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.

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

BACKGROUND: The 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. OBJECTIVE: To 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. METHODS: Prospective 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. RESULTS: 804 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. CONCLUSIONS: A 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.

vNOTES retroperitoneal transient uterine artery occlusion: a new approach to control bleeding during a high-risk evacuation of products of conception.

OBJECTIVE: To describe a retroperitoneal transient occlusion of the uterine or internal iliac artery in conjunction with a high-risk evacuation of products of conception. The procedure was performed vaginally, minimally invasively, via vaginal natural orifice transluminal endoscopic surgery. DESIGN: Description of the surgical technique using original video footage. This study was exempted from requiring hospital institutional review board approval. SETTING: Teaching hospital. PATIENT(S): A 34-year-old woman (G8P3) with a medical history of 2 cesarean sections, 1 partial mole, and a missed abortion with 2.8 L of blood loss. The patient presented after 10 weeks of amenorrhea. Ultrasound revealed a large blood-filled niche in the cesarean section scar with a thin overlying myometrium. A partial mole was suspected as well as increased vascularization in the myometrium and enhanced myometrial vascularity with arterial flow velocities of 100 cm/s. A risk of heavy blood loss in conjunction with curettage was anticipated. The patient had a strong preference for a fertility-preserving treatment, and after informed consent, she opted for transient occlusion of the uterine arteries with subsequent suction evacuation of the molar pregnancy. The patient signed a consent form accepting the procedure. The patient included in this video provided consent for publication of the video and posting of the video online including social media, the journal website, and scientific literature websites. Institutional review board approval was not required in accordance with the IDEAL guidelines. INTERVENTION(S): A vaginal incision was made over the bladder, and the vaginal mucosa was dissected. The paravesical space was dissected over the arcus tendinous, and the pelvic retroperitoneal space was opened. A small (7 cm) GelPOINT V-Path (Applied Medical, Rancho Santa Margarita, California) was inserted into the obturator fossa and insufflated with 10 CO2 mm Hg. Standard laparoscopic instruments were used through the gel port. Under endoscopic view, dissection to the right obturator fossa and iliac vessels was made, and the internal iliac artery was identified. A removable clip was placed on the origin of the right uterine artery. The same procedure was performed on the left side where the internal iliac artery was clipped. Different vessels were clipped to demonstrate and investigate the feasibility of both approaches. Both vessels were equally accessible. Care should be taken not to injure the uterine vein at the time of clipping. Dilation and evacuation was performed under transanal ultrasound surveillance. When hemostatic control was assured, first, the right clip was removed from the iliac artery. Hemostatic control was ensured, and after 10 minutes, the second clip on the left iliac artery was removed. The GelPOINT was removed, and the vaginal incision was sutured. The patient bled in total 500 mL. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): The patient recovered swiftly without complications. Pathology confirmed a partial molar pregnancy. CONCLUSION(S): Uterine or internal iliac artery ligation can be lifesaving in situations with massive bleeding from the uterus. Current minimally invasive approaches are laparoscopic vessel ligation and, more commonly, uterine artery embolization, which has unclear impact on fertility and has shown an increased risk of intrauterine growth restriction, miscarriage, and prematurity. As the patient was undergoing a vaginal evacuation of pregnancy, a vaginal and retroperitoneal approach of artery ligation was deemed least invasive. In patients with fertility-preserving wishes, care should to be taken to avoid as much trauma as possible to the endometrium. Optimized blood control, and a shorter duration of using a curette, may potentially reduce the risk of endometrial damage. We present a novel minimally invasive approach via vaginal natural orifice transluminal endoscopic surgery-retroperitoneal transient occlusion of the internal iliac or uterine artery. The whole procedure can be performed by the operating gynecologist, and the occlusion is transient and can be reversed in a stepwise controlled manner.

Application value of ultrasound elastography for screening of early pregnancy cervical insufficiency: a retrospective case-control study.

