Characteristics of women concordant and discordant for urine drug screens for cannabis exposure and self-reported cannabis use during pregnancy.

BACKGROUND: Increasing cannabis use among pregnant people and equivocal evidence linking prenatal cannabis exposure to adverse outcomes in offspring highlights the need to understand its potential impact on pregnancy and child outcomes. Assessing cannabis use during pregnancy remains a major challenge with potential influences of stigma on self-report as well as detection limitations of easily collected biological matrices. OBJECTIVE: This descriptive study examined the concordance between self-reported (SR) cannabis use and urine drug screen (UDS) detection of cannabis exposure during the first trimester of pregnancy and characterized concordant and discordant groups for sociodemographic factors, modes of use, secondhand exposure to cannabis and tobacco, and alcohol use and cotinine positivity. STUDY DESIGN: The Cannabis Use During Development and Early Life (CUDDEL) Study is an ongoing longitudinal study that recruits pregnant individuals presenting for obstetric care, who report lifetime cannabis use as well as using (n = 289) or not using cannabis (n = 169) during pregnancy. During the first trimester pregnancy visit, SR of cannabis use and a UDS for cannabis, other illicit drugs and nicotine are acquired from eligible participants, of whom 333 as of 05/01/2023 had both. RESULTS: Using available CUDDEL Study data on both SR and UDS (n = 333; age 26.6 ± 4.7; 88.6% Black; 45.4% below federal poverty threshold; 56.5% with paid employment; 89% with high school education; 22% first pregnancy; 12.3 ± 3.6 weeks gestation), we classified pregnant individuals with SR and UDS data into 4 groups based on concordance (k = 0.49 [95% C.I. 0.40-0.58]) between SR cannabis use and UDS cannabis detection during the first trimester: 1) SR+/UDS+ (n = 107); 2) SR-/UDS- (n = 142); 3) SR+/UDS- (n = 44); 4) SR-/UDS+ (n = 40). Those who were SR+/UDS- reported less frequent cannabis use and fewer hours under the influence of cannabis during their pregnancy. Those who were SR-/UDS+ were more likely to have joined the study at a lower gestational age with 62.5% reporting cannabis use during their pregnancy prior to being aware that they were pregnant. Of the 40 SR-/UDS+ women, 14 (i.e., 35%) reported past month secondhand exposure, or blunt usage. In the subset of individuals with SR and UDS available at trimester 2 (N = 160) and 3 (N = 140), concordant groups were mostly stable and > 50% of those in the discordant groups became concordant by the second trimester. Classifying individuals as exposed or not exposed who were SR+ and/or UDS+ resulted in minor changes in group status based on self-report at screening. CONCLUSION: Overall, there was moderate concordance between SR and UDS for cannabis use/exposure during pregnancy. Instances of SR+/UDS- discordancy may partially be attributable to lower levels of use that are not detected on UDS. SR-/UDS+ discordancy may arise from recent use prior to knowledge of pregnancy, extreme secondhand exposure, deception, and challenges with completing questionnaires. Acquiring both self-report and biological detection of cannabis use/exposure allows for the examination of convergent evidence. Classifying those who are SR+ and/or UDS+ as individuals who used cannabis during their first trimester after being aware of their pregnancy resulted in only a minor change in exposure status; thus, relying on self-report screening, at least in this population and within this sociocultural context likely provides an adequate approximation of cannabis use during pregnancy.

Prenatal exposure to maternal disadvantage-related inflammatory biomarkers: associations with neonatal white matter microstructure.

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation's effects on white matter development diverge depending on the availability of foundational resources in utero.

Maternal prenatal social disadvantage and neonatal functional connectivity: Associations with psychopathology symptoms at age 12 months.

