Early development and later psychological outcome

INTRODUCTION
The term children at risk has often been used to denote an individual or a population with an increased probability of having or acquiring a handicapping condition. Infants at biological risk have a history of prenatal, antenatal and neonatal events suggestive of biological insults to the developing central nervous system – (CNS) (1). The most frequent risk factors (RF) are prematurity, low birth weight, perinatal asphyxia (PA), intracranial haemorrhage (ICH) and neonatal convulsions. The severe developmental outcomes in these conditions are cerebral palsy, epilepsy and mental retardation. The mild neurodevelopmental problems in children with normal cognitive status are delayed motor and speech development, behavioural disorders (restlessness, irritability, short attention span), low visual - motor performance, memory deficits and specific learning disabilities (2, 3). The clear clinical signs of mild disorders can only be seen when the development processes of the CNS have reached a certain degree of the topographic and functional organization (4, 5). Neuropsychological outcome takes longer to emerge in comparison to the neurological signs, especially in children at lower risk. This is the main reason for psychological follow-up of children at neuro risk to school age.
Asphyxia is connected to all the factors which could cause lack of oxygen in the brain and can be of central (e. g. ICH) or peripheral origin (e.g. lung immaturity), in preterm, as well as in term children. PA in full-term children is mostly caused by respiratory difficulties and delivery problems (e.g. forceps, vacuum extraction, prolonged birth, umbilical cord problems) (6). During the first year of life there is a possibility for cerebral recovery after the lesion, due to the plasticity of the CNS (4, 7).

In children at neuro risk or in children with neurodevelopmental problems, PA is one of the most common RF - it is registered in 33 - 47% of children at risk (8). Early and later developmental outcome in children with the same RF is individual and not predictable for a specific case. Other factors important for the outcome are CNS plasticity, individual vulnerability and various environmental conditions, e.g. parental education, social support, treatment (5, 7, 9).
The special hospital for children with neurodevelopmental and motor disorders “Goljak” is a regional centre with a program for observing the development of children at neuro-risk from birth to school age. The multidisciplinary diagnostic team proposes a habilitation program for each child, if necessary, such as physical, occupational and speech therapy. It is very important to start with treatment at a very early age because of the plasticity of the CNS and possibility for recovery (4). Low risk is defined as t he presence of a) one or two risk factors, b) mild developmental delays or c) ICH lower grade (10). In this group of children 10% of them show mild neurodevelopmental problems and very rarely have severe neurological deficits (10). Most of the children in this group did not complete the psychological follow - up because severe developmental problems were not observed in early childhood and they were not referred to a psychologist. Only a small proportion of the children with PA are included in follow - up to school age. The majority of studies of developmental outcome at a later age have focused on preterm children, but only a few are focused on term children with PA as the only risk factor (8, 11, 12).

AIM
In this study we were interested in early and later development and behaviour, as well as in intellectual performance in full-term children with perinatal asphyxia (PA). The aims were: 1. To compare overall development at early and later ages with those of the general population.
2. To evidence the incidence of disharmonic early developmental profile
3. To evidence the incidence of behavioural problems in the ADHD domain at an early and later age.
4. To compare the results of the cognitive measures at the later age with those of the general population and to evidence the incidence of specific cognitive deficits.
5. To compare the groups with varying degrees of PA in terms of overall development, profile discrepancy, behavioural problems, global IQ and specific cognitive deficits.
It was hypothesized that the children at risk could have more developmental and behavioural problems, as well as more later cognitive deficits in comparison to the general population and also that the degree of PA would be associated with more developmental deviations.

