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Background: Concern about side effects is a common reason for SARS-CoV-2 vaccine hesitancy., Objective: To determine whether short-term side effects of SARS-CoV-2 messenger RNA (mRNA) vaccination are associated with subsequent neutralizing antibody (nAB) response., Design: Prospective cohort study., Setting: San Francisco Bay Area., Participants: Adults who had not been vaccinated against or exposed to SARS-CoV-2, who then received 2 doses of either BNT162b2 or mRNA-1273., Measurements: Serum nAB titer at 1 month and 6 months after the second vaccine dose. Daily symptom surveys and objective biometric measurements at each dose., Results: 363 participants were included in symptom-related analyses (65.6% female; mean age, 52.4 years [SD, 11.9]), and 147 were included in biometric-related analyses (66.0% female; mean age, 58.8 years [SD, 5.3]). Chills, tiredness, feeling unwell, and headache after the second dose were each associated with 1.4 to 1.6 fold higher nAB at 1 and 6 months after vaccination. Symptom count and vaccination-induced change in skin temperature and heart rate were all positively associated with nAB across both follow-up time points. Each 1 °C increase in skin temperature after dose 2 was associated with 1.8 fold higher nAB 1 month later and 3.1 fold higher nAB 6 months later., Limitations: The study was conducted in 2021 in people receiving the primary vaccine series, making generalizability to people with prior SARS-CoV-2 vaccination or exposure unclear. Whether the observed associations would also apply for neutralizing activity against non-ancestral SARS-CoV-2 strains is also unknown., Conclusion: Convergent self-report and objective biometric findings indicate that short-term systemic side effects of SARS-CoV-2 mRNA vaccination are associated with greater long-lasting nAB responses. This may be relevant in addressing negative attitudes toward vaccine side effects, which are a barrier to vaccine uptake., Primary Funding Source: National Institute on Aging., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2956.

Telomeres are ribonucleoprotein structures at the end of all eukaryotic chromosomes that protect DNA from damage and preserve chromosome stability. Telomere length (TL) has been associated with various exposures, biological processes, and health outcomes. This article describes the monochrome multiplex quantitative polymerase chain reaction (MMqPCR) assay protocol routinely conducted in our laboratory for measuring relative mean TL from human DNA. There are several different PCR-based TL measurement methods, but the specific protocol for the MMqPCR method presented in this publication is repeatable, efficient, cost-effective, and suitable for population-based studies. This detailed protocol outlines all information necessary for investigators to establish this assay in their laboratory. In addition, this protocol provides specific steps to increase the reproducibility of TL measurement by this assay, defined by the intraclass correlation coefficient (ICC) across repeated measurements of the same sample. The ICC is a critical factor in evaluating expected power for a specific study population; as such, reporting cohort-specific ICCs for any TL assay is a necessary step to enhance the overall rigor of population-based studies of TL. Example results utilizing DNA samples extracted from peripheral blood mononuclear cells demonstrate the feasibility of generating highly repeatable TL data using this MMqPCR protocol.

Exposure to stress related to the COVID-19 pandemic contributes to psychopathology risk, yet not all children are negatively impacted. The current study examined a parasympathetic biomarker of stress sensitivity, respiratory sinus arrhythmia (RSA), as a moderator of the effects of exposure to pandemic stress on child internalizing and externalizing behaviors in a sample of children experiencing economic marginalization. Three to five years pre-pandemic, when children were preschool-aged, RSA during baseline and a challenging parent-child interaction were collected. Mid-pandemic, between November 2020 and March 2021, children's exposure to pandemic stress and internalizing and externalizing behaviors were collected. Results demonstrated that children who, pre-pandemic, demonstrated blunted parasympathetic reactivity (i.e., no change in RSA relative to baseline) during the dyadic challenge exhibited elevated risk for externalizing behaviors mid-pandemic. Further, this risk was greatest for children exposed to high and moderate levels of pandemic stress. Consistent with diathesis stress and polyvagal frameworks, these conditional effects suggest that blunted parasympathetic reactivity in response to stress in early childhood may escalate the development of externalizing behaviors following stress exposure at school age.

