Clinical characteristics, longitudinal adaptive functioning, and association with electroencephalogram activity in PPP2R5D-related neurodevelopmental disorder.

Protein phosphatase 2 regulatory subunit B56δ related neurodevelopmental disorder (PPP2R5D-related NDD) is largely caused by de novo heterozygous missense PPP2R5D variants. We report medical characteristics, longitudinal adaptive functioning, and in-person neurological, motor, cognitive, and electroencephalogram (EEG) activity for PPP2R5D-related NDD. Forty-two individuals (median age 6 years, range = 0.8-25.3) with pathogenic/likely pathogenic PPP2R5D variants were assessed, and almost all variants were missense (97.6%) and de novo (85.7%). Common clinical symptoms were developmental delay, hypotonia, macrocephaly, seizures, autism, behavioral challenges, and sleep problems. The mean Gross motor functional measure-66 was 60.2 ± 17.3% and the mean Revised upper limb module score was 25.9 ± 8.8. The Vineland-3 adaptive behavior composite score (VABS-3 ABC) at baseline was low (M = 61.7 ± 16.8). VABS-3 growth scale value scores increased from baseline in all subdomains (range = 0.6-5.9) after a mean follow-up of 1.3 ± 0.3 years. EEG beta and gamma power were negatively correlated with VABS-3 score; p < 0.05. Individuals had a mean Quality-of-life inventory-disability score of 74.7 ± 11.4. Twenty caregivers (80%) had a risk of burnout based on the Caregiver burden inventory. Overall, the most common clinical manifestations of PPP2R5D-related NDD were impaired cognitive, adaptive function, and motor skills; and EEG activity was associated with adaptive functioning. This clinical characterization describes the natural history in preparation for clinical trials.

Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression.

Sensitive developmental periods shape neural circuits and enable adaptation. However, they also engender vulnerability to factors that can perturb developmental trajectories. An understanding of sensitive period phenomena and mechanisms separate from sensory system development is still lacking, yet critical to understanding disease etiology and risk. The dopamine system is pivotal in controlling and shaping adolescent behaviors, and it undergoes heightened plasticity during that time, such that interference with dopamine signaling can have long-lasting behavioral consequences. Here we sought to gain mechanistic insight into this dopamine-sensitive period and its impact on behavior. In mice, dopamine transporter (DAT) blockade from postnatal (P) day 22 to 41 increases aggression and sensitivity to amphetamine (AMPH) behavioral stimulation in adulthood. Here, we refined this sensitive window to P32-41 and identified increased firing of dopaminergic neurons in vitro and in vivo as a neural correlate to altered adult behavior. Aggression can result from enhanced impulsivity and cognitive dysfunction, and dopamine regulates working memory and motivated behavior. Hence, we assessed these behavioral domains and found that P32-41 DAT blockade increases impulsivity but has no effect on cognition, working memory, or motivation in adulthood. Lastly, using optogenetics to drive dopamine neurons, we find that increased VTA but not SNc dopaminergic activity mimics the increase in impulsive behavior in the Go/NoGo task observed after adolescent DAT blockade. Together our data provide insight into the developmental origins of aggression and impulsivity that may ultimately improve diagnosis, prevention, and treatment strategies for related neuropsychiatric disorders.

Combining developmental and sleep health measures for autism spectrum disorder screening: an ECHO study.

BACKGROUND: Sleep problems are reported for up to 80% of autistic individuals. We examined whether parsimonious sets of items derived from the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Brief Infant Sleep Questionnaire (BISQ) are superior to the standard M-CHAT-R in predicting subsequent autism spectrum disorder (ASD) diagnoses. METHODS: Participants from 11 Environmental influences on Child Health Outcomes (ECHO) cohorts were included. We performed logistic LASSO regression models with 10-fold cross-validation to identify whether a combination of items derived from the M-CHAT-R and BISQ are superior to the standard M-CHAT-R in predicting ASD diagnoses. RESULTS: The final sample comprised 1552 children. The standard M-CHAT-R had a sensitivity of 44% (95% CI: 34, 55), specificity of 92% (95% CI: 91, 94), and AUROC of 0.726 (95% CI: 0.663, 0.790). A higher proportion of children with ASD had difficulty falling asleep or resisted bedtime during infancy/toddlerhood. However, LASSO models revealed parental reports of sleep problems did not improve the accuracy of the M-CHAT-R in predicting ASD diagnosis. CONCLUSION: While children with ASD had higher rates of sleep problems during infancy/toddlerhood, there was no improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. IMPACT: Parental-reported sleep problems are common in autism spectrum disorder (ASD). We investigated whether the inclusion of parental-reports of infant/toddler sleep patterns enhanced the effectiveness of developmental screening for autism. We reported higher rates of difficulty falling asleep and resisting bedtime during infancy and toddlerhood among children later diagnosed with ASD; however, we did not find an improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. In our sample, the standard M-CHAT-R had a sensitivity of 39% among children of mothers with government insurance compared with a sensitivity of 53% among children of mothers with employer-based insurance.

