Abnormal Uterine Artery Research Articles

Assessment of the cerebroplacental ratio and uterine arteries in low-risk pregnancies in early labour for the prediction of obstetric and neonatal outcomes

BackgroundThe evidence-based management of human labor includes the antepartum identification of patients at risk for intrapartum hypoxia. However, available evidence has shown that most of the hypoxic-related complications occur among pregnancies classified at low-risk for intrapartum hypoxia, thus suggesting that the current strategy to identify the pregnancies at risk for intrapartum fetal hypoxia has limited accuracy. ObjectiveTo evaluate the role of the combined assessment of the cerebroplacental ratio (CPR) and uterine arteries (UtA) Doppler in the prediction of obstetric intervention (OI) for suspected intrapartum fetal compromise (IFC) within a cohort of low-risk singleton term pregnancies in early labor. MethodsProspective multicentre observational study conducted across four tertiary Maternity Units between January 2016 and September 2019. Low-risk term pregnancies with spontaneous onset of labor were included. A two-step multivariable model was developed to assess the risk of OI for suspected IFC. The baseline model included antenatal and intrapartum characteristics, while the combined model included antenatal and intrapartum characteristics plus Doppler anomalies such as CPR MoM < 10th percentile and mean UtA Doppler PI MoM ≥ 95th percentile. Predictive performance was determined by receiver–operating characteristics curve analysis. Results804 women were included. At logistic regression analysis, CPR MoM < 10th percentile (aOR 1.269, 95 % CI 1.188–1.356, P < 0.001), mean UtA PI MoM ≥ 95th percentile (aOR 1.012, 95 % CI 1.001–1.022, P = 0.04) were independently associated with OI for suspected IFC. At ROC curve analysis, the combined model including antenatal characteristics plus abnormal CPR and mean UtA PI yielded an AUC of 0.78, 95 %CI(0.71–0.85), p < 0.001, which was significantly higher than the baseline model (AUC 0.61, 95 %CI(0.54–0.69), p = 0.007) (p < 0.001). The combined model was associated with a 0.78 (95 % CI 0.67–0.89) sensitivity, 0.68 (95 % CI 0.65–0.72) specificity, 0.15 (95 % CI 0.11–0.19) PPV, and 0.98 (0.96–0.99) NPV, 2.48 (95 % CI 2.07–2.97) LR + and 0.32 (95 % CI 0.19–0.53) LR- for OI due to suspected IFC. ConclusionsA predictive model including antenatal and intrapartum characteristics combined with abnormal CPR and mean UtA PI has a good capacity to rule out and a moderate capacity to rule in OI due to IFC, albeit with poor predictive value.

Effects of uterine Doppler on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study

Objective To investigate midbrain growth, including corpus callusum (CC), cerebellar vermis (CV) and cortical development in late fetal growth restriction (FGR) depending on uterine artery (UtA) Pulsatility Index (PI) values. Methods This was a prospective study including singleton fetuses with late FGR characterized by abnormal cerebral placental ratio (CPR). According to UtA PI values, the FGR fetuses were subdivided into normal ≤95th centile) and abnormal (>95th centile). Neurosonography was performed at 33–44 weeks of gestations to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size. Results The study cohort included 60 fetuses with late FGR, 39 with normal UtA PI and 21 with abnormal PI values. The latter group showed significant differences in CC (median (interquartile range) normal 35.9 (28.49–45.53) vs abnormal UtA PI 25.31(19.76–35.13) mm; p < 0.0022), CV (normal 25.78 (18.19–29.35) abnormal UtA PI 17.03 (14.07–24.16)mm; p = 0.0067); SF (normal 10.58 (8.99–11.97)vs abnormal UtA PI 7.44 (6.23–8.46) mm; p < 0.0001), POF (normal 6.85 (6.35–8.14) vs abnormal UtA PI 4.82 (3.46–7.75) mm; p < = 0.0184) and CF (normal 04.157 (2.85–5.41) vs abnormal UtA PI 2.33 (2.49–4.01)); p < 0.0382). Conclusions Late onset FGR fetuses with abnormal UtA PI showed shorter CC and CV length and delayed cortical development compared to those with normal uterine PI. These findings support the existence of a link between abnormal brain development and changes in utero placental circulation.

The Ability of Doppler Uterine Artery Ultrasound to Predict Premature Birth.

Demonstration of the predictive capacity of Doppler Uterine Artery (UtA) on preterm birth (PB) by serial measurement at various ages of pregnancy. The prospective study included a group of 116 pregnant women, of whom 85 gave birth prematurely and 31 pregnant women gave birth at term, constituting the control group. UtA Doppler measurement was performed by the abdominal approach. Quantitative wave evaluations were performed by the pulsatility index (PI), the systole/diastole ratio (S/D), as well as the qualitative analysis of the flow rate waveform (notch). UtA Doppler evaluation was performed in 3 pregnancy periods: 18.0-22.6 weeks, 28.0-31.6 weeks, and 32.0-35.6 weeks. Only at the third examination, at 32.0-35.5 weeks of gestation, was there a statistically significant difference between the S/D-UtA ratio and PI-UtA correlated with the risk of premature birth (p<0.05). Although there was an association between UtA Doppler and late preterm birth, the predictive ability was low. Also, UtA Doppler was not statistically significant for preterm birth before 32 weeks of gestation. Although we did not find a statistical association between second-trimester UtA Doppler and preterm birth, we do suggest a closer look at women with abnormal UtA Doppler in the second trimester. We believe that, according to the results obtained, UtA Doppler can predict especially iatrogenic premature birth depending on the prediction of the most severe complications, severe preeclampsia, and SGA.

