Evaluation of a prophylactic transfusion program on obstetric outcomes in pregnant women with sickle cell disease: A single centre retrospective cohort study.

OBJECTIVE: To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD). METHODS: This retrospective cohort study included all singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication [year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score] were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death. RESULTS: In total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 [119/148 (80.4%) vs 38/76 (50%); p < 0.001]. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-1.02]. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08-0.97; p = 0.04). CONCLUSION: A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.

[Reprint of: Severe pre-eclampsia: guidelines for clinical practice from the French Society of anesthesiology and intensive care (SFAR) and the French College of gynaecologists and obstetricians (CNGOF)]. / Republication de : recommandations formalisées d'experts. Prise en charge de la patiente avec une pré-éclampsie sévère­RFE communes Société française d'anesthésie-réanimation (SFAR)­Collège national des gynécologues et obstétriciens français (CGNOF).

OBJECTIVE: To provide national guidelines for the management of women with severe preeclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.

Antenatal screening of small for gestational age: Impact on obstetrical management and neonatal outcomes in case of trial of labor after 37 weeks.

OBJECTIVE: Antenatal screening of small fetuses for gestational age (SGA) is a public health challenge. The aim of this study is to assess the obstetrical management and the immediate neonatal outcomes, according to the antenatal screening of the SGA fetuses. METHODS: We performed a retrospective study in a French tertiary care hospital between January 1, 2016 and December 31, 2018. Women were eligible if they had a monofetal pregnancy with a fetus in head presentation and a trial of labor after 37 weeks. A fetus was considered SGA when the estimated fetal weight was less than the 10th percentile at the third trimester ultrasound. A newborn was considered hypotrophic when the birthweight was less than the 10th percentile. RESULTS: 8 153 newborns were included and 948 of the newborns were hypotrophic (308 were suspected for SGA, 640 were not suspected for SGA) and 7205 were eutrophic. Among the hypotrophic neonates, we observed no significant difference regarding the immediate neonatal outcomes between the two groups of fetuses suspected and not suspected for SGA. Among the fetuses not suspected for SGA, the rate of arterial umbilical cord pH below 7.10 was significantly higher in the hypotrophic newborns compared to the non hypotrophic newborns (4.7% vs 3.1%, p = 0.041). CONCLUSION: In our population, unsuspected fetal hypotrophy may be associated with an increased risk of neonatal acidosis. These results emphasize the benefit of improving prenatal screening to identify the SGA fetuses.

Aspirin for the prevention of placenta-mediated complications in pregnant women with chronic hypertension.

Chronic hypertension affects 1-5% of women of childbearing age. During pregnancy, chronic hypertension is associated with an increased risk of vascular disease such as superimposed preeclampsia (PE), intrauterine growth retardation (IUGR), placental abruption, and preterm delivery. These serious and frequent pathologies, specific to pregnancy, carry a particularly high risk of maternal complications (HELLP syndrome, eclampsia, maternal death) and perinatal complications (perinatal death, neurological disorders). To date, there is no curative treatment of vascular complications of chronic hypertension during pregnancy. The only effective treatment, once the complications are established, is usually stopping the pregnancy and delivering the placenta. Some recommendations suggest the use of low dose aspirin in the prevention of these complications. Although the efficacy of low-dose aspirin is assumed in patients with previous preeclampsia, few studies have evaluated its efficacy in patients with chronic hypertension. Controlled prospective studies using very low doses of aspirin (less than 100 mg) and started after 15 weeks of gestation do not seem conclusive. The objective of this work is first to detail the complications of chronic hypertension during pregnancy, then to analyze the studies which evaluated the interest of low dose aspirin in prevention of the placental vascular complications of the pregnancy in patients with chronic hypertension. We also propose an update on the European and North American national recommendations for the prevention of preeclampsia by low dose aspirin in the high-risk population of patients with chronic hypertension. Finally we present the CHASAP (Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy) trial (NCT04356326), a multicentric prospective randomized double-blind superiority trial, which will compare, in pregnant women with chronic hypertension, the efficacy of low dose aspirin (150 mg/day) with a placebo, in the prevention of maternal-fetal morbidity and mortality (preeclampsia, placental abruption, IUGR, perinatal death, maternal death, and preterm delivery).

