Linking caregiving quality during infancy to brain activity in early childhood and later executive function.

There is no relationship more vital than the one a child shares with their primary caregivers early in development. Yet many children worldwide are raised in settings that lack the warmth, connection, and stimulation provided by a responsive primary caregiver. In this study, we used data from the Bucharest Early Intervention Project (BEIP), a longitudinal study of institutionally-reared and family-reared children, to test how caregiving quality during infancy is associated with average EEG power over the first 3.5 years of life in alpha, beta, and theta frequency bands, and associations with later executive function (EF) at age 8 years. The sample comprised 189 children (129 institutionally-reared; 60 family-reared) who contributed data on observed caregiving quality during infancy (baseline; average age of 22 months), resting EEG power at baseline, 30, and 42 months, and performance-based data on a series of EF tasks at 8 years. Using Bayesian estimation, observed caregiving quality at baseline was marginally linked with higher average alpha and beta power, and lower theta power, from baseline to 42 months. In turn, higher average beta power and lower average theta power were marginally associated with higher EF at 8 years. In indirect effects models, higher caregiving quality at baseline was associated with higher EF at 8 years, with a marginal indirect effect through average theta power from baseline to 42 months. Variation in the quality of the early caregiving environment may be associated with later executive function, which is partially underpinned by individual differences in brain activity during early childhood. RESEARCH HIGHLIGHTS: Examined associations between caregiving quality during infancy, brain activity during early childhood, and executive function during mid-childhood in sample of never-institutionalized and institutionally-reared children. Significant associations between higher quality caregiving during infancy and higher executive function during middle childhood. Marginal associations between caregiving quality during infancy and brain activity during early childhood. Marginal associations between brain activity during early childhood and executive function during mid-childhood.

Effects of foster care intervention and caregiving quality on the bidirectional development of executive functions and social skills following institutional rearing.

Institutional rearing negatively impacts the development of children's social skills and executive functions (EF). However, little is known about whether childhood social skills mediate the effects of the foster care intervention (FCG) and foster caregiving quality following early institutional rearing on EF and social skills in adolescence. We examined (a) whether children's social skills at 8 years mediate the impact of the FCG on the development of EF at ages 12 and 16 years, and (b) whether social skills and EF at ages 8 and 12 mediate the relation between caregiving quality in foster care at 42 months and subsequent social skills and EF at age 16. Participants included abandoned children from Romanian institutions, who were randomly assigned to a FCG (n = 68) or care as usual (n = 68), and a never-institutionalized group (n = 135). At ages 8, 12, and 16, social skills were assessed via caregiver and teacher reports and EF were assessed via the Cambridge Neuropsychological Test Automated Battery. Caregiving quality of foster caregivers was observed at 42 months. FCG predicted better social skills at 8 years, which in turn predicted better EF in adolescence. Higher caregiver quality in foster care at 42 months predicted better social skills at 8 and 12 years, and better EF at 12 years, which in turn predicted 16-year EF and social skills. These findings suggest that interventions targeting caregiving quality within foster care home environments may have long-lasting positive effects on children's social skills and EF.

Infant behavioral inhibition predicts personality and social outcomes three decades later.

Does infant temperament predict adult personality and life-course patterns? To date, there is scant evidence examining relations between child temperament and adult outcomes, and extant research has relied on limited methods for measuring temperament such as maternal report. This prospective longitudinal study followed a cohort of infants (n = 165) for three decades to examine whether infant behavioral inhibition, a temperament characterized by cautious and fearful behaviors to unfamiliar situations, shapes long-term personality, social relationships, vocational/education, and mental health outcomes in adulthood. At age 14 mo, behavioral inhibition was assessed using an observation paradigm. In adolescence (15 y; n = 115), error monitoring event-related potentials were measured in a flanker task. In adulthood (26 y; n = 109), personality, psychopathology, and sociodemographics were self-reported using questionnaires. We found that infants with higher levels of behavioral inhibition at 14 mo grew up to become more reserved and introverted adults (ß = 0.34) with lower social functioning with friends and family (ß = -0.23) at age 26. Infant behavioral inhibition was also a specific risk factor for adult internalizing (i.e., anxiety and depression, ß = 0.20) psychopathology, rather than a transdiagnostic risk for general and externalizing psychopathology. We identified a neurophysiologic mechanism underlying risk and resilience for later psychopathology. Heightened error monitoring in adolescence moderated higher levels of adult internalizing psychopathology among behaviorally inhibited individuals. These findings suggest meaningful continuity between infant temperament and the development of adult personality. They provide the earliest evidence suggesting that the foundation of long-term well-being is rooted in individual differences in temperament observed in infancy.

