Neurodevelopmental Trajectories Research Articles

Associations of prenatal PFAS exposure and early childhood neurodevelopment: Evidence from the Shanghai Maternal-Child Pairs Cohort

Epidemiological data on the effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) on infant neurodevelopment trajectories are far from being sufficiently addressed. In this study, 1285 mother–child pairs were recruited during 2016–2017. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure 16 PFAS levels in cord serum. Ages and Stages Questionnaires were used to examine children's neurodevelopment at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Children with relatively low scores from 2 to 24 months were classified into a low-score group and were used as a risk group in each domain. Multiple linear regression, logistic regression, and quantile-based g-computation were performed to assess associations of single or mixture PFAS exposures with neurodevelopment and trajectories. Perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and 6:2 chlorinated polyfluorooctane ether sulfonate (6:2Cl-PFESA) were detected in over 90 % samples. PFOA had the highest concentration (median: 4.61 μg/L). Each ln-unit (μg/L) increase of PFAS (e.g., PFOA, PFOS, PFHxS, 6:2Cl-PFESA) was associated with poor scores of communication domain at 6 months, with the effect size ranging from −0.69 to −0.44. PFOS (OR: 1.14, (1.03, 1.26), PFDA (OR:1.08, (1.02, 1.15)), PFHxS (OR:1.31, (1.12, 1.56)), and 6:2Cl-PFESA (OR:1.08, (1.00, 1.16)) were associated with an increased risk of being in the low-score group in the early childhood communication domain's trajectory. Each mixture quartile increment was associated with a 1.60 (−2.76, −0.45) decrease in communication domain scores of 6-month-old infants, and the mixture effect was mainly attributed to PFOS. Each mixture quartile increase was associated with a 1.23-fold (1.03, 1.46) risk of being in the low-score group of the communication domain, and the mixture effect was mainly attributed to PFOS. In conclusion, PFAS and their mixtures might adversely affect childhood neurodevelopment. The gender-specific associations existed in the above associations.

Measures of Brain Connectivity and Cognition by Sex in US Children

The neurobiological underpinnings underlying sex differences in cognition during adolescence are largely unknown. To examine sex differences in brain circuitry and their association with cognitive performance in US children. This cross-sectional study analyzed behavioral and imaging data from 9- to 11-year-old children from the Adolescent Brain Cognitive Development (ABCD) study between August 2017 and November 2018. The ABCD study is an open-science, multisite study following up more than 11 800 youths into early adulthood for 10 years with annual laboratory-based assessments and biennial magnetic resonance imaging (MRI). The selection of ABCD study children for the current analysis was based on the availability of functional and structural MRI data sets in ABCD Brain Imaging Data Structure Community Collection format. Five hundred and sixty participants who had excessive level of head motion (>50% of time points with framewise displacement >0.5 mm) during resting-state functional MRI were excluded from the analyses. Data were analyzed between January and August 2022. The main outcomes were the sex differences in (A) global functional connectivity density at rest and (B) mean water diffusivity (MD) and (C) the correlation of these metrics with total cognitive scores. A total of 8961 children (4604 boys and 4357 girls; mean [SD] age, 9.92 [0.62] years) were included in this analysis. Girls had higher functional connectivity density in default mode network hubs than boys, predominantly in the posterior cingulate cortex (Cohen d = -0.36), and lower MD and transverse diffusivity, predominantly in the superior corticostriatal white matter bundle (Cohen d = 0.3). Age-corrected fluid and total composite scores were higher for girls than for boys (Cohen d = -0.08 [fluid] and -0.04 [total]; P = 2.7 × 10-5). Although total mean (SD) brain volume (1260 [104] mL in boys and 1160 [95] mL in girls; t = 50; Cohen d = 1.0; df = 8738) and the proportion of white matter (d = 0.4) were larger for boys than for girls, the proportion of gray matter was larger for girls than for boys (d = -0.3; P = 2.2 × 10-16). The findings of this cross-sectional study on sex differences in brain connectivity and cognition are relevant to the future creation of brain developmental trajectory charts to monitor for deviations associated with impairments in cognition or behavior, including those due to psychiatric or neurological disorders. They could also serve as a framework for studies investigating the differential contribution of biological vs social or cultural factors in the neurodevelopmental trajectories of girls and boys.

Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity.

Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevated plus maze, and sucrose preference tests, respectively. The gene expression levels of NMDA NR1-2A subunits, mGluR5, and their respective scaffold proteins PSD95 and Homer1, as well as CB1R and the neuromodulatory protein HINT1, were measured in the hippocampus. pTHC offspring exhibited deficits in spatial and object recognition memory and reversal learning, increased locomotor activity, increased NR1-, decreased NR2A- and PSD95-, increased mGluR5- and Homer1-, and augmented CB1R- and HINT1-hippocampal mRNA levels. Our data shows that pTHC is associated with specific impairment in spatial cognitive processing and effectors of hippocampal neuroplasticity and suggests novel targets for future pharmacological challenges.

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P≤0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

Sex differences in neurodevelopmental trajectories in children with different levels of autistic traits.

Little is known about early manifestations of autism spectrum disorders (ASD) in females, including those who may be overlooked by the current diagnostic criteria. We longitudinally explored sex differences in the trajectories of cognitive and motor functions and adaptive behaviors in children with different levels of autistic traits. The participants were 824 children from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study), Japan, who were classified into three autistic trait groups-low, moderate, and high-based on the Social Responsiveness Scale-Second Edition. Cognitive and motor functions were measured at seven time-points from 0.5 to 3.5 years of age using the Mullen Scales of Early Learning. Adaptive behaviors were measured at five time-points from 2.7 to 9 years of age using the Vineland Adaptive Behavior Scales-Second Edition. Trajectories were depicted using latent growth curve modeling. Sex-specific trajectories were observed in the high-autistic-trait group, with only males showing a temporary decline in expressive language around the age of 2 years and a slight improvement thereafter. They also showed a slight improvement around 3 years in the adaptive behavior communication domain but a gradual downward trend later. Females in the high-autistic-trait group showed no distinct manifestation before the age of 3 years but showed a downward trend after 3.5 years in the adaptive behavior communication domain. Females and males with higher autistic traits than their same-sex peers, independent of clinical diagnosis, may have different phenotypes in certain neurodevelopmental domains during infancy and early childhood.

A prospective, longitudinal, case–control study to evaluate the neurodevelopment of children from birth to adolescence exposed to COVID-19 in utero

BackgroundThe Coronavirus disease (COVID-19) pandemic has created unprecedented acute global health challenges. However, it also presents a set of unquantified and poorly understood risks in the medium to long term, specifically, risks to children whose mothers were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Infections during pregnancy can increase the risk of atypical neurodevelopment in the offspring, but the long-term neurodevelopmental impact of in utero COVID-19 exposure is unknown. Prospective, longitudinal studies are needed to evaluate children exposed in utero to SARS-CoV2 to define this risk.MethodsWe have designed a prospective, case-controlled study to investigate the long-term impacts of SARS-CoV2 exposure on children exposed in utero. Women infected with SARS-CoV-2 during pregnancy will be recruited from Monash Health, the Royal Women’s Hospital and Western Health (Melbourne, Australia) and Londrina Municipal Maternity Hospital Lucilla Ballalai and PUCPR Medical Clinical (Londrina, Brazil). A control group in a 2:1 ratio (2 non-exposed: 1 exposed mother infant dyad) comprising women who gave birth in the same month of delivery, are of similar age but did not contract SARS-CoV-2 during their pregnancy will also be recruited. We aim to recruit 170 exposed and 340 non-exposed mother-infant dyads. Clinical and socio-demographic data will be collected directly from the mother and medical records. Biospecimens and clinical and epidemiological data will be collected from the mothers and offspring at multiple time points from birth through to 15 years of age using standardised sample collection, and neurological and behavioural measures.DiscussionThe mapped neurodevelopmental trajectories and comparisons between SARS-CoV-2 exposed and control children will indicate the potential for an increase in atypical neurodevelopment. This has significant implications for strategic planning in the mental health and paediatrics sectors and long-term monitoring of children globally.