Prognostic value of diffusion-weighted magnetic resonance imaging of brain in fetal growth restriction: results of prospective multicenter study.

OBJECTIVE: To measure prospectively apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5th centile, and analyze their association with adverse perinatal outcome. METHODS: This was a prospective study involving six tertiary-level perinatal centers. In the period 22 November 2016 to 11 September 2017, we included singleton, small-for-gestational-age (SGA) fetuses with EFW ≤ 5th percentile, between 28 and 32 weeks of gestation, regardless of the umbilical artery Doppler and maternal uterine artery Doppler findings. A fetal magnetic resonance imaging (MRI) examination with diffusion-weighted sequences (DWI) was performed within 14 days following inclusion and before 32 weeks. ADC values were calculated in the frontal and occipital white matter, basal ganglia and cerebellar hemispheres. An ultrasound examination was performed within 1 week prior to the MRI examination. The primary outcome was a composite measure of adverse perinatal outcome, defined as any of the following: perinatal death; admission to neonatal intensive care unit with mechanical ventilation > 48 h; necrotizing enterocolitis; Grade III-IV intraventricular hemorrhage; periventricular leukomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with and those without adverse perinatal outcome was performed. The association between ADC values and adverse perinatal outcome was then analyzed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses. RESULTS: MRI was performed in 64 patients, of whom five were excluded owing to fetal movement artifacts on DWI and two were excluded for termination of pregnancy with no link to fetal growth restriction (FGR). One intrauterine death occurred secondary to severe FGR. Among the 56 liveborn neonates, delivered at a mean ± SD gestational age of 33.6 ± 3.0 weeks, with a mean birth weight of 1441 ± 566 g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotizing enterocolitis. Overall, therefore, seven out of 57 (12.3%) cases had an adverse perinatal outcome (95% CI, 3.8-20.8%). The ADC values in the frontal region were significantly lower in the group with adverse perinatal outcome vs those in the group with favorable outcome (mean values of both hemispheres, 1.68 vs 1.78 × 10-3 mm2 /s; P = 0.04). No significant difference in ADC values was observed between the two groups in any other cerebral territory. A cut-off value of 1.70 × 10-3 mm2 /s was associated with a sensitivity of 57% (95% CI, 18-90%), a specificity of 78% (95% CI, 63-88%), a positive predictive value of 27% (95% CI, 8-55%) and a negative predictive value of 93% (95% CI, 80-98%) for the prediction of adverse perinatal outcome. A mean frontal ADC value < 1.70 × 10-3 mm2 /s was not associated significantly with an increased risk of adverse perinatal outcome, either in the univariate analysis (P = 0.07), or when adjusting for gestational age at MRI and fetal sex (odds ratio (OR), 6.06 (95% CI, 0.9-37.1), P = 0.051) or for umbilical artery Doppler (OR, 6.08 (95% CI, 0.89-41.44)). CONCLUSION: This first prospective, multicenter, cohort study using DWI in the setting of SGA found lower ADC values in the frontal white-matter territory in fetuses with, compared with those without, adverse perinatal outcome. To determine the prognostic value of these changes, further standardized evaluation of the neurodevelopment of children born with growth restriction is required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Aspirin for Prevention of Preeclampsia.

Aspirin is currently the most widely prescribed treatment in the prevention of cardiovascular complications. The indications for the use of aspirin during pregnancy are, however, the subject of much controversy. Since the first evidence of the obstetric efficacy of aspirin in 1985, numerous studies have tried to determine the effect of low-dose aspirin on the incidence of preeclampsia, with very controversial results. Large meta-analyses including individual patient data have demonstrated that aspirin is effective in preventing preeclampsia in high-risk patients, mainly those with a history of preeclampsia. However, guidelines regarding the usage of aspirin to prevent preeclampsia differ considerably from one country to another. Screening modalities, target population, and aspirin dosage are still a matter of debate. In this review, we report the pharmacodynamics of aspirin, its main effects according to dosage and gestational age, and the evidence-based indications for primary and secondary prevention of preeclampsia.