Pregnancy can exacerbate or prompt the onset of stress-related disorders, such as post-traumatic stress disorder (PTSD). PTSD is associated with heightened stress responsivity and emotional dysregulation, as well as increased risk of chronic disorders and mortality. Further, maternal PTSD is associated with gestational epigenetic age acceleration in newborns, implicating the prenatal period as a developmental time period for the transmission of effects across generations. Here, we evaluated the associations between PTSD symptoms, maternal epigenetic age acceleration, and infant gestational epigenetic age acceleration in 89 maternal-neonatal dyads. Trauma-related experiences and PTSD symptoms in mothers were assessed during the third trimester of pregnancy. The MethylationEPIC array was used to generate DNA methylation data from maternal and neonatal saliva samples collected within 24 h of infant birth. Maternal epigenetic age acceleration was calculated using Horvath's multi-tissue clock, PhenoAge and GrimAge. Gestational epigenetic age was estimated using the Haftorn clock. Maternal cumulative past-year stress (GrimAge: p  = 3.23e-04, PhenoAge: p  = 9.92e-03), PTSD symptoms (GrimAge: p  = 0.019), and difficulties in emotion regulation (GrimAge: p  = 0.028) were associated with accelerated epigenetic age in mothers. Maternal PTSD symptoms were associated with lower gestational epigenetic age acceleration in neonates ( p  = 0.032). Overall, our results suggest that maternal cumulative past-year stress exposure and trauma-related symptoms may increase the risk for age-related problems in mothers and developmental problems in their newborns.

Background and Aim: Tissue source has been shown to exert a significant effect on the magnitude of associations between telomere length and various health outcomes and exposures. The purpose of the present qualitative review and meta-analysis is to describe and investigate the impact of study design and methodological features on the correlation between telomere lengths measured in different tissues from the same healthy individual., Methods: This meta-analysis included studies published from 1988 to 2022. Databases searched included PubMed, Embase, and Web of Science and studies were identified using the keywords "telomere length" and "tissues" or "tissue." A total of 220 articles of 7856 initially identified studies met inclusion criteria for qualitative review, of which 55 met inclusion criteria for meta-analysis in R RESULTS: Studies meeting inclusion criteria for meta-analysis tended to have enhanced demographic and methodological reporting relative to studies only included in the qualitative review. A total of 463 pairwise correlations reported for 4324 unique individuals and 102 distinct tissues were extracted from the 55 studies and subject to meta-analysis, resulting in a significant effect size z = 0.66 (p < 0.0001) and meta-correlation coefficient of r = 0.58. Meta-correlations were significantly moderated by sample size and telomere length measurement methodology, with studies of smaller size and those using hybridization-based analyses exhibiting the largest meta-correlation. Tissue source also significantly moderated the meta-correlation, wherein correlations between samples of a different lineage (e.g., blood vs. non-blood) or collection method (e.g., peripheral vs. surgical) were lower than correlations between samples of the same lineage or collection method., Conclusion: These results suggest that telomere lengths measured within individuals are generally correlated, but future research should be intentional in selecting a tissue for telomere length measurement that is most biologically relevant to the exposure or outcome investigated and balance this with the feasibility of obtaining the sample in sufficient numbers of individuals., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The authors report financial support was provided by the National Institute on Aging. The authors report administrative support was provided by the Tulane University Meta-Analysis Systematic Review Support Program., (Copyright © 2023. Published by Elsevier B.V.)

The primary aim of this prospective study was to examine the single and combined effect of prenatal exposure to perceived stress, probable depression, and lead on toddlers' neurodevelopment using the Bayley Scales of Infant and Toddler Development, third edition. Data from 363 mother-toddler pairs enrolled in the Caribbean Consortium for Research in Environmental and Occupational Health prospective cohort study were analyzed. A prenatal lead exposure of ≥3.5 µg/dL was associated with significantly lower receptive ( p = 0.008) and expressive ( p = 0.006) communication scaled scores. Moderate and severe maternal prenatal probable depression scores were associated with significantly lower fine ( p = 0.009) and gross ( p = 0.009) motor scaled scores. However, a maternal report of prenatal stress was not associated with neurodevelopmental outcomes. After adjusting for maternal demographics, prenatal stress and lead exposure, prenatal probable depression remained predictive of the toddlers' gross motor scaled scores (β -0.13, 95% CI [-0.24--0.02]). Similarly, when adjusting for demographics, prenatal stress and probable depression, prenatal lead exposure remained a significant predictor of their receptive communication scaled scores (β -0.26, 95% CI [-0.49--0.02]). An analysis testing combined exposure to perceived stress, probable depression, and lead exposure, measured using a cumulative risk index, significantly predicted the child fine motor scaled scores after adjusting for other covariates (β -0.74, 95% CI: [-1.41--0.01]).

