Radiation damage by extensive local water ionization from two-step electron-transfer-mediated decay of solvated ions.

Biomolecular radiation damage is largely mediated by radicals and low-energy electrons formed by water ionization rather than by direct ionization of biomolecules. It was speculated that such an extensive, localized water ionization can be caused by ultrafast processes following excitation by core-level ionization of hydrated metal ions. In this model, ions relax via a cascade of local Auger-Meitner and, importantly, non-local charge- and energy-transfer processes involving the water environment. Here, we experimentally and theoretically show that, for solvated paradigmatic intermediate-mass Al3+ ions, electronic relaxation involves two sequential solute-solvent electron transfer-mediated decay processes. The electron transfer-mediated decay steps correspond to sequential relaxation from Al5+ to Al3+ accompanied by formation of four ionized water molecules and two low-energy electrons. Such charge multiplication and the generated highly reactive species are expected to initiate cascades of radical reactions.

Tri-layered constitutive modelling unveils functional differences between the pig ascending and lower thoracic aorta.

The arterial wall's tri-layered macroscopic and layer-specific microscopic structure determine its mechanical properties, which vary at different arterial locations. Combining layer-specific mechanical data and tri-layered modelling, this study aimed to characterise functional differences between the pig ascending (AA) and lower thoracic aorta (LTA). AA and LTA segments were obtained for n=9 pigs. For each location, circumferentially and axially oriented intact wall and isolated layer strips were tested uniaxially and the layer-specific mechanical response modelled using a hyperelastic strain energy function. Then, layer-specific constitutive relations and intact wall mechanical data were combined to develop a tri-layered model of an AA and LTA cylindrical vessel, accounting for the layer-specific residual stresses. AA and LTA behaviours were then characterised for in vivo pressure ranges while stretched axially to in vivo length. The media dominated the AA response, bearing>2/3 of the circumferential load both at physiological (100 mmHg) and hypertensive pressures (160 mmHg). The LTA media bore most of the circumferential load at physiological pressure only (57±7% at 100 mmHg), while adventitia and media load bearings were comparable at 160 mmHg. Furthermore, increased axial elongation affected the media/adventitia load-bearing only at the LTA. The pig AA and LTA presented strong functional differences, likely reflecting their different roles in the circulation. The media-dominated compliant and anisotropic AA stores large amounts of elastic energy in response to both circumferential and axial deformations, which maximises diastolic recoiling function. This function is reduced at the LTA, where the adventitia shields the artery against supra-physiological circumferential and axial loads.

Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. METHODS: In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z-scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z-scores, with gradients hypothesised to represent directionality of neurodegeneration. RESULTS: At group-level, z-scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient - 0.24, [95% CI - 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001). DISCUSSION: Analysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.

High water vs. ad libitum water intake for autosomal dominant polycystic kidney disease: a randomized controlled feasibility trial.

BACKGROUND: Vasopressin stimulates cyst growth in autosomal dominant polycystic kidney disease (ADPKD) and is a key therapeutic target. Evaluation of high water intake as an alternative to pharmacological vasopressin blockade is supported by patients. However feasibility, safety and adherence-promoting strategies required to deliver this remain unknown. AIMS: Assess the feasibility of a definitive randomized high water intake trial in ADPKD. METHODS: In this prospective open-label randomized trial, adult ADPKD patients with eGFR ≥ 20 ml/min/1.73 m2 were randomized to prescribed high water (HW) intake targeting urine osmolality (UOsm) ≤270 mOsm/kg, or ad libitum (AW) intake (UOsm >300 mOsm/kg). Self-management strategies including home-monitoring of urine-specific gravity (USG) were employed to promote adherence. RESULTS: We enrolled 42 participants, baseline median eGFR (HW 68.4 [interquartile range (IQR) 35.9-107.2] vs. AW 75.8 [IQR 59.0-111.0 ml/min/1.73 m2, P = 0.22) and UOsm (HW 353 [IQR 190-438] vs. AW 350 [IQR 240-452] mOsm/kg, P = 0.71) were similar between groups. After 8 weeks, 67% in the HW vs. 24% in AW group achieved UOsm ≤270 mOsm/kg, P = 0.001. HW group achieved lower UOsm (194 [IQR 190-438] vs. 379 [IQR 235-503] mOsm/kg, P = 0.01) and higher urine volumes (3155 [IQR 2270-4295] vs. 1920 [IQR 1670-2960] ml/day, P = 0.02). Two cases of hyponatraemia occurred in HW group. No acute GFR effects were detected. In total 79% (519/672) of USG were submitted and 90% (468/519) were within target. Overall, 17% withdrew during the study. CONCLUSION: DRINK demonstrated successful recruitment and adherence leading to separation between treatment arms in primary outcomes. These findings suggest a definitive trial assessing the impact of high water on kidney disease progression in ADPKD is feasible.

