Identifying a biological signature of prenatal maternal stress.

James M Keane,Fergus P Mccarthy,Jillian Brown,Louise C Kenny,Ali S Khashan,Sarah O’Donovan,James M Collins,John F Cryan,Timothy G Dinan,Siobhain M O’Mahony,Gerard Clarke

doi:10.1172/jci.insight.143007

James M Keane, Fergus P Mccarthy + Show 9 more

Open Access

https://doi.org/10.1172/jci.insight.143007

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Journal: JCI insight	Publication Date: Jan 25, 2021
Citations: 17	License type: CC BY 4.0

Affiliation: York University, University of Liverpool

Abstract

Psychological stress affects maternal gastrointestinal (GI) permeability, leading to low-grade inflammation, which can negatively affect fetal development. We investigated a panel of circulating markers as a biological signature of this stress exposure in pregnant women with and without the stress-related GI disorder irritable bowel syndrome (IBS). Markers of GI permeability and inflammation were measured in plasma from healthy and IBS cohorts of women at 15 and 20 weeks’ gestation. Biomarkers were evaluated with respect to their degree of association to levels of stress, anxiety, and depression as indicated by responses from the Perceived Stress Scale, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale. High levels of stress were associated with elevations of soluble CD14, lipopolysaccharide binding protein (LBP), and tumor necrosis factor–α, while anxiety was associated with elevated concentrations of C-reactive protein (CRP) in otherwise healthy pregnancies. Prenatal depression was associated with higher levels of soluble CD14, LBP, and CRP in the healthy cohort. High levels of prenatal anxiety and depression were also associated with lower concentrations of tryptophan and kynurenine, respectively, in the IBS cohort. These markers may represent a core maternal biological signature of active prenatal stress, which can be used to inform intervention strategies via stress reduction techniques or other lifestyle approaches. Such interventions may need to be tailored to reflect underlying GI conditions, such as IBS.

Highlights

Maternal prenatal stress is associated with several unfavorable pregnancy outcomes, including preterm birth [1] and low infant birth weight [2], while anxiety and depression early in pregnancy are considered risk factors for preeclampsia, a potentially fatal complication of pregnancy [3]
Significant differences in State-Trait Anxiety Inventory (STAI) scoring groups across gestational time points are outlined in Figure 2. Soluble CD14 (sCD14) levels were found to significantly increase in the high- (113.02 ± 42.46 ng/mL, P = 0.025) and low-scoring groups (100.72 ± 38.36 ng/mL, P = 0.027) compared with moderate scorers
Significant differences in lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP) levels between scoring groups were complemented by the presence of positive linear associations between their circulating concentrations and STAI scores in both simple and adjusted models, as outlined in Supplemental Table 5

Summary

Introduction

Maternal prenatal stress is associated with several unfavorable pregnancy outcomes, including preterm birth [1] and low infant birth weight [2], while anxiety and depression early in pregnancy are considered risk factors for preeclampsia, a potentially fatal complication of pregnancy [3]. Preclinical studies have demonstrated that induction of prenatal stress impedes optimum cognitive [5], behavioral [6], and psychosocial [7] development in the offspring. Conventional pathways of translocation of maternal glucocorticoids [11] and proinflammatory cytokines [12] across the placenta and their direct action on the developing fetal brain have been the focus of many mechanistic studies in this area. It is becoming increasingly apparent, that alternative indirect routes may be more relevant to eliciting the downstream effects of prenatal stress, via neuroimmune interactions along the microbiota-gut-brain axis [13]

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