Estereología en placentas procedentes de gestaciones gemelares / Stereology in placentas from twin pregnancies

Introducción: La disfunción placentaria origina complicaciones fetales; de manera más frecuente, la restricción del crecimiento intrauterino y la preclampsia. Objetivo: Identificar el patrón estereológico en placentas gemelares, y su relación con la corionicidad y el peso del recién nacido. Métodos: Se realizó un estudio descriptivo en una muestra de 16 gestantes gemelares, 25 placentas y 32 recién nacidos. Se estudiaron las variables peso del recién nacido, número de vellosidades, superficie vellositaria total, área vellositaria, área de nodos, densidad óptica de fibrina en la superficie vellositaria y densidad óptica de fibrina alrededor del vaso. Resultados: Existió relación directa entre el número de vellosidades y la superficie vellositaria total. En las placentas monocoriónicas hubo predominio de recién nacidos bajo peso. Se percibe una diferencia en los resultados de área, según el tipo placentario y la región topográfica. En las placentas monocoriales se observó mayor área, tanto de la vellosidad placentaria como en los nodos sincitiales, siendo el área de la vellosidad mayor en la periferia placentaria, y el área de nodos sincitiales en la región 4 cm del cordón umbilical. Conclusiones: La estereología microscópica a nivel pericordón, a 4 cm del cordón y en la periferia del disco placentario, arrojó diferencias significativas para el área de la vellosidad y la densidad óptica de fibrina en la superficie de la vellosidad. Los valores promedio para el área de nodos sincitiales y la densidad óptica de fibrina alrededor del vaso no mostraron diferencias estadísticamente significativas. Es la corionicidad un predictor del bajo peso al nacer(AU)

Introduction: Placental dysfunction causes fetal complications; more frequently, intrauterine growth restriction and preeclampsia. Objective: To identify the stereological pattern in twin placentas, and its relationship with chorionicity and weight of the newborn. Methods: A descriptive study was carried out in a sample of 16 women with twin pregnancy, 25 placentas and 32 newborns. The variables weight of the newborn, number of villi, total villous surface, villous area, node area, optical density of fibrin on the villous surface and optical density of fibrin around the vessel were studied. Results: There was a direct relationship between the number of villi and the total villous surface. In monochorionic placentas there was a predominance of low birth weight newborns. A difference is observed in the area results according to the placental type and the topographic region. In monochorionic placentas, a greater area was observed, both in the placental villus and in the syncytial nodes, with the villus area being greater in the placental periphery and the area of syncytial nodes in the region 4 cm from the umbilical cord. Conclusions: Microscopic stereology at the perichordal level, 4 cm from the cord and at the periphery of the placental disc showed significant differences for the villus area and fibrin optical density on the villus surface. The average values for the area of syncytial nodes and the optical density of fibrin around the vessel did not show statistically significant differences. Chorionicity is a predictor of low birth weight(AU)

Predictors of perinatal outcome in early-onset fetal growth restriction: A study from an emerging economy country.

OBJECTIVE: To identify antenatal predictors of adverse perinatal outcomes in a population of preterm fetuses with early placental insufficiency diagnosed by Doppler abnormalities. METHOD: In this cross-sectional study of a cohort of singleton pregnant women diagnosed with early placental insufficiency, relationships between perinatal variables (arterial and venous Doppler, gestational age, birth weight, oligohydramnios, estimated fetal weight, and fetal weight z-scores) and major neonatal complications were analyzed by logistic regression. RESULTS: Two hundred sixty-five women were delivered, between 24 and 33 weeks gestation. The overall frequency of intact survival was 57.9% (n = 154). Gestational age thresholds for best prediction of survival was 27 + 6 weeks and for intact survival was 29 + 0 weeks gestation. Fetal weight and absent/reversed ductus venosus a-wave were the main predictors of survival in the regression model. When fetal weight was substituted for fetal weight z-score, ductus venosus abnormal Doppler predicted mortality and absent or reversed umbilical artery diastolic velocities predicted intact survival. CONCLUSIONS: This study illustrates the impact of gestational age and fetal weight on perinatal outcomes in early placental insufficiency, with well-defined thresholds. Gestational age and fetal weight, or a combination of fetal weight z-scores and fetal Doppler parameters, were the best predictors of intact survival in our sample.