Background: Immigrant Arab American families face multiple stressors related to migration and resettlement. Telomere length (TL) is an established biomarker of aging and psychosocial stress. No published studies have concurrently examined the association between maternal and paternal psychosocial factors and infants' TL. The purpose of this study was to: (1) compare mother, father, and infant TLs; (2) explore the association of maternal and paternal psychosocial factors (acculturative stress and depressive symptoms) with maternal and paternal TL; and (3) explore the association of maternal and paternal psychosocial factors with infants' TL among Arab American immigrants. Method: Using a cross-sectional exploratory design, a sample of 52 immigrant Arab American mother-father-infant triads were recruited from community centers. Data were collected in a single home visit when the infant was 6-24 months old. Each parent completed the study questionnaires addressing their psychosocial factors (acculturative stress, and depressive symptoms), then parents and infants provided buccal cell for TL measurement. Results: Maternal TL was positively correlated to infants' TL ( r = .31, p = .04) and significantly shorter ( p < .001). Paternal TL was not correlated with infant TL but was significantly shorter than infant's TL ( p < .001). Maternal depression was significantly correlated with mothers' TL ( r = .4, p = .007). Higher levels of maternal depressive symptoms were significantly associated with shorter infant TL when controlling for background characteristics. Conclusions: Our pilot study is the first study to examine maternal and paternal psychosocial factors related to migration and infants' TL. More research is needed to advance our understanding of the effects of immigration on the intergenerational transfer of stress and trauma.

Screening for prenatal stress is not routine in Suriname, despite its significant impact on maternal and newborn health. This study assessed the prevalence of high perceived prenatal stress and its sociodemographic predictors in three geographic areas in Suriname. In this cross-sectional study, data from 1190 participants of the Caribbean Consortium for Research in Environmental and Occupational Health cohort study were analyzed. Cohen's Perceived Stress Scale was completed during pregnancy to ascertain high perceived stress (cut-off score 20). The association between maternal sociodemographic factors and high perceived stress was examined using the chi-square test and logistic regression models; 27.5% of all participants had high perceived stress with statistically significant lower rates in Nickerie (18.8%) compared with Paramaribo (29.8%; p = 0.001) and the Interior (28.6%; p = 0.019). Maternal sociodemographic factors moderated the difference between the Interior and Nickerie. Participants from Paramaribo had statistically significant higher odds of high perceived stress compared to those from Nickerie, independent of their age and educational level (adjusted OR = 1.94; 95% confidence interval 1.32-2.86). Perceived stress during pregnancy is predicted by sociodemographic factors. These findings identified target groups for interventions in Suriname. Policy makers should consider integrating perceived stress assessment as a routine part of prenatal care., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Advances in developmental psychology, child psychiatry, and allied disciplines have pointed to events and experiences in the early years as the origin of many adult mental health challenges. Yet, children's mental health services still largely lack a developmental or prevention-focused orientation, with most referrals to mental health professionals occurring late, once problems are well established. An early childhood mental health system rooted in the principles of life-course health development would take a very different approach to designing, testing, and implementing prevention and intervention strategies directed toward early child mental health. Priorities for such a system include supporting healthy family environments, parent-child and family relationships, parents' emotional/behavioral health, and family routines as a means of providing the best possible neurobiological foundation for mental health across the life span. The system would include proactive, trauma-informed, multidisciplinary care, with integrated mental health and social services support embedded in pediatric primary care settings. Novel intervention approaches in need of further research include 2-generational dyadic interventions designed to improve the mental health of parents and children, mental health-oriented telemedicine, and contingency management (CM) strategies. Integral to this Life Course Health Development reformulation is a commitment by all organizations supporting children to primordial and primary prevention strategies to reduce racial and socioeconomic disparities in all settings. We contend that it is the family, not the individual child, that ought to be the identified target of these redesigned approaches, delivered through a transformed pediatric system with anticipated benefits for multiple health outcomes across the life course., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD., Methods: One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant's first 18 months of life. Prenatal smoking was assessed from maternal report and medical records. TL was measured from infant buccal swab DNA obtained across the first 18 months of life. ADHD symptoms were obtained from maternal report on the Child Behavior Check List. Multiple regression models tested the relation between prenatal smoking and both ADHD symptoms and infant TL. Additional analyses tested whether the change in infant TL influenced the relation between prenatal smoking and ADHD symptoms., Results: Sixteen percent of mothers reported prenatal smoking. Infant TL at 4, 12, and 18 months of age were correlated. Consistent with previous cross-sectional studies linking shorter offspring TL to maternal prenatal smoking, maternal prenatal smoking predicted greater telomere shortening from four to 18 months of infant age (β = - 5.797, 95% CI [-10.207, -1.386]; p = 0.010). Maternal depression was positively associated with both prenatal smoking (odds ratio (OR): 4.614, 95% CI [1.733, 12.282]; p = 0.002) and child ADHD symptoms (β = 4.713, 95% CI [2.073, 7.354]; p = 0.0006). To prevent confounding, analyses examined the relation between TL, ADHD symptoms, and prenatal smoking only in non-depressed mothers. In non-depressed mothers, infant TL attrition across the first 18 months moderated the relation between smoking and child ADHD., Conclusions: The findings extend previous studies linking prenatal smoking to shorter infant TL by providing data demonstrating the effect on TL trajectory. The relation between prenatal smoking and early infant ADHD symptoms was moderated by the change in TL. The findings provide novel initial evidence suggesting that TL dynamics are one mechanistic pathway influencing the relation between maternal prenatal smoking and ADHD., (© 2022. The Author(s).)

