Integrating Data Across Multiple Sites in the Northeastern United States to Examine Associations Between a Prenatal Metal Mixture and Child Cognition.

We applied a novel hierarchical Bayesian weighted quantile sum (HBWQS) regression to combine data across 3 study sites to examine associations between prenatal exposure to metals and cognitive functioning in childhood. Data from 326 mother-child dyads enrolled in an ongoing cohort study, the Programming of Intergenerational Stress Mechanisms (PRISM) Study, based in New York, New York (recruitment in 2013-2020) and Boston, Massachusetts (recruitment 2011-2013), and the First Thousand Days of Life (FTDL) cohort study (recruitment 2012-2019), based in northern Virginia, were used. Arsenic, cadmium, manganese, lead, and antimony were measured in urine collected during pregnancy. Cognitive functioning was assessed in children aged 3-11 years using the National Institutes of Health Toolbox Cognition Battery. The HBWQS regression showed a negative association between the urinary metal mixture and the Cognition Early Childhood Composite Score in the PRISM New York City (ß = -3.67, 95% credible interval (CrI): -7.61, -0.01) and FTDL (ß = -3.76, 95% CrI: -7.66, -0.24) samples, with a similar trend in the PRISM Boston sample (ß = -3.24, 95% CrI: -6.77, 0.144). We did not detect these associations in traditionally pooled models. HBWQS regression allowed us to account for site heterogeneity and detect associations between prenatal metal-mixture exposure and cognitive outcomes in childhood. Given the ubiquity of metals exposure, interventions aimed at reducing prenatal exposure may improve cognitive outcomes in children. This article is part of a Special Collection on Environmental Epidemiology.

Associations between a metal mixture and infant negative affectivity: Effect modification by prenatal cortisol and infant sex.

In-utero exposures interact in complex ways that influence neurodevelopment. Animal research demonstrates that fetal sex moderates the impact of joint exposure to metals and prenatal stress measures, including cortisol, on offspring socioemotional outcomes. Further research is needed in humans. We evaluated the joint association of prenatal exposures to a metal mixture and cortisol with infant negative affectivity, considering sex differences. Analyses included 226 (29% White, Non-Hispanic) mother-infant pairs with data on exposures and negative affectivity assessed using the Infant Behavior Questionnaire-Revised in 6-month-olds. Results showed that girls whose mothers had higher cortisol had significantly higher scores of Fear and Sadness with greater exposure to the mixture. Examining higher-order interactions may better elucidate the effects of prenatal exposure to metals and cortisol on socioemotional functioning.

Temperament and sex as moderating factors of the effects of exposure to maternal depression on telomere length in early childhood.

Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children's susceptibility to the effects of maternal depression on telomere dynamics in early life.

Negative versus withdrawn maternal behavior: Differential associations with infant gray and white matter during the first 2 years of life.

Distinct neural effects of threat versus deprivation emerge by childhood, but little data are available in infancy. Withdrawn versus negative parenting may represent dimensionalized indices of early deprivation versus early threat, but no studies have assessed neural correlates of withdrawn versus negative parenting in infancy. The objective of this study was to separately assess the links of maternal withdrawal and maternal negative/inappropriate interaction with infant gray matter volume (GMV), white matter volume (WMV), amygdala, and hippocampal volume. Participants included 57 mother-infant dyads. Withdrawn and negative/inappropriate aspects of maternal behavior were coded from the Still-Face Paradigm at four months infant age. Between 4 and 24 months (M age = 12.28 months, SD = 5.99), during natural sleep, infants completed an MRI using a 3.0 T Siemens scanner. GMV, WMV, amygdala, and hippocampal volumes were extracted via automated segmentation. Diffusion weighted imaging volumetric data were also generated for major white matter tracts. Maternal withdrawal was associated with lower infant GMV. Negative/inappropriate interaction was associated with lower overall WMV. Age did not moderate these effects. Maternal withdrawal was further associated with reduced right hippocampal volume at older ages. Exploratory analyses of white matter tracts found that negative/inappropriate maternal behavior was specifically associated with reduced volume in the ventral language network. Results suggest that quality of day-to-day parenting is related to infant brain volumes during the first two years of life, with distinct aspects of interaction associated with distinct neural effects.