Recent research has reported effects of socioeconomic status on neurobehavioral development as early as infancy, including positive associations between income and brain structure, functional connectivity, and behavior later in childhood (Ramphal, Whalen, et al., 2020; Triplett et al., 2022). This study extends this literature by investigating the relation of maternal prenatal social disadvantage (PSD) to neonatal amygdala and hippocampus functional connectivity and whether socioeconomic-related alterations in functional connectivity subsequently predict behavior at age 12 months in a large, socioeconomically diverse sample (N = 261 mother-infant dyads). PSD was assessed across gestation; neonatal magnetic resonance imaging was completed within the first weeks of life; and infant internalizing and externalizing symptoms were evaluated using the Infant-Toddler Social and Emotional Assessment at age 12 months. The results showed that PSD was significantly related to neonatal right amygdala and left hippocampus functional connectivity with prefrontal and motor-related regions. Social disadvantage-related right amygdala and left hippocampus functional connectivity with these regions was subsequently related to infant externalizing and internalizing symptoms at age 12 months. Building off an emerging literature exploring prenatal impacts on neonatal functional connectivity, this study further emphasizes the important role of the maternal environment during gestation on infant brain function and its relationship with externalizing and internalizing behavior in the first years of life. The results suggest that the prenatal socioeconomic environment may be a promising target for interventions aimed at improving infant neurobehavioral outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Newborn Brain Function and Early Emerging Callous-Unemotional Traits.

Importance: Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments. Objective: To determine whether newborn brain function is associated with early-emerging empathy, prosociality, and callous-unemotional traits. Design, Setting, and Participants: In this prospective, longitudinal cohort study, pregnant women were recruited from obstetric clinics in St Louis, Missouri, from September 1, 2017, to February 28, 2020, with longitudinal data collected until March 20, 2023. Mothers were recruited during pregnancy. Newborns underwent brain magnetic resonance imaging shortly after birth. Mothers completed longitudinal follow-up when the children were aged 1, 2, and 3 years. Exposures: The sample was enriched for exposure to socioeconomic disadvantage. Main Outcome and Measure: Functional connectivity between hypothesized brain regions was assessed using newborn-specific networks and voxel-based connectivity analyses. Children's callous-unemotional traits were measured using the Inventory of Callous-Unemotional Traits. Empathy and prosociality were assessed using the Infant and Toddler Socio-Emotional Assessment. Results: A total of 283 children (mean [SD] gestational age, 38 [2] weeks; 159 male [56.2%]; 2 Asian [0.7%], 171 Black [60%], 7 Hispanic or Latino [2.5%], 106 White [38%], 4 other racial or ethnic group [1.4%]) were included in the analysis. Stronger newborn functional connectivity between the cingulo-opercular network (CO) and medial prefrontal cortex (mPFC) was associated with higher callous-unemotional traits at age 3 years (ß = 0.31; 95% CI, 0.17-0.41; P < .001). Results persisted when accounting for parental callous-unemotional traits and child externalizing symptoms. Stronger newborn CO-mPFC connectivity was also associated with lower empathy and lower prosociality at ages 1, 2, and 3 years using multilevel models (ß = -0.12; 95% CI, -0.21 to -0.04; P = .004 and ß = -0.20; 95% CI, -0.30 to -0.10; P < .001, respectively). Conclusions and Relevance: Newborn functional connectivity was associated with early-emerging empathy, prosociality, and callous-unemotional traits, even when accounting for parental callous-unemotional traits and child externalizing symptoms. Understanding the neurobiological underpinnings of empathy, prosociality, and callous-unemotional traits at the earliest developmental point may help early risk stratification and novel intervention development.

Neighborhood Crime and Externalizing Behavior in Toddlers: A Longitudinal Study With Neonatal fMRI and Parenting.

OBJECTIVE: Prenatal exposure to neighborhood crime has been associated with weaker neonatal frontolimbic connectivity; however, associations with early childhood behavior remain unclear. We hypothesized that living in a high-crime neighborhood would be related to higher externalizing symptoms at age 1 and 2 years, over and above other adversities, and that neonatal frontolimbic connectivity and observed parenting behaviors at 1 year would mediate this relationship. METHOD: Participants included 399 pregnant women, recruited as part of the Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders (eLABE) study. Geocoded neighborhood crime data was obtained from Applied Geographic Solution. A total of 319 healthy, non-sedated neonates underwent scanning using resting-state functional magnetic resonance imaging (fMRI) on a Prisma 3T scanner and had ≥10 minutes of high-quality data. Infant-Toddler Socioemotional Assessment Externalizing T scores were available for 274 mothers of 1-year-olds and 257 mothers of 2-year-olds. Observed parenting behaviors were available for 202 parent-infant dyads at 1 year. Multilevel and mediation models tested longitudinal associations. RESULTS: Living in a neighborhood with high violent (ß = 0.15, CI = 0.05-0.27, p = .004) and property (ß = 0.10, CI = 0.01-0.20, p = .039) crime was related to more externalizing symptoms at 1 and 2 years, controlling for other adversities. Weaker frontolimbic connectivity was also associated with higher externalizing symptoms at 1 and 2 years. After controlling for other adversities, parenting behaviors mediated the specific association between crime and externalizing symptoms, but frontolimbic connectivity did not. CONCLUSION: These findings provide evidence that early exposure to neighborhood crime and weaker neonatal frontolimbic connectivity may influence later externalizing symptoms, and suggest that parenting may be an early intervention target for families in high-crime areas. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Neonatal neural responses to novelty related to behavioral inhibition at 1 year.