Objective: The COVID-19 pandemic and mitigation strategies amplified racial and income-based health disparities, profoundly shifted family life, and altered delivery systems for support services. We report pilot data from a telehealth adaptation of Mom Power, an evidence-based, attachment-informed multifamily preventive intervention (clinicaltrials.gov: de-identified )., Method: Virtual Mom Power (VMP), adapted for economically marginalized, predominantly Black mothers and their young children ( n = 9) was implemented in New Orleans, an early COVID-19 hotspot with an entrenched history of structural racism and trauma. We outline our approach to adaptation of curriculum and service delivery, using a trauma-informed lens., Results: Maternal reports of maternal and child functioning from pre to post were consistent with improvements in maternal depressive and posttraumatic stress symptoms and child competence, comparable to outcomes from in-person trials. Feasibility and acceptability data were strong., Discussion: Preliminary results and reflections on process suggest that telehealth service delivery of a multifamily preventive intervention, with attention to decreasing barriers to online access and consideration of culture and context, facilitated engagement while maintaining fidelity and effects on intervention targets. Future research using larger samples, randomized controlled design, and multi-method assessment should continue to guide dissemination of reflective, group-based telehealth parenting programs.

Serologic testing of residual blood samples from 812 children from a hospital in New Orleans, LA, between March and May 2020, demonstrated a SARS-CoV-2 seroprevalence of 6.8% based on S and N protein IgG; Black and Hispanic children, and children living in zip codes with lower household incomes were over-represented., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: A valid and reliable measure of infant neurodevelopment is needed in Suriname, South America. The Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), was created for evaluation of United States infants and toddlers and subsequently validated for use in Dutch speaking infants of the Netherlands (BSID-III-NL). Given that Suriname was a previous Dutch colony and Dutch remains the national language of Suriname, this study sought to evaluate the psychometric properties of the BSID-III-NL in Suriname., Aims: Given that the cultural context differs between Suriname, the United States, and the Netherlands, the aims of this study were to determine if any cultural adaptations of the BSID-III-NL were needed for Surinamese infants and to evaluate its psychometric properties., Methods: Two hundred and ninety-nine infants between the ages of 10 to 26 months were assessed in three geographic regions of Suriname between May 2018 and July 2019. Minor adaptations to the BSID-III-NL imagery were made based on the input of Surinamese pediatricians and neuropsychologists who were also involved in the administration of the BSID-III-NL in Suriname. Raw scores were collected for the cognitive, communicative, and motor subscales of the BSID-III-NL. Factor structure was evaluated with exploratory factor analysis and cluster analysis, and reliability of internal consistency was assessed using Cronbach's alpha coefficient for each subscale., Results: Content validity was endorsed by pediatricians and neuropsychologists in Suriname who participated in the administration of the BSID-III-NL. Construct validity was demonstrated through agreement of items from cluster analysis where at least 81.56% of all variability was explained by clustering with correct or incorrect responses and mean raw scores in subscales increased with age group. Cronbach's alpha coefficient was above 0.77 for all subscales., Conclusions: This internationally validated developmental measure was found to be valid and reliable in assessing neurodevelopment of infants in Suriname., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To quantify the rate of change in epigenetic age compared with chronological age over time in youth with perinatally acquired HIV (YPHIV) and youth who are perinatally HIV-exposed uninfected (YPHEU)., Design: Longitudinal study of 32 YPHIV and 8 YPHEU with blood samples collected at two time points at least 3 years apart., Methods: DNA methylation was measured using the Illumina MethylationEPIC array and epigenetic age was calculated using the Horvath method. Linear mixed effects models were fit to estimate