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1.  Stress-Related Programming of Autonomic Imbalance: Role in Allergy and Asthma 
Evidence linking psychological stress to allergy has grown with our increased understanding of the natural history and pathophysiology of these disorders and the neurobiology of stress vulnerability. However, the specific pathways that increase vulnerability to developing allergy and associated disorders remain to be elucidated. Autonomic nervous system functioning (autonomic balance) has been implicated in allergy for some time albeit links between autonomic balance and immune function in early development have been under studied. Starting in utero, stress may influence the programming of brain neurotransmitter systems, sympathetic and parasympathetic nervous system functioning, and the hypothalamic-pituitary-adrenal axis, which in turn may alter neural regulation of immune function. Epigenetic dysregulation of gene expression may be a fundamental mechanism for programming of early neural-immune processes.
PMCID: PMC3888825  PMID: 22767056
2.  Association between birth weight and DNA methylation of IGF2, glucocorticoid receptor and repetitive elements LINE-1 and Alu 
Epigenomics  2013;5(3):271-281.
We examined the association between birth weight and methylation in the imprinted IGF/H19 loci, the nonimprinted gene NR3C1 and repetitive element DNA (LINE-1 and Alu).
Materials & methods
We collected umbilical cord venous blood from 219 infants born in Mexico City (Mexico) as part of a prospective birth cohort study and analyzed DNA methylation using pyrosequencing.
Birth weight was not associated with DNA methylation of the regions studied. One of the CpG dinucleotides in the IGF2 imprinting control region (ICR)1 includes a potential C–T SNP. Among individuals with an absence of methylation at this site, probably due to a paternally inherited T allele, birth weight was associated with mean methylation status of both IGF2 ICR1 and ICR2. However, this association would not have survived adjustment for multiple testing.
While we did not detect an association between DNA methylation and birth weight, our study suggests a potential gene–epigene interaction between a T allele in the IGF2 ICR1 and methylation of ICRs of IGF2, and fetal growth.
PMCID: PMC3787720  PMID: 23750643
Alu; birth weight; DNA methylation; fetal growth; glucocorticoid receptor; IGF2; imprinting; LINE-1; NR3C1; SNP
3.  Childhood Abuse and Age at Menarche 
Physical and sexual abuse are prevalent social hazards. We sought to examine the association between childhood physical and sexual abuse and age at menarche.
Among 68,505 participants enrolled in the Nurses’ Health Study II we investigated the association between childhood physical abuse and sexual abuse on menarche prior to age 11 (early) or after age 15 (late) using multivariate logistic regression analysis, mutually adjusting for both types of abuse.
Fifty-seven percent of respondents reported some form of physical or sexual abuse in childhood. We found a positive dose-response association between severity of sexual abuse in childhood and risk for early menarche. Compared to women who reported no childhood sexual abuse, the adjusted odds ratio [AOR] for early menarche was 1.20 (95% confidence interval [CI], 1.10, 1.37) for sexual touching and 1.49 (95% CI, 1.34, 1.66) for forced sexual activity. Only severe physical abuse predicted early menarche (AOR=1.22, 95% CI, 1.10–1.37). Childhood physical abuse had a dose-response association with late age at menarche: AOR 1.17 (95% CI, 1.04, 1.32) for mild, 1.20 (95% CI, 1.08, 1.33) for moderate, and 1.50 (95% CI, 1.27, 1.77) for severe physical abuse. Sexual abuse was not associated with late menarche.
Childhood abuse was very prevalent in this large cohort of U.S. women. Severity of childhood sexual abuse was associated with risk for early onset of menarche, and physical abuse was associated with both early and late onset menarche.
Implications and Contribution
The severity of childhood sexual abuse and severe physical abuse were associated with risk for accelerated menarche, while severity of childhood physical was associated with risk for delayed onset of menarche. The nature of the association between different forms of childhood adversities and reproductive lifespan may vary.
PMCID: PMC3950206  PMID: 23332491
menarche; adversities; child abuse; emotional support
4.  Child Abuse and Smoking Among Young Women: The Importance of Severity, Accumulation, and Timing 
We examined the association between severity, accumulation, and timing of abuse in childhood and adolescence and smoking status among young women.
Retrospective self-reported childhood abuse was ascertained with the modified Conflict Tactics Scale from 91,286 Nurses Health Study II participants in 2001 (68,505 returned; 75.0% response rate). Childhood abuse was categorized by severity (mile/moderate/severe), type (physical/sexual), and timing (childhood/adolescence). Smoking status during adolescence was reported at baseline (1989). Logistic regression was used to predict smoking initiation by age 14 and smoking status between the ages of 15 and 19.