Intrathecal hematoma and arachnoiditis mimicking bacterial meningitis after an epidural blood patch.

We present a case of arachnoiditis and an intrathecal hematoma after an epidural blood patch. A 24-year-old parturient underwent an epidural blood patch three days after an accidental dural puncture during epidural labor analgesia. Four days later, the patient developed severe lower back pain, bilateral leg pain, persistent headache and fever. Bacterial meningitis was initially suspected and antibiotics started. Lumbar magnetic resonance imaging was performed and showed an intrathecal hematoma, with no blood in the epidural space. This report briefly reviews the few cases in the literature of arachnoiditis caused by an intrathecal hematoma and discusses the mechanism which resulted in blood in the subarachnoid space.

Relevance of routine Doppler sampling at the two umbilical arteries in the follow-up of dichorionic twin pregnancies with intrauterine growth-restricted fetuses.

OBJECTIVE: The aim of this study is to assess if the presence of bilateral absent or reverse end-diastolic velocity (AREDV) indicates a poorer prognosis than unilateral AREDV in dichorionic-diamniotic twin pregnancies complicated by intrauterine growth restriction. METHODS: A prospective observational study of 36 dichorionic-diamniotic twin pregnancies complicated by intrauterine growth restriction. One hundred and fifty seven ultrasound (US) examinations were performed. The pulsatility indexes (PI) of the two umbilical arteries (UA-perivesical site), the middle cerebral artery (MCA) and the ductus venosus (DV) were recorded. The fetal hemodynamic status was represented by the existence of a bilateral positive end-diastolic velocity (PEDV), a unilateral AREDV or a bilateral AREDV in the umbilical arteries. RESULTS: Bilateral PEDV, unilateral AREDV and bilateral AREDV represented respectively 66.0%, 10.6% and 23.4% of the US examinations. Intervals between Doppler examinations and delivery were significantly longer (P<0.005) in the bilateral PEDV group (26.5 days±19.7) than in the unilateral AREDV group (11.8 days±11.7) and in the bilateral AREDV group (11.0 days±8.6). MCA-PI, DV-PI, IFI and early neonatal outcomes did not differ between the unilateral and bilateral AREDV groups. CONCLUSION: The routine measurement of the Doppler indices of the two umbilical arteries seems to be no more relevant than unilateral measurement in fetuses of dichorionic-diamniotic twin pregnancies complicated by intrauterine growth restriction.

[Per partum acidosis: Interest and feasibility of cerebral Doppler during labor]. / Intérêt et faisabilité du Doppler cérébral en cours de travail pour prédire une acidose néonatale.

OBJECTIVES: To evaluate feasibility and interest of fetal cerebral Doppler during labor and the link with fetal pH to predict perinatal fetal asphyxia. METHODS: Our prospective study in a university perinatal center, included patients during labor. There were no risk factors during pregnancy and patients were included after 37 weeks of pregnancy. For each patient an ultrasound with cerebral Doppler was done concomitant to a fetal scalp blood sample. We collected maternal and fetal characteristics as well as cervix dilatation, fetal heart rate analysis and fetal presentation. RESULTS: Among 49 patients included over a period of 4 months, cerebral Doppler failed in 7 cases (11%). Majority of failure occurred at 10cm of dilatation (P=0.007, OR=14.1 [1.483; 709.1275]). Others factors like: maternal age, body mass index, parity, history of C-Section were not associated with higher rate of failure. We did not found either significant correlation between cerebral fetal Doppler and pH on fetal scalp blood sample (r=0.15) nor pH at cord blood sample (r=0.13). No threshold of cerebral Doppler is significant for fetal asphyxia prediction. CONCLUSION: Fetal cerebral Doppler is feasible during labor with a low rate of failure but not a good exam to predict fetal acidosis and asphyxia.

[Predictive and prognostic factors of preeclampsia: Interest of PlGF and sFLT-1]. / Facteurs prédictifs et pronostiques de la prééclampsie : intérêt du dosage du PlGF et du sFLT-1.