OBJECTIVE: This study aimed to investigate changes in the cervical strain rate (SR), cervical length (CL), and uterine artery blood flow parameters during early pregnancy in women with cervical insufficiency and evaluate the clinical efficacy of these markers for screening of cervical insufficiency in early pregnancy. METHODS: This retrospective study in 60 pregnant women with cervical insufficiency and 100 normal pregnant women was conducted between September 2021 and January 2023 and measured ultrasound parameters of the cervix during early pregnancy. The cervical SR, CL, and uterine artery resistance index (RI) were measured in both groups at 11-14 weeks of gestation. Strain elastography represented by the SR was used to assess the hardness of the internal and external cervical openings. RESULTS: During early pregnancy, the SR at the internal and external cervical openings were significantly higher in the cervical insufficiency group than those in the normal pregnancy group (SR I: 0.19 ± 0.018% vs. 0.16 ± 0.014%; SR E: 0.26 ± 0.028% vs. 0.24 ± 0.025%; p < .001). The CL was significantly shorter in the cervical insufficiency group than that measured in the normal pregnancy group (34.3 ± 2.9 mm vs. 35.2 ± 1.99 mm; p = .036), while cervical blood perfusion was also poorer in the cervical insufficiency group than that in the normal pregnancy group (uterine artery RI: 0.76 ± 0.07 vs. 0.74 ± 0.05; p = .048). Receiver operating characteristic (ROC) curve analysis showed that the optimal critical values for diagnosing cervical insufficiency were 0.17% for SR I, 0.25% for SR E, 33.8 mm for CL, and 0.78 for uterine artery RI. Of these parameters, the ROC curve for SR I had the largest area under the curve [AUC = 0.89 (p < .001)], with the highest sensitivity (78%) and specificity (82%). Multivariate logistic regression analysis demonstrated that the SR at the internal cervical opening (OR 17.47, 95% confidence interval (CI) 5.08-60.08; p < .001) and CL (OR 5.05, 95% CI 1.66-15.32; p = .004) still showed significant differences between the two groups. CONCLUSION: Cervical elastography is an effective tool for screening early pregnancy cervical insufficiency. The SR at the internal cervical opening is a valuable indicator for screening cervical insufficiency and has superior clinical efficacy for screening for this condition compared to that of CL and the uterine artery blood flow index.

Spiral, uterine artery doppler and placental ultrasound in relation to preeclampsia.

Preeclampsia (PE) is a multiorgan disorder that complicates around 2-8% of pregnancies and is a major cause of perinatal and maternal morbidity and mortality. PE is a clinical syndrome characterized by hypertension secondary to systemic inflammation, endothelial dysfunction, and syncytiotrophoblast stress leading to hypertension and multiorgan dysfunction. The uterine arteries are the main blood vessels that supply blood to the uterus. They give off branches and plays an important role in maintaining blood supply during pregnancy. The arcuate artery originates from the uterine artery and runs medially through the myometrium. The arcuate arteries divide almost directly into anterior and posterior branches, from which the radial artery leads directly to the uterine cavity during their course. Near the endometrium-myometrium junction, the radial artery generates spiral arteries within the basal layer and functional endometrium. The walls of radial and spiral arteries are rich in smooth muscle, which is lost when trophoblast cells invade and become large-caliber vessels. This physiological transformation of uteroplacental spiral arteries is critical for successful placental implantation and normal placental function. In normal pregnancy, the luminal diameter of the spiral arteries is greatly increased, and the vascular smooth muscle is replaced by trophoblast cells. This process and changes in the spiral arteries are called spiral artery remodeling. In PE, this genetically and immunologically governed process is deficient and therefore there is decreased vascular capacitance and increased resistance in the uteroplacental circulation. Furthermore, this defect in uteroplacental spiral artery remodeling is not only associated with early onset PE, but also with fetal growth restriction, placental abruption, and spontaneous premature rupture of membranes. Doppler ultrasound allows non-invasive assessment of placentation, while the flow impedance decreases as the pregnancy progresses in normal pregnancies, in those destined to develop preeclampsia the impedance is increased.

Prediction of preeclampsia in asymptomatic women.

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. It is important to identify women who are at high risk of developing this disorder in their first trimester of pregnancy to allow timely therapeutic intervention. The use of low-dose aspirin initiated before 16 weeks of gestation can significantly reduce the rate of preterm preeclampsia by 62 %. Effective screening recommended by the Fetal Medicine Foundation (FMF) consists of a combination of maternal risk factors, mean arterial pressure, uterine artery pulsatility index (UtA-PI) and placental growth factor (PLGF). The current model has detection rates of 90 %, 75 %, and 41 % for early, preterm, and term preeclampsia, respectively at 10 % false-positive rate. Similar risk assessment can be performed during the second trimester in all pregnant women irrespective of first trimester screening results. The use of PLGF, UtA-PI, sFlt-1 combined with other investigative tools are part of risk assessment.

