Mijna Hadders-Algra

How much loss to follow-up is acceptable in long-term randomised trials and prospective studies?

to test early nutritional interventions and prospective observational cohorts. RCTs are generally accepted as methodologically the best approach for informing health policy. They can equalise unknown as well as known confounding factors and so can demonstrate causation; they permit estimation of effect size and so can be used to assess likely economic

Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development

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.

A systematic review of the effects of early intervention on motor development

We present a systematic review on the effect of early intervention, starting between birth and a corrected age of 18 months, on motor development in infants at high risk for, or with, developmental motor disorders. Thirty-four studies fulfilled the selection criteria. Seventeen studies were performed within the neonatal intensive care unit (NICU) environment. Eight studies had a high methodological quality. They evaluated various forms of intervention. Results indicated that the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) intervention might have a temporary positive effect on motor development. Twelve of the 17 post-NICU studies had a high methodological quality. They addressed the effect of neurodevelopmental treatment (NDT) and specific or general developmental programmes. The results showed that intervention in accordance with the principles of NDT does not have a beneficial effect on motor development. They also indicated that specific or general developmental programmes can have a positive effect on motor outcome. We concluded that the type of intervention that might be beneficial for infants at preterm age differs from the type that is effective in infants who have reached at least term age. Preterm infants seem to benefit most from intervention that aims at mimicking the intrauterine environment, such as NIDCAP intervention. After term age, intervention by means of specific or general developmental programmes has a positive effect on motor development.

Two distinct forms of minor neurological dysfunction: perspectives emerging from a review of data of the Groningen Perinatal Project

In the past 40 years, children with minor developmental motor disorders have been studied by professionals from various fields: paediatricians, neurologists, psychiatrists, psychologists, and physical and occupational therapists. The differences in background of these professionals led to a plethora of terms used to refer to these conditions: e.g. minimal cerebral palsy, minimal cerebral dysfunction, developmental apraxia or dyspraxia, minimal brain dysfunction, sensory integrative dysfunction, and developmental coordination disorder.1,2 It was generally acknowledged that such a multitude of names was confusing and so, in 1994, an international consensus meeting of professionals from various fields agreed to use the term ‘developmental coordination disorder’ (DCD).3,4 DCD in general refers to children with normal intelligence who have poor motor coordination without clear evidence of a neurological pathology, such as cerebral palsy (CP) or muscular dystrophy. In other words, DCD is a ‘final common output’ term, without aetiological or pathophysiological foundation. The advantage of such an umbrella term is that it includes all children with motor problems that interfere with their daily life, i.e. children who deserve clinical attention. However, the disadvantage of the term DCD is its aspecificity. Indeed, it is becoming increasingly clear that children with DCD constitute a heterogeneous population with various types of motor dysfunction.5,6 Neurological examination is an excellent tool for assessing types of motor dysfunction in children with DCD. With the help of a standardized and age-adequate neurological examination technique7,8 various forms of minor neurological dysfunction (MND), such as mild dysfunctions in muscle tone regulation, choreiform dyskinesia, or fine manipulative disability, can be diagnosed accurately and reliably.8,9 At times, MND or ‘soft neurological signs’ meet with a sceptical response.10 This is usually due to lack of neurological expertize which should include a thorough knowledge of the child’s age-dependent neurological repertoire. The term MND is preferable to the expression ‘soft neurological signs’ as the word ‘soft’ has the connotation of malleability and is an imprecise definition.11,12 Children with DCD are at a higher risk for learning and behavioural disorders, such as attention problems, than children without DCD.1,13 Children presenting with both DCD and attention problems are also known as children with deficits in attention, motor control, and perception (DAMP).13 Little is known about the perinatal aetiology of the relatively new entities DCD and DAMP. More data are available on the role of perinatal adversities in the broader category of minor developmental disorders and the more specific category of MND. The present paper starts with a discussion of the literature on this subject. This is followed by an overview of the results of the Groningen Perinatal Project, which focuses on the contribution of perinatal risk factors to the development of different forms of MND. The paper concludes with the description of two aetiologically and clinically different forms of MND.

