Dominique Mannaerts

Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function

Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy (P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy (P < 0.001). Endothelial function, obtained by FMD, is deteriorated in PE versus normal pregnancy (P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy (P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy.

Are neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or mean platelet volume (MPV) clinically useful as predictive parameters for preeclampsia?

Abstract Objective: Preeclampsia (PE) is a severe pregnancy complication with significant maternal and neonatal morbi–mortality resulting in high health care costs. Prevention, mainly based on the administration of acetylsalicylic acid, is only possible if timely identification of high-risk patients can be realized in an easy, nonexpensive, and widely available method. This paper explores the clinical usability of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and/or mean platelet volume (MPV) in discriminating between women that will and those that will not develop PE. Study design: Demographic data and laboratory results were retrospectively collected and compared in 2050 pregnant women (164 PE and 1886 controls) between 1 January 2014 and 31 January 2016. Results: In the PE group, gravidity, parity, gestational age, and birth weight were significantly lower compared to the control group. Before the 20th pregnancy week, MPV was significantly elevated in the PE group compared to the controls (p = .006), hence analysis revealed an optimal cut-off point of 8.15 (sensitivity 66.7%, specificity 56.3%) for predicting PE. At the end of pregnancy, NLR and MPV appeared to be higher and PLR lower in the PE group compared to the controls, which strengthens the current knowledge on the pathogenesis of PE. Conclusions: MPV is significantly elevated in the first half of pregnancy in women who later develop PE and might therefore be implemented in combination with other parameters in a PE prediction model.

Use of ticagrelor in human pregnancy, the first experience.

Ticagrelor was daily administered throughout pregnancy to a 37-year-old pregnant woman until 36 weeks of gestation. The patient, with Behçet disease, suffered from a non-ST elevation myocardial infarction 4 months before conception, possibly related to hypertension and tobacco abuse. Pregnancy and postpartum periods were uneventful. She delivered a healthy but small-for-gestational-age term neonate.

Re : Prenatal detection of congenital heart disease-results of a national screening programme

Sir, We have read with interest the article by van Velzen and co-workers that reports a significant increase in the prenatal detection rate of congenital heart disease (CHD) after the introduction of a national screening programme in the Netherlands. Recently we analysed the prenatal detection rate of 1865 fetuses with a morphological CHD, diagnosed during pregnancy up until their first birthday, in the province of Antwerp, Belgium, using data from the European Surveillance of Congenital AnomaliesAntwerp (EUROCAT) over 16 years. Antwerp represents almost 30% of all births in Flanders (the northern part of Belgium). In contrast to the results reported by van Velzen et al., our data revealed a disappointingly low prenatal detection rate of 29.3% for allmorphological CHD, and 40.2% for severe CHD. Only 48.0% of these were diagnosed before the end of the 24th week of pregnancy. This was 51.0% for severe CHD. Therefore, the detection rate of morphological CHD before the end of 24 weeks of gestation is 14.1%, and 20.5% for severe CHD. The increasing trend of the detection rate over this 16-year period is significant (P < 0.0001; Table 1). This is probably the effect of the mandatory ultrasound course during training for obstetrics. Both our group and the group reported on by van Velzen have similar demographic characteristics: Flanders and the Netherlands constitute geographic neighbours. In Flanders, standard mid-trimester anomaly scans have been performed for over 18 years already. Local guidelines are based on the guidelines of the International Society of Ultrasound. For the last 10 years, the Flemish Association of Gynaecology and Obstetrics (VVOG), in collaboration with the Flemish Society of Ultrasound (VVVE), have made major efforts to offer training to all sonographers. In contrast to the Netherlands, no licence is required to perform the anomaly scan, and reimbursement by national health insurance is independent from training and qualification. The improving detection rate in the group studied by van Velzen is clearly the result of better ultrasound screening. The study shows that training, followed by certification and permanent quality control, are mandatory to maintain the standards expected by women. Our numbers confirm that continuing training can significantly improve the detection percentage of CDH in a general population.&

Adverse Effects of Carbetocin versus Oxytocin in the Prevention of Postpartum Haemorrhage after Caesarean Section: A Randomized Controlled Trial

Purpose To compare the incidence of nausea, vomiting, and arterial hypotension between carbetocin and oxytocin to prevent haemorrhage after caesarean section (CS). Methods A randomized controlled trial in term pregnant women undergoing planned CS. Groups were randomized to carbetocin or oxytocin. Blood pressure (BP), heart rate, presence of nausea/vomitus, and need for vasopressors were evaluated throughout surgery. Preoperative and postoperative haemoglobin and haematocrit levels were compared. Results Fifty-eight women were randomized (carbetocin n = 32; oxytocin n = 26). Both medications had hypotensive effect, difference in BP for carbetocin versus oxytocin: systolic (14.4 ± 2.4 mmHg versus 8.5 ± 1.8 mmHg); diastolic (7.8 ± 1.6 mmHg versus 8.9 ± 3.0 mmHg) without significant difference between the drugs (p = 0.1 and p = 0.7). Both groups had similar needs for vasopressors. The presence of nausea was not rare, but the difference was not statistically significant (p = 0.4). Average blood loss was slightly lower in the carbetocin group but not statistically significant (p = 0.8). Conclusion In planned CS, a possible clinical significant lower incidence of nausea after carbetocin was noted but this was not statistically significant. There were no differences regarding BP, heart rate, the need for vasopressor, and blood loss. The study was registered in the International Journal of Clinical Trials (ISRCTN 95504420, 2/2017).

