Abnormal Umbilical Artery Doppler Velocimetry Research Articles

Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction.

BACKGROUNDSevere, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, thus preventing accurate patient counseling. We investigated the use of maternal serum protein and ultrasound measurements at diagnosis to predict fetal or neonatal death and 3 secondary outcomes: fetal death or delivery at or before 28+0 weeks, development of abnormal umbilical artery (UmA) Doppler velocimetry, and slow fetal growth.METHODSWomen with singleton pregnancies (n = 142, estimated fetal weights [EFWs] below the third centile, less than 600 g, 20+0 to 26+6 weeks of gestation, no known chromosomal, genetic, or major structural abnormalities) were recruited from 4 European centers. Maternal serum from the discovery set (n = 63) was analyzed for 7 proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease, and 5 proteins identified through pooled liquid chromatography and tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n = 60), with final models calculated from combined data.RESULTSThe most discriminative model for fetal or neonatal death included the EFW z score (Hadlock 3 formula/Marsal chart), gestational age, and UmA Doppler category (AUC, 0.91; 95% CI, 0.86-0.97) but was less well calibrated than the model containing only the EFW z score (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery at or before 28+0 weeks included maternal serum placental growth factor (PlGF) concentration and UmA Doppler category (AUC, 0.89; 95% CI, 0.83-0.94).CONCLUSIONUltrasound measurements and maternal serum PlGF concentration at diagnosis of severe, early-onset FGR predicted pregnancy outcomes of importance to patients and clinicians.TRIAL REGISTRATIONClinicalTrials.gov NCT02097667.FUNDINGThe European Union, Rosetrees Trust, Mitchell Charitable Trust.

Maternal plasma syndecan-1: a biomarker for fetal growth restriction

Objective The identification of fetal growth disorders is an important clinical priority given that they increase the risk of perinatal morbidity and mortality as well as long-term diseases. A subset of small-for-gestational-age (SGA) infants are growth-restricted, and this condition is often attributed to placental insufficiency. Syndecan-1, a product of the degradation of the endothelial glycocalyx, has been proposed as a biomarker of endothelial damage in different pathologies. During pregnancy, a “specialized” form of the glycocalyx—the “syncytiotrophoblast glycocalyx”—covers the placental villi. The purpose of this study was to determine whether the concentration of maternal plasma syndecan-1 can be proposed as a biomarker for fetal growth restriction. Study design A cross-sectional study was designed to include women with normal pregnancy (n = 130) and pregnant women who delivered an SGA neonate (n = 50). Doppler velocimetry of the uterine and umbilical arteries was performed in women with an SGA fetus at the time of diagnosis. Venipuncture was performed within 48 h of Doppler velocimetry and plasma concentrations of syndecan-1 were determined by a specific and sensitive immunoassay. Results (1) Plasma syndecan-1 concentration followed a nonlinear increase with gestational age in uncomplicated pregnancies (R2 = 0.27, p < .001); (2) women with a pregnancy complicated with an SGA fetus had a significantly lower mean plasma concentration of syndecan-1 than those with an appropriate-for-gestational-age fetus (p = .0001); (3) this difference can be attributed to fetal growth restriction, as the mean plasma syndecan-1 concentration was significantly lower only in the group of women with an SGA fetus who had abnormal umbilical and uterine artery Doppler velocimetry compared to controls (p = .00071; adjusted p = .0028). A trend toward lower syndecan-1 concentrations was also noted for SGA with abnormal uterine but normal umbilical artery Doppler velocimetry (p = .0505; adjusted p = .067); 4) among women with an SGA fetus, those with abnormal umbilical and uterine artery Doppler findings had a lower mean plasma syndecan-1 concentration than women with normal Doppler velocimetry (p = .02; adjusted p = .04); 5) an inverse relationship was found between the maternal plasma syndecan-1 concentration and the umbilical artery pulsatility index (r = −0.5; p = .003); and 6) a plasma syndecan-1 concentration ≤ 850 ng/mL had a positive likelihood ratio of 4.4 and a negative likelihood ratio of 0.24 for the identification of a mother with an SGA fetus who had abnormal umbilical artery Doppler velocimetry (area under the ROC curve 0.83; p < .001). Conclusion Low maternal plasma syndecan-1 may reflect placental diseases and this protein could be a biomarker for fetal growth restriction. However, as a sole biomarker for this condition, its accuracy is low.

