Introduction 59 From perinatal asphyxia to neonatal encephalopathy 30 4 54 3 20 35 37 40 51 16 35 4 30 30 22 52 25 10 6 38 25 4 30 27 19 33 50 Grades of neonatal encephalopathy in relation to developmental outcome 43 44 46 41 27 45 4 45 47 13 34 16 Need for long-term follow-up and focus on cognitive and behavioral outcomes 8 23 32 35 43 44 46 7 21 31 42 56 14 16 28 57 To gain insight into the long-term effects of NE on development, follow-up is required throughout the school-age period. Specific cognitive functions continue to develop throughout childhood. As it is impossible to examine a function that has not developed yet, short-term follow-up cannot exclude minor cognitive and behavioral difficulties at school age. Moreover, subtle functional deficits usually do not become apparent until a child faces increasing demands to master complex abilities in school. 17 34 11 18 26 61 32 47 53 1 2 3 4 5 6 7 8 Table 1 Griffiths Mental Development Scale* at 1 year   CP No CP 12 Moderate NE, N=13 Moderate NE, N=27 • N=10: <−2 SD • N=4: between −2 SD and −1 SD • N=1: between −2 SD and −1 SD • N=23: >−1 SD • N=1: >−1 SD  • N=1: untestable  24 Moderate NE, N=10 Moderate NE, N=9 • N=9: <55 Mean =118 (N=1 not assessed) • N=1: 87  55 No grades of NE recorded, N=16 No grades of NE recorded, N=24 Mean =47, range: 7–101 Mean =16, range 94–128 9  No grades of NE recorded, N=59  Mean =100.34, SD=15.05, range: 55–130 49 Moderate NE, N=8 Mild NE, N=4 All below normal (cut-off point not reported) All normal Severe NE, N=1  Below normal  *Griffiths mean of standardization sample =100.18, SD=12.76 Table 2 IQ at 2–6 years (no CP)   Age (years) Mild NE Moderate NE Severe NE b 9 2 f a 43 3.5 N=66, Stanford-Binet: mean IQ =101.5, SD=14.0 2 2 c b 53 5 f b d 8 5.5–6.5 N=20, WPPSI-R: mean IQ =109.7, SD=14.6 (N=1: 76, rest: >90) N=12, WPPSI-R: (N=1: untestable) N=11: mean IQ =106.2, SD=11.8 (N=1: 84, rest: >94)  b 9 5–6 f e 44 5.5  N=56, Stanford-Binet: mean IQ =106, SD=12 N=71, Stanford-Binet: mean IQ =99, SD=18)  a b c 50 d e f Table 3 IQ at 7–9 years (no CP)   Age (years) Mild NE Moderate NE Severe NE b 32 7  N=65, BAS-II:  Group 1 (N=34): GCS=112.3, SD=11.2 d a 46 8 N=56, WISC-R: mean IQ =106, SD=13 N=66, WISC-R: mean IQ =102, SD=17 5, WISC-R: mean IQ =36, SD=7 c 47 9  N=64, WISC-R: mean IQ =100, SD=14  a b c d 50 Table 4 Scholastic abilities at 7–13 years (no CP)   Mild NE Moderate NE Severe NE Reading 46 13% >1 grade level below expected level for age a b 47  d  32  c    f d  35 d d d Writing 32  Group 1: = control group  f e 35 NE = control group NE = control group NE = control group Spelling 46 2% >1 grade level below expected level for age a b 32  c  f d 35 NE = control group NE = control group NE = control group Math 46 16% >1 grade level below expected level for age a b 47  d  32  Group 1:  = control group  f d 35 c c c 46 32 35 a b c d e f 50 Table 5 43 44 46 Tests 3.5 years 5.5 years 8 years Receptive vocabulary Mild NE: in the mean range Mild NE = control group Mild NE = control group a b a a c c Visual- motor integration Mild NE: in the mean range Mild NE = control group Mild NE = control group a a a c a c  a b c Table 6 32 Age: 7 years Moderate NE group 1 Moderate NE group 2* Attention and executive Group 1 = control group (p=0.08) Group 2 < control group (p < 0.01) Language Group 1 < control group (p=0.01) Group 2 < control group (p < 0.01) Sensorimotor Group 1 < control group (p=0.04) Group 2 = control group (p=0.10) Visuospatial Group 1 = control group (p=0.14) Group 2 < control group (p=0.02) Memory and learning Group 1 = control group (p=0.61) Group 2 < control group (p < 0.01) 50 Table 7 31 Age: 16 years Moderate NE Total words learned trial 1–5 NE: 52.5, SD=8.7 Control group: 57, SD=5.8 Delayed recall (p=0.034) NE: 11.6, SD=2.2 Control group: 13.3, SD=1.6 Recognition (p=0.011) NE: 14.2, SD=1.0 Control group: 15, SD=0.0 *Raw scores (number correct) Table 8 47 Age: 9 years Moderate NE a NE: 98, SD=16 Control group: 104, SD=15 a NE: 96, SD=18 Control group: 105, SD=15 a NE: 95, SD=15 Control group: 103, SD=16 Recognition accuracy b Control group: 27% delayed Total intrusions b Control group: 20% delayed Immediate attention NE: 97, SD=15 Control group: 100, SD=15 a b General cognitive development Infancy (0–24 months) 2 9 12 24 39 49 50 55 2 55 1 24 49 Two to six years, without CP 8 9 43 44 53 2 43 9 53 Seven to nine years, without CP 32 46 47 3 Educational achievement 24 4 32 35 46 47 Neuropsychological functions 5 6 7 8 43 44 46 29 31 47 47 Behavioral problems 32 35 44 35 5 Discussion and conclusion In the introduction section of this review, problems were mentioned with regard to the comparability of different outcome studies of NE. Even after careful selection on the basis of predetermined criteria, comparing studies remained difficult. The main reason for this was the way test results were presented. In many cases, outcome of the children was reported in two or more categories, e.g., normal/mildly delayed/abnormal. One of the problems that arise due to such categorization, is the subjectivity involved in determining the cut-off points of the categories. Often, these cut-off points seemed to be chosen arbitrarily or not justified at all. Another issue that adds to this problem is the use of different tests of development, cognitive ability or behavioral problems. One can hardly compare, for example, the proportions of children with developmental delay in two studies when these are represented by a score below 85 on the Bayley Scales of Infant Development in one of the studies and by a score below 70 on the Griffiths Mental Developmental Scales in the other. To enable readers to compare studies, results of significance testing between subgroups of children with NE and comparison groups were added to the tables whenever available. 12 24 Children with severe NE appear to be impaired in every cognitive domain. They are less intelligent and perform worse at school and at neuropsychological tests than both healthy controls and children with mild or moderate NE. 32 29 50 21 58 1 60 48 From this review it is concluded that general intellectual, educational and neuropsychological outcomes are consistently positive for children with mild NE and negative for severely affected children. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. Difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, neuropsychological functioning of children with NE has received relatively little attention. The studies that were selected for this review have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Therefore, behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE.