Neurological assessment at five years of age in infants born preterm

AIM: To evaluate the agreement between Touwen's neurological examination and a derived simplified one, created to be applied at the age of 5 y to infants born preterm. METHODS: 185 children born at a gestational age (GA) of <33 wk and/or with a birthweight <1501 g, free of cerebral palsy, underwent Touwen's neurological examination at a mean age of 5 y and 8 mo (5-6.5 y). One-hundred and seventy had a full examination and were included into the study. They were born at a mean GA of 30 wk (range 24-35 wk) with a mean birthweight of 1250 g (range 600-2690 g). A simplified examination, based on the clinical experience of two of the authors, was created a priori. The data were reviewed retrospectively and the concordance between the two forms was assessed. The reviewers were blinded to the original categorization from the long form. RESULTS: On the basis of the original Touwen's neurological examination, the 170 children were classified into 122 with a normal neurological examination, 41 with grade 1 minor neurological dysfunction (MND) and 7 with grade 2 MND, giving 28% of the cohort with MND. The concordance between the two forms was excellent, with an agreement in 169 out of 170 subjects. None of the infants with the most complex form of MND was misclassified. CONCLUSION: The simplicity of this examination could allow its diffusion and its use in follow-up programmes. It could improve the quality of routinely collected follow-up data of preterm neonates.     

Physical growth and neurodevelopmental outcome of nonhandicapped low-risk children born preterm

BACKGROUND: Outcome studies on the effects of prematurity are increasingly restricted to extremely immature infants with birth weight below 1000 g or gestational age below 26 weeks. In contrast, studies comprising low-risk preterm infants are rare. AIM: To examine growth and neurodevelopmental outcome, 70 low-risk low birth weight (LBW) children without neurological impairment were followed from birth to 7 years of age. At 7 years of age, LBW children were compared to a matched control group born at term. METHODS: Postnatal growth was measured at 20 months in the LBW group and at 7 years in LBW and control children. At 20 months, the LBW group was assessed with the Griffiths Scales. At 7 years, LBW and control children were assessed with a neuropsychological test battery comprising tests for language, visual-perceptual, visual-motor, fine and gross motor abilities. RESULTS: At 7 years of age, the frequency of children with low (3rd-9th percentile) or subnormal (<3rd percentile) growth parameters was increased in the LBW group. The Mean Griffiths Developmental Quotient (DQ) of the preterm group was normal (102.3+/-8.4), and there were only two results below DQ 85. There was no difference between 49 children appropriate for gestational age and 21 small for gestational age (SGA) children. At 7 years of age, reduced mean test results in the range of -0.5 SDS were observed for language and visual-motor abilities in the preterm group. This was due to an increased frequency of LBW children with moderately (SDS -1.0 to -2.0 SDS) subnormal test results. Even for the slightly LBW group (2000 to 2499 g), poorer language abilities were confirmed. CONCLUSION: All LBW infants, including low-risk populations, should be included in a follow-up program in order to detect deficits early in life and begin treatment before school entry.     

Ophthalmic impairment at 7 years of age in children born very preterm

AIMS: To determine the prevalence of ophthalmic impairments in very preterm compared with term infants, the relation between impairments and cerebral ultrasound appearances and retinopathy, and the correlation with visual perception and motor and cognitive measures. SUBJECTS: 279 children at 7 years of age born before 32 weeks gestation within Liverpool during 1991-92 and attending mainstream schools, and 210 term controls. METHODS: Visual acuity was assessed by Snellen chart, and strabismus by the cover test. Stereopsis was determined using the TNO random dot test, and contrast sensitivity using the Cambridge low contrast gratings. Visual and motor abilities were assessed using the Developmental test of motor integration (VMI) and the Movement ABC. Intelligence was measured with the Wechsler intelligence scale for children UK. Perinatal cranial ultrasound and retinopathy data were extracted from clinical records. RESULTS: Children born preterm were significantly more likely to wear glasses, to have poor visual acuity, reduced stereopsis, and strabismus than term controls, but they showed no significant decrease in contrast sensitivity. Ophthalmic impairments were significantly related to poorer scores on the VMI, Movement ABC, and Wechsler IQ tests, but were not significantly related to neonatal cranial ultrasound appearances. Stage 3 retinopathy was related to poorer subsequent acuity. CONCLUSIONS: Children born very preterm and without major neurodevelopmental sequelae have an increased prevalence of ophthalmic impairments at primary school age which are associated with visual perceptional, motor, and cognitive defects. The cause may be a generalised abnormality of cortical development rather than perinatally acquired focal lesions of the brain.     