Isolated abdominal circumference vs. estimated fetal weight, which matters more?

Fetal growth restriction (FGR) is a leading cause of neonatal morbidity and mortality. In 2020, the Society of Maternal Fetal Medicine and the American College of Obstetricians and Gynecologists redefined fetal growth restriction from estimated fetal weight (EFW) less than the 10th percentile to EFW or abdominal circumference (AC) less than the 10th percentile. In our study, we seek to assess the rate of abnormal umbilical artery Doppler velocimetry in fetuses with FGR diagnosed by isolated AC less than the 10th percentile versus those diagnosed by EFW less than the 10th percentile.

The diagnosis and management of suspected fetal growth restriction: an evidence-based approach

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Prediction Model Assessing Risk of Delivery after Diagnosis of Abnormal Umbilical Artery Doppler.

Umbilical artery Doppler (UAD) velocimetry abnormalities are associated with increased neonatal morbidity and mortality. Currently, there are no risk stratification methods to assist in antepartum management such as timing of antenatal corticosteroids (ACS). Therefore, we sought to develop a model to predict risk of delivery within 7 days following diagnosis of abnormal UAD velocimetry in patients with fetal growth restriction (FGR). Retrospective single referral center study of liveborn singleton pregnancies complicated by FGR and ≥1 abnormal UAD velocimetry value (≥95th percentile for gestational age [GA]). We considered 17 variables and used backward stepwise logistic regression to create a multivariable model for the prediction of delivery within 7 days. We assessed model fit with calibration, discrimination, likelihood ratios, and area under the curve. Internal validation of the model was assessed by using the bootstrap method. Between 2008 and 2015, a total of 176 patients were eligible and included for model development. Median (range) GA at initial eligibility was 32.1 weeks (28.1-36.1 weeks) and from initial eligibility until delivery was 21 days (0-104 days). Fifty-two patients (30%) were delivered in the 7 days following inclusion. GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and pre-pregnancy BMI were included in the model. The model had an area under the ROC curve of 0.94 (95% confidence interval [CI]: 0.90-0.98), sensitivity of 85%, and specificity of 91%. If the model alone were used for ACS timing, 85% of the cohort who delivered in the following week would have received ACS, and ACS would not have been given to 91% who delivered later. Internal validation yielded similar results with a mean area under the curve (95% CI) of 0.94 (0.88-0.98). If validated externally, our model can be used to predict risk of delivery in patients with FGR and abnormal UAD velocimetry, potentially improving timing of ACS. · Risk of delivery in seven days can be predicted.. · Risk of delivery can inform corticosteroid timing.. · External validation can further develop a clinical aid..

753 Umbilical artery doppler improvement after steroid administration is associated with improved fetal growth

Betamethasone (BMZ) is commonly given for fetal growth restriction (FGR) with abnormal umbilical artery Doppler (UAD) velocimetry. Improvement of UAD can be seen after BMZ, but the impact of such improvement on fetal growth remains unclear. We tested the hypothesis that UAD improvement after BMZ is associated with improved growth and decreased risk for small for gestational age (SGA) infants. This was a retrospective cohort study of pregnancies complicated by FGR with abnormal UAD between 24-34 weeks gestational age. Abnormal UAD included elevated (pulsatility index >95%ile), absent end diastolic flow (EDF), or reversed EDF. We included patients who received BMZ at provider discretion within 1 week of abnormal UAD and had a growth assessment performed before and after BMZ administration. Improvement was defined as any improvement in category of UAD within 2 weeks of BMZ. The primary outcome was SGA. Secondary outcomes included growth velocity, GA at delivery, latency from BMZ administration to delivery, and neonatal morbidity. These outcomes were compared between patients with and without UAD improvement. Multivariable logistic regression was used to adjust for confounders. Of the 49 pregnancies meeting inclusion criteria, UAD improved in 28 (57.1%) after BMZ. Patients with improved UAD were significantly less likely to deliver an SGA infant compared to those without UAD improvement (aOR 0.21, 95% CI 0.05-0.93). Improved UAD was associated with higher growth velocity over the remainder of the pregnancy. Patients with UAD improvement had longer latency and delivered at a later gestational age than those without improvement. Composite neonatal morbidity was similar between groups after controlling for severity of UAD at diagnosis and GA at delivery. UAD improved in more than half of growth restricted fetuses following BMZ. UAD improvement was associated with a reduced risk of SGA, improved growth velocity, longer latency and later gestational age at delivery. UAD response to BMZ may be useful to further risk stratify FGR.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Induction of labour with unfavourable local conditions for suspected fetal growth restriction after 36 weeks of gestation: Factors associated with the risk of caesarean

IntroductionInduction of labour in women with an unfavourable cervix is associated with a risk of caesarean delivery. When a diagnosis of fetal growth restriction (FGR) is also involved, the risk of intrapartum fetal acidosis increases. The main objective was to identify prognostic factors for the risk of caesarean delivery after induction for suspected FGR after 36 weeks of gestation with an unripe cervix. Material and methodsThis was a retrospective, single-centre (Port Royal, Paris, France) study of women with a singleton fetus in cephalic presentation, with labour induced at or after 36 weeks for suspected FGR diagnosed during second or third trimester of pregnancy with an unripe cervix (Bishop score under 6) who gave birth between 1 January 2015 and 31 December 2019. A multivariable analysis was performed to identify the factors related to an increased risk of caesarean section. ResultsOf the 146 women included, 56 (38.4 %) had caesarean deliveries. After adjustment, the factors significantly associated with the risk of caesarean were maternal age greater than 39 years (ORa = 4.33 [1.22−17.2], reference: 25−39 years), nulliparity (ORa = 3.49 [1.25−11.2]), and an abnormal fetal umbilical artery Doppler velocimetry (ORa = 3.50 [1.47–8.70]). The risk of poor neonatal condition did not differ significantly between women with vaginal and caesarean deliveries (2.3 % vs 7.3 %, P = 0.21). ConclusionWhen FGR is suspected at 36 weeks of gestation and later, induction of labour is a reasonable option, even if the cervix is unripe, as the risk of caesarean delivery appears acceptable and neonatal status is good and similar with both modes of delivery.

Early Onset Fetal Growth Restriction: Does Path to Diagnosis Impact Outcomes and Pathology?

Objective:To evaluate demographics and outcomes of maternal-fetal pairs in early onset fetal growth restriction (FGR) requiring delivery prior to 34 weeks’ gestation based on ultrasound indication leading to diagnosis.Study Design:This is a descriptive study of maternal-fetal pairs with early FGR diagnosed prior to 30 weeks’ gestation and delivering between 22w0d and 34w0d under the care of Wake Forest University Perinatology 01/2012–12/2016. Serial ultrasounds to assess fetal growth and umbilical artery flow Doppler velocimetry were evaluated. Pairs were dichotomized into those with maternal comorbidities leading to ultrasound diagnosis, and those with ultrasound indicated only by appreciation of uterine size less than dates on exam. Patient characteristics and outcomes were tracked. Univariate and multivariate analyses were performed as appropriate.Results:56 pregnancies were identified with FGR prior to 30 weeks and subsequent delivery prior to 34 weeks. Common comorbidities present in the group with maternal comorbidities included chronic hypertension (30.5%), hypertensive disorders of pregnancy (36.1%), preexisting diabetes (13.9%), gestational diabetes (5.6%). None of the women in the S<D group developed hypertensive disorders of pregnancy or GDM. Other background characteristics were similar. Pregnancies evaluated for size less than dates were diagnosed on average 3 weeks later in gestation, had higher incidence of reverse end diastolic flow on Doppler evaluation both at diagnosis (80% vs. 22.9%, p=0.01, OR 0.08 (<0.01,0.74) and were more likely to be delivered for an urgent indication. Both groups of babies had similar survival to discharge rates and length of stay in the NICU. A subanalysis evaluating only babies with abnormal Doppler studies showed a shorter diagnosis to delivery interval and continued to show increased risk of urgent delivery due to fetal status in those pregnancies diagnosed based on size<dates.Conclusion:Women measuring size less than dates in the mid-trimester should be evaluated by ultrasound without delays. Early FGR carries a high mortality rate in all cases and in our pilot data, women measuring small were diagnosed later with fetal growth restriction and may represent a severe phenotype with poor fetal-placental circulation. These pregnancies often met criteria for urgent delivery in a short time frame, especially if abnormal umbilical artery Doppler velocimetry was noted.

Overexpression of the aryl hydrocarbon receptor nuclear translocator partially rescues fetoplacental angiogenesis in severe fetal growth restriction.

