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The effect of prenatal exposure to coumarins (acenocoumarol, phenprocoumon) on neurological outcome was assessed in a cohort of 306 children aged 7-15 years. Findings were compared with those in a non-exposed cohort of 267 children, matched for sex, age, and demographic region. We used a neurological examination technique which pays special attention to minor neurological dysfunction (MND). None of the children was found to be neurologically abnormal. However, exposure to coumarins during gestation increases the risk for MND in children of school age, odds ratio (OR) 1.9 (CI(95) 1.1-3.4), predominantly after exposure in the second or third trimester, odds ratio 2.1 (CI(95) 1.2-3.8). We found a dose-response relationship with an odds ratio of 1.2 (CI(95) 1.0-1.5) per mg coumarin derivative prescribed per day. The results suggest that coumarins have an influence on the development of the brain which can lead to mild neurological dysfunctions in children of school age.

Anticoagulation during pregnancy is complicated because of potential risks for mother and foetus. Unfractionated or low-molecular-weight heparin is used for most anticoagulant indications. Its efficacy, however, in pregnant women with prosthetic heart valves is questioned, therefore coumarins are preferred for this indication. We studied long-term effects of prenatal coumarin-exposure on growth and on neurological, behavioural and cognitive development in 274 school-age children in comparison with 231 age-matched non-exposed controls. No major abnormalities were found. The exposed children had an increased risk for minor neurological dysfunction and for a low intelligence quotient (IQ below 80). The risk for a combination of two or more (minor) abnormalities was higher for the exposed children, RR = 7.6. We conclude that prenatal exposure to coumarins is associated with an increased risk for disturbances in development in school-age children. However, for the vast majority of children there is no clinical significant effect on growth and long-term development.

Objective: To assess the cognitive abilities in school-aged children who have been exposed to coumarins in utero., Background: Coumarin derivatives are an effective option for anticoagulant therapy in pregnant women. However, case reports describe anomalies of the fetal central nervous system after in utero exposure to coumarins. It is unclear whether prenatal exposure has an effect on cognitive functioning later in childhood., Methods: The exposed cohort consisted of 291 children from mothers who were prospectively registered because of coumarin treatment during pregnancy. The nonexposed cohort included 253 age-matched peers. An IQ was estimated using subtests of the Weschler Intelligence Scale for Children-Revised. Educational achievement was examined with tests for reading, spelling, and arithmetic. In addition, schoolteachers were asked to judge performance on language and arithmetic. The observers were not aware of the exposure status of the child., Results: No differences in mean IQ were found between the exposed and nonexposed cohort (mean difference: -1.1; 95% confidence interval [CI]: -3.2-1.1), but an IQ score below 80 was found in 11 children in the exposed compared with 3 children in the nonexposed cohort (odds ratio [OR] = 3.1; CI: 0.8-11.6). Regarding the tests for educational achievement, exposed children as a group performed as well as nonexposed controls. Exposed boys, in comparison with nonexposed boys, showed a higher frequency of poor performance on reading (OR = 2.9; CI: 1.1-7.4) and spelling (OR = 2.5; CI: 1.0-6.0)., Conclusion: Cognitive functioning in coumarin-exposed children does not differ from nonexposed controls, but a minority of children seem to be prone to the potential negative effects of coumarins during pregnancy.

In utero exposure to coumarin derivatives may affect the development of the central nervous system of the child, irrespective of the period of exposure in pregnancy. Little is known about effects on development in the long term. The aim of the present study was to determine whether prenatal exposure to coumarins affects behavioural outcome in children at school age. Behavioural outcome was assessed in a cohort of 305 exposed children, aged 7-15 years. Findings were compared with those in a cohort of 263 non-exposed controls, matched for sex, age, and demographic region. Behaviour was rated by parents and teachers using standardized questionnaires: the Groningen Behaviour Checklist Family situation (GBF) and the Groningen Behaviour Checklist School situation (GBS), respectively. The findings of the GBF were supported by the results of the GBS, filled in by teachers who were blind for the exposure status of the child. In comparison to the non-exposed children, the coumarin-exposed children scored lower on the cluster 'positive task orientation' (GBF P<0.05, GBS P<0.01), they scored higher on 'emotional instability' (GBF P<0.001, GBS P<0.05), and they had more problems on the social clusters (P<0.01). Based on the results of both questionnaires, we conclude that behavioural development may be negatively influenced in school-age children after in utero exposure to coumarins, leading to less favourable task-oriented and social-emotional behaviour. However, the frequency of clinically relevant 'problem behaviour' (GBF) was not increased in relation to coumarin exposure, the odds ratio was 1.2 (CI(95) 0.7-1.8).