Risk for internalizing symptom development in young children: Roles of child parasympathetic reactivity and maternal depression and anxiety exposure in early life.

Intergenerational transmission of internalizing disorders (anxiety and depression) is well documented, but the responsible pathways are underspecified. One possible mechanism is via programming of the child's parasympathetic nervous system (PNS). For example, maternal depression and anxiety, via multiple pathways, may heighten child PNS reactivity, which has been linked to increased risk for internalizing disorders. Heightened PNS reactivity also may sensitize a child to their environment, increasing the vulnerability to developing psychopathology when exposed to stressors, such as maternal psychopathology. In a prospective longitudinal study of mother-child dyads (N = 446), we examined relations among maternal depression and anxiety symptoms when children were infants and aged 3 and 5 years, child respiratory sinus arrythmia (RSA) reactivity (measure of PNS reactivity) at 3 years, and child internalizing symptoms at age 5 years. Consistent with an adaptive calibration perspective, analyses tested the roles of child RSA reactivity as both a mediator and a moderator of associations between maternal and child symptoms. Greater child RSA reactivity in response to a fearful video predicted higher internalizing symptoms among children exposed to higher levels of maternal depression or anxiety symptoms at age 5 years (moderation effects). Child RSA reactivity did not mediate relations between maternal depression or anxiety symptoms in infancy and child internalizing symptoms at age 5 years. The results suggest that heightened PNS reactivity may represent a biological vulnerability to stressful environments early in life: When coupled with maternal depression or anxiety exposure, child PNS reactivity may promote the development of internalizing psychopathology in early childhood.

Frontal asymmetry assessed in infancy using functional near-infrared spectroscopy is associated with emotional and behavioral problems in early childhood.

Frontal asymmetry (FA), the difference in brain activity between the left versus right frontal areas, is thought to reflect approach versus avoidance motivation. This study (2012-2021) used functional near-infrared spectroscopy to investigate if infant (Mage  = 7.63 months; N = 90; n = 48 male; n = 75 White) FA in the dorsolateral prefrontal cortex relates to psychopathology in later childhood (Mage  = 62.05 months). Greater right FA to happy faces was associated with increased internalizing (η2  = .09) and externalizing (η2  = .06) problems at age 5 years. Greater right FA to both happy and fearful faces was associated with an increased likelihood of a lifetime anxiety diagnosis (R2 > .13). FA may be an informative and early-emerging marker for psychopathology.

Association of Gestational Diabetes Mellitus and Perinatal Maternal Depression with Early Childhood Behavioral Problems: An Environmental Influences on Child Health Outcomes (ECHO) Study.

This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009-2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.

Associations among maternal lifetime trauma, psychological symptoms in pregnancy, and infant stress reactivity and regulation.

Maternal trauma has intergenerational implications, including worse birth outcomes, altered brain morphology, and poorer mental health. Research investigating intergenerational effects of maternal trauma on infant stress reactivity and regulation is limited. Maternal mental health during pregnancy may be a contributor: psychopathology is a sequela of trauma exposure and predictor of altered self-regulatory capacity in offspring of affected mothers. We assessed associations among maternal lifetime trauma and infant stress responsivity, mediated by psychological symptoms in pregnancy. Mothers reported lifetime trauma history and anxiety, depressive, and posttraumatic stress symptoms during pregnancy. At infant age 6 months, stress reactivity and regulation were assessed via maternal behavior ratings (Infant Behavior Questionnaire-Revised, IBQ-R) and behavioral (negative mood) and physiological (respiratory sinus arrhythmia, RSA) markers during a laboratory stressor (Still-Face Paradigm). Maternal trauma was directly associated with lower infant physiological regulation and indirectly associated with lower levels of both infant behavioral and physiological regulation via higher maternal anxiety during pregnancy. Maternal trauma was also indirectly associated with higher infant reactivity via higher maternal anxiety during pregnancy. Post hoc analyses indicated differential contributions of maternal prenatal versus postnatal anxiety to infant outcomes. Findings highlight potential contributory mechanisms toward maladaptive child stress response, which has been associated with poor behavioral, cognitive, and academic outcomes.