Age-related trends in aperiodic EEG activity and alpha oscillations during early- to middle-childhood.

Age-related structural and functional changes that occur during brain development are critical for cortical development and functioning. Previous electroencephalography (EEG) and magnetoencephalography (MEG) studies have highlighted the utility of power spectra analyses and have uncovered age-related trends that reflect perceptual, cognitive, and behavioural states as well as their underlying neurophysiology. The aim of the current study was to investigate age-related change in aperiodic and periodic alpha activity across a large sample of pre- and school-aged children (N = 502, age range 4 -11-years-of-age). Power spectra were extracted from baseline EEG recordings (eyes closed, eyes open) for each participant and parameterized into aperiodic activity to derive the offset and exponent parameters and periodic alpha oscillatory activity to derive the alpha peak frequency and the associated power estimates. Multilevel models were run to investigate age-related trends and condition-dependent changes for each of these measures. We found quadratic age-related effects for both the aperiodic offset and exponent. In addition, we observed increases in periodic alpha peak frequency as a function of age. Aperiodic measures and periodic alpha power were larger in magnitude during eyes closed compared to the eyes open baseline condition. Taken together, these results advance our understanding of the maturational patterns/trajectories of brain development during early- to middle-childhood.

Prenatal smoking and drinking are associated with altered newborn autonomic functions.

BACKGROUND: Prenatal smoking and drinking are associated with sudden infant death syndrome and neurodevelopmental disorders. Infants with these outcomes also have altered autonomic nervous system (ANS) regulation. We examined the effects of prenatal smoking and drinking on newborn ANS function. METHODS: Pregnant women were enrolled in Northern Plains, USA (NP) and Cape Town (CT), South Africa. Daily drinking and weekly smoking data were collected prenatally. Physiological measures were obtained during sleep 12-96 h post-delivery. RESULTS: In all, 2913 infants from NP and 4072 from CT were included. In active sleep, newborns of mothers who smoked throughout pregnancy, compared to non-smokers, had higher breathing rates (2.2 breaths/min; 95% CI: 0.95, 3.49). Quit-early smoking was associated with reductions in beat-to-beat heart rate variability (HRV) in active (-0.08 s) and quiet sleep (-0.11 s) in CT. In girls, moderate-high continuous smoking was associated with increased systolic (3.0 mmHg, CI: 0.70, 5.24) and diastolic blood pressure (2.9 mmHg, CI: 0.72, 5.02). In quiet sleep, low-continuous drinking was associated with slower heart rate (-4.5 beat/min). In boys, low-continuous drinking was associated with a reduced ratio of low-to-high frequency HRV (-0.11, CI: -0.21, -0.02). CONCLUSIONS: These findings highlight potential ANS pathways through which prenatal drinking and smoking may contribute to neurodevelopment outcomes. IMPACT: In this prospective cohort study of 6985 mother-infant dyads prenatal drinking and smoking were associated with multiple ANS parameters. Smoking was associated with increased neonatal breathing rates among all infants, and heart rate variability (HRV) and blood pressure (BP) among girls. Drinking was associated with reductions in HR and BP among all newborns, and reductions in the ratio of low to-high frequency HRV among boys. These findings suggest that prenatal smoking and drinking alter newborn ANS which may presage future neurodevelopmental disorders.

Pandemic beyond the virus: maternal COVID-related postnatal stress is associated with infant temperament.

BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.

Longitudinal characterization of EEG power spectra during eyes open and eyes closed conditions in children.

This study is the first to examine spectrum-wide (1 to 250 Hz) differences in electroencephalogram (EEG) power between eyes open (EO) and eyes closed (EC) resting state conditions in 486 children. The results extend the findings of previous studies by characterizing EEG power differences from 30 to 250 Hz between EO and EC across childhood. Developmental changes in EEG power showed spatial and frequency band differences as a function of age and EO/EC condition. A 64-electrode system was used to record EEG at 4, 5, 7, 9, and 11 years of age. Specific findings were: (1) the alpha peak shifts from 8 Hz at 4 years to 9 Hz at 11 years, (2) EC results in increased EEG power (compared to EO) at lower frequencies but decreased EEG power at higher frequencies for all ages, (3) the EEG power difference between EO and EC changes from positive to negative within a narrow frequency band which shifts toward higher frequencies with age, from 9 to 12 Hz at 4 years to 32 Hz at 11 years, (4) at all ages EC is characterized by an increase in lower frequency EEG power most prominently over posterior regions, (5) at all ages, during EC, decreases in EEG power above 30 Hz are mostly over anterior regions of the scalp. This report demonstrates that the simple challenge of opening and closing the eyes offers the potential to provide quantitative biomarkers of phenotypic variation in brain maturation by employing a brief, minimally invasive protocol throughout childhood.

Association of Gestational Diabetes Mellitus and Perinatal Maternal Depression with Early Childhood Behavioral Problems: An Environmental Influences on Child Health Outcomes (ECHO) Study.

This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009-2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.

Maternal hair cortisol predicts periodic and aperiodic infant frontal EEG activity longitudinally across infancy.

Maternal stress is known to be an important factor in shaping child development, yet the complex pattern of associations between stress and infant brain development remains understudied. To better understand the nuanced relations between maternal stress and infant neurodevelopment, research investigating longitudinal relations between maternal chronic physiological stress and infant brain function is warranted. In this study, we leveraged longitudinal data to disentangle between- from within-person associations of maternal hair cortisol and frontal electroencephalography (EEG) power at three time points across infancy at 3, 9, and 15 months. We analyzed both aperiodic power spectral density (PSD) slope and traditional periodic frequency band activity. On the within-person level, maternal hair cortisol was associated with a flattening of frontal PSD slope and an increase in relative frontal beta. However, on the between-person level, higher maternal hair cortisol was associated with steeper frontal PSD slope, increased relative frontal theta, and decreased relative frontal beta. The within-person findings may reflect an adaptive neural response to relative shifts in maternal stress levels, while the between-person results demonstrate the potentially detrimental effects of chronically elevated maternal stress. This analysis offers a novel, quantitative insight into the relations between maternal physiological stress and infant cortical function.

Aperiodic electrophysiological activity in preterm infants is linked to subsequent autism risk.

Approximately 7% of preterm infants receive an autism spectrum disorder (ASD) diagnosis. Yet, there is a significant gap in the literature in identifying prospective markers of neurodevelopmental risk in preterm infants. The present study examined two electroencephalography (EEG) parameters during infancy, absolute EEG power and aperiodic activity of the power spectral density (PSD) slope, in association with subsequent autism risk and cognitive ability in a diverse cohort of children born preterm in South Africa. Participants were 71 preterm infants born between 25 and 36 weeks gestation (34.60 ± 2.34 weeks). EEG was collected during sleep between 39 and 41 weeks postmenstrual age adjusted (40.00 ± 0.42 weeks). The Bayley Scales of Infant Development and Brief Infant Toddler Social Emotional Assessment (BITSEA) were administered at approximately 3 years of age adjusted (34 ± 2.7 months). Aperiodic activity, but not the rhythmic oscillatory activity, at multiple electrode sites was associated with subsequent increased autism risk on the BITSEA at three years of age. No associations were found between the PSD slope or absolute EEG power and cognitive development. Our findings highlight the need to examine potential markers of subsequent autism risk in high-risk populations other than infants at familial risk.

Prenatal Exposure to Tobacco and Alcohol Alters Development of the Neonatal Auditory System.

Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.