A graded association between severity of abuse and early initiation of smoking (by age 14 years) was demonstrated (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.7–2.1 for severe physical violence). Young women with both physical and sexual abuse were two times more likely to start smoking by age 14 than were those reporting no abuse (OR = 2.0, 95% CI = 1.8–2.3). Although abuse during childhood increased risk for adolescent smoking (OR = 1.7, 95% CI = 1.8–2.1) for those with childhood physical and sexual abuse, inclusion of adolescent physical and sexual abuse (OR = 2.2, 95% CI 2.1–2.4) diminished the impact of childhood abuse (OR = 1.1, 95% CI 1.1–1.2). The degree of familial emotional support was protective against smoking, and reduced the impact of abuse by 40% among those with high emotional support versus those without (p < .0001).
A strong and graded association was observed between both severity and accumulation of abuse and the risk of early initiation of smoking among girls. Smoking status during late adolescence was more strongly associated with adolescent abuse than childhood abuse. Early smoking onset is associated with both heightened risk for disease in adolescence but also increased morbidity and mortality in adulthood. Identifying and intervening in potentially modifiable risk factors for smoking onset in young women, such as early-life physical and sexual abuse, and building familial strengths, such as emotional support, may have significant public health implications.
PMCID: PMC3932335  PMID: 18565438
Smoking initiation; Childhood abuse; Young women
5.  Disparities in Child Abuse Victimization in Lesbian, Bisexual, and Heterosexual Women in the Nurses’ Health Study II 
Journal of women's health (2002)  2008;17(4):597-606.
A growing body of research documents multiple health disparities by sexual orientation among women, yet little is known about the possible causes of these disparities. One underlying factor may be heightened risk for abuse victimization in childhood in lesbian and bisexual women. Using survey data from 63,028 women participating in the Nurses’ Health Study II, we investigated sexual orientation group differences in emotional, physical, and sexual abuse in childhood and adolescence. Multivariable log-binomial and linear regression models were used to examine orientation group differences in prevalence and severity of abuse, with heterosexual as the referent and controlling for sociodemographics. Results showed strong evidence of elevated frequency, severity, and persistence of abuse experienced by lesbian and bisexual women. Comparing physical abuse victimization occurring in both childhood and adolescence, lesbian (30%; prevalence ratio [PR] 1.61; 95% confidence interval [CI] 1.40, 1.84) and bisexual (24%; PR 1.26; 95% CI 1.00, 1.60) women were more likely to report victimization than were heterosexual women (19%). Similarly, comparing sexual abuse victimization occurring in both age periods, lesbian (19%; PR 2.16; 95% CI 1.80, 2.60) and bisexual (20%; PR 2.29; 95% CI 1.76, 2.98) women were more likely to report victimization than were heterosexual women (9%). This study documents prevalent and persistent abuse disproportionately experienced by lesbian and bisexual women.
PMCID: PMC3912575  PMID: 18447763
bisexual; child abuse; lesbian; sexual orientation; victimization
6.  Interpersonal Trauma Exposure and Cognitive Development in Children to Age 8 Years: A Longitudinal Study 
Childhood trauma exposure has been associated with deficits in cognitive functioning. The influence of timing of exposure on the magnitude and persistence of deficits is not well understood. The impact of exposure in early development has been especially under-investigated. This study examined the impact of interpersonal trauma exposure (IPT) in the first years of life on childhood cognitive functioning.
Children (N = 206) participating in a longitudinal birth cohort study were assessed prospectively for exposure to IPT (physical or emotional abuse or neglect, sexual abuse, witnessing maternal partner violence) between birth and 64 months. Child intelligent quotient scores (IQ) were assessed at 24, 64, and 96 months of age. Race/ethnicity, gender, socioeconomic status, maternal IQ, birth complications, birthweight, and cognitive stimulation in the home were also assessed.
IPT was significantly associated with decreased cognitive scores at all time points, even after controlling for sociodemographic factors, maternal IQ, birth complications, birthweight, and cognitive stimulation in the home. IPT in the first two years appeared to be especially detrimental. On average, compared to children not exposed to IPT in the first two years, exposed children scored one-half standard deviation lower across cognitive assessments.
IPT in early life may have adverse effects on cognitive development. IPT during the first two years may have particular impact, with effects persisting at least into later childhood.
PMCID: PMC3731065  PMID: 22493459
cognitive development; IQ; trauma; child abuse; domestic violence
7.  Perinatal stress and early life programming of lung structure and function 
Biological psychology  2010;84(1):46-56.
Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding.
PMCID: PMC2888999  PMID: 20080145
maternal prenatal stress; postnatal stress; programming; hypothalamic-pituitary-adrenal axis; immunomodulation; autonomic nervous system; lung function; airway inflammation; airway hyperresponsiveness
8.  Women who remember, women who do not: A methodological study of maternal recall of smoking in pregnancy 
Nicotine & Tobacco Research  2009;11(10):1166-1174.