Progress in Brain Magnetic Resonance Imaging of Individuals with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS), a rare epigenetic disease mapping the imprinted chromosomal domain of 15q11.2-q13.3, manifests a regular neurodevelopmental trajectory in different phases. The current multimodal magnetic resonance imaging (MRI) approach for PWS focues on morphological MRI (mMRI), diffusion MRI (dMRI) and functional MRI (fMRI) to uncover brain alterations. This technique offers another perspective to understand potential neurodevelopmental and neuropathological processes of PWS, in addition to specific molecular gene expression patterns, various clinical manifestations and metabolic phenotypes. Multimodal MRI studies of PWS patients demonstrated common brain changes in the volume of gray matter, the integrity of the fiber tracts and the activation and connectivity of some networks. These findings mainly showed that brain alterations in the frontal reward circuit and limbic system were related to molecular genetics and clinical manifestations (e.g., overwhelming eating, obsessive compulsive behaviors and skin picking). Further exploration using a large sample size and advanced MRI technologies, combined with artificial intelligence algorithms, will be the main research direction to study the structural and functional changes and potential pathogenesis of PWS.

A guide to prenatal counseling regarding neurodevelopment in congenital heart disease.

Advances in cardiac surgical techniques taking place over the past 50years have resulted in the vast majority of children born with congenital cardiac malformations now surviving into adulthood. As the focus shifts from survival to the functional outcomes of our patients, it is increasingly being recognized that a significant proportion of patients undergoing infant cardiac repair experience adverse neurodevelopmental (ND) outcomes. The etiology of abnormal brain development in the setting of congenital heart disease is poorly understood, complex, and likely multifactorial. Furthermore, the efficacy of therapies available for the learning disabilities, attention deficit, and hyperactivity disorders and other ND deficits complicating congenital heart disease is currently uncertain. This situation presents a challenge for prenatal counseling as current antenatal testing does not usually provide prognostic information regarding the likely ND trajectories of individual patients. However, we believe it is important for parents to be informed about potential issues with child development when a new diagnosis of congenital heart disease is disclosed. Parents deserve a comprehensive and thoughtful approach to this subject, which conveys the uncertainties involved in predicting the severity of any developmental disorders encountered, while emphasizing the improvements in outcomes that have already been achieved in infants with congenital heart disease. A balanced approach to counseling should also discuss what local arrangements are in place for ND follow-up. This review presents an up-to-date overview of ND outcomes in patients with congenital heart disease, providing possible approaches to communicating this information to parents during prenatal counseling in a sensitive and accurate manner.

Electroencephalography signals and neurodevelopment after Kawasaki disease: A pilot study.

Acute Kawasaki disease (KD) induces central nervous system inflammation and excessive irritability. Long-term impacts on children's neurodevelopment have only been studied marginally. This pilot study aimed to describe the neuropsychological profile of primary school-aged children with a history of KD and to explore the impacts of KD on electroencephalography (EEG) markers associated with attention and brain maturation. Fifteen children (8.8 ± 2.5 years) were recruited 4.9 ± 2.7 years after KD onset. Intellectual abilities, long-term memory, and auditory sustained attention were evaluated. Parents completed standardized questionnaires assessing (1) executive functioning; (2) internalizing and externalizing difficulties; (3) attention deficit hyperactivity disorder symptoms; and (4) autism spectrum disorder symptoms. Theta/beta ratio (TBR) and alpha peak (AP) were extracted from resting-state EEG and compared with 32 controls (8.9 ± 2.1 years). The alpha band was analyzed using a feature reduction algorithm to detect potential groupings. Performances showed preserved intellectual abilities and memory. Sustained attention performance was within the lower range for 4/14 participants (29%), with considerable parental reports of inattention (43%), working memory difficulties (50%), and hyperactivity-impulsivity (36%). No alterations in the TBR were found but the KD group presented a significantly lower AP amplitude ratio. A clear separation of KD cohort into two clusters showed that acute irritability is associated with a weaker AP. Despite overall preserved cognitive functions, there is a possible association between KD and attention deficit concerns. This first EEG-based study indicates alpha peak abnormality after KD, predominantly in children with acute irritability. Longitudinal studies are warranted to better characterize patients' neurodevelopmental trajectory.