A Comparison of Changes in the Mean Arterial Blood Pressure and Mean Uterine Artery Pulsatility Index from 11-14 to 19-24 + 6 Gestation Weeks in Low-Risk and High-Risk Asian Indian Pregnant Women.

Aim The aim of this study was to determine the changes in the mean arterial blood pressure (MAP) and mean uterine artery (UtA) pulsatility index (PI) from 11-14 to 19-24 + 6 gestation weeks in Asian Indian pregnant women. Methods Clinical and demographic details, MAP, and mean UtA PI measures were ascertained for pregnant women at 11 to 14 gestation weeks and 19-24 + 6 gestation weeks. Women were categorized as a high-or-low risk for preterm preeclampsia using the Fetal Medicine Foundation algorithm and 1 in 150 cutoff. High-risk pregnant women were recommended low-dose aspirin 150 mg daily at bedtime. Changes in MAP and mean UtA PI were compared for gestational age intervals and high-and-low risk women using nonparametric tests. Results The study analyzed the results of 1,163 pregnant women. Both MAP (mean difference: 5.14, p < 0.001) and mean UtA PI (mean difference: 0.14, p < 0.001) remained significantly higher at the second-trimester assessment in high-risk pregnant women compared to low-risk pregnant women. Seventy-seven (35.16%) of the 219 pregnant women with abnormal mean UtA PI in the first trimester had an abnormal mean UtA PI in the second-trimester assessment. One hundred (10.59%) of the 944 pregnant women with normal mean UtA PI in the first trimester had an abnormal mean UtA PI in the 19-24 + 6 weeks assessment. Seventy-seven pregnant women (6.62% of 1,163 women, 95% confidence interval: 5.33, 8.20) had an abnormal mean UtA PI at both gestation age intervals. High-risk pregnant women taking low-dose aspirin daily showed a larger reduction in mean UtA PI compared to high-risk pregnant women that did not report the use of low-dose aspirin (0.89 vs. 0.62, p <0.001) Conclusion MAP and mean UtA PI decreased significantly from the first to the second trimester of pregnancy. Sequential assessment of the MAP and mean UtA PI in the first and second trimesters of pregnancy will be useful for fetal radiologists in India to identify a subgroup of women with abnormal mean UtA PI at both trimesters that may need more intense surveillance and follow-up till childbirth.

Colour Doppler and Adverse Perinatal Outcomes in Pregnancies with Foetal Growth Restriction: A Prospective Longitudinal Study

Introduction: Foetal Growth Restriction (FGR) accounts for a significant proportion of perinatal morbidity and mortality. The study was done to diagnose the foetuses “at risk”, so that timely intervention could prevent perinatal morbidity and mortality, as FGR foetuses with deranged velocimetry of Uterine Artery (UA), Umbilical Artery (UMA), Middle Cerebral Arteries (MCA) are associated with high perinatal morbidity and mortality. Aim: To evaluate the usefulness of blood flow velocimetry of UA, UMA, and MCA as well as a Cerebroplacental Ratio (CPR) on colour doppler and their prediction of adverse perinatal outcome. Materials and Methods: This was a prospective longitudinal study done in the Department of Obstetrics and Gynaecology, Government Medical College and Rajindra Hospital, Patiala, Punjab, India from October 2021 to March 2022. The study was conducted among 200 antenatal patients, who had a singleton pregnancy, irrespective of age and parity and had FGR foetuses. Blood flow velocities in the UA, UMA, MCA, and CPR were measured. Patients were divided into four groups with 50 patients in each group. Group I included FGR foetuses with normal blood velocities, group II included FGR foetuses with abnormal UA velocimetry, group III included FGR foetuses with abnormal UMA and MCA velocimetry and group IV included FGR foetuses with abnormal CPR. Adverse perinatal outcomes in the form of Respiratory Distress Syndrome (RDS), prematurity, Appearance, Pulse, Grimace, Activity and Respiration (APGAR) &lt;7 at 5 minutes, admission to Neonatal Intensive Care Unit (NICU), and perinatal mortality were assessed in relation to these doppler blood flow patterns. Categorical variables were analysed with the help of Chi-square test and Fisher-exact Test. Continuous variables were analysed with ANOVA when data were normally distributed otherwise Kruskal Wallis H test was used. Results: The mean birth weight was 2432±423, 2209±329, 2100±223 and 1329±403 grams in Groups-I, II, III, and IV (p-value of &lt;0.001.) The mean gestational age was 38.1±2.3, 37.3±3.2, 36±3.6 and 33.1±3.1 weeks in groups I, II, III, and IV (p-value of &lt;0.001). Perinatal morbidity in the form of RDS and prematurity were compared among four groups with 0, 3 (6%), 17 (34%), and 39 (78%) in Groups I, II, III, and IV (p-value of &lt;0.001). APGAR score &lt;7 at 5 minutes was 0, 2 (4%), 9 (18%), and 13 (26%) in groups 1, II, III, and IV (p-value of &lt;0.001). A total of 6 (12%), 16 (32%), 37 (74%) and 46 (92%) C-sections were performed in group I, II, III and IV, respectively, p-value of &lt;0.001. Maternal mortality of 1 (2%) in group III and 2 (4%) was observed in group IV. But no maternal death was there in group I and II. Conclusion: The adverse perinatal outcomes were seen with changes in Pulsatility Index (PI) value of UA, UMA, MCA. But the patients with a deranged CPR ratio had got worse perinatal outcomes than either deranged MCA, PI or UMA PI alone. Hence, doppler ultrasound especially CPR ratio should be an integral component of routine evaluation of FGR pregnancies, as it helps in obstetrical surveillance and management, and thereby improving adverse perinatal outcomes.