Behavioral inhibition (BI), an early-life temperament characterized by vigilant responses to novelty, is a risk factor for anxiety disorders. In this study, we investigated whether differences in neonatal brain responses to infrequent auditory stimuli relate to children's BI at 1 year of age. Using functional magnetic resonance imaging (fMRI), we collected blood-oxygen-level-dependent (BOLD) data from N = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from n = 27 of these children 1 year later using an observational assessment. Whole-brain analyses corrected for multiple comparisons identified 46 neonatal brain regions producing novelty-evoked BOLD responses associated with children's BI scores at 1 year of age. More than half of these regions (n = 24, 52%) were in prefrontal cortex, falling primarily within regions of the default mode or frontoparietal networks or in ventromedial/orbitofrontal regions without network assignments. Hierarchical clustering of the regions based on their patterns of association with BI resulted in two groups with distinct anatomical, network, and response-timing profiles. The first group, located primarily in subcortical and temporal regions, tended to produce larger early oddball responses among infants with lower subsequent BI. The second group, located primarily in prefrontal cortex, produced larger early oddball responses among infants with higher subsequent BI. These results provide preliminary insights into brain regions engaged by novelty in infants that may relate to later BI. The findings may inform understanding of anxiety disorders and guide future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Association Between Maternal Cortisol and Infant Amygdala Volume Is Moderated by Socioeconomic Status.

Background: It has been well established that socioeconomic status is associated with mental and physical health as well as brain development, with emerging data suggesting that these relationships begin in utero. However, less is known about how prenatal socioeconomic environments interact with the gestational environment to affect neonatal brain volume. Methods: Maternal cortisol output measured at each trimester of pregnancy and neonatal brain structure were assessed in 241 mother-infant dyads. We examined associations between the trajectory of maternal cortisol output across pregnancy and volumes of cortisol receptor-rich regions of the brain, including the amygdala, hippocampus, medial prefrontal cortex, and caudate. Given the known effects of poverty on infant brain structure, socioeconomic disadvantage was included as a moderating variable. Results: Neonatal amygdala volume was predicted by an interaction between maternal cortisol output across pregnancy and socioeconomic disadvantage (standardized ß = -0.31, p < .001), controlling for postmenstrual age at scan, infant sex, and total gray matter volume. Notably, amygdala volumes were positively associated with maternal cortisol for infants with maternal disadvantage scores 1 standard deviation below the mean (i.e., less disadvantage) (simple slope = 123.36, p < .01), while the association was negative in infants with maternal disadvantage 1 standard deviation above the mean (i.e., more disadvantage) (simple slope = -82.70, p = .02). Individuals with disadvantage scores at the mean showed no association, and there were no significant interactions in the other brain regions examined. Conclusions: These data suggest that fetal development of the amygdala is differentially affected by maternal cortisol production at varying levels of socioeconomic advantage.

Social and psychological adversity are associated with distinct mother and infant gut microbiome variations.

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in the mothers and children indicate that different discriminatory taxa and related pathways are involved, including many species of Bifidobacterium and related pathways across several comparisons. The lowest inter-individual gut microbiome similarity was observed among high-social disadvantage/high-psychosocial stressors mothers, suggesting distinct environmental exposures driving a diverging gut microbiome assembly compared to low-social disadvantage/low-psychosocial stressors controls (P = 3.5 × 10-5 for social disadvantage, P = 2.7 × 10-15 for psychosocial stressors). Children's gut metagenome profiles at 4 months also significantly predicted high/low maternal prenatal IL-6 (P = 0.029), with many bacterial species overlapping those identified by social disadvantage and psychosocial stressors. These differences, based on maternal social and psychological status during a critical developmental window early in life, offer potentially modifiable targets to mitigate health inequities.