the average change in epigenetic age for a 1-year change in chronological age separately for YPHIV and YPHEU., Results: Median age was 10.9 and 16.8 years at time 1 and 2, respectively. Groups were balanced by sex (51% male) and race (67% black). Epigenetic age increased by 1.23 years (95% CI 1.03--1.43) for YPHIV and 0.95 years (95% CI 0.74--1.17) for YPHEU per year increase in chronological age. Among YPHIV, in a model with chronological age, a higher area under the curve (AUC) viral load was associated with an increase in epigenetic age over time [2.19 years per log10 copies/ml, (95% CI 0.65--3.74)], whereas a higher time-averaged AUC CD4+ T-cell count was associated with a decrease in epigenetic age over time [-0.34 years per 100 cells/μl, (95% CI -0.63 to -0.06)] in YPHIV., Conclusion: We observed an increase in the rate of epigenetic aging over time in YPHIV, but not in YPHEU. In YPHIV, higher viral load and lower CD4+ T-cell count were associated with accelerated epigenetic aging, emphasizing the importance of early and sustained suppressive treatment for YPHIV, who will receive lifelong ART., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Neonatal opiate withdrawal syndrome (NOWS), previously known as neonatal abstinence syndrome (NAS), is a growing public health concern as opiate misuse and opioid-related overdoses, from both prescription and illicit sources, continue to rise in the USA. As more than 90% of females abusing opioids are of child-bearing age, the failure to adequately address the opioid epidemic continues to negatively impact the next generations. Accurate and timely identification of infants at risk for withdrawal from in-utero exposure is critical to ensure high-quality perinatal and neonatal care. Beginning with an evaluation of current best practices and performing a literature review, we identify the challenges to current screening processes and how these limitations limit the ability to provide appropriate care to infants at the risk of withdrawal. We first describe the limitations of the available assays for the detection of opioid and opioid metabolites across different biological sources from both the mother and the infant. We then present a discussion surrounding factors that contribute to maternal willingness to disclose use. Particularly, in light of the limitations of biological screening, any barrier to maternal disclosure further complicates effective care delivery. Barriers to disclosure include legal ramifications and state policies, provider and societal behaviors and biases, and maternal factors. Moving forward, universal prenatal screening surveys coupled with enhanced outreach and education to providers centering on the limitations of both patient report and biological sampling, as well as comprehensive and supportive services for women of reproductive age with substance use disorders, are needed to both enhance detection for NOWS and improve long-term maternal-child health.

Increasing evidence suggests intergenerational effects of maternal early adversity on offspring self-regulation. Prior work has demonstrated associations between maternal adverse childhood experiences (ACEs) and infant respiratory sinus arrhythmia (RSA), a parasympathetic biomarker associated with emotional and behavioral self-regulation. The present study examined these associations and additional potential pathways including children's violence exposure and maternal psychopathology among 123 biological mother-child dyads. Families were low-income and oversampled for violence exposure; children were 3-5 years old. RSA was examined during dyadic interaction using latent growth curve modeling (LGCM). On average, females exhibited greater RSA reactivity. Greater RSA withdrawal across the interaction was associated with greater child negative affect during the interaction, linking RSA reactivity to concurrent child behavior. Consistent with previous findings among infants, high maternal ACEs were associated with lower child RSA at task initiation but not with RSA reactivity across the interaction. Findings suggest that the association between high maternal ACEs and a lower set point for offspring RSA persists into the early childhood period, beyond the influence of maternal psychopathology and children's own violence exposure. These data provide further evidence for the biological embedding of maternal early adversity across generations as well as for the relevance of RSA to child behavioral regulation., (© 2020 Wiley Periodicals LLC.)