Pulmonary Vein Flow Impedance: An Early Predictor of Cardiac Dysfunction in Intrauterine Growth Restriction.

INTRODUCTION: In intrauterine growth restriction (IUGR), increased uteroplacental vascular impedance contributes to preferential flow to left ventricle (LV), with consequent alteration of its compliance and increased left atrial (LA) pressure. Pulmonary vein pulsatility index (PVPI) reflects the increased impedance to LA filling and could be used as a cardiac monitoring parameter in IUGR. MATERIAL AND METHODS: A total of 27 IUGR fetuses (group 1), 28 fetuses with appropriate growth for gestational age from hypertensive mothers (group 2), and 28 controls (group 3) were studied. Pulsatility indices (PIs) of pulmonary veins and ductus venosus were calculated by Doppler echocardiography. Obstetric ultrasound was used to assess the PIs of uterine, umbilical, and middle cerebral arteries. Statistical analysis used analysis of variance, post-hoc Tukey, and Pearson's tests. RESULTS: Mean PVPI was higher in IUGR group (1.27 ± 0.39) when compared to groups 2 (1.02 ± 0.37; p = 0.01) and 3 (0.75 ± 0.12; p < 0.001). In group 2, moderate correlation between PVPI and ductus venosus pulsatility index (DVPI) was found but not between PVPI and cerebroplacental ratio (CPR). DISCUSSION: Higher PVPI in IUGR reflects decreased LV compliance and altered LA dynamics. As LV dysfunction precedes right ventricle, our results suggest that PVPI could be an early echocardiographic parameter of fetal diastolic function in IUGR.

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol.

INTRODUCTION: Fetal growth restriction (FGR) affects 5%-10% of all pregnancies, contributing to 30%-50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. METHODS AND ANALYSIS: The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19+0-22+6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36+0-37+6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36+0-37+6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT02907242; pre-results.

Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices.

OBJECTIVES: To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). METHODS: This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. RESULTS: There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. CONCLUSION: The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Computerized fetal heart rate analysis in the prediction of myocardial damage in pregnancies with placental insufficiency.

OBJECTIVE: To evaluate the reliability of fetal heart rate (FHR) parameters analyzed by computerized cardiotocography (cCTG) in predicting myocardial damage in pregnancies with placental insufficiency. STUDY DESIGN: We evaluated 38 patients with placental insufficiency detected before 34 weeks of gestation. All patients underwent 30 min of cCTG (Sonicaid Fetal Care, version 2.2) and Doppler of umbilical artery, middle cerebral artery, and ductus venosus. Umbilical vein blood samples were collected at birth to determine fetal cardiac Troponin T, and a ≥0.09ng/ml value was deemed a sign of myocardial damage. RESULTS: The fetuses with myocardial damage (39%) showed significantly increased values of umbilical artery pulsatility index z-score (P=0.003), ductus venosus pulsatility index z-score (P=0.007), basal FHR (P=0.033) and periods of low episodes (P=0.038). The number of small accelerations and the short-term variation (STV) were significantly reduced in the group with myocardial damage (P=0.013 and P=0.003, respectively). Logistic regression analysis identified STV and gestational age at delivery as independent predictors for fetal myocardial damage, with area under ROC curve of 0.91. CONCLUSIONS: Computerized cardiotocography parameters may be useful in the management of early onset placental insufficiency, and the association of STV with gestational age could play a role in detecting myocardial injury in pregnancies with placental insufficiency.

Fetal growth according to different reference ranges in twin pregnancies with placental insufficiency.