Social disadvantage during pregnancy: effects on gestational age and birthweight.

OBJECTIVE: Whether psychosocial adversity during pregnancy impacts fetal health outcomes at birth remains underexplored. This is a critical issue given significant social disadvantage and psychosocial stress faced by pregnant women worldwide. STUDY DESIGN: Measures of social disadvantage and psychological factors, and medical/reproductive and nutritional health status in pregnant women were obtained at each trimester. Using Structural Equation Modeling (SEM), we investigated the relationship of forms of adversity to each other and to infant gestational age, and birthweight. RESULTS: Among 399 singletons, Social Disadvantage significantly predicted gestational age (p = 0.003), and residual birthweight (p = 0.006). There was a 0.4 week decrease in gestational age and a 3% decrease in birthweight for each standard deviation increase in Social Disadvantage. CONCLUSION: Significant negative effects of social adversity on the developing fetus were found. Notably, these effects emerged despite good prenatal care and after accounting for maternal age and medical reproductive risk factors.

Socioeconomic disadvantage and parental mood/affective problems links negative parenting and executive dysfunction in children born very preterm.

Poverty increases the risk of poorer executive function (EF) in children born full-term (FT). Stressors associated with poverty, including variability in parenting behavior, may explain links between poverty and poorer EF, but this remains unclear for children born very preterm (VPT). We examine socioeconomic and parental psychosocial adversity on parenting behavior, and whether these factors independently or jointly influence EF in children born VPT. At age five years, 154 children (VPT = 88, FT = 66) completed parent-child interaction and EF tasks. Parental sensitivity, intrusiveness, cognitive stimulation, and positive and negative regard were coded with the Parent-Child Interaction Rating Scale. Socioeconomic adversity spanned maternal demographic stressors, Income-to-Needs ratio, and Area Deprivation Index. Parents completed measures of depression, anxiety, inattention/hyperactivity, parenting stress, and social-communication interaction (SCI) problems. Parental SCI problems were associated with parenting behavior in parents of children born VPT, whereas socioeconomic adversity was significant in parents of FT children. Negative parenting behaviors, but not positive parenting behaviors, were related to child EF. This association was explained by parental depression/anxiety symptoms and socioeconomic adversity. Results persisted after adjustment for parent and child IQ. Findings may inform research on dyadic interventions that embed treatment for parental mood/affective symptoms and SCI problems to improve childhood EF.

Parental ADHD and ASD symptoms and contributions of psychosocial risk to childhood ADHD and ASD symptoms in children born very preterm.

OBJECTIVES: Examine maternal and paternal ADHD and ASD symptoms in relation to very preterm (VPT) and full-term (FT) children's ADHD and ASD symptoms. STUDY DESIGN: In this longitudinal study, maternal- and teacher-report of child ADHD and ASD symptoms were obtained for 119 children (VPT = 79, FT = 40) at age 5-years using the Conner's Rating Scale-Revised (CRS-R) and Social Responsiveness Scale-2 (SRS-2). A biological parent completed self- and observer-report CRS-R and SRS-2, and measures of mood/affect, stress, and social support to assess psychosocial distress. Data were analyzed using mixed-effect models adjusted for covariates. RESULTS: Child ADHD symptoms were associated with VPT birth, maternal distress, and maternal ADHD symptoms (p ≤ 0.02), and paternal ADHD symptoms (p < 0.001). Regarding ASD, VPT birth and parental ASD symptoms were associated with child ASD symptoms (p ≤ 0.009). Parental symptoms and birth group had no interaction. CONCLUSIONS: VPT birth and parental psychopathology represent independent risks for ADHD and ASD.

Maturation of large-scale brain systems over the first month of life.

The period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child's earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain "growth curve" that could be used to identify atypical brain maturation in infancy.

Prenatal exposure to maternal social disadvantage and psychosocial stress and neonatal white matter connectivity at birth.