Pregnancies complicated by severe fetal growth restriction with abnormal umbilical artery Doppler velocimetry (FGRadv) are at substantial risk for adverse perinatal and long-term outcomes. Impaired angiogenesis of the placental vasculature in these pregnancies results in a sparse, poorly branched vascular tree, which structurally contributes to the abnormally elevated fetoplacental vascular resistance that is clinically manifested by absent or reversed umbilical artery Doppler indices. Previous studies have shown that aryl hydrocarbon receptor nuclear translocator (ARNT) is a key mediator of proper placental angiogenesis, and within placental endothelial cells (ECs) from human FGRadv pregnancies, low expression of ARNT leads to decreased vascular endothelial growth factor A (VEGFA) expression and deficient tube formation. Thus, the aim of the present study was to determine the effect of VEGFA administration or ARNT overexpression on angiogenic potential of FGRadv ECs. ECs were isolated and cultured from FGRadv or gestational age-matched control placentas and subjected to either vehicle vs VEGFA treatment or transduction with adenoviral-CMV (ad-CMV) vs adenoviral-ARNT (ad-ARNT) constructs. They were then assessed via wound scratch and tube formation assays. We found that VEGFA administration nominally improved FGRadv EC migration (P<0.01) and tube formation (P<0.05). ARNT overexpression led to significantly enhanced ARNT expression in FGRadv ECs (P<0.01), to a level similar to control ECs. Despite this, FGRadv EC migration (P<0.05) and tube formation (P<0.05) were still only partially rescued. This suggests that although ARNT does play a role in fetoplacental EC migration, other factors in addition to ARNT are likely also important in placental angiogenesis.

Achieving orphan designation for placental insufficiency: annual incidence estimations in Europe.

To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. Incidence estimation based on literature review and published national and EU statistics. European Union. Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93-3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10000 EU population (95% CI 3.07-3.60 per 10000 EU population). This fell below the EMA threshold of 5 per 10000 EU population. Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.

113: A prediction model to assess risk of delivery following abnormal umbilical artery doppler velocimetry

113: A prediction model to assess risk of delivery following abnormal umbilical artery doppler velocimetry

Clinical implications of umbilical artery Doppler changes after betamethasone administration†

Background: Betamethasone (BMZ) is commonly administered to patients with fetal growth restriction (FGR) and abnormal umbilical artery Doppler (UAD) velocimetry due to the increased risk of preterm delivery; however, the clinical impact of UAD changes after BMZ exposure is unknown.Objective: To test the hypothesis that lack of UAD improvement after BMZ administration is associated with shorter latency and greater neonatal morbidity in patients with FGR.Study design: This was a retrospective cohort study of pregnancies complicated by FGR and abnormal UAD between 240 and 336 weeks gestation. Abnormal UAD included the following categories of increasing severity: elevated (pulsatility index >95%), absent end diastolic flow (EDF), or reversed EDF improvement was defined as any improvement in category of UAD within two weeks of BMZ. Sustained improvement was defined as improvement until the last ultrasound before delivery, whereas transient improvement was considered as unsustained. The primary outcome was latency, defined as interval from betamethasone administration to delivery. Secondary outcomes were gestational age at delivery, umbilical artery pH, and a composite of neonatal morbidity (intubation, necrotizing enterocolitis, ionotropic support, intraventricular hemorrhage, total parenteral nutrition, neonatal death). Outcomes were compared between (a) patients with and without UAD improvement and (b) patients with sustained and unsustained improvement, using univariable, multivariable and time-to-event analyses.Results: Of the 222 FGR pregnancies with abnormal UAD, 94 received BMZ and had follow-up ultrasounds. UAD improved in 48 (51.1%), with 27 (56.3%) having sustained improvement. Patients with hypertension and drug use were less likely to have UAD improvement. Patients without UAD improvement had shorter latency (21.5 days [interquartile range (IQR) 8,45] versus 35 [IQR 22,61], p = .02) and delivered at an earlier gestational age (34 weeks [IQR 31,36] versus 37 [IQR 33,37], p < .01) than those with improvement. There were no differences in umbilical artery pH between groups. Composite neonatal morbidity was higher in patients without UAD improvement, but this was not statistically significant after adjusting for confounders (aOR 2.0; 95% CI 0.08–5.1). There were no differences in outcomes between patients with sustained versus unsustained improvement.Conclusions: UAD improved in half of patients following BMZ. Lack of UAD improvement was associated with shorter latency and earlier gestational age at delivery, but no difference in composite neonatal morbidity. UAD response to BMZ may be useful to further risk stratify FGR pregnancies.

