Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis

Abstract

Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions.

Family Ruptures, Stress, and the Mental Health of the Next Generation

“…26 As shown in online Appendix Tables A1 and A2 for maternal and paternal characteristics, respectively, we find little evidence for a systematic relationship between parental characteristics and the occurrence of death during pregnancy. 27 Out of the 16 coefficients reported in these tables, only 2 are statistically significant (we find a positive correlation between treatment and first parity births and a negative correlation between treatment and the likelihood of the mother being foreign-born) and the magnitudes are relatively small when compared to sample means.…”

“…However, results that include father characteristics as controls are generally very similar to those reported here. 27 Since our analyses compare individuals who experience a relative death in utero to those who experience a relative death after birth while controlling for year-of-conception fixed effects, there is a mechanical correlation between the treatment variable and age of the relative: those who die during the mother's pregnancy are mechanically slightly younger than those who die in the year after childbirth. Thus, all of the regressions in online Appendix Tables A1 and A2 control for the relative's age and age squared.…”

Maternal Depressive Symptoms During the Pre‐ and Postnatal Periods and Infant Attention to Emotional Faces

“…Prenatal exposure to maternal psychological stress, such as depression and anxiety, has been associated with alterations in child neurodevelopment and stress regulation systems (Sandman, Class, Glynn, & Davis, ; Van den Bergh et al., ). Changes in offspring hypothalamic–pituitary–adrenal axis function and glucocorticoid receptor sensitivity (Frasch et al., ; Loman & Gunnar, ), as well as alterations in brain functional and structural development (e.g., cortical thinning, amygdala‐prefrontal connectivity), and related problems in attention and emotion regulation have been reported (Dunkel Schetter & Tanner, ; Posner et al., ; Sandman, Glynn, & Davis, ; Sandman, Class, et al., ). Moreover, higher rates of symptoms of depression and anxiety as well as attention deficit hyperactivity disorder and conduct disorders have been reported in children with prenatal stress (PS) exposure (Glover, , ; Van den Bergh et al., ).…”

“…Prenatal exposure to maternal psychological stress, such as depression and anxiety, has been associated with alterations in child neurodevelopment and stress regulation systems (Sandman, Class, Glynn, & Davis, 2016;Van den Bergh et al, 2017). Changes in offspring hypothalamic-pituitary-adrenal axis function and glucocorticoid receptor sensitivity (Frasch et al, 2018;Loman & [Article updated on November 8, 2018 after first online publication on October 8, 2018: The scale and confidence intervals in Figure 4 were incorrect. This figure is now corrected.…”

Mice tracking using the YOLO algorithm

“…Multidisciplinary research areas such as Neuroscience can benefit from the improvement of laboratory experiments to complex data analysis using modern machine learning techniques (Vu et al, 2018). In this way, it is possible to perform the detection and classification of brain patterns, correlations between behavioral tasks and electrophysiological recordings, social stress tests and animal interaction, among other experimental designs with rodents (Henriques-Alves and Queiroz, 2016;Frasch et al, 2017).…”