The development of postural adjustments during reaching movements was longitudinally studied in seven infants with cerebral palsy (CP) between 4 and 18 months of age. Five infants developed spastic hemiplegia, one spastic tetraplegia, and one spastic tetraplegia with athetosis. Each assessment consisted of a simultaneous recording of video data and surface EMGs of arm, neck, trunk, and leg muscles during reaching in various lying and sitting positions. The basic organization of postural adjustments of the children developing spastic CP was intact. Their main problem was a deficient capacity to modulate the postural adjustments to task-specific constraints - a deficit which was attributed to a combination of an impaired motor coordination and deficits in sensory integration. The child with spastic-dyskinetic CP showed distinct abnormalities in the basic organization of postural adjustments.

This paper reports on a neural network model for early sensori-motor development and on the possible implications of this research for our understanding and, eventually, treatment of motor disorders like cerebral palsy. We recapitulate the results we published in detail in a series of papers [1-4]. The neural circuits in the model self-organize on the basis of rhythmic activity spontaneously generated in the model. This indicates the importance of endogenously generated activity in the developing brain. We also show that afferent feed-back from the mechanical part of the model is easily incorporated in the neural part of the model. In this way the model acquires reflex-related properties which have long been demonstrated in man. In the discussion we relate these experimental findings to the variability concept from developmental neurology and show how variable motor performance is important for motor learning. We also discuss possible implications of our modelling effort for movement disorders, specifically spastic cerebral palsy.

This study investigated the effect of early feeding mode on the neurological condition at 42 months. For this purpose, healthy pregnant women were recruited in Groningen and Rotterdam, The Netherlands. Children were healthy and born at term. At 42 months, the children were neurologically examined by means of the Touwen/Hempel technique. In addition to the clinical diagnosis, the neurological findings were interpreted in terms of optimality. Special attention was paid to the quality of movements in terms of fluency. In total, 200 (51%) exclusively breastfed(for > or = 6 weeks) and 194 (49%) formula-fed children were studied. Twelve (3%) 42-month-old children were considered to be neurologically mildly abnormal and 1 child was diagnosed as abnormal. No effect of the type of feeding was found on the clinical diagnosis or the neurological optimality. After adjustments for study centre and social, obstetric, perinatal and neonatal neurological differences, a beneficial effect of breastfeeding on the fluency of movements was found (odds ratio for non-optimal fluency 0.56; 95% confidence interval 0.37-0.85). The prolongation of full breastfeeding beyond 6 weeks did not influence the quality of movements. In conclusion, among Dutch preschool children, there was a small advantageous effect of full breastfeeding during the first 6 weeks of life on the fluency of movements.

Adverse neurological effects of exposure to PCBs have been found up to 18 months of age. Now we report on the effect of pre- and postnatal exposure to PCBs and dioxins on the neurological condition at 42 months of age. For this purpose, PCB levels were determined in cord and maternal plasma, and used as a measure of prenatal exposure. Breast milk was analyzed for PCBs and dioxins. In addition, PCBs were determined in plasma sampled from the child at 42 months of age. We evaluated the neurological condition of 394 children using the Touwen/Hempel method. After adjustment for covariates, neither prenatal PCB exposure nor postnatal exposure to PCBs and dioxins was found to be related to the neurological condition at 42 months of age.