Retrospective recall of smoking during pregnancy is assumed to be substantially biased, but this has rarely been tested empirically.
We examined the validity of an interview-based retrospective recall more than a decade after pregnancy, in a cohort with repeated, multimethod characterization of pregnancy smoking (N = 245). Retrospective smoking patterns were examined in relation to prospective reported and biological estimates of overall and trimester-specific smoking status and intensity. We also compared characteristics of women whose smoking status was misclassified by either prospective or retrospective measures with women whose status was congruent for nonsmoking across timepoints.
In general, sensitivity and specificity of recalled smoking were excellent relative to both prospective self-reported and cotinine-validated smoking status and trimester-specific intensity. However, measures were less congruent for amount smoked for women who recalled being heavy smokers. Further, retrospective measures captured some smokers not identified prospectively due to smoking that occurred prior to assessments. Women who would have been misclassified as nonsmokers based on either prospective or retrospective assessment differed significantly from congruently classified nonsmokers in a number of maternal, family, and neighborhood, but not child behavior, characteristics.
When epidemiological studies of the impact of smoking in pregnancy use retrospective methods, misclassification may not be a significant problem if prenatal smoking is assessed in terms of the pattern across pregnancy. This type of interview-based recall of pregnancy smoking may be relatively accurate, although optimal measurement should combine retrospective and prospective self-report and biological assays, as each provide unique information and sources of error.
PMCID: PMC2746835  PMID: 19640836
9.  Moving towards making social toxins mainstream in children’s environmental health 
Current opinion in pediatrics  2009;21(2):222-229.
Purpose of Review
While traditional disciplinary research theory and methods have focused separately on how social and physical environmental factors affect children’s health, evolving research underscores important integrated effects.
Recent findings
This review outlines the specific reasons why social determinants should be considered mainstream in children’s environmental health research with particular focus on interactive effects between social and physical hazards. These include (a) sensitivity of overlapping physiological systems, via epigenesis, programming, and plasticity to social and physical environmental moderation that may impact health across the life span; (b) ways in which social environmental vulnerabilities moderate the effects of physical environmental factors providing specific examples related to respiratory health and neurodevelopment; (c) overlapping exposure distribution profiles; and (d) relevance to pediatric health disparities.
Because of the covariance across exposures and evidence that social stress and other environmental toxins (e.g., pollutants, tobacco smoke) may influence common physiological pathways (e.g., oxidative stress, pro-inflammatory immune pathways, autonomic disruption), understanding the potential synergistic effects promises to more completely inform children’s environmental health risk. While this discussion focuses around the respiratory and neurological systems, these concepts extend more broadly to children’s psychological and physical development.
PMCID: PMC2752500  PMID: 19300262
children; social toxins; physical hazards; health disparities
10.  Posttraumatic stress disorder across two generations: concordance and mechanisms in a population-based sample 
Biological psychiatry  2012;72(6):505-511.
Research conducted using small samples of persons exposed to extreme stressors has documented an association between parental and offspring posttraumatic stress disorder (PTSD), but it is unknown whether this association exists in the general population and whether trauma exposure mediates this association. We sought to determine whether mothers’ posttraumatic stress symptoms were associated with PTSD in their young adult children and whether this association was mediated by higher trauma exposure in children of women with PTSD.
Using data from a cohort of mothers (n=6924) and a cohort of their children (n=8453), we calculated risk ratios (RR) for child’s PTSD and examined mediation by trauma exposure.
Mother’s lifetime posttraumatic stress symptoms were associated with child’s PTSD in dose-response fashion (mother’s 1 to 3 symptoms, child’s RR=1.2; mother’s 4-5 symptoms, RR=1.3; mother’s 6-7 symptoms, RR=1.6, compared to children of mothers with no symptoms, p<0.001 for each). Mother’s lifetime symptoms were also associated with child’s trauma exposure in dose-response fashion. Elevated exposure to trauma substantially mediated elevated risk for PTSD in children of women with symptoms (mediation proportion, 74%, p<0.001).
Intergenerational association of PTSD is clearly present in a large population-based sample. Children of women who had PTSD were more likely than children of women without PTSD to experience traumatic events; this suggests, in part, why the disorder is associated across generations. Health care providers who treat mothers with PTSD should be aware of the higher risk for trauma exposure and PTSD in their children.
PMCID: PMC3412195  PMID: 22521146
Posttraumatic stress disorder; trauma; childhood abuse; epidemiology; family studies; violence
11.  Maternal interpersonal trauma and cord blood IgE levels in an inner-city cohort: A life-course perspective 
Prenatal stress affects immunocompetence in offspring, although the underlying mechanisms are not well understood.
