White Matter Injury and General Movements in High-Risk Preterm Infants.

BACKGROUND AND PURPOSE: Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. MATERIALS AND METHODS: In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. RESULTS: Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. CONCLUSIONS: Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays.

The Baby Moves prospective cohort study protocol: using a smartphone application with the General Movements Assessment to predict neurodevelopmental outcomes at age 2†years for extremely preterm or extremely low birthweight infants.

INTRODUCTION: Infants born extremely preterm (EP; <28 weeks' gestation) and/or with extremely low birth weight (ELBW; <1000 g birth weight) are at increased risk for adverse neurodevelopmental outcomes. However, it is challenging to predict those EP/ELBW infants destined to have long-term neurodevelopmental impairments in order to target early intervention to those in most need. The General Movements Assessment (GMA) in early infancy has high predictive validity for neurodevelopmental outcomes in preterm infants. However, access to a GMA may be limited by geographical constraints and a lack of GMA-trained health professionals. Baby Moves is a smartphone application (app) developed for caregivers to video and upload their infant's general movements to be scored remotely by a certified GMA assessor. The aim of this study is to determine the predictive ability of using the GMA via the Baby Moves app for neurodevelopmental impairment in infants born EP/ELBW. METHODS AND ANALYSIS: This prospective cohort study will recruit infants born EP/ELBW across the state of Victoria, Australia in 2016 and 2017. A control group of normal birth weight (>2500 g birth weight), term-born (≥37 weeks' gestation) infants will also be recruited as a local reference group. Parents will video their infant's general movements at two time points between 3 and 4 months' corrected age using the Baby Moves app. Videos will be scored by certified GMA assessors and classified as normal or abnormal. Parental satisfaction using the Baby Moves app will be assessed via survey. Neurodevelopmental outcome at 2 years' corrected age includes developmental delay according to the Bayley Scales of Infant and Toddler Development-III and cerebral palsy diagnosis. ETHICS AND DISSEMINATION: This study was approved by the Human Research and Ethics Committees at the Royal Children's Hospital, The Royal Women's Hospital, Monash Health and Mercy Health in Melbourne, Australia. Study findings will be disseminated via peer-reviewed publications and conference presentations.

How can clinicians detect and treat autism early? Methodological trends of technology use in research.

UNLABELLED: We reviewed original research papers that used quantifiable technology to detect early autism spectrum disorder (ASD) and identified 376 studies from 34 countries from 1965 to 2013. Publications have increased significantly since 2000, with most coming from the USA. Electroencephalogram, magnetic resonance imaging and eye tracking were the most frequently used technologies. CONCLUSION: The use of quantifiable technology to detect early ASD has increased in recent decades, but has had limited impact on early detection and treatment. Further scientific developments are anticipated, and we hope that they will increasingly be used in clinical practice for early ASD screening, diagnosis and intervention.

General movements in infants with autism spectrum disorders.

General movements (GMs) are a distinct movement pattern carried out spontaneously without external stimulation and seen in fetuses of 9 weeks gestational age till 21 weeks postterm. GMs are helpful in the early diagnosis of an impaired central nervous system and the specific prediction of later neurological deficits. Autism spectrum disorder (ASD) is a neurodevelopmental disorder involving a life-long deficit in several aspects of the social and communicative behavior. Recently there appeared studies proving that children with ASD demonstrate disorders of motor development. To detect whether abnormalities in spontaneous motor activity can be observed already in the first months of life in infants with ASD. A retrospective study was performed by analyzing the family videos provided by parents of 20 children (male 17, female 3) later diagnosed as ASD. Home videos provided by parents of a control group of healthy children (n=20; male 10, female 10) matched for age with the ASD subjects and recorded in similar conditions were also analysed. In total 70 sequences were studied. Two independent observers, blind of the infants' outcome (ASD or normal), assessed the cases applying a global and a more detailed assessment of GMs. Hence, the age-specific GM pattern (normal or abnormal) as well as motor optimality scores were determined for each video sequence. Cohen kappa was 0.614. During the writhing movement period 70.0% sequences of infants with ASD showed poor repertoire GMs. In the control group, poor repertoire GMs were only seen in 12.5% of the sequences. In the fidgety movement period 20.8% of sequences were assessed as absent fidgety movements, 29.2% as abnormal fidgety movements. The large majority of the videos for the control cases were scored as normal (88.9%), 11.1% had no fidgety movements. According to the Mann-Whitney U test there were significant differences between the ASD and the control groups' optimality scores. The optimality scores were lower in the ASD group. The reduced optimality scores were mainly due to a lack of variable sequences, amplitude and speed of writhing GMs and an altered quality of fidgety and other spontaneous movements in the ASD group. Infants with ASD had more often poor repertoire writhing GMs as well as abnormal or absent fidgety movements than control infants. These data encourage further studies involving a larger number of family videos.