Preeclampsia is characterized by the association of hypertension and a de novo proteinuria in the second half of pregnancy. Currently, obstetrical teams do not have any tool to detect during the first trimester of pregnancy, in low risk population, the patients likely to develop early and severe preeclampsia. On the other hand, there is no diagnostic/prognostic tool in case of strong suspicion of preeclampsia. The Placental Growth Factor (PIGF) and soluble receptor of the Vascular Endothelial Growth Factor (sFlt-1) are respectively two molecules pro- and anti-angiogenic released mainly by the placenta during pregnancy. Numerous experimental and clinical results suggest that an imbalance of pro/anti-angiogenic factors is involved in the pathophysiology of preeclampsia. We selected and analyzed the main studies that have evaluated the predictive, diagnostic and prognostic value of these two biomarkers for preeclampsia.

Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications.

INTRODUCTION: In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. MATERIAL AND METHODS: To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. RESULTS: The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 dyn.cm-2). The increase of WSS from 0.15 to 5 dyn.cm-2 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 dyn.cm-2 applied for one hour. CONCLUSION: Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 dyn.cm-2). These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB.

Analysis of placental vascularization in a pharmacological rabbit model of IUGR induced by L-NAME, a nitric oxide synthase inhibitor.

OBJECTIVES: We have previously validated the use of L-nitro-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, to induce placental hypoperfusion in a rabbit model. Here, the effects of L-NAME on placental vascularization were explored. Transplacental transfer of L-NAME and/or its active metabolite, NG-nitro-L-arginine (L-NOARG), was evaluated. METHODS: 25 pregnant female rabbits were allocated on day 24 to one of 5 groups: L-NAME groups (31.35, 62.5, 125 and 250 mg/kg/day) or Control group (C). On Day 28, the labyrinthine area was analyzed for stereology and gene expression. L-NAME and L-NOARG were quantified in maternal and fetal blood. RESULTS: The volume density of fetal vessels was significantly decreased in L-NAME (including 62.5-250 mg/kg/day which induced an IUGR) compared to C groups. L-NAME induced an increase of the volume and surface density of the maternal blood space. The trophoblast volume density remained unchanged as well as the surface density of fetal vessels. Relative expression of eNOS, VEGFA, VEGFR-1 and VEGFR-2 in placentas was not affected by 125 mg/kg/day L-NAME treatment, whereas IGF-2 expression was significantly increased in this L-NAME group compared to C. L-NAME was not detected in maternal nor fetal plasma. In contrast, fetal to maternal L-NOARG ratio was 100% in all L-NAME groups. CONCLUSION: These data demonstrate that L-NAME induced placental hypovascularization. The active L-NOARG metabolite is found in maternal and fetal plasma at similar concentrations. This could impact the fetal growth and reduces the interest of this model to study fetal outcomes of placental hypoperfusion.

Role of both actin-myosin cross bridges and NO-cGMP pathway modulators in the contraction and relaxation of human placental stem villi.

INTRODUCTION: Human placental stem villi (PSV) present contractile properties. We studied the role of actin-myosin cross bridges (CBs) and the effects of NO-cGMP pathway modulators in the PSV contraction and relaxation. METHODS: In vitro contractile properties were investigated in 71 PSV from term human placentas studied according to their long axis. Contraction was induced by both KCl and electrical tetanic stimulation. Relaxation was induced by inhibiting the CB cycle with either 2,3-butanedione monoxime (BDM) or blebbistatin (BLE) and by activating the NO-cGMP pathway with isosorbide dinitrate (ISDN), sildenafil (SIL) or ISDN + SIL. RESULTS: PSV tension slowly increased by 140% of the basal tone after KCl exposure and by 85% after tetanus. The addition of BDM, BLE, ISDN, SIL and ISDN + SIL induced a relaxation of PSV, the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). the overall time course of relaxation (in s) was respectively (means ± SD) 3412 ± 1904, 14,250 ± 3095*, 3813 ± 1383, 2883 ± 1188 and 2440 ± 477; significantly longer in BLE compared with BDM, ISDN, SIL and ISDN + SIL:*p < 0.001). These relaxation kinetics were particularly slow. Other relaxation parametres, i.e., maximum lengthening, -peak dT/dt, and resting tension, did not differ between these 5 subgroups. DISCUSSION AND CONCLUSION: Isolated human PSV were able to contract after both KCl exposure and tetanus. This increase in contractility was reversed by inhibiting the CB cycle with BDM or BLE and by stimulating the NO-cGMP pathway with ISDN or SIL. The association ISDN + SIL did not potentiate the relaxing processes.

