How does childhood maltreatment influence cardiovascular disease? A sequential causal mediation analysis.

BACKGROUND: Childhood maltreatment has been consistently associated with cardiovascular disease (CVD). However, the mechanisms of this relationship are not yet fully understood. We explored the relative contribution of anxiety/depression, smoking, body mass index (BMI) and inflammation (C-reactive protein, CRP) to the association between childhood maltreatment and CVD in men and women aged 40-69 years in the UK. METHODS: We used data from 40 596 men and 59 511 women from UK Biobank. To estimate the indirect effects of childhood maltreatment (physical, sexual and emotional abuse, and emotional and physical neglect) on incident CVD via each of the mediators, we applied a sequential mediation approach. RESULTS: All forms of maltreatment were associated with increased CVD risk [hazard ratios (HRs) ranging from 1.09 to 1.27]. Together, anxiety/depression, smoking, BMI and inflammation (indexed by CRP) mediated 26-90% of the association between childhood maltreatment and CVD, and the contribution of these mediators differed by type of maltreatment and sex. Anxiety/depression mediated the largest proportion of the association of sexual abuse, emotional abuse and emotional neglect with CVD (accounting for 16-43% of the total effect), especially in women. In men, BMI contributed the most to the indirect effect of associations of physical abuse and physical neglect with CVD; in women, anxiety/depression and BMI had similar contributions. CONCLUSIONS: These findings add to the understanding of how childhood maltreatment affects CVD risk and identify modifiable mediating factors that could potentially reduce the burden of CVD in people exposed to maltreatment in early life.

Associations between Adverse Childhood Experiences and the novel inflammatory marker glycoprotein acetyls in two generations of the Avon Longitudinal Study of Parents and Children birth cohort.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of non-communicable diseases in adulthood, potentially mediated by chronic low-grade inflammation. Glycoprotein acetyls (GlycA) is a marker of chronic and cumulative inflammation. We investigated associations between ACEs and GlycA at different ages, in two generations of the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. METHODS: ALSPAC offspring's total ACE scores were generated for two age periods using prospectively collected data: 0-7y and 0-17y. GlycA was measured using high-resolution proton nuclear magnetic resonance at mean ages 8y, 18y, and 24y. Sample sizes ranged from: n = 5116 (8y) to n = 3085 (24y). ALSPAC mothers (n = 4634) retrospectively reported ACEs experienced before age 18y and GlycA was assessed at mean age 49y. We used multivariable linear regression to estimate associations between ACEs (total ACE score and individual ACEs) and subsequent GlycA in both samples, adjusting for key confounders. RESULTS: Mean GlycA levels were similar in offspring and mothers and over time. In offspring, there was no evidence that ACEs (total score or individual ACE) were associated with GlycA at age 8y or 18y, or 24y after adjustment for maternal age at birth and parity, maternal marital status, household occupational social class, maternal education, maternal smoking, own ethnicity, sex, and age in months. In mothers, there was evidence of a positive association between the total ACE score and GlycA at age 49y (adjusted mean difference 0.007 mmol/L; 95%CI: 0.003, 0.01). Emotional neglect was the only individual ACE associated with higher GlycA after adjusting for confounders and other ACEs. CONCLUSION: Results suggest the association between ACEs and GlycA may emerge in middle age. Future research should explore the extent to which inflammation in adulthood mediates well-documented associations between ACEs and adverse health outcomes in later life.

Intimate partner violence and growth outcomes through infancy: A longitudinal investigation of multiple mediators in a South African birth cohort.

Intimate partner violence (IPV) has been linked to poor fetal and infant growth. However, factors underlying this relationship are not well understood, particularly in the postnatal time period. In a South African cohort, we investigated (1) associations between IPV in pregnancy and growth at birth as well as postnatal IPV and child growth at 12 months and (2) whether maternal depression, tobacco or alcohol use or infant hospitalizations mediated IPV-growth relationships. Mothers were enrolled in pregnancy. Maternal IPV was measured during pregnancy and 10 weeks postpartum; depression, alcohol and tobacco use were measured during pregnancy and at 6 months postpartum. Child weight and length were measured at birth and 12 months and converted to z-scores for analysis. Linear regression and structural equation models investigated interrelationships between IPV and potential mediators of IPV-growth relationships. At birth, among 1,111 mother-infant pairs, maternal emotional and physical IPV were associated with reduced weight-for-age z-scores (WFAZ). Only physical IPV was associated with length-for-age z-scores (LFAZ) at birth. Antenatal maternal alcohol and tobacco use mediated IPV-growth relationships at birth. Postnatally, among 783 mother-infant pairs, emotional and physical IPV were associated with reduced WFAZ at 12 months. Only emotional IPV was associated with LFAZ at 12 months. Maternal tobacco use was a mediator postnatally. Findings highlight the role of physical and emotional IPV as risk factors for compromised fetal and infant growth. Findings underscore the importance of programmes to address interrelated risk factors for compromised infant growth, specifically IPV and substance use, which are prevalent in high-risk settings.