Music is widely used in the neonatal intensive care unit. The objectives of this systematic review are: (1) clarify the current literature in regards to the impact of music on neonatal physiologic parameters, (2) highlight the variability in definitions utilized for music interventions, and (3) provide a foundation for future music therapy research focused on influencing neonatal physiology. A systematic literature review was conducted in accordance with PRISMA guidelines, with search terms including "music," "music therapy," "neonates," "newborn," and "NICU." Four hundred and fifty-eight studies were reduced to 16 clinical trials divided based on methodological description of music intervention. Our review highlights variability in the existing literature specifically on neonatal physiological impact of music. Future studies should focus on consistent and well-defined data collection, utilization of standardized definitions for music interventions, and consideration of more sensitive markers of physiology, such as heart rate variability, to enhance study rigor and reproducibility.

Purpose: The Caribbean Consortium for Research in Environmental and Occupational Health prospective environmental epidemiologic cohort study addresses the impact of chemical and non-chemical environmental exposures on mother/child dyads in Suriname. The study determines associations between levels of environmental elements and toxicants in pregnant women, and birth outcomes and neurodevelopment in their children., Participants: Pregnant women (N=1143) were enrolled from December 2016 to July 2019 from three regions of Suriname: Paramaribo (N=738), Nickerie (N=204) and the tropical rainforest interior (N=201). Infants (N=992) were enrolled at birth. Follow-up will take place until children are 48 months old., Findings to Date: Biospecimens and questionnaire data on physiological and psychosocial health in pregnant women have been analysed. 39.1% had hair mercury (Hg) levels exceeding values considered safe by international standards. Median hair Hg concentrations in women from Paramaribo (N=522) were 0.64 µg/g hair (IQRs 0.36-1.09; range 0.00-7.12), from Nickerie (N=176) 0.73 µg/g (IQR 0.45-1.05; range 0.00-5.79) and the interior (N=178) 3.48 µg/g (IQR 1.92-7.39; range 0.38-18.20). 96.1% of women ate fish, respective consumption of the three most consumed carnivorous species, Hoplias aimara , Serrasalmus rhombeus and Cichla ocellaris, known to have high Hg levels, was 44.4%, 19.3% and 26.3%, respectively, and was greater among the interior subcohort. 89% frequently consumed the vegetable tannia, samples of which showed presence of worldwide banned pesticides. 24.9% of pregnant women had Edinburgh Depression Scale scores indicative of probable depression., Future Plans: Fish consumption advisories are in development, especially relevant to interior women for whom fish consumption is likely to be the primary source of Hg exposure. Effects of potentially beneficial neuroprotective factors in fish that may counter neurotoxic effects of Hg are being examined. A pesticide literacy assessment in pregnant women is in progress. Neurodevelopmental assessments and telomere length measurements of the children to evaluate long-term effects of prenatal exposures to toxicant mixtures are ongoing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Adverse childhood experiences (ACEs) are associated with mental and physical health risks that, through biological and psychosocial pathways, likely span generations. Within an individual, telomere length (TL), an established marker of cellular stress and aging, is associated with both ACE exposure and psychopathology, providing the basis for an emerging literature suggesting that TL is a biomarker of the health risks linked to early-life adversity both within and across generations. The authors tested the effect of maternal ACEs on both the trajectory of infant TL and infant social-emotional problems at 18 months of age., Methods: Pregnant women were recruited, and maternal scores on the Adverse Childhood Experience questionnaire were obtained, along with demographic and prenatal stress measures. Postnatal visits with 155 mother-infant dyads occurred when infants were 4, 12, and 18 months of age. At each visit, infant buccal swabs were collected for TL measurement, and mothers completed measures of maternal depression. Mothers also completed the Child Behavior Checklist at the 18-month visit. Mixed-effects modeling was used to test how maternal ACEs influenced infant TL trajectory. Linear regression was used to test the association between maternal ACEs and infant internalizing and externalizing behaviors. Finally, the interaction between telomere attrition from 4 to 18 months and maternal ACEs was examined as a predictor of infant scores on the Child Behavior Checklist., Results: Higher maternal ACEs were associated with shorter infant TL across infancy and higher infant externalizing behavioral problems at 18 months. No associations were found with internalizing behavioral problems. Telomere attrition from 4 to 18 months interacted with maternal ACEs to predict externalizing behaviors. In infants whose mothers reported higher scores on the Adverse Childhood Experience questionnaire, greater telomere attrition predicted higher externalizing problems, even when accounting for maternal postnatal depression and prenatal stress., Conclusions: These data demonstrate an interactive pathway between maternal early-life adversity and infant TL that predicts emerging behavioral problems in the next generations.