The aim of this study was to compare different fetal growth curves in twin pregnancies with severe placental insufficiency. A retrospective cross-sectional analysis of 47 twin pregnancies with absent or reverse end diastolic flow in the umbilical artery of one fetus was performed. Pregnancies with major fetal abnormalities, twin-twin transfusion or three or more fetuses were not included. The estimated fetal weight zeta-scores were calculated for both fetuses (abnormal Doppler and co-twin) according to the following criteria: Hadlock, Liao and Araújo. The abdominal circumference zeta-scores were calculated according to Hadlock, Liao, Araújo, Ong and Stirrup. The mean estimates of the zeta-score values were calculated using generalized estimating equation regression analysis. The mean gestational age at inclusion was 27.4 ± 4.7 weeks. The fetal sex and the interaction Doppler findings × criteria correlated significantly with the zeta-score values (p < 0.001 for both variables). The estimated fetal weight mean zeta-scores (standard error) according to each criteria were as follows: Hadlock - abnormal Doppler: -2.98 (0.18), co-twin: -1.16 (0.15); Liao - abnormal Doppler: -2.89 (0.24), co-twin: -0.58 (0.19); and Araújo - abnormal Doppler: -3.05 (0.29), co-twin: -0.75 (0.18). Values for abdominal circumference were as follows: Hadlock - abnormal Doppler: -3.14 (0.26), co-twin: -1.13 (0.19); Liao - abnormal Doppler: -2.63 (0.27), co-twin: -0.42 (0.19); Araújo - abnormal Doppler: -2.44 (0.22), co-twin: -0.71 (0.14); Ong - abnormal Doppler: -3.36 (0.34), co-twin: -1.48 (0.23); and Stirrup AD -- -2.36 (0.14), co-twin: -1.18 (0.10). Sex- and plurality-specific charts should be used in the evaluation of fetal growth in twin pregnancies with placental insufficiency.

Is there a role for cervical assessment and uterine artery Doppler in the first trimester of pregnancy as a screening test for spontaneous preterm delivery?

OBJECTIVE: To evaluate the role of cervical length (CL) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks as predictors of spontaneous preterm delivery (sPTD) in a Chilean population. METHODS: This was a prospective study of asymptomatic women with singleton pregnancies attending for a nuchal translucency scan at 11+0 to 13+6 weeks' gestation and who underwent a transvaginal scan for evaluation of CL and UtA-PI. Exclusion criteria were fetal and pregnancy complications (other than sPTD) and iatrogenic delivery at<34 weeks. Measurements of CL and UtA-PI were adjusted for fetal crown-rump length and maternal characteristics and expressed as multiples of the median (MoM) of the unaffected group. Prediction of sPTD using maternal and pregnancy characteristics was studied using logistic regression analysis. RESULTS: A total of 3480 women were recruited into the study and, after application of exclusion criteria, 3310 were included in the analysis. The rate of sPTD at<34 weeks was 0.9% (n=31). A previous PTD had occurred in 7.4% of parous women. Patients with sPTD in the index pregnancy were characterized by a significantly higher prevalence of previous PTD (12.9% vs 3.7%, P<0.05). No significant difference was found in either CL or UtA-PI between pregnancies with and without subsequent sPTD. Logistic regression analysis showed that smoking and previous PTD were significantly associated with sPTD at<34 weeks. The combination of these characteristics provided a detection rate of 26% with a false-positive rate of 8%. CONCLUSIONS: Neither UtA-PI nor CL during the first trimester was shown to be a useful predictor of early sPTD. However, a combined model that includes smoking and previous PTD predicts approximately one-quarter of those women destined to deliver at<34 weeks, with a false-positive rate of 8%.

Myocardial velocities, dynamics of the septum primum, and placental dysfunction in fetuses with growth restriction.

INTRODUCTION: Diastolic dysfunction may occur in fetuses with intrauterine growth restriction (IUGR) and may be assessed by myocardial tissue Doppler (MTD). We previously have shown that excursion index of the septum primum (EISP) is reduced in IUGR fetuses over 30 weeks because of a higher left atrial pressure. PATIENTS, SETTING, AND DESIGN: The sample was made up of 14 fetuses with IUGR. MTD examination was carried out with the sample volume placed at the basal lateral wall of the left ventricle (LV), interventricular septum (IVS), and free wall of the right ventricle (RV) to determine E'/A' ratios. EISP was calculated as the ratio between the maximal excursion of the septum primum into the left atrium during diastole and the maximal diastolic diameter of the left atrium. Mitral and tricuspid flows were assessed by the conventional Doppler method. OUTCOME MEASURES: Pearson's correlation test was used to analyze the correlations between the parameters. RESULTS: A positive correlation was observed between UARI and E'/A' ratios for RV (r = 0.63, P = .02), IVS (r = 0.59, P = .03), and LV (r = 0.41, P = .15). There was a negative correlation between EISP and IVS E'/A' ratios (r = -0.58, P = .03), and a positive correlation for LV (r = 0.49, P = .08). At the RV position, a weak negative correlation was observed (r = -0.32, P = .26). CONCLUSIONS: A higher left atrial pressure in fetuses with IUGR, indicated by the lower mobility of the septum primum, is accompanied by higher ratios between early and late diastolic myocardial velocities. Placental dysfunction was correlated to septal E'/A' ratios. Fetal MTD can be a useful method to assess severity of placental dysfunction and fetal distress.