Infant temperament prospectively predicts general psychopathology in childhood.

Recent models of psychopathology suggest the presence of a general factor capturing the shared variance among all symptoms along with specific psychopathology factors (e.g., internalizing and externalizing). However, few studies have examined predictors that may serve as transdiagnostic risk factors for general psychopathology from early development. In the current study we examine, for the first time, whether observed and parent-reported infant temperament dimensions prospectively predict general psychopathology as well as specific psychopathology dimensions (e.g., internalizing and externalizing) across childhood. In a longitudinal cohort (N = 291), temperament dimensions were assessed at 4 months of age. Psychopathology symptoms were assessed at 7, 9, and 12 years of age. A bifactor model was used to estimate general, internalizing, and externalizing psychopathology factors. Across behavioral observations and parent-reports, higher motor activity in infancy significantly predicted greater general psychopathology in mid to late childhood. Moreover, low positive affect was predictive of the internalizing-specific factor. Other temperament dimensions were not related with any of the psychopathology factors after accounting for the general psychopathology factor. The results of this study suggest that infant motor activity may act as an early indicator of transdiagnostic risk. Our findings inform the etiology of general psychopathology and have implications for the early identification for children at risk for psychopathology.

Children's shyness and neural responses to social exclusion: Patterns of midfrontal theta power usually not observed until adolescence.

Adverse peer experiences, such as social exclusion, are known risks for socioemotional problems among shy youth. Yet, little is known about how shy children and adolescents process social exclusion in the brain and whether these responses are amplified in adolescence. Using the Cyberball task, we examined mediofrontal theta (4-7 Hz) event-related EEG spectral power during conditions of fair play and social exclusion in 122 participants (58 children, ages 10-12 years, and 64 adolescents, ages 14-17 years). Age effects of the task showed that adolescents displayed heightened theta power to both outright rejection and baseline "not my turn" events, whereas children showed higher theta power to rejection compared with "not my turn" events. Further results on individual differences showed that children with relatively higher levels of shyness displayed enhanced theta power to both rejection and "not my turn" events-a pattern that also was observed in adolescents. These findings suggest that a pattern of heightened neural sensitivity to both outright social exclusion and threats of exclusion, which is the norm by adolescence, also is observed in children with higher levels of shyness. The similar neural response pattern might be driven by salient social motivations that similarly modify the social cognition and behaviors of these groups and might reflect neural antecedents of rejection sensitivity.

Long-Term Effects of Institutional Care and Enhanced Attachment Relationships on Close Adolescent Friendships.

This study examined whether early institutional rearing and attachment security influence the quality and quantity of friendships at age 16 in 138 participants, including children abandoned to institutions in Bucharest, Romania, who were randomized to care as usual (n = 45, 26 female), or foster care (n = 47, 25 female), and a never-institutionalized group (n = 46, 18 female). Adolescents in the foster care group with secure attachment to their foster mothers at 42 months were comparable to never-institutionalized adolescents in having more friends and more positive behaviors with their friend during dyadic interactions, compared to the foster care group with insecure attachment and care as usual group. Interventions targeting early child-caregiver attachment relationships may help foster the ability to build positive friendships in adolescence.

The long-term effects of institutional rearing, foster care intervention and disruptions in care on brain electrical activity in adolescence.