The long-term outcome of infantile apparent life-threatening event (ALTE): a follow-up study until midpuberty.

The neurological long-term sequelae of an idiopathic apparent life-threatening event (ALTE) were studied in 14 ALTE cases and 12 controls (of similar sex, age, and maturation of puberty). One ALTE case had developed motor and severe learning disabilities. Four other cases and one control were judged as MND (minor neurological deficits). Touwen's neurological profile was less optimal in children with an ALTE history than in controls (p < 0.05). A high amount of associated movements were found in combination with an inability of certain gross motor functions, such as standing or hopping on one leg for sufficiently long or walking on tip-toes or on heels. Fine and gross motor performance tested with the Bruininks-Oseretsky test and behaviour judged with Connors' Rating Scales--Revised, were not different between ALTE cases and controls. Our study provides evidence of neurological long-term sequelae of ALTE.

Sudden infant death syndrome risk questionnaire: a mirror of parental awareness rather than a prospective diagnostic tool.

AIM: In 1989, a scoring system that aimed to identify infants at risk of sudden infant death syndrome (SIDS) by a structured questionnaire [SIDS risk questionnaire (SRQ)] consisting of 25 items was introduced in Styria (Austria). It was the aim of the study to compare SIDS rates in the population that had access to the SRQ with the population that had no access. Furthermore, for the population receiving the SRQ, the responding (compliant) and non-responding (non-compliant) groups were compared concerning the incidence of SIDS. METHODS: Within the study period, 53 865 births and 57 SIDS cases were recorded (incidence 1.06/1000) and analysed retrospectively. RESULTS: The incidence of SIDS was significantly higher in the non-responding population (2.36/ 1000) than in the responding group (0.81/1000, p < 0.001). However, the incidence of SIDS was not significantly different in the population that had access to the risk questionnaire (1.29/1000) and the group without access (0.86/1000, p = 0.145). CONCLUSION: The value of any questionnaire used for SIDS prevention may be limited by the existence of a non-compliant population which represents a risk group and should be targeted by other preventive measures.

General movements detect early signs of hemiplegia in term infants with neonatal cerebral infarction.

Background. Studies have reported that infants with hemiplegia of congenital origin may have a period between birth and up to 12 months when clinical signs of hemiplegia are not evident. The aim of this study was to establish whether the assessment of general movements (GMs) may help in the earlier detection of signs of hemiplegia. Subjects and Methods. Eleven infants with cerebral infarction on brain MRI, and eleven normal controls were enrolled in the study. Quality of GMs was assessed from videotapes between 3 and 6 weeks and between 9 and 16 weeks. Neurological outcome was evaluated at least at two years. Results. Seven of the 11 infants had an assessment performed between 3 and 6 weeks: abnormal GMs were observed in all the infants who developed hemiplegia, but one child had abnormal GMs and a normal outcome. All 11 infants had a scorable assessment between 9 and 16 weeks. In all a specific type of GMs, fidgety movements (FMs), were predictive of neurological outcome. The presence of early asymmetries at both 3 - 6 and 9 - 16 weeks was also significantly associated with later signs of hemiplegia. Conclusions. The assessment of GMs after the neonatal period appears to be very useful in the early identification of hemiplegia in infants with cerebral infarction. Whilst the prediction of hemiplegia should be possible from early neonatal MRI brain scans, this facility is not always available. Observation of GMs is a bedside clinical approach that allows confirmation of early prediction from MRI, early rehabilitation if needed and reassurance that neurological outcome will be good where that is appropriate.

The early markers for later dyskinetic cerebral palsy are different from those for spastic cerebral palsy.