The neurological optimality of 418 Dutch children was evaluated at the age of 18 months, in order to determine whether prenatal and breast milk mediated exposure to polychlorinated biphenyls (PCBs) and dioxins affected neurological development. Half of the infants were breast-fed, the other half were formula-fed. PCB concentrations in cord and maternal plasma were used as a measure of prenatal exposure to PCBs. To measure postnatal exposure, PCB and dioxin congeners were determined in human milk and in formula milk. After adjusting for covariates, transplacental PCB exposure was negatively related to the neurological condition at 18 months. Although greater amounts of PCBs and dioxins are transferred via nursing than via placental passage, an effect of lactational exposure to PCBs and dioxins could not be detected. We even found a beneficial effect of breast-feeding on the fluency of movements. We conclude that transplacental PCB passage has a small negative effect on the neurological condition in 18-month-old toddlers.

Polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs)) are widespread environmental contaminants which are neurotoxic in animals. Perinatal exposure to PCBs, PCDDs, and PCDFs occurs prenatally via the placenta and postnatally via breast milk. To investigate whether such an exposure affects the neonatal neurological condition, the neurological optimality of 418 Dutch newborns was evaluated with the Prechtl neurological examination. Half of the infants were breast-fed, the other half were formula-fed, representing a relatively high against a relatively low postnatally exposed group, respectively. As an index of prenatal exposure, four non-planar PCBs in cord and maternal plasma were used. These PCB levels were not related to neurological function. As measures of combined pre- and early neonatal exposure, 17 dioxin congeners, three planar, and 23 non-planar PCB congeners were determined in human milk in the second week after delivery. Higher levels of PCBs, PCDDs, and PCDFs in breast milk were related to reduced neonatal neurological optimality. Higher levels of planar PCBs in breast milk were associated with a higher incidence of hypotonia. This study confirms previous reports about the neurotoxic effects of these compounds on the developing brain of newborn infants.

From the developmental neurological point of view prehension is an important function as it involves the total sensorimotor nervous system. In order to make efficient performance possible both postural activity and motility of arms and hands must be coordinated, implying an intricate interplay between tonic and phasic activities. The analysis of the development of the different contributors suggests that they are based on independently developing brain mechanisms. This independency guarantees the variability which is required for adequately adaptive and purposeful functioning. A lack of this ability to vary, i.e. monotonous and stereotyped function resulting from deficient or deficiently coupled brain mechanisms leads to maladaptive and impaired motor function. Identification of the dysfunctioning brain mechanisms may inform treatment strategies.

The presence of minor neurological dysfunction is associated with behavioural and cognitive development at school age. We have previously shown a relation between minor neurological dysfunction and perinatal disorders, especially abnormal neonatal neurological condition. We have now investigated the relation between breastfeeding and long-term neurological development. We studied 135 breastfed (for > or = 3 weeks) and 391 formula-fed children, born at term in the University Hospital Groningen between 1975 and 1979. A standard neonatal neurological examination was used to classify the infants as normal (247), slightly abnormal (213), or frankly abnormal (66). At 9 years of age the children were reexamined. In 1993 their mothers were asked to complete a questionnaire about how the children were fed as infants. After adjustment for obstetric, perinatal, neonatal neurological, and social differences, a small advantageous effect of breastfeeding on neurological status at 9 years of age was found (odds ratio for neurological non-normality 0.54 [95% CI 0.30-0.97]). Although a retrospective design cannot lead to definite conclusions, our data suggest a beneficial effect of breast-feeding on postnatal neurological development. Longer-chain polyunsaturated fatty acids, which are present in breast-milk but not in most formula-milks, may have a role since they are vital for brain development.

Minor neurological dysfunction (MND) and quality of movement were studied in relation to neonatal cerebral damage and developmental assessments at 3 1/2 years of age in 66 very low-birthweight children without obvious disability. MND was found in 19 children and was significantly related to the quality of movement. The results demonstrate that MND is associated with neonatal cerebral damage at preschool-age, but that the assessment of quality of movement is associated with more complex sensory motor tasks and simultaneous processing. At preschool-age, quality of movement might therefore be a better marker of later learning problems than traditional signs of minor neurological dysfunction.