An integrated approach based on advanced CTG parameters and Doppler measurements for late growth restriction management.

BACKGROUND: The clinical diagnosis of late Fetal Growth Restriction (FGR) involves the integration of Doppler ultrasound data and Fetal Heart Rate (FHR) monitoring through computer assisted computerized cardiotocography (cCTG). The aim of the study was to evaluate the diagnostic power of combined Doppler and cCTG parameters by contrasting late FGR -and healthy controls. METHODS: The study was conducted from January 2018 to May 2020. Only pregnant women who had the last Doppler measurement obtained within 1 week before delivery and cCTG performed within 24 h before delivery were included in the study. Two hundred forty-nine pregnant women fulfilling the inclusion criteria were enrolled in the study; 95 were confirmed as late FGR and 154 were included in the control group. RESULTS: Among the extracted cCTG parameters, Delta Index, Short Term Variability (STV), Long Term Variability (LTV), Acceleration and Deceleration Phase Rectified Slope (APRS, DPRS) values were lower in the late FGR participants compared to the control group. In the FGR cohort, Delta, STV, APRS, and DPRS were found different when stratifying by MCA_PI (MCA_PI <5th centile or > 5th centile). STV and DPRS were the only parameters to be found different when stratifying by (UA_PI >95th centile or UA_PI <95th centile). Additionally, we measured the predictive power of cCTG parameters toward the identification of associated Doppler measures using figures of merit extracted from ROC curves. The AUC of ROC curves were accurate for STV (0,70), Delta (0,68), APRS (0,65) and DPRS (0,71) when UA_PI values were > 95th centile while, the accuracy attributable to the prediction of MCA_PI was 0.76, 0.77, 0.73, and 0.76 for STV, Delta, APRS, and DPRS, respectively. An association of UA_PI>95th centile and MCA_PI<5th centile with higher risk for NICU admission, was observed, while CPR < 5th centile resulted not associated with any perinatal outcome. Values of STV, Delta, APRS, DPRS were significantly lower for FGR neonates admitted to NICU, compared with the uncomplicated FGR cohort. CONCLUSIONS: The results of this study show the contribution of advanced cCTG parameters and fetal Doppler to the identification of late FGR and the association of those parameters with the risk for NICU admission. TRIAL REGISTRATION: Retrospectively registered.

Child-parent cardiac transference is decreased following disrupted/absent early care.

Parental input shapes youth self-regulation development, and a lack of sensitive caregiving is a risk factor for youth mental health problems. Parents may shape youth regulation through their influence over biological (including neural) and behavioral development during childhood at both micro (moment-to-moment) and macro (global) levels. Prior studies have shown that micro-level parent-child interactions shape youth's biology contributing to youth mental health. However, it remains unclear whether prior disrupted/absent care affects those moment-to-moment parent-youth interactions in ways that increase risk for youth psychopathology. In the current study, we calculated transfer entropy on cardiac data from parent-youth dyads where the youth had either been exposed to disrupted care prior to adoption or not. Transfer Entropy (TE) tracks information flow between two signals, enhancing quantification of directional coupling, allowing for the examination of parent-child and child-parent influences. Using this novel approach, we identified lower cardiac information transfer from youth-to-parents in dyads where the youth had been exposed to disrupted/absent early care. Moreover we showed that the degree to which the parent's physiology changed in response to youth's physiology was negatively related to the youth's mental health, representing a potential pathway for elevated mental health risk in populations exposed to disrupted/absent early care.

Entropy Information of Cardiorespiratory Dynamics in Neonates during Sleep.