Biomarkers of cardiovascular risk across phenotypes of osteoarthritis.

BACKGROUND: The objective of this study was to explore the associations between ultrasonographic and radiographic joint scores and levels of arterial CVD risk markers in patients with osteoarthritis (OA). Secondly, to compare the levels of arterial CVD risk markers between OA phenotypes and controls. METHOD: The "Musculoskeletal pain in Ullensaker" Study (MUST) invited residents of Ullensaker municipality with self-reported OA to a medical examination. OA was defined according to the American College of Rheumatology (ACR) criteria and phenotyped based on joint distribution. Joints of the hands, hips and knees were examined by ultrasonography and conventional radiography, and scored for osteosteophytes. Hands were also scored for inflammation by grey scale (GS) synovitis and power Doppler (PD) signal. Control populations were a cohort of inhabitants of Oslo (OCP), and for external validation, a UK community-based register (UKPC).Pulse pressure augmentation index (AIx) and pulse wave velocity (PWV) were measured using the Sphygmocor apparatus (Atcor®). Ankel-brachial index (ABI) was estimated in a subset of patients. In separate adjusted regression models we explored the associations between ultrasonography and radiograph joint scores and AIx, PWV and ABI. CVD risk markers were also compared between phenotypes of OA and controls in adjusted analyses. RESULTS: Three hundred and sixty six persons with OA were included (mean age (range); 63.0 (42.0-75.0)), (females (%); 264 (72)). Of these, 155 (42.3%) had isolated hand OA, 111 (30.3%) had isolated lower limb OA and 100 (27.3%) had generalized OA. 108 persons were included in the OCP and 963 persons in the UKPC; (mean age (range); OCP: 57.2 (40.4-70.4), UKPC: 63.9 (40.0-75.0), females (%); OCP: 47 (43.5), UKPC: 543 (56.4%). Hand osteophytes were associated with AIx while GS and PD scores were not related to CVD risk markers. All OA phenotypes had higher levels of AIx compared to OCP in adjusted analyses. External validation against UKPC confirmed these findings. CONCLUSIONS: Hand osteophytes might be related to higher risk of CVD. People with OA had higher augmented central pressure compared to controls.Words 330.

Methods and considerations concerning cardiac output measurement in pregnant women: recommendations of the International Working Group on Maternal Hemodynamics.

Cardiac output (CO), along with blood pressure and vascular resistance, is one of the most important parameters of maternal hemodynamic function. Substantial changes in CO occur in normal pregnancy and in most obstetric complications. With the development of several non-invasive techniques for the measurement of CO, there is a growing interest in the determination of this parameter in pregnancy. These techniques were initially developed for use in critical-care settings and were subsequently adopted in obstetrics, often without appropriate validation for use in pregnancy. In this article, methods and devices for the measurement of CO are described and compared, and recommendations are formulated for their use in pregnancy, with the aim of standardizing the assessment of CO and peripheral vascular resistance in clinical practice and research studies on maternal hemodynamics. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Reduced vitamin D levels in painful diabetic peripheral neuropathy.

AIM: Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls. METHODS: Forty-five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during the summer months, July to September. RESULTS: After adjusting for age, BMI, activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25-hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01). CONCLUSIONS: We have demonstrated a significant difference in 25-hydroxyvitamin D levels in well-characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.

Motion artifacts in standard clinical setting obscure disease-specific differences in quantitative susceptibility mapping.