Mid-trimester uterine artery Doppler for aspirin discontinuation in pregnancies at high risk for preterm pre-eclampsia: Post-hoc analysis of StopPRE trial.

OBJECTIVE: To assess whether aspirin treatment can be discontinued in pregnancies with normal uterine artery pulsatility index (≤90th percentile) at 24-28 weeks. DESIGN: Post-hoc analysis of a clinical trial. SETTING: Nine maternity hospitals in Spain. POPULATION OR SAMPLE: Pregnant individuals at high risk of pre-eclampsia at 11-13 weeks and normal uterine artery Doppler at 24-28 weeks. METHODS: All participants received treatment with daily aspirin at a dose of 150 mg. Participants were randomly assigned, in a 1:1 ratio, either to continue aspirin treatment until 36 weeks (control group) or to discontinue aspirin treatment (intervention group), between September 2019 and September 2021. In this secondary analysis, women with a UtAPI >90th percentile at 24-28 weeks were excluded. The non-inferiority margin was set at a difference of 1.9% for the incidence of preterm pre-eclampsia. MAIN OUTCOME MEASURES: Incidence of preterm pre-eclampsia. RESULTS: Of the 1611 eligible women, 139 were excluded for UtAPI >90th percentile or if UtAPI was not available. Finally, 804 were included in this post-hoc analysis. Preterm pre-eclampsia occurred in three of 409 (0.7%) women in the aspirin discontinuation group and five of 395 (1.3%) women in the continuation group (-0.53; 95% CI -1.91 to 0.85), indicating non-inferiority of aspirin discontinuation. CONCLUSIONS: Discontinuing aspirin treatment at 24-28 weeks in women with a UtAPI ≤90th percentile was non-inferior to continuing aspirin treatment until 36 weeks for preventing preterm pre-eclampsia.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Uterine arteries pulsatility index by Doppler ultrasound in the prediction of preeclampsia: an updated systematic review and meta-analysis.

BACKGROUND: Preeclampsia is a common pregnancy complication with serious potential risks for maternal and neonatal health. Early prediction of preeclampsia is crucial for timely prevention, surveillance, and treatment to improve maternal and neonatal outcomes. This systematic review aimed to summarize the available evidence on the prediction of preeclampsia based on Doppler ultrasound of uterine arteries at different gestational ages. METHODS: A systematic literature search and meta-analysis were conducted to evaluate the sensitivity and specificity of the pulsatility index of Doppler ultrasound of uterine arteries for predicting preeclampsia. The timing of ultrasound scans within and beyond 20 weeks of gestational age was compared to assess its effect on the sensitivity and specificity of the pulsatility index. RESULTS: This meta-analysis included 27 studies and 81,673 subjects (3309 preeclampsia patients and 78,364 controls). The pulsatility index had moderate sensitivity (0.586) and high specificity for predicting preeclampsia (0.879) (summary point: sensitivity 0.59; 1-specificity 0.12). Subgroup analysis revealed that ultrasound scans performed within 20 weeks of gestational age did not significantly affect the sensitivity and specificity for predicting preeclampsia. The summary receiver operator characteristic curve showed the pulsatility index's optimal range of sensitivity and specificity. CONCLUSIONS: The uterine arteries pulsatility index measured by Doppler ultrasound is useful and effective for predicting preeclampsia and should be implemented in the clinical practice. The timing of ultrasound scans at different gestational age ranges does not significantly affect the sensitivity and specificity.

The predictive value of uterine artery Doppler in the success rate of pregnancy from the first frozen embryo transfer during the implantation window.