Mapping access to meaning in adolescents with autism: Atypical lateralization and spatiotemporal patterns as a function of language ability

Individuals with autism spectrum disorders (ASD) vary in their language abilities, associated with atypical patterns of brain activity. However, few studies have examined the spatiotemporal profiles of lexico-semantic processing in ASD, particularly as a function of language heterogeneity. Thirty-nine high-functioning adolescents with ASD and 21 typically developing (TD) peers took part in a lexical decision task that combined semantic access with demands on cognitive control. Spatiotemporal characteristics of the processing stages were examined with a multimodal anatomically-constrained magnetoencephalography (aMEG) approach, which integrates MEG with structural MRI. Additional EEG data were acquired from a limited montage simultaneously with MEG. TD adolescents showed the canonical left-dominant activity in frontotemporal regions during both early (N250m) and late (N400m) stages of lexical access and semantic integration. In contrast, the ASD participants showed bilateral engagement of the frontotemporal language network, indicative of compensatory recruitment of the right hemisphere. The left temporal N400m was prominent in both groups, confirming preserved attempts to access meaning. In contrast, the left prefrontal N400m was reduced in ASD participants, consistent with impaired semantic/contextual integration and inhibitory control. To further investigate the impact of language proficiency, the ASD sample was stratified into high- and low-performing (H-ASD and L-ASD) subgroups based on their task accuracy. The H-ASD subgroup performed on par with the TD group and showed greater activity in the right prefrontal and bilateral temporal cortices relative to the L-ASD subgroup, suggesting compensatory engagement. The L-ASD subgroup additionally showed reduced and delayed left prefrontal N400m, consistent with more profound semantic and executive impairments in this subgroup. These distinct spatiotemporal activity profiles reveal the neural underpinnings of the ASD-specific access to meaning and provide insight into the phenotypic heterogeneity of language in ASD, which may be a result of different neurodevelopmental trajectories and adoption of compensatory strategies.

Clinical Trajectories in Adolescents with and without a History of Non-Suicidal Self-Injury: The BRIDGES Longitudinal Study.

Non-suicidal self-injury (NSSI) is a highly prevalent clinical concern in adolescents and is associated with impaired functioning and suicide risk. The BRIDGES (BRain Imaging Development of Girls' Emotion and Self) study was designed to collect longitudinal clinical and neurobiological data to advance our understanding of NSSI in adolescents. The purpose of this paper is to describe the clinical data collected as part of this study, including psychiatric diagnoses, depression symptoms, episodes of non-suicidal self-injury, suicidal thoughts and behaviors, childhood trauma, and personality domains. The baseline sample included 164 adolescents aged 12-16 assigned female at birth (Mean age = 14.97, SD = 1.20) with NSSI histories ranging from none to severe. Participants and their parent/guardian were invited to provide data at three time points spaced approximately one year apart. Descriptive analyses were conducted to provide estimates of rates and trajectories of clinical data. Of the 164 study participants, 75.61% and 57.93% completed the second and third time points, respectively. Visual inspection of the data suggests an overall trend of decreasing severity of psychopathology over time, and adolescents with a history of NSSI appeared to have higher rates of psychopathology than those without. This paper describes longitudinal clinical trajectories in adolescents with a range of NSSI histories and presents readers with an overview of the rich, publicly available dataset that we hope will inspire future research to advance the understanding of the neurodevelopmental trajectories associated with NSSI, depression, and suicide risk.

Sulcal pits as potential markers of sex-specific neurodevelopmental trajectories

Sulcal pits as potential markers of sex-specific neurodevelopmental trajectories

Distinct childhood neurodevelopmental trajectories following very preterm birth

Distinct childhood neurodevelopmental trajectories following very preterm birth

Neurodevelopmental Trajectory in a Child with Congenital Heart Disease

Neurodevelopmental Trajectory in a Child with Congenital Heart Disease

Vinpocetine, a PDE1 modulator, regulates markers of cerebral health, inflammation, and oxidative stress in a rat model of prenatal alcohol-induced experimental attention deficit hyperactivity disorder.

Prenatal alcohol exposure (PAE) has been shown to induce symptomatology associated with attention deficit hyperactivity disorder (ADHD) by altering neurodevelopmental trajectories. Phosphodiesterase-1 (PDE1) is expressed centrally and has been used in various experimental brain conditions. We investigated the role of vinpocetine, a PDE1 inhibitor, on behavioral phenotypes and important biochemical deficits associated with a PAE rat model of ADHD. Protein markers of cerebral health (synapsin-IIa, BDNF, and pCREB), inflammation (IL-6, IL-10, and TNF-α), and oxidative stress (TBARS, GSH, and SOD) were analyzed in three brain regions (frontal cortex, striatum, and cerebellum). Hyperactivity, inattention, and anxiety introduced in the offspring due to PAE were assayed using open-field, Y-maze, and elevated plus maze, respectively. Administration of vinpocetine (10 & 20mg/kg, p.o. [by mouth]) to PAE rat offspring for 4 weeks resulted in improvement of the behavioral profile of the animals. Additionally, levels of protein markers such as synapsin-IIa, BDNF, pCREB, IL-10, SOD, and GSH were found to be significantly increased, with a significant reduction in markers such as TNF-α, IL-6, and TBARS in selected brain regions of vinpocetine-treated animals. Vinpocetine, a selective PDE1 inhibitor, rectified behavioral phenotypes associated with ADHD, possibly by improving cerebral function, reducing brain inflammation, and reducing brain oxidative stress. This study provides preliminary analysis and suggests that the PDE1 enzyme may be an important pharmacological tool to study ADHD as a result of PAE.

Maximum downward slope of sleep slow waves as a potential marker of attention-deficit/hyperactivity disorder clinical phenotypes

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous diagnostic category, encompassing several endophenotypes and comorbidities, including sleep problems. However, no predictor of clinical long-term trajectories or comorbidity has yet been established. Sleep EEG has been proposed as a potential tool for evaluating the synaptic strength during development, as well as the cortical thickness, which is presumed to be altered in ADHD. We investigated whether the slope of the Slow Waves (SWs), a microstructural parameter of the sleep EEG, was a potential predictive parameter for psychiatric comorbidities and neuropsychological dimensions in ADHD. Methods70 children (58 m; 8.76 ± 2.77 y) with ADHD who underwent psychiatric and neurologic evaluations and a standard EEG recording during naps were investigated. After sleep EEG analysis, we grouped the extracted SWs in bins of equal amplitude and then measured the associations, through generalized linear regression, between their maximum downward slopes (MDS) and the individual scores obtained from clinical rating scales. ResultsThe presence of Multiple Anxiety Disorders was positively associated with MDS of medium amplitude SWs in temporo-posterior left areas. The Child Behavior Checklist scores showed negative associations in the same areas for small SWs. The presence of autistic traits was positively associated with MDS of high amplitude SWs in bilateral anterior and temporal left areas. The WISC-IV Processing Speed Index showed negative associations with MDS of small-to-medium SWs in anterior and temporal right areas, while positive associations in posterior and temporal left areas. ConclusionsConsistency of association clusters' localization on the scalp suggests that variations in the local MDS, revealing alterations of local synaptic strength and/or in daytime use of certain cortical circuits, could underlie specific neurodevelopmental trajectories resulting in different ADHD clinical phenotypes.

Preschool Depression and Hippocampal Volume: The Moderating Role of Family Income.

