Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria.

A total of 599 children with phenylketonuria, who had been treated early, were followed up prospectively in order to examine the association between intellectual progress from 4 to 14 years of age and control of phenylalanine concentrations. The phenylalanine rose from around 400 mumol/l during the first four years to above 900 mumol/l by 12 years. The children were divided into two cohorts: cohort I comprised 224 children born in the United Kingdom between 1964 and 1971 and cohort II 375 children born between 1972 and 1978. In a previous study it was shown that by 4 years of age these children already had a mean intelligence quotient (IQ) over half a standard deviation below general population norms, and that IQ fell linearly as average phenylalanine concentrations rose. Multiple regression was used to estimate the size of the associations between IQ at later ages and average phenylalanine concentrations in the periods between assessments, after controlling for previous IQ and phenylalanine control, social class, type of phenylketonuria, and factors relating to diagnosis and early management. For each 300 mumol/l rise in average phenylalanine concentrations for those aged 5 to 8 years IQ at 8 years fell by 4-6 points. This compared with a 7-10 point fall in IQ at 4 years for a similar rise in phenylalanine. After 8 years of age the association between IQ and phenylalanine control disappeared in cohort I but persisted in cohort II and was significant up to 10 years of age, although the association was smaller than at 8 years.     

Intelligence in mild atypical phenylketonuria

In 82 children with mild phenylketonuria (PKU) (blood phenylalanine (Phe) concentrations consistently below 900 mol/l throughout follow up) the relationship between intelligence at age 4 (IQ by Stanford-Binet) and average blood Phe concentrations from birth to 4 years was examined. Of the 82 children 24 had received no treatment. In the group as a whole, and in the 24 untreated subjects alone, mean IQs were significantly below population norms, with deficits of approximately 4.5 points and 9 points respectively. After allowing for social class IQ fell progressively by approximately 6 points for each 100 mol/l rise in mean Phe concentrations in both the treated and untreated subjects. This relationship resembled that previously reported in early treated children with more severe forms of PKU, except that the scale of the relationship was even greater. We conclude that all children whose blood Phe concentrations reach 400 mol/l or above should receive a low Phe diet, at least during the pre-school years, and that the aim should be to control blood Phe levels below 400 mol/l throughout early childhood in all forms of PKU.     

Breast milk feeding and cognitive ability at 7-8 years

OBJECTIVE: To examine the association between duration of breast milk feeding and cognitive ability at 7-8 years in a birth cohort of very low birthweight infants. DESIGN: 280 survivors from a national birth cohort of 413 New Zealand very low birthweight infants born in 1986 were assessed at age 7-8 years on measures of verbal and performance intelligence quotient (IQ) using the WISC-R. At the same time mothers were questioned as to whether they had elected to provide expressed breast milk at birth and the total duration of breast milk feeding. RESULTS: Some 73% of mothers provided expressed breast milk and 37% breast fed for four months or longer. Increasing duration of breast milk feeding was associated with increases in both verbal IQ (p < 0.001) and performance IQ (p < 0.05): children breast fed for eight months or longer had mean (SD) verbal IQ scores that were 10.2 (0.56) points higher and performance IQ scores that were 6.2 (0.35) points higher than children who did not receive breast milk. These differences were substantially reduced after control for selection factors associated with receipt of breast milk. Nevertheless, even after control for confounding, there remained a significant (p < 0.05) association between duration of breast milk feeding and verbal IQ: children breast fed for eight months or longer had adjusted mean (SD) verbal IQ scores that were 6 (0.36) points higher than the scores of those who did not receive breast milk. CONCLUSIONS: These findings add to a growing body of evidence to suggest that breast milk feeding may have small long term benefits for child cognitive development.     

Wechsler subscale IQ and subtest profile in early treated phenylketonuria.