Quantification of utero-placental vascularization in a rabbit model of IUGR with three-dimensional power Doppler angiography.

OBJECTIVES: Our objective was to evaluate the 3D power Doppler angiography (PDA) in terms of feasibility and ability to detect placental hypo-perfusion in an experimental rabbit model of intrauterine growth restriction (IUGR). STUDY DESIGN: 14 pregnant females were treated with NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, from day 24 to day 28 of gestation, to induce an IUGR. Concomitantly, 8 pregnant rabbits were used as controls. On day 28, 3D power Doppler indices were quantified in each utero-placental unit. Morphological examination of the placentas for the control group (n = 4) and the L-NAME group (500 mg/day, n = 4) were performed with immunohistochemical staining to discriminate the fetal capillaries in the labyrinthine area. RESULTS: A total of 180 live fetuses were obtained, 108 from the L-NAME group and 72 from the control group. G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40 ± 0.55 g vs 33.14 ± 0.62 g, p < 0.0001). In the L-NAME group the vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were significantly lower than in the control group (2.6 [1.4; 6.0] vs 7.6 [3.5; 12.6], p < 0.05; 28.7 [26.5; 31.3] vs 32.9 [28.3; 38.1], p < 0.05; 0.8 [0.4; 1.8] vs 2.5 [1.1; 4.1], p < 0.05, for VI, FI and VFI, respectively). Morphological examinations revealed a substantial disorganization of the placental vascular architecture in the L-NAME group. CONCLUSION: This experimental study demonstrates that quantitative 3D PDA indices are sensitive enough to detect placental vascular insufficiency in an experimental rabbit model of IUGR.

OS047. Quantification of placental vascularization in a rabbit model ofIUGR with three-dimensional power doppler angiography.

INTRODUCTION: Placental dysfunction is known to be a major cause of pregnancy complications, such as perinatal loss, preeclampsia, and intrauterine growth restriction (IUGR). Inadequate remodeling of the spiral arteries resulting in decreased blood flowto the placenta has been implicated in the pathophysiology of preeclampsia and IUGR. 3D power Doppler angiography (PDA) is a noninvasive and safe way to study blood flow within an organ or region of interest. The aim of this study was to evaluate PDA as a method to quantify placental perfusion in a pharmacological rabbit model of vascular IUGR induced by inhibition of NO synthesis. OBJECTIVES: Our objective was to evaluate the 3D power Doppler angiography (PDA) in terms of feasibility and ability to detect placental hypo-perfusion in an experimental rabbit model of intrauterine growth restriction (IUGR). METHODS: Fourteen pregnant females were treated with NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, from day 24 to day 28 of gestation, to induce an IUGR. Concomitantly, 8 pregnant rabbits were used as controls. On day 28, 3D power Doppler indices were quantified in each uteroplacental unit. RESULTS: A total number of 180 live fetuses were obtained, 180 from the L-NAME group and 72 from the control group. G28 fetal weight was significantly lower in the L-NAME group than in the control group (27.40±0.55g vs 33.14±0.62g,p<0.0001). In the L-Name group the vascularization index (VI) was significantly lower than in the control group (2.6 [1.4;6.0] vs 7.6 [3.5;12.6],p<0.05). Similar results were obtained for the Flow Index (FI) and the Vascularization Flow Index (VFI). The number of fetuses considered as small for gestational age (SGA;weight<10th centile) was significantly higher in the L-NAME group than in the control group (47/108 vs 7/72,p<0.0001). The VI was significantly lower in the SGA group than in the eutrophic group (3.46 [0.46;5.9] vs 7.50 [4.22;10.9] p<0.05). Similar results were obtained for FI and VFI. CONCLUSIONS: This experiment study demonstrates that quantitative 3D PDA indices are sensitive enough to detect placental vascular insufficiency in an experimental model of IUGR.