Neurological, cognitive and behavioural development were assessed in a group of 21, 8- to 10-year old children whose mothers took coumarins during pregnancy. Findings were compared with those in a group of 17 control children. The study was performed to test whether it is feasible to carry out a reliable retrospective study of late effects of prenatal exposure to coumarins. This turned out to be the case. In this small pilot study, no statistical significant differences were found between the study and control group, nevertheless a few findings were remarkable. One child showed severe neurological abnormalities, which may be due to prenatal exposure to oral anticoagulants. The children with the lowest scores on the neurological assessment and the lowest IQ-scores, were found in the exposed group. Obviously, the number of children in this study is too small to conclude if there has been definite effects from coumarin, but these results indicate that a large follow-up study is required. In the present paper, we have shown that such a study is feasible.

The behavioural and cognitive development were studied of 68 children with and 259 without minor neurological function (MND) at 14 years, when the majority of children showed three or more physical signs of puberty. MND was differentiated into fine manipulative disability, co-ordination problems, choreiform dyskinesia and hypotonia. The normal group was subdivided into those who had been normal at 12 years and those who had had MND. All types of MND were related to cognitive and behavioural problems. Fine manipulative disability was related to behavioural and cognitive difficulties; co-ordination problems to learning difficulties; and choreiform dyskinesia and hypotonia were related to attention difficulties and school failure, notwithstanding normal IQ. Besides MND, socio-economic class, family adversities and female gender contributed to the development of behavioural and cognitive problems. The behaviour of children with MND at 12 years who were normal at 14 years did not differ from that of normal children.

Variability is an important property of the central nervous system, and it shows characteristic changes during infancy and childhood. The large amount of variations in the performance of sensomotor functions in infancy is called indiscriminate or primary variability. During toddling age the child develops the capacity to select adaptive variations, and then automatize them: secondary or adaptive variability. The latter is required for the development of motor skills during later preschool age and school age. The question 'How normal is variable or how variable is normal is a wrong question, as any form of variability must be interpreted according to its extent, type and age adequacy.

The normal central nervous system is characterized by both activity and reactivity. Under normal circumstances the former leads the latter. In abnormal conditions reactivity may predominate, usually in the form of reflexes and abnormal postural reactions. Ultrasound registration shows that the first spontaneous motor movements can be seen in the seventh to eighth gestational week. Movement patterns develop fast, and in mid-pregnancy all patterns are observed that can be found in the term newborn baby. During the second half of pregnancy movement patterns are refined: the first differentiation leading to variable and fluent movements. The intrauterine movements are qualitatively more or less similar to those seen in normal preterm babies, the main difference being that the latter as to counteract gravity forces to a greater extent. Qualitative changes of the movement patterns signal deteriorating intrauterine conditions. Stereotyped quality of movement can be a sign of abnormal development. During infancy normal development is characterized by great variability in performance, developmental sequences and relationships. Stereotype performance and strong relationship between the various motor functions, reactions and reflexes should arouse the suspicion that there may be a disturbance in development.

In order to study the hypotheses that puberty is related to a decrease of minor neurological dysfunction (MND) and that persisting MND is associated with perinatal factors, two groups (174 normal, 172 MND) of the Groningen Perinatal Project were followed from 12 to 14 years. At 14 years almost all the children had entered puberty (n = 329) defined as the presence of three or more puberty signs. In the MND group 55% of the children were normal at 14 years and in 45% MND signs were still present, though in a less extensive form. The latter phenomenon was most clear in children who had just begun puberty. The effect of puberty was similar in both sexes. MND which persisted into puberty was related to neonatal neurological deviancy, lower social class, lower obstetrical optimality score and male sex. After differentiation with specific MND clusters, it appeared that fine manipulative disability was associated with neonatal neurological deviancy, with minor physical anomalies and with lower social class; choreiform dyskinesia with asphyxia; hypotonia with constitutionally related factors; and coordination problems with pre-maturity (< 32 weeks).