AIM: Mildly depressed IQ is common in treated phenylketonuria. This study explored whether a particular intellectual ability profile typifies early and continuously treated phenylketonuria and whether component skills comprising the IQ relate to socioeconomic and treatment factors. METHODS: IQ scores were collected retrospectively from variants of the "Wechsler intelligence scale for children" performed at age 8 on 57 children with early treated, classic phenylketonuria. The mental ability pattern underlying IQ was investigated by analysing subscale and subtest scores and dietary factors, such as historical phenylalanine blood concentrations. RESULTS: The children's mean full scale IQ of 91.11 was significantly below the healthy population norm. There was a significant discrepancy between their mean verbal IQ (94.65) and mean performance IQ (89.42), suggestive of a spatial deficit, but the data did not support a biochemical or sociological explanation. Individual Wechsler subtests had no distinctive pattern. Phenylalanine control at age 2 was predictive of overall IQ. At this age, children with annual median phenylalanine < 360 micromol/litre (recommended UK upper limit) had a mean IQ 10 points higher than those above. CONCLUSIONS: Early and continuous treatment of phenylketonuria does not necessarily lead to normalisation of overall IQ. Verbal intelligence in the primary school years appears to normalise if blood phenylalanine is maintained below 360 micromol/litre in infancy, but spatial intelligence may remain poor. However, the discrepancy in skill development is not the result of social status or treatment variables. Perhaps weak spatial intelligence is an ancillary effect of a protective rearing style occasioned by the dietary treatment regimen.     

Intellectual development in 12-year-old children treated for phenylketonuria

Intelligence and achievement test scores were evaluated for 95 12-year-old children with phenylketonuria who had begun dietary therapy during the neonatal period. Dietary control of blood phenylalanine below 900 mumol/L was maintained beyond age 10 years in 23 children; 72 others had blood phenylalanine persistently above that level at ages ranging from 18 months to 10 years. Test scores at age 12 years were negatively correlated with the age at initiation of diet and with blood phenylalanine levels from ages 4 to 10 years, and positively correlated with parent IQ scores and the age at loss of dietary control. Children who maintained phenylalanine levels below 900 mumol/L beyond age 10 years showed no deficits in test scores, except for arithmetic, the scores of which declined between ages 6 and 12 years in 90% of the children in this study. These data strongly support a recommendation that dietary restriction of phenylalanine should be maintained through adolescence.     

Intellectual and functional status at school entry of children who weighed 1000 grams or less at birth: a regional perspective of births in the 1980s

The intellectual and functional status of a regional cohort of children who weighed 501 to 1000 gm when born between 1980 and 1982 was evaluated at a mean age of 5 1/2 years by standard psychometric tests. Of 90 long-term survivors (survival rate 49%), 78 children (87%) had the full test battery, 5 children (6%) had other tests (4 were blind), and one child was untestable. Most of the mean scores were within 1 SD of the test norms; the lowest scores were in the McCarthy Motor scale and in the Beery Test of Visual-Motor Integration. Children without neurologic impairments and those with an IQ greater than or equal to 68 (n = 60) had higher overall scores but still performed poorly on the Motor subscale and the Beery test. Children who weighed less than 800 gm at birth (n = 28) were similar to those who weighed greater than 800 gm (n = 50), except in the Memory and Motor subscales, in which they performed significantly less well. At a functional level, determined by the Vineland Adaptive Behaviour Scales, two thirds of the children were performing in the adequate range and the remainder in the moderately low to low range. Of the 43 children with no neurosensory impairments and an IQ greater than or equal to 84, 49% were identified (by the Florida Kindergarten Screening Battery) to be at mild to high risk for future learning disabilities. The data from this unselected population provide an unbiased estimate of the prevalence of intellectual and functional problems in children who weighed less than or equal to 1000 gm at birth.     

Are there critical periods for brain growth in children born preterm?

BACKGROUND: Children born very preterm who attend mainstream schools have a high prevalence of minor motor, behavioural, and learning disorders. These appear to be associated with reduced postnatal growth, particularly of the head. It is unclear when this poor growth occurs and whether growth restriction during different periods has different effects on later function. OBJECTIVE: To identify periods during early development, in children born preterm, when impaired head growth may influence minor motor and cognitive function. POPULATION: A geographically defined cohort of 194 infants born in Merseyside during 1980-81 and weighing less than 1500 g. METHODS: Measurements of head circumference (occipitofrontal circumference (OFC)) were available at birth, hospital discharge, 4 years, and 15 years of age. Assessments of intelligence (intelligence quotient (IQ)) and minor motor impairment (test of motor impairment (TOMI)) were made at 8 years of age. Clinical, social, and demographic variables were obtained from the clinical record and maternal interviews. RESULTS: IQ correlated significantly with OFC at 4 and 15 years of age after correction for growth restriction at birth (intrauterine growth restriction (IUGR)) and social class. TOMI scores correlated significantly with OFC at all four times, but especially with OFC at discharge and with change in OFC between birth and discharge. They were not affected by correction for social class or IUGR. CONCLUSION: Although both IQ and minor motor impairments correlate strongly with each other at school age in very low birthweight children, the factors determining them and their timing of operation are different. Interventions designed to improve IQ in this population would need to reduce IUGR and improve later childhood growth. Those aimed to improve motor ability need to be targeted more at brain protection during the neonatal period.     