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. Mean diffusivity (MD) and fractional anisotropy (FA) were measured for the dorsal and inferior cingulum bundle (CB), uncinate, and fornix using probabilistic tractography in FSL. Social disadvantage and psychosocial stress were fitted to dMRI parameters using regression models adjusted for infant postmenstrual age at scan and sex. Social disadvantage, but not psychosocial stress, was independently associated with lower MD in the bilateral inferior CB and left uncinate, right fornix, and lower MD and higher FA in the right dorsal CB. Results persisted after accounting for maternal medical morbidities and prenatal drug exposure. In moderation analysis, psychosocial stress was associated with lower MD in the left inferior CB among the lower-to-higher socioeconomic status (SES) (INR ≥ 200%) group, but not the extremely low SES (INR < 200%) group. Increasing access to social welfare programs that reduce the burden of social disadvantage and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways.

The Effects of Prenatal Exposure to Neighborhood Crime on Neonatal Functional Connectivity.

BACKGROUND: Maternal exposure to adversity during pregnancy has been found to affect infant brain development; however, the specific effect of prenatal crime exposure on neonatal brain connectivity remains unclear. Based on existing research, we hypothesized that living in a high-crime neighborhood during pregnancy would affect neonatal frontolimbic connectivity over and above other individual- and neighborhood-level adversity and that these associations would be mediated by maternal psychosocial stress. METHODS: Participants included 399 pregnant women, recruited as part of the eLABE (Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders) study. In the neonatal period, 319 healthy, nonsedated infants were scanned using resting-state functional magnetic resonance imaging (repetition time = 800 ms; echo time = 37 ms; voxel size = 2.0 × 2.0 × 2.0 mm3; multiband = 8) on a Prisma 3T scanner and had at least 10 minutes of high-quality data. Crime data at the block group level were obtained from Applied Geographic Solution. Linear regressions and mediation models tested associations between crime, frontolimbic connectivity, and psychosocial stress. RESULTS: Living in a neighborhood with high property crime during pregnancy was related to weaker neonatal functional connectivity between the thalamus-anterior default mode network (aDMN) (ß = -0.15, 95% CI = -0.25 to -0.04, p = .008). Similarly, high neighborhood violent crime was related to weaker functional connectivity between the thalamus-aDMN (ß = -0.16, 95% CI = -0.29 to -0.04, p = .01) and amygdala-hippocampus (ß = -0.16, 95% CI = -0.29 to -0.03, p = .02), controlling for other types of adversity. Psychosocial stress partially mediated relationships between the thalamus-aDMN and both violent and property crime. CONCLUSIONS: These findings suggest that prenatal exposure to crime is associated with weaker neonatal limbic and frontal functional brain connections, providing another reason for targeted public policy interventions to reduce crime.

Neonatal Intensive Care Unit Network Neurobehavioral Scale Profiles in Full-Term Infants: Associations with Maternal Adversity, Medical Risk, and Neonatal Outcomes.

OBJECTIVES: To examine healthy, full-term neonatal behavior using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) in relation to measures of maternal adversity, maternal medical risk, and infant brain volumes. STUDY DESIGN: This was a prospective, longitudinal, observational cohort study of pregnant mothers followed from the first trimester and their healthy, full-term infants. Infants underwent an NNNS assessment and high-quality magnetic resonance imaging 2-5 weeks after birth. A latent profile analysis of NNNS scores categorized infants into neurobehavioral profiles. Univariate and multivariate analyses compared differences in maternal factors (social advantage, psychosocial stress, and medical risk) and neonatal characteristics between profiles. RESULTS: The latent profile analysis of NNNS summary scales of 296 infants generated 3 profiles: regulated (46.6%), hypotonic (16.6%), and fussy (36.8%). Infants with a hypotonic profile were more likely to be male (χ2 = 8.601; P = .014). Fussy infants had smaller head circumferences (F = 3.871; P = .022) and smaller total brain (F = 3.522; P = .031) and cerebral white matter (F = 3.986; P = .020) volumes compared with infants with a hypotonic profile. There were no differences between profiles in prenatal maternal health, social advantage, or psychosocial stress. CONCLUSIONS: Three distinct neurobehavioral profiles were identified in healthy, full-term infants with hypotonic and fussy neurobehavioral features related to neonatal brain volumes and head circumference, but not prenatal exposure to socioeconomic or psychosocial adversity. Follow-up beyond the neonatal period will determine if identified profiles at birth are associated with subsequent clinical or developmental outcomes.

Association of Prenatal Exposure to Early-Life Adversity With Neonatal Brain Volumes at Birth.