In a longitudinal study individual trajectories were traced for the developing relationship between active and passive muscle power in preterm (n = 37) and fullterm (n = 20) infants from term to 24 weeks (corrected) age. Such trajectories should enable the identification of those infants at highest risk for later neurological dysfunctions. This contention is supported by the findings of this study: those preterm infants who showed marked discrepancies between the two sorts of muscle power or rigidity in both beyond 12 weeks corrected age were most likely to manifest neurological problems at 52 weeks of age.

Behavioural and cognitive development at 12 years were studied in 172 children with and 174 children without minor neurological dysfunction (MND). MND could be differentiated into fine manipulative disability, co-ordination problems, hypotonia and choreiform dyskinesia. Fine manipulative disability related significantly to problems of cognition and behaviour; co-ordination problems to cognitive problems; and hypotonia and choreiform dyskinesia to behavioural problems, the former more than the latter. Socio-economic status and family adversity contributed to the risk for development of both cognitive and behavioural problems; gender did not. The onset of puberty seemed to change these relationships: follow-up is needed for definite conclusions.

The effect of intra-uterine movement restriction on the development of motor functions was studied longitudinally by comparing infants born after uncomplicated breech position (n = 13) with control infants (vertex position, n = 5-10). Before birth, fetal leg posture was studied at regular intervals by means of real time ultrasound observations, and classified as complete (n = 1), inconsistent (n = 6), or incomplete (n = 6) breech position. Limited extension of the hips, preference posture and joint position in percentage of time (each until 12 weeks), withdrawal reflex and magnet response (until 26 weeks) and posture while sitting, standing and walking without support (up to 12-18 months) were assessed longitudinally. The results showed statistically significant, positive relationships between intra-uterine breech position and neonatal limited extension of the hip-joint, between limited extension of the hip-joint and the percentage of time that the hips are in flexion during the first 12 weeks, between this flexion of the hips (in percentage of time) and an abnormally 'flexed' walking pattern at 12-18 months, and finally, between a positive magnet response at 6 months and an abnormal walking pattern at 12-18 months. These findings suggest that intra-uterine movement restriction of the legs can cause long term alterations in the development of motor functions (leg posture, reflexes and posture while walking), possibly mediated by alterations in proprioceptive feedback mechanisms.

Fifty-eight infants were assessed with an instrument which is designed to evaluate the development of the relationship between active and passive muscle power. The purpose of this longitudinal assessment was to investigate whether preterms show a different development course than fullterms in the relationship between these two components of muscle power. Thirty-seven low-risk preterms and twenty-one healthy fullterms were followed from term until 24 weeks corrected age. It is concluded that preterms differ markedly from fullterms in the developing interrelationship between active and passive muscle power. The value of the instrument for detecting signs of early pathology is discussed.

In a group of 570 nine-year-old children (315 boys and 255 girls) without an overtly handicapping neurological condition, relationships were studied between the presence of minor neurological dysfunction (MND) on the one hand and cognitive and behavioral problems on the other hand. The aim of the study was to investigate whether MND was more closely related to learning problems than to behavioral difficulties. The group was a subpopulation of the birth cohort of the Groningen Perinatal Project in the Netherlands, in which perinatal developmental relationships are studied. The age-specific and standardized neurological examination technique of Touwen (1979) was used, resulting in a description of the neurological condition in terms of the number of deviant clusters. The absence of deviant clusters indicated a normal neurological condition (n = 418); children with one or two deviant clusters were classified as MND-1 (n = 86) and those with more than two deviant clusters as MND-2 (n = 66). The presence and severity of MND was significantly related to poor performance on standardized reading, spelling, and arithmetic tests. MND was also related to ratings of distractible behavior on parent and teacher questionnaires, but to a lesser extent than the cognitive problems. Ratings of so-called "troublesome" and "timid" behavior were not related to MND. Our conclusion is that learning problems are more closely related to MND than are behavioral difficulties. This has implications for prevention and intervention: In the former the focus should be more on biological hazards, in the latter on environment and rearing attitudes.