Proprioceptive control of posture: a review of new concepts.

The assumption that proprioceptive inputs from the lower legs are used to trigger balance and gait movements is questioned in this review (an outgrowth of discussions initiated during the Neural Control of Movement Satellite meeting held in Cozumel, Mexico, April 1997). Recent findings presented here suggest that trunk or hip inputs may be more important in triggering human balance corrections and that proprioceptive input from the lower legs mainly helps with the final shaping and intermuscular coordination of postural and gait movements. Three major questions were considered. First, what role, if any, do lower-leg proprioceptive inputs play in the triggering of normal balance corrections? If this role is negligible, which alternative proprioceptive inputs then trigger balance corrections? Second, what is the effect of proprioceptive loss on the triggering of postural and gait movements? Third, how does proprioceptive loss affect the output of central pattern generators in providing the final shaping of postural movements? The authors conclude that postural and gait movements are centrally organized at two levels. The first level involves the generation of the basic directional-specific response pattern based primarily on hip or trunk proprioceptive input secondarily on vestibular inputs. This pattern specifies the spatial characteristics of muscle activation, that is which muscles are primarily activated, as well as intermuscular timing, that is, the sequence in which muscles are activated. The second level is involved in the shaping of centrally set activation patterns on the basis of multisensorial afferent input (including proprioceptive input from all body segments and vestibular sensors) in order that movements can adapt to different task conditions. Copyright 1998 Elsevier Science B.V.

The Neuronal Group Selection Theory: a framework to explain variation in normal motor development

During the last century, knowledge of the mechanisms governing the functions of the central nervous system increased rapidly as sophisticated physiological, neurochemical, and imaging techniques developed. In the field of motor control, better understanding of neurophysiology caused a gradual shift from the concept that motor behaviour is largely controlled by reflex mechanisms1,2 towards the notion that motility is the net result of complex spinal or brainstem activity, which is subtly modulated by segmental afferent information and ingeniously controlled by supraspinal networks3,4. Nowadays it is assumed that motor control of rhythmical movements like locomotion, respiration, sucking, and mastication is based on so-called central pattern generators (CPGs): neuronal networks which can generate complex basic activation patterns of the muscles without any sensory signals. Nevertheless, sensory information of the movement is important in adapting the movement to the environment. The activity of the networks, which are usually located in the spinal cord or brainstem, is controlled from supraspinal areas via descending motor pathways4. The supraspinal activity itself is organized in large-scale networks in which cortical areas are functionally connected through direct recursive interaction or through intermediary cortical or subcortical (striatal, cerebellar) structures5–7. Concurrently, albeit at a considerably slower pace, knowledge of motor development has increased. Consequently, theoretical frameworks for the processes involved in the development of motor control have changed. The aim of the present paper is to discuss the two major current but conflicting theories; the Neural-Maturationist Theories and the Dynamic Systems Theory. A third theory, the Neuronal Group Selection Theory (NGST) will also be discussed. The NGST combines the ‘nature’ part of the Neural-Maturationist Theories with the ‘nurture’ part of the Dynamic Systems Theory. Application of the concepts of the NGST could facilitate the understanding of motor disorders and, thereby, offer new possibilities for intervention therapies – an issue which will be discussed in a forthcoming publication8.

