A growth chart of brain function from infancy to adolescence based on EEG.

BACKGROUND: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. METHODS: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). FINDINGS: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69-1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30-1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90-2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). INTERPRETATION: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. FUNDING: This research was supported by the National Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.

Charting infants' motor development at home using a wearable system: validation and comparison to physical growth charts.

BACKGROUND: Early neurodevelopmental care and research are in urgent need of practical methods for quantitative assessment of early motor development. Here, performance of a wearable system in early motor assessment was validated and compared to developmental tracking of physical growth charts. METHODS: Altogether 1358 h of spontaneous movement during 226 recording sessions in 116 infants (age 4-19 months) were analysed using a multisensor wearable system. A deep learning-based automatic pipeline quantified categories of infants' postures and movements at a time scale of seconds. Results from an archived cohort (dataset 1, N = 55 infants) recorded under partial supervision were compared to a validation cohort (dataset 2, N = 61) recorded at infants' homes by the parents. Aggregated recording-level measures including developmental age prediction (DAP) were used for comparison between cohorts. The motor growth was also compared with respective DAP estimates based on physical growth data (length, weight, and head circumference) obtained from a large cohort (N = 17,838 infants; age 4-18 months). FINDINGS: Age-specific distributions of posture and movement categories were highly similar between infant cohorts. The DAP scores correlated tightly with age, explaining 97-99% (94-99% CI 95) of the variance at the group average level, and 80-82% (72-88%) of the variance in the individual recordings. Both the average motor and the physical growth measures showed a very strong fit to their respective developmental models (R2 = 0.99). However, single measurements showed more modality-dependent variation that was lowest for motor (σ = 1.4 [1.3-1.5 CI 95] months), length (σ = 1.5 months), and combined physical (σ = 1.5 months) measurements, and it was clearly higher for the weight (σ = 1.9 months) and head circumference (σ = 1.9 months) measurements. Longitudinal tracking showed clear individual trajectories, and its accuracy was comparable between motor and physical measures with longer measurement intervals. INTERPRETATION: A quantified, transparent and explainable assessment of infants' motor performance is possible with a fully automated analysis pipeline, and the results replicate across independent cohorts from out-of-hospital recordings. A holistic assessment of motor development provides an accuracy that is comparable with the conventional physical growth measures. A quantitative measure of infants' motor development may directly support individual diagnostics and care, as well as facilitate clinical research as an outcome measure in early intervention trials. FUNDING: This work was supported by the Finnish Academy (314602, 335788, 335872, 332017, 343498), Finnish Pediatric Foundation (Lastentautiensäätiö), Aivosäätiö, Sigrid Jusélius Foundation, and HUS Children's Hospital/HUS diagnostic center research funds.

Intelligent wearable allows out-of-the-lab tracking of developing motor abilities in infants.

Background: Early neurodevelopmental care needs better, effective and objective solutions for assessing infants' motor abilities. Novel wearable technology opens possibilities for characterizing spontaneous movement behavior. This work seeks to construct and validate a generalizable, scalable, and effective method to measure infants' spontaneous motor abilities across all motor milestones from lying supine to fluent walking. Methods: A multi-sensor infant wearable was constructed, and 59 infants (age 5-19 months) were recorded during their spontaneous play. A novel gross motor description scheme was used for human visual classification of postures and movements at a second-level time resolution. A deep learning -based classifier was then trained to mimic human annotations, and aggregated recording-level outputs were used to provide posture- and movement-specific developmental trajectories, which enabled more holistic assessments of motor maturity. Results: Recordings were technically successful in all infants, and the algorithmic analysis showed human-equivalent-level accuracy in quantifying the observed postures and movements. The aggregated recordings were used to train an algorithm for predicting a novel neurodevelopmental measure, Baba Infant Motor Score (BIMS). This index estimates maturity of infants' motor abilities, and it correlates very strongly (Pearson's r = 0.89, p < 1e-20) to the chronological age of the infant. Conclusions: The results show that out-of-hospital assessment of infants' motor ability is possible using a multi-sensor wearable. The algorithmic analysis provides metrics of motility that are transparent, objective, intuitively interpretable, and they link strongly to infants' age. Such a solution could be automated and scaled to a global extent, holding promise for functional benchmarking in individualized patient care or early intervention trials.

Endogenous erythropoietin at birth is associated with neurodevelopmental morbidity in early childhood.

BACKGROUND: New biomarkers that predict later neurodevelopmental morbidity are needed. This study evaluated the associations between umbilical cord serum erythropoietin (us-EPO) and neurodevelopmental morbidity by the age of 2-6.5 years in a Finnish cohort. METHODS: This study included 878 non-anomalous children born alive in 2012 to 2016 in Helsinki University Hospitals and whose us-EPO concentration was determined at birth. Data of these children were linked to data from the Finnish Medical Birth Register and the Finnish Hospital Discharge Register. Neurodevelopmental morbidity included cerebral palsy, epilepsy, intellectual disability, autism spectrum disorder, sensorineural defects, and minor neurodevelopmental disorders. RESULTS: In the cohort including both term and preterm children, us-EPO levels correlated with gestational age (r = 0.526) and were lower in premature children. High us-EPO levels (>100 IU/l) were associated with an increased risk of severe neurodevelopmental morbidity (OR: 4.87; 95% CI: 1.05-22.58) when adjusted for the gestational age. The distribution of us-EPO levels did not differ in children with or without the later neurodevelopmental diagnosis. CONCLUSIONS: Although high us-EPO concentration at birth was associated with an increased risk of neurodevelopmental morbidity in early childhood, the role of us-EPO determination in clinical use appears to be minor. IMPACT: We determined whether endogenous umbilical cord serum erythropoietin would be a new useful biomarker to predict the risk of neurodevelopmental morbidity. This study evaluated the role of endogenous erythropoietin at birth in neurodevelopmental morbidity with a study population of good size and specific diagnoses based on data from high-quality registers. Although high umbilical cord serum erythropoietin concentration at birth was associated with an increased risk of neurodevelopmental morbidity in early childhood, the clinical value of erythropoietin determination appears to be minor.