[Introduction of a bar coding pharmacy stock replenishment system in a prehospital emergency medical unit: economical impact]. / Mise en place d'un système de gestion informatique de la pharmacie au sein d'un service médical d'urgence et de réanimation: impact sur les dépenses.

OBJECTIVE: To assess economical impact after introduction of a bar coding pharmacy stock replenishment system in a prehospital emergency medical unit. STUDY DESIGN: Observational before and after study. METHODS: A computer system using specific software and bare-code technology was introduced in the pre hospital emergency medical unit (Smur). Overall activity and costs related to pharmacy were recorded annually during two periods: the first 2 years period before computer system introduction and the second one during the 4 years following this system installation. RESULTS: The overall clinical activity increased by 10% between the two periods whereas pharmacy related costs continuously decreased after the start of pharmacy management computer system use. Pharmacy stock management was easier after introduction of the new stock replenishment system. The mean pharmacy related cost of one patient management was 13 Euros before and 9 Euros after the introduction of the system. The overall cost savings during the studied period was calculated to reach 134,000 Euros. CONCLUSION: The introduction of a specific pharmacy management computer system allowed to do important costs savings in a prehospital emergency medical unit.

Invasive arterial blood pressure monitoring in an out-of-hospital setting: an observational study.

BACKGROUND: Non-invasive arterial blood pressure measurement is often inaccurate in emergency unstable patients. A study was undertaken to assess the feasibility of out-of-hospital intra-arterial catheterisation in haemodynamically unstable patients and to evaluate the correlation between invasive and non-invasive arterial pressure values. METHODS: In this prospective 2-year observational study conducted by mobile emergency medical units, the success rate of arterial catheterisation was calculated and blood pressure values measured invasively and non-invasively after successful catheterisation were compared. RESULTS: 94 patients were included. The success rate for catheterisation (44 radial access, 50 femoral access) was 86% (95% CI 79% to 93%). Bias and precision in invasive versus non-invasive comparisons were -0.1, 38 mm Hg for systolic pressure and 4.2, 27 mm Hg for diastolic pressure. Values differed by more than 20 mm Hg in over 40% of patients. Invasive measurement led to 79 changes in vasoactive treatment in 51 patients. CONCLUSION: Emergency out-of-hospital invasive arterial blood pressure monitoring in haemodynamically unstable patients is highly feasible. Discrepancies between invasive and non-invasive measurements are common and highlight the value of early out-of-hospital monitoring.

Cough reflex sensitivity after elective Caesarean section under spinal anaesthesia and after vaginal delivery.

BACKGROUND: In pregnancy, airway oedema and heartburn may increase cough sensitivity, whereas spinal anaesthesia (SA) with local anaesthetics and opiates may decrease it. Decreased cough sensitivity increases the risk for pneumonia or retained secretions. The aim of this study was to determine whether cough sensitivity is increased in pregnant patients and if it is decreased after planned Caesarean section (CS) under SA. METHODS: Twenty-seven non-pregnant volunteers, 27 patients after vaginal delivery (VD group), and 28 patients after CS under SA (CS group) were studied. For SA, hyperbaric bupivacaine 8-12 mg, sufentanil 5 microg, and morphine 100 microg was given. Increasing concentrations of nebulized citric acid were delivered until eliciting cough. The concentration eliciting one (C1) and two coughs (C2) were recorded and log transformed for analysis (log C1 and log C2). RESULTS: Median (inter-quartile) log C1 was 1.3 (0.6) mg ml(-1) in the VD group, 1.6 (0.6) mg ml(-1) in the non-pregnant group (P < 0.01 vs VD group), and 2.2 (0.7) mg ml(-1) in the CS group (P < 0.0001 and P < 0.01 vs VD and non-pregnant groups, respectively). Similar results were observed with log C2. In CS group, log C1 and log C2 remained increased up to 4 h after SA. CONCLUSIONS: Cough sensitivity was increased after VD but decreased for up to 4 h after SA.