Introduction

Top Abstract Introduction Participants and methods Results Discussion References

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. 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

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This follow up study is based on data from the 1717 children who survived an acute attack of meningitis between 1985 and 1987. 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. Information from general practitioners and parents was combined to provide a complete picture of each child's health.

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

	Results

Top Abstract Introduction Participants and methods Results Discussion References

Altogether, 1717 children survived an acute attack of meningitis. Information was 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.

Deaths
Of the 1717 children who survived the initial attack 32 later died. Two children who had otherwise been healthy died, one of septicaemic shock at age 4 years and the other of acute bronchiolitis at the age of 22 months. Sixteen children had had conditions consistent with the sequelae of meningitis. Fourteen had had conditions associated with extreme prematurity, congenital abnormalities (four had Down's syndrome), or non-related conditions such as lymphoblastic leukaemia. The cause of death was unknown for one child. An additional five children (one with Down's syndrome) were reported to have died at the time of the acute attack of meningitis.

Health and development at five years
The proportion of children with health and developmental problems is summarised in table 1 . The risk of problems was increased among children who had had meningitis, particularly the risk of having learning and neuromotor disabilities.

Learning and neuromotor disabilities
In 16 children learning difficulties were described as very severe; all of these children had had meningitis (1% of children in the meningitis group). Information on schooling was available for 90 children who had learning difficulties, and 70 were reported to have had special educational provision; 82 of the children with learning difficulties had had meningitis. Ten of the children who had had meningitis and who had learning difficulties also had congenital conditions associated with mental impairment: five had Down's syndrome, two had congenital mental impairment, two had dysmorphic features, and one had agenesis of the corpus callosum. Eighty four (5.3%) children who had had meningitis had severe neuromotor disabilities compared with two (0.1%) controls (²=69.3, P<0.001) (table 2). Cerebral palsy was the most common condition reported.

Seizure disorders
Regular anticonvulsant medication was taken by 53 (45.7%) of the 116 children who had seizure disorders and had had meningitis; a further 24 had discontinued treatment. In contrast, only 5 (13.5%) of the children with seizure disorders in the control group regularly took anticonvulsant medication.

Hearing impairment
The overall relative risk of sensorineural hearing loss was 22.8 (95% confidence interval 7.22 to 72.1), with 90 (5.6%) of the children who had had meningitis being affected; 29 (1.8%) had a severe or profound bilateral loss. Three children in the control group (0.2%) had mixed sensorineural-conductive loss. Middle ear problems were more prevalent among children who had had meningitis (272 children; 17.1%) than among controls (100 children; 7.2%) (²=67.22, P<0.001). However, 108 of 1399 (7.7%) parents of children who had had meningitis and 144 of 1180 (12.2%) parents of controls reported that their children's hearing had not been tested.

Visual and ocular problems
Six children were blind; they had all had meningitis. The most common condition reported was squint (116 children in the meningitis group (7.3%) v 31 controls (2.2%)). Parents reported that their children's vision had not been tested for 382 of 1414 (27%) children who had had meningitis and 276 of 1200 (23%) controls.

Speech and language problems
Fifty five children had severe communication problems or an absence of speech; all had had meningitis. A further 149 (9.4%) children in the meningitis group and 53 in the control group (3.8%) had speech or language delay, or both. In both groups children with speech and language problems also had hearing impairment, intellectual impairment, or both, (217/247 (87.8%) children with meningitis v 39/64 (60.9%) controls).

Behavioural problems
Behavioural problems were more frequently described by parents than by general practitioners. The most common problems among children who had had meningitis were severe temper tantrums (44 children; 2.8%), hyperactivity (17; 1.1%), and having poor concentration or being slow at school (42; 2.6%). Among the 32 children classed as having poor concentration or being slow at school there was no other apparent health problem. The behavioural problems reported for children in the control group were similar but less common.

Categories of disability
Table 3 classes the children by severity of disability. Children who had had meningitis had a 10-fold increase in the risk of having severe or moderate disabilities (relative risk 10.33, 95% confidence interval 6.6 to 16.0, P<0.001). Altogether, 617 of 1584 (38.9%) affected children had multiple conditions. They also had an increased risk of mild disorders, such as middle ear disease, squint, and behavioural problems (relative risk 1.47, 95% confidence interval 1.29 to 1.68, P<0.001).

Age at infection and organism of infection
Children who were infected as neonates had more health and developmental problems than those who had meningitis when they were older than one month (²=4.5, P=0.03). In each area of health and development evaluated, prevalence rates for problems were significantly higher for children who had had neonatal meningitis; this was particularly marked for neuromotor disabilities, seizure disorders, and learning difficulties (data not shown). Although children with neonatal meningitis had an overall increase in the risk of having hearing problems, there was no significant difference in the prevalence of sensorineural hearing loss between the age groups. Children with neonatal meningitis were significantly more likely to have moderate disabilities (² = 72.2, P<0.001), but the rate of severe disability was not significantly different between the groups. The rates of severe or moderate disability differed widely between children infected with different organisms (table 4). Although some of the differences may relate to the age at which the child contracted meningitis, infection with certain organisms was consistently associated with a poorer long term prognosis.

Effects of gestational age and birth weight
Since prematurity and low birth weight are likely to have independent effects on outcome, the relative risk of severe or moderate disability when birth weight and gestational age were controlled for were calculated. In these analyses children with pre-existing conditions, such as Down's syndrome or cerebral palsy, were excluded. A sevenfold increase in the risk of severe or moderate disability remained after birth weight and gestational age were controlled for.

	Discussion

Top Abstract Introduction Participants and methods Results Discussion References

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 disabilityespecially neuromotor disabilities and seizure disordersthan 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 4). 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

	Acknowledgments

We thank the parents and general practitioners who completed the questionnaires and the paediatricians for assisting in the follow up of the children. We thank David Dunn for statistical advice and Janet Masters for assistance in coding and entering the data.

	Footnotes

Funding: Action Research and the Fayed Charitable Foundation.

Competing interests: None declared.

The full version of this paper appears on the BMJ's website

	References

Top Abstract Introduction Participants and methods Results Discussion References

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(Accepted 8 March 2001)