METHOD
Sample
The random clinical sample consisted of 35 children, 25 boys and 10 girls with PA, evidenced in maternity hospitals and assessed at the special hospital “Goljak”. 29 children participated in the psychological follow - up and 6 children were included at a later age. All children were full-term, all but one were in the range of the normal birth weight. Delivery was spontaneous in 21 children, Caesarean section was conducted for 8 of them and vacuum extraction in 6 children. Children who were born at known prenatal risk were excluded (intrauterine growth retardation - IUGR, foetal distress or twin pregnancy). No one had a severe neurological impairment such as cerebral palsy, epilepsy or mental retardation. The neurological status of the subjects was also followed up and only 8 of them had normal neurological results and 27 of them had aberrant results (EEG, ultrasound, CT). In the habilitation program 19 children were included at an early age.

Measures
PA was established by neonatologists in maternity hospitals. The anamnesis factors from the official hospital records we had at disposal, were Apgar score (AS) and the presence of delivery difficulties. In the mild risk group (AS in the first minute was 4 – 10, umbilical cord problems or oxygen required) there were 26 children, and in the severe risk group (AS in the first minute was 0 - 3, reanimation was required, in 3 children ICH lower grade attendance) there were 9 children .

Early and later developmental level was assessed using the Čuturić Developmental Scale (RTČ). The global Developmental Quotient (DQ) was used, as well as the partial DQs for the analysis of the early developmental profile (gross and fine motor, visual perception, sociability, verbal comprehension and expression). Behavioral disorders in the ADHD domain, connected with cerebral dysfunction, were estimated using DSM - IV criteria. These criteria were hyperactivity, distractibility and impulsiveness. Cognitive functions were measured by standard psychological tests. Binet - Simone Scale (BS - NBR) and Wechsler Intelligence Scale for Children (WISC) were used as measures of overall intellectual level (Deviation Mental Quotient and Intelligence Quotient, we used onward IQ). Goodenough Draw a Man Test (DMT) and L. Bender Gestalt Test (LB - Koppitz system) were also administered. Some additional tests were used - Kohs Block Design Test, Raven Progressive Matrices and Columbia Mental Maturity Scale. Specific deficits were determined on the basis of all measures and observation. The need for specific educational intervention was determined on the basis of delayed start of schooling or specific learning difficulties at the beginning of schooling.

Procedure
All parents were informed in advance about the procedure and follow-up in accordance to ethical norms. The early psychological testing was conducted at the age of 2 (modal score), with RTČ and a behaviour check list. The later assessments were carried out at the age of 5 - 10, once or several times, using the RTČ, behaviour check list and cognitive tests. The parents were first interviewed by means of a structured interview and then the children were tested and observed. At the end of procedure the results were presented to the parents and, if necessary, a habilitation program was suggested, as well as specific educational intervention.