Qualitative abnormalities of spontaneous motor activity in newborns and young infants are early predictive markers for later spastic cerebral palsy. Aim of this research was to identify which motor patterns may be specific for later dyskinetic cerebral palsy. In a large, prospectively performed longitudinal study involving four European hospitals we identified twelve cases with the relatively rare condition of dyskinetic cerebral palsy and compared their early motor development with twelve spastic cerebral palsy cases and twelve controls. From birth to the fifth month post-term, all infants were repeatedly videoed and their spontaneous motor patterns, including general movements, were assessed. Until the second month post-term, the infants that later became dyskinetic displayed a poor repertoire of general movements, "arm movements in circles" and finger spreading. Abnormal arm and finger movements remained until at least five months and were then concurrent with a lack of arm and leg movements towards the midline. Later dyskinetic infants share with later spastic infants the absence of fidgety movements, a spontaneous movement pattern that is normally present from three to five months. Qualitative assessment of spontaneous motor patterns enabled us to identify infants at high risk for dyskinetic cerebral palsy early in life. Additionally, we were able to discriminate them from those infants at high risk for later spastic cerebral palsy. This is a matter of significant clinical relevance because the two types of cerebral palsy ask for different management and early intervention.

Role of vision on early motor development: lessons from the blind.

For a better understanding of the contribution vision makes to the development of other sensory systems and to movement and posture, we studied effects of early blindness by examining video recordings of 14 totally blind infants. Infants were born at term or preterm and showed no evidence of brain damage. During preterm and term periods no noticeable changes in motor activity were observed. Around 2 months postterm all infants showed clear delay in head control and abnormal, exaggerated type of 'fidgety movements'. Later, postural control was characterized by a prolonged period of ataxic features. Results indicate a lack of normal calibration exerted by vision on proprioceptive and vestibular systems. Early visuomotor coordination such as coordinated eye-head scanning and head orientating were present but disappeared after several weeks.

International Child Care Practices Study: infant sleeping environment.

BACKGROUND: The International Child Care Practices Study (ICCPS) has collected descriptive data from 21 centres in 17 countries. In this report, data are presented on the infant sleeping environment with the main focus being sudden infant death syndrome (SIDS) risk factors (bedsharing and infant using a pillow) and protective factors (infant sharing a room with adult) that are not yet well established in the literature. METHODS: Using a standardised protocol, parents of infants were surveyed at birth by interview and at 3 months of age mainly by postal questionnaire. Centres were grouped according to geographic location. Also indicated was the level of SIDS awareness in the community, i.e. whether any campaigns or messages to "reduce the risks of SIDS" were available at the time of the survey. RESULTS: Birth interview data were available for 5488 individual families and 4656 (85%) returned questionnaires at 3 months. Rates of bedsharing varied considerably (2-88%) and it appeared to be more common in the samples with a lower awareness of SIDS, but not necessarily a high SIDS rate. Countries with higher rates of bedsharing appeared to have a greater proportion of infants bedsharing for a longer duration (>5 h). Rates of room sharing varied (58-100%) with some of the lowest rates noted in centres with a higher awareness of SIDS. Rates of pillow use ranged from 4% to 95%. CONCLUSIONS: It is likely that methods of bedsharing differ cross-culturally, and although further details were sought on different bedsharing practices, it was not possible to build up a composite picture of "typical" bedsharing practices in these different communities. These data highlight interesting patterns in child care in these diverse populations. Although these results should not be used to imply that any particular child care practice either increases or decreases the risk of SIDS, these findings should help to inject caution into the process of developing SIDS prevention campaigns for non-Western cultures.

Early neurological signs in preterm infants with unilateral intraparenchymal echodensity.

UNLABELLED: The aim of the study was to document the early developmental course of neurological signs in a group of preterm infants at risk for hemiplegia due to unilateral intraparenchymal echodensity (UIPE). Sixteen preterm infants with UIPE and sixteen controls were given serial neurological examinations, according to the protocols currently adopted in the different NICUs of the project. Moreover, the quality assessment of their general movements (GMs) was assessed subsequently from videotapes, from birth until around four months postterm. At two years, 12 of the UIPE infants showed hemiplegia and one suffered from asymmetrical diplegia. The findings of the traditional neurological examination were abnormal for the large majority of the UIPE infants, although normal findings were also recorded in some cases, especially during the preterm period. Asymmetries were found after term age in nine UIPE and in two control infants. From the first observation onwards, all infants with UIPE showed bilaterally abnormal GMs and in those with unfavourable outcome fidgety movements (FMs) were absent. At the FMs period (9-16 weeks postterm), all infants with subsequent hemiplegia showed asymmetry of distal segmental movements which were reduced or absent on the side contralateral to the lesion. CONCLUSIONS: Unilateral brain lesions induce clear neurological signs and abnormal GMs in particular, although these abnormalities are not initially asymmetrical. A reduction of segmental movements on one side of the body during the third month postterm is highly predictive of hemiplegia.