Sleep is a central activity in human adults and characterizes most of the newborn infant life. During sleep, autonomic control acts to modulate heart rate variability (HRV) and respiration. Mechanisms underlying cardiorespiratory interactions in different sleep states have been studied but are not yet fully understood. Signal processing approaches have focused on cardiorespiratory analysis to elucidate this co-regulation. This manuscript proposes to analyze heart rate (HR), respiratory variability and their interrelationship in newborn infants to characterize cardiorespiratory interactions in different sleep states (active vs. quiet). We are searching for indices that could detect regulation alteration or malfunction, potentially leading to infant distress. We have analyzed inter-beat (RR) interval series and respiration in a population of 151 newborns, and followed up with 33 at 1 month of age. RR interval series were obtained by recognizing peaks of the QRS complex in the electrocardiogram (ECG), corresponding to the ventricles depolarization. Univariate time domain, frequency domain and entropy measures were applied. In addition, Transfer Entropy was considered as a bivariate approach able to quantify the bidirectional information flow from one signal (respiration) to another (RR series). Results confirm the validity of the proposed approach. Overall, HRV is higher in active sleep, while high frequency (HF) power characterizes more quiet sleep. Entropy analysis provides higher indices for SampEn and Quadratic Sample entropy (QSE) in quiet sleep. Transfer Entropy values were higher in quiet sleep and point to a major influence of respiration on the RR series. At 1 month of age, time domain parameters show an increase in HR and a decrease in variability. No entropy differences were found across ages. The parameters employed in this study help to quantify the potential for infants to adapt their cardiorespiratory responses as they mature. Thus, they could be useful as early markers of risk for infant cardiorespiratory vulnerabilities.

Remote data collection of infant activity and sleep patterns via wearable sensors in the HEALthy Brain and Child Development Study (HBCD).

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Wearable and remote sensing technologies have advanced data collection outside of laboratory settings to enable exploring, in more detail, the associations of early experiences with brain development and social and health outcomes. In the HBCD Study, the Novel Technology/Wearable Sensors Working Group (WG-NTW) identified two primary data types to be collected: infant activity (by measuring leg movements) and sleep (by measuring heart rate and leg movements). These wearable technologies allow for remote collection in the natural environment. This paper illustrates the collection of such data via wearable technologies and describes the decision-making framework, which led to the currently deployed study design, data collection protocol, and derivatives, which will be made publicly available. Moreover, considerations regarding actual and potential challenges to adoption and use, data management, privacy, and participant burden were examined. Lastly, the present limitations in the field of wearable sensor data collection and analysis will be discussed in terms of extant validation studies, the difficulties in comparing performance across different devices, and the impact of evolving hardware/software/firmware.

In Utero Exposure to Alcohol and Tobacco and Electroencephalogram Power During Childhood.

Importance: Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. Objective: To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). Design, Setting, and Participants: This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. Exposures: Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. Main Outcomes and Measures: EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. Results: The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] µV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] µV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] µV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] µV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] µV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] µV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] µV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] µV2; P = .04) power compared with those with no PTE. Conclusions and Relevance: These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.

The development and structure of the HEALthy Brain and Child Development (HBCD) Study EEG protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Electroencephalography (EEG) is one of two brain imaging modalities central to the HBCD Study. EEG records electrical signals from the scalp that reflect electrical brain activity. In addition, the EEG signal can be synchronized to the presentation of discrete stimuli (auditory or visual) to measure specific cognitive processes with excellent temporal precision (e.g., event-related potentials; ERPs). EEG is particularly helpful for the HBCD Study as it can be used with awake, alert infants, and can be acquired continuously across development. The current paper reviews the HBCD Study's EEG/ERP protocol: (a) the selection and development of the tasks (Video Resting State, Visual Evoked Potential, Auditory Oddball, Face Processing); (b) the implementation of common cross-site acquisition parameters and hardware, site setup, training, and initial piloting; (c) the development of the preprocessing pipelines and creation of derivatives; and (d) the incorporation of equity and inclusion considerations. The paper also provides an overview of the functioning of the EEG Workgroup and the input from members across all steps of protocol development and piloting.

Longitudinal effects of prenatal alcohol exposure on visual neurodevelopment over infancy.