Fetal venous circulation in monochorionic twin pregnancies with placental insufficiency: prediction of acidemia at birth or intrauterine fetal death.

OBJECTIVES: To investigate fetal venous Doppler measurements in monochorionic twin pregnancies complicated by placental insufficiency and the relationship between fetal venous flow and acidemia at birth or intrauterine fetal death. METHODS: This was a prospective study of 18 monochorionic twin pregnancies with placental insufficiency. Inclusion criteria were monochorionic-diamniotic twin pregnancy, abnormal umbilical artery (UA) Doppler indices, intact membranes and absence of fetal congenital abnormalities. Cases of twin-to-twin transfusion syndrome were excluded. The following Doppler measurements were studied: UA pulsatility index (PI), ductus venosus PI, middle cerebral artery PI and peak systolic velocity, intra-abdominal umbilical vein (UV) time-averaged maximum velocity (TAMXV) and left portal vein (LPV) TAMXV. Doppler parameters were transformed into Z-scores (SD values from the mean) or multiples of the median according to normative references. RESULTS: UA pH < 7.20 occurred in nine (25.0%) neonates, pH < 7.15 in four (11.1%) and intrauterine death in four (11.1%) fetuses. The UV-TAMXV and LPV-TAMXV Z-scores were significantly lower in the group with pH < 7.20 or intrauterine fetal death (-1.79 vs -1.22, P = 0.006 and -2.26 vs -1.13, P = 0.04, respectively). In cases with pH < 7.15 or intrauterine fetal death, UV pulsations were more frequent (50.0% vs 10.7%, P = 0.03) and UV-TAMXV Z-score was significantly lower (-1.89 vs -1.26, P = 0.003). Mixed effects logistic regression analysis, accounting for the paired nature of the outcomes for the two twins in each pregnancy, demonstrated that the UV-TAMXV Z-score significantly predicted UA pH at birth < 7.20 or intrauterine fetal death. The Doppler parameter that independently predicted pH < 7.15 or intrauterine fetal death was presence of pulsation in the UV. CONCLUSION: UV Doppler parameters may predict acidemia at birth or intrauterine fetal death in monochorionic twins complicated by placental insufficiency.

Placental findings in late-onset SGA births without Doppler signs of placental insufficiency.

OBJECTIVES: To describe placental pathological findings in late-onset small-for-gestational age (SGA) births for which Doppler signs of placental insufficiency are lacking. METHODS: A series of placentas were evaluated from singleton pregnancies of SGA births (birth weight below the 10th percentile) delivered after 34 weeks with normal umbilical artery Doppler (pulsatility index below the 95th percentile), that were matched by gestational age with adequate-for-gestational age (AGA) controls. Using a hierarchical and standardized system, placental lesions were classified histologically as consequence of maternal underperfusion, fetal underperfusion or inflammation. RESULTS: A total of 284 placentas were evaluated (142 SGA and 142 AGA). In the SGA group, 54.2% (77/142) of the placentas had weights below the 3rd percentile for GA while it was a 9.9% (14/142) in the AGA group (p < 0.001). Only 21.8% (31/142) of SGA placentas were free of histological abnormalities, while it was 74.6% (106/142) in the AGA group (p < 0.001). In the abnormal SGA placentas (111/142) there were a total of 161 lesions, attributable to MUP in 64% (103/161), FUP in 15.5% (25/161), and inflammation in 20.5% (33/161). DISCUSSION: In most placentas of term SGA neonates with normal UA Doppler histological abnormalities secondary to maternal underperfusion prevail, reflecting latent insufficiency in uteroplacental blood supply. This is consistent with the higher risk of adverse perinatal outcome reported in this population and underscores a need for new markers of placental disease. CONCLUSIONS: A significant proportion of late-onset SGA births with normal umbilical artery Doppler may still be explained by placental insufficiency.

Ductus venosus versus cerebral transverse sinus Doppler velocimetry for predicting acidemia at birth in pregnancies complicated by placental insufficiency.