We sought to examine associations between maternal lifetime interpersonal trauma (IPT) and cord blood total IgE levels in a sample of urban newborns (n = 478).
Maternal IPT during childhood and adolescence (birth to 17 years), adulthood (18 years to index pregnancy), and the index pregnancy were ascertained by using the Revised Conflict Tactics Scale at 28.4 ± 7.9 weeks’ gestation. Cord blood IgE levels were derived by using a fluoroenzyme immunoassay. We examined effects of maternal IPT on increased cord blood IgE levels (upper quartile, 1.08 IU/mL) by using logistic regression, adjusting for confounders and mediating variables.
Maternal trauma was categorized as unexposed (n = 285 [60%]), early (childhood and/or teenage years only, n = 107 [22%]), late (adulthood and/or index pregnancy only, n = 29 [6%]), and chronic (early and late, n = 57 [12%]) exposure. Relative to no IPT, early (odds ratio [OR], 1.78; 95% CI, 1.05–3.00) and chronic maternal IPT (OR, 2.25; 95% CI, 1.19–4.24) were independently associated with increased IgE levels in unadjusted analyses. When adjusting for standard controls, including maternal age and race, season of birth, child’s sex, and childhood and current socioeconomic status, early effects became nonsignificant (OR, 1.48; 95% CI, 0.85–2.58). Chronic exposure remained significant in fully adjusted models, including standard controls, current negative life events, allergen exposure, and potential pathway variables (maternal atopy, prenatal smoking, and birth weight; OR, 2.18; 95% CI, 1.06–4.50).
These data link chronic trauma over the mother’s life course with increased IgE levels in infants at birth. Research examining associations between maternal trauma and indicators of offspring’s atopic risk might be particularly relevant in inner-city high-risk populations. (J Allergy Clin Immunol 2009;124:954–60.)
PMCID: PMC3744584  PMID: 19748657
Interpersonal trauma; life course; pregnancy; cord blood IgE; urban asthma
12.  Growing up in a domestic violence environment: relationship with developmental trajectories of body mass index during adolescence into young adulthood 
This study investigated the relationship between growing up in a violent home and developmental trajectories of body mass index (BMI) in a cohort of adolescents followed longitudinally from 1996 to 2003-4.
6,043 girls and 4,934 boys aged 9–14 years in 1996 who reported height and weight at least two times and whose mothers completed intimate partner violence (IPV) questions at the 2001 Nurses’ Health Study. Main exposure was experiencing the first family violence during early (0–5 years) or later (6–11 years) childhood, based on mother’s year-specific exposure of IPV and the birth year of each participant. Mother’s report of IPV was ascertained by the abuse assessment screen. Four distinct BMI trajectory groups were estimated from age-specific BMI (age 12–20 years), using general growth mixture modeling.
Four distinct BMI trajectories were identified separately for girls and boys: healthy growth; healthy to obese; steady overweight and consistently obese. Compared with boys not exposed to violence at home, boys raised in violent homes before 5 years were at increased risk of being in the consistently obese (OR =2.0; 95% CI 1.2 to 3.5) and steady overweight (OR 1.4; 95% CI 1.1 to 1.9) groups after adjusting for confounders. Girls raised in violent homes were more likely to be in the steady overweight group, but associations did not maintain statistical significance after adjusting for confounding.
These data link children’s exposure to domestic violence to a risk of unhealthy weight trajectories during adolescence in boys. Detrimental effects of exposure to a domestic violence environment may take root in the first few years of development for boys.
PMCID: PMC3734797  PMID: 21296904
13.  Prenatal and Postnatal Maternal Stress and Wheeze in Urban Children 
Rationale: Critical periods for programming early wheeze risk may include pregnancy and infancy. Effects of timing remain poorly understood.
Objectives: Associations among prenatal and postnatal maternal stress and children’s wheeze were prospectively examined in 653 families. Effect modification by maternal sensitization was also examined.
Methods: Stress was indexed by a maternal negative life events (NLEs) score (range, 0–9) ascertained during pregnancy and between 1 and 2 years postpartum. Mothers reported child wheeze every 3 months up to age 2 years. Relationships of prenatal and postnatal maternal NLEs with repeated wheeze (≥2 episodes) were examined using logistic regression adjusting for covariates. Penalized splines were implemented to explore possible nonlinear associations. We also examined the interaction between prenatal stress and maternal sensitization indexed by allergen-specific IgE from maternal prenatal serum.
