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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., (Copyright © 2022. Published by Elsevier Inc.)

Background: To date, no research has focused on the sonographic quantification of the degree of flexion of the fetal head in relation to the labor outcome in women with protracted active phase of labor., Objective: This study aimed to assess the relationship between the transabdominal sonographic indices of fetal head flexion and the mode of delivery in women with protracted active phase of labor., Study Design: Prospective evaluation of women with protracted active phase of labor recruited across 3 tertiary maternity units. Eligible cases were submitted to transabdominal ultrasound for the evaluation of the fetal head position and flexion, which was measured by means of the occiput-spine angle in fetuses in nonocciput posterior position and by means of the chin-to-chest angle in fetuses in occiput posterior position. The occiput-spine angle and the chin-to-chest angle were compared between women who had vaginal delivery and those who had cesarean delivery. Cases where obstetrical intervention was performed solely based on suspected fetal distress were excluded., Results: A total of 129 women were included, of whom 43 (33.3%) had occiput posterior position. Spontaneous vaginal delivery, instrumental delivery, and cesarean delivery were recorded in 66 (51.2%), 17 (13.1%), and 46 (35.7%) cases, respectively. A wider occiput-spine angle was measured in women who had vaginal delivery compared with those submitted to cesarean delivery owing to labor dystocia (126±14 vs 115±24; P<.01). At the receiver operating characteristic curve, the area under the curve was 0.675 (95% confidence interval, 0.538-0.812; P<.01), and the optimal occiput-spine angle cutoff value discriminating between cases of vaginal delivery and those delivered by cesarean delivery was 109°. A narrower chin-to-chest angle was measured in cases who had vaginal delivery compared with those undergoing cesarean delivery (27±33 vs 56±28 degrees; P<.01). The area under the curve of the chin-to-chest angle in relation to the mode of delivery was 0.758 (95% confidence interval, 0.612-0.904; P<.01), and the optimal cutoff value discriminating between vaginal delivery and cesarean delivery was 33.0°., Conclusion: In women with protracted active phase of labor, the sonographic demonstration of fetal head deflexion in occiput posterior and in nonocciput posterior fetuses is associated with an increased incidence of cesarean delivery owing to labor dystocia. Such findings suggest that intrapartum ultrasound may contribute in the categorization of the etiology of labor dystocia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: A primary role of maternal heart dysfunction in the pathophysiology of preeclampsia had been previously advocated although if contradictory results have been reported., Objectives: The objectives of the study were to describe maternal hemodynamic parameters according to 2 main preeclampsia phenotypes and to investigate whether cardiac findings may be helpful in characterizing the severity and the progression of the disease., Study Design: This was a prospective cohort study. We used an ultrasonic cardiac output monitor system to compare the hemodynamic parameters of women with preeclampsia with a group of healthy normotensive women enrolled as controls with a ratio of 1:2. Cardiac output, systemic vascular resistance, and stroke volume were compared among controls and preeclamptic women who were grouped in accordance to the following characteristics: early preeclampsia (<34 weeks' gestation) vs late preeclampsia onset (≥34 weeks' gestation); preeclampsia associated with appropriate for gestational age or small-for-gestational-age newborns. Hemodynamic characteristics were also compared between preeclamptic women with a mild form vs those who progressed toward a severe form., Results: A total of 38 preeclamptic women and 61 normotensive women were included in the study. Both cases of preeclampsia associated with small-for-gestational-age neonates as those with normal-sized ones showed higher systemic vascular resistance compared with the control group (respectively, 1580.6 ± 483.2 vs 1479.1 ± 433.3 vs 1105.3 ± 293.1; P < .0001), while a lower cardiac output was reported only for preeclamptic women with small-for-gestational-age neonates compared with controls (5.7 ± 1.5 vs 6.5 ± 1.3; P = .02). Maternal cardiac parameters were comparable between these 2 groups of preeclamptic women (small-for-gestational-age vs appropriate-for-gestational-age preeclampsia) with the exception of a lower stroke volume in the