OBJECTIVES: The objectives of this study is to compare ductus venosus (DV) and cerebral transverse sinus (CTS) Doppler velocimetry for predicting acidemia at birth in pregnancies complicated by placental insufficiency. METHODS: A prospective cross-sectional study involving 69 cases. Doppler assessment of the DV and CTS was carried out in the last 24 hours prior to delivery. The sensitivity, specificity, positive and negative predictive values, and the accuracy and false-positive and false-negative rates were calculated for those parameters considered to be good predictors of acidemia. The McNemar test was used to compare the various parameters. RESULTS: The DV pulsatility index(PI), S/A, and (S - A)/S ratios as well as the CTS PI and the (S - A)/S ratio were good predictors of acidemia. The comparison between DV and CTS showed that for pulsatility index for veins, the sensitivity was 52.4% versus 66.7%, p = 0.508; the specificity was 81.2% versus 77.1%, p = 0.774; and the accuracy was 72.5% versus 73.9%, p = 1.00. For the (S - A)/S ratio the sensitivity was 52.4% versus 52.4%, p = 1.00; the specificity was 85.4% versus 79.2%, p = 0.508; and the accuracy was 75.4% versus 71%, p = 0.647. CONCLUSIONS: In pregnancies with placental insufficiency, the PI and the (S - A)/S ratio of both DV and CTS were equally effective in predicting acidemia at birth.

Doppler velocimetry of the fetal middle cerebral artery and other parameters of fetal well-being in neonatal survival during pregnancies with placental insufficiency.

OBJECTIVE: To study the Doppler velocimetry of the fetal middle cerebral artery in pregnancies complicated by placental insufficiency, and to verify its role in the prognosis of neonatal survival. METHODS: This was a prospective study of 93 pregnant women with diagnosis of placental insufficiency detected before the 34(th) week of pregnancy. Placental insufficiency was characterized by abnormal umbilical artery (UA) Doppler (> 95(th) percentile). The following parameters were analyzed: umbilical artery (UA) pulsatility index (PI); middle cerebral artery (MCA) PI; brain-placenta ratio--BPR (MCA-PI/UA-PI); MCA peak systolic velocity (MCA-PSV); and PI for veins (PIV) of ductus venosus (DV). The parameters were analyzed in terms of absolute values, z-scores (standard deviations from the mean), or multiples of the median (MoM). The outcome investigated was neonatal death during the hospitalization period after birth. RESULTS: Of the 93 pregnancies analyzed, there were 25 (26.9%) neonatal deaths. The group that died, when compared to the survival group, presented a significant association with the diagnosis of absent or reversed end-diastolic flow (88% vs. 23.6%, p<0.001), with a higher median of UA PI (2.9 vs. 1.7, p<0.001) and UA PI z-score (10.4 vs. 4.9, p<0.001); higher MCA-PSV MoM (1.4 vs. 1.1, p=0.012); lower BPR (0.4 vs. 0.7, p<0.001); higher PIV-DV (1.2 vs. 0.8, p<0.001) and DV z-score (3.6 vs. 0.6, p<0.001). In the logistic regression, the independent variables predictive of neonatal death were: gestational age at birth (OR=0.45; 95% CI: 0.3 to 0.7; p<0.001) and UA PI z-score (OR=1.14, 95% CI: 1.0 to 1.3, p=0.046). CONCLUSION: Despite the association verified by the univariate analysis between neonatal death and the parameters of fetal cerebral Doppler velocimetry, the multivariate analysis identified prematurity and degree of insufficiency of placental circulation as independent factors related to neonatal death in pregnancies complicated by placental insufficiency.

Gender-specific differences in fetal cardiac troponin T in pregnancies complicated by placental insufficiency.