Objective: Telomere length (TL) has been linked to several psychiatric conditions in children and adults. Telomere shortening is accelerated by early adversity, including maltreatment and psychosocial deprivation. These experiences also increase the risk of psychopathology in many domains. Two fundamental issues remain unresolved. The first concerns the specificity of the relations between TL and different dimensions of psychopathology; and the second relates to the direction of association between TL and psychopathology., Method: This study addressed these shortcomings in a 2-fold manner. First, the association between TL and statistically independent general, internalizing, and externalizing psychopathology factors was examined to determine the specificity of this relation. Second, a 2-wave longitudinal cross-lagged model was used to explicitly examine the direction of the relation between TL and each psychopathology factor. Data were drawn from the Bucharest Early Intervention Project, a longitudinal study exploring the impact of severe psychosocial deprivation on child health and development (N = 195). At 8 to 10 and 12 to 14 years of age, buccal DNA was collected and teachers and/or caregivers reported on different domains of psychopathology., Results: Longitudinal path analyses showed that shorter TL was specifically associated with higher internalizing psychopathology at 8 to 10 years of age. In contrast, at 12 to 14 years, shorter TL was associated with higher general psychopathology. Most telling, internalizing psychopathology at 8 to 10 years predicted shorter TL at 12 to 14 years, with no reciprocal effects., Conclusion: Results suggest that telomere erosion could be a consequence of distress-related psychopathology rather than a selection mechanism for later psychiatric problems., Clinical Trial Registration Information: The Bucharest Early Intervention Project; https://clinicaltrials.gov/; NCT00747396., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To test alterations in placental cellular aging as one pathway by which maternal early adversity influences physiologic development in her offspring., Methods: Maternal report of her adverse childhood experiences (ACE) was obtained prenatally along with measures of prenatal stress and demographic information. Placentas (N = 67) were collected at birth and telomere length (TL) was measured in four separate fetally-derived placental tissues: amnion, chorion, villus, and umbilical cord. At four months of age, infants completed the still-face paradigm (SFP) during which respiratory sinus arrhythmia (RSA) data were collected; RSA reactivity and RSA recovery was available from 44 and 41 infants respectively. Multi-level mixed effects models examined the impact of maternal ACE score on placental TL. Generalized linear models tested the relation between composite placental TL and infant RSA, as well as the moderation of maternal ACE score and infant RSA by composite placental TL., Results: Higher maternal ACE score significantly predicted shorter placental TL across tissues (β = -0.015; P = 0.036) and infant RSA across the SFP. No direct relation was found between placental TL and RSA, however composite placental TL moderated the relation between ACE score and both infant RSA reactivity (β = 0.025; P = 0.005) and RSA recovery (β = -0.028; P = 0.032). In infants with shorter composite placental TL, higher ACE score predicted greater RSA suppression during the still-face epoch relative to play period 1 and greater RSA augmentation during play period 2 relative to the still-face epoch., Conclusions: These data are the first, to our knowledge, to report that changes in placental TL influence the transgenerational impact of maternal early life adversity on the development of her offspring's autonomic nervous system., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Exposure to violence and obesity continues to be growing epidemics, particularly among children. Our objective was to increase our understanding of the association between neighborhood violence exposure and children's weight and how biologic stress may mediate this relation. A matched, community-recruited cross-sectional study of 90 children, ages 5-16 years, from 52 neighborhoods took place in the greater New Orleans, LA area between 2012 and 2013. Children were matched on their propensity for living in a high violence neighborhood and previous exposure to Hurricane Katrina. Primary neighborhood exposure included violent crime, operationalized as crime rates within specific radii of children's home. Rates of exposure within 500, 1000 and 2000 meter radii from the child's home were calculated. Primary outcomes were body mass index (BMI) and waist circumference, and the primary mediator was telomere length (TL), a marker of cellular aging. Significant variation in obesity and TL was observed at the neighborhood level and violent crime was significantly associated with weight status, with an increase of 1.24 units in BMI for each additional violent crime in the child's neighborhood and a significant mediated or indirect effect of TL in the crime-BMI relation (0.32, 95% bootstrapped CI = 0.05, 0.81; 32% total mediated effect). Findings strengthen existing evidence linking neighborhood violence to childhood health and identify biologic stress, indexed by TL, as one mechanistic pathway by which neighborhood violence may influence childhood obesity. Neighborhood violence may be an important target for interventions focused on reducing obesity and other stress related health outcomes in children.