Infants' neural responses to emotional faces are related to maternal anxiety.

BACKGROUND: Postnatal maternal anxiety is common (estimates as high as 40% prevalence) and is associated with altered mother-infant interactions (e.g., reduced maternal emotional expression and engagement). Neural circuitry supporting infants' face and emotion processing develops in their first year. Thus, early exposure to maternal anxiety may impact infants' developing understanding of emotional displays. We examine whether maternal anxiety is associated with individual differences in typically developing infants' neural responses to emotional faces. METHODS: One hundred and forty two mother-infant dyads were assessed when infants were 5, 7, or 12 months old. Infants' electroencephalographic (EEG) data were recorded while passively viewing female happy, fearful, and angry faces. Three event-related potential (ERP) components, each linked to face and emotion processing, were evaluated: NC, N290, and P400. Infant ERP amplitude was related to concurrent maternal-report anxiety assessed with the Spielberger State-Trait Anxiety Inventory (Trait form). RESULTS: Greater maternal anxiety predicted more negative NC amplitude for happy and fearful faces in left and mid-central scalp regions, beyond covarying influences of maternal depression symptoms, infant negative emotionality, and infant age. CONCLUSIONS: Postnatal maternal anxiety is related to infants' neural processing of emotional expressions. Infants of mothers endorsing high trait anxiety may need additional attentional resources to process happy and fearful faces (expressions less likely experienced in mother-infant interactions). Future research should investigate mechanisms underlying this association, given possibilities include experiential, genetic, and prenatal factors.

Temperament and psychopathology: The "community" to which you belong matters.

We utilized a community detection approach to longitudinally (a) identify distinct groups of children with common temperament profiles in infancy and at 2 and 3 years of age and (b) determine whether co-occurrence of certain temperament traits may be early predictors of internalizing problems at 5 years of age. Seven hundred and seventy-four infants (360 girls; 88.6% White, 9.8% Hispanic, and 1.6% other races) were recruited from the Boston area. Data collection spanned from 2012 to 2021. The analysis yielded three distinct groups of children with different temperament traits and was associated with significant variation in levels of internalizing symptoms and anxiety diagnosis rate. Our findings suggest that stable temperament "communities" can be detected in early childhood and may predict risk for psychopathology later in life.

Early Adverse Experiences and Repeated Wheezing From 6 to 30 Months of Age: Investigating the Roles of Hypothalamic-Pituitary-Adrenal Axis Functioning, Child Sex, and Caregiving Sensitivity.

This study examined associations among early adversity, diurnal cortisol, child sex, and caregiver sensitivity at age 6 months in relation to wheezing in children (47% male) followed to 30 months. Analyses included 676 mother-child dyads, 393 of whom completed an observational caregiver sensitivity measure. Participants were primarily ethnic minorities (42.7% Black, 25.4% Hispanic); 22.1% of children had ≥ 1 wheezing episode. Higher adversity was associated with increased wheeze frequency and blunted diurnal cortisol slope. The indirect effect of adversity on wheezing through cortisol slope was significant for females, but not males. Higher caregiver sensitivity was protective against wheezing for males, but not females, with high cortisol. Findings suggest complex associations among adversity, cortisol, child sex, and caregiver sensitivity in predicting wheezing.

Associations of Maternal Trait Anger Expression and Lifetime Traumatic and Non-traumatic Experiences with Preterm Birth.