Abnormal umbilical artery Doppler velocimetry and placental histopathological correlation in fetal growth restriction

Background . Doppler velocimetry (DV) is widely used to assess the vascular formation of the placenta in fetal growth restriction (FGR) and to estimate the haemodynamic condition of the growth-restricted fetus. Umbilical artery (UA) flow is essentially placental, rather than fetal. Hence, DV provides information about the fetal side of the placenta and, alongside placental histopathology, it could possibly help to decipher aetiopathogenesis in FGR cases. Objective . To correlate UA DV findings occurring in FGR with placental findings. Methods. The study was prospective and conducted in a low-income setting. A total of 130 non-anomalous singleton FGR pregnancies (≥24 weeks) were included in the study. All pregnancies were confirmed to be small for gestational age (SGA) after the birth of the neonate. The placental lesions and neonatal outcomes were correlated with DV findings before delivery: 65 cases with normal DV results constituted group 1, and group 2 had 65 cases with abnormal DV results such as reduced flow, absent UA end diastolic flow or reversal of UA end diastolic flow. Results . Group 2 had significantly lower mean (standard deviation) birth weights of 1.59 (0.4) kg v. 1.87 (0.23) kg for group 1 ( p <0.001). Considerably higher NICU mortality was seen in group 2 (30.5%) compared with group 1 (6.7%) ( p <0.001). The group 2 placentas weighed less, had a higher number of maternal underperfusion (MUP) lesions, higher levels of calcification. Among lesions of MUP, 4 lesions i.e. villous infarction ( p <0.001), villous agglutination ( p <0.001), syncytial knots ( p =0.003) and intervillous fibrin deposition ( p =0.001) were present in significantly higher numbers in the abnormal Doppler group compared with the normal Doppler group. Abnormal Doppler had a sensitivity of 80% and specificity of 92.3% for abnormal placental pathology (placental lesions ≥3). Conclusions. There was a significantly higher number of MUP lesions and neonatal morbidity in SGA patients with abnormal DV findings

Perinatal outcome of placental massive perivillous fibrin deposition: a case-control study.

The objectives of the study are to describe the obstetric outcomes associated with massive perivillous fibrin deposition (MFD) compared with a control series and to determine if outcome differs according to the extent of fibrin deposition. Retrospective case-control study based on placentas analyzed over a consecutive 12-year period. MFD was considered severe if it extended over more than 50% of the placenta and moderate between 25% and 50%. During the study period, MFD was observed on 71 placentas, 39 severe and 32 moderate. Compared with the 142 control women, the 39 women with severe MFD more often had histories of autoimmune disease and intrauterine fetal death. The case women with MFD were associated with elevated levels of maternal alpha-fetoprotein and with a high risk of severe growth restriction and/or intrauterine death. Compared with the infants with moderate MFD, those with severe MFD had also more abnormal umbilical artery Doppler velocimetry findings and more often intrauterine deaths and lower birthweights. Regardless of their extent, MFD that covered at least 25% of the placenta was almost always accompanied by severe growth restriction and by a high risk of intrauterine fetal death. Moreover, severe MFD tend to be associated with autoimmune diseases of the mothers, and pregnancies show more often a pathologic Doppler of the umbilical arteries and more often intrauterine fetal death that the moderate form. © 2017 John Wiley & Sons, Ltd.

The Placenta in Pre-Eclampsia: Association of Histology with Umbilical Artery Doppler Velocimetry

Objectives: To study the association of umbilical artery Doppler velocimetry with histological changes of the placenta in pre-eclampsia. Method: This was an observational study, conducted at two tertiary care centers in Sri Lanka between 2009 and 2010. A total of fifty placentae were studied; forty from women with pre-eclampsia and ten from normotensive women with uncomplicated pregnancies. Twenty pre-eclamptic patients with abnormal umbilical artery Doppler velocimetry were recruited in group 1. Group 2 included twenty gestational age-matched, pre-eclamptic patients with normal umbilical artery Doppler velocimetry. Ultra sound scan for umbilical artery Doppler was carried out to obtain the pulsatility index (PI) and resistance index (RI) approximately 24 hours prior to delivery. Five randomly selected, haematoxylin and eosin-stained sections from the maternal surface of each placenta were examined under high power (magnification 40) of light microscopy. Hundred terminal villi in each slide were examined to identify the presence of four histological features; syncytial knots, proliferative villous cytotrophoblast cells, thickening of sub-trophoblastic basement membrane, and villous hypovascularity. Results:All four histological features were present in a significantly higher proportion of placentae from pre-eclamptic patients (P 34 weeks). In hypertensive placentae, all four histological features were present in comparatively higher proportions in Group 1 (abnormal umbilical artery Doppler velocimetry) compared to Group 2 (normal umbilical artery Doppler velocimetry). But statistical significance was observed only invillous cytotrophoblast proliferation (P = 0.005), and villous hypovascularity (P = 0.002). Conclusion: The placental histological changes are significantly increased in pre-eclampsia. Further deterioration of placental histology is associated with abnormal umbilical artery Doppler velocimetry.

