Prenatal stress perturbs fetal iron homeostasis in a sex specific manner

Abstract

The adverse effects of maternal prenatal stress (PS) on child’s neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

Current perspectives on perinatal mental health and neurobehavioral development: focus on regulation, coregulation and self-regulation

“…Fetal measures of transition between different states (based on motor and eye movements measured with ultrasound and heart rate variability patterns) reflecting optimal regulation were related to maternal reported better self-regulation (effortful control) at ages 8-9 and 14-15 years [179]. However, although regulation patterns [165,166,177] can already be detected in the fetal life period, they are difficult to study, especially in large cohorts. It is more feasible to study regulation problems in infants and toddlers and more work is necessary on the characterization, detection and understanding of (self-)regulation problems and their precursors.…”

“…Some challenges in this field relate to specific topics studied in perinatal mental health/ exposome research, for instance, the predictive values of fetal measures for later (self-)regulation problems [165,166,177]. Fetal biobehavioral measures are shown to be related to later temperamental regulation and difficulties [178].…”

Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns

“…A cohort of 18 -45 years old women with singleton pregnancies was recruited (July 2016 -May 2018) by the Department of Obstetrics and Gynecology at Klinikum Rechts der Isar Hospital of the Technical University of Munich, as part of the FELICITy project (45,46). PPS was assessed during their early third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire (11).…”

“…Based on these and other studies, we hypothesized that CholinotRFs may present a promising avenue to study newborns reactions to PPS. This study is a part of the 'FELICITy' study collection (43)(44)(45)(46), exploring the influence of PPS on the fetus. This unique cohort explores roughly 120 mother-baby dyads using a comprehensive battery of biomarkers, with the goal of identifying the stressed newborns at as early a stage as possible.…”

“…This unique cohort explores roughly 120 mother-baby dyads using a comprehensive battery of biomarkers, with the goal of identifying the stressed newborns at as early a stage as possible. Previous studies yielded the fetal stress index (FSI), a measurement of the fetal heart rate reactivity in response to fluctuations in the maternal heart rate measured in the third trimester, maternal hair cortisol levels at birth (46), umbilical cord serum (UCS) iron homeostasis biomarkers (45), and DNA methylation in newborn saliva (44). All of these biomarkers presented differences between stress and control groups, some in a sex-specific manner, as in the case of transferrin saturation levels which were changed only in male newborns in the PPS group (45).…”