Uterine artery Doppler for the prediction of outcome in pregnancies complicated by hypertensive disorders of pregnancy.

To evaluate, in pregnancies complicated by hypertensive disorders of pregnancy (HDP), the predictive role of uterine artery (UtA) Doppler for pregnancy outcome compared to the definition of preeclampsia (PE) established by ISSHP recommendations. Retrospective cohort study including singleton pregnancies diagnosed with HDP, who underwent UtA Doppler assessment at admission in 2011-2017. The study population was classified considering the presence or absence of PE and according to the presence or absence of abnormal UtA Doppler (mean pulsatility index>95th percentile). Pregnancy outcome, maternal and fetal complications, evaluated as composite outcomes (CO), and duration of pregnancy (from admission to delivery). A total of 311 mother-infant couples was included.The diagnostic ability of the two classifications was analysed comparing the relative likelihood ratio in the Biggerstaff graph. ISSHP definition turned out to be more efficient in detecting maternal adverse CO in comparison to UtA Doppler, relative positive likelihood ratio 1.50 (1.35-1.66) and 1.31 (1.07-1.60). UtA Doppler classification resulted more efficient in predicting adverse neonatal CO than PE definition, relative positive likelihood ratio 2.21 (1.77-2.75) and 1.61 (1.37-1.90). UtA Doppler was significantly associated with delivery at earlier gestational ages both for patients affected by PE and for women affected by HDP without superimposed PE (respectively p=0.009 and p=0.037). UtA Doppler at HDP diagnosis is a useful bedside marker of fetal/neonatal complications, and is associated with pregnancy duration.

Marijuana use, fetal growth, and uterine artery Dopplers

Objective Marijuana (MJ) use is associated with adverse effects on fetal growth. We aimed to investigate the timing of suboptimal fetal growth onset in MJ-exposed pregnancies. In addition, we aimed to explore the relationship between MJ-exposure and both abnormal uterine artery (UtA) Doppler parameters and small for gestational age (SGA). Study design This was a secondary analysis of a prospective multicenter cohort that enrolled nulliparous individuals delivering non-anomalous fetuses beyond 20 weeks’ gestation. Marijuana exposure was ascertained by self-report or clinical urine toxicology testing. Ultrasound estimated fetal weights (EFWs) were assessed in participants at both 16w0d–21w6d and 22w0d–29w6d. EFWs and birth weight (BW) were converted to weight percentiles (wPCT). EFW and BW wPCTs were calculated using population-based standards. Additionally, a customized standard designed to be applicable to both EFWs and BWs within the same model was also used to allow for EFW to BW percentile trajectories. The primary outcome, longitudinal wPCT, was compared between individuals with and without MJ use in a linear mixed-effects regression model adjusting for tobacco. For modeling, wPCT was smoothed across gestational age; MJ was estimated as an intercept and linear difference in the slope of gestational age. UtA Doppler notching, resistance index (RI), and pulsatility index (PI) at 16w0d–21w6d were compared using t-test and χ 2. SGA at delivery was also compared. Results Nine thousand one hundred and sixty-three individuals met inclusion criteria; 136 (1.5%) used MJ during pregnancy. Individuals who used MJ were more likely to be younger, identify as non-Hispanic Black, and have had less education. Fetuses exposed to MJ had lower wPCT beginning at 28 weeks using population-based and customized standards, when compared to those without exposure. UtA notching, PI, and RI were similar between groups. SGA was more frequent in neonates exposed to MJ using both population-based (22 vs. 9%, p<.001) and customized (25 vs. 14%, p<.001) curves. Conclusions MJ-exposed fetuses were estimated to be smaller than unexposed fetuses starting at 28 weeks’ gestation across both growth standards without a difference in UtA Doppler parameters.

Association of combined second trimester maternal serum Homocysteine and Uterine Artery Doppler to predict adverse pregnancy outcome.