former one (64.8 ± 24.4 vs 75.2 ± 17.8; P = .04). Similarly, women with both early and late preeclampsia showed higher systemic vascular resistance compared with controls (1559.5 ± 528.3 vs 1488.5 ± 292.9 vs 1105.3 ± 293.1, respectively; P < .001), while a lower cardiac output was noted only in the early-onset group compared with controls (5.5 ± 1.2 P = .02). Maternal cardiac findings were similar between women with early vs late-onset preeclampsia. Hemodynamic parameters are significantly different between those women with mild preeclampsia who remained stable compared with those who progressed toward a severe disease. Cardiac output Z-score, systemic vascular resistance Z-score, and uterine arteries' pulsatility index Z-score showed similar sensitivity (80% vs 75% vs 80%, respectively) and specificity (73% vs. 73% vs 74%, respectively), while the association of systemic vascular resistance Z-score and uterine arteries pulsatility index Z-score showed a sensitivity of 95% and a specificity of 80% (area under the curve, 0.90) in predicting evolution toward severe forms., Conclusion: Evaluation of maternal cardiovascular system could help clinician in defining a subset of preeclamptic patients with more profound placental impairment and might predict the likelihood of progression toward a severe condition in cases with a mild preeclampsia at clinical onset., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: A limited number of studies have addressed the role of intrapartum ultrasound in the prediction of the mode of delivery in women with prolonged second stage of labor., Objective: The objective of the study was to evaluate the role of transabdominal and transperineal sonographic findings in the prediction of spontaneous vaginal delivery among nulliparous women with prolonged second stage of labor., Study Design: This was a 2-center prospective study conducted at 2 tertiary maternity units. Nulliparous women with a prolonged active second stage of labor, as defined by active pushing lasting more than 120 minutes, were eligible for inclusion. Transabdominal ultrasound to evaluate the fetal head position and transperineal ultrasound for the measurement of the midline angle, the head-perineum distance, and the head-symphysis distance were performed in between uterine contractions and maternal pushes. At transperineal ultrasound the angle of progression was measured at rest and at the peak of maternal pushing effort. The delta angle of progression was defined as the difference between the angle of progression measured during active pushing at the peak of maternal effort and the angle of progression at rest. The sonographic findings of women who had spontaneous vaginal delivery vs those who required obstetric intervention, either vacuum extraction or cesarean delivery, were evaluated and compared., Results: Overall, 109 were women included. Spontaneous vaginal delivery and obstetric intervention were recorded in 40 (36.7%) and 69 (63.3%) patients, respectively. Spontaneous vaginal delivery was associated with a higher rate of occiput anterior position (90% vs 53.2%, P < .0001), lower head-perineum distance and head-symphysis distance (33.2 ± 7.8 mm vs 40.1 ± 9.5 mm, P = .001, and 13.1 ± 4.6 mm vs 19.5 ± 8.4 mm, P < .001, respectively), narrower midline angle (29.6° ± 15.3° vs 54.2° ± 23.6°, P < .001) and wider angle of progression at the acme of the pushing effort (153.3° ± 19.8° vs 141.8° ± 25.7°, P = .02) and delta-angle of progression (17.3° ± 12.9° vs 12.5° ± 11.0°, P = .04). At logistic regression analysis, only the midline angle and the head-symphysis distance proved to be independent predictors of spontaneous vaginal delivery. More specifically, the area under the curve for the prediction of spontaneous vaginal delivery was 0.80, 95% confidence interval (0.69-0.92), P < .001, and 0.74, 95% confidence interval (0.65-0.83), P = .002, for the midline angle and for the head-symphysis distance, respectively., Conclusion: Transabdominal and transperineal intrapartum ultrasound parameters can predict the likelihood of spontaneous vaginal delivery in nulliparous women with prolonged second stage of labor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Early-onset fetal growth restriction represents a particular dilemma in clinical management balancing the risk of iatrogenic prematurity with waiting for the fetus to gain more maturity, while being exposed to the risk of intrauterine death or the sequelae of acidosis., Objective: The Trial of Umbilical and Fetal Flow in Europe was a European, multicenter, randomized trial aimed to determine according to which criteria delivery should be triggered in early fetal growth restriction. We