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.

Associations between Parenting and Cognitive and Language Abilities at 2 Years of Age Depend on Prenatal Exposure to Disadvantage.

OBJECTIVE: To investigate whether parenting or neonatal brain volumes mediate associations between prenatal social disadvantage (PSD) and cognitive/language abilities and whether these mechanisms vary by level of disadvantage. STUDY DESIGN: Pregnant women were recruited prospectively from obstetric clinics in St Louis, Missouri. PSD encompassed access to social (eg, education) and material (eg, income to needs, health insurance, area deprivation, and nutrition) resources during pregnancy. Neonates underwent brain magnetic resonance imaging. Mother-child dyads (n = 202) returned at age 1 year for parenting observations and at age 2 years for cognition/language assessments (Bayley Scales of Infant and Toddler Development, Third Edition). Generalized additive and mediation models tested hypotheses. RESULTS: Greater PSD associated nonlinearly with poorer cognitive/language scores. Associations between parenting and cognition/language were moderated by disadvantage, such that supportive and nonsupportive parenting behaviors related only to cognition/language in children with lesser PSD. Parenting mediation effects differed by level of disadvantage: both supportive and nonsupportive parenting mediated PSD-cognition/language associations in children with lesser disadvantage, but not in children with greater disadvantage. PSD-associated reductions in neonatal subcortical grey matter (ß = 0.19; q = 0.03), white matter (ß = 0.23; q = 0.02), and total brain volume (ß = 0.18; q = 0.03) were associated with lower cognition, but did not mediate the associations between PSD and cognition. CONCLUSIONS: Parenting moderates and mediates associations between PSD and early cognition and language, but only in families with less social disadvantage. These findings, although correlational, suggest that there may be a critical threshold of disadvantage, below which mediating or moderating factors become less effective, highlighting the importance of reducing disadvantage as primary prevention.

Less attention to emotional faces is associated with low empathy and prosociality in 12-to 20-month old infants.

The development of empathy and prosocial behavior begins in infancy and is likely supported by emotion processing skills. The current study explored whether early emerging deficits in emotion processing are associated with disruptions in the development of empathy and prosociality. We investigated this question in a large, diverse sample of 147, 11- to 20-month-old infants (42% female; 61% Black; 67% low socioeconomic status). Infants completed two observational tasks assessing prosocial helping and one task assessing empathy and prosocial comforting behavior. Infants also completed an eye-tracking task assessing engagement and disengagement with negative emotional faces. Infants who attended less to angry, sad, and fearful faces (i.e., by being slower to look at and/or quicker to look away from negative compared to neutral faces) engaged in fewer helping behaviors, and effect sizes were larger when examining infants' attention toward the eye regions of faces. Additionally, infants who were quicker to look away from the eye regions of angry faces, but not the whole face, displayed less empathy and comforting behaviors. Results suggest that as early as 12 months of age, infants' decreased attention toward negative emotional faces, particularly the eye regions, is associated with less empathy and prosociality during a developmental period in which these abilities are rapidly maturing.

Maternal emotional intelligence and negative parenting affect are independently associated with callous-unemotional traits in preschoolers.

Deficits in emotion intelligence (EI) are a key component of early-childhood callous-unemotional (CU) traits. Children's EI may be influenced by their mother's EI through both familial genetic and environmental mechanisms; however, no study has directly tested the role of maternal EI in the development of CU traits. This study investigated whether maternal EI had a direct relationship with children's CU traits when controlling for the potential influence of parenting affect and other psychiatric diagnoses. Mothers and their 3- to 5-year-old preschoolers (N = 200) were recruited as part of a parent-child interaction-emotion development therapy treatment trial for preschool clinical depression and comorbid psychopathology. Using data collected prior to treatment, regression models tested whether maternal EI was related to children's CU traits, which specific aspects of maternal EI were most strongly associated with CU traits, and whether associations held after accounting for observed parenting affect. Maternal EI (p < 0.005), specifically the ability to understand others' emotions (p < 0.01), was significantly associated with children's CU traits. This relationship was specific, as maternal EI did not predict depression or oppositional defiant disorder. Both maternal EI and observed negative parenting affect were independently and significantly related to CU traits (p < 0.05) in a combined model. Given that maternal EI and observed negative parenting affect were independent predictors of CU traits in preschoolers with comorbid depression, findings suggest that current treatments for CU traits that focus solely on improving parenting could be made more effective by targeting maternal EI and helping mothers better model emotional competence.