The neuronal group selection theory: promising principles for understanding and treating developmental motor disorders

There are two major forms of developmental motor disorders: cerebral palsy (CP) and clumsiness. CP is an umbrella term covering a group of non-progressive, but often changing, motor impairment syndromes secondary to lesions or anomalies of the brain arising in the early stages of development1. It affects about 1 in 500 live-born children2. Clumsy children nowadays are classified according to DSM-IV as having developmental coordination disorder (DCD), a term denoting children who have such poor motor coordination that it affects daily activities at home and at school, but with normal intelligence and without obvious neurological pathology3. The prevalence of DCD is about 10% (6 to 13%4–6). The understanding of the motor problems in both groups of children is hampered by the large heterogeneity within each group. In both groups children differ in the expression of their motor dysfunction, in comorbidity such as the presence of cognitive and behavioural disorders, and in aetiology. In addition, the relation between the various motor disorders and the structural abnormalities of the brain is far from simple. CP is, by definition, attributed to lesions or anomalies of the young brain, but the abnormalities of the brain cannot always be visualized with imaging techniques. Despite there being some relation between lesions of the periventricular white matter and spastic diplegia, and between unilateral lesions and spastic hemiplegia, the site of the lesion does not correlate exactly with the type of motor dysfunction7–9. In children with DCD the connection between structural abnormalities of the brain and motor dysfunction is still more ambiguous. Recently Hadders-Algra and Touwen10 argued that indications for preand perinatal brain damage can be found only in one third of children with minor motor dysfunction. This could imply that most clumsy children do not have macroscopic anomalies of the brain, but dysfunctions at the microscopic level of the nervous system, with abnormalities in the neurotransmitter or receptor systems, for example.

Quality of general movements in infancy is related to neurological dysfunction, ADHD, and aggressive behaviour

The quality of general movements (GMs) was assessed repeatedly during the first postnatal months in a mixed group of 52 children at either low or high risk for neurodevelopmental disorders. In addition, all children were reexamined at 4 to 9 years. The follow‐up assessment consisted of a neurological examination and an evaluation of behaviour by means of parental questionnaires. The quality of GMs changed frequently, to stabilize in the final phase. The final GM phase is that of the so‐called fidgety GMs which occurs between 2 and 4 months postterm. The quality of the fidgety GMs predicted outcome very well. Definitely abnormal GMs were associated with a high risk for the development of cerebral palsy, whereas mildly abnormal GMs were associated with the development of minor neurological dysfunction, attention‐deficit–hyperactivity disorder, and aggressive behaviour.

Postural Control in Sitting Children with Cerebral Palsy

Children with cerebral palsy (CP) display postural problems, largely interfering with daily life activities. Clarification of neural mechanisms controlling posture in these children could serve as a base for more successful intervention. Studies on postural adjustments following horizontal forward and backward displacements of a movable platform in ten school-age children with spastic diplegia and non-disabled controls revealed that sitting CP children, like standing CP children, show direction specific postural adjustments, indicating that the basic pattern of muscle coordination in these conditions is conserved. Dysfunctions are especially present in the modulation of the response pattern of ventral muscles during forward translations. They consist of: (1) a stereotyped and non-variable activation of all ventral muscles; (2) an abnormal top-down muscle recruitment; and (3) an excessive degree of antagonistic co-activation. The altered patterns of muscle coordination could be the result of two interacting mechanisms, the primary deficit due to the early brain damage and a compensation due to the postural instability. Especially the latter dysfunction furnishes opportunities for therapeutic help.

Variation and Variability: Key Words in Human Motor Development

This article reviews developmental processes in the human brain and basic principles underlying typical and atypical motor development. The Neuronal Group Selection Theory is used as theoretical frame of reference. Evidence is accumulating that abundance in cerebral connectivity is the neural basis of human behavioral variability (ie, the ability to select, from a large repertoire of behavioral solutions, the one most appropriate for a specific situation). Indeed, typical human motor development is characterized by variation and the development of adaptive variability. Atypical motor development is characterized by a limited variation (a limited repertoire of motor strategies) and a limited ability to vary motor behavior according to the specifics of the situation (ie, limited variability). Limitations in variation are related to structural anomalies in which disturbances of cortical connectivity may play a prominent role, whereas limitations in variability are present in virtually all children with atypical motor development. The possible applications of variation and variability in diagnostics in children with or at risk for a developmental motor disorder are discussed.