Wechsler subscale IQ and subtest profile in early treated phenylketonuria

AIM—Mildly depressed IQ is common in treated phenylketonuria. This study explored whether a particular intellectual ability profile typifies early and continuously treated phenylketonuria and whether component skills comprising the IQ relate to socioeconomic and treatment factors.
METHODS—IQ scores were collected retrospectively from variants of the "Wechsler intelligence scale for children" performed at age 8 on 57 children with early treated, classic phenylketonuria. The mental ability pattern underlying IQ was investigated by analysing subscale and subtest scores and dietary factors, such as historical phenylalanine blood concentrations.
RESULTS—The children''s mean full scale IQ of 91.11 was significantly below the healthy population norm. There was a significant discrepancy between their mean verbal IQ (94.65) and mean performance IQ (89.42), suggestive of a spatial deficit, but the data did not support a biochemical or sociological explanation. Individual Wechsler subtests had no distinctive pattern. Phenylalanine control at age 2 was predictive of overall IQ. At this age, children with annual median phenylalanine < 360 µmol/litre (recommended UK upper limit) had a mean IQ 10 points higher than those above.
CONCLUSIONS—Early and continuous treatment of phenylketonuria does not necessarily lead to normalisation of overall IQ. Verbal intelligence in the primary school years appears to normalise if blood phenylalanine is maintained below 360 µmol/litre in infancy, but spatial intelligence may remain poor. However, the discrepancy in skill development is not the result of social status or treatment variables. Perhaps weak spatial intelligence is an ancillary effect of a protective rearing style occasioned by the dietary treatment regimen.
     

Intellectual development after relaxing the diet at the age of 5 years in typical phenylketonuria]

BACKGROUND. No satisfactory controlled trial has yet been completed on typical phenylketonuria (PKU) patients whose treatment was relaxed at the age of 5 years. METHODS. 27 children having typical PKU were treated before the age of 3 months. The intake of phenylalanine and protein was carefully regulated during the first 5 years of life, after which the treatment was relaxed. All children were evaluated after at least 6 years on the relaxed diet. Their IQ scores and school performance were related to the degree of dietary control and plasma phenylalanine values. RESULTS. The IQ scores at 5 years of age were 100 +/- 10.8. Continued evaluation showed that IQ scores remained unchanged. Poor school performance was twice as frequent as in general population; the deficit in the IQ score of this group was 8 points below that of normal sibs. There was no correlation between plasma phenylalanine and the IQ score after the age of 5 years. The positive control decreased with aged. CONCLUSIONS. Children with typical PKU have an IQ deficit relative to their normal sibs just before relaxing treatment. Good dietary control until 5 years of age, maternal intelligence and continuing evaluation during relaxing diet are the best conditions for optimal intellectual progress. There is no evidence that continued treatment during adolescence is beneficial.     

Intellectual assessment of 111 four-year-old children with phenylketonuria

Of the 216 children with phenylketonuria (PKU) who were initially enrolled in the Collaborative Study of Children Treated for Phenylketonuria, 203 were placed on dietary therapy between 3 and 92 days of age. Of these, 111 are now at least 4 years of age and constituted the sample for the present analysis. Their mean IQ on the Stanford Binet Intelligence Scale was 93 (1972 norms). The children assigned to two treatment groups based on "moderate" and "low" serum phenylalanine levels were comparable on their IQs at age 4, although many of the children could not be maintained in the specified categories. Females scored a significantly higher mean IQ than males (97 vs 90). Those children for whom dietary treatment was initiated during the first month of life scored a mean IQ of 95, compared with 85 for those initially treated from 31 to 65 days. However, the interpretation of dietary inception data may have been contaminated by familial and psychosocial factors. The PKU Collaborative Study is still in progress in 15 clinics located in 11 states.     