As quantitative susceptibility mapping (QSM) is maturing, more clinical applications are being explored. With this comes the question whether QSM is sufficiently robust and reproducible to be directly used in a clinical setting where patients are possibly not cooperative and/or unable to suppress involuntary movements sufficiently. Twenty-nine patients with Alzheimer's disease, 31 patients with mild cognitive impairment and 41 healthy controls were scanned on a 3 T scanner, including a multi-echo gradient-echo sequence for QSM and an inversion-prepared segmented gradient-echo sequence (T1-TFE, MPRAGE). The severity of motion artifacts (excessive/strong/noticeable/invisible) was categorized via visual inspection by two independent raters. Quantitative susceptibility was reconstructed using 'joint background-field removal and segmentation-enhanced dipole inversion', based on segmented subcortical gray-matter regions, as well as using 'morphology enabled dipole inversion'. Statistical analysis of the susceptibility maps was performed per region. A large fraction of the data showed motion artifacts, visible in both magnitude images and susceptibility maps. No statistically significant susceptibility differences were found between groups including motion-affected data. Considering only subjects without visible motion, significant susceptibility differences were observed in caudate nucleus as well as in putamen. Motion-effects can obscure statistically significant differences in QSM between patients and controls. Additional measures to restrict and/or compensate for subject motion should be taken for QSM in standard clinical settings to avoid risk of false findings.

Preconception and early pregnancy maternal haemodynamic changes in healthy women in relation to pregnancy viability.

STUDY QUESTION: Are there differences in preconception cardiovascular function between women who have a viable pregnancy and those who have a first trimester miscarriage? SUMMARY ANSWER: Preconception cardiovascular function of central haemodynamics and arterial function are similar between women who have a viable pregnancy and those who have a first trimester miscarriage. WHAT IS KNOWN ALREADY: Miscarriages have been associated with increased long-term cardiovascular disease risk, and arterial and cardiovascular dysfunction has been hypothesised as the common link. It is not known if these risks are present prior to pregnancy or are a reflection of poor arterial and haemodynamic adaptation to pregnancy. STUDY DESIGN, SIZE, DURATION: This prospective longitudinal preconception cohort study was conducted over 18 months. In total, 367 participants were recruited pre-pregnancy, from which 197 pregnancies were recorded; 39 of these pregnancies ended in first trimester miscarriage. Complete longitudinal data were available for 172 pregnancies (140 viable pregnancies, 32 first trimester miscarriages) from pre-pregnancy to 6 weeks gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: This was a single site study based at a maternity hospital in London. Healthy women were recruited prior to natural conception and followed up once they became pregnant. All underwent haemodynamic [cardiac output (CO), peripheral vascular resistance (PVR)] and arterial function [aortic augmentation index (AIx) and pulse wave velocity (PWV)] testing prior to pregnancy and at 6 weeks gestation, using non-invasive devices (gas re-breathing method, Innocor® and an occilometric device, Vicorder®). Cross-sectional measurements at pre-pregnancy and 6 weeks gestation and a longitudinal analysis of changes were compared between women who had a subsequent viable pregnancy, and those who had a subsequent first trimester miscarriage. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences between women destined to have a healthy ongoing pregnancy compared to those who miscarried, in terms of baseline cardiovascular function, assessed by CO, PVR, PWV or AIx. Similarly, between the groups, there were no differences in pregnancy adaptation with similar trends in cardiovascular function changes from pre-pregnancy to 6 weeks gestation. LIMITATIONS, REASONS FOR CAUTION: Whilst this is the first study to investigate preconception and early pregnancy haemodynamic and arterial function in relation to viability, the relatively modest number of miscarriages may not be sufficient to show subtle differences in haemodynamic changes if these were present. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that pre-pregnancy haemodynamic and arterial function is unlikely to be the causal link between miscarriages and future cardiovascular disease. Our findings suggests that factors other than the presence of a viable embryo drive cardiovascular changes in early pregnancy. This study raises new questions about miscarriages as an independent risk event which predisposes women to increased cardiovascular risk later in life. STUDY FUNDING/COMPETING INTEREST(S): The investigators are funded by NIHR Imperial BRC, NIHR Cambridge BRC, Action Medical Research, Imperial College Healthcare Charity and Tommy's Charity. We acknowledge the loan of ultrasound equipment from Samsung Medison (South Korea)/MIS Ltd and provision of fertility monitors from SPD Development Company Ltd (Bedford, UK). There are no competing interests. C.C.L. is supported by the UK National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare National Health Service Trust and Imperial College London. TRIAL REGISTRATION NUMBER: N/A.