A3. Oxidative stress in maternal serum as endothelial dysfunction marker in preeclampsia, an electron paramagnetic resonance (EPR) pilot study

Abstract Aims: Oxidative stress is crucial in the pathophysiology of preeclampsia. Reactive oxygen species (ROS) like the superoxide radical O2–, are produced by the ischemic placenta, causing systemic inflammation and endothelial dysfunction. EPR uses microwave radiation and a high magnetic field and is the most direct and reliable method to detect free radicals. We explored the feasibility of determining O2– concentration in maternal serum and compared pre-eclamptic and uncomplicated pregnancies. Methods: In this study a CMH (1–hydroxyl-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) spin trap stabilizing free O2-radicals for EPR detection, has been used. Twenty-four patients were included of which 12 pre-eclamptic pregnancies and 12 uncomplicated pregnancies. Results: EPR successfully detects O2– concentration in maternal serum. Results are presented in Figure 1. Since there was an overt difference (p = 0.007) between patients with HELLP syndrome versus pre-eclamptic patients with only hypertension and proteinuria, these patients were observed as a distinct group. A significant difference between uncomplicated and pre-eclamptic pregnancies (p = 0.005) was observed.Figure 1. Results are reported as mean ± standard error of mean. Level of significance was assessed at the nominal level α = 0.05. Discussion: We hypothesize that an increased protective scavenger system for ROS is activated in pre-eclampsia. In case of further decompensation as in HELLP syndrome, this system collapses resulting in increased vascular endothelial damage.

Oxidative stress in healthy pregnancy and preeclampsia is linked to chronic inflammation, iron status and vascular function

Background During normal pregnancy, placental oxidative stress (OS) is present during all three trimesters and is necessary to obtain normal cell function. However, if OS reaches a certain level, pregnancy complications might arise. In preeclampsia (PE), a dangerous pregnancy specific hypertensive disorder, OS induced in the ischemic placenta causes a systemic inflammatory response and activates maternal endothelial cells. In this study, we aimed to quantify superoxide concentrations (as a measure of systemic OS) using electron paramagnetic resonance (EPR) and correlate them to markers of systemic inflammation, iron status and vascular function. Methods Fifty-nine women with a healthy pregnancy (HP), 10 non-pregnant controls (NP) and 28 PE patients (32±3.3weeks) were included. During HP, blood samples for superoxide, neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV) and iron status were taken at 10, 25 and 39 weeks. Vascular measurements for arterial stiffness (carotid-femoral pulse wave velocity (CF-PWV), augmentation index (AIx), augmentation Pressure (AP)) and microvascular endothelial function (reactive hyperemia index (RHI)) were performed at 35 weeks. In PE, all measurements were performed at diagnosis. CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) was used as spin probe for EPR, since the formed CM radical corresponds to the amount of superoxide. Results Superoxide concentration remains stable during pregnancy (p = 0.92), but is significantly higher compared to the NP controls (p<0.0001). At 25 weeks, there is a significant positive correlation between superoxide and ferritin concentration. (p = 0.04) In PE, superoxide, systemic inflammation and iron status are much higher compared to HP (all p<0.001). During HP, superoxide concentrations correlate significantly with arterial stiffness (all p<0.04), while in PE superoxide is significantly correlated to microvascular endothelial function (p = 0.03). Conclusions During HP there is an increased but stable oxidative environment, which is correlated to ferritin concentration. If superoxide levels increase, there is an augmentation in arterial stiffness. In PE pregnancies, systemic inflammation and superoxide concentrations are higher and result in a deterioration of endothelial function. Together, these findings support the hypothesis that vascular function is directly linked to the amount of OS and that measurement of OS in combination with vascular function tests might be used in the prediction of PE.

Relapsing fetal bilateral hydrothorax, an isolated expression of a vein of Galen aneurysmal malformation.

We report a case of bilateral fetal hydrothorax presenting at 20 weeks of pregnancy, spontaneously resolving at 22 weeks and severely relapsing at 28 weeks in a fetus with normal karyotype. The cause was a high-output heart failure caused by vein of Galen malformation.

A rare cause of primary amenorrhoea, the XY female with gonadal dysgenesis

Disorders of sexual development are conditions where sexual phenotype and genotype are discordant. Genetic sex is determined at conception as the ovum is fertilised by a spermatozoon that contains either an X or Y chromosome. A complex pathway determined by genes and hormones leads to gonadal differentiation into testis or ovary and promotes the development of internal and external genitalia. We present a case of an 18-year-old woman who presented with primary amenorrhoea. She was a virgin, and apart from hirsutism and overweight, had no complaints. Her family history was insignificant. The patient was tall and had underdeveloped breasts. Her blood results showed hypergonadotropic hypogonadism. A 46, XY genotype was detected with karyotype analysis. Ultrasound and MRI demonstrated the presence of a uterus, but no overt gonads. Laparoscopy was performed, with bilateral removal of streak ovaries.