In vivo localisation and vascular effects of nano-vesicles derived from normal first trimester human placentae

In vivo localisation and vascular effects of nano-vesicles derived from normal first trimester human placentae

Prediction of Neonatal Outcome by Umbilical Artery Velocimetry in Intrauterine Growth Restriction: A Study in Western Nepal

The introduction of Doppler velocimetry to obstetrics offered a noninvasive and safe imaging modality of indirectly assessing the fetal and uteroplacental circulation. Obstetric Doppler ultrasound plays an important role in detecting Intra Uterine Growth Restriction (IUGR). The early diagnosis of IUGR with the help of abnormal flow patterns in umbilical, uterine and middle cerebral arteries using Doppler ultrasound may help in reducing perinatal and neonatal mortality and morbidity as well as reducing perinatal complications. This provides for timely interventions to prevent progression from IUGR to Intrauterine death (IUD).The study was carried out in 140 patients in Manipal Teaching Hospital, Pokhara for a period of twenty months from October 2013 to June 2015. All the cases presented to Radiology department for obstetric Doppler with clinical suspicion of IUGR were taken up for the study and obstetric doppler of umbilical artery was performed. Seventy two out of 140 (51.50%) had abnormal umbilical artery Doppler velocimetry. Fifty seven out of these 72 subjects (positive predictive value – 79.2%) with abnormal umbilical artery Doppler were later born with small for gestational age (SGA). The S/D ratio of umbilical artery of 3 or greater was considered abnormal in predicting IUGR and it showed sensitivity, specificity, positive predictive value, and negative predictive value of 76%, 76.9%, 79.2% and 73.5% respectively. Admission to the Neonatal Intensive Care Unit (NICU) and incidence of perinatal and neonatal mortality increased with the worsening of Doppler velocimetry. Twenty seven out of one hundred and forty neonates developed perinatal asphyxia, out of which 26 (96.3%) had abnormal umbilical artery velocimetry. NICU admissions comprised of a total of 30 neonates, out of which 27(90%) had abnormal umbilical artery Doppler velocimetry prenatally. Fifteen out of thirty didn’t survive, all of whom had abnormal umbilical artery Doppler velocimetry prenatally. There were 3 still born and all of them had abnormal umbilical artery velocimetry prenatally. The study could underline that abnormal Doppler velocimetry has a fairly good sensitivity and specificity for predicting IUGR and it is related with poor neonatal outcomes.

Impaired fetoplacental angiogenesis in growth-restricted fetuses with abnormal umbilical artery doppler velocimetry is mediated by aryl hydrocarbon receptor nuclear translocator (ARNT).

Fetal growth restriction with abnormal umbilical artery Doppler velocimetry (FGRadv), reflective of elevated fetoplacental vascular resistance, is associated with increased risks of fetal morbidity and mortality even in comparison to those of growth-restricted fetuses with normal placental blood flow. One major cause of this abnormally elevated fetoplacental vascular resistance is the aberrantly formed, thin, elongated villous vessels that are seen in FGRadv placentas. The purpose of this study was to determine the role of fetoplacental endothelial cells (ECs) in angiogenesis in normal pregnancies and in those complicated by FGRadv. Human placental specimens were obtained from FGRadv and gestational age-matched, appropriately grown control pregnancies for EC isolation/culture and for immunohistochemical studies. Additional mechanistic studies were performed on ECs isolated from subjects with term, uncomplicated pregnancies. We evaluated tube formation and differential angiogenic gene expression in FGRadv and control ECs, and we used ECs from uncomplicated pregnancies to further elucidate the molecular mechanisms by which angiogenesis is impaired in FGRadv pregnancies. Tube formation assays showed that FGRadv ECs demonstrate fewer branch points and total length compared with those from gestational age-matched controls, and this defect was not rescued by exposure to hypoxia. FGRadv ECs also demonstrated lower aryl hydrocarbon receptor nuclear translocator (ARNT) expression. ARNT knockdown resulted in suppression of key angiogenic genes including vascular endothelial growth factor A expression and led to deficient tube formation. ARNT expression in the placental vasculature mediates key angiogenic expression and fetoplacental EC angiogenesis, and low ARNT expression in FGRadv ECs appears to be a key factor in deficient angiogenesis. This, in turn, results in malformed thin villous vessels that structurally contribute to the abnormally elevated fetoplacental vascular resistance that is associated with high morbidity and mortality in fetal growth restriction.