The Influence of Pandemic-Related Worries During Pregnancy on Child Development at 12 Months.

The COVID-19 pandemic has been linked to increased risk for perinatal anxiety and depression among parents, as well as negative consequences for child development. Less is known about how worries arising from the pandemic during pregnancy are related to later child development, nor if resilience factors buffer negative consequences. The current study addresses this question in a prospective longitudinal design. Data was collected from a sub-study (n = 184) of a longitudinal study of pregnant individuals (total n = 1173). During pregnancy (April 17-July 8, 2020) and the early postpartum period (August 11, 2020-March 2, 2021), participants completed online surveys. At 12 months postpartum (June 17, 2021-March 23, 2022), participants completed online surveys and a virtual laboratory visit, which included parent-child interaction tasks. We found more pregnancy-specific pandemic worries were prospectively related to lower levels of child socioemotional development based on parent report (B = - 1.13, SE = .43, p = .007) and observer ratings (B = - 0.13, SE = .07, p = .045), but not to parent-reported general developmental milestones. Parental emotion regulation in the early postpartum period moderated the association between pregnancy-specific pandemic worries and child socioemotional development such that pregnancy-specific pandemic worries did not relate to worse child socioemotional development among parents with high (B = - .02, SE = .10, t = - .14, p = .89) levels of emotion regulation. Findings suggest the negative consequences of parental worry and distress during pregnancy on the early socioemotional development of children in the context of the COVID-19 pandemic. Results highlight that parental emotion regulation may represent a target for intervention to promote parental resilience and support optimized child development.

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.

Observations of Positive Parenting from Online Parent-Child Interactions at Age 1.

Objective: Brief, reliable, and cost-effective methods to assess parenting are critical for advancing parenting research. Design: We adapted the Three Bags task and Parent Child Interaction Rating System (PCIRS) for rating online visits with 219 parent-child dyads (White, n = 104 [47.5%], Black, n = 115 [52.5%]) and combined the video data with survey data collected during pregnancy and when children were aged 1. Results: The PCIRS codes of positive regard, stimulation of child cognitive development, and sensitivity showed high reliability across the three parent-child interaction tasks. A latent positive parenting factor combining ratings across codes and tasks showed good model fit, which was similar regardless of parent self-identified race or ethnicity, age, socioeconomic disadvantage, marital/partnered status, and parity, as well as methodological factors relevant to the online video assessment method (e.g., phone vs. laptop/tablet). In support of construct validity, observed positive parenting was related to parent-reported positive parenting and child socioemotional development. Finally, parent reports of supportive relationships in pregnancy, but not neighborhood safety or pandemic worries, were prospectively related to higher positive parenting observed at age 1. With the exception of older parental age and married/partnered status, no other parent, child, sociodemographic, or methodological variables were related to higher overall video exclusions across tasks. Conclusions: PCIRS may provide a reliable approach to rate positive parenting at age 1, providing future avenues for developing more ecologically valid assessments and implementing interventions through online encounters that may be more acceptable, accessible, or preferred among parents of young children.

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.

The Influence of Pandemic-Related Worries During Pregnancy on Child Development at 12 Months.

The COVID-19 pandemic has been linked to increased risk for perinatal anxiety and depression among parents, as well as negative consequences for child development. Less is known about how worries arising from the pandemic during pregnancy are related to later child development, nor if resilience factors buffer negative consequences. The current study addresses this question in a prospective longitudinal design. Data was collected from a sub-study ( n = 184) of a longitudinal study of pregnant individuals (total n = 1,173). During pregnancy (April 17-July 8, 2020) and the early postpartum period (August 11, 2020-March 2, 2021), participants completed online surveys. At 12 months postpartum (June 17, 2021-March 23, 2022), participants completed online surveys and a virtual laboratory visit, which included parent-child interaction tasks. We found more pregnancy-specific pandemic worries were prospectively related to lower levels of child socioemotional development based on parent report (B=-1.13, SE = .43, p = .007) and observer ratings (B=-0.13, SE = .07, p = .045), but not to parent-reported general developmental milestones. Parental emotion regulation in the early postpartum period moderated the association between pregnancy-specific pandemic worries and child socioemotional development such that pregnancy-specific pandemic worries did not related to worse child socioemotional development among parents with high (B=-.02, SE = .10, t=-.14, p = .89) levels of emotion regulation. Findings suggest the negative consequences of parental worry and distress during pregnancy on the early socioemotional development of children in the context of the COVID-19 pandemic. Results highlight that parental emotion regulation may represent a target for intervention to promote parental resilience and support optimized child development.