OBJECTIVES: Most studies examining psychosocial factors contributing to preterm birth (PTB) have focused on negative life events. Studies examining the influence of negative emotion, in particular maternal anger, remain sparse. We examined associations of maternal trait anger expression and lifetime traumatic and non-traumatic experiences with the risk of PTB. METHODS: Mother-newborn pairs were enrolled in the PRogramming of Intergenerational Stress Mechanisms pregnancy cohort based in Boston and New York City. Women completed the State-Trait Anger Expression Inventory-2 (STAXI-2), Life Stressor Checklist-Revised (LSC-R), and Childhood Trauma Questionnaire (CTQ) in pregnancy. We used modified Poisson regression to estimate the relative risk (RR) of PTB (1) in relation to continuous STAXI-2 Anger Expression-In (AX-I) and Anger Expression-Out (AX-O) subscales, (2) in relation to continuous LSC-R scores, and (3) between women who did versus did not experience childhood sexual, emotional, and/or physical abuse in six separate models. We also examined interactions between maternal anger expression and lifetime stress/childhood trauma. RESULTS: Younger, single, minority women had higher outward anger expression and inward anger suppression. AX-I and AX-O scores were higher among women who experienced abuse in childhood and who had higher lifetime stress. Maternal lifetime stress, outward anger expression, and inward anger suppression were associated with an increased risk of PTB in separate models; however, stress, trauma and anger did not interact to further increase the risk of PTB. CONCLUSIONS FOR PRACTICE: Higher anger expression and higher lifetime stress experiences were associated with an increased risk of PTB among a racially and ethnically diverse sample of pregnant women.

Maternal experiences of childhood maltreatment moderate patterns of mother-infant cortisol regulation under stress.

The relation between maternal and infant cortisol responses has been a subject of intense research over the past decade. Relatedly, it has been hypothesized that maternal history of childhood maltreatment (MCM) impacts stress regulation across generations. The current study employed four statistical approaches to determine how MCM influences the cortisol responses of 150 mothers and their 4-month-old infants during the Still-Face Paradigm. Results indicated that MCM moderated cortisol patterns in several ways. First, lower MCM mothers and infants had strong positive associations between cortisol levels measured at the same time point, whereas higher MCM mothers and infants did not show an association. Second, infants of higher MCM mothers had cortisol levels that were moderately high and remained elevated over the procedure, whereas infants of lower MCM mothers had decreasing cortisol levels over time. Third, higher MCM mothers and infants showed increasingly divergent cortisol levels over time, compared to lower MCM dyads. Finally, patterns of cross-lagged influence of infant cortisol on subsequent maternal cortisol were moderated by MCM, such that lower MCM mothers were influenced by their infants' cortisol levels at earlier time points than higher MCM mothers. These findings highlight MCM as one contributor to processes of stress regulation in the mother-infant dyad.

Data-driven discovery of mid-pregnancy immune markers associated with maternal lifetime stress: results from an urban pre-birth cohort.

Changes to the maternal inflammatory milieu may be a mechanism through which maternal psychosocial stress is transmitted to the fetus. Research investigating a limited number of immune markers may miss important signals. We take a proteomics approach to investigate maternal lifetime stress and 92 biomarkers of immune system status. Participants were enrolled in an urban, dual-site (Boston, n = 301 and New York City, n = 110) pregnancy cohort. We measured maternal lifetime history of stress and trauma using the validated Life Stressor Checklist-Revised (LSC-R). We measured a panel of 92 immune-related proteins in mid-pregnancy serum using proximity extension assay technology. We leveraged the dual-site study design to perform variable selection and inference within the cohort. First, we used LASSO to select immune markers related to maternal stress among Boston mothers. Then, we performed OLS regression to examine associations between maternal stress and LASSO-selected proteins among New York City mothers. LASSO regression selected 19 immune proteins with non-null coefficients (CCL11, CCL23, CD244, CST5, CXCL1, CXCL5, CXCL10, CX3CL1, FGF-23, IL-5, IL-7, IL-10, IL-17C, MCP-2, MMP-1, SLAMF1, ST1A1, TNF-ß, and TWEAK). Of these, only the chemotactic cytokine CX3CL1 (i.e. fractalkine) was significantly associated with maternal stress among the validation sample (percent change in LSC-R score per 1% increase in relative fractalkine expression: 0.74, 95% confidence interval: 0.19, 1.28). Expanding research suggests fractalkine plays an important role in many aspects of pregnancy and fetal development and is stress-sensitive. We found that maternal lifetime history of stress and trauma was significantly associated with elevated serum fractalkine levels during pregnancy.