BACKGROUND: Worldwide, frozen embryo transfer (FET) has become a new strategy for the treatment of infertility. The success of FET is closely related to endometrial receptivity. Does uterine artery Doppler during the implantation window predict pregnancy outcome from the first FET? METHODS: A total of 115 retrospectively collected cycles were included in the study, with 64 cycles of clinical pregnancy and 51 cycles of nonclinical pregnancy; There were 99 nonabsent end-diastolic flow (NAEDF) cycles and 16 absent end-diastolic flow (AEDF) cycles. The differences in uterine artery Doppler findings between different pregnancy outcomes were investigated. The clinical pregnancy rate and spontaneous abortion rate in the NAEDF and AEDF groups were compared. The predictive value of uterine artery Doppler during the implantation window in the success rate of pregnancy from the first FET was also investigated. RESULTS: Between the clinical pregnancy group and the nonclinical pregnancy group, there were no significant differences in the mean resistance index (mRI) (Z = -1.065, p = 0.287), mean pulsatility index (mPI) (Z = -0.340, p = 0.734), and mean peak systolic/end-diastolic velocity(mS/D) (Z = -0.953, p = 0.341); there were significant differences in the mean peak systolic velocity (mPSV) (Z = -1.982, p = 0.048) and mean end-diastolic velocity (mEDV) (Z = -2.767, p = 0.006). Between the NAEDF and AEDF groups, there was no significant difference in the clinical pregnancy rate (χ2 = 0.003, p = 0.959), and there was a significant difference in the spontaneous abortion rate (χ2 = 3.465, p = 0.019). Compared with uterine artery Doppler alone, its combination with artificial abortion history, waist-to-hip ratio, LH (Luteinizing hormone) of P (Progesterone) administration day, mPSV and mEDV had a higher predictive value regarding clinical pregnancy from the first FET [ROC-AUC 0.782, 95% CI (0.680-0.883) vs. 0.692, 95% CI (0.587-0.797)]. CONCLUSIONS: Uterine artery Doppler, particularly mPSV and mEDV during the implantation window, was useful for predicting clinical pregnancy, and AEDF was related to spontaneous abortion in the first trimester. Uterine artery Doppler combined with artificial abortion history, waist-to-hip ratio, LH of P administration day, mPSV and mEDV have a higher predictive value than uterine artery Doppler alone regarding the pregnancy from the first FET.

Association between abnormal uterine artery pulsatility index and the risk of fetal congenital heart defects: a hospital-based cohort study.

To explore the associations between high uterine artery pulsatility index (UtA-PI) values and congenital heart disease (CHD) risk and whether they differed between singleton and multiple pregnancies. This hospital-based cohort study involving 52,047 pregnant women who underwent prenatal examinations from 2012 to 2016. Infants born to the included pregnant women were followed until 42 days after birth to identify those with CHDs. Generalized estimating equations were used to estimate the associations of high right UtA-PI (> 95th percentile) values with maternal preeclampsia and fetal CHDs. Logistic regression analyses were conducted using path analysis models to quantify the effect of high right UtA-PI values on fetal CHD risk. A total of 42,552 women and 43,470 infants (147 with CHDs) were included. Preeclampsia risk was associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 3.01; 95% CI 2.57-3.52). CHD risk was marginally associated with a high right UtA-PI in singleton-pregnant women (adjusted PR, 2.26, 95% CI 1.03-4.95). Considering only two factors, 96.0% of the fetal CHD risk was mediated by preeclampsia in singleton-pregnant women, while 93.8% of the risk was related to a high right UtA-PI in multiple-pregnant women. A high right UtA-PI was marginally associated with an increased fetal CHD risk in singleton-pregnant women and might play an important role in multiple-pregnant women. Further studies are warranted to confirm these findings given the high loss to follow-up rate.

Is a sFlt-1/PlGF cutoff of 38 suitable to predict adverse outcomes in pregnancies with abnormal uterine artery Doppler velocimetry in the second trimester?

OBJECTIVE: To determine the optimal cutoff value for the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio to predict maternal and fetal adverse events in pregnancies with uterine artery Doppler scans results above the 95th percentile in the late second trimester. STUDY DESIGN: Retrospective, observational cohort study on 116 asyntomatic patients with abnormal uterine artery Doppler scans at gestational week 25. The sFlt-1/PlGF ratio was determined within the weeks 25 to 29 of gestation and ROC curve analysis performed. The diagnostic validity of different cutoff values to predict severe maternal and fetal complications, i.e. preeclampsia, fetal growth restriction, placental abruption, and fetal death, was analyzed. MAIN OUTCOME MEASURES: An ideal cutoff for sFlt-1/PlGF ratios in pregnancies with abnormal uterine artery Doppler in the second trimester. RESULTS: Applying a cutoff point of 38, the area under the ROC curve was 0.89, generally considered low risk in fetal and maternal complication prediction. The sensitivity was 32.1%, the specificity 98.4%, the positive predictive value (PPV) 94.4%, and the negative predictive value (NPV) 63.3%. A cutoff value of 10, leading to the highest Youden index, performed best at detecting overall complications, increasing sensitivity to 69.8% and the NPV to 76.8%. at the cost of a reduced specificity and PPV. CONCLUSIONS: In pregnancies with abnormal uterine artery Doppler in the second trimester, an sFlt-1/PlGF cutoff value greater than equal to 38 improves its predictive power for adverse events.