Disturbances in placentation increase the risk of maternal and fetal complications. Several biochemical and imaging modalities have been studied, but the hunt for a single effective screening test never became a reality as the causes of this complex condition are multifactorial and polygenetic, many of which we are only beginning to discover. Not many studies have been conducted in the developing countries like India and other low resource settings to consider whether it would be worthwhile to combine inexpensive and effective markers together for better prediction of adverse pregnancy outcome.This study primarily aims to investigate the predictability of combined screening with maternal serum homocysteine and second trimester uterine artery Doppler in diagnosis of adverse pregnancy outcome. A prospective cohort study which involved 100 women with singleton gestation, meeting the inclusion criteria, attending the inpatient or outpatient of Obstetrics and Gynaecology in Amrita Institute of Medical Sciences, Kerala, a tertiary care centre in Southern India from July 2016 and September 2018 was conducted. Serum Homocysteine estimation (tHcy) was done between 18 and 28weeks of gestation with informed consent, and uterine artery (UA) Doppler PI which is a non-invasive routine study was done along with targeted second trimester anomaly scan (18-24weeks) in Fetal Medicine Department. Cutoff values of tHcy and UA PI were computed at 95th (> / = 9.7mmol/l) and 90th percentile, respectively as reported by Onalan et al. [9] and Nicholaides et al. [4]. Statistical analysis was performed using IBM SPSS version 20.0 software. Chi-square test and diagnostic measures were also used. Of the 100 patients, 15% (n = 15) developed hypertensive disorder. 7% (n = 7) had FGR and 7%(n = 7) had spontaneous preterm birth. 6% (n = 6) neonates had an APGAR score < 7 and 8% neonates (n = 8) required immediate NICU admission. Statistically significant association was found when tHcy and UA PI were used together for the prediction of FGR (p = 0.003), preterm birth (p = 0.002) and low APGAR score at birth (p = 0.009) with a specificity of 83.4%. With regard to PIH, both parameters were found to be statistically significant only when used independently (p = 0.001) but not when used in combination (p = 0.17). Both elevated tHcy and abnormal UA PI used in combination predicted adverse pregnancy outcome like FGR but with a low sensitivity of 14.3% and high specificity of 98.9%. However, when used independently these markers predicted FGR with a better sensitivity (tHcy- 28.6% and UA PI- 44.4%). Findings from this study have been promising with potential clinical implications for the diagnosis and management of high-risk pregnancies. Though the independent role of the two markers in screening various adverse pregnancy outcomes could be proved, their combined use to improve predictivity of more complications warrants further studies on a larger population with appropriate randomisation.

First-trimester miscarriage rate decreases with hydralazine therapy in pregnancies with early uterine vascular insufficiency: a cohort study

Background Miscarriage is the most frequent cause of pregnancy loss, affecting 15–20% of clinically recognized pregnancies. Early uterine vascular insufficiency (EUVI), defined as abnormal uterine artery (UA) Doppler impedance indices in early pregnancy, is present in two-thirds of pregnancies ending in miscarriage after embryonic cardiac activity has been detected. There is currently no available therapy for reducing the risk of miscarriage in these cases. Objective To determine whether vasodilator therapy with hydralazine can reduce abnormally high UA impedance indices and miscarriage rates in pregnancies with EUVI when administered from before 9 weeks’ gestation until completing 13 weeks’ gestation. Methods A total of 253 consecutive singleton pregnancies with a live embryo and scanned before 9 weeks’ gestation were included in the study. Ninety-two pregnancies (36.3%) were classified as having EUVI. Hydralazine was administered in daily doses of 50 mg, starting 24–36 h after the initial diagnosis of EUVI and continuing throughout the first trimester. The miscarriage rate in the hydralazine-treated EUVI group was compared with the one observed in our previously reported untreated cohort and the pregnancies with EUVI that declined treatment with hydralazine. Results The miscarriage rate among the hydralazine-treated EUVI group was significantly lower than the previously reported untreated cohort (7.8% versus 26.2%, p = .003; odds ratio (OR) = 4.3, 95% confidence interval (CI) = 1.6–11.9). In 15 untreated pregnancies with EUVI, the miscarriage rate was similar to that of the previously reported untreated cohort (26.7% versus 26.2%; p = .603) and higher than the hydralazine-treated group (26.7% versus 7.8%, p = .05; OR = 4.4, 95% CI = 1.1–18.2). Conclusions Hydralazine therapy in pregnancies with EUVI was associated with a significant decrease in the rate of miscarriage. We suggest a sequence of events leading to a higher risk of miscarriage in pregnancies with EUVI and propose a potential mechanism through which hydralazine may reduce this risk.

Understanding the uterine artery Doppler waveform and its relationship to spiral artery remodelling

Analysis of the uterine artery (UtA) Doppler waveform is frequently used in high-risk pregnancies to assess the likelihood of adverse pregnancy outcomes, including preeclampsia and fetal growth restriction. Whilst abnormal UtA waveforms at 18–20 weeks are associated with adverse outcomes, the underlying cause of these waveform changes remains unknown. Current evidence suggests the long-held dogma that the UtA waveform is merely a reflection of trophoblast-induced spiral artery remodelling is incorrect. Hence, the origins of the waveform changes must be reassessed. Recent data from human and animal models suggests that the arcuate arteries, placental bed arterio-venous anastomoses and, most notably, the radial arteries may be more important in determining the UtA waveform profile than previously appreciated. Furthermore, there is increasing evidence implicating the maternal cardiovascular system in the pathophysiology of the complications predicted by the waveform changes, particularly preeclampsia, and therefore its underlying association with the UtA waveform warrants further investigation.