Pathways to social-emotional functioning in the preschool period: The role of child temperament and maternal anxiety in boys and girls.

Individual differences in social-emotional functioning emerge early and have long-term implications for developmental adaptation and competency. Research is needed that specifies multiple early risk factors and outcomes simultaneously to demonstrate specificity. Using multigroup longitudinal path analysis in a sample of typically developing children (N = 541), we examined child temperament dimensions (surgency, negative affectivity, and regulation/effortful control) and maternal anxiety in infancy and age 2 as predictors of child externalizing, internalizing, dysregulation, and competence behaviors at age 3. Four primary patterns emerged. First, there was stability in temperament dimensions and maternal anxiety from infancy to age 3. Second, negative affectivity was implicated in internalizing problems and surgency in externalizing problems. Third, effortful control at age 2 was a potent mediator of maternal anxiety in infancy on age 3 outcomes. Fourth, there was suggestive evidence for transactional effects between maternal anxiety and child effortful control. Most pathways operated similarly for boys and girls, with some differences, particularly for surgency. These findings expand our understanding of the roles of specific temperamental domains and postnatal maternal anxiety in a range of social-emotional outcomes in the preschool period, and have implications for efforts to enhance the development of young children's social-emotional functioning and reduce risk for later psychopathology.

Hair cortisol in pregnancy interacts with maternal depressive symptoms to predict maternal disrupted interaction with her infant at 4 months.

Disrupted maternal interaction in early infancy is associated with maladaptive child outcomes. Thus, identifying early risk factors for disrupted interaction is an important challenge. Research suggests that maternal depressive symptoms and maternal cortisol dysregulation are associated with disrupted maternal interaction, but both factors have rarely been considered together as independent or interactive predictors of disrupted interaction. In a sample of 51 women, hair cortisol concentrations (HCC) and depressive symptoms were assessed during pregnancy, and depressive symptoms were assessed again at 4-month postpartum. Maternal disrupted interaction was assessed during the Still-Face Paradigm at 4 months. Results indicated that HCC and depressive symptoms interacted to predict both maternal withdrawing and inappropriate/intrusive interaction. Withdrawing interaction was associated with high levels of HCC in pregnancy in the context of high depressive symptoms at 4 months; inappropriate/intrusive interaction was associated with high levels of HCC in the context of low depressive symptoms. Thus, high HCC potentiated both forms of disrupted interaction. Results raised questions about the meaning of very low reported depressive symptoms, and underscored the importance of chronic stress physiology and maternal depressed mood as risk factors for distinct forms of maternal disrupted interaction, both of which are deleterious for infant development.

Sex-specific associations between prenatal negative life events and birth outcomes.