Measurements and Main Results: Adjusted models considering prenatal or postnatal NLEs alone both showed an exposure-response relationship between higher stress and child wheeze. When considering prenatal and postnatal stress concurrently, only children of mothers with high stress in both periods were significantly more likely to wheeze (adjusted odds ratio, 3.04; 95% confidence interval, 1.67–5.53) than children of mothers reporting low stress in both periods. Associations between high prenatal stress and wheeze were significant in children born to nonsensitized mothers (any IgE <0.35 kU/L) but not in the sensitized group (P for interaction = 0.03).
Conclusions: Although children have heightened sensitivity to maternal stress in utero and in early childhood, those with higher stress in both periods were particularly at risk for wheeze. The prenatal maternal immune milieu modified effects.
PMCID: PMC3406080  PMID: 22582161
negative life events; stress; pregnancy; maternal sensitization; childhood wheeze
14.  Cumulative stress and maternal prenatal corticotropin-releasing hormone in an urban U.S. cohort 
Psychoneuroendocrinology  2011;37(7):970-979.
To date, there have been conflicting reports of the association of psychosocial stressors with prenatal corticotropin-releasing hormone (CRH) levels.
We examined whether racial discrimination, community violence, interpersonal violence (IPV), negative life events, considered independently, and as a composite measure of cumulative stress, were associated with prenatal CRH levels in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a multiethnic pre-birth cohort in urban Boston. Blood was collected between 20 and 37 weeks gestation (Mean = 28.1, SD = 4.6 weeks gestation). During pregnancy, women were administered the Conflict Tactics Scale survey to assess IPV, the Crisis in Family Systems-Revised survey to assess negative life events, the My Exposure to Violence survey to assess community violence, and the Experiences of Discrimination survey. A cumulative stress measure was derived from these instruments to characterize exposure to high levels of multiple stressors.
None of the individual stressors or cumulative stress was associated with CRH in combined analyses including Whites (n=20), Blacks (n=46), and Hispanics (n=110). In separate analyses of Blacks and Hispanics, racial discrimination, community violence, and cumulative stress were associated with CRH in Blacks, but were not associated with CRH in Hispanics.
Though these results require replication, they suggest that the effects of stress on prenatal CRH levels may be mediated by factors that differ between racial/ethnic groups. Further studies in larger samples are warranted to clarify whether associations of chronic stressors and prenatal CRH levels differ by race/ethnicity and to better understand underlying mechanisms.
PMCID: PMC3400107  PMID: 22154479
15.  Associations between Traffic-Related Black Carbon Exposure and Attention in a Prospective Birth Cohort of Urban Children 
Environmental Health Perspectives  2013;121(7):859-864.
Background: Ambient air pollution may have neurotoxic effects in children. Data examining associations between traffic-related air pollution and attention domains remain sparse.
Objectives: We examined associations between black carbon (BC), a marker of traffic particles, and attention measures ascertained at 7–14 years of age among 174 children in a birth cohort based in the Boston, Massachusetts, area.
Methods: We estimated BC levels using a validated spatial–temporal land-use regression model based on residence during children’s lifetime. Children completed the Conner’s Continuous Performance Test (CPT) measuring omission errors, commission errors, and hit reaction time (HRT), with higher scores indicating increased errors or slower reaction time. Multivariable-adjusted linear regression analyses were used to examine associations between BC and each attention outcome.
Results: Children were primarily Hispanic (56%) and Caucasian (41%); 53% were boys. We found a positive association between higher BC levels with increased commission errors and slower HRT, adjusting for child IQ, age, sex, blood lead level, maternal education, pre- and postnatal tobacco smoke exposure, and community-level social stress. Notably, the association was weaker, though still positive, for the highest BC quartile relative to the middle two quartiles. Sex-stratified analysis demonstrated statistically significant associations between BC and both commission errors and HRT in boys, but BC was not significantly associated with any of the CPT outcomes in girls.
Conclusions: In this population of urban children, we found associations between BC exposure and higher commission errors and slower reaction time. These associations were overall more apparent in boys than girls.
PMCID: PMC3701996  PMID: 23665743
attention; children; Conners’ Continuous Performance Test; hit reaction time; traffic-related air pollution; urban
16.  The stressor criterion for posttraumatic stress disorder: Does it matter? 
The Journal of clinical psychiatry  2012;73(2):e264-e270.
The definition of the stressor criterion for posttraumatic stress disorder (“Criterion A1”) is hotly debated with major revisions being considered for DSM-V. We examine whether symptoms, course, and consequences of PTSD vary predictably with the type of stressful event that precipitates symptoms.