Temporal disparity between reduction of cot death and reduction of prone sleeping prevalence.

According to several reports sudden infant death rates have decreased significantly after public campaigns aimed at reducing the incidence of sleeping in a prone position. The Styrian population (1.2 million inhabitants), who have been studied from 1984, also showed a significant drop in the incidence of cot death during 1989 (from 2/1000 to 1/1000%). The year before, a campaign for the prevention of cot death had been launched. This included the recommendation to prevent infants from lying in a prone position during sleep. Part of the prevention programme consisted of a detailed questionnaire filled in and returned by the parents. These data, on 29970 infants from 1989 to 1994, provided information on the frequency of prone sleeping in 37% of our total population and as a consequence on parental response to the campaign. Calculating the data per year led to the surprising result that the reduction by half (from 50% to 25%) in the prevalence of sleeping in a prone position did not occur in 1989, when the drop in the incidence of cot death occurred, but 3 years later, in 1992. The following years saw a further decrease of prone position to 7% but no appreciable change in the incidence of cot death. However, during those 11 years of study about 80% of the victims were consistently found dead lying in a prone position. Our results show a temporal disparity between the reduction of sudden infant death and the decrease of prone sleeping in a population. Although we do not deny sleeping in a prone position as a risk factor for cot death, there cannot be a simple relationship between sleeping habits in the population and incidence of cot death.

Comparison between observation of spontaneous movements and neurologic examination in preterm infants.

OBJECTIVE: The Prechtl method of qualitative assessment of general movements (GMs) has been shown to be a good predictor of neurologic outcome in fetuses, preterm infants, and term infants. The aim of this study was to compare the results of this new technique with those of traditional neurologic examination and of cranial ultrasonography in preterm infants. METHODS: Serial videotape recordings (with off-line assessment of GMs), ultrasound examination of the brain, and neurologic examinations were performed from birth until about 6 months of corrected age, on a group of 66 preterm infants whose gestational age ranged from 26 to 36 weeks (mean 30.7 weeks). The agreement between the two techniques and their predictive power, with respect to the neurologic outcome at 2 years of corrected age, were evaluated for five different age groups from preterm age to 65 weeks of postmenstrual age. RESULTS: Overall agreement of the neurologic and GM findings was 80.3% and strongly age related (lower during the preterm and term periods and higher thereafter). At all ages the results of GM observation correlated highly with neurologic outcome; they showed higher sensitivity and specificity than the neurologic examination. This held true in particular before term age, when poor neurologic responses might be related to transient complications, and at term age, mainly because of infants with normal neurologic examination results but unfavorable outcome. During the preterm period the ultrasound results showed a better specificity and a lower sensitivity to outcome than GM findings. CONCLUSIONS: The results of this study indicate that quality assessment of GMs should be added to traditional neurologic assessment, neuroimaging, and other tests of preterm infants for diagnostic and prognostic purposes.

An early marker for neurological deficits after perinatal brain lesions.

BACKGROUND: In normal awake infants, fidgety movements are seen from the age of 6 weeks to 20 weeks. The aim of the study was to test the predictive value of absent or abnormal spontaneous movements in young infants for the later development of neurological deficits. METHODS: In a collaborative study involving five hospitals we collected data on the normal and abnormal quality of fidgety movements of 130 infants and compared it with assessments of neurological development done longitudinally until the age of 2 years. On the basis of ultrasound scans infants were classified as at low-risk or at high-risk of neurological deficits. Infants were videoed for 1 h every week from birth to discharge and then for 15 min every 3 to 4 weeks; quality of general movements was assessed. Repeated neurological assessments were also done until 24 months of corrected age. FINDINGS: 67 (96%) of 70 infants with normal fidgety movements had a normal neurological outcome. Abnormal quality or total absence of fidgety movements was followed by neurological abnormalities in 57 (95%) of the 60 infants (49 had cerebral palsy and eight had developmental retardation or minor neurological signs). Specificity and sensitivity of fidgety movement assessment were higher (96% and 95%, respectively) than of ultrasound imaging of the infants' brain (83% and 80%, respectively). INTERPRETATION: Our technique of assessing spontaneous motor activity can identify and distinguish between those infants who require early intervention for neurological abnormalities and those who do not. Our technique is simple, non-intrusive, reliable, quick, and can be done on very young infants.

