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The risk factors used as entry criteria to a service follow-up clinic for a group of neonatal intensive care unit graduates over a 10-year period were compared with neurodevelopmental outcome at one year corrected age. Although most of the individual risk factors did not show significance, two markers associated with the risk factors did: severe encephalopathy and abnormal cranial ultrasound. Of the patients who came for a year, 46% were detected as being abnormal. One-third of the abnormal children weighed more than 1500 g.
Les facteurs de risque utilisés comme critères d’entrée dans une clinique de suivi pour un groupe d’enfants provenant d’une unité de soins intensifs néonatals sur une période de dix ans ont été comparés à l’issue neurodéveloppementale à un an d’âge corrigé. Bien que la plupart des facteurs de risque individuels se soient révélés non significatifs, deux marqueurs associés à ces facteurs de risque l’étaient, soit une grave encéphalopathie et une échographie crânienne anormale. Sur les patients qui se sont présentés pendant un an, 46 % ont été décelés comme anormaux. Un tiers de ces enfants anormaux pesait plus de 1 500 g à la naissance.
In 1987, Taeusch and Ware (1), in their chapter entitled “Mechanics of follow-up clinics”, justified the use of ‘follow-up clinics’ as a coordinating centre for future medical appointments, a preventive strategy clinic, a primary physician support service and a place for developmental follow-up including hearing screening. As well, they see these clinics as educating those who do neonatal intensive care about long term outcome, and as training centres for house staff and nurses (1).
Their entry criteria, “those at highest risk”, specified those children with one of the following criteria: those who weighed under 1250 g, those with specific neurological problems including hypoxic-ischemic encephalopathy, abnormal cranial ultrasounds and hearing or visual problems, those with complex sociofamilial situations, and those with chronic lung disease.
In research studies completed on perinatal risk factors and neurodevelopmental outcome, many separate risk factors have been shown to be independently associated with abnormal neurodevelopmental outcome. These include fetal asphyxia (2), neonatal ventilation, (3), hypoxemia, hypotension (4), neonatal encephalopathy (5), hypocarbia (6) and maternal drug use (7).
The Canadian experience in service follow-up clinics seems to be centre-specific, with all but one centre using prematurity as the common entry criterion, whether prematurity is defined by birth weight (defined as less than 1500 g in some and less than 801 g in one) or gestational age (defined as younger than 29 weeks). Although the majority of children with cerebral palsy were term at birth, the likelihood of a premature infant younger than 32 weeks having cerebral palsy is higher, and so this association factor is used to determine entry into follow-up clinics, rather than specific risk factors. Some centres include neurological criteria, and one centre looks at those who required respiratory care for more than two weeks (unpublished data).
Despite the guidelines for audit purposes listed in the Seventh Canadian Ross Conference of 1987 (8), there seem to be no uniform entry criteria or standardized outcome measures used by the various follow-up clinics in Canada. There are plans for a Canadian national neonatal follow-up study to be conducted.
This paper is an account of one centre’s 10-year experience in a service-oriented follow-up clinic. As entry criteria the centre used not only the association factor of birth weight, but also factors that are known to act as mechanisms for neurodevelopmental consequences (fetal asphyxia, ventilation for more than 24 h, severe sepsis and maternal drug use) and factors that are markers for later neurological sequelae (abnormal cranial ultrasounds and neonatal encephalopathy).
All children (n=633) born between from April 1, 1986 to March 31, 1995, who were graduates of the Kingston General Hospital NICU, who fulfilled the following entry criteria and who resided within the normal catchment area of the Kingston General Hospital NICU (within an approximately 100 km radius of Kingston) were offered follow-up appointments at the Special Infant Clinic of the Hotel Dieu Hospital.
Entry criterion was one of: weight less than 1500 g at birth; ventilation for more than 24 h; septicemia or meningitis; a cord artery buffer base less than 30 mmol/L; seizures; cranial ultrasounds that showed ventricular dilation or a parenchymal lesion; or a mother who took street drugs such as cocaine or heroin.
Children were identified as Special Infant Clinic children before discharge from the NICU, and the parents went home with an appointment for the child to come to clinic at six weeks corrected age. At the time of NICU discharge, computer sheets listing detailed maternal, labour and delivery history, and NICU care of the neonate were completed. Eight children had no weight determined at birth.
Enrolled children were assessed at six weeks and three, six, nine, 12, 18, 24 and 30 months of corrected age or sooner if medically indicated. They were seen by a physiotherapist or occupational therapist who assessed development, tone and posture, a physician with interests in developmental paediatrics, and a social worker. Nutritional advice was available from a dietician if requested. All children had a follow-up cranial ultrasound within the first three months of life.
