behaviour, and to indicate whether the child had a seizure disorder. Parents of children in both groups also completed a questionnaire about their child's health, development, and schooling. The questionnaires were specially designed for this study and contained both open ended and closed questions. Questionnaires were sent to parents and general practitioners.

Information from general practitioners and parents was combined to provide a complete picture of each child's health. Conditions reported either by the general practitioner or the parent were coded and double entered onto a database. When the evaluation of the severity of a condition differed between the two reports, the more severe condition was included. All information, including the type of schooling, was used to determine the degree of disability.

Children were allocated to one of four categories of disability based on a model developed by McIntyre et al.3 Children were classed as having a severe disability if they were unable to attend a mainstream school. This category included children with multiple problems such as severe neuromotor impairment, significant intellectual impairment, severe seizure disorders, and severe visual or auditory impairment.

Children were classed as having a moderate disability if their disability impaired their functioning but was not associated with severe intellectual or developmental impairment. Children in this category attended mainstream schools with or without additional support. This category included children with mild neuromotor disabilities, intellectual impairment, moderate sensorineural hearing loss, mild or moderate visual impairment, epilepsy that was controlled with treatment, and hydrocephalus without complications.

Children were classed as having mild disorders if they had a condition that is prevalent among children of the same age but is not typically associated with meningitis. This category included children with middle ear disease, squint, febrile convulsions, and behavioural problems.

Children were classed as having no disability if there was no evidence of developmental problems, however, conditions such as asthma and eczema were included in this category.

Results

Altogether, 1717 children survived an acute attack of meningitis. Thirty three children could not be traced and 20 had emigrated, leaving 1664 possible participants. Altogether, 1539 of 1631 (94.3%) general practitioners caring for children who had had meningitis and 1423 of 1543 (92.2%) parents of these children responded to questionnaires. In the control group 1320 of 1485 (88.8%) general practitioners and 1203 of 1400 (85.9%) parents responded. Information was thus available from general practitioners or parents, or both, for 1584 (92.2%) of children who survived an acute attack of meningitis and for 1391 of 1485 (93.6%) controls.

Discussion

This study shows that meningitis in infancy has serious consequences. Two per cent of children who survived the acute attack died before the age of 5 years. Among the survivors there was a 10-fold increase in the risk of severe or moderate disability compared with the control group. Neonatal meningitis was associated with a higher frequency of disability—especially neuromotor disabilities and seizure disorders—than meningitis after one month of age; however, there was no difference in the prevalence of sensorineural hearing loss between the groups. Infection with Streptococcus pneumoniae was associated with a higher rate of disability than infection with Haemophilus influenzae and Neisseria meningitidis. This is consistent with the rates reported by Baraff et al and other prospective investigations, although their rates were not specific to infants. 1 3 4 In this national cohort, severe disability was significantly more common in infants with meningitis associated with Group B streptococcus than with Escherichia coli. The highest rates of severe disability occurred among children whose meningitis was associated with Gram positive and Gram negative organisms classed as “other” (table 5). Our finding that 56% of infants with meningitis associated with Gram negative bacteria had severe or moderate disability is comparable with the 69% reported from a 20 year (1969-89) study in the United States.11

Although meningitis is more common during the first year of life than at any other age, it remains relatively uncommon. Because of the difficulty in finding adequate numbers of children in specific age groups for studies, reports of outcomes have relied on retrospective investigations, often done over many years, or on data from children referred to specialist centres, which by definition attract the more serious cases. As a result, there are few reliable estimates of the risk of long term disability associated with meningitis, particularly during the first year of life and during the neonatal period.2 The findings in this paper, based on follow up at five years of age of children enrolled in a national prospective study of meningitis in infancy, provide a complete picture of the range of problems experienced by children from England and Wales who have had meningitis in infancy.10

The objective of this study was to describe the effects of meningitis that could have an important impact on a child's life. However, subtle deficits, such as middle ear disease, squint, and behavioural problems, were also found to be more common among children who had had meningitis; this has been reported elsewhere.4 The higher rates of these conditions reported among the children who had had meningitis may reflect parental anxiety or the fact that closer attention is being paid to these children; thus, these higher rates need confirmation. This would require detailed investigation using standardised procedures to examine both children who have had and children who have not had meningitis. Although not as devastating as more disabling conditions, these are important problems that may adversely affect a child's wellbeing.

This study confirms the increased risk of hearing and visual problems among children who have had meningitis: many parents reported that their children's hearing and vision had not been tested. This lack of testing for hearing problems has been reported previously for children who have had meningitis.12^–14 Units that treat children with meningitis should ensure that all survivors have their hearing and vision checked, even if they are asymptomatic.

The 1985 study found that 50% of neonates and 84% of infants were treated with chloramphenicol, usually in combination with either ampicillin or penicillin.10 Third generation cephalosporins were used to treat 46% of neonates but only 14% of post-neonatal infants.10 Treatment practice in the United Kingdom has changed since the earlier study: the majority of neonates now receive third generation cephalosporins and few receive chloramphenicol.15

These findings not only provide information on the consequences of meningitis in infancy to assist health professionals in counselling parents but also provide background information for determining the effectiveness of new treatments and the need for preventive measures.