Maternal psychosocial stress can negatively impact gestational length and development of the fetus. These effects may be sex-specific but have not been extensively studied. The objective of this study was to examine the associations between prenatal maternal stress and birth outcomes and whether effects are modified by sex. Prenatal maternal stress was indexed by a maternal negative life events (NLEs) score ascertained in 527 urban mothers; a higher NLE score indicates greater stress. Birth outcomes included gestational age, preterm birth (PTB) (<37 weeks), and birthweight for gestational age z-scores. Modified Poisson regression and linear models were used to evaluate associations of prenatal NLE scores with birth outcomes. Sex differences were assessed by inclusion of an interaction term for sex by NLE score and in sex-stratified analyses. In analyses adjusted for maternal age, education, race/ethnicity, and pre-pregnancy body mass index (BMI), increasing prenatal stress was associated with shortened gestational age (days) (ß = -0.63, [95% CI -1.20, -0.06]). This effect was sex specific, with increasing prenatal stress associated with shortened gestational age, as well as increased risk of PTB, in male infants (ß = -1.35 [95% CI -2.17, -0.54] and RR = 1.18 [95% CI 0.99, 1.42], respectively) but not female infants (ß = 0.15 [95%CI -0.63, 0.94] and RR = 0.85, [95%CI 0.65, 1.11], respectively). Prenatal stress was not associated with birthweight z-scores. Our results support the importance of psychosocial stress as a programming factor that may have sex-specific effects for adverse fetal outcomes. Understanding sex-specific effects of prenatal stress on birth outcomes may inform prevention strategies. LAY SUMMARY Higher stress experienced by mothers in pregnancy was associated with shorter length of pregnancy and the effect was stronger in male infants when compared to female infants.

Maternal Childhood Maltreatment History and Child Mental Health: Mechanisms in Intergenerational Effects.

The objectives of this study were to examine whether a maternal history of maltreatment in childhood has a detrimental impact on young children's mental health and to test theoretically and empirically informed pathways by which maternal history may influence child mental health. Mother-child dyads (N = 187) were evaluated between birth and 64 months of age via home and laboratory observations, medical and child protection record reviews, and maternal interviews to assess maternal history of childhood maltreatment and microsystem and exosystem measures of the caregiving context, including child maltreatment, maternal caregiving quality, stress exposures, and social support. When the children were 7 years of age, mothers and teachers reported on child emotional and behavioral problems. Analyses examined whether the caregiving context variables linked maternal maltreatment history with child emotional and behavioral problems, controlling for child sex (54% male), race/ethnicity (63% White), and family sociodemographic risk at birth. Maltreated mothers experienced greater stress and diminished social support, and their children were more likely to be maltreated across early childhood. By age 7, children of maltreated mothers were at increased risk for clinically significant emotional and behavioral problems. A path analysis model showed mediation of the effects of maternal childhood maltreatment history on child symptoms, with specific effects significant for child maltreatment. Interventions that reduce child maltreatment risk and stress exposures and increase family social support may prevent deleterious effects of maternal childhood maltreatment history on child mental health.

Maternal Lifetime Stress and Prenatal Psychological Functioning and Decreased Placental Mitochondrial DNA Copy Number in the PRISM Study.

Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health.

Mother-infant attachment and the intergenerational transmission of posttraumatic stress disorder.

Evidence for the intergenerational transmission of posttraumatic stress disorder (PTSD) is documented in the literature, although the underlying mechanisms are poorly understood. Attachment theory provides a framework for elucidating the ways in which maternal PTSD may increase offspring PTSD vulnerability. The current study utilized two independent prospective data sets to test the hypotheses that (a) maternal PTSD increases the probability of developing an insecure mother-infant attachment relationship and (b) an insecure mother-infant attachment relationship increases the risk of developing PTSD following trauma exposure in later life. In the first study of urban, primarily low-income ethnic/racial minority mothers and infants (N = 45 dyads), elevated maternal PTSD symptoms at 6 months were associated with increased risk for an insecure, particularly disorganized, mother-infant attachment relationship at 13 months. In the second birth cohort of urban, low-income mothers and children (N = 96 dyads), insecure (avoidant or resistant) attachment in infancy was associated in a dose-response manner with increased lifetime risk for a diagnosis of PTSD by adolescence. A history of disorganized attachment in infancy predicted severity of PTSD symptoms, including reexperiencing, avoidance, hyperarousal, and total symptoms, at 17.5 years. In both studies, associations between attachment and PTSD were not attributable to numerous co-occurring risk factors. The findings suggest that promoting positive mother-child relationships in early development, particularly in populations at high risk for trauma exposure, may reduce the incidence of PTSD.