RESULTS
The distributions of the results for psychological measures (frequency and relative frequency in three categories) are presented in order to compare the developmental problems in this clinical sample with those in the general population. 1. The median score of the global DQ was in the range of average results at the early and the later age, similar to the general population. The results are presented in Table 1.
At the later age the distribution of DQ's results was asymmetric toward higher scores, as presented in Graph l.
2. The early developmental profile was estimated as disharmonic when one or more partial DQs deviated in 2 or more categories from the global DQ. A disharmonic profile was found in 10 children (34%), whereas mostly a harmonic profile is expected in the general population. The partial DQs in fine motor, verbal expression and visual perception deviated most in our sample.
3. Behavioural problems in the ADHD domain, presented in Table 2, were registered in the majority of the subjects at the early and the later ages and their incidence was much higher in comparison with the general population. Different clinical signs of behavioural deviations and attention problems were observed in 59% younger and in 69% and 74% older children in follow up sample (74% in total sample) in comparison to 10-20% children in the general population (13). Older children showed a tendency of increasing behavioural problems. There was no evidence for sex difference with the early behavioural deviations – 60% boys and 56% girls showed problems ( t-test = 0.91, p > 10%, - not statistically significant, onward – ns). At the later age boys showed more disorders (76%) in comparison to the early age (60%, t-test = 0.43, p > 10%, ns) and also had more problems (76%) than girls (50%) at the later age (t-test = 0.63, p > 10%, ns). No difference was statistically significant.
4. The results on the cognitive tests at the age of 5 - 10 (N = 35) are presented in Table 3.
The median score was in the average range for IQ for DMT and LB performance (percentiles), but the distribution of results was asymmetric towards lower scores. The median score of global IQ results felt between the average and above average category and the distribution of results was asymmetric towards higher values.
In Graph 2 it is seen that different cognitive measures were disharmonic in all used tests in comparison to the general population, what could be related to often specific cognitive deficits in this sample, despite of the relatively high global IQ. The specific deficits, registered in 15 subjects (43%), were in visual-motor perception and spatial integration (11), visual perception (4), verbal expression (2), memory (2), spatial orientation (1), arithmetic (1) and reading (1). A delay in start of schooling was suggested for 4 subjects and a specific educational intervention for another 4 out of the 13 school age children. 5. The significance of the difference between the proportions of the measures used was tested for two groups at different risk degree - the mild and the severe degree of PA. There were no statistically significant differences, but there was a tendency for a larger proportion of developmental problems in children at higher risk.
In Table 4 it is seen that children at higher risk were also at higher risk for disharmonic early profile (0.29 : 0.50) and early behavioural problems (0.52 : 0.75). At the later age the children with the mild and severe risk showed almost the same proportion of behavioural disorders (0.69 and 0.66). The children at severe risk were at higher risk for later specific cognitive deficits (0.38 : 0.52) and lower results from the LB test (0.46 : 0.64). However, the global IQ in the high risk group showed a mild tendency toward higher scores (lower proportion of below average global IQ than in the mild risk group).
The children with a disharmonic early profile had a higher proportion of early behavioural problems (0.80) in comparison to those with harmonic development (0.47, t-test = 0.77, ns). Furthermore, children with more later behavioural disorders had a higher proportion of specific cognitive deficits (0.64) in comparison to the group with less behavioural problems (0.18, t-test = 0.67, ns).

DISCUSSION
The main tendency found according to our results could indicate that children at risk in this clinical sample showed developmental disharmony at the early and at the later age more often than in the general population, especially those at higher risk. Biological risk has an impact on child development in different areas and the higher the risk, the greater the disharmony (1, 14, 15), which persists and even increases at a later age (16). Although the global developmental and cognitive median scores were in the average category, we found more specific cognitive deficits in our sample. These deficits are commonly found in perinatal risk studies in various child age samples and are mentioned as mild neurodevelopmental problems (3, 17, 18).
At the early age, behavioural problems were found more often in the group of children at severe degree of PA, but these problems were equally common at the later age, independent of the risk degree. The higher risk includes more negative biological and environmental impacts and behavioural consequences may be cumulative in children with neurological disorders (5). It could be possible that children in follow-up really had more different developmental problems and they therefore stayed all these years in our follow-up program. Also some of children at risk came the first time to our hospital at school age because of different behavioural and learning problems (6 subjects in our sample). The degree of PA did not discriminate enough between children with and those without problems, but the risk could be discriminative in itself. The later outcome could not be predicted for the individual child and this is the reason for the psychological follow up to school age (5, 7).
To establish the main effects of the long - term outcome in term children with PA, further research should include a much larger risk sample and should also provide a control of various environmental factors, such as treatment, parental education, relation child - parents, etc. A behavioural – system approach from M a s h a n d T e r d a l is one of the new concepts for the explanation of the long term outcome (19). Also D e n n i s gave the outcome algorithm for later developmental outcome (5). A longitudinal study should include a control group and follow - up of children from the early age to at least school age so that one could clearly establish the neuro-risk impact on various variables in order to clearly recognize the specific developmental problems of children at risk.
The basic aim of this study was a description of specific developmental problems in term children with perinatal asphyxia in order to demonstrate the importance of follow-up procedure to school age, while early developmental disharmony and behavioural problems could indicate possible later specific problems in behaviour and cognition, increasing with age. We would like to emphasize the importance of early inclusion in follow-up program, even for children with only one RF or those at mild risk for the sake of early diagnosis of possible developmental problems. This would enable inclusion in an appropriate and early habilitation program.