Risk factors during pregnancy and delivery and neurological morbidity of newborns were assessed in a birth cohort in Dominica, the Caribbean. The data were compared with two reference groups, one from Grenada, the Caribbean, and the other from Groningen, the Netherlands. Despite variations in cultural and socio-economic situation, the similarities in obstetrical conditions, neonatal neurological morbidity and perinatal relationships between the three groups were more striking than the differences. The Dominican group showed a significantly higher rate of preterm births than the two other groups. Preterm birth was associated with a significant increase in neurological deviancy. In general motility and muscle tone were found to be lower in the Caribbean region than in the Netherlands.

The purpose of this paper is to report a detailed description of an instrument for evaluating the development of active and passive muscle power in preterms beyond term age. The instrument is constructed on a basis of age-specific items that assess these two components of muscle power and on the assumption that a persistent discrepancy between them serves to detect those preterms at most risk for disturbances in motor development. The application of the instrument is illustrated by reporting the individual trajectories of five case studies without any serious medical complications. It is concluded that if a marked discrepancy between active and passive power persists beyond the corrected age of 3 months, then this may be a sign of underlying pathology which will eventuate in abnormal postural outcomes and thereby disturbances in the control and coordination of movement. Having now provided a detailed description of how this instrument should be applied in postterm follow-up of preterm infants, we are currently examining its sensitivity and specificity on a much larger sample of similar subjects.

To determine whether puberty is related to decreased minor neurological dysfunction (MND), 174 children from the Groningen Perinatal Project who had had MND at nine years were re-examined at 12 years. No signs of MND could be demonstrated in 39 of the children, 33 of whom showed at least three signs of puberty. The presence of minor physical anomalies was associated with persisting MND. The authors hypothesise that puberty is related to a decrease in MND, and discuss the role of hormonal changes in relation to the decrease in minor signs. Re-examination at 14 years will be necessary to confirm this hypothesis, since 68 per cent of the children had not yet reached puberty. Children with MND reached puberty no later than those without.

To study the hypothesis that the frequency of minor neurological dysfunction (MND) stabilizes around the age of nine years, two groups of the Groningen Perinatal Project (GPP) were re-examined at 12 years. The study group (N = 174) was selected on the basis of the presence of MND at nine years; the control group comprised 172 neurologically normal children. The hypothesis was rejected: extrapolation of the findings to the total GPP population showed that the over-all rate of MND increased. Control children who developed MND were mainly boys who had been neurologically abnormal at birth or were born preterm and/or had experienced an adversity in combination with asphyxia. Interval complications between nine and 12 years were related to the emergence of MND.

Various quantitative and qualitative aspects of crawling were analysed in small groups of carefully selected normal toddlers of 1 1/2, two, 2 1/2, three, 3 1/2 and four years of age in a cross-sectional design. Between two and three years of age, major changes occurred in all observed aspects, resulting in differentiated, adaptive and efficient crawling. It is proposed that these changes are based on so-called adaptive variability, an age-related developmental process which seems to be a prerequisite for the development of cognition.

On follow-up at 12 years to assess the relationship between minor neurological dysfunction (MND) and primary nocturnal enuresis (NE), the frequency of NE was found to be significantly higher in children with MND (N = 167) than in those who were neurologically normal (N = 174). There was no relationship between NE and sex in the MND group, nor with the neonatal neurological condition. Among MND children, those with NE more often had language comprehension and arithmetic problems and they required special help for behavioural problems more than did those without such problems. The relationship between NE and MND was affected by socio-economic class and family history. It is concluded that children with MND are more vulnerable to NE, particularly in the presence of lower social class and a positive family history.

In a follow-up study long-term effects of antenatal exposure to two anticonvulsant drugs, phenobarbital and carbamazepine on central nervous system development were evaluated. Children aged 6 to 13 years of epileptic mothers who used phenobarbital (n = 13), carbamazepine (n = 12), phenobarbital plus carbamazepine (n = 12), or no medication (n = 24) during pregnancy were studied. None of the mothers had seizures during pregnancy. A control group carefully matched for confounding variables was selected of children of nonepileptic mothers (n = 61). Minor and major congenital anomalies appeared to be more related to mother's epilepsy than to maternal medication. There were no neurologic differences between the groups. Exposure to phenobarbital was associated with smaller head circumference. An accompanying negative effect of phenobarbital on cognitive development was suggested. Further research on this intriguing phenomenon seems warranted.