We used data from the 2009 PTSD diagnostic subsample (N=3,013) of the Nurses Health Study II. We asked respondents about exposure to stressful events qualifying under 1) DSM-III, 2) DSM-IV, or 3) not qualifying under DSM Criterion A1. Respondents selected the event they considered worst and reported subsequent PTSD symptoms. Among participants who met all other DSM-IV PTSD criteria, we compared distress, symptom severity, duration, impairment, receipt of professional help, and nine physical, behavioral, and psychiatric sequelae (e.g. physical functioning, unemployment, depression) by precipitating event group. Various assessment tools were used to determine fulfillment of PTSD Criteria B through F and to assess these 14 outcomes.
Participants with PTSD from DSM-III events reported on average 1 more symptom (DSM-III mean=11.8 symptoms, DSM-IV=10.7, non-DSM=10.9) and more often reported symptoms lasted one year or longer compared to participants with PTSD from other groups. However, sequelae of PTSD did not vary systematically with precipitating event type.
Results indicate the stressor criterion as defined by the DSM may not be informative in characterizing PTSD symptoms and sequelae. In the context of ongoing DSM-V revision, these results suggest that Criterion A1 could be expanded in DSM-V without much consequence for our understanding of PTSD phenomenology. Events not considered qualifying stressors under the DSM produced PTSD as consequential as PTSD following DSM-III events, suggesting PTSD may be an aberrantly severe but nonspecific stress response syndrome.
PMCID: PMC3687542  PMID: 22401487
Criterion A; posttraumatic stress disorder; nosology; stress response syndromes; trauma exposure; diagnosis
17.  Prenatal negative life events increases cord blood IgE: Interactions with dust mite allergen and maternal atopy 
Allergy  2012;67(4):545-551.
Prenatal exposure to both stress and aeroallergens (dust mite) may modulate the fetal immune system. These exposures may interact to affect the newborn immune response. We examined associations between prenatal maternal stress and cord blood total IgE in 403 predominately low-income minority infants enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project. We also examined potential modifying effects of maternal atopy and maternal dust mite exposure.
The Crisis in Family Systems survey was administered to mothers prenatally and a negative life event domain score was derived to characterize stress. Dust mite allergen was quantified in dust from pregnant mothers’ bedrooms. Cord blood was analyzed for total IgE. Using linear regression, we modeled the relationship of stress with cord blood IgE and interactions of stress with dust mite and/or maternal atopy, adjusting for potential confounders.
Higher prenatal maternal stress (β=0.09; P=0.01) was associated with increased cord blood IgE. The interactive effects between stress and dust mite groups (high vs. low) were significantly different for children of atopic vs. nonatopic mothers (p for three-way interaction =0.005). Among children of atopic mothers, the positive association between stress and IgE was stronger in the high dust mite group. In children of mothers without a history of atopy, the positive association between stress and IgE was most evident in the low allergen group.
Prenatal stress was independently associated with elevated cord blood IgE. Mechanisms underlying stress effects on fetal immunomodulation may differ based on maternal atopic status.
PMCID: PMC3303977  PMID: 22309645
Allergens; cord blood IgE; dust mite; prenatal stress; urban
18.  Associations among maternal childhood socioeconomic status, cord blood IgE levels, and repeated wheeze in urban children 
Independent of current socioeconomic status (SES), past maternal SES might influence asthma outcomes in children.
We examined associations among the mother’s SES in the first 10 years of her life (maternal childhood SES), increased cord blood IgE levels (upper 20% [1.37 IU/mL]), and repeated wheeze (≥2 episodes by age 2 years) in an urban pregnancy cohort (n = 510).
Data on sociodemographics, discrimination, financial strain, community violence, interpersonal trauma, and other negative events were obtained prenatally. Prenatal household dust was assayed for cockroach and murine allergens, and traffic-related air pollution was estimated by using spatiotemporal land-use regression. Maternal childhood SES was defined by parental home ownership (birth to 10 years). Maternally reported child wheeze was ascertained at 3-month intervals from birth. Using structural equation models, we examined whether outcomes were dependent on maternal childhood SES directly versus indirect relationships operating through (1) cumulative SES-related adversities, (2) the mother’s socioeconomic trajectory (adult SES), and (3) current prenatal environmental exposures.
Mothers were largely Hispanic (60%) or black (28%), 37% had not completed high school, and 56% reported parental home ownership. When associations between low maternal childhood SES and repeated wheeze were examined, there were significant indirect effects operating through adult SES and prenatal cumulative stress (β = 0.28, P = .003) and pollution (β = 0.24, P = .004; P value for total indirect effects ≤ .04 for both pathways). Low maternal childhood SES was directly related to increased cord blood IgE levels (β = 0.21, P = .003). Maternal cumulative adversity (interpersonal trauma) was also associated with increased cord blood IgE levels (β = 0.19, P = .01), although this did not explain maternal childhood SES effects.