Exposure to early psychosocial deprivation as a result of institutional care disrupts typical brain development. The Bucharest Early Intervention Project (BEIP) is the first longitudinal study to investigate the neurodevelopment of institutionalized infants randomized to a foster care (FCG) intervention versus care as usual (CAUG). Here, we present findings from a follow-up assessment of brain electrical activity as indexed by resting EEG at age 16 years. In addition, we examined the effects of disruption of foster care placement (e.g. the number of moves among foster care placements) on brain electrical activity. Resting-state EEG was collected from 48 CAUG, 46 FCG and 48 never institutionalized (NIG) control participants. Absolute (µV2 ) and relative (proportion) power were computed from eyes closed, resting EEG data for theta, alpha and beta frequency bands. The CAUG displayed higher relative theta and lower relative alpha power compared to the FCG at 16 years of age. The FCG showed brain activity comparable to the NIG. The results further showed that disruptions following the original foster care placement had an adverse effect on brain electrical activity. Within the foster care group, there were no effects of age of placement on EEG power. Placement of children who have experienced early institutional rearing into stable foster care settings ensure long-term improvement in brain functioning.

The prospective association between stressful life events and inflammation among adolescents with a history of early institutional rearing.

Early adversity has been shown to sensitize individuals to the effects of later stress and enhance risk of psychopathology. Using a longitudinal randomized trial of foster care as an alternative to institutional care, we extend the stress sensitization hypothesis to examine whether early institutional rearing sensitizes individuals to stressful events in adolescence engendering chronic low-grade inflammation. At baseline, institutionalized children in Romania (ages 6-31 months) were randomly assigned to foster care or to remain in usual care within institutions. A group of never-institutionalized children was recruited as an in-country comparison sample. At ages 12 and 16, participants reported stressful events. At age 16, Interleukin-6 (IL-6) and C-reactive protein (CRP) were derived from blood spots. Among children assigned to care as usual, more stressful events at age 12, but not age 16, were associated with higher IL-6. In the same group, stressful events at age 16 were associated with higher CRP, though these effects attenuated after adjusting for covariates. These associations were not observed in the foster care or never-institutionalized groups. The findings suggest that heightened inflammation following stress exposure is one pathway through which early neglect could compromise physical health. In contrast, early family care might buffer against these risks.

Conducting Event-Related Potential (ERP) Research with Young Children: A Review of Components, Special Considerations and Recommendations for Research on Cognition and Emotion.

There has been an unprecedented increase in the number of research studies employing event-related potential (ERP) techniques to examine dynamic and rapidly-occurring neural processes with children during the preschool and early childhood years. Despite this, there has been little discussion of the methodological and procedural differences that exist for studies of young children versus older children and adults. That is, reviewers, editors, and consumers of this work often expect developmental studies to simply apply adult techniques and procedures to younger samples. Procedurally, this creates unrealistic expectations for research paradigms, data collection, and data reduction and analyses. Scientifically, this leads to inappropriate measures and methods that hinder drawing conclusions and advancing theory. Based on ERP work with preschoolers and young children from 10 laboratories across North America, we present a summary of the most common ERP components under study in the area of emotion and cognition in young children along with 13 realistic expectations for data collection and loss, laboratory procedures and paradigms, data processing, ERP averaging, and typical challenges for conducting this type of work. This work is intended to supplement previous guidelines for work with adults and offer insights to aid researchers, reviewers, and editors in the design and evaluation of developmental research using ERPs. Here we make recommendations for researchers who plan to conduct or who are conducting ERP studies in children between ages 2 and 12, focusing on studies of toddlers and preschoolers. Recommendations are based on both data and our cumulative experience and include guidelines for laboratory setup, equipment and recording settings, task design, and data processing.

The Consequences of Foster Care Versus Institutional Care in Early Childhood on Adolescent Cardiometabolic and Immune Markers: Results From a Randomized Controlled Trial.