Large variability in performance IQ associated with postnatal morbidity,and reduced verbal IQ among school-aged children born preterm

Aim: To assess cognitive ability in a population-based group of prematurely born school-aged children and to relate these findings to postnatal morbidity. Method: The study group consisted of a cohort of 51 children born preterm, 43 (26 boys, 17 girls) of whom were available for psychological evaluation At evaluation, their median age was 10 y (range 8-11 y). They were all born between 1988 and 1991, with gestational age less than 29 wk (median 27, range 24-28). Their median birthweight was 1060 g (range 450-1450). The Wechsler Intelligence Scale for Children (WISC-III) was used, and the test results were compared with those of a standardized, age-matched, normative group of children. Results: Thirteen children (30%) performed below average [intelligence quotient (IQ) 380] for Full Scale IQ (FSIQ). Thirty-six children had a Verbal IQ (VIQ) below the mean value of 100 [84%, 95% confidence interval 73-95%], p 3 0.0001. The Performance IQ (PIQ) was within the expected range of a normal population, although a large variability was observed. Discrepancies between VIQ and PIQ of more than 15 IQ units were found in 42% of the children. High postnatal morbidity (days with assisted ventilation, number of blood transfusions) and low birthweight standard deviation scores (SDS) were associated with lower PIQ than VIQ, while low postnatal morbidity and high birthweight were associated with higher PIQ than VIQ. Conclusion: This cohort of preterm children had reduced overall verbal capacity independent of morbidity, and a large variability in performance capacity that was associated with postnatal morbidity. The findings suggest that there are different mechanisms influencing the outcome of verbal and performance capacity in preterm children.     

Loss of intellectual function in children with phenylketonuria after relaxation of dietary phenylalanine restriction

Fourteen patients with classic phenylketonuria (PKU) were treated with a phenylalanine restricted diet from early infancy. All had satisfactory dietary control, with serum phenylalanine concentrations ranging between 2 to 5 mg/dL. Dietary restriction was discontinued in all these children between ages 5 and 6 years, and a free diet allowed. Developmental testing was performed using the Cattell Infant Intelligence Scales (1 to 2 years), Stanford-Binet Intelligence Scale (2 to 4 years), Wechsler Intelligence Scale for Children (WISC) and the revised version (WISC-R) (less than 5 years). Mean IQ for the group (Stanford-Binet and WISC) at termination of dietary therapy was 104 +/- 13. Four to 7 years after discontinuation of dietary therapy, mean IQ for the group was 90 +/- 13. The severity correlated, to some degree, with duration of unrestricted diet, but not with initial serum phenylalanine concentrations, age at initiation of therapy, or IQ at time diet was discontinued. Several children are experiencing difficulties, both attentional and academic, in school. Two children have had a change in the EEG from normal to abnormal. Neurologic testing performed after 4 to 7 years off diet demonstrated deficits in visual-motor integration or cognitive problem-solving in most children. The mean developmental age for the group for perceptual-motor integration was 1.2 years below the mean chronologic age of the group. This deterioration in intellectual function suggests that discontinuation of the phenylalanine-restricted diet is hazardous for some children with classic phenylketonuria.     

Predictors of mean phenylalanine levels during the first five years of life in patients with phenylketonuria who were treated early

We studied the relationship between plasma phenylalanine level at first diagnostic visit, country of origin of the mother, birth cohort, child clinic, sex, and social class on the one hand and mean plasma phenylalanine levels in the first five years of life on the other hand in patients with phenylketonuria (PKU) who were treated early. The study population consisted of 131 early treated patients with PKU born during the period from September 1st, 1974 to December 31st, 1988 in The Netherlands. Plasma phenylalanine levels from first diagnostic visit (usually before the age of three weeks) up until the fifth birthday were registered. For each patient the mean phenylalanine level during that period was calculated. Our results suggest that 1) it is more difficult to maintain low phenylalamine levels in patients with a more severe form of PKU, 2) in recent years paediatricians have treated their patients with a stricter diet, 3) there are differences in perception between paediatricians of different clinics as to what levels are acceptable, and 4) treatment of patients from non-Dutch mothers is more difficult than treatment of patients with Dutch mothers.     