Clinical effectiveness of routine first-trimester combined screening for pre-eclampsia in Spain with the addition of placental growth factor.

INTRODUCTION: Pre-eclampsia affects 2%-8% of pregnancies and is one of the leading causes of maternal and perinatal morbidity and mortality. First-trimester screening using an algorithm that combines maternal characteristics, mean arterial blood pressure, uterine artery pulsatility index and biomarkers (pregnancy-associated plasma protein-A and placental growth factor) is the method that achieves a greater diagnostic accuracy. It has been shown that daily salicylic acid administration before 16 weeks in women at a high risk for pre-eclampsia can reduce the incidence of preterm pre-eclampsia. However, no previous studies have evaluated the impact of routine first-trimester combined screening for pre-eclampsia with placental growth factor after being implemented in the clinical practice. MATERIAL AND METHODS: This was a multicenter cohort study conducted in eight different maternities across Spain. Participants in the reference group were prospectively recruited between October 2015 and September 2017. Participants in the study group were retrospectively recruited between March 2019 and May 2021. Pre-eclampsia risk was calculated between 11+0 and 13+6 weeks using the Gaussian algorithm combining maternal characteristics, mean arterial pressure, uterine arteries pulsatility index, pregnancy-associated plasma protein-A and placental growth factor. Patients with a risk greater than 1/170 were prescribed daily salicylic acid 150 mg until 36 weeks. Patients in the reference group did not receive salicylic acid during gestation. RESULTS: A significant reduction was observed in preterm pre-eclampsia (OR 0.47; 95% CI: 0.30-0.73), early-onset (<34 weeks) pre-eclampsia (OR 0.35; 95% CI: 0.16-0.77), preterm small for gestational age newborn (OR 0.57; 95% CI: 0.40-0.82), spontaneous preterm birth (OR 0.72; 95% CI: 0.57-0.90), and admission to intensive care unit (OR 0.55; 95% CI: 0.37-0.81). A greater treatment adherence resulted in a significant reduction in adverse outcomes. CONCLUSIONS: Routine first-trimester screening for pre-eclampsia with placental growth factor leads to a reduction in preterm pre-eclampsia and other pregnancy complications. Aspirin treatment compliance has a great impact on the effectiveness of this screening program.

Ovarian and uterine arteries blood flow velocities waveform, hormones and nitric oxide in relation to ovulation in cows superstimulated with equine chorionic gonadotropin and luteolysis induction 10 and 17 days after ovulation.

To investigate the ovarian responses, ovarian and uterine hemodynamics, circulating ovarian hormones, and nitric oxide (NO) with their relations in superstimulated cows. Eight Holstein Friesian dry cows previously synchronized with CIDR underwent rectal Doppler ultrasound scanning and blood sampling after administrating eCG (1500 I.U) on day 10 of the second ovulation (day -5). Cows were treated with 12.5 mg prostaglandin F2α (PGF2α) on days 10 and 17 after ovulation. Estradiol, progesterone, and NO were measured. Results showed that from ≥ 13 follicles, five follicles ovulated from both ovaries. The ovulated follicles increased antrum colored area and colored area % till day -1. The developed corpora lutea (CLs) attained similar diameter, area, colored area, and colored area % from day 2 till day 15. The peak point of velocity (PSV) of uterine arteries decreased while that of ovarian arteries increased from day -4 to day 0. Both ovarian arteries diameter, resistance index (RI), PSV, end velocity (EDV) and systolic/diastolic ratio (S/D) positively correlated (P < 0.0001), but their pulsatility index (PI) negatively correlated (P < 0.0001). The uterine arteries PI, RI, PSV, EDV, time average velocity (TAMV) and S/D negatively correlated (P < 0.0001) but their diameters positively correlated. Estradiol increased but progesterone decreased from day -5 till day 0. After ovulation, P4 reached maximum values on day 9 and started to decrease till day 19.NO showed one peak on day -3 and another one from day 3 to day 9. Conclusions: Blood flow of ovarian arteries is different from uterine arteries and depended on pre- or post-ovulation.