Pravastatin plus L-arginine prevents adverse pregnancy outcomes in women with uteroplacental vascular dysfunction

BackgroundUteroplacental vascular dysfunction, characterized by diminished uterine artery (UtA) blood flow in the second trimester is a clinically useful predictor of the further development of preeclampsia, fetal growth restriction and stillbirth. Efforts to develop effective treatments to protect pregnancies with abnormal UtA Dopplers would be of significant clinical benefit for mothers and their fetuses. ObjectiveThe aim of this pilot non randomized control study was to use pravastatin +L-arginine to improve uteroplacental haemodynamics and prevent adverse maternal and neonatal outcomes in women with abnormal Dopplers and high risk for developing adverse pregnancy outcomes. Study designThis study was performed between 2015 and 2018. All women received primary care at OB/GYN Polyclinic Jurisic and Narodni Front University Hospital, University of Belgrade Medical School, Serbia. Approval for investigational drug use was obtained and all women gave informed consent.10 pregnant women with a poor obstetric history that developed uteroplacental dysfunction (UtA pulsatility index (PI) above the 95th percentile and notching) at 20.5 weeks IQR [17.7–22] gave consent to be treated daily with pravastatin (40 mg) and L-arginine (1.5 g) to improve placental blood flow and pregnancy outcomes. 5 women remained untreated after diagnosis at 21 weeks [20−22] (control group). Due to presence of risk factors for pregnancy complications, close maternal and fetal monitoring was undertaken in all patients. Doppler examinations were performed to monitor changes in placental vascular resistance and fetal well-being and growth. ResultsPRAV+L-arginine improved uteroplacental haemodynamics, increased fetal growth and prevented early onset preeclampsia leading to delivery close to term (delivery date: median 38 weeks, IQR[36.5–39]) and appropriate weight for gestational age compared to controls, in which placental blood flow did not improve and 2 women developed severe early onset preeclampsia. Neonates from the control group were born preterm (25 weeks IQR[23.5–25]), growth restricted and spent several months at NICU. Two neonates died due to prematurity-associated complications. PRAV+L-arginine treatment prolonged pregnancies for 4.1 months, compared to 26 days in the untreated group, preventing neonatal complications associated with prematurity. The infants are now 1–3 years old and show normal growth and development. ConclusionThis study describes the successful management with pravastatin+L-arginine of 10 pregnant patients with uteroplacental vascular dysfunction and high risk of adverse maternal and fetal outcomes. A larger study is being organized to confirm these observations.

Maternal Amino Acid Profiles to Distinguish Constitutionally Small versus Growth-Restricted Fetuses Defined by Doppler Ultrasound: A Pilot Study.

Fetuses measuring below the 10th percentile for gestational age may be either constitutionally small for gestational age (SGA) or have pathologic fetal growth restriction (FGR). FGR is associated with adverse outcomes; however, identification of low-risk SGA cases is difficult. We performed a pilot study evaluating maternal markers of pathologic FGR, hypothesizing there are distinct amino acid signatures that might be used for diagnosis and development of new interventions. This was a cohort study of healthy women with sonographic fetal estimated fetal weight <5th percentile divided into two groups based upon umbilical artery (UmA) Doppler studies or uterine artery (UtA) Doppler studies. We collected maternal blood samples prior to delivery and used ion pair reverse phase liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry to assess 44 amino acids. Among 14 women included, five had abnormal UmA, and three had abnormal UtA Doppler results. Those with abnormal UmA showed elevated ornithine. Those with abnormal UtA had lower dimethylglycine, isoleucine, methionine, phenylalanine, and 1-methylhistidine. We found several amino acids that might identify pregnancies affected by pathologic FGR. These findings support the feasibility of future larger studies to identify maternal metabolic approaches to accurately stratify risk for small fetuses.

288: Is endothelial function impaired among women with placenta-mediated fetal growth restriction?