Umbilical artery Doppler velocimetry study on prediction of adverse pregnancy outcomes among pregnant women with hypertensive disorders in Kano, Nigeria

Background: Doppler velocimetry studies have been widely used to predict adverse pregnancy outcomes in hypertensive disorders of pregnancies. Objective: To identify the pregnant women with hypertensive disorders for umbilical artery Doppler velocimetry to predict adverse pregnancy outcomes. Methods: This was a prospective study among 264 pregnant women with hypertensive disorders. The umbilical artery Doppler velocimetry study was conducted using 3.5 m Hz convex of the Mindry Digital Ultrasound Imaging System (Model DP-8800Plus; Shenzen Mindray Biomed Electronics, China). Results: A total of 264 pregnant women within the age of 18–40 years with a mean ± standard deviation of 31.33 ± 5.92 were studied. One hundred and twenty-four (29.90%) presented with pregnancy-induced hypertension (PIH), 72 (58.06%) had abnormal resistive indices (RIs) of at least 0.58 of which 4 had diastolic notches. The remaining 52 (41.94%) had normal RIs with no diastolic notch. Twenty (4.80%) presented with preeclampsia, 12 (60.00%) had abnormal RI of which four had diastolic notches. One hundred and twenty (28.90%) women presented with chronic hypertension, 72 (60.00%) had abnormal RI of which 16 had diastolic notches. Abnormal RI was associated with low Apgar scores and early neonatal death among the patients with PIH, low Apgar scores among patients with preeclampsia and low birth weight among chronic hypertensive pregnant women. Conclusion: We found abnormal umbilical artery Doppler velocimetry RI to be associated with adverse pregnancy outcomes. However, diverse nature of the hypertensive disorders and adverse pregnancy outcomes revealed different optimum cut-off points for various hypertensive disorders following ROC analysis.

Umbilical artery Doppler velocimetry study on prediction of adverse pregnancy outcomes among pregnant women with recurrent miscarriage at Aminu Kano Teaching Hospitals

Background: Pregnant women with previous history of recurrent miscarriage have higher risks of adverse pregnancy outcomes. Management of current pregnancies in patients with recurrent miscarriage is distressing for the patient and frustrating for the health care provider, especially where treatment options are limited. Doppler velocimetry studies of pregnant women in second trimester with recurrent miscarriage can predict adverse pregnancy outcomes. In this paper, we predict pregnancy outcomes using Doppler velocimetry among women with recurrent miscarriage. Patients and Methods: It was a prospective study among pregnant women with history of recurrent miscarriage. The umbilical artery Doppler velocimetry was carried out in second trimester using 3.5 mHz convex of the Mindry Digital Ultrasound Imaging System (Model DP-8800Plus; Shenzen Mindray Biomed electronics, China). Results: A total of 67 pregnant women with history of recurrent miscarriage were recruited for the study. The mean age ± standard deviation was 28.94 ± 5.59. Thirty-nine (58.21%) had abnormal resistive indices of which 15 (22.39%) had diastolic notches. Others had normal resistive indices. There were significant associations between high resistive index (RI) and the occurrence of preterm birth, low Apgar scores, low birth weight, and intra uterine fetal death. Conclusion: Majority of high risk pregnant women with history of recurrent miscarriage have high umbilical artery RI in second trimester of gestation. RI of at least 0.715 of the umbilical artery Doppler velocimetry is associated with adverse pregnancy outcomes following receiver operating characteristic analysis. Abnormal umbilical artery Doppler velocimetry among pregnant women with recurrent miscarriages predicted adverse neonatal outcomes.