Hyperbilirubinemia in preterm infants and neurodevelopmental outcome at 2 years of age: results of a national collaborative survey

As part of a prospective national survey of preterm and small for gestational age infants in the Netherlands, the relationship between maximal serum total bilirubin concentration in the neonatal period and neurodevelopmental outcome at the corrected age of 2 years was studied. Initially, 1,338 infants with a gestational age of less than 32 completed weeks and/or a birth weight of less than 1,500 g were enrolled in the study; 146 were subsequently excluded because of congenital malformations and 361 died during the study period. At the corrected age of 2 years, 831 children were available for follow-up. Children with minor and major handicaps had significantly greater maximal serum total bilirubin concentrations than children with a normal neurodevelopmental outcome (P = .02). A consistent increase in prevalence of handicaps was found for each 50-mumol/L (2.9 mg/dL) increase of maximal serum total bilirubin concentration. The handicaps consisted mainly of cerebral palsy. Logistic regression analysis involving seven suspected confounding factors (gestational age, birth weight, seizures, intracranial hemorrhage, respiratory distress syndrome, ventriculomegaly, and bronchopulmonary dysplasia) revealed that the odds ratio was 1.3. This indicates that, on a multiplicative scale, the risk of a handicap increased by 30% for each 50-mumol/L (2.9 mg/dL) increase of maximal serum total bilirubin concentration (P = .02). Further analysis treated bilirubin as a categorized exposure. A striking systematic increase was found, suggesting a causal relationship between maximal serum total bilirubin concentration and neurodevelopmental outcome.     

Comparison of abilities of preterm and maturely born children at 5 years of age

This study investigated whether the development of 5 year old preterm born children was appropriate for age and equivalent to or different from their peers who were full term at birth.
At the adjusted age of 5 years, the development of 106 children born 5 or more weeks before term was compared with the development of 103 children who were born at term. This latter group of children were matched to the preterm group in sex, year of birth, birthplace, race and residential location. No cerebral palsy children were included in either subject group.
The results indicated a significant difference between the two groups. Factors distinguishing the preterm children from their full term peers included small involuntary hand movements, less competent gross motor ability, poorer verbal performance and more variability in behaviour, postural response and balance. A higher than average incidence of minor motor, speech, behaviour and learning problems in early school years is probable.     

Comparison of abilities of preterm and maturely born children at 5 years of age

This study investigated whether the development of 5 year old preterm born children was appropriate for age and equivalent to or different from their peers who were full term at birth. At the adjusted age of 5 years, the development of 106 children born 5 or more weeks before term was compared with the development of 103 children who were born at term. This latter group of children were matched to the preterm group in sex, year of birth, birthplace, race and residential location. No cerebral palsy children were included in either subject group. The results indicated a significant difference between the two groups. Factors distinguishing the preterm children from their full term peers included small involuntary hand movements, less competent gross motor ability, poorer verbal performance and more variability in behaviour, postural response and balance. A higher than average incidence of minor motor, speech, behaviour and learning problems in early school years is probable.     

Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia

OBJECTIVE: To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia (BPD), compared with a preterm control group of children. METHODS: Seventy preterm infants with BPD and 61 birth weight matched controls were prospectively followed-up to school-age. The Weschler Intelligence Scale for Children - III (WISC), the Wide Range Achievement Test (WRAT) and the Developmental Test of Visual Motor Integration (VMI) were administered. The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables. RESULTS: The children in the BPD group performed less well on the Full Scale IQ (mean 86.7 vs 93.5; 95% CI, 1.9-11.7), Verbal IQ (mean 87.1 vs 94.1; 95% CI, 2.0-12.0) and the Performance IQ (mean 88.6 vs 95.2; 95% CI, 2.0-11.2) of the WISC, the reading component of the WRAT (mean 93.8 vs 98.9; 95% CI, 0.3-9.8) and the VMI (mean 88.9 vs 93.3; 95%, CI 1.1-7.8). Despite controlling for social and biological variables, statistical differences persisted for Full Scale and Verbal IQ and reading. A Verbal IQ >1 SD below the mean was found in 41% of BPD children compared to 21% of controls, while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean. CONCLUSION: Impaired psychoeducational performance was found in preterm children with BPD compared to controls, especially in the areas of language abilities and reading skills. This supports a greater need for special educational services and counseling for parents for these children.     

Early diet of preterm infants and bone mineralization at age five years

Bone disease with significantly reduced bone mineralization is common in preterm infants, and associated with later linear growth stunting at 18 months of age. Dietary insufficiency of calcium and phosphorus is thought to be the principal aetiological factor. We studied 54 children at mean age 5 years who were born preterm and had participated in a prospective multicentre study of effects of early diet on later growth and development. Diets compared were banked donor breast milk and preterm formula fed as a supplement to mother's own milk. Increasing human milk intake was strongly positively associated with later bone mineral content. Children fed predominantly human milk had greater bone mineral content than children of similar size born at term. These data suggest that the early nutritional environment of the preterm infant could play an important role in determining later skeletal growth and mineralization.     

Neurodevelopmental outcome at three years of age after fetal `brain-sparing'

Intrauterine growth restriction (IUGR), occurring preterm, may be related to impaired neurodevelopmental outcome. We measured neurodevelopmental outcome (Hempel examination) at the age of three years in a cohort of infants born between 26 and 33 weeks in 1989. Fetuses were studied haemodynamically, using Doppler ultrasound. The ratio between the umbilical and the cerebral artery Pulsatility Index (U/C ratio) was calculated. This is a measure of redistribution of fetal blood preferentially to the brain and this may be a marker of fetal adaptation to placental insufficiency. Impaired fetal growth was also measured by the fetal growth ratio. Neonatal cranial ultrasound was performed to document intracranial haemorrhages and/or ischaemia. From the original cohort of 106 infants, 96 (91%) infants were examined at three years. After adjustment for obstetric variables, adverse Hempel outcome was related to neonatal cranial ultrasound abnormality and low head circumference at three years. Neither the U/C ratio nor fetal growth were independently associated with Hempel outcome. Fetal `brain-sparing' in IUGR appears to be a benign adaptive mechanism preventing severe brain damage.     

Fiber tracking at term displays gender differences regarding cognitive and motor outcome at 2 years of age in preterm infants

White matter microstructural changes can be detected with diffusion tensor imaging. It was hypothesized that diffusion parameters in the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) bundles in preterm infants at term equivalent age (TEA) were associated with neurodevelopment at 2 y corrected age. In 67 preterm infants, fiber tracking was performed at TEA for the CC and both PLIC bundles. Volume, length, fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity were determined for the three bundles. These parameters were assessed in relation to outcome on the Bayley Scales of Infant and Toddler Development III. In girls, volume and length of the CC bundle and right PLIC bundle volume were associated with cognition. In boys, volume, FA, mean and radial diffusivity, and length of the left PLIC were associated with fine motor scores. Correction for GA, birth weight, intraventricular hemorrhage, white matter injury, and maternal education did not change the results. Fiber tracking parameters in the PLIC and CC bundles in preterm infants at TEA revealed different associations with neurodevelopment between boys and girls. This study suggested that fiber tracking is a useful method to predict neurodevelopment in preterm infants.     

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14-15 years of age in very preterm infants

BACKGROUND: Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN: Prospective cohort study. SUBJECTS: 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES: Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS: A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS: Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.     

