ABSTRACT
Adaptations of the immune system throughout gestation have been proposed as important mechanisms regulating successful pregnancy. Dysregulation of the maternal immune system has been associated with adverse maternal and fetal outcomes. To translate findings from mechanistic preclinical studies to human pregnancies, studies of serum immune markers are the mainstay. The design and interpretation of human biomarker studies require additional insights in the trajectories and drivers of peripheral immune markers. The current study mapped maternal inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, IL-17A, IL-23, interferon- γ ) during pregnancy and investigated the impact of demographic, environmental and genetic drivers on maternal inflammatory marker levels in four multi-ethnic and socio-economically diverse population-based cohorts with more than 12,000 pregnant participants. Additionally, pregnancy inflammatory markers were compared to pre-pregnancy levels. Cytokines showed a high correlation with each other, but not with CRP. Inflammatory marker levels showed high variability between individuals, yet high concordance within an individual over time during and pre-pregnancy. Pre-pregnancy body mass index (BMI) explained more than 9.6% of the variance in CRP, but less than 1% of the variance in cytokines. The polygenic score of CRP was the best predictor of variance in CRP (>14.1%). Gestational age and previously identified inflammation drivers, including tobacco use and parity, explained less than 1% of variance in both cytokines and CRP. Our findings corroborate differential underlying regulatory mechanisms of CRP and cytokines and are suggestive of an individual inflammatory marker baseline which is, in part, genetically driven. While prior research has mainly focused on immune marker changes throughout pregnancy, our study suggests that this field could benefit from a focus on intra-individual factors, including metabolic and genetic components.
ABSTRACT
Food-approach eating behaviors are associated with an increased risk of developing overweight/obesity and binge-eating disorder, while obesity and binge-eating disorder have also been linked with altered brain morphology in adults. To understand these associations, we examined the association of food-approach eating behaviors during childhood with adolescents' brain morphology. The sample included 1,781 adolescents with assessments of eating behaviors at ages 4 and 10 years and brain imaging data at 13 years from a large, population-based cohort. Food approach eating behaviors (enjoyment of food, emotional overeating, and food responsiveness) were assessed using the Child Eating Behavior Questionnaire. Additionally, we assessed binge eating symptoms using two items from the Development and Well-Being Assessment at 13 years of age. Adolescents participated in an MRI procedure and measures of brain morphology, including cerebral white, cerebral gray and subcortical gray matter volumes, were extracted from T1-weighted images processed using FreeSurfer. Enjoyment of food and food responsiveness at the age of 4 and 10 years were positively associated with cerebral white matter and subcortical gray matter volumes at age 13 years (e.g., enjoyment of food at 4 years and cerebral white matter: ß = 2.73, 95% CI 0.51, 4.91). Enjoyment of food and food responsiveness at 4 years of age, but not at 10 years, were associated with a larger cerebral gray matter volume at 13 years of age (e.g., enjoyment of food at 4 years: ß = 0.24, 95% CI 0.03, 0.45). No statistically significant associations were found for emotional overeating at both ages and brain measurements at 13 years of age. post-hoc analyses showed no associations of food-approach eating behaviors with amygdala or hippocampus. Lastly, we did not observe significant associations of binge-eating symptoms with global brain measurements and a priori-defined regions of interest, including the right frontal operculum, insular and orbitofrontal cortex. Our findings support an association between food-approach eating behaviors, especially enjoyment of food and food responsiveness, and brain morphology in adolescence. Our findings add important knowledge to previous studies that were mostly conducted in adults, by suggesting that the eating behavior-brain link may be visible earlier in life. Further research is needed to determine causality.