Maternal phenylketonuria: report from the United Kingdom Registry 1978-97

Background: The effects of maternal phenylalanine on the fetus include facial dysmorphism, microcephaly, intrauterine growth retardation, developmental delay, and congenital heart disease. Aims: To evaluate the impact of phenylalanine restricted diet in pregnant women with phenylketonuria (PKU) on their offspring. Methods: Data on virtually all pregnancies of women with PKU in the United Kingdom between 1978 and 1997 were reported to the United Kingdom PKU Registry. The effect of the use and timing in relation to pregnancy of a phenylalanine restricted diet on birth weight, birth head circumference, the presence or absence of congenital heart disease (CHD), 4 year developmental quotient, and 8 year intelligence quotient were examined. Results: A total of 228 pregnancies resulted in live births (seven twin pregnancies were excluded). In 110 (50%), diet started before conception. For this group mean (SD) birth weight was 3160 (612) g, birth head circumference 33.6 (1.9) cm, 4 year DQ 108.9 (13.2), 8 year IQ 103.4 (15.6), and incidence of CHD was 2.4%. In comparison, for those born where treatment was started during pregnancy (n = 91), birth weight was 2818 (711) g, birth head circumference 32.7 (2.0) cm, 4 year DQ 96.8 (15.0), 8 year IQ 86.5 (13.0), and incidence of CHD was 17%. Month-by-month regression analyses suggested that metabolic control by 12–16 weeks gestation had most influence on outcome. Conclusions: Many features of the maternal PKU syndrome are preventable by starting a phenylalanine restricted diet. Women with PKU and their carers must be aware of the risks and should start the diet before conception, or as soon after as possible.     

Secular trend of growth in Malaysian children

Over the past hundred years in industrialised countries and recently in some developing countries, children have been getting larger and growing to maturity more rapidly. This paper compares the growth of Malaysian children with similar socioeconomic backgrounds but born about twelve years apart. Data were obtained from records of 227 children born between 1968 and 1973 and 238 children born between 1980 and 1985. The children were followed-up regularly at the University Hospital Child Health Clinic in Kuala Lumpur for a variable period from birth to five years of age. Measurements for their weight, length and head circumference were taken at each visit. There is a directional indication that boys and girls of the 1980-1985 cohort are taller, heavier and have bigger head circumferences from birth to five years of age and the difference widens as the child grows older. This study clearly shows that a positive secular trend has taken place in the last decade, reflecting an improvement of living conditions with time. The factors involved in the positive secular trend are manifold and the most important is probably nutrition.     

Maternal phenylketonuria: report from the United Kingdom Registry 1978-97.

BACKGROUND: The effects of maternal phenylalanine on the fetus include facial dysmorphism, microcephaly, intrauterine growth retardation, developmental delay, and congenital heart disease. AIMS: To evaluate the impact of phenylalanine restricted diet in pregnant women with phenylketonuria (PKU) on their offspring. METHODS: Data on virtually all pregnancies of women with PKU in the United Kingdom between 1978 and 1997 were reported to the United Kingdom PKU Registry. The effect of the use and timing in relation to pregnancy of a phenylalanine restricted diet on birth weight, birth head circumference, the presence or absence of congenital heart disease (CHD), 4 year developmental quotient, and 8 year intelligence quotient were examined. RESULTS: A total of 228 pregnancies resulted in live births (seven twin pregnancies were excluded). In 110 (50%), diet started before conception. For this group mean (SD) birth weight was 3160 (612) g, birth head circumference 33.6 (1.9) cm, 4 year DQ 108.9 (13.2), 8 year IQ 103.4 (15.6), and incidence of CHD was 2.4%. In comparison, for those born where treatment was started during pregnancy (n = 91), birth weight was 2818 (711) g, birth head circumference 32.7 (2.0) cm, 4 year DQ 96.8 (15.0), 8 year IQ 86.5 (13.0), and incidence of CHD was 17%. Month-by-month regression analyses suggested that metabolic control by 12-16 weeks gestation had most influence on outcome. CONCLUSIONS: Many features of the maternal PKU syndrome are preventable by starting a phenylalanine restricted diet. Women with PKU and their carers must be aware of the risks and should start the diet before conception, or as soon after as possible.     