REFFERENCES
1. Bendersky M, Lewis M. Environmental risk, biological risk and developmental outcome. Dev Psychol 1994;30:484–4.
2. Križ M, Mikloušić A, Gazdik M, ur. Rano oštećenje mozga - cerebralna paraliza. Zagreb: August Cesarec, 1988.
3. Mussen PH, Conger JJ, Kagan J, Huston AC. Child development and personality. Harper and Row, Publishers, Inc. 1990;77-81.
4. Kostović I, Judaš M, Bogdanović N. Razvojno – neuroanatomska osnova ranog oštećenja mozga. U: Križ M, Mikloušić A, Gazdik M, ur. Rano oštećenje mozga – cerebralna paraliza. Zagreb: August Cesarec, 1988;21-8.
5. Dennis M. Childhood medical disorders and cognitive impairment : Biological risk, time, development, and reserve. U : Yeates KO, Ris MD, Taylor HG, ur. Pediatric neuropsychology. Research, theory and practice. New York – London: The Guilford press, 1999;3-22.
6. Raju TNK. Hypoxic – Ischemic Encephalopathy. eMedicine 2003
7. Katz KS, Dubowitz LMS, Henderson S, Jongmans M, Kay GG, Nolte CA, De Vries L. Effect of cerebral lesions on CPT responses of school age children born prematurely. J Pediatr Psychol 1996; 21:841–56.
8. Popović-Miočinović Lj, Bošnjak–Nađ K, Sremić Š, Hlača–Mikloušić A, Sunarić D. Kasne posljedice - neurorazvojne smetnje. Medicina 1997;33:97-103. 9. Huber C, Hoditch-Davis D, Brandon D. High - risk preterm infants at 3 years of age: Parental response to the presence of developmental problems. Child Health Care 1993;22:107-24.
10. Bošnjak–Nađ K, Popović–Miočinović Lj, Mejaš ki–Bošnjak V, Kapitanović–Vidak H, Grubešić Z, Sremić Š. Dugoročni ishod neurorizične novorođ enčadi – novi pristup prepoznavanju i praćenju. Gynaecol Perinatol 2004;13:56.
11. Dilenge ME, Majnemer A, Shevell MI. Long–term developmental outcome of asphyxiated term neonates. J Child Neurol 2001;16:781-92.
12. Stevens CP, Raz S, Sander CJ. Peripartum hypoxic risk and cognitive outcome: a study of term and preterm birth children at early school age. Neuropsychology 1999;13:598-608.
13. Barkley RA. Attention–deficit/hyperactivity disorder. U: Mash EJ, Terdal LG, ur. Assessment of childhood disorders. New York-London: The Guilford press, 1997;71-129.
14. Molfese VJ. Perinatal risk and infant development. Assessment and prediction. New York–London, The Guilford press, 1989.
15. Maneru C, Junque C. Cognitive deficits in perinatal asphyxia. Rev Neurol 2002;43:1171-7.
16. Kostović M. Kognitivni ishod i strukturna obiljež ja mozga djece adolescentske dobi s perinatalnim oštećenjem mozga, Zagreb, Hrvatska, 2002. Magistarski rad
17. Rose SA, Feldman JF. Prediction of IQ and specific cognitive abilities at 11 years from infancy measures. Develop Psychol 1995;31:685-96. 18. Bohr L, Greisen G. Prognosis after perinatal asphyxia in full – term infants. Ugeskr Laeger 1998; 160:2845-50.
19. Mash EJ, Terdal LG. Assessment of child and family disturbance: A behavioural system approach. U: Mash EJ, Terdal LG, ur. Assessment of childhood disorders. New York–London, The Guilford press, 1997;3-68.