Neurodevelopmental outcome of premature infants born at less than 33 weeks of gestational age and not cerebral palsy at the age of 5 years]

AIM: To appreciate the impact of prematurity, fetal hypotrophy and familial environment on the neurodevelopmental performances of very premature infants without cerebral palsy at the age of five years. POPULATION AND METHODS: We followed a regional cohort of 171 very premature infants (< or = 32 weeks of gestation) until they were five years of age. Cognitive functions were tested with the WPPSI test and the development quotient was assessed by the ability to draw a "bonhomme". Twenty-two premature infants suffered from cerebral palsy diagnosed before the age of two years. Another infant had a moderate diplegia at the five-year examination. We had no information for 16 prematures (9.3% of survivors). Twenty-eight premature infants were considered as having no severe disability on phone or mailed contact, and another child had a severe isolated mental retardation. We examined 104/148 infants, and 96/148 survivors without cerebral palsy passed the tests. The cognitive functions of these premature infants are compared to the performances of a control group made up of 108 children born at term > or = 37 weeks, matched for birthplace and single or twin characteristics of the pregnancy. RESULTS: The values of the different quotients are significantly decreased in the preterm group. The global IQ and the performance IQ are 0.8 SD, verbal IQ is 0.5 SD and the development quotient is 0.4 SD below the values observed in the control group. A performance IQ less than -2 SD for the mean of the control group is observed three times more than in the controls (13.5% vs 3.7%, P < 0.01). Multiple linear regression shows that prematurity explains, independent of hypotrophy and socioeconomic environment, 8% of the variation of the performance IQ (P < 0.01), 2% of the variation of the verbal IQ and 2% of the development quotient (P < 0.05). CONCLUSION: The five-year neurologic outcome of the children born prematurely in this regional study is similar to the results observed in regional studies conducted in Europe: 13.4% of the survivors have cerebral palsy, and the cognitive functions of the children with no cerebral palsy are significantly lower than the term control group. Other risk factors such as hypotrophy, which modulates the developmental quotient, and the socioeconomic status, which modulates the verbal IQ, are underlined.     

Neurological outcome at 6 and 12 months corrected age in hospitalised late preterm infants -a prospective study

Late preterm infants (34-0/7 to 36-6/7 weeks“ gestation) account for 10–20% of NICU admissions and are at increased risk for morbidity and mortality. Although they are prone to developmental delays, reports on neurological outcome during the first 2 years of life are scarce.The aim of the study was to assess neurological/neuromotor outcome in high risk late preterm infants at 6 and 12 months corrected age and the change in neurological scores over time, and to identify factors associated with the neurological outcome.The Hammersmith Infant Neurological Examination was performed in a cohort of 157 late preterm infants admitted in the NICU. The infants were examined at 6 and 12 months corrected age respectively and scored with the optimality score system including 26 items assessing cranial nerve function, posture, movements, tone and reflexes. Also parents reported neurological milestones in the follow up visit.Infants at 6 months had a global score of 59 (47–76) and optimal scores achieved in 25.4%. At 12 months they had a global score of 70 (58–78) and achieved optimal scores in 63.2%. The subscores of posture, tone and reflexes gradually increased from 6 to 12 months corrected age. Being born small for gestational age was the only factor that adversely influenced HINE score at 6 and 12 months. At 12 months 58.5% achieved independent walking. High risk late preterm infants have suboptimal HINE scores at 6 and 12 months of age, suggesting a need for closer follow up and early intervention programs.     

Cognitive and language development of healthy preterm infants at 10 years of age

In this longitudinal study, forty-three Canadian 10-year-olds, 20 born preterm without significant health problems and 23 born at term, were compared. Cognitive development was measured by the Wechsler Intelligence Scale for Children-III. Language development was measured by the Clinical Evaluation of Language Fundamentals-3 (CELF-3) and language used in a 5 minute interview. The children born preterm had subtle delays. They scored significantly lower on Performance IQ and the CELF-3. The subtests on which they had lower scores appear to require visual-spatial skills. Early intervention focusing on parent behaviours that encourage language development and early screening for delays in visual-spatial skills may be useful.