Faculty Bibliography

Allostatic load provides a valuable framework for examining how cumulative stress impacts multiple physiological systems simultaneously, making it a powerful tool for understanding the mechanisms through which stress contributes to adverse pregnancy outcomes. This multisystem perspective is especially important during pregnancy, a period characterized by heightened vulnerability to stress and significant physiological changes that can themselves contribute to allostatic load. Although the impact of allostatic load during pregnancy is well documented, the mechanisms and moderators involved by trimester remain unclear, particularly given wide variation in social, cultural, and structural determinants of maternal health worldwide. In this review, we discuss the progress that has been made over the past two decades in studying prenatal allostatic load and describe the clinical implications of this by highlighting sensitive periods of interest throughout gestation. Despite these advances, key questions remain regarding the intergenerational transmission of risk, the specificity of findings to the pregnancy period, and the role of factors that often accompany elevated allostatic load, such as poor sleep, limited social support, systemic inequities, and comorbid mental or physical health conditions, which may manifest differently across global contexts. Most existing studies have been conducted in high-income settings, yet the burden of adverse pregnancy outcomes is greatest in low- and middle-income countries, where structural, environmental, and social stressors are pervasive. Expanding this framework to include diverse global contexts is essential for understanding how social inequities and chronic stressors shape maternal physiology worldwide. We discuss these issues and offer directions for future research, including the goal of developing a standardized metric for measuring allostatic load - one that we believe will advance the field's understanding of how prenatal allostatic load markers by trimester relate to maternal and infant outcomes.

Toddler visual attention development correlates with subsequent language, cognitive, and social developmental outcomes. This study investigates the association of maternal trauma on toddler looking behaviors in 39 mother-child dyads from the Western Cape Province, South Africa. At 15 months postpartum, maternal trauma was assessed using the Life Events Checklist and toddler multisensory attention skills were measured using the Multisensory Attention Assessment Protocol (MAAP) during eye-tracking. We used two-way mixed ANOVA to analyze the association of maternal trauma and MAAP condition with attention maintenance, intersensory matching, and attention shifting. This study provides support for the MAAP's reliability with a sample of 15-month-old toddlers from a low-income setting. We observed a significant interaction between MAAP condition and maternal trauma group on attention maintenance, but pairwise comparisons did not meet the threshold for statistical significance. In a stratified analysis, toddlers of mothers in the low trauma exposure group demonstrated significant differences in attention maintenance, intersensory matching, and attention shifting by condition. Unexpectedly, toddlers of mothers in the high trauma exposure group did not exhibit significant differences in these attentional skills, potentially indicating attentional adaptations. Further research is needed to explore the relationship between the intergenerational transmission of trauma on infant and toddler multisensory attention skills in low-income settings.

Research suggests that socioeconomic circumstances and stress predict memory skills in adults and older children, yet few studies have addressed this question in infancy. The current study used the visual-paired comparison paradigm to examine whether socioeconomic circumstances, maternal perceived stress, and/or maternal physiological stress, all measured prenatally, predict memory performance among 6-month-old infants. We found no significant associations between infant memory and any measure of socioeconomic circumstance or stress. Potential explanations for these null findings are discussed.

BACKGROUND:A growing body of literature links prenatal mood and substance use to children's cognitive and behavioral development. The relative contribution of these risk factors on children's executive function (EF) in the context of socioeconomic adversities needs further evaluation. To address this gap, we investigated the role of prenatal maternal anxiety and depression on childhood EF, specifically inhibitory control and working memory, within the context of socioeconomic adversities and prenatal substance use. We hypothesized that higher maternal mood symptoms, higher persistent prenatal drinking and smoking, and lower socioeconomic status would be associated with lower EF skills during early childhood. METHODS:We used data from 334 mother-child dyads followed prospectively through pregnancy and the offspring's childhood. Prenatal maternal depression and anxiety were assessed via standardized questionnaires. Prenatal alcohol and tobacco consumption were assessed via a timeline follow-back interview. The EF touch battery assessed child inhibitory control and working memory at 3-5 years of age (4.76 ± 0.58 years, 171 females). Separate linear regression models were used to estimate the association of prenatal tobacco, alcohol, anxiety, and depression exposure with our two components of child EF, inhibitory control and working memory, while adjusting for gestational age, sex, and age at assessment. The following variables were also included as covariates: maternal educational achievement, employment status, parity, and household crowding index. RESULTS:Children of mothers with high trait anxiety scores had reduced inhibitory control compared to children of mothers without trait anxiety or depression (β = -0.12, 95% CI:-0.22,-0.01). Children of mothers in the moderate to high continuous smoking group showed lower inhibitory control (β = - 0.19, 95% CI:-0.38,-0.01) compared to children of mothers in the none smoking group. Additionally, lower maternal education and higher household crowding were each associated with reduced inhibitory control. We found no significant association between prenatal maternal depression, anxiety, or socioeconomic factors with working memory. CONCLUSIONS:These results underscore the need for comprehensive context-specific intervention packages, including mental health support for women to promote healthy inhibitory control development in children.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Electroencephalography (EEG) is one of two brain imaging modalities central to the HBCD Study. EEG records electrical signals from the scalp that reflect electrical brain activity. In addition, the EEG signal can be synchronized to the presentation of discrete stimuli (auditory or visual) to measure specific cognitive processes with excellent temporal precision (e.g., event-related potentials; ERPs). EEG is particularly helpful for the HBCD Study as it can be used with awake, alert infants, and can be acquired continuously across development. The current paper reviews the HBCD Study's EEG/ERP protocol: (a) the selection and development of the tasks (Video Resting State, Visual Evoked Potential, Auditory Oddball, Face Processing); (b) the implementation of common cross-site acquisition parameters and hardware, site setup, training, and initial piloting; (c) the development of the preprocessing pipelines and creation of derivatives; and (d) the incorporation of equity and inclusion considerations. The paper also provides an overview of the functioning of the EEG Workgroup and the input from members across all steps of protocol development and piloting.

IMPORTANCE/UNASSIGNED:Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. OBJECTIVE/UNASSIGNED:To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. EXPOSURES/UNASSIGNED:Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. RESULTS/UNASSIGNED:The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

BACKGROUND:The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS:3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS:Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION/CONCLUSIONS:The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT/CONCLUSIONS:Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

BACKGROUND:Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels. METHODS:Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category. RESULTS: = 0.03). No associations were observed among non-OWOB participants. CONCLUSIONS:Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development.

Inhibitory control plays an important role in children's cognitive and socioemotional development, including their psychopathology. It has been established that contextual factors such as socioeconomic status (SES) and parents' psychopathology are associated with children's inhibitory control. However, the relations between the neural correlates of inhibitory control and contextual factors have been rarely examined in longitudinal studies. In the present study, we used both event-related potential (ERP) components and time-frequency measures of inhibitory control to evaluate the neural pathways between contextual factors, including prenatal SES and maternal psychopathology, and children's behavioral and emotional problems in a large sample of children (N = 560; 51.75% females; M

IMPORTANCE/UNASSIGNED:Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. OBJECTIVE/UNASSIGNED:To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. EXPOSURES/UNASSIGNED:Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. MAIN OUTCOMES AND MEASURES/UNASSIGNED:EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. RESULTS/UNASSIGNED:The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] μV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] μV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] μV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] μV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] μV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] μV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] μV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] μV2; P = .04) power compared with those with no PTE. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.