Importance: Exposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood. Objective: To examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding. Design, Setting, and Participants: This prospective, longitudinal cohort study included 399 mother-infant dyads of sociodemographically diverse mothers recruited in the first or early second trimester of pregnancy and their infants, who underwent brain magnetic resonance imaging in the first weeks of life. Mothers were recruited from local obstetric clinics in St Louis, Missouri from September 1, 2017, to February 28, 2020. Exposures: Maternal social disadvantage and psychosocial stress in pregnancy. Main Outcomes and Measures: Confirmatory factor analyses were used to create latent constructs of maternal social disadvantage (income-to-needs ratio, Area Deprivation Index, Healthy Eating Index, educational level, and insurance status) and psychosocial stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, and Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellum, hippocampus, and amygdala volumes were generated using semiautomated, age-specific, segmentation pipelines. Results: A total of 280 mothers (mean [SD] age, 29.1 [5.3] years; 170 [60.7%] Black or African American, 100 [35.7%] White, and 10 [3.6%] other race or ethnicity) and their healthy, term-born infants (149 [53.2%] male; mean [SD] infant gestational age, 38.6 [1.0] weeks) were included in the analysis. After covariate adjustment and multiple comparisons correction, greater social disadvantage was associated with reduced cortical gray matter (unstandardized ß = -2.0; 95% CI, -3.5 to -0.5; P = .01), subcortical gray matter (unstandardized ß = -0.4; 95% CI, -0.7 to -0.2; P = .003), and white matter (unstandardized ß = -5.5; 95% CI, -7.8 to -3.3; P < .001) volumes and cortical folding (unstandardized ß = -0.03; 95% CI, -0.04 to -0.01; P < .001). Psychosocial stress showed no association with brain metrics. Although social disadvantage accounted for an additional 2.3% of the variance of the left hippocampus (unstandardized ß = -0.03; 95% CI, -0.05 to -0.01), 2.3% of the right hippocampus (unstandardized ß = -0.03; 95% CI, -0.05 to -0.01), 3.1% of the left amygdala (unstandardized ß = -0.02; 95% CI, -0.03 to -0.01), and 2.9% of the right amygdala (unstandardized ß = -0.02; 95% CI, -0.03 to -0.01), no regional effects were found after accounting for total brain volume. Conclusions and Relevance: In this baseline assessment of an ongoing cohort study, prenatal social disadvantage was associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that associations between poverty and brain development begin in utero and are evident early in life. These findings emphasize that preventive interventions that support fetal brain development should address parental socioeconomic hardships.

EEG/ERP as a pragmatic method to expand the reach of infant-toddler neuroimaging in HBCD: Promises and challenges.

Though electrophysiological measures (EEG and ERP) offer complementary information to MRI and a variety of advantages for studying infants and young children, these measures have not yet been included in large cohort studies of neurodevelopment. This review summarizes the types of EEG and ERP measures that could be used in the HEALthy Brain and Cognitive Development (HBCD) study, and the promises and challenges in doing so. First, we provide brief overview of the use of EEG/ERP for studying the developing brain and discuss exemplar findings, using resting or baseline EEG measures as well as the ERP mismatch negativity (MMN) as exemplars. We then discuss the promises of EEG/ERP such as feasibility, while balancing challenges such as ensuring good signal quality in diverse children with different hair types. We then describe an ongoing multi-site EEG data harmonization from our groups. We discuss the process of alignment and provide preliminary usability data for both resting state EEG data and auditory ERP MMN in diverse samples including over 300 infants and toddlers. Finally, we provide recommendations and considerations for the HBCD study and other studies of neurodevelopment.

Neonatal Brain Response to Deviant Auditory Stimuli and Relation to Maternal Trait Anxiety.

OBJECTIVE: Excessive response to unexpected or "deviant" stimuli during infancy and early childhood represents an early risk marker for anxiety disorders. However, research has yet to delineate the specific brain regions underlying the neonatal response to deviant stimuli near birth and the relation to risk for anxiety disorders. The authors used task-based functional MRI (fMRI) to delineate the neonatal response to deviant stimuli and its relationship to maternal trait anxiety. METHODS: The authors used fMRI to measure brain activity evoked by deviant auditory stimuli in 45 sleeping neonates (mean age, 27.8 days; 60% female; 64% African American). In 41 of the infants, neural response to deviant stimuli was examined in relation to maternal trait anxiety on the State-Trait Anxiety Inventory, a familial risk factor for offspring anxiety. RESULTS: Neonates manifested a robust and widespread neural response to deviant stimuli that resembles patterns found previously in adults. Higher maternal trait anxiety was related to higher responses within multiple brain regions, including the left and right anterior insula, the ventrolateral prefrontal cortex, and multiple areas within the anterior cingulate cortex. These areas overlap with brain regions previously linked to anxiety disorders and other psychiatric illnesses in adults. CONCLUSIONS: The neural architecture sensitive to deviant stimuli robustly functions in newborns. Excessive responsiveness of some circuitry components at birth may signal risk for anxiety and other psychiatric disorders.

