Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of perinatal survival in early-onset fetal growth restriction: role of placental growth factor.

OBJECTIVE: To analyze the ability to predict perinatal survival and severe neonatal morbidity of cases with early-onset fetal growth restriction (eoFGR) using maternal variables, ultrasound parameters and angiogenic markers at the time of diagnosis. METHODS: This was a prospective observational study in a cohort of singleton pregnancies with a diagnosis of eoFGR (< 32 weeks of gestation). At diagnosis of eoFGR, complete assessment was performed, including ultrasound examination (anatomy, biometry and Doppler assessment) and maternal serum measurement of the angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Logistic regression models for the prediction of perinatal survival (in cases diagnosed at < 28 weeks) and severe neonatal morbidity (in all liveborn cases) were calculated. RESULTS: In total, 210 eoFGR cases were included, of which 185 (88.1%) survived perinatally. The median gestational age at diagnosis was 27 + 0 weeks. All cases diagnosed at ≥ 28 weeks survived. In cases diagnosed < 28 weeks, survivors (vs non-survivors) had a higher gestational age (26.1 vs 24.4 weeks), estimated fetal weight (EFW; 626 vs 384 g), cerebroplacental ratio (1.1 vs 0.9), PlGF (41 vs 18 pg/mL) and PlGF multiples of the median (MoM; 0.10 vs 0.06) and lower sFlt-1/PlGF ratio (129 vs 479) at the time of diagnosis (all P < 0.001). The best combination of two variables for predicting perinatal survival was provided by EFW and PlGF MoM (area under the receiver-operating-characteristics curve (AUC), 0.84 (95% CI, 0.75-0.92)). These were also the best variables for predicting severe neonatal morbidity (AUC, 0.73 (95% CI, 0.66-0.80)). CONCLUSIONS: A model combining EFW and maternal serum PlGF predicts accurately perinatal survival in eoFGR cases diagnosed before 28 weeks of gestation. Prenatal prediction of severe neonatal morbidity in eoFGR cases is modest regardless of the model used. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of postnatal circulation in pulmonary atresia/critical stenosis with intact ventricular septum: systematic review and external validation of models.

OBJECTIVE: A favorable postnatal prognosis in cases of pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS) is generally equated with the possibility of achieving biventricular (BV) repair. Identification of fetuses that will have postnatal univentricular (UV) circulation is key for prenatal counseling, optimization of perinatal care and decision-making regarding fetal therapy. We aimed to evaluate the accuracy of published models for predicting postnatal circulation in PA/CS-IVS using a large internationally derived validation cohort. METHODS: This was a systematic review of published uni- and multiparametric models for the prediction of postnatal circulation based on echocardiographic findings at between 20 and 28 weeks of gestation. Models were externally validated using data from the International Fetal Cardiac Intervention Registry. Sensitivity, specificity, predictive values, area under the receiver-operating-characteristics curves (AUCs) and proportion of cases with true vs predicted outcome were calculated. RESULTS: Eleven published studies that reported prognostic parameters of postnatal circulation were identified. Models varied widely in terms of the main outcome (UV (n = 3), non-BV (n = 3), BV (n = 3), right-ventricle-dependent coronary circulation (n = 1) or tricuspid valve size at birth (n = 1)) and in terms of the included predictors (single parameters only (n = 6), multiparametric score (n = 4) or both (n = 1)), and were developed on small sample sizes (range, 15-38). Nine models were validated externally given the availability of the required parameters in the validation cohort. Tricuspid valve diameter Z-score, tricuspid regurgitation, ratios between right and left cardiac structures and the presence of ventriculocoronary connections (VCC) were the most commonly evaluated parameters. Multiparametric models including up to four variables (ratios between right and left structures, right ventricular inflow duration, presence of VCC and tricuspid regurgitation) had the best performance (AUC, 0.80-0.89). Overall, the risk of UV outcome was underestimated and that of BV outcome was overestimated by most models. CONCLUSIONS: Current prenatal models for the prediction of postnatal outcome in PA/CS-IVS are heterogeneous. Multiparametric models for predicting UV and non-BV circulation perform well in identifying BV patients but have low sensitivity, underestimating the rate of fetuses that will ultimately have UV circulation. Until better discrimination can be achieved, fetal interventions may need to be limited to only those cases in which non-BV postnatal circulