Exploratory study evaluating the relationships between perinatal adversity, oxidative stress, and infant neurodevelopment across the first year of life.

Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed prospectively, at scale, to assess risk in pediatric settings. The goal of this two-site longitudinal study was to determine if the gold standard measure of oxidative stress, F2-Isoprostanes, is potentially a reliable measure of a physiological response to adversity of the infant and mother. The study evaluated the independent relationships between F2-Isoprostanes, perinatal adversity and infant neurocognitive development. The study included mother-infant dyads born >36 weeks' gestation. Maternal demographic information and mental health assessments were utilized to generate a perinatal cumulative risk score. Infants' development was assessed at 6 and 12 months and both mothers and infants were assayed for F2-isoprostane levels in blood and urine, respectively. Statistical analysis revealed that cumulative risk scores correlated with higher maternal (p = 0.01) and infant (p = 0.05) F2-isoprostane levels at 6 months. Infant F2-isoprostane measures at 2 months were negatively associated with Mullen Scales of Early Learning Composite scores at 12 months (p = 0.04). Lastly, higher cumulative risk scores predicted higher average maternal F2-isoprostane levels across the 1-year study time period (p = 0.04). The relationship between perinatal cumulative risk scores and higher maternal and infant F2-isoprostanes at 6 months may reflect an oxidative stress status that informs a sensitive period in which a biomarker can be utilized prospectively to reveal the physiological impact of early adversity.

Analysis and novel methods for capture of normative eye-tracking data in 2.5-month old infants.

Development of attention systems is essential for both cognitive and social behavior maturation. Visual behavior has been used to assess development of these attention systems. Yet, given its importance, there is a notable lack of literature detailing successful methods and procedures for using eye-tracking in early infancy to assess oculomotor and attention dynamics. Here we show that eye-tracking technology can be used to automatically record and assess visual behavior in infants as young as 2.5 months, and present normative data describing fixation and saccade behavior at this age. Features of oculomotor dynamics were analyzed from 2.5-month old infants who viewed videos depicting live action, cartoons, geometric shapes, social and non-social scenes. Of the 54 infants enrolled, 50 infants successfully completed the eye-tracking task and high-quality data was collected for 32 of those infants. We demonstrate that modifications specifically tailored for the infant population allowed for consistent tracking of pupil and corneal reflection and minimal data loss. Additionally, we found consistent fixation and saccade behaviors across the entire six-minute duration of the videos, indicating that this is a feasible task for 2.5-month old infants. Moreover, normative oculomotor metrics for a free-viewing task in 2.5-month old infants are documented for the first time as a result of this high-quality data collection.

Maternal stress and development of infant attention to threat-related facial expressions.

Attentional biases to threat-related stimuli, such as fearful and angry facial expressions, are important to survival and emerge early in development. Infants demonstrate an attentional bias to fearful facial expressions by 5-7 months of age and an attentional bias toward anger by 3 years of age that are modulated by experiential factors. In a longitudinal study of 87 mother-infant dyads from families predominantly experiencing low income, we examined whether maternal stress and depressive symptoms were associated with trajectories of attentional biases to threat, assessed during an attention disengagement eye-tracking task when infants were 6-, 9-, and 12-month old. By 9 months, infants demonstrated a generalized bias toward threat (both fearful and angry facial expressions). Maternal perceived stress was associated with the trajectory of the bias toward angry facial expressions between 6 and 12 months. Specifically, infants of mothers with higher perceived stress exhibited a greater bias toward angry facial expressions at 6 months that decreased across the next 6 months, compared to infants of mothers with lower perceived stress who displayed an increased bias to angry facial expressions over this age range. Maternal depressive symptoms and stressful life events were not associated with trajectories of infant attentional bias to anger or fear. These findings highlight the role of maternal perceptions of stress in shaping developmental trajectories of threat-alerting systems.

An exploratory study of predictors of cognition in two low-income samples of infants across the first year of life.

OBJECTIVE: In this exploratory longitudinal study we assessed cognitive development in a community sample of infants born into predominantly low-income families from two different urban sites, to identify family and community factors that may associate with outcomes by 1 year of age. METHOD: Infant-mother dyads (n = 109) were recruited in Boston and Los Angeles community pediatric practices. Infant cognition was measured using the Mullen Scales of Early Learning when the infant was aged 2, 6, 9, and 12 months. Longitudinal linear mixed effects modeling and linear regression models explored potential predictors of cognitive outcomes. RESULTS: Cognitive scores were lower than the reference population mean at both 6 and 12 months. There were site differences in demographics and cognitive performance. Maternal education predicted expressive language in Boston, and speaking Spanish and lower rates of community poverty were associated with greater increases in overall cognition in Los Angeles. CONCLUSION: This exploratory study identified a number of drivers of child development that are both shared across cohorts and unique to specific community samples. Factors influencing heterogeneity within and across populations both may be important contributors to prevention and intervention in supporting healthy development among children.

Association of Perceived Maternal Stress During the Perinatal Period With Electroencephalography Patterns in 2-Month-Old Infants.

Importance: Variation in child responses to adversity creates a clinical challenge to identify children most resilient or susceptible to later risk for disturbances in cognition and health. Advances in establishing scalable biomarkers can lead to early identification and mechanistic understanding of the association of early adversity with neurodevelopment. Objectives: To examine whether maternal reports of stress are associated with patterns in resting electroencephalography at 2 months of age and whether unique electroencephalographic profiles associated with risk and resiliency factors can be identified. Design, Setting, and Participants: For this cohort study, a population-based sample of 113 mother-infant dyads was recruited from January 1, 2016, to March 1, 2018, during regularly scheduled pediatric visits before infants were 2 months of age from 2 primary care clinics in Boston, Massachusetts, and Los Angeles, California, that predominantly serve families from low-income backgrounds. Data are reported from a single time point, when infants were aged 2 months, of an ongoing cohort study longitudinally following the mother-infant dyads. Exposures: Maternal reported exposure to stressful life events and perceived stress. Main Outcomes and Measures: Spectral power (absolute and relative) in different frequency bands (Δ, θ, low and high α, ß, and γ) from infant resting electroencephalography (EEG) and EEG profiles across frequency bands determined by latent profile analysis. Results: Of 113 enrolled infants, 70 (mean [SD] age, 2.42 [0.37] months; 35 girls [50%]) provided usable EEG data. In multivariable hierarchical linear regressions, maternal perceived stress was significantly and negatively associated with absolute ß (ß = -0.007; 95% CI, -0.01 to -0.001; semipartial r = -0.25) and γ power (ß = -0.008; 95% CI, -0.01 to -0.002; semipartial r = -0.28). Maternal educational level was significantly and positively associated with power in high α, ß, and γ bands after adjusting for covariates (high school: γ: ß = 0.108; 95% CI, 0.014-0.203; semipartial r = -0.236; associate's degree or higher: high α: ß = 0.133; 95% CI, 0.018-0.248; semipartial r = 0.241; ß: ß = 0.167; 95% CI, 0.055-0.279; semipartial r = 0.309; and γ: ß = 0.183; 95% CI, 0.066-0.299; semipartial r = 0.323). Latent profile analysis identified 2 unique profiles for absolute and relative power. Maternal perceived stress (ß = 0.13; 95% CI, 0.01-0.25; adjusted odds ratio [AOR], 1.14; 95% CI, 1.01-1.28) and maternal educational level (high school: ß = 3.00; 95% CI, 0.35-5.65; AOR, 20.09; 95% CI, 1.42-283.16; associate's degree or higher: ß = 4.12; 95% CI, 1.45-6.79; AOR, 61.56; 95% CI, 4.28-885.01) were each associated with unique profile membership. Conclusions and Relevance: These findings suggest that unique contributions of caregiver stress and maternal educational level on infant neurodevelopment are detectable at 2 months; EEG might be a promising tool to identify infants most susceptible to parental stress and to reveal mechanisms by which neurodevelopment is associated with adversity. Additional studies validating subgroups across larger cohorts with different stressors and at different ages are required before use at the individual level in clinical settings.

Eyetracking of social preference choices reveals normal but faster processing in autism.

People with Autism Spectrum Disorder (ASD) have been reported to show atypical attention and evaluative processing, in particular for social stimuli such as faces. The usual measure in these studies is an explicit, subjective judgment, which is the culmination of complex-temporally extended processes that are not typically dissected in detail. Here we addressed a neglected aspect of social decision-making in order to gain further insight into the underlying mechanisms: the temporal evolution of the choice. We investigated this issue by quantifying the alternating patterns of gaze onto faces, as well as nonsocial stimuli, while subjects had to decide which of the two stimuli they preferred. Surprisingly, the temporal profile of fixations relating to choice (the so-called "gaze cascade") was entirely normal in ASD, as were the eventual preference choices. Despite these similarities, we found two key abnormalities: people with ASD made choices more rapidly than did control subjects across the board, and their reaction times for social preference judgments were insensitive to choice difficulty. We suggest that ASD features an altered decision-making process when basing choice on social preferences. One hypothesis motivated by these data is that a choice criterion is reached in ASD regardless of the discriminability of the options.