Change in maternal cardiac output from preconception to mid-pregnancy is associated with birth weight in healthy pregnancies.

OBJECTIVE: Birth weight (BW) is thought to be determined by maternal health and genetic, nutritional and placental factors, the latter being influenced by anatomical development and perfusion. Maternal cardiovascular changes contribute to uteroplacental perfusion; however, they have not yet been investigated in relation to fetal growth or BW. Our aim was to explore the relationship between maternal cardiovascular adaptation, fetal growth and BW in healthy pregnancies. METHODS: This was a longitudinal prospective study of women planning to conceive a pregnancy. Maternal cardiac output (CO), cardiac index (CI), pulse-wave velocity, aortic augmentation index, central blood pressure and peripheral vascular resistance were assessed prior to pregnancy and at 6, 23 and 33 weeks' gestation. Fetal growth was assessed using serial ultrasound measurements of biometry. RESULTS: In total, 143 women volunteered to participate and were eligible for study inclusion. A total of 101 women conceived within 18 months and there were 64 live births with normal pregnancy outcome. There were positive correlations between BW and the pregnancy-induced changes in CO (ρ = 0.4, P = 0.004), CI (ρ = 0.3, P = 0.02) and peripheral vascular resistance (ρ = 0.3, P = 0.02). There were significant associations between second-to-third-trimester fetal weight gain and the prepregnancy-to-second-trimester increase in CO (Δ, 0.8 ± 1.2 L/min; ρ = 0.3, P = 0.02) and CI (Δ, 0.4 ± 0.6 L/min/m2 ; ρ = 0.3, P = 0.04) and reduction in aortic augmentation index (Δ, -10 ± 9%; ρ = -0.3, P = 0.04). CONCLUSIONS: In healthy pregnancy, incremental changes in maternal CO in early pregnancy are associated with third-trimester fetal growth and BW. It is plausible that this association is causative as the changes predate third-trimester fetal growth and eventual BW. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Hypertension in pregnancy: natural history and treatment options.

Hypertensive disorders of pregnancy affect approximately 5-10% of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored.

The role of epoxyeicosatrienoic acids in the cardiovascular system.

There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of cardiovascular risk factors. This review discusses the current knowledge on the role of EETs in endothelium-dependent control of vascular tone in the healthy and in subjects with cardiovascular risk factors, and considers the pharmacological potential of targeting this pathway.

Multi-channel electronic and vibrational dynamics in polyatomic resonant high-order harmonic generation.

High-order harmonic generation in polyatomic molecules generally involves multiple channels of ionization. Their relative contribution can be strongly influenced by the presence of resonances, whose assignment remains a major challenge for high-harmonic spectroscopy. Here we present a multi-modal approach for the investigation of unaligned polyatomic molecules, using SF6 as an example. We combine methods from extreme-ultraviolet spectroscopy, above-threshold ionization and attosecond metrology. Fragment-resolved above-threshold ionization measurements reveal that strong-field ionization opens at least three channels. A shape resonance in one of them is found to dominate the signal in the 20-26 eV range. This resonance induces a phase jump in the harmonic emission, a switch in the polarization state and different dynamical responses to molecular vibrations. This study demonstrates a method for extending high-harmonic spectroscopy to polyatomic molecules, where complex attosecond dynamics are expected.

Neural basis of auditory expectation within temporal cortex.

Predictive coding frameworks of perception propose that neural networks form predictions of expected input and generate prediction errors when the external input does not match expectation. We therefore investigated the processing of unexpected sounds and silence in the auditory cortex using fMRI. Unexpected sounds, when compared to expected sounds, evoked greater activation in large areas of the left temporal and insular cortices. Additionally the left middle temporal gyrus exhibited greater activation to unexpected events in general, whether sounds or silence, when compared to the corresponding expected events. These findings support predictive coding models of perception, which suggest that regions of the temporal cortex function to integrate sensory information with predictive signals during auditory perception.

Unsafe health and safety: sphygmomanometer cuffs are not interchangeable.