BACKGROUND: Placental insufficiency and fetal growth restriction may lead to fetal hypoxia and acidemia, which result in fetal cardiac injury. OBJECTIVE: The goal of this study was to compare the levels of fetal cardiac troponin T (cTnT) at birth and fetal Doppler parameters according to fetal gender in pregnancies complicated by placental insufficiency before 34 weeks' gestation. METHODS: Between March 2007 and November 2010, singleton pregnancies with placental insufficiency characterized by abnormal umbilical artery Doppler results were prospectively studied. All the patients delivered by cesarean section, and Doppler examinations were performed up to 48 hours before birth. Immediately after delivery, umbilical artery blood samples were obtained for fetal cTnT measurements. RESULTS: Fifty high-risk pregnant women met the study criteria. The study groups were as follows: group 1 consisted of 23 male fetuses (46%) and group 2 consisted of 27 female fetuses (54%). cTnT levels were significantly higher in the group of male fetuses (median, 0.14; range, 0.01-0.85) compared with the group of female fetuses (median, 0.05; range, 0.01-0.27) (P = 0.039). In the group of male fetuses, Doppler results of the ductus venosus assessment revealed values of pulsatility index for veins ≥1.0 in 15 male fetuses (65.2%) and 9 female fetuses (33.3%) (P = 0.032). CONCLUSIONS: Fetal gender was associated with cTnT level at birth in pregnancies complicated by placental insufficiency before 34 weeks' gestation, although the Doppler findings did not support gender differences. The fetal cardiac compromise and cardiac injury may be influenced by fetal gender, suggesting differences in the cardiovascular response to fetal hypoxia.

Transdermal nitroglycerin in patients with severe pre-eclampsia with placental insufficiency: effect on uterine, umbilical and fetal middle cerebral artery resistance indices.

OBJECTIVES: To evaluate the effect of transdermal nitroglycerin on Doppler velocity waveforms of the uterine, umbilical and fetal middle cerebral arteries in patients with severe pre-eclampsia. METHODS: This was a prospective study of 30 singleton pregnancies (gestational age range: 24-31 weeks) with severe pre-eclampsia and abnormal uterine and umbilical artery Doppler waveforms. We compared maternal blood pressure as well as the resistance index (RI) and the pulsatility index (PI) of the uterine, umbilical and fetal middle cerebral arteries before and after application of a transdermal nitroglycerin patch (average dose 0.4 mg/h) for a period of 3 days. Intra-day comparisons before and after administration of nitroglycerin and a comparison between days 0 (no patch) and 3 after administration of the first dose of nitroglycerin were performed using ANOVA for paired samples. RESULTS: A significant decrease in the PI and RI of the uterine (25.3 ± 4.9% and 21.2 ± 6.2%, respectively, P < 0.001) and umbilical (23.1 ± 6.9% and 19.7 ± 6.1%, respectively, P < 0.001) arteries was noted when comparing the first day without medication against the third day with the patch. No significant change in the PI and RI of the middle cerebral artery was observed. The mean arterial blood pressure decreased from 119.5 ± 4.5 mmHg to 114.8 ± 4.4 mmHg (P < 0.05). CONCLUSION: The use of transdermal nitroglycerin in patients with severe pre-eclampsia is associated with a significant reduction in the RI and PI of the uterine and umbilical arteries, as well as of maternal blood pressure. Transdermal nitroglycerin does not affect the RI and PI of the fetal middle cerebral artery.

Prediction of acidemia at birth by Doppler assessment of fetal cerebral transverse sinus in pregnancies with placental insufficiency.

OBJECTIVES: To evaluate the prediction of acidemia at birth using cerebral transverse sinus (CTS) Doppler velocimetry and to determine the best parameter and cut-off values for its prediction in pregnancies complicated with placental insufficiency. METHODS: This was a prospective cross-sectional study involving 69 pregnant women (26-40 weeks' gestation) with placental insufficiency managed in two Brazilian hospitals. Doppler assessment of the CTS was carried out in the last 24 h before delivery, and the peak ventricular systolic (S-wave) and diastolic (D-wave) velocities as well as the atrial systolic velocity (A-wave) were recorded and the pulsatility index for veins (PIV) was calculated. At birth, arterial and venous umbilical cord blood samples were collected to determine acid-base and pH status. A receiver-operating characteristics (ROC) curve was constructed for each Doppler parameter with birth acidemia as the dependent variable. Sensitivity, specificity, positive and negative predictive values, accuracy and false-positive and false-negative rates were calculated for the parameters considered to be good predictors of acidemia. RESULTS: The S, D and A peak velocities and the S/A ratio were not good predictors of acidemia at birth. The PIV and the (S - A)/S ratio were good predictors of acidemia (area under the ROC curve = 0.698 (P = 0.009) and 0.654 (P = 0.009), respectively). The cut-off values were PIV = 0.855 and (S - A)/S = 0.703). CONCLUSIONS: The PIV and the (S - A)/S ratio of the CTS were good predictors of acidemia at birth in this high-risk population with placental insufficiency.