present the key findings of the primary and secondary analyses., Study Design: Women with fetal abdominal circumference <10th percentile and umbilical pulsatility index >95th percentile between 26-32 weeks were randomized to 1 of 3 monitoring and delivery protocols. These were: fetal heart rate variability based on computerized cardiotocography; and early or late ductus venosus Doppler changes. A safety net based on fetal heart rate abnormalities or umbilical Doppler changes mandated delivery irrespective of randomized group. The primary outcome was normal neurodevelopmental outcome at 2 years., Results: Among 511 women randomized, 362/503 (72%) had associated hypertensive conditions. In all, 463/503 (92%) of fetuses survived and cerebral palsy occurred in 6/443 (1%) with known outcome. Among all women there was no difference in outcome based on randomized group; however, of survivors, significantly more fetuses randomized to the late ductus venosus group had a normal outcome (133/144; 95%) than those randomized to computerized cardiotocography alone (111/131; 85%). In 118/310 (38%) of babies delivered <32 weeks, the indication was safety-net criteria: 55/106 (52%) in late ductus venosus, 37/99 (37%) in early ductus venosus, and 26/105 (25%) in computerized cardiotocography groups. Higher middle cerebral artery impedance adjusted for gestation was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02-1.52) and infant survival without neurodevelopmental impairment at 2 years (odds ratio, 1.33; 95% confidence interval, 1.03-1.72) although birthweight and gestational age were more important determinants., Conclusion: Perinatal and 2-year outcome was better than expected in all randomized groups. Among survivors, 2-year neurodevelopmental outcome was best in those randomized to delivery based on late ductus venosus changes. Given a high rate of delivery based on the safety-net criteria, deciding delivery based on late ductus venosus changes and abnormal computerized fetal heart rate variability seems prudent. There is no rationale for delivery based on cerebral Doppler changes alone. Of note, most women with early-onset fetal growth restriction develop hypertension., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses., Objective: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome., Study Design: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European "TRUFFLE" trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome., Results: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19-1.0]; delta short-term variation, 0.54 [confidence interval, 0.13-0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52-0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40-0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85)., Conclusion: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Fetal head "attitude" (relationship of fetal head to spine) in the first stage of labor may have a substantial impact on labor outcome. The diagnosis of fetal head deflexion traditionally is based on digital examination in labor, although the use of ultrasound to support clinical diagnosis has been recently reported., Objectives: The aims of this study were: (1) to quantify the degree of fetal head deflection via the use of sonography during the first stage of labor; and (2) to determine whether a parameter derived from ultrasound examination (the occiput-spine angle) has a relationship with the course and outcome of labor., Study Design: This was a prospective multicentric, cross-sectional study conducted at the Maternity Unit of the University of Bologna and Parma from January 2014 to April 2015. A nonconsecutive series of women with uncomplicated singleton pregnancies at term gestation (37 weeks or more) were submitted to transabdominal ultrasound during the first stage of labor. If fetal position was occiput anterior or transverse, the angle between the fetal occiput and the cervical spine (the occiput-spine angle) was sonographically obtained on the sagittal plane. The measurements of the occiput spine-angle were performed offline by 2 operators who were blinded to the labor outcome. The intra- and interobserver reproducibility and the correlation between the occiput-spine angle and the mode of delivery were evaluated., Results: A total of 108 pregnant women were recruited, 79 of which underwent a spontaneous vaginal delivery and 29 were submitted to obstetric intervention (19 cesarean delivery and 10 instrumental vaginal deliveries). The mean value of the occiput-spine angle measured in the active phase of the first stage was 126° ± 9.8° (SD). The occiput-spine angle measurement showed a very good intraobserver (r = 0.86; 95% confidence