Neonatal morbidity, in particular neurological morbidity is a more relevant measure of the effectiveness of obstetrical care than perinatal mortality. Neurological morbidity was assessed in a birth cohort in Grenada, and appeared to be lower than in a reference group examined in Groningen, the Netherlands, in 1975-1978. Perinatal mortality, however, was higher. The results support the thesis that some children may have died who, if they would have survived, would have been neurologically abnormal. It is concluded that whereas a decrease in perinatal deaths is an essential goal in Grenada, a concomitant increase in morbidity should be carefully avoided.

Observations of the variability stereotypy ratio of spontaneous motility in a group of 47 preterm infants showed that stereotyped motor activity was related to the neurological diagnosis at term age. A minority of the neurologically deviant infants at term recovered during infancy. The presence of absence of intra-uterine growth retardation and an accumulation of obnoxious antenatal, perinatal and postnatal events seemed to affect outcome, particularly in the presence of extensive and permanent ultrasound findings. A normal neurological condition at term indicates a high probability of normal development.

In three groups of low birth weight (LBW) infants: full term, small-for-gestational-age (FT-SGA, N = 142); preterm, appropriate-for-gestational-age (PT-AGA, N = 47); preterm, small-for-gestational-age (PT-SGA, N = 20); and a reference group of FT-AGA infants (N = 185) the relationship between body weight, body length and head circumference and the presence of minor neurological dysfunction (MND) was studied. Non-caucasian and handicapped children were excluded from the analysis. Data were collected on behaviour and school achievement. The parameters of physical growth in the three LBW groups were reduced significantly compared to the FT-AGA group. In both preterms and full-terms body measurements were related to weight at term age; in the preterm groups no relation with gestational age at birth was found. MND was not related to body weight or length. In the group of FT severely growth retarded infants a relation was found between a skull circumference below the third centile and the presence of MND. Body measurements, behaviour at home and at school and school achievement were not related. The significance of severe intrauterine growth retardation for developmental disorders is emphasized. The data suggest a different aetiology and clinical significance of small head size for AGA and SGA born children.

Of 1655 newborns examined neurologically at term, 80 were found to be abnormal. 76 were traced at six years of age, together with a control group of 77 neonatally normal children. In the study group five children had died, six were severely handicapped and 21 had minor neurological dysfunction (MND). In the control group two had died and four had MND. Obstetrical and neonatal paediatric effects, as well as complications in the intervening years, appeared to have a cumulative effect on the relationship between the neonatal neurological condition and the neurological findings at six years. There were no large differences in behaviour between the study group and the controls, but the study-group MND children showed a stronger tendency for undesirable behaviour and poor school achievements. Although environmental influences are preponderant for the development of behaviour and school performance, a contribution of both neonatal and later neurological conditions seems likely.

A study was conducted of all children delivered in breech presentation from 1969 to 1977 in the university's department of obstetrics. One-fifth of the deliveries were by caesarean section. Perinatal mortality was high (13.2%) but was due almost exclusively to causes other than the birth itself. The 256 surviving children and their matched controls were neurologically examined at 18 months or at ages varying between 3 and 10 years. The attrition rate was 5.7%, but in most cases data on development were available. Significant differences between the study and control groups existed for only minor neurological dysfunctions. It is concluded that the main danger of breech presentation is in the associated complications of pregnancy and that there is no reason to advocate a higher frequency of abdominal delivery than the 20% found in this study.

Neonatal condition was assessed in a group of 82 infants born at term after maternal treatment with ritodrine for an average of 28.5 days, and compared with that in a matched control group of infants. No statistically significant differences were found in umbilical pH, Apgar scores, head circumference, and neurological condition. Although the difference was not statistically significant, doubt remains as to a possible icterogenic effect of ritodrine.