OBJECTIVE: Children exposed to institutional rearing often exhibit problems across a broad array of developmental domains. We compared the consequences of long-term, high-quality foster care versus standard institution-based care, which began in early childhood on cardiometabolic and immune markers assessed at the time of adolescence. METHODS: The Bucharest Early Intervention Project is a longitudinal investigation of children institutionalized during early childhood (ages 6 to 30 months at baseline) who were subsequently randomized to either high-quality foster care or continued institutional care. At the age of 16 years, 127 respondents participated in a biomarker collection protocol, including 44 institutionalized children randomly assigned to receive care as usual, 41 institutionalized children randomized to be removed from institutional care and placed in high-quality foster care in infancy, and a control group of 42 demographically matched children raised in biological families. Outcomes included body mass index (BMI), systolic and diastolic blood pressure, C-reactive protein, interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor α, glycosylated hemoglobin A1c, and Epstein-Barr virus antibody titers. RESULTS: Early institutional rearing was not associated with differences in cardiometabolic or immune markers. Randomization to foster care and age of placement into foster care were also unrelated to these markers, with the exception of BMI z-score, where children assigned to care as usual had lower BMI z-scores relative to children assigned to foster care (-0.23 versus 0.08, p = .06), and older age at placement was associated with lower BMI (ß = -0.07, p = .03). CONCLUSIONS: The impact of institutional rearing on measures of cardiometabolic health and immune system functioning is either absent or not evident until later in development. These findings provide new insights into the biological embedding of adversity and how it varies developmentally and across regulatory systems and adversity type. CLINICAL TRIAL REGISTRATION: NCT00747396.

Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial.

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.

Catch-up growth, metabolic, and cardiovascular risk in post-institutionalized Romanian adolescents.

BACKGROUND: Reduced prenatal growth followed by rapid postnatal weight gain are risk factors for developing metabolic and cardiovascular disease. Children reared in institutions experience a similar pattern of growth restriction followed by catch-up growth after removal. We explored whether patterns of catch-up growth affect metabolic and cardiovascular outcomes in previously institutionalized adolescents. METHOD: A longitudinal study of institutionalized infants randomized to care as usual (n = 68) or foster care intervention (n = 68), and never institutionalized controls (n = 127). Body mass index (BMI) was measured at baseline (20 months), 30, 42 months, and ages 8, 12, 16. At age 16, metabolic and pro-inflammatory markers were derived from blood samples. RESULTS: Four BMI trajectories were derived (i.e., average-stable, low-stable, elevated, and accelerated). The accelerated trajectory was comprised predominately of children randomized to foster care, who also exhibited higher levels of glycosylated hemoglobin and C-reactive protein than the other three trajectories. Also, children placed in foster care at younger ages were more likely to be on the accelerated rather than the average-stable trajectory. CONCLUSIONS: Although catch-up growth is viewed as a positive improvement among post-institutionalized children, rapid/continuous increases in body size pose a health concern. Attention should be given to monitoring weight gain, diet, and physical activity.

Longitudinal Associations Among Child Maltreatment, Resting Frontal Electroencephalogram Asymmetry, and Adolescent Shyness.

Child maltreatment is linked to distinct neurophysiological patterns and social-emotional vulnerability. Relations among maltreatment, relative resting frontal alpha asymmetry, shyness, and psychopathology were examined prospectively. Adolescent girls (age 14-16) who experienced child maltreatment (N = 55) were compared to nonmaltreated controls (N = 25), and returned for 6- and 12-month follow-ups. Among participants exhibiting relative right frontal asymmetry, maltreated adolescents reported higher shyness than controls at Time 1. Low-stable and high-stable shyness trajectories were observed for maltreated participants. Compared to low shy, participants in high-shy trajectory reported at Time 3: higher neuroticism and generalized anxiety; and lower extraversion if they also exhibited relative right frontal asymmetry. Thus, right frontal brain activity and shyness are involved in social-emotional vulnerability of adolescents who experienced child maltreatment.

Trajectories of resting frontal brain activity and psychopathology in female adolescents exposed to child maltreatment.

Resting frontal electroencephalogram (EEG) alpha asymmetry patterns reflecting different affective and motivational tendencies have been proposed as a putative mechanism underlying resilience among maltreated youth. This 2-year prospective study examined whether developmental stability of resting frontal alpha asymmetry moderated the relation between child maltreatment severity and psychopathology in female adolescents (n = 43; ages 12-16) recruited from child protection agencies. Results identified two trajectories of resting frontal asymmetry: 60.5% displayed stable right and 39.5% displayed stable left frontal alpha asymmetry. Although individuals with these alpha asymmetry profiles experienced comparable childhood trauma severity, adolescents with stable left alpha asymmetry and lower levels of trauma were less likely to present symptoms or an episode of posttraumatic stress disorder (PTSD) and depression over 2 years than those with stable right alpha asymmetry and lower levels of trauma. These findings suggest that developmental patterns of resting left frontal brain activity may buffer against psychopathology in maltreated female youth.