Prenatal alcohol exposure (PAE) affects neurodevelopment in over 59 million individuals globally. Prior studies using dichotomous categorization of alcohol use and comorbid substance exposures provide limited knowledge of how prenatal alcohol specifically impacts early human neurodevelopment. In this longitudinal cohort study from Cape Town, South Africa, PAE is measured continuously-characterizing timing, dose, and drinking patterns (i.e., binge drinking). High-density electroencephalography (EEG) during a visual-evoked potential (VEP) task was collected from infants aged 8 to 52 weeks with prenatal exposure exclusively to alcohol and matched on sociodemographic factors to infants with no substance exposure in utero. First trimester alcohol exposure related to altered timing of the P1 VEP component over the first 6 months postnatally, and first trimester binge drinking exposure altered timing of the P1 VEP components such that increased exposure was associated with longer VEP latencies while increasing age was related to shorter VEP latencies (n = 108). These results suggest alcohol exposure in the first trimester may alter visual neurodevelopmental timing in early infancy. Exploratory individual-difference analysis across infants with and without PAE tested the relation between VEP latencies and myelination for a subsample of infants with usable magnetic resonance imaging (MRI) T1w and T2w scans collected at the same time point as EEG (n = 47). Decreased MRI T1w/T2w ratios (an indicator of myelin) in the primary visual cortex (n = 47) were linked to longer P1 VEP latencies. Results from these two sets of analyses suggest that prenatal alcohol and postnatal myelination may both separately impact VEP latency over infancy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neonatal rhinorrhea, heart rate variability, and childhood exercise-induced wheeze.

Background: There is increasing evidence linking infant rhinorrhea to school-age exercise-induced wheeze (EIW) via a parasympathetic nervous system pathway. The ratio of the root mean square of successive differences in heart beats (RMSSD) measured in quiet sleep versus active sleep (RMSSDQS:AS) is a novel biomarker in asthma. Objective: We tested the hypotheses that (1) neonatal rhinorrhea predicts childhood EIW independent of other neonatal respiratory symptoms, (2) neonatal RMSSDQS:AS predicts childhood EIW, and (3) RMSSDQS:AS mediates the association between neonatal rhinorrhea and childhood EIW. Methods: Participants from the Safe Passage/Environmental Influences on Child Health Outcomes (PASS/ECHO) prospective birth cohort had heart rate variability extracted from electrocardiogram traces acquired in the first month of life. Parents reported on rhinorrhea in their child at age 1 month and on EIW in their child at ages 4 to 11 years. Results: In models (N = 831) adjusted for potential confounders and covariates, including neonatal wheeze, cough and fever, neonatal rhinorrhea-predicted childhood EIW (relative risk [RR] = 2.22; P = .040), specifically, among females (RR = 3.38; P = .018) but not males (RR = 1.39; P = .61). Among participants contributing data in both active and quiet sleep (n = 231), RMSSDQS:AS predicted EIW (RR = 2.36; P = .003) and mediated the effect estimate of neonatal rhinorrhea predicting EIW among females. Half of the females with a higher RMSSDQS:AS and neonatal rhinorrhea (n = 5 of 10) developed EIW as compared with 1.8% of the other females (n = 2 of 109) (P < .001). Conclusions: Our findings support dysregulation of the parasympathetic nervous system in infancy as one of the possible underlying mechanisms for the development of EIW later in childhood among females, which could aid in the development of future interventions.

A comprehensive wireless neurological and cardiopulmonary monitoring platform for pediatrics.

Neurodevelopment in the first 10 years of life is a critical time window during which milestones that define an individual's functional potential are achieved. Comprehensive multimodal neurodevelopmental monitoring is particularly crucial for socioeconomically disadvantaged, marginalized, historically underserved and underrepresented communities as well as medically underserved areas. Solutions designed for use outside the traditional clinical environment represent an opportunity for addressing such health inequalities. In this work, we present an experimental platform, ANNE EEG, which adds 16-channel cerebral activity monitoring to the existing, USA FDA-cleared ANNE wireless monitoring platform which provides continuous electrocardiography, respiratory rate, pulse oximetry, motion, and temperature measurements. The system features low-cost consumables, real-time control and streaming with widely available mobile devices, and fully wearable operation to allow a child to remain in their naturalistic environment. This multi-center pilot study successfully collected ANNE EEG recordings from 91 neonatal and pediatric patients at academic quaternary pediatric care centers and in LMIC settings. We demonstrate the practicality and feasibility to conduct electroencephalography studies with high levels of accuracy, validated via both quantitative and qualitative metrics, compared against gold standard systems. An overwhelming majority of parents surveyed during studies indicated not only an overall preference for the wireless system, but also that its use would improve their children's physical and emotional health. Our findings demonstrate the potential for the ANNE system to perform multimodal monitoring to screen for a variety of neurologic diseases that have the potential to negatively impact neurodevelopment.