Tract-Specific Relationships Between Cerebrospinal Fluid Biomarkers and Periventricular White Matter in Posthemorrhagic Hydrocephalus of Prematurity.

BACKGROUND: Posthemorrhagic hydrocephalus (PHH) is associated with neurological morbidity and complex neurosurgical care. Improved tools are needed to optimize treatments and to investigate the developmental sequelae of PHH. OBJECTIVE: To examine the relationship between diffusion magnetic resonance imaging (dMRI) and cerebrospinal fluid (CSF) biomarkers of PHH. METHODS: A total of 14 preterm (PT) infants with PHH and 46 controls were included. PT CSF was collected at temporizing surgery in PHH infants (PHH PT CSF) or lumbar puncture in controls. Term-equivalent age (TEA) CSF was acquired via implanted device or at permanent CSF diversion surgery in PHH (PHH-TEA-CSF) or lumbar puncture in controls. TEA dMRI scans were used to measure fractional anisotropy (FA) and mean diffusivity (MD) in the genu of corpus callosum (gCC), posterior limb of internal capsule (PLIC), and optic radiations (OPRA). Associations between dMRI measures and CSF amyloid precursor protein (APP), neural cell adhesion-1 (NCAM-1), and L1 cell adhesion molecule (L1CAM) were assessed using Pearson correlations. RESULTS: APP, NCAM-1, and L1CAM were elevated over controls in PHH-PT-CSF and PHH-TEA-CSF. dMRI FA and MD differed between control and PHH infants across all tracts. PHH-PT-CSF APP levels correlated with gCC and OPRA FA and PLIC MD, while L1CAM correlated with gCC and OPRA FA. In PHH-TEA-CSF, only L1CAM correlated with OPRA MD. CONCLUSION: Tract-specific associations were observed between dMRI and CSF biomarkers at the initiation of PHH treatment. dMRI and CSF biomarker analyses provide innovative complementary methods for examining PHH-related white matter injury and associated developmental sequelae.

Microstructure of the Dorsal Anterior Cingulum Bundle in Very Preterm Neonates Predicts the Preterm Behavioral Phenotype at 5 Years of Age.

BACKGROUND: The cingulum bundle (CB), specifically the dorsal anterior portion of the CB, plays an important role in psychiatric illnesses; however, its role during early development is unclear. This study investigated whether neonatal white matter microstructure in the CB and its subregions is associated with subsequent preterm behavioral phenotype symptoms (internalizing, inattention, and social deficits) in very preterm (VPT) children. METHODS: Diffusion magnetic resonance imaging data were obtained on a 3T scanner in 138 sleeping nonsedated neonates: 55 full-term neonates (gestational age ≥ 36 weeks) and 83 VPT neonates (gestational age < 30 weeks). The CB was tracked using probabilistic tractography and split into anterior and posterior portions. When children were 5 years of age, parents (n = 80) and teachers (n = 63) of VPT children completed questionnaires of preterm behavioral phenotype symptoms. Linear regression models were used to relate measures of neonatal CB microstructure and childhood preterm behavioral phenotype symptoms (n = 56 parent report, n = 45 teacher report). RESULTS: Mean diffusivity in the anterior and posterior CB was increased in VPT neonates compared with full-term neonates. Increased fractional anisotropy and decreased mean diffusivity in the right anterior CB, but not in the posterior CB, were related to increased preterm behavioral phenotype symptoms in VPT children as reported by parents and teachers. CONCLUSIONS: Aberrations in the anterior portion of the right CB may underlie the early development of the preterm behavioral phenotype. This finding provides the foundation for future mechanistic and therapeutic investigations into the role of the anterior cingulum in the development of psychopathology in VPT infants.