interval [95% CI] 0.80-0.90) and a fair-to-good interobserver (r = 0.64; 95% CI 0.51-0.74) agreement. The occiput-spine angle was significantly narrower in women who underwent obstetric intervention (cesarean or vacuum delivery) due to labor arrest (121° ± 10.5° vs 127° ± 9.4°, P = .03). Multivariable logistic regression analysis showed that narrow occiput-spine angle values (OR 1.08; 95% CI 1.00-1.16; P = .04) and nulliparity (OR 16.06; 95% CI 1.71-150.65; P = .02) were independent risk factors for operative delivery. A larger occiput-spine angle width (i.e., >125°) showed to be significantly associated with a shorter duration of labor (hazard ratio = 1.62; 95% CI 1.07-2.45; P = .02)., Conclusion: We described herein the "occiput-spine angle," a new sonographic parameter to assess fetal head deflection during labor. Fetuses with smaller occiput-spine angle (<125°) are at increased risk for operative delivery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of this prospective study was to determine the impact of thrombophilia on the recurrence of preeclampsia., Study Design: In a multicenter, observational, cohort design, 172 white patients with a previous pregnancy complicated by preeclampsia were observed in the next pregnancy. They were evaluated for heritable thrombophilia (factor V Leiden and factor II G20210A mutations, protein S, protein C, and antithrombin deficiency), hyperhomocystinemia, lupus anticoagulant, and anticardiolipin antibodies. Development of preeclampsia and maternal complications and both gestational age at delivery and birthweight were recorded., Results: Sixty women (34.9%) showed the presence of a thrombophilic defect. They had a higher risk for the recurrence of preeclampsia (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.1), compared to patients without thrombophilia. Similar findings were observed considering only heritable thrombophilia. Thrombophilic patients were at increased risk for the occurrence of very early preterm delivery (< 32 weeks; OR, 11.6; 95% CI, 3.4-43.2)., Conclusion: When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management.

Objective: We conducted a cohort study in growth-retarded fetuses to establish if absent or reverse end-diastolic flow in the umbilical artery was associated with increased perinatal mortality and morbidity and neurologic damage at long-term follow-up., Study Design: Thirty-one fetuses with intrauterine growth retardation and absent or reverse end-diastolic flow in the umbilical artery (study group) and 40 growth-retarded fetuses with detectable diastolic flow in the umbilical artery, divided into two control groups, were followed up with serial nonstress tests, Doppler flow studies, and biophysical profiles. Twenty newborns from the study group survived the perinatal period and were observed for a mean of 18 months (range 12 to 24 months). Their neurologic outcomes were compared with those of 26 neonates from the two control groups., Results: Study group fetuses had a higher incidence of abnormal karyotype (9.7% vs 0%) and corrected perinatal mortality (26% vs 6% and 4%) and a greater risk of permanent neurologic sequelae (35% vs 0% and 12%) compared with the fetuses from the two control groups., Conclusions: Growth-retarded fetuses with absent or reverse end-diastolic flow in the umbilical artery not only have an increased fetal and neonatal mortality but also a higher incidence of long-term permanent neurologic damage when compared with growth-retarded fetuses with diastolic flow in the umbilical circulation.

Systemic and renal hemodyanmic changes in normal pregnancy have been attributed in part to altered vascular synthesis of vasodilatory prostaglandins. Besides vasodilatory substances, endothelium also generates vasoconstrictors, including endothelin. We evaluated the capacity of placental tissue from normal pregnant women to express endothelin gene and to generate endothelin. Placental tissue expressed a single 2.3 kb preproendothelin messenger ribonucleic acid and produced comparable amounts of endothelin 3, Big endothelin 1, and endothelin 1 and a minor quantity of endothelin 2. To investigate the possible influence of placental endothelin production on plasma levels of the peptide, plasma endothelin concentrations were measured in normal pregnant women at delivery and were found to be numerically higher than those measured in nonpregnant subjects. Urinary excretion of endothelin, taken as a marker of the renal synthesis of the peptide, tended to increase, although not significantly, in the first 14 weeks of pregnancy. This trend continued throughout pregnancy, resulting in a significant increase from the second trimester to delivery.