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Objective: To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function., Methods: This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN)., Results: PAPP-A was correlated with skin microvascular endothelial function index (β = 1.008 (95% CI, 0.34-1.68), r 2  = 0.17, P = 0.004). PAPP-A also correlated inversely with FMD (β = -0.052 (95% CI, -0.094 to -0.011), r 2  = 0.13, P = 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors., Conclusions: First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To examine alterations in maternal vascular structure and function during normal pregnancy., Methods: We assessed brachial and central blood pressure, pulse-wave velocity and augmentation index (by pulse-wave analysis and applanation tonometry), common carotid artery structure (by ultrasonography) and endothelial function in the brachial artery (by postischemic hyperemia-induced flow-mediated vasodilatation by glyceryl trinitrate) and in the forearm skin microcirculation (by laser Doppler perfusion imaging during iontophoretic administration of acetylcholine and sodium nitroprusside) in 52 healthy nulliparous women at 14, 24 and 34 weeks' gestation, and at 9 months postpartum., Results: During pregnancy, brachial and central systolic and diastolic blood pressures initially decreased but subsequently increased (all P < 0.05). Flow-mediated vasodilatation in the brachial artery increased during early pregnancy (P < 0.05), whereas non-specific vasodilatation by glyceryl trinitrate decreased (P < 0.01), indicating improved endothelial function. Thus, endothelial function index (forearm blood flow/glyceryl trinitrate) increased during pregnancy (0.30 ± 0.18 in the non-pregnant state at 9 months postpartum and 0.51 ± 0.19, 0.61 ± 0.39 and 0.49 ± 0.30 in the first, second and third trimesters, respectively) (P < 0.001). Endothelium-dependent skin microvascular reactivity to acetylcholine also increased (P < 0.01). Carotid-femoral pulse-wave velocity decreased during pregnancy (5.88 ± 0.91 m/s in the non-pregnant state and 5.55 ± 0.67, 5.12 ± 0.66 and 5.62 ± 0.74 m/s in the first, second and third trimesters, respectively) (P < 0.001)., Conclusion: During normal pregnancy, the blood volume expansion necessary for sufficient fetal growth is accommodated by early and marked changes in the matvascular system. This seems to be dependent on normal adaptive endothelial and vascular function. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate the relationship between maternal endothelial function in the first trimester, assessed in both the brachial artery and the forearm skin microcirculation, and fetal growth., Methods: Vascular function was assessed in 56 pregnant women during gestational weeks 11-14. Vascular reactivity in the brachial artery was evaluated by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by vasodilatation following administration of sublingual glyceryl trinitrate (GTN). Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Fetal growth was measured at study inclusion and birth-weight centile was calculated after delivery., Results: FMD and GTN-induced vasodilatation were both associated with birth-weight centile. On multivariate analysis (adjusted for brachial artery diameter at rest, blood pressure, maternal age and heart rate), for FMD β = 1.7 (95% CI, 0.06-3.34), r 2  = 0.26 and P = 0.042, and for GTN-induced vasodilatation β = 2.6 (95% CI, 0.44-4.68), r 2  = 0.15 and P = 0.02. Endothelium-dependent and -independent microvascular reactivity were also associated with birth-weight centile: for ACh β = 7.82 (95% CI, 1.81-13.83), r 2  = 0.12 and P = 0.029, and for SNP β = 6.27 (95% CI, 1.20-11.34), r 2  = 0.11 and P = 0.016., Conclusion: First-trimester maternal vascular dilatation capacity (rather than endothelial function alone) is associated with fetal growth. These findings were consistent in both the brachial artery and the forearm skin microcirculation. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)