Adverse Childhood Events and Health Biomarkers: A Systematic Review

Background: This systematic review aimed to summarize evidence reporting epigenetic and/or neuro-immuno-endocrine embedding of adverse childhood events (ACEs) in children, with a particular focus on the short-term biological effect of those experiences. Methods: A search was conducted in PsycINFO®, PubMed®, Isi Web of Knowledge and Scopus, until July 2019, to identify papers reporting the short-term biological effects of exposure to ACEs. Results: The search identified 58 studies, that were included in the review. Regarding exposure, the type of ACE more frequently reported was sexual abuse (n = 26), followed by life stressors (n = 20) and physical abuse (n = 19). The majority (n = 17) of studies showed a positive association between ACEs and biomarkers of the immune system. Regarding DNA methylation 18 studies showed more methylation in participants exposed to ACEs. Two studies presented the effect of ACEs on telomere length and showed that exposure was associated with shorter telomere length. Conclusion: Overall the associations observed across studies followed the hypothesis that ACEs are associated with biological risk already at early ages. This is supporting evidence that ACEs appear to get “under the skin” and induce physiological changes and these alterations might be strongly associated with later development of disease.This work was supported by the European Regional Development Fund (ERDF) through the Operational Program Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education under the projects BioAdversity: How childhood social adversity shapes health: The biology of social adversity (POCI-01- 0145-FEDER-016838; Reference info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/DTP-EPI/1687/2014/PT), HIneC: When do health inequalities start? Understanding the impact of childhood social adversity on health trajectories from birth to early adolescence (POCI-01-0145-FEDER-029567; Reference info:eu-repo/grantAgreement/FCT/9471 - RIDTI/info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC/SAU-PUB/29567/2017/PT017/PT). It is also supported by the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Reference info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/DTP/04750/2013/PT), PhD Grants info:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH/BD/108742/2015/PT (to SSo) and SFRH/BD/103726/2014 (to VR) co-funded by FCT and the Human Capital Operational Programme (POCH/FSE Program); FCT Investigator contract info:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND/01516/2017/CP1406/CT0001/PT (to SF). We also thank the support of the LIFEPATH project funded by the European Commission (Horizon 2020 Grant No. 633666)

Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2013: the Influenza Complications Alert Network

The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season. This work i

Mechanisms of life-course socioeconomic inequalities in adult systemic inflammation: Findings from two cohort studies

Disadvantaged socioeconomic conditions in childhood heighten systemic inflammatory levels in adulthood; however, life-course mechanisms underlying this association are largely unknown. In the present observational study, we investigated the roles of adulthood socioeconomic and lifestyle factors in mediating this association. Participants were from two prospective Swiss population-based cohorts (N = 5,152, mean age 60 years). We estimated the total effect of paternal occupational position on adult heightened systemic inflammatory levels (C-reactive protein>3 mg/L), and the indirect effects via adulthood socioeconomic positions (SEPs: education and occupational position), financial hardship, and lifestyle factors (body mass index, smoking status, physical inactivity, and alcohol consumption). We estimated odds ratio (OR) and proportion mediated using counterfactual-based mediation models. Individuals whose father had a low occupational position had an OR of 1.51 [95% confidence interval (CI): 1.25, 1.84] for heightened inflammation compared to their more advantaged counterparts. This was jointly mediated (33 [95% CI: 14, 69]%) by adulthood SEPs, whereby the pathway through education followed by occupational position mediated 30 [95% CI: 11, 64]%, while the pathway via occupational position only mediated 3 [95% CI: 4, 13]%. Individuals with the lowest life-course SEPs had an OR of 2.27 [95% CI: 1.71, 2.98] for heightened inflammation compared to having the highest life-course SEPs. This was jointly mediated (63 [95% CI: 44, 97]%) by financial hardship and lifestyle factors. Our study supports a cumulative effect of life-course SEPs on adult heightened systemic inflammation along the pathway paternal occupational position -> education -> adult occupational position. Financial hardship and lifestyle factors in adulthood mediate half of that effect

Influenza Vaccine Effectiveness against Hospitalisation with Confirmed Influenza in the 2010-11 Seasons: A Test-negative Observational Study

Immunisation programs are designed to reduce serious morbidity and mortality from influenza, but most evidence supporting the effectiveness of this intervention has focused on disease in the community or in primary care settings. We aimed to examine the effectiveness of influenza vaccination against hospitalisation with confirmed influenza. We compared influenza vaccination status in patients hospitalised with PCR-confirmed influenza with patients hospitalised with influenza-negative respiratory infections in an Australian sentinel surveillance system. Vaccine effectiveness was estimated from the odds ratio of vaccination in cases and controls. We performed both simple multivariate regression and a stratified analysis based on propensity score of vaccination. Vaccination status was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384 test-negative patients. Overall estimated crude vaccine effectiveness was 57% (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status, the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis accounting for a propensity score for vaccination, the estimated vaccine effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was moderately protective against hospitalisation with influenza in the 2010 and 2011 seasons