Lower maternal childhood SES was associated with increased cord blood IgE levels and repeated wheeze through both direct and indirect effects, providing new insights into the role of social inequalities as determinants of childhood respiratory risk.
PMCID: PMC3593081  PMID: 21704362
Childhood socioeconomic status; intergenerational; cord blood IgE; inner-city; childhood wheeze; structural equation models; life course
19.  Respiratory Sinus Arrhythmia as an Index of Vagal Activity during Stress in Infants: Respiratory Influences and Their Control 
PLoS ONE  2012;7(12):e52729.
Respiratory sinus arrhythmia (RSA) is related to cardiac vagal outflow and the respiratory pattern. Prior infant studies have not systematically examined respiration rate and tidal volume influences on infant RSA or the extent to which infants' breathing is too fast to extract a valid RSA. We therefore monitored cardiac activity, respiration, and physical activity in 23 six-month old infants during a standardized laboratory stressor protocol. On average, 12.6% (range 0–58.2%) of analyzed breaths were too short for RSA extraction. Higher respiration rate was associated with lower RSA amplitude in most infants, and lower tidal volume was associated with lower RSA amplitude in some infants. RSA amplitude corrected for respiration rate and tidal volume influences showed theoretically expected strong reductions during stress, whereas performance of uncorrected RSA was less consistent. We conclude that stress-induced changes of peak-valley RSA and effects of variations in breathing patterns on RSA can be determined for a representative percentage of infant breaths. As expected, breathing substantially affects infant RSA and needs to be considered in studies of infant psychophysiology.
PMCID: PMC3530477  PMID: 23300753
20.  Maternal Posttraumatic Stress Symptoms and Infant Emotional Reactivity and Emotion Regulation 
Infant behavior & development  2011;34(4):487-503.
The current study examined associations between maternal posttraumatic stress disorder (PTSD) symptoms and infant emotional reactivity and emotion regulation during the first year of life in a primarily low-income, urban, ethnic/racial minority sample of 52 mother-infant dyads. Mothers completed questionnaires assessing their own trauma exposure history and current PTSD and depressive symptoms and their infants’ temperament when the infants were 6 months old. Dyads participated in the repeated Still-Face Paradigm (SFP-R) when the infants were 6 months old, and infant affective states were coded for each SFP-R episode. Mothers completed questionnaires assessing infant trauma exposure history and infant current emotional and behavioral symptoms when the infants were 13 months old. Maternal PTSD symptoms predicted infants’ emotion regulation at 6 months as assessed by (a) infant ability to recover from distress during the SFP-R and (b) maternal report of infant rate of recovery from distress/arousal in daily life. Maternal PTSD symptoms also predicted maternal report of infant externalizing, internalizing, and dysregulation symptoms at 13 months. Maternal PTSD was not associated with measures of infant emotional reactivity. Neither maternal depressive symptoms nor infant direct exposure to trauma accounted for the associations between maternal PTSD symptoms and infant outcomes. These findings suggest that maternal PTSD is associated with offspring emotion regulation difficulties as early as infancy. Such difficulties may contribute to increased risk of mental health problems among children of mothers with PTSD.
PMCID: PMC3180882  PMID: 21862136
infant; emotion regulation; reactivity; maternal PTSD
21.  Social Determinants: Taking the Social Context of Asthma Seriously 
Pediatrics  2009;123(Suppl 3):S174-S184.
While asthma has emerged as a major contributor to disease and disability in American children, the burden of this disease is unevenly distributed within the population. This paper provides a brief overview of social status variables that predict variation in asthma risks and social exposures such as stress and violence that are emerging as important risk factors. However, the central focus of the paper is on the distal social variables that have given rise to unhealthy residential environments in which the risk factors for asthma and other diseases are clustered. Effective initiatives for the prevention and treatment of childhood asthma need to address these non-medical determinants of the prevalence of asthma.
PMCID: PMC3489274  PMID: 19221161
childhood asthma prevalence; low-income population; poverty; race; risk factors
23.  Lifetime maternal experiences of abuse and risk of pre-natal depression in two demographically distinct populations in Boston 
Background To investigate lifetime history of interpersonal abuse and risk of pre-natal depression in socio-economically distinct populations in the same city.
Methods We examined associations of physical and sexual abuse with the risk of pre-natal depression in two cohorts in the Boston area, including 2128 participants recruited from a large urban- and suburban-managed care organization (Project Viva) and 1509 participants recruited primarily from urban community health centres (Project ACCESS). Protocols for the studies were designed in parallel to allow us to merge data to enhance ethnic and socio-economic diversity in the combined sample. In mid-pregnancy, the Personal Safety Questionnaire and Edinburgh Postnatal Depression Scale (EPDS) were administered in both cohorts. An EPDS score ≥13 indicated probable pre-natal depression. Logistic regression was used to estimate the odds ratio (OR) of pre-natal depression associated with lifetime abuse history.
