Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

Cardiovascular effects of prenatal stress-Are there implications for cerebrovascular, cognitive and mental health outcome?

Prenatal stress programs offspring cognitive and mental health outcome. We reviewed whether prenatal stress also programs cardiovascular dysfunction which potentially modulates cerebrovascular, cognitive and mental health disorders. We focused on maternal stress and prenatal glucocorticoid (GC) exposure which have different programming effects. While maternal stress induced cortisol is mostly inactivated by the placenta, synthetic GCs freely cross the placenta and have different receptor-binding characteristics. Maternal stress, particularly anxiety, but not GC exposure, has adverse effects on maternal-fetal circulation throughout pregnancy, probably by co-activation of the maternal sympathetic nervous system, and by raising fetal catecholamines. Both effects may impair neurodevelopment. Experimental data also suggest that severe maternal stress and GC exposure during early and mid-gestation may increase the risk for cardiovascular disorders. Human data are scarce and especially lacking for older age. Programming mechanisms include aberrations in cardiac and kidney development, and functional changes in the renin-angiotensin-aldosterone-system, stress axis and peripheral and coronary vasculature. Adequate experimental or human studies examining the consequences for cerebrovascular, cognitive and mental disorders are unavailable.

Effects of maternal stress and nutrient restriction during gestation on offspring neuroanatomy in humans.

Cognitive and mental health are major determinants of quality of life, allowing integration into society at all ages. Human epidemiological and animal studies indicate that in addition to genetic factors and lifestyle, prenatal environmental influences may program neuropsychiatric disorders in later life. While several human studies have examined the effects of prenatal stress and nutrient restriction on brain function and mental health in later life, potentially mediating effects of prenatal stress and nutrient restriction on offspring neuroanatomy in humans have been studied only in recent years. Based on neuroimaging and anatomical data, we comprehensively review the studies in this emerging field. We relate prenatal environmental influences to neuroanatomical abnormalities in the offspring, measured in utero and throughout life. We also assess the relationship between neuroanatomical abnormalities and cognitive and mental disorders. Timing- and gender-specific effects are considered, if reported. Our review provides evidence for adverse effects of an unfavorable prenatal environment on structural brain development that may contribute to the risk for cognitive, behavioral and mental health problems throughout life.

Rapid increases in nitrogen oxides are associated with acute myocardial infarction: A case-crossover study.

Aims High concentrations of air pollutants are associated with increased risk for myocardial infarction. The European Union has defined statutory limits for air pollutants based on upper absolute concentrations. We evaluated the association between rapid changes in air pollutants and the risk of myocardial infarction independently of absolute concentrations. Methods and results Using a hospital-based case-crossover study, effects of 24h changes of nitrogen oxides (NOX/2), particulate matter (PM10), and ozone on the risk of myocardial infarction was assessed in 693 patients. In the overall population, increases of NOX of more than 20 µg/m3 within 24 h were associated with an increase in the risk of myocardial infarction by up to 121% (odds ratio (OR) 2.21, 95% confidence interval (CI) 1.19-4.08). Comparably, rapid increases of NO2 of more than 8 µg/m3 tended to increase myocardial infarction risk by 73% (OR 1.73, 95% CI 0.91-3.28) while myocardial infarction risk decreased by 60% after a decrease of NO2 concentration of more than 8 µg/m3 (OR 0.4, 95% CI 0.21-0.77), suggesting a close-to-linear association. While results for ozone concentrations were ambiguous, rapid change in PM10 was not associated with myocardial infarction risk. Conclusion Dynamics and extent of increase in nitrogen oxide concentrations may be an independent risk factor for myocardial infarction. As there are currently no European Union statutory limits reflecting this dynamic variation of air pollutants on a daily basis, the results urgently call for confirming studies in different geographical regions to verify the observations.