Depression Predicts Functional Outcome in Geriatric Inpatient Rehabilitation.

OBJECTIVE: To evaluate the effect of depression on functional recovery in geriatric patients who have completed an inpatient rehabilitation program. DESIGN: Prospective cohort study. SETTING: Inpatient rehabilitation unit of a university-affiliated geriatric hospital. PARTICIPANTS: Convenience sample of patients (N=65; mean age, 81.6y; 25 men) admitted to rehabilitation over a 10-month period. Patients >60 years of age who were proficient in English and capable of providing informed consent were eligible to participate in the study. INTERVENTIONS: Depression was assessed using both the Geriatric Depression Scale-short form (GDS-15) and the Patient Health Questionnaire (9-item screen for depression) (PHQ-9). Measures of well-established predictors of rehabilitation outcome, which may interact with depression, were also obtained, and multiple regression linear modeling was used to evaluate the relation between depression and functional outcome over and above the contribution of these other factors. MAIN OUTCOME MEASURE: FIM (Functional Independence Measure) at discharge from the rehabilitation program. RESULTS: Depression, as assessed by the GDS-15, but not the PHQ-9, was predictive of functional outcome (standardized beta=-.151, P=.030) after controlling for other significant predictors, which included baseline disability, pain, cognition, and educational level. Participation in recreational, but not physio- or occupational, therapy additionally contributed to a small amount of variance in the functional outcome. CONCLUSIONS: Our findings suggest that self-report of depression is an independent predictor of functional outcome in high-tolerance, short-duration geriatric rehabilitation. Routine assessment of depressive symptoms in older adults using an instrument (eg, GDS-15) may help identify those at risk for poorer outcomes in rehabilitation.

Developmental programming of happiness.

Being born at an extremely low birth weight (ELBW; <1,000 grams) is presumed to reflect a suboptimal intrauterine environment and thus presents an opportunity for examining developmental programming hypotheses. Interfacing prenatal programming and differential susceptibility hypotheses, we tested whether individuals with ELBW in different childhood rearing environments showed different attention biases to positive and negative facial emotions in adulthood. Using the oldest known, prospectively followed cohort of ELBW survivors, we found that relative to normal birth weight controls (NBW; >2,500 grams), ELBW survivors displayed the highest and lowest attention bias to happy faces at age 30-35, depending on whether their total family income at age 8 was relatively low (environmental match) or high (environmental mismatch), respectively. This bias to happy faces was associated with a reduced likelihood of emotional problems. Findings suggest that differential susceptibility to positive emotions may be prenatally programmed, with effects lasting into adulthood. We discuss implications for integrating prenatal programming and differential susceptibility hypotheses, and the developmental origins of postnatal plasticity and resilience.

Personality Development Within a Generational Context: Life Course Outcomes of Shy Children.

Studies have shown that shy children born in the 1920s and 1950s had delayed marriage and parenthood, less stable careers, and lower occupational attainment as adults than other children. Do these effects still hold true? We examined demographic and social outcomes of children born between 1977 and 1982 in a prospective longitudinal study. We assessed shyness in childhood (age 8), adolescence (age 12-16), young adulthood (age 22-26), and adulthood (age 30-35), and derived three shyness trajectories (i.e., decreasing, increasing, and low-stable). Social and demographic outcomes for shy children who outgrew their shyness (i.e., decreasing trajectory) were indistinguishable from those who were consistently low on shyness measures. However, a shyness trajectory beginning in adolescence and increasing to adulthood was associated with poorer outcomes, similar to previous studies. These findings highlight the importance of multiple assessments in long-term longitudinal studies and the need to consider personality development within a generational context.

Distinguishing shyness and sociability in children: An event-related potential study.