Sonographic evaluation of maternal uterine artery from 11 - 30 weeks 6 days of gestational age in a Nigerian population: A predictive index for pre-eclampsia and intrauterine growth restriction.

INTRODUCTION: Uterine artery (UtA) Doppler sonography is a potential screening tool for pregnancy complications in placental insufficiency. Evaluation of the maternal and fetal vessels in pregnancy ensures accurate identification and prediction of pregnancy complications, such as preeclampsia (PE) and intrauterine growth restrictions (IUGR). The study aims to establish local reference values for UtA in a Nigerian population. METHODS: This prospective longitudinal study was conducted among 230 pregnant women. All participants had their left (Lt) and right (RT) UtAs evaluated with a Doppler ultrasound from 11 to 30 weeks 6 days of gestational age. Peak systolic velocity (PSV), End diastolic Velocity (EDV), Systolic/Diastolic ratio (S/D), Pulsatility Index (PI), and Resistivity Index (RI) were measured and documented. RESULTS: The mean values of UtA at 11-30 weeks 6 days of GA ranged as follows: 0.79-0.53 (RI), 1.83-0.79 (PI), 5.16-2.23 (S/D), 96.37-98.00 (PSV) & 26.07-44.14 (EDV). While the mean values of the Rt. & Lt. UtA 's ranged as follows: 0.79-0.50 (RI. Rt), 0.78-0.56 (RI. Lt), 2.05-0.80 (PI. Rt), 1.61-0.78 (PI. Lt), 6.03-2.13 (S/D. Rt), 4.29-2.33 (S/D. Lt), 89.79-99.23 (PSV. Rt), 102.76-96.71 (PSV. Lt) & 23.31-45.25 (EDV. Rt), 28.83-43.02 (EDV. Lt) respectively. CONCLUSION: UtA Doppler reference range was established in the study population. These reference ranges will be of clinical value in daily obstetric practice. IMPLICATION FOR PRACTICE: Obstetricians and sonographers will apply these values for early prediction of pregnancies at risk of complications in the locality.

First trimester SHARP1 and second-trimester uterine artery Doppler to predict preeclampsia.

OBJECTIVES: The objective of this study was to identify the predictive value of the first-trimester serum SHARP1 level and the second-trimester uterine artery Doppler in singleton pregnancy for the prediction of preeclampsia. METHODS: A prospective study including singleton pregnancy presenting at an antenatal clinic, King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University from 2019-March 2020 was conducted. Serum SHARP1 was collected at the gestational age (GA) of 11-13+6 weeks, and transabdominal uterine artery Doppler ultrasound was performed at GA of 18-24 weeks. Serum SHARP1 level and uterine artery pulsatility index (PI) were combined to calculate the predictive value for preeclampsia detection. RESULTS: 288 pregnant women were enrolled in the first trimester, but only 249 participants completed the study. Thirteen patients had preeclampsia (5.2%), which three cases (1.2%) had early-onset preeclampsia. The median serum SHARP1 level in the first trimester of pregnant women with preeclampsia was lower than the normal pregnancy group (1392 pg/ml vs. 1941 pg/ml, p = 0.046). The second-trimester uterine artery PI and prevalence of early diastolic notching were higher in the preeclampsia group than in the normal pregnancy group (p = 0.029 and p = 0.001, respectively). When the first-trimester serum SHARP1 level is combined with the second-trimester uterine artery PI, the sensitivity, specificity, PPV, and NPV for preeclampsia prediction were 84.6%, 47.5%, 8.2%, and 98.3%, respectively. CONCLUSIONS: This study demonstrated that serum SHARP1 level in the first trimester combined with the uterine artery PI in the second trimester had good sensitivity to predict preeclampsia.

Association between transabdominal uterine artery Doppler and small-for-gestational-age: a systematic review and meta-analysis.

