Low indoleamine 2, 3 dioxygenase (IDO) activity is associated with psycho-obstetric risk.

OBJECTIVES: Preeclampsia and depression in pregnancy are among the most prevalent obstetric disorders with no known cures. While depression and preeclampsia each increase risk for the other, shared mechansisms are unclear. One possibility is low levels of Indoleamine 2,3 dioxygenase (IDO), which links immune dysregulation and oxidative arterial damage resulting in poor vascular function in both preeclampsia and depression. We hypothesized low circulating IDO activity levels in pregnancy would correspond to poor vascular function and depression symptoms. STUDY DESIGN: In this nested case-control study, clinical, demographic, and biologic data from a cohort of pregnant women recruited to longitudinal studies measuring noninvasive vascular function and circulating factors were analyzed. MAIN OUTCOME MEASURE: IDO activity across all three trimesters of pregnancy was measured using a colorimetric assay. Carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, was also assessed throughout gestation by non-invasive applanation tonometry. Depression symptoms were assessed in pregnancy via the validated patient health questionnaire 9 (PHQ9). RESULTS: Participants with low second and third trimester IDO activity had significantly decreased cfPWV. This association remained statistically significant when controlled for confounders such as BMI and chronic hypertension in the third but not second trimester. While PHQ9 scores were not associated with cfPWV differences, IDO activity was lower in moderate and severely depressed relative to non-depressed pregnant individuals. CONCLUSION: These results implicate IDO in arterial stiffness and depression symptoms, suggesting that decreased IDO may be a central target for improved psycho-obstetric health.

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort: Relation With Aortic Stiffness.

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P=0.001; second: 5.1±1.8 versus 3.8±1.1, P=0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P=0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27-2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P=0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P=0.002) and was associated with BPV after adjustment for mean blood pressure (r=0.26; P=0.005). First trimester baroreflex sensitivity did not differ between groups (P=0.23) and was not related to BPV (P=0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.