Exposure to adversity and inflammatory outcomes in mid and late childhood

Background We aimed to estimate the association between exposure to adversity and inflammatory markers in mid (4 years) and late (11-12 years) childhood, and whether effects differ by type and timing of exposure. Methods Data sources: Barwon Infant Study (BIS; N = 510 analyzed) and Longitudinal Study of Australian Children (LSAC; N = 1156 analyzed). Exposures: Adversity indicators assessed from 0 to 4 (BIS) and 0-11 years (LSAC): parent legal problems, mental illness and substance abuse, anger in parenting responses, separation/divorce, unsafe neighborhood, and family member death; a count of adversities; and, in LSAC only, early (0-3), middle (4-7), or later (10-11) initial exposure. Outcomes: Inflammation quantified by high sensitivity C-reactive protein (hsCRP, Log (ug/ml)) and glycoprotein acetyls (GlycA, Log (umol/L)). Analyses: Linear regression was used to estimate relative change in inflammatory markers, adjusted for sociodemographic characteristics, with exposure to adversity. Outcomes were log-transformed. Results Evidence of an association between adversity and hsCRP was weak and inconsistent (e.g., 3+ versus no adversity: BIS: 12% higher, 95%CI -49.4, 147.8; LSAC 4.6% lower, 95%CI: −36.6, 48.3). A small positive association between adversity and GlycA levels was observed at both 4 years (e.g., 3+ versus no adversity: 3.3% higher, 95%CI -3.0, 9.9) and 11-12 years (3.2% higher, 95%CI 0.8, 5.8). In LSAC, we did not find evidence that inflammatory outcomes differed by initial timing of adversity exposure. Conclusions Small positive associations between adversity and inflammation were consistently observed for GlycA, across two cohorts with differing ages. Further work is needed to understand mechanisms, clinical relevance, and to identify opportunities for early intervention.Meredith O'Connor and Sarah Arnup were supported by the Melbourne Children's LifeCourse initiative, funded by a Royal Children's Hospital Foundation Grant (2018-984). Anne-Louise Ponsonby is supported by a National Health and Medical Research Council (NHMRC) Fellowship (1110200). Peter Sly is sup- ported by an NHMRC Fellowship (APP1102590). Naomi Priest is sup- ported by an NHMRC Career Development Fellowship (APP1123677). Kate Lycett is supported by an NHMRC Early Career Fellowship (APP1091124) and Honorary National Heart Foundation Postdoctoral Fellowship (101239). Sharon Goldfeld is supported by an NHMRC Career Development Fellowship (1082922). David Burgner is supported by an NHMRC Investigator Grant (1175744)