BACKGROUND: The association between uterine artery Doppler (UtA) measurements and small for gestational age (SGA) has not been quantitatively analyzed throughout the whole pregnancy. This systematic review and meta-analysis aims to comprehensively explore the association between UtA measurements and SGA in the first, second, and third trimesters. METHODS: Studies were searched from Pubmed, Embase, Cochrane Library, and Web of Science. Weighted mean difference (WMD), odds ratio (OR), and relative risk (RR) with 95% confidence interval (CI) were used as the effect size. Heterogeneity of all effect sizes was tested and quantified using I2 statistics. Sensitivity analysis was conducted for all outcomes, and publication bias was evaluated using Begg's test. RESULTS: A total of 41 studies were finally included in our meta-analysis. In the first trimester, mean PI was significantly higher in the SGA group than the non-SGA group (WMD: 0.31, 95%CI: 0.19-0.44). In the second trimester, odds of notch presence (OR: 2.54, 95%CI: 2.10-3.08), mean PI (WMD: 0.21, 95%CI: 0.12-0.30), and mean RI (WMD: 0.05, 95%CI: 0.05-0.06) were higher in the SGA group. Also, abnormal UtA measurements were associated with the increased odds of SGA (all P < 0.05). In the third trimester, PI z-score (WMD: 0.62, 95%CI: 0.33-0.91) and PI MoM (WMD: 0.08, 95%CI: 0.06-0.09) showed a significant increase in the SGA group. The odds of SGA were higher in the women with mean PI > 95% (OR: 6.03, 95%CI: 3.24-11.24). CONCLUSIONS: Abnormal UtA measurements were associated with high odds of SGA, suggesting that UtA might be an adjunctive screening method for SGA in the whole pregnancy.

Evaluation of first trimester maternal serum inhibin-A for preeclampsia screening.

BACKGROUND: International professional organizations recommend aspirin prophylaxis to women screened high risk for preterm preeclampsia (PE) in the first trimester. The UK Fetal Medicine Foundation (FMF) screening test for preterm PE using mean arterial pressure (MAP), uterine artery pulsatility index (UTPI) and placental growth factor (PlGF) was demonstrated to have lower detection rate (DR) in Asian population studies. Additional biomarkers are therefore needed in Asian women to improve screening DRs as a significant proportion of women with preterm and term PE are currently not identified. OBJECTIVES: To evaluate maternal serum inhibin-A at 11-13 weeks as an alternative to PlGF or as an additional biomarker within the FMF screening test for preterm PE. STUDY DESIGN: This is a nested case-control study using pregnancies initially screened at 11-13 weeks for preterm PE using the FMF triple test in a non-intervention study conducted between December 2016 and June 2018. Inhibin-A levels were retrospectively measured in 1,792 singleton pregnancies, 112 (1.7%) with PE matched for time of initial screening with 1,680 unaffected pregnancies. Inhibin-A levels were transformed to multiple of the expected median (MoM). The distribution of log10 inhibin-A MoM in PE and unaffected pregnancies and the association between log10 inhibin-A MoM and gestational age (GA) at delivery in PE were assessed. The screening performance determined by area under receiver operating characteristic curves (AUC) and detection rates (DRs) at a 10% fixed false positive rate (FPR), for preterm and term PE was determined. All risks for preterm and term PE were based on the FMF competing risk model and Bayes theorem. Differences in AUC (ΔAUC) between different biomarker combinations were compared using the Delong test. McNemar's test was used to assess the off-diagonal change in screening performance at a fixed 10% FPR after adding inhibin-A or replacing PlGF in the preterm PE adjusted risk estimation model. RESULTS: Inhibin-A levels in unaffected pregnancies were significantly dependent on GA, maternal age and weight and were lower in parous women with no previous history of PE. Mean log10 inhibin-A MoM in any-onset PE (p<0.001), preterm (p<0.001) and term PE (p = 0.015) pregnancies were all significantly higher than that of unaffected pregnancies. Log10 inhibin-A MoM was inversely but not significantly correlated (p = 0.165) with GA at delivery in PE pregnancies. Replacing PlGF with inhibin-A in the FMF triple test reduced AUC and DR from 0.859 and 64.86% to 0.837 and 54.05%, the ΔAUC was not statistically significant. AUC and DR when adding inhibin-A to the FMF triple test were 0.814, 54.05% and the -0.045 reduction in AUC was statistically significant (p = 0.001). At a fixed 10% FPR, replacing PlGF with inhibin-A identified 1 (2.7%) additional pregnancy but missed 5 (13.5%) pregnancies which subsequently developed preterm PE identified by the FMF triple test. Adding inhibin-A missed 4 (10.8%) pregnancies and did not identify any additional pregnancies with preterm PE. CONCLUSION: Replacing PlGF by inhibin-A or adding inhibin-A as an additional biomarker in and to the FMF triple screening test for preterm PE does not improve screening performance and will fail to identify pregnancies that are currently identified by the FMF triple test.