Faculty Bibliography

BACKGROUND/UNASSIGNED:Pregnancy requires finely tuned immune changes that support implantation, placental development, maternal-fetal tolerance, and preparation for labor, yet the normative trajectories of circulating inflammatory proteins across gestation remain poorly defined. This cross-sectional study investigates how circulating inflammatory proteins vary with gestational age in pregnancy and examines the impacts of fundamental biological characteristics, such as gravidity and fetal sex. METHODS/UNASSIGNED:Data were drawn from 1154 pregnant individuals from six study sites of the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Cohort. We used Olink high-throughput proteomic profiling to map cross-sectional associations between protein expression levels and gestational age at blood draw using linear, spline-based, and generalized additive modeling approaches. RESULTS/UNASSIGNED:Generalized additive models provided the best fit, revealing that immune changes across pregnancy were predominantly nonlinear. Sixty-one proteins showed significant associations with gestational age, with many exhibiting shared inflection points that aligned with major physiological transitions. A small subset of proteins also showed evidence of modification by fetal and maternal characteristics. CD244 displayed different gestational patterns by fetal sex, while CST5 and SIRT2 showed varied gestational associations by maternal gravidity. CONCLUSION/UNASSIGNED:The findings highlight pregnancy as a sequence of coordinated immune transitions rather than a simple linear shift and provide one of the most detailed characterizations to date of circulating inflammatory protein dynamics across human gestation. Establishing these normative trajectories offers a crucial reference for detecting early deviations that may signal risk for pregnancy complications and for identifying biomarkers in maternal and fetal health research.

A large body of evidence supports the role of the prenatal environment in shaping childhood development. The relative contributions of prenatal alcohol use (PAE), maternal socioeconomic, and nutritional status on child development vary in high- versus low-income settings. We analyzed data from a prospective cohort study among mother-infant dyads from Cape Town (CT), South Africa and the Northern Plains (NP), USA. The Mullen Scales of Early Learning were administered by trained assessors to evaluate cognitive, motor, and language development of 1-year old children. We used multiple linear regression models to assess standardized mean differences in development scores by (1) maternal prenatal factors, (2) delivery factors and (3) child factors within each study site. 1,728 infants from CT and 1,140 infants from the NP were included in the analyses. In CT, infants with moderate-to-high PAE had 0.17 SD (95% CI -0.30, -0.04) lower cognitive and 0.15 SD (-0.29, -0.2) lower expressive language scores compared to infants without PAE. In the NP, maternal obesity (BMI > 30 kg/m2) was significantly associated with -0.21 SD (-0.36, -0.06), and -0.13 SD (-0.27, -0.02) reductions in cognitive, and expressive language scores, respectively. Household crowding, lower levels of maternal educational attainment, prenatal maternal depression, low birthweight, admission to neonatal intensive care unit, and male sex had significant negative associations with cognitive and language development in both sites with effects ranging from -0.32 to -0.11 SDs. These results highlight the importance of assessing risk factors by populations across diverse social and cultural environments and emphasize the imperative to formulate intervention packages tailored to the local context.

Individuals with Down syndrome (DS) are at risk for early-onset Alzheimer's disease (AD), marked by neurodegeneration in hippocampal and basal forebrain circuits. Early-life interventions offer therapeutic potential, including maternal choline supplementation (MCS). MCS improves cognitive outcomes and neuroplasticity in rodent models of neurodevelopmental and neurodegenerative disorders, yet cell-type specific molecular effects remain unknown. We investigated the effect of MCS upon the onset of septohippocampal degeneration at 6 months of age in the Ts65Dn mouse model of DS/AD. Using laser capture microdissection and single population RNA-sequencing, transcriptomic changes were profiled within hippocampal CA1 and CA3 pyramidal neurons and dentate gyrus granule cells comparing trisomic and disomic offspring. Bioinformatic analysis revealed MCS-mediated downregulation of apoptotic pathways and upregulation of cognition-related functions across all populations, alongside cell-specific responses. These findings highlight MCS as a promising strategy for modulating disease-relevant pathways in a hippocampal cell-type-specific manner during early neurodegeneration in DS/AD.