To assess maternal endothelial function in pregnancies complicated by IUGR due to placental dysfunction. Prospective study assessing endothelial function using EndoPAT device in 2 populations of pregnant patients: 1. women with estimated fetal weight (EFW) below 10th percentile and abnormal uterine arteries and/or umbilical artery flow (n=15); and 2. Women with AGA fetus without placental complications matched by gestational age at testing (control group, n=22). Exclusion criteria included multifetal gestation, hypertensive diseases, diabetes mellitus, renal disease, smoking and pregnancies complicated by fetal anomalies or genetic abnormalities. EndoPAT evaluates the change in peripheral vascular tone in reaction to temporal ischemia in a process called reactive hyperemia. The ratio of the readings before and after ischemia is used to calculate the score for endothelial function and called reactive hyperemia index (RHI). Abnormal RHI indicating endothelial dysfunction is defined as RHI ≤ 1.67 in the non-pregnant population. Demographic and clinical characteristics did not differ between the two groups. The mean gestational age at endoPAT examination was comparable between the IUGR and control group (32.5 ± 2.2 vs, 31.6 ± 3.2, p=0.21). The mean RHI was significantly lower in the IUGR group compared to the control group (1.32 ± 0.16 vs 1.51 ± 0.31, p= 0.02, respectively). As expected, mean gestational age at delivery as well as neonatal birth weight were lower in the FGR group compared to the control group (35.4 ± 2.3 vs 37.3 ± 2.6 p=0.04; 1640 ± 414 grams vs 2785 ± 587 grams, p< 0.001 respectively). Pregnant women with fetal growth restriction due to placental dysfunction are characterized by endothelial dysfunction. Further studies are required in order to determine whether endothelial dysfunction is the cause or the consequence of placental dysfunction. Furthermore, delivery of IUGR has been associated with the development of cardiovascular condition later in life. Thus, the results of the present study may provide a putative explanation for this association.

OC25.07: Maternal hemodynamics in small‐for‐gestational‐age pregnancies with and without fetal growth restriction

Small-for-gestational-age (SGA) pregnancies, and in particular those with fetal growth restriction (FGR) are associated with an increased risk of adverse outcomes. Abnormal uterine artery (UtA) Doppler and other measures of maternal hemodynamics appear to be independently associated with adverse fetal outcome. The aim of this study was to describe the maternal hemodynamic differences in normotensive, SGA pregnancies with and without FGR. This was a prospective study of SGA and control pregnancies. Measurements of maternal hemodynamics, using a non-invasive device (USCOM-1A) were obtained. Variables that are affected by gestational age and maternal characteristics were corrected for using device-specific reference ranges. Pregnancies with evidence of FGR were compared to those with SGA only and normal pregnancies using descriptive statistics. Statistical analysis was performed using the Chi-squared test and Mann-Whitney test. A total of 102 FGR, 64 SGA and 401 control pregnancies at 28-41 weeks were included in the analysis. Compared to controls, the FGR group had significantly lower median heart rate (HR) (80bpm vs 85bpm, p = 0.001), lower cardiac output (CO) (0.91MoM vs 0.98MoM, p = 0.003), and higher systemic vascular resistance (SVR) (1.2MoM vs 1.0MoM, p < 0.001). There was no significant difference in stroke volume (SV) (1.0MoM vs 0.98MoM, p = 0.647) between the FGR and normal pregnancy groups. In contrast, there were no significant differences in maternal hemodynamics between the SGA and control groups. FGR pregnancies present with maternal cardiovascular dysfunction, as evidenced by lower HR and CO as well as higher mean arterial pressure (MAP), SVR and UtA resistance. SV is unchanged in FGR pregnancy suggesting that the observed drop in CO is a consequence of lower maternal HR. Pregnancies resulting in SGA neonate, without evidence of fetal hypoxemia or adverse outcome have normal cardiovascular adaptation. Maternal HR and other hemodynamic parameters may be of value in distinguishing SGA from FGR.

Correlation of Doppler Velocimetry of Uterine and Umbilical Arteries with Placental Pathology in Pregnancy Associated with Intrauterine Growth Restriction

AbstractTo correlate histomorphology of the placenta with Doppler studies of uterine and umbilical arteries. A comparative observational study conducted on 75 pregnant women divided into 2 groups: Group 1 included 25 women with appropriate for gestational age fetuses. Group 2 included 50 women with FGR. Uterine and umbilical artery Doppler, study of placental pathology and immunohistochemistry of placental villous tissues were evaluated. There was a significant difference between the two study groups regarding both abnormal uterine (0 vs. 58%) and umbilical artery (0 vs. 58%) Doppler (p≤&lt;≤0.001). Syncytial knots≤&gt;≤30% (44 vs. 60%), fibrinoid necrosis≤&gt;≤5% (8 vs. 46.7%), placental infarction≤&gt;≤5% (0 vs. 15%), perivillous fibrinoid deposition≤&gt;≤5% (1.8 vs. 16.7%) (p≤&lt;≤0.001) but not calcifications (56 vs. 60%, p≤=≤0.121) were significantly higher in FGR placentas. A statistically significant (p≤&lt;≤0.001) increase in the expression of VEGF in FGR placentas when compared with normal placentas. Abnormal uterine artery but not umbilical artery Doppler was significantly associated with abnormal placental pathology. Women with both abnormal uterine and umbilical artery Doppler velocimetries were delivered earlier and their babies had lower mean birth and placental weight (p≤&lt;≤0.001). Incidence of abnormal placental pathology was significantly higher in this specific group of FGR pregnancies (p≤&lt;≤0.001). There is high association between abnormal uterine and umbilical artery Doppler and placental pathology in FGR associated pregnancies. Trial Registration NCT03081754.

Usefulness of uterine artery Doppler velocimetry as a predictor for hypertensive disorders in pregnancy in women with prehypertension before 20 weeks gestation.