Results Project ACCESS participants were twice as likely as Project Viva participants to report symptoms consistent with pre-natal depression: 22% of Project ACCESS participants had EPDS scores ≥13, compared with 11% of Project Viva participants. Fifty-seven percent of women in ACCESS and 46% in Viva reported lifetime physical and/or sexual abuse. In merged analysis, women reporting lifetime physical or sexual abuse had an OR for mid-pregnancy depression of 1.63 [95% confidence interval (95% CI): 1.29–2.07], adjusted for age and race/ethnicity. Lifetime histories of physical abuse [OR 1.48 (95% CI 1.15–1.90)] and sexual abuse [OR 1.68 (95% CI 1.24–2.28)] were independently associated with pre-natal depression. When child/teen, pre-pregnancy adult and pregnancy life periods were considered simultaneously, abuse in childhood was independently associated with an OR of 1.23 (95% CI 1.00–1.59), pre-pregnancy adult abuse with an OR of 1.70 (95% CI 1.31–2.21) and abuse during pregnancy with an OR of 1.77 (95% CI 1.14–2.74). Further adjustment for childhood socio-economic position made no material difference, and there were no clear interactions between abuse and adult socio-economic position.
Conclusions Physical and sexual abuse histories were positively associated with pre-natal depression in two economically and ethnically distinct populations. Stronger associations with recent abuse may indicate that the association of abuse with depression wanes with time or may result from less accurate recall of remote events.
PMCID: PMC3066428  PMID: 21169318
Depression; pregnancy; violence; pre-natal care; adult survivors of child abuse; partner abuse; spouse abuse
24.  Epidemiology of stress and asthma: From constricting communities and fragile families to epigenetics 
A number of epidemiologic frameworks, exemplified through extant research examples, provide insight into the role of stress in the expression of asthma and other allergic disorders. Biological, psychological, and social processes interact throughout the life course to influence disease expression. Studies exploiting a child development framework focus on critical periods of exposure, including the in utero environment, to examine the influence of stress on disease onset. Early stress effects that alter the normal course of morphogenesis and maturation that affect both structure and function of key organ systems (e.g., immune, respiratory) may persist into adult life underscoring the importance of a life course perspective. Other evidence suggests that maternal stress influences programming of integrated physiological systems in their offspring (e.g., neuroendocrine, autonomic, immune function) starting in pregnancy, consequently stress effects may be transgenerational. A multi-level approach which includes an ecological perspective may help to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries that to date remain largely unexplained. Evolving studies incorporating psychological, behavioral, and physiological correlates of stress more specifically inform underlying mechanisms operating in these critical periods of development. The role of genetics, gene by environment interactions, and epigenetic mechanisms of gene expression have been sparsely examined in epidemiologic studies on stress and asthma although overlapping evidence provides proof of concept for such studies in the future.
PMCID: PMC3052958  PMID: 21094921
25.  Abuse in Childhood and Adolescence As a Predictor of Type 2 Diabetes in Adult Women 
Although child abuse is associated with obesity, it is not known whether early abuse increases risk of type 2 diabetes.
To investigate associations of child and adolescent abuse with adult diabetes
Proportional hazards models were used to examine associations of lifetime abuse reported in 2001 with risk of diabetes from 1989 to 2005 among 67,853 women in the Nurses Health Study II. Data were analyzed in 2009.
Child or teen physical abuse was reported by 54% and sexual abuse by 34% of participants. Models were adjusted for age, race, body type at age 5 years, and parental education and history of diabetes. Compared to women who reported no physical abuse, the hazards ratio (HR) was 1.03 (95% CI: 0.91, 1.17) for mild physical abuse, 1.26 (1.14, 1.40) for moderate physical abuse, and 1.54 (1.34, 1.77) for severe physical abuse. Compared with women reporting no sexual abuse in childhood or adolescence, the HR was 1.16 (1.05, 1.29) for unwanted sexual touching, 1.34 (1.13, 1.59) for one episode of forced sexual activity, and 1.69 (1.45, 1.97) for repeated forced sex. Adult BMI accounted for 60% (32%, 87%) of the association of child and adolescent physical abuse and 64% (38%, 91%) of the association of sexual abuse with diabetes.
Moderate to severe physical and sexual abuse in childhood and adolescence have dose response associations with risk of type 2 diabetes among adult women. This excess risk is partially explained by the higher BMI of women with a history of early abuse.
PMCID: PMC3003936  PMID: 21084073

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