Unknown to its hypertension specialists, a major teaching hospital changed the cuffs on its sphygmomanometers from manufacturer-validated to a uniform washable alternative, in line with 'Health and Safety' concerns surrounding potential cross-contamination between patients. When clinic doctors suspected serious under-reading with the new cuffs, a systematic comparison was undertaken in 54 patients (mean±s.d. age, 61±17 years), using two UM-101 sphygmomanometers, one using the original, manufacturer-supplied cuff and the other with the washable replacement. The study confirmed an average under-reading of 8±10/5±5 mm Hg using the washable cuff, and a third of patients with poorly controlled hypertension were considered normotensive, after using this cuff. The UM-101 sphygmomanometers have now been re-fitted with the original cuffs. Sphygmomanometer cuffs are not interchangeable between devices and a modicum of common sense should be shown to prevent changes made in the name of Health and Safety from having the opposite effect to that intended.

Impact of ovulation and implantation timing on first-trimester crown-rump length and gestational age.

OBJECTIVE: To determine the impact of ovulation and implantation timing on first-trimester crown-rump length (CRL) and the derived gestational age (GA). METHOD: One hundred and forty-three women who were trying to conceive were recruited prospectively. The timing of ovulation and implantation and the ovulation to implantation (O-I) interval were established in 101 pregnancies using home urinary tests for luteinizing hormone and human chorionic gonadotropin. In 71 ongoing pregnancies, GA determined by measurement of fetal CRL at 10-14 weeks' gestation was compared with GA based on ovulation and implantation day. First-trimester growth was determined by serial ultrasound scans at 6-7, 8-9 and 10-14 weeks. RESULTS: The median ovulation and implantation days were 16 and 27, respectively, with an O-I interval of 11 days. GA estimated from CRL at 10-14 weeks was on average 1.3 days greater than that derived from ovulation timing. CRL Z-score was inversely related to O-I interval (ρ= -0.431, P=0.0009). There was no significant relationship between CRL growth rate and the difference between observed CRL and expected CRL based on GA from last menstrual period (ρ=0.224, P=0.08). CONCLUSIONS: Early implantation leads to a larger CRL and late implantation to a smaller CRL at 10-14 weeks, independent of CRL growth rate. Implantation timing is a major determinant of fetal size at 10-14 weeks and largely explains the variation in estimates of GA in the first trimester derived from embryonic or fetal CRL.

Raised uterine artery impedance is associated with increased maternal arterial stiffness in the late second trimester.

OBJECTIVE: To assess the relationship between uterine artery Doppler pulsatility index (PI) and maternal global arterial stiffness and aortic stiffness in women at high a priori risk of preeclampsia in the late second trimester of pregnancy. METHODS: A prospective cohort study was performed. 99 women were recruited from the high-risk obstetric ultrasound clinic in the second trimester; median (±IQR) age and gestation were 33 (29-37) years and 23(+6) (23(+3)-24(+4)) weeks respectively. Transabdominal uterine artery Doppler was performed and mean values recorded. Women returned at a later date, median gestation (±IQR) 26(+5) (25(+6)-28(+0)) weeks, for measurement of blood pressure, augmentation index (AIx) and aortic pulse wave velocity (aPWV). RESULTS: Uterine artery PI is positively associated with both AIx (r = 0.4, P <0.0001, 95% CI: 0.22-0.55) and aPWV (r = 0.22, P = 0.03, 95% CI: 0.02-0.40). No relationship was found between uterine artery PI and mean arterial pressure or pulse pressure. AIx was significantly higher in women with uterine artery PI > 1.45 (P = 0.003, 95% CI: 3.1-14.9) but not aPWV (P = 0.45). AIx, but not aPWV, was significantly higher in women who developed preeclampsia (14% vs 9%, 95% CI: 2.0-8.6, P = 0.0018) or IUGR (11% vs 9%, 95% CI: 0.3-4.2, P = 0.027). AIx showed a negative correlation with birth weight z-score (r = -0.25, 95% CI: -0.43 to -0.06, P = 0.013). CONCLUSION: Increasing uterine artery Doppler PI reflects impaired placentation and increasing risk of preeclampsia. We show a positive association between uterine artery Doppler PI and both global arterial and aortic stiffness. We also show that increased maternal arterial stiffness is associated with a lower birth weight. These findings may represent evidence of an early effect of impaired placentation on the maternal vasculature. Alternatively, given the association between preeclampsia and later cardiovascular disease, ineffective placentation may result from impaired arterial function.