Depression and low socioeconomic status have both been associated with hippocampal volume alterations. Whether these factors interact to predict neurobehavioral outcomes has not been adequately studied. The authors investigated family income as a moderator of the relationship between depression and hippocampal volume in a longitudinal sample. Longitudinal behavioral data, beginning at preschool age, and behavioral and neuroimaging data from school age to adolescence were used to assess the impact of preschool only and total preschool to adolescent depression symptoms on hippocampal volumes using family income as a moderator (N= 176). Depression severity during the preschool period interacted with family income to predict hippocampal volumes at the intercept (ie, age 13 years; B=-0.078, p= .003). Interaction decomposition revealed that only individuals with relatively high family income exhibited smaller hippocampal volume with increasing depression severity (B=-0.146, p= .005). Family income was associated with hippocampus volumes only in individuals with low to moderate preschool depression severity (B= 0.289, p= .007 and B= 0.169, p= .030, respectively). Preschool depression severity interacts with family income to predict hippocampal volume across development, such that the effects of early depression are evident only in those with higher income. These findings suggest that hippocampal volume may not be an effective marker of risk for depression at different levels of socioeconomic status, and emphasizes the importance of the environmental context when assessing risk markers for depression. Future research should explore how socioeconomic stress may eclipse the effects of depression on hippocampal development, setting alternative neurodevelopmental risk trajectories.

Neurodevelopment assessment of small for gestational age children in a community-based cohort from Pakistan

BackgroundChildren born small for gestational age (SGA) may experience more long-term neurodevelopmental issues than those born appropriate for gestational age (AGA). This study aimed to assess differences in the neurodevelopment...

Distinct Neurodevelopmental Trajectories in Groups of Very Preterm Children Screening Positively for Autism Spectrum Conditions.

Very preterm (VPT; < 33weeks' gestation) toddlers screening positively for autism spectrum conditions (ASC) may display heterogenous neurodevelopmental trajectories. Here we studied neonatal brain volumes and childhood ASC traits evaluated with the Social Responsiveness Scale (SRS-2) in VPT-born toddlers (N = 371; median age 20.17months) sub-divided into three groups based on their Modified-Checklist for Autism in Toddlers scores. These were: those screening positively failing at least 2 critical items (critical-positive); failing any 3 items, but less than 2 critical items (non-critical-positive); and screening negatively. Critical-positive scorers had smaller neonatal cerebellar volumes compared to non-critical-positive and negative scorers. However, both positive screening groups exhibited higher childhood ASC traits compared to the negative screening group, suggesting distinct aetiological trajectories associated with ASC outcomes.

Feasibility of Passive ECG Bio-sensing and EMA Emotion Reporting Technologies and Acceptability of Just-in-Time Content in a Well-being Intervention, Considerations for Scalability and Improved Uptake.

Researchers increasingly use passive sensing data and frequent self-report to implement personalized mobile health (mHealth) interventions. Yet, we know that certain populations may find these technical protocols burdensome and intervention uptake as well as treatment efficacy may be affected as a result. In the present study, we predicted feasibility (participant adherence to protocol) and acceptability (participant engagement with intervention content) as a function of baseline sociodemographic, mental health, and well-being characteristics of 99 women randomized in the personalized preventive intervention Wellness-for-Two (W-4-2), a randomized trial evaluating stress-related alterations during pregnancy and their effect on infant neurodevelopmental trajectories. The W-4-2 study used ecological momentary assessment (EMA) and wearable electrocardiograph (ECG) sensors to detect physiological stress and personalize the intervention. Participant adherence to protocols was 67% for EMAs and 52% for ECG bio-sensors. Higher baseline negative affect significantly predicted lower adherence to both protocols. Women assigned to the intervention group engaged on average with 42% of content they received. Women with higher annual household income were more likely to engage with more of the intervention content. Researchers should carefully consider tailoring of the intensity of technical intervention protocols to reduce fatigue, especially among participants with higher baseline negative affect, which may improve intervention uptake and efficacy findings at scale.