Screening for placental insufficiency by transvaginal uterine artery Doppler at 22-24 weeks of gestation.

OBJECTIVE: To determine the value of routine transvaginal color Doppler assessment of the uterine arteries at 22-24 weeks of gestation in the prediction of placental insufficiency. METHODS: Women with singleton pregnancies scheduled for routine ultrasound scans at 22-24 weeks were offered Doppler assessment of the uterine arteries by transvaginal ultrasound. The pulsatility index (PI) was obtained for each artery and the mean value was calculated. A mean PI >95th percentile was considered increased. Screening characteristics for predicting placental insufficiency, defined as preeclampsia, fetal growth restriction or intrauterine death, were calculated. RESULTS: Doppler examination of the uterine arteries was carried out in 1,057 singleton pregnancies. The mean uterine artery PI was 1.03 and the 95th percentile was 1.55. In 54 cases (5.1%) the mean PI was >1.55 (screen-positive). In the study population there were 48 cases of preeclampsia (5.1%), 72 fetal growth restrictions (7.5%) and 7 intrauterine deaths (0.7%). The screen-positive group showed an incidence of 47.1% of combined adverse results. The relative risks after a positive screening test were 7.3 (CI 4.2-12.6) for pre-eclampsia, 3.9 (CI 2.3 - 6.6) for fetal growth restriction and 4.5 (CI 3.2-6.4) for overall placental insufficiency. CONCLUSIONS: Uterine artery Doppler at 22-24 weeks identifies women at higher risk for the development of subsequent complications of placental insufficiency. This test could be used in combination with other markers to stratify the level of care offered in the third trimester of pregnancy.

[Brain sparing effect: from placental insufficiency to fetal circulatory adaptation]. / Mecanismo de centralização: da insuficiência placentária à adaptação circulatória fetal.

The application and development of obstetric Doppler velocimetry provide a basis for the investigation of placental insufficiency and demonstrate the dynamic behavior of fetal circulation during hypoxia. In clinical practice, assessing hemodynamics in three vascular regions involved in pregnancy, namely the uterine, umbilical and middle cerebral arteries, has become routine. Roughly, the cerebral artery expresses the balance between uterine artery oxygen supply and umbilical artery oxygen uptake. Currently, when such balance is unfavorable, the fetal cardiac reserve is investigated by assessing the venous duct. However, determining and interpreting vascular resistance indexes is not an easy task. The starting point is to know the physiopathology of placental insufficiency and fetal circulatory adaptation through which Doppler confirmed its role in the assessment of fetal well-being.

Predicting adverse neonatal outcome in severe fetal compromise: a pivotal role for estimated fetal weight Z scores.

OBJECTIVE: To identify significant predictors for adverse neonatal outcome in severe by compromised fetuses. METHODS: Consecutive premature fetuses at between 25 and 32 weeks' with severe placental insufficiency were examined prospectively. Inclusion criteria were: singletons; normal anatomy; abnormal umbilical artery Doppler pulsatility index; abnormal cerebroplacental ratio; middle cerebral artery pulsatility index (PI)

Venous-arterial Doppler ratios in the prediction of acidemia at birth in pregnancies with placental insufficiency.

OBJECTIVES: Investigate the prediction of birth acidemia in pregnancies with placental insufficiency using two newly created venous-arterial Doppler ratios: pulsatility index (PI) of the ductus venosus (DV) over PI of the middle cerebral artery (MCA) and PI of the DV over PI of the umbilical artery and establish cut-off values for this prediction. METHODS: This was a prospective cross-sectional study involving 47 patients with placental insufficiency managed in two Brazilian hospitals. All pregnancies were singleton, over 26 weeks of age and without structural or chromosome anomalies. A ROC curve was calculated for the venous-arterial ratios (independent variable) and acidemia (dependent variable). RESULTS: The DV/AU PI ratio was not a good predictor of acidemia at birth. The DV/MCA PI ratio was related to fetal acidemia (area under the ROC curve 0.785, p = 0.004). The cut-off value was 0.582, sensibility 66.7%, specificity 77.1% and accuracy 74.5%. CONCLUSIONS: The DV/MCA PI ratio is adequate for the diagnosis of acidemia at birth in pregnancies with placental insufficiency. The cut-off value was 0.582.