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.

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.

Abnormal spontaneous movements in infants with repeated sleep apnoeas.

Infants with repeated apnoea during sleep have received great attention for the assumed reason of being at-risk for sudden infant death. The present paper reports findings which indicate a different risk, namely for neurological impairment during infancy due to repeated hypoxia. A very strong correlation exists between the respiratory measurements based on a polygraphic all-night recording (PtcO2 drops and apnoea incidence and duration) and the impairment of the spontaneous movement repertoire in 114 infants, aged between 3 and 26 weeks. All infants have been video recorded at the same day as the registration of the sonogram. As there was a gradient of respiratory abnormalities from absent to severe, a similar gradient was present in the degree of motor deviations in these infants. A variety of qualitative changes in the spontaneous movement patterns was found which was similar to those previously described in cases with documented brain damage. These abnormalities could not be attributed to pre- and perinatal complications. It is concluded that infants with repeated sleep apnoea need special attention for prevention of neurological impairment irrespective of the supposed risk for sudden infant death.

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.

The predictive value of behavioural risk factors for sudden infant death.

In order to examine the predictive value of risk factors for the Sudden Infant Death Syndrome (SIDS), we have interviewed the parents of 80 SIDS victims and 80 parents of a healthy control group. From these interviews a list of 24 clinical and behavioural symptoms was assembled which appeared to be associated with the risk for SIDS. Out of this list of 24 symptoms the average number of symptoms reported to be observable in SIDS victims was twice as large as the average number of symptoms reported for healthy controls. The following symptoms appeared markedly more often in SIDS victims than in the controls: difficulties in awakening the baby, shrill crying, apathy, few movements during sleep, and cyanosis. We have attempted to consider a possible bias in the report of the parents of deceased infants by the introduction of an "exaggeration factor". By application of Bayes' theorem the highest predictive probability, 2.7%, was found for difficulties in awakening the baby. This is approximately nine times the assumed a priori probability of SIDS of 0.3%. We conclude that behavioural risk factors have a low but still remarkable predictive probability. A behavioural pattern of apathy and sleepiness indicates risk with a high probability.

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.

Observation of movements during sleep in ALTE (apparent life threatening event) and apnoeic infants--a pilot study.

Fourteen infants of 2 months or 6 months of age were video-recorded during polysomnography. Four were normal infants, five had a history of ALTE (apparent life threatening event) and five had repeated and prolonged apnoea during sleep. Two ALTE infants have been recorded at 2 months as well as at 6 months of age. Movements during sleep could be classified into general movements, isolated movements of the upper extremity, startles, head rotations, and trunk rotations. In the ALTE cases at 2 months of age, the motility was quantitatively not different from the control infants but was markedly reduced at 6 months of age. (All cases had their event before 8 weeks of age.) In contrast to these findings, infants with repeated apnoea did not show a clear change in the quantity of their movements. With the exception of one ALTE case at 2 months, all observed cases of ALTE and apnoeic infants showed an abnormal quality of their spontaneous movements during sleep. As reported in a previous study, all these cases had also been found moving abnormally during wakefulness. It is suggested that the abnormal motility is a sequelae of the event (ALTE or repeated apnoeas) with as a consequence, an impairment of neural functions.

Neurological status, sleep apnea frequency and blood oxygenation in six weeks old infants.

A study was carried out to investigate the correlation between sleep apnea frequency, blood oxygenation and neurological condition in 21 infants at six weeks of age with inconspicuous medical history. Polygraphic recordings of respiratory behaviour and transcutaneous blood gas monitoring lasted for at least five hours. To quantify the results of the neurological examination we established a neurological optimality score (NOS). We found statistically significant correlations between several indexes of apneas and indexes of blood oxygenation and NOS. Thus, a reduced NOS was strongly correlated with higher apnea frequencies and with pronounced drops of transcutaneous PO2-values. In addition all but one infant who were diagnosed as having a sleep apnea syndrome showed a greater than ten percent reduction of NOS. Some pathophysiological considerations to explain our findings are put forward and the possible role of the neuromodulator adenosine is emphasized.

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.

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.

Is neurological assessment of the fetus possible?

The possibility to assess the functional condition of the fetal nervous system is of great importance to the obstetrician, since a considerable part of early brain damage is of prenatal origin. Several attempts to develop such a technique are reviewed. In addition, a new method, the qualitative assessment of fetal general movements, is described as a successful tool to obtain reliable data on the fetal brain dysfunction. This new method is robust, non-intrusive and cost-effective. There is also the advantage that the same criteria for the diagnostic assessment can be used for the fetus as well as for the young infant.

[Air pollution and sudden infant death in Graz 1982 to 1987]. / Luftverschmutzung und plötzlicher Säuglingstod in Graz im Zeitraum von 1982 bis 1987.

We correlated the incidence of the sudden infant death syndrome (SIDS) and the degree of air pollution in each district of Graz over a time period of five years. The degree of air pollution was derived from a mapping of epiphytical lichen vegetation by Grill et al. (1988). We found an increased incidence of SIDS in districts with poor air quality. Although this result is not statistically significant a possible increase in SIDS risk because of air pollution cannot be excluded. Some pathophysiological explanations are discussed.

Computer-based sleep monitoring in SIDS-risk infants--preliminary results.

A computerized, PC-based system is introduced for sleep monitoring in infants. The system is capable of digitizing and storing 22 physiological variables over a whole-night sleep period. The preprocessed data can be displayed on a single page; further processing can be done on the digitally stored data.

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.

[The 1-hour oxycardiorespirography as routine study in the diagnosis of cardiorespiratory dysregulation in infancy--an attempt at establishing normal values]. / Die einstündige Oxycardiorespirographie als Routineuntersuchung zur Diagnose kardiorespiratorischer Dysregulationen im Säuglingsalter--Ein Versuch zur Aufstellung von "Normalwerten".

Because of the growing demand to evaluate cardiorespiratory dysfunctions the short-time oxycardiorespirography becomes a more and more important and powerful tool in the daily clinical routine. Therefore, from about one hour lasting records we studied the distribution of MA-values (mean apnea duration), duration of the longest apnea, percentage of periodic breathing time, lowest heart rate values, lowest transcutaneous PO2 values and highest transcutaneous PCO2 values in an obstetrical optimal low-risk group of 90 infants and a obstetrical non-optimal group of 152 infants between four and ten weeks of age. Percentiles of each variable were calculated, and we suggest the 90th percentiles as new threshold values to judge these short-time recordings. In comparison to relevant data from the literature we could demonstrate that deviating threshold values have to be applied to short-time recordings in comparison to long-time recordings. In addition, the respiratory behaviour of the optimal group is compared to that of the non-optimal group of the same age. Interestingly enough, no difference in the respiratory behaviour between these groups could be demonstrated.