Assessment of the quality of general movements in fetuses and infants of women with type-I diabetes mellitus.

The effect of type-I diabetes on the quality of general movements (GMs) was studied longitudinally in 12 human fetuses. GMs were analysed at two-weekly intervals from 16 weeks until delivery. A pregnancy optimality-score and a diabetes optimality-score were used to cover the course of the pregnancy and delivery and the severity of diabetes. GMs of infants were analysed 1, 4-6, and 12-18 weeks after birth and the Bayley developmental test was performed at 10 months. All fetuses showed normal GMs at 16 weeks. From 20 weeks onwards until delivery five fetuses developed abnormal GMs. The diabetes optimality-score was significantly lower in the group with abnormal GMs (P = 0.018) whereas the pregnancy optimality-score did not differ between fetuses with normal and abnormal GMs. Our results indicate that type-I diabetes can have a negative impact on prenatally observed GMs. Consistently normal GMs indicate normal neurodevelopmental outcome at 10 months whereas in the group with abnormal GMs reduced Bayley-scores may occur.

The qualitative assessment of general movements in preterm, term and young infants--review of the methodology.

We describe the state of the art of Prechtl's method for the qualitative assessment of general movements as a diagnostic tool for early detection of brain dysfunction. After discussing the optimal technique for video recording general movements in preterm, term and young infants, attention is focused on the proper analysis of this spontaneous motor pattern. Recently, a group of active researchers in the field reached consensus on the various qualities of normal and abnormal general movements. These definitions are reported here in full. Since it is a newly introduced method careful investigation into its reliability is required. Various groups of investigators have obtained data which demonstrate the robust character of the method (interscorer agreement: 78-98%). Finally, we discuss the validity of this early assessment method on the basis of the reports published so far. While the method's sensitivity is similar in all age groups studied (preterm, term, first month, second month, and third month age epochs), and averages 94.5%, the specificity of the method is age-dependent. It is low during the early ages, increases gradually and reaches 82 to 100% at 3 months post-term. This phenomenon is explained by spontaneous recovery of early dysfunction. In contrast, consistent abnormalities of general movements are linked to neurological deficits found at the 2 year follow-up.

Which better predicts later outcome in full-term infants: quality of general movements or neurological examination?

The qualitative assessment of general movements (GMs) has been shown to be a better predictor of neurological outcome than the traditional neurological examination in brain-damaged preterm infants. The aim of this study was to compare the results of the two techniques in term infants. Off-line assessment of GMs from videorecordings and neurological examinations were carried out, from birth till about 6 months of postterm age, in a group of 58 term infants, the majority of which were affected by mild to severe hypoxic-ischaemic encephalopathy. The agreement between the two techniques and their predictive power, with respect to the neurological outcome at 2 years, were evaluated for four age groups. The range of agreement between neurological and GM findings was between 78 and 83%. At all ages the results of GM observation correlated highly with the neurological outcome; their sensitivity and specificity with respect to outcome were consistently slightly superior to those of neurological examination. In infants normalize after an initial period of transient abnormalities, GMs normalize earlier than the neurological results.

Posture, spontaneous movements, and behavioural state organisation in infants affected by brain malformations.

Posture, quantity of spontaneous movement patterns, quality of general movements (GMs), and behavioural state organisation were studied in nine infants affected by documented brain malformations. A single 1 h video recording of five infants and two or more serial video recordings of another four infants were performed after birth. The graphic representation of single movement patterns (actogram) and of behavioural states of one video recording was performed in eight out of nine infants. The quality of GMs was assessed according to Prechtl's method in all video recordings. All nine infants showed a less variable posture than normal newborn infants and an unusual resting posture was detected in seven infants. Poor behavioural state organisation without sleep cycles was common to the nine infants and excessive wakefulness was observed in six infants. As for the quantity of single movement patterns, six infants lacked one or two movement patterns normally present in healthy newborn infants. An abnormal quality of GMs was noted in all nine infants and distinct motor abnormalities were observed in single infants. A monotonous and sometimes stereotyped sequence of different body parts involved in the movement (i.e. poor repertoire GMs) was common to all infants. In the four infants of whom two or more video recordings were available, initial poor repertoire GMs were followed by a further deterioration in movement quality. No relationship was found between the quantity of defective brain tissue, lack of a specific part of the brain, type and severity of GM and posture abnormalities.