Parenting very preterm infants and stress in Neonatal Intensive Care Units

BACKGROUND: Assessing parental stress during infants' hospitalization in Neonatal Intensive Care Units (NICU) is essential to identify parents at risk for immediate and extended physical and emotional burden. AIMS: To identify sources of stress in mothers and fathers of very preterm infants hospitalized in NICU, and their association with sociodemographic, obstetric and infants' characteristics. STUDY DESIGN: Observational and cross-sectional study conducted between July 2013 and June 2014. SUBJECTS: Parents of very preterm infants hospitalized in all level III NICU in the Northern Health Region of Portugal were consecutively and systematically invited to participate in this study, being included 120 mothers and 91 fathers (participation rate: 96.8%). OUTCOME MEASURES: The Portuguese version of the Parental Stressor Scale: Neonatal Intensive Care Unit was used. RESULTS: The overall experience of hospitalization was classified as more stressful than the median for the subscales. "Change in parental role" was classified as the most stressful subscale by mothers (Median (P25-P75): 4.1(3.2-4.7)) and fathers (Median (P25-P75): 3.2(2.4-4.0)). Mothers scored significantly higher in all subscales. For mothers, multiple pregnancy was associated with lower levels of stress regarding "change in parental role" (β=-0.597; 95% CI=-1.020 to -0.174) and "overall stress" (β=-0.603; 95% CI=-1.052 to -0.153). Being ≥30years old was found to be a significant predictor for decreased fathers' stress. CONCLUSIONS: This study raises awareness for the need to develop sensitive instruments that take notice of gender, social support and family-centered care. The implementation of interventions focused on reducing parental stress is crucial to diminish disparities in family health

Epigenetic modification of cytosines fine tunes the stability of i-motif DNA

i-Motifs are widely used in nanotechnology, play a part in gene regulation and have been detected in human nuclei. As these structures are composed of cytosine, they are potential sites for epigenetic modification. In addition to 5-methyl- and 5-hydroxymethylcytosine modifications, recent evidence has suggested biological roles for 5-formylcytosine and 5-carboxylcytosine. Herein the human telomeric i-motif sequence was used to examine how these four epigenetic modifications alter the thermal and pH stability of i-motifs. Changes in melting temperature and transitional pH depended on both the type of modification and its position within the i-motif forming sequence. The cytosines most sensitive to modification were next to the first and third loops within the structure. Using previously described i-motif forming sequences, we screened the MCF-7 and MCF-10A methylomes to map 5-methylcytosine and found the majority of sequences were differentially methylated in MCF7 (cancerous) and MCF10A (non-cancerous) cell lines. Furthermore, i-motif forming sequences stable at neutral pH were significantly more likely to be epigenetically modified than traditional acidic i-motif forming sequences. This work has implications not only in the epigenetic regulation of DNA, but also allows discreet tunability of i-motif stability for nanotechnological applications

Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort

The concept of allostatic load (AL) refers to the idea of a global physiological ‘wear and tear’ resulting from the adaptation to the environment through the stress response systems over the life span. The link between socioeconomic position (SEP) and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. In order to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including eleven year mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load) reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysis revealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to 5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and young adulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)]. Regarding the ability of each physiological system and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous compared to evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biological embodiment in response to stress which ultimately affects mortality.</p

Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort.

The concept of allostatic load (AL) refers to the idea of a global physiological 'wear and tear' resulting from the adaptation to the environment through the stress response systems over the life span. The link between socioeconomic position (SEP) and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. In order to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including eleven year mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load) reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysis revealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to 5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and young adulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)]. Regarding the ability of each physiological system and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous compared to evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biological embodiment in response to stress which ultimately affects mortality

Adverse childhood experiences and premature all-cause mortality

Events causing stress responses during sensitive periods of rapid neurological development in childhood may be early determinants of all-cause premature mortality. Using a British birth cohort study of individuals born in 1958, the relationship between adverse childhood experiences (ACE) and mortality ≤50 year was examined for men (n = 7,816) and women (n = 7,405) separately. ACE were measured using prospectively collected reports from parents and the school: no adversities (70 %); one adversity (22 %), two or more adversities (8 %). A Cox regression model was carried out controlling for early life variables and for characteristics at 23 years. In men the risk of death was 57 % higher among those who had experienced 2+ ACE compared to those with none (HR 1.57, 95 % CI 1.13, 2.18, p = 0.007). In women, a graded relationship was observed between ACE and mortality, the risk increasing as ACE accumulated. Women with one ACE had a 66 % increased risk of death (HR 1.66, 95 % CI 1.19, 2.33, p = 0.003) and those with ≥2 ACE had an 80 % increased risk (HR 1.80, 95 % CI 1.10, 2.95, p = 0.020) versus those with no ACE. Given the small impact of adult life style factors on the association between ACE and premature mortality, biological embedding during sensitive periods in early development is a plausible explanatory mechanism

Early-life inequalities and biological ageing: A multisystem Biological Health Score approach in U nderstanding S ociety

Social position is known to play a role in the quality of ageing, notably through the stimulation/dysregulation of key physiological systems in response to external stresses. Using data from one wave of Understanding Society including 9088 participants, we defined, as an extension of the allostatic load, a synthetic Biological Health Score (BHS) capturing the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). We used 16 established blood-derived biomarkers of these systems to calculate the BHS and explored the relative contribution of socioeconomic position to the BHS and its main components across age groups. We identified a systematic decreasing education-related gradient of the BHS (p<0.001) leading to lower biological risk in participants with longer education. Education-related differences in the BHS were detected early in life, and were not attributable to lifestyle and behavioural factors. We found a consistent contribution of the inflammatory and metabolic systems to the overall score throughout from early adulthood onwards, while the contribution of the other four systems seems to vary across age groups and gender. Our findings highlight the social-to-biological processes ultimately leading to health inequalities, and suggest that such disparities can already be detected in the 20-40 years old age group and cannot be fully explained by lifestyle and behavioural factors. This may define early adulthood social condition as a precursor to accelerated biological ageing and as an important target for public health policies