Hypertensive disorders of pregnancy (HDP) is major complication of maternal-fetal outcomes in obstetric field. Although HDP is mainly defined by high blood pressure, the information about the relationship between prehypertension (preHTN, 120-139mmHg and 80-89mmHg) and HDP development is limited. The objective of this study is to determine the usefulness of preHTN before 20 weeks gestation and uterine artery (UtA) Doppler velocimetry as a predictor of HDP. A total of 2039 singleton pregnant women who had received continuous prenatal care were included in this study. The participants were classified into 2 groups based on the highest blood pressure (BP) under 20 gestational weeks as defined by the Joint National Committee 7: Normotensive (n = 1816) and preHTN pregnant women (n = 223). All preHTN pregnant women were assessed using UtA Doppler velocimetry, and the numbers of preHTN assessments were recorded. The risk of HDP was assessed in the PreHTN groups through patient history and Doppler velocimetry. Compared to normotensive patients, a total of 223 preHTN patients had a higher risk of preeclampsia (OR: 2.3; CI: 1.2–4.3), gestational hypertension (OR: 3.3; CI: 2.0–5.4) and any HDP (OR: 3.0; CI: 2.0–4.5). In the preHTN group, 134 (60.1%) patients had preHTN measured at least twice and 89 (39.9%) patients had preHTN. The results showed that two or more preHTN measurements have high sensitivity for predicting HDP (OR: 1.9; CI: 1.0–3.1; sensitivity: 83.8%; specificity: 47.2%). Additionally, the combination of abnormal UtA Doppler velocimetry results and at least two preHTN measurements showed a high accuracy in predicting HDP (OR: 2.9; CI: 1.1–4.1; sensitivity: 67.6%; specificity: 98.4%). In conclusion, close BP monitoring and recording of every preHTN event are important for pregnant women with preHTN history, and UtA Doppler examination in those women during the 2nd trimester can be a further aid in determining the risk of HDP.

Maternal cardiac function, uterine artery hemodynamics and natriuretic peptides at 22-24weeks of gestation and subsequent development of hypertensive disorders of pregnancy.

Maternal cardiac dysfunction as well as abnormal uterine artery (UtA) Doppler are associated with hypertensive disorders of pregnancy (HDP), but their relation is unclear. We investigated the correlation between maternal cardiac function, UtA hemodynamics and natriuretic peptides, and explored differences between women who subsequently developed HDP and those who did not. This wasa prospective cross-sectional cohort study of 347 pregnant women at 22-24weeks. Maternal cardiac function and systemic hemodynamics were investigated at baseline and after 90seconds of passive leg raising using impedance cardiography. Preload reserve was defined as percent change (Δ%) in stroke volume and cardiac output from baseline to passive leg raising. UtA hemodynamics was studied using Doppler ultrasonography. UtA blood flow, resistance and pulsatility index were calculated. Fasting venous blood samples were analyzed for natriuretic peptides (pro atrial natriuretic peptide [proANP], N-terminal pro brain natriuretic peptide [Nt-proBNP] and C-type natriuretic peptide [CNP]). The course and outcome of pregnancy were recorded. At baseline, ProANP correlated significantly with cardiac output (r=-0.122; P= .023) and left cardiac work index (r=-0.112; P= .037), whereas Nt-ProBNP correlated significantly with acceleration index (r= .127; P= .018) and velocity index (r=-0.111; P= .039. CNP correlated significantly with UtA blood flow (r= .118; P= .028) and resistance (r=-0.112; P= .037) but not with UtA pulsatility index (r= .034; P= .523). None of the natriuretic peptides correlated with preload reserve. At 22-24weeks, women who subsequently developed HDP had lower UtA blood flow (552 vs 692mL/min; P= .028), higher UtA resistance (0.28 vs .17mmHg/mL/min; P= .004) and higher mean UtA pulsatility index (1.12 vs .84; P< .001) compared with those who did not; however, the natriuretic peptide levels were similar in the two groups. Women developing HDP had a significantly higher increase in stroke volume and cardiac output and more reduction in systemic vascular resistance following passive leg raising compared with the reference group. Left cardiac work index, acceleration index and velocity index decreased following passive leg raising in the reference group but increased in women who later developed HDP. ProANP correlated with cardiac output and cardiac work, Nt-proBNP with indices of cardiac contractility, and CNP with UtA blood flow and resistance. None of these natriuretic peptides measured at 22-24weeks of gestation reflected cardiac preload reserve or predicted development of HDP.

De-novo abnormal uteroplacental circulation in third trimester: pregnancy outcome and pathological implications.