Behavior disturbance in 8-year-old children with early treated phenylketonuria. Report from the MRC/DHSS Phenylketonuria Register

Using the Rutter Behavior Questionnaire, schoolteachers assessed the frequency of common abnormal behavior in 544 8-year-old children with phenylketonuria who were born in the United Kingdom and in whom the diagnosis was made by routine testing in infancy, either during the early years of screening (cohort 1, births 1964 to 1971) or after a national reorganization of the program (cohort 2, births 1972 to 1977). All children received treatment before 4 months of age. Two matched control subjects were assessed for each patient. Compared with the controls, patients in cohorts 1 and 2 receiving a strict low-phenylalanine (phe) diet (average phe concentration less than 600 mumol/L) were 1.5 and 1.7 times, respectively, more likely to have deviant behavior; those receiving a less well controlled diet were 2.5 and 1.9 times, respectively, more likely to show such behavior. Patients more often had mannerisms, hyperactivity, and signs of anxiety and were less responsive and more solitary than were controls. On the other hand, they were not more aggressive, untruthful, or disobedient, nor absent from school more frequently. The increased frequency of deviant behavior may be the result of both psychologic stress and neurologic impairment.     

Early nasal continuous positive airway pressure in a cohort of the smallest infants in Denmark: neurodevelopmental outcome at five years of age

AIM: To evaluate neurodevelopmental outcome at age 5 y of age in a cohort of preterm children treated mainly with nasal continuous positive airway pressure (CPAP) in the neonatal period. METHODS: A national prospective observational study was conducted in Denmark which included all 269 surviving children with a birthweight below 1000 g or a gestational age below 28 wk born in Denmark in between 1994 and 1995. A total of 164 children (61%) had been treated with nasal CPAP only in the neonatal period. A reference group (n = 76) of term children was studied in parallel. RESULTS: Of the 269 surviving children, 252 (94%) were examined. Twenty-four children (10%) had cerebral palsy, and three children were blind. No case of hearing impairment was detected. Nineteen percent of the index children had an IQ score <-- 2 SD and 42% had an IQ score <-- 1 SD of the mean score of the reference group. CONCLUSIONS: The intellectual development of children in this cohort treated with early nasal CPAP did not suggest a higher proportion of adverse effects on the brain compared to the published follow-up studies of preterm children treated with mechanical ventilation. In our population-based cohort, however, the survival rate for infants below 25 wk of gestation was relatively low and this may indicate a limit for the use of early nasal CPAP.     

Outcome at 14 years of extremely low birthweight infants: a regional study

OBJECTIVES: To determine the neurosensory outcome at 14 years of age of a regional cohort of extremely low birthweight (ELBW) children, to contrast their prognosis with normal birthweight (NBW) controls, and to determine the predictive value of assessments earlier in childhood. DESIGN: Geographically determined cohort study. SETTING: The state of Victoria, Australia. PATIENTS: Consecutive ELBW survivors of birth weight 500-999 g (n = 88) born during 1979-1980, and 60 randomly selected contemporaneous NBW (birth weight > 2499 g) controls. MAIN OUTCOME MEASURES: Rates of neurosensory impairments and disabilities at 14 years of age, and earlier in childhood. RESULTS: Of 351 ELBW consecutive live births, 88 (25%) survived and 79 (90%) of the survivors were assessed at 14 years of age. Of the 79 ELBW children assessed, eight (10%) had cerebral palsy, five (6%) had bilateral blindness, four (5%) were deaf requiring hearing aids, and 36 (46%) had an intelligence quotient (IQ) < -1 SD compared with the mean for the NBW controls. Overall 11 (14%) ELBW children were severely disabled, 12 (15%) were moderately disabled, 20 (25%) were mildly disabled, and 36 (46%) had no disability. In contrast, only one (2%) of 42 NBW children assessed had a severe disability, six (14%) had a mild disability, and the remaining 35 (83%) were not disabled. Comparing psychological test scores for ELBW children with those for NBW controls, rather than test norms, avoided bias in the assessment of disability earlier in childhood. Relative to assessments earlier in childhood, the prediction of disability at 14 years of age was highly significant at each of 2, 5, and 8 years of age, but the accuracy progressively increased with age. CONCLUSIONS: ELBW children have substantially higher rates of neurosensory impairments and disabilities at 14 years of age than NBW controls. Comparison of ELBW children with NBW controls avoids bias in the assessment of disability. Early childhood assessments are highly predictive of disability at 14 years of age.