Shyness and sociability are independent personality dimensions, each with distinct behavioral and psychophysiological correlates that are conserved across development, culture, and phylogeny. However, relatively little is known regarding how shyness and sociability are instantiated in the brain, particularly during childhood and during the processing of nonsocial stimuli. Using a three-stimulus auditory oddball task, we examined whether variations in shyness and sociability were related to the N200 and P300 event-related potential (ERP) brain responses to processing task-relevant, novel, and standard auditory tones in 53 typically developing 10-year-old children. ERP amplitudes were measured at four midline scalp sites: Fz, FCz, Cz, and Pz. We found that increases in shyness were correlated with increases in target P300 amplitudes across all four head sites, increases in standard P300 amplitudes, and decreases in target P300 latencies in anterior sites. No relations were found for sociability and P300 responses. We also found that P300 amplitude in the frontal region to standard tones mediated the relation between conflicted shyness (i.e., high shyness and high sociability) and emotional instability. These results suggest that shyness and sociability are distinguishable on neurocognitive measures and that these neurocognitive measures may be putative mechanisms in understanding risk for emotional instability and a broad range of dysregulated behavioral problems observed in individuals characterized by conflicted shyness.

Longitudinal patterns of childhood homelessness and early adolescent trajectories of internalising and externalising behaviour.

BACKGROUND: Child homelessness has been associated with elevated mental health problems during early adolescence, a period of onset for psychiatric problems. Prior literature has relied on cross-sectional studies, limiting the understanding of temporality and trajectories of psychopathology. We extend prior literature by examining associations between child homelessness and internalising and externalising symptom trajectories in early adolescence, with consideration of timing and persistence of homelessness. METHODS: Using population-based longitudinal data from the Avon Longitudinal Study of Parents and Children, we used multilevel models to examine the effects of homelessness prior to age 9, the timing of homelessness (eg, early vs middle childhood) and cumulative exposure to homelessness on internalising and externalising trajectories across ages <0-9 years. We also tested for sex differences in these associations. RESULTS: Of the 8391 participants, 5.5% reported exposure to homelessness at least once before age 9. Children who experienced homelessness had elevated internalising and externalising symptoms compared with their consistently housed peers, with excess risk evident among children who first experienced homelessness in middle childhood (relative to early childhood) and children who experienced recurrent homelessness. We did not observe changes in symptom trajectories over the course of 4 years. Men who experienced homelessness displayed a more pronounced risk of internalising symptoms relative to women and men who did not experience homelessness. CONCLUSION: Childhood homelessness is associated with persistently elevated internalising and externalising symptoms across early adolescence compared with their consistently housed peers. Interventions and policies to address family homelessness may lead to better mental health among adolescents.

Parent-child separation and cardiometabolic outcomes and risk factors in adulthood: A systematic review.

BACKGROUND: Parent-child separation has been associated with negative mental health across childhood and adulthood, yet little is known about the long-term impacts for cardiovascular health. This systematic review synthesized and evaluated the quality of the literature examining the association between exposures to parent-child separation and cardiometabolic outcomes in adulthood. METHODS: Following a registered protocol, online databases (Pubmed, PsycInfo, and Web of Science) were searched for relevant studies. Studies were included if they (a) defined the exposure before age 18 as institutionalization, foster care placement, parental incarceration, separation due to parents migrating for economic reasons, or asylum and war; and (b) quantified the association between parent-child separation and cardiometabolic events and diagnoses (e.g., coronary heart disease, diabetes) and risk factors (e.g., body mass index, fat distribution, serum-based metabolic markers, inflammatory markers in adulthood (≥ age 18). Studies lacking an unexposed comparison group were excluded. The risk for bias in each study was assessed with a modified Newcastle-Ottawa Scale. RESULTS: Of the 1938 studies identified, 13 met our inclusion criteria. Two of the four studies examining associations between parent-child separation and cardiometabolic events and diagnoses found positive associations with coronary heart disease and diabetes. Amongst the 13 studies examining associations with any type of adult cardiometabolic risk factors, eight studies reported at least one positive association. Sub-analyses considering separate reasons for parent-child separation provided clearer insights: War evacuation was associated with hypertension and high blood pressure across four studies from the same cohort; out-of home care experiences largely evidenced null results across five different studies, and two studies on parental incarceration suggested positive associations with elevated inflammation, BMI and blood pressure. CONCLUSIONS: The connections between parent-child separation and adult cardiometabolic outcomes and risk factors are currently inconsistent. The results may depend on the reason for separation, age of assessment, analytic differences and other psychosocial variables that are often unmeasured in this literature.