Hyperextension of the neck and trunk associated with shoulder retraction is often regarded as an early sign of a developing neurological impairment, which may lead to cerebral palsy. Follow-up results over the first 18 months of life in a group of 105 infants presenting this symptomatology showed that the presence of additional neurological symptomatology rather than hyper-extension as an isolated phenomenon determines prognosis. Neonatal neurological abnormality increases the risk for an abnormal development. Although more boys than girls presented hyperextension, no clear sex differences were found with regard to the influence of additional neurological symptomatology. Physiotherapy appeared to be of limited value only.

A study concerning the relationship between neonatal neurological abnormality and 3 parameters of pre- and perinatal condition in a birth cohort of 1507 infants was replicated in a second cohort of 1655 infants. The 3 parameters chosen were preterm birth, intrauterine growth retardation and neonatal acidemia. The neurological examination in the second cohort was carried out by other examiners than in the first cohort. The incidence of neurological abnormality was again found to be raised in all 3 categories and again least in the acidemic subgroup. Also the finding could be confirmed that only in about half of the neurologically abnormal infants could the 3 parameters have exerted any effect at all, which implies the necessity of further analysis. This replication study shows that neurological examination in the newborn period is a reliable tool for the evaluation of the condition of infants with respect to their pre- and perinatal history.

A follow-up study at six and/or nine years of age was carried out on subpopulations of the three years cohort of the Groningen Perinatal Project. Neurological handicap and minor neurological dysfunction (MND) were associated with different sets of risk factors. The findings suggest a temporal difference in potentially harmful factors. At nine years of age two different kinds of MND could be distinguished, each of them related in a specific way to perinatal risk factors and behavioural and cognitive development. The finding that social factors, sex and present neurological condition of the child appeared to be more important than pre- and perinatal events for the development of learning and behavioural problems illustrates the complex aetiology of the latter.

A prospective study was carried out on 747 infants: 147 neurologically abnormal, 300 with mild neurological abnormalities and 300 normal infants. They were re-examined at nine years of age, with special attention being paid to minor neurological dysfunction (MND). Extensive data on obstetrical history, neonatal course and interval complications were collected. Neurological handicap was not found on follow-up in the group of normal newborns. Other than neonatal neurological abnormality, risk factors contributing significantly to later handicap were low one-minute Apgar scores, a disturbed neonatal course, low social-class and interval complications; obstetrical events were conspicuous by their absence. Two aetiologically and clinically distinct kinds of MND were distinguished on the basis of a neurological cluster profile: MND-1 (one or two abnormal clusters) was only associated with a birthweight below the 2.3 centile and male gender, and MND-2 (more than two abnormal clusters) was associated with neonatal neurological findings, social class, obstetrical optimality score and gender.

From a cohort of 1507 infants in the Perinatal Project at University Hospital, Groningen, 80 infants who had been neurologically abnormal in the neonatal period and 80 controls were neurologically re-examined at 18 months of age. Of the 80 abnormal infants, one had died at age three months and 13 other remained abnormal at 18 months, of whom five had severe neurological dysfunction. Two of the control infants had mild abnormalities at 18 months. The rate of false negative results was low, but there was a high rate of false positive results, indicating a high frequency of transient neonatal morbidity. This study demonstrates the sensitivity of the neonatal neurological examination in selecting newborn infants who are in special need of attention.

A neurological follow up study was done of 143 full-term infants who were small for gestational age based on intrauterine growth retardation and of 49 preterm appropriate-for-gestational-age (PTAGA) infants at the age of 6 years. Findings were compared with those of a reference group of 192 full-term appropriate-for-gestational-age (FTAGA) children. In 11% of the children of both study groups, hypotonia was found without any other neurological deviancy. This type of hypotonia was absent in the reference group, whereas minor neurological dysfunction consisting of hypotonia with other neurological signs was found in all the three groups of children. No relation was found with obstetrical or neonatal variables, including severity of growth retardation and gestational age, or with weight, body height or head circumference at 6 years. The possible interference of preterm birth or intrauterine growth retardation with, and the role of placental mechanisms in, fetal and early postnatal muscle development is discussed.