If developmental delay was suspected, intervention services such as specific exercises to promote neurodevelopment were taught to the mother, or an infant stimulation worker in the home was arranged. Reassessment of the child was completed in clinic. If a diagnosis of cerebral palsy or significant developmental delay was confirmed, the child was referred to the Child Development Centre of the Hotel Dieu Hospital or another appropriate agency nearer to his or her home for continuing care.
At each visit, outcome notes were filled out. Included in outcome were growth parameters, social circumstances, interventions used, physical signs and neurodevelopmental status.
The entry criteria that enrolled children who were seen to 11 or 12 months of corrected age were studied in relation to neurodevelopmental outcome (classified as normal or abnormal) using χ2 analysis. P<0.05 was considered significant.
Six hundred and thirty-three children were enrolled in the study, and 324 were followed to age 11 or 12 months. One hundred and forty-eight were considered abnormal at one year (46%). Forty-eight of the abnormal children weighed more than 1500 g at birth. One hundred and twenty-two children did not keep their first appointment and 187 who were deemed normal at their last visit dropped out before 11 months corrected age.
Individual entry criteria were studied to determine significance (Table 1). Significance was found for severe encephalopathy and abnormal cranial ultrasounds. There were not significant numbers of children with meningitis or whose mothers took cocaine to permit analysis of these criteria.
The relationship of two or more entry criteria were studied to determine whether there was a change in the significance, ie, birth weight and ultrasound, were compared with the results from each individual criterion separately. The significant relationships between multiple criteria are shown in Tables 2,,33.
The value of having specific entry criteria in neurodevelopmental follow-up clinics instead of only enrolling children under a certain birth weight needs to be addressed by all physicians who enrol children in NICU follow-up clinics.
Because prematurity is associated with increased incidence of specific neonatal problems, there will be hypotension, hypocarbia, hypoxemia or infections in the NICU environment. Term infants are admitted to the NICU with perinatal problems such as fetal asphyxia or infection. Children with these problems have been shown to be at risk of neurodevelopmental damage in research studies. It seems reasonable, therefore, to take research data proven to have prognostic significance and apply these data clinically.
The question this paper endeavours to answer is: “Can the factors shown in research studies to be predictive of later adverse neurodevelopmental outcome translate into deciding which children need to be followed in a follow-up service clinic?”
We start with the caveat that because many NICU graduates had more than one risk factor in the NICU, it is probably simplistic to presume one can isolate one specific entry risk factor using χ2 analysis and directly link that individual criterion to later neurodevelopmental damage. A more sophisticated method of statistical analysis, such as multivariate regression analysis, needs to be applied. As well, the nature of the selection process in a service clinic setting requires that the analysis compares high risk children with each other, rather than with a control population without risk factors. We were unable to show statistically the relationship between an individual risk mechanism and later neurodevelopmental damage, although the high incidence of abnormality detected (46%) in our clinic using these entry criteria suggests their usefulness.
Nor were we able to show statistically a relationship between the association factor of birth weight and later neurodevelopmental damage, in that infants of very low birth weight were comparable to adverse outcome with our high risk infants weighing more than 1500 g.
However, looking at this population for evidence of acquired brain damage secondary to risk factors, two markers, moderate or severe encephalopathy and abnormal cranial ultrasound results (more than intraventricular hemorrhage), were highly prognostic of neurodevelopmental damage.
Using all entry criteria, neurodevelopmental problems were detected in 148 of 324 children enrolled to one year of corrected age, an incidence of 46%. If only a birth weight of less than 1500 g alone was used, 48 or one-third of all neurodevelopmentally abnormal children would have been missed.
It is our belief, therefore, that specific entry criteria shown to be associated with adverse neurodevelopmental outcome are of more value than using birth weight alone as entry criteria for follow-up purposes.
The purpose of our Special Infant Clinic is to provide support for the primary care physicians looking after children in the community, provide reassurance to parents of NICU graduates and provide early referral for children with neurodevelopmental problems. (Ninety-five per cent of all the children referred to our paediatric rehabilitation centre with cerebral palsy come from this clinic [personal communication]. Because the paediatric rehabilitation does not follow all children from the NICU population this clinic does not serve as an audit of the NICU care.)
NICU care is constantly evolving; during the 10-year period covered by this study refinements in ventilator management, blood pressure control, surfactant use, increasingly sophisticated ultrasound probes and better gas monitoring of infants have occurred. However, when we analyzed the data using two successive five-year periods, there was no difference shown between the two time periods in the incidence of neurodevelopmental adverse outcome.
This study reflects the outcome of NICU care in a selected population during a 10-year period. Using specific entry criteria that reflect the individual characteristics of an NICU stay is of more value than using birth weight alone to determine neurodevelopmental outcome.