Neonatal motor functional connectivity and motor outcomes at age two years in very preterm children with and without high-grade brain injury.

Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born <32 weeks' gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury.

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.

Postoperative Analgesia Protocol: A Resident-Led Effort to Standardize Opioid Prescribing Patterns.

OBJECTIVES: The combined impact of variable surgeon prescribing preferences and low resident prescribing comfort level can lead to significant disparity in opioid prescribing patterns for the same surgery in the same academic surgical practice. We report the results of a resident led initiative to standardize postoperative prescription practices within the Department of Otolaryngology at a single tertiary-care academic hospital in order to reduce overall opioid distribution. STUDY DESIGN: Retrospective cohort study. METHODS: Following approval by the Institutional Review Board, performed a retrospective review of 12 months before (July 2016-June 2017) and after (July 2017-June 2018) implementation of the Postoperative Analgesia Protocol, which included all adults undergoing tonsillectomy, septoplasty, thyroidectomy, parathyroidectomy, tympanoplasty, middle ear exploration, stapedectomy, and ossicular chain reconstruction. RESULTS: Seven hundred and thirty eight procedures met inclusion criteria. Following implementation, total morphine milligram equivalents decreased by 26% (P < .0001). The number of patients requiring opioid refills decreased by 49%, and morphine milligram equivalents received as refills decreased by 16% (P < .001). Thyroid and parathyroid surgery had the greatest reduction in morphine milligram equivalents prescribed (84%, P < .001), followed by septoplasty (30%, P = .001) and tonsillectomy (18%, P < .001). The number of patients receiving refills of opioid medications decreased for all procedures (tonsillectomy 54%; septoplasty 67%; thyroid/parathyroid surgery 80%, middle ear surgery 100%). CONCLUSIONS: While every patient and surgery must be treated individually, this study demonstrates that a resident led standardization of pain control regimes can result in significant reductions in total quantity of opioids prescribed. LEVEL OF EVIDENCE: IV Laryngoscope, 131:982-988, 2021.

Functional Connectivity Relationships to Longitudinal Motor Outcomes Differ in Very Preterm Children With and Without Brain Injury.

Background and Objectives: Children born very preterm (VPT) have high rates of motor disability, but mechanisms for early identification remain limited, especially for children who fall behind in early childhood. This study examines the relationship between functional connectivity (FC) measured at term-equivalent age and motor outcomes at 2 and 5 years. Methods: In this longitudinal observational cohort study, VPT children (gestational age 30 weeks and younger) with and without high-grade brain injury underwent FC MRI at term-equivalent age. Motor development was assessed using the Bayley Scales of Infant Development, Third Edition, at corrected age 2 years and Movement Assessment Battery for Children, Second Edition, at age 5 years. Logistic and negative binomial/Poisson regression models examined relationships between FC measures and 5-year task scores, with and without 2-year scores as covariates. Infants were categorized as "injured" or "uninjured" based on structural MRI findings at term-equivalent age. Results: In the injured group (n = 34), each 1 SD decrease in neonatal left-right motor cortex FC was related to approximately 4× increased odds of being unable to complete a fine motor task at age 5 (log odds = -1.34, p < 0.05). In the uninjured group (n = 41), stronger basal ganglia-motor cortex FC was related to poorer fine motor scores (Est = -0.40, p < 0.05) and stronger cerebellum-motor cortex FC was related to poorer balance and fine motor scores (Est = -0.05 to -0.23, p < 0.05), with balance persisting with adjustment for 2-year scores. Discussion: In VPT children with brain injury, interhemispheric motor cortex FC was related to motor deficits at 5-year assessment, similar to previous findings at 2 years. In uninjured children, FC-measured disruption of the motor system during the neonatal period was associated with motor planning/coordination difficulties that were not apparent on 2-year assessment but emerged at 5 years, suggesting that the neural basis of these deficits was established very early in life. Subsequently, 2-year follow-up may not be sufficient to detect milder motor deficits in VPT children, and they should be monitored for motor difficulties throughout the preschool years. For all VPT children, FC at term-equivalent age has the potential to improve our ability to predict disability before it presents behaviorally.