Hypertensive disorders of pregnancy (HDP) are associated with impaired placentation, as evidenced by abnormal uterine artery (UtA) Doppler. In normal pregnancy, mean UtA pulsatility index (PI) shows a progressive decline with gestational age (GA). However, previous studies have reported that a proportion of pregnancies demonstrate worsening UtA Doppler in later pregnancy. The aim of this study was to investigate the incidence of HDP according to the change in mean UtA-PI between the second and third trimesters. This was a retrospective cohort study of singleton pregnancies between March 1997 and March 2016 that underwent longitudinal UtA Doppler assessment in the second and third trimesters. All parameters were converted into centiles or multiples of the median (MoM), adjusting for GA. The study cohort was divided into two groups, according to change in mean UtA-PI between the second and third trimesters (those with a decrease or no change and those with an increase). HDP included women who developed pre-eclampsia and/or gestational hypertension. Logistic regression analysis was used to adjust for potential confounders. The analysis included 5887 pregnancies. The incidence of HDP was significantly higher in the group with increasing mean UtA-PI compared with those without (7.9% vs 5.8%; P= 0.002). Logistic regression analysis demonstrated that both third-trimester UtA-PI MoM (odds ratio (OR), 7.35; 95% CI, 4.66-11.6; P< 0.001) and stable or decrease in UtA-PI MoM between the second and third trimesters (OR, 0.43; 95% CI, 0.31-0.60; P< 0.001) were significant independent predictors for the development of HDP. Worsening of UtA Doppler is associated with HDP, independent of the value recorded in the second trimester. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Perinatal outcome and placental apoptosis in patients withlate-onset pre-eclampsia and abnormal uterine artery Doppler at diagnosis.

To determine the rate of placental apoptosis and adverse perinatal outcome in patients with late-onset pre-eclampsia (PE) and abnormal uterine artery (UtA) Doppler at diagnosis. This was a prospective cohort study of women with singleton pregnancy diagnosed with late PE, performed between August 2011 and January 2014 at the Maternal-Fetal Medicine Unit of Hospital Carlos Van Buren. Patients were stratified according to UtA Doppler status at diagnosis (pulsatility index (PI) ≤ or > 95th percentile). Logistic regression analysis was performed to identify associations between abnormal UtA Doppler and adverse maternal and perinatal outcomes. In a subset of this cohort for whom placental samples were available, immunohistochemical analysis of the placenta was performed to identify the rate of apoptosis and its association with UtA Doppler by comparing samples from those with normal and those with abnormal UtA Doppler and normotensive controls. Non-parametric linear trend analysis was performed for assessment of the apoptotic index. Eighty-six patients were included in the final analysis. Of these, UtA-PI was above the 95th percentile in 33 (38.4%) patients. Gestational age at diagnosis and delivery were significantly lower in this group compared with patients with normal UtA Doppler. Abnormal UtA Doppler was associated with increased risk of severe PE (odds ratio (OR) = 7.5; 95% CI, 2.76-20.46; P < 0.001), late preterm delivery (OR = 13.7; 95% CI, 4.53-41.46; P < 0.001), small-for-gestational age at birth (OR = 12.3; 95% CI, 3.17-47.57; P < 0.001) and admission to the neonatal intensive care unit (OR = 12.8; 95% CI, 2.61-62.36; P = 0.002). Moreover, UtA Z-score demonstrated a significant inverse correlation with birth-weight Z-score (r = -0.34; P = 0.0013). Mean placental apoptotic index demonstrated an ascending linear trend according to UtA Doppler status (P = 0.04). In patients with late PE, UtA Doppler was useful for clinical classification and as an indicator of placental histological findings. Correlation between UtA Doppler and the apoptotic index provides new evidence of a subgroup of late PE with a placental origin. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

EP16.04: The value of uterine artery Doppler at 18–24 weeks' gestation in predicting adverse pregnancy outcomes among pregnant women with chronic hypertension

To evaluate the value of uterine artery Doppler in predicting adverse pregnancy outcomes among women with chronic hypertension in a tertiary hospital. This is a retrospective diagnostic validity study evaluating the value of uterine artery (UA) Doppler at 18-24 weeks age of gestation in predicting adverse pregnancy outcomes among women with Chronic Hypertension (CH) in a tertiary hospital from January 1, 2012 to December 31, 2013, who delivered 24 weeks or more. CH was defined as persistent BP greater than 140/90 mmHg diagnosed before pregnancy or before 20 gestation. Abnormal UA Doppler was described as the presence of an elevated uterine artery resistance index or the presence of a diastolic notch or both. Patients diagnosed with fetal congenital anomaly, other medical problems and higher order gestation were excluded. Fifty-five % CH women had an abnormal UA Doppler and 45%of them had normal results. Among the CH patients with abnormal UA Doppler, the most common adverse pregnancy outcomes were superimposed pre-eclampsia (SPE) (57%), preterm delivery (43%), and IUGR (27%). The findings of abnormal UA Doppler has a high sensitivity of 92.6% and specificity of 63.3% for the development of SPE, with a PPV of 57% and a high negative predictive value of 94%. The positive likelihood ratio (LR) of CH women with abnormal UA Doppler to develop SPE is 2.5 higher compared to those with normal UA Doppler. Abnormal UA Doppler has a sensitivity of 38.1% and a specificity of 83.3% to have babies that are SGA with a positive LR of 2.29, PPV of 72.7% and negative predictive value of 53.6%. Abnormal UA Doppler has a low sensitivity of 5% and but a high specificity of 100% for stillbirth with a PPV 100% and negative predictive value of 46%. UA Doppler study between 18-24 weeks gestation among CH women could be a good predictor and screening tool to asses high risk women to develop adverse pregnancy outcomes especially superimposed pre-eclampsia.