Search

Contains fulltext : 251842.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Placental syndrome is an umbrella term encompassing the clinical phenotypes of preeclampsia and fetal growth restriction, and is associated with high maternal and neonatal morbidity. In women with placental syndrome, histologicl examination of the uteroplacental unit commonly demonstrates pathological lesions, such as decidual vasculopathy. Decidual vasculopathy are pathological changes in the spiral arteries, which are associated with adverse outcome in preeclampsia and long-term maternal cardiovascular health. The relation between placental syndrome phenotypes and placental pathology has been previously demonstrated; however, the role of uteroplacental Doppler measurements as a link between placental syndrome phenotypes and the underlying placental pathology is still unclear. We hypothesized that decidual vasculopathy is associated with abnormal uteroplacental Doppler profiles and ultrasound placental parameters, independent of clinical phenotype. MATERIAL AND METHODS: We performed a retrospective analysis of data from a prospective cohort of pregnancies with placental syndrome, as well as cases without hypertensive disease or fetal growth restriction. The study group was divided into women with decidual vasculopathy on histologic analysis of placental specimen and those without the lesions. Outcome parameters included maternal and fetal Dopplers, estimated fetal weight, placental weight and thickness, placental lacunae and abnormal placental calcification. RESULTS: Compared with the women without the lesions (n = 91), the group with decidual vasculopathy (n = 25) had a higher mean uterine artery pulsatility index (1.70 vs 0.81, p < 0.001) and uterine artery pulsatility index percentile (>p99 vs p67, p < 0.001). Decidual vasculopathy was associated with abnormal uterine artery Doppler profile (defined as pulsatility index p > 95 and/or bilateral notch) (82%) compared with women without the lesions (33%) (odds ratio [OR] 9.3, 95% CI 2.4-36.0), which r

01 augustus 2021, Item does not contain fulltext, Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis. Graphical Abstract.

Contains fulltext : 238786.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Impaired utero-placental perfusion is a well-known feature of early preeclampsia and is associated with placental hypoxia and oxidative stress. Although aberrations at the level of the mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to placental oxidative stress is unknown. METHODS: We explored whether abnormalities in mitochondrial metabolism contribute to hypoxia-induced placental oxidative stress by using both healthy term placentae as well as a trophoblast cell line (BeWo cells) exposed to hypoxia. Furthermore, we explored the therapeutic potential of the antioxidants MitoQ and quercetin in preventing hypoxia-induced placental oxidative stress. RESULTS: Both in placental explants as well as BeWo cells, hypoxia resulted in reductions in mitochondrial content, decreased abundance of key molecules involved in the electron transport chain and increased expression and activity of glycolytic enzymes. Furthermore, expression levels of key regulators of mitochondrial biogenesis were decreased while the abundance of constituents of the mitophagy, autophagy and mitochondrial fission machinery was increased in response to hypoxia. In addition, placental hypoxia was associated with increased oxidative stress, inflammation, and apoptosis. Moreover, experiments with MitoQ revealed that hypoxia-induced reactive oxygen species originated from the mitochondria in the trophoblasts. DISCUSSION: This study is the first to demonstrate that placental hypoxia is associated with mitochondrial-generated reactive oxygen species and significant alterations in the molecular pathways controlling mitochondrial content and function. Furthermore, our data indicate that targeting mitochondrial oxidative stress may have therapeutic benefit in the management of pathologies related to placental hypoxia.

Contains fulltext : 229421.pdf (Publisher’s version ) (Closed access), OBJECTIVES: Given the crucial role of the placenta in establishing a healthy pregnancy, reliable non-invasive methods to measure placental perfusion are desirable. The aim of this study is to determine the reproducibility and potential bias in different three-dimensional power Doppler (3DPD) methods assessing placenta perfusion. METHODS: Ten singleton pregnancies around 16 weeks of gestation, with an anteriorly located placenta and centrally inserted umbilical cord were included in this study. Eight different combinations of a specific placental sweep and sonobiopsy method were used to evaluate placental perfusion. Vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) were determined offline using the 4D-view program. Reproducibility and repeatability of the methods, expressed as correlation coefficients and Bland-Altman mean differences, were calculated. Differences between sampling methods were analyzed using t-test or Mann-Whitney U test. RESULTS: Intra- and inter-class correlation coefficient (CC) was highest when using a spherical centrally placed sonobiopsy of 2 cm(3) in a whole placenta sweep (method 1; IntraCC VI 0.985, FI 0.769, VFI 0.993, InterCC VI 0.986, FI 0.784, VFI 0.987). Overall, intraCCs were higher compared to interCCs. Lowest mean differences in VI and FI were found comparing spherical to manual sonobiopsies, whereas the mean differences in VFI were lowest when comparing central versus peripheral located sonobiopsies. Comparing the three vascular indices, best median intra- and interCC and lowest mean differences were found for VFI. CONCLUSIONS: Three dimensional placental vascularization analysis showed best reproducibility using whole placental sweep volume and centrally located, spherical sonobiopsy of 2 cm(3).

Contains fulltext : 229316.pdf (Publisher’s version ) (Open Access)

Importance: Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective: To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants: This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions: Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures: The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results: Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weig

Contains fulltext : 229296.pdf (Publisher’s version ) (Closed access), BACKGROUND: Even though a lot of research has been done on postnatal growth and the occurrence of catch-up growth in small-for-gestational age (SGA) neonates, this phenomenon has not been studied well in appropriate-for-gestational age (AGA) neonates. Postnatal catch-up growth may also occur in AGA neonates indicating a compensatory mechanism for undiagnosed intrauterine growth restriction, especially in AGA neonates with reduced fetal growth velocity. AIMS: To describe postnatal growth during the first 5 years of life in SGA and AGA neonates and evaluating the role of fetal growth velocity in catch-up growth. STUDY DESIGN: Retrospective study in a Dutch tertiary hospital. SUBJECTS: 740 singleton neonates, without congenital anomalies, with ultrasound fetal growth data from 20 weeks and 32 weeks of pregnancy. OUTCOME MEASURES: Postnatal growth measurements of height (cm) and weight (kg) from birth until five years of age. Postnatal catch-up growth defined as difference (delta) in both height and weight between 4 weeks and 3 years of age. RESULTS AND CONCLUSIONS: SGA neonates had a significantly lower height and weight compared to the AGA group for all available measurement moments till 3 years. The catch-up growth between the SGA and AGA groups from 4 weeks up to 3 years after birth was not different between the two groups. However, neonates with reduced fetal growth velocity had a significantly higher risk for catch-up growth in height during the first 3 years after birth. This suggests a role for fetal growth velocity measurement in predicting fetal and subsequent postnatal growth potential.