Reducing health disparities requires an understanding of the mechanisms that generate disparities. Life course approaches to health disparities leverage theories that explain how socially patterned physical, environmental, and socioeconomic exposures at different stages of human development shape health within and across generations and can therefore offer substantial insight into the etiology of health disparities. Life course approaches are informed by developmental and structural perspectives. Developmental perspectives emphasize how socially patterned exposures to risk factors during sensitive life stages shift health trajectories, whereas structural perspectives emphasize how social identity and position within socially patterned environments disproportionately allocate risk factors and resources, resulting in altered health trajectories. We conclude that the science of health disparities will be advanced by integrating life course approaches into etiologic and intervention research on health disparities. The following 4 strategies are offered to guide in this process: (1) advance the understanding of multiple exposures and their interactions, (2) integrate life course approaches into the understanding of biological mechanisms, (3) explore transgenerational transmission of health disparities, and (4) integrate life course approaches into health disparities interventions.

Objectives: To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence., Study Design: This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development., Results: Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with ≥2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with ≥2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions., Conclusions: For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental., Trial Registration: clinicaltrials.gov: NCT00747396., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To examine the impact of polymorphic variation in the solute carrier family 5 member 7 (SLC5A7) gene on autonomic nervous system (ANS) reactivity indexed by respiratory sinus arrhythmia (RSA) and heart rate (HR) in infants during a dyadic stressor, as well as maternal report of infant self-regulation. Given evidence of race differences in older individuals, race was specifically examined., Methods: RSA and HR were collected from 111 infants during the still-face paradigm (SFP). Mothers completed the Infant Behavior Questionnaire-Revised short-form. Multi-level mixed effects models examined the impact of SLC5A7 genotype on RSA and HR across the SFP. Linear models tested the influence of genotype on the relation between RSA, HR, and maternal report of infant self-regulation., Results: SLC5A7 genotype significantly predicted RSA stress responsivity (β = -0.023; p = 0.028) and HR stress responsivity (β = 0.004; p = 0.002). T-allele carriers exhibited RSA suppression and HR acceleration in response to stress while G/G homozygotes did not suppress RSA and exhibited less HR acceleration. All infants exhibited modest RSA augmentation and HR deceleration during recovery. Race-stratified analyses revealed that White T-allele carriers drove the overall results for both RSA (β = -0.044; p = 0.007) and HR (β = 0.006; p = 0.008) with no relation between SLC5A7 genotype and RSA or HR in Black infants. Maternal report of infant orienting/regulation was predicted by the interaction of SLC5A7 genotype and both RSA recovery (β = 0.359; p = 0.001) and HR recovery (β = -1.659; p = 0.020). RSA augmentation and HR deceleration during recovery were associated with higher maternal reports of self-regulation among T-allele carriers, a finding again primarily driven by White infants., Conclusions: Early in development, genetic contributions to ANS are evident and predict maternal report of infant self-regulation within White infants, consistent with prior literature. The lack of associations in Black infants suggest that race differences in physiological reactivity and self-regulation are emerging during the first year of life potentially providing early evidence of disparities in health risk trajectories., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The molecular, neurobiological, and physical health impacts of child maltreatment are well established, yet mechanistic pathways remain inadequately defined. Telomere length (TL) decline is an emerging molecular indicator of stress exposure with definitive links to negative health outcomes in maltreated individuals. The multiple confounders endemic to human maltreatment research impede the identification of causal pathways. This study leverages a unique randomized, cross-foster, study design in a naturalistic translational nonhuman primate model of infant maltreatment. At birth, newborn macaques were randomly assigned to either a maltreating or a competent control mother, balancing for sex, biological mother parenting history, and social rank. Offspring TL was measured longitudinally across the first 6 months of life (infancy) from peripheral blood. Hair cortisol accumulation was also determined at 6, 12, and 18 months of age. TL decline was greater in animals randomized to maltreatment, but also interacted with biological mother group. Shorter TL at 6 months was associated with higher mean cortisol levels through 18 months (juvenile period) when controlling for relevant covariates. These results suggest that even under the equivalent social, nutritional, and environmental conditions feasible in naturalistic translational nonhuman primate models, early adverse caregiving results in lasting molecular scars that foreshadow elevated health risk and physiologic dysregulation.