Trauma exposure in children and adolescents is a significant public health concern due to its profound impact on mental health and development. This study explores the complexities of trauma in youth, including the differentiation between trauma exposure and posttraumatic stress disorder, and the long-term effects of adverse childhood experiences. The study discusses the risks and benefits of polypharmacy in treating complex trauma and comorbid conditions in youth. Given the current gaps in research, the study emphasizes the need for comprehensive, individualized treatment plans that integrate psychotherapy, pharmacologic interventions, and psychosocial support to foster resilience and improve outcomes for trauma-exposed youth.

Exposure to trauma is common and frequently overlooked in behaviorally dysregulated youth. Common trauma-related symptoms, such as exaggerated startle responses, dissociative episodes, and irritability, may resemble behavioral dysregulation. These responses may not be recognized as being related to trauma. As a result, traumatized young people are often misdiagnosed and treated with antipsychotics. Trauma-informed care in health care settings, which includes systematic screening, staff training, trauma skills groups, and ongoing monitoring, is one way of addressing the effects of trauma and ensuring that young people receive access to the evidence-based care they deserve.

Currently, the identification of individuals experiencing suicidal thoughts and behaviours (STBs) rely predominantly on self-report. Previous research on children and young people highlighted an association between difficulties in arousal regulation (reflected, for example, in reduced heart rate variability and altered electrodermal activity patterns) and STBs, but this has not been meta-analytically explored in adults. This systematic review and meta-analysis aimed to quantify the association between STBs and markers of autonomic functioning/regulation in adults. Based on a pre-registered protocol (PROSPERO CRD42024596886), we searched PubMed/MEDLINE, Embase, PsycINFO and Web of Science until 2^nd August 2025 for empirical studies assessing the association between measures of autonomic functioning and/or regulation and STBs in adults. Quality of cross-sectional and cohort studies was assessed through the Newcastle-Ottawa Scale. Pooled effect sizes (Hedge's g) were estimated with random-effects meta-analytic models in R. Out of 2,726 articles screened, 40 studies were included in the systematic review, and 22 in the meta-analyses (6,290 individuals, 28% with STBs). We found reduced heart rate variability in adults with STBs (g = -0.2469, p = 0.0069) but no significant associations between electrodermal activity patterns and STBs (g = -0.2563, p = 0.3953). Our results highlight the connection between reduced cardiac regulation and STBs, providing a rationale for further exploration of cardiac regulation as a potential objective marker for assessing and monitoring STBs in adults. Further research is warranted to understand how these markers can be used in clinical practice to assess and support the management of suicide risk in adults.

OBJECTIVE:To identify optimal strategies to integrate early relational health (ERH) programs in pediatric primary care (PPC) and to describe the development of a best practices toolkit to provide guidance and useful tools that clinicians can use to navigate this process. METHODS:A two-phased approach to develop, assess, and refine a best practices toolkit for the integration of multiple ERH programs in PPC through a modified Delphi process. Phase One included identification and assessment around barriers to ERH program integration and strategies to address them through surveys and focus groups of PPC clinics nationwide. Phase Two then utilized the identified barriers and strategies from Phase One to create a toolkit of best practices on integrating ERH programs in PPC that included two rounds of revision for a final version. RESULTS:126 PPC personnel from 44 clinics nationwide completed the Phase One survey, with respondents reporting many notable strengths and challenges to ERH program integration. 18 survey participants also participated in follow-up focus groups, which reiterated the strengths and challenges found in the surveys. An initial toolkit was then drafted, and experts provided qualitative, free-response feedback around clarity and presentation. Further improvement was made to create the final toolkit, which was rated highly useful and important, though slightly less feasible, by practitioners using formal feedback questions. CONCLUSION/CONCLUSIONS:This study employed a modified Delphi process to create a consensus-based best practices toolkit for integrating multiple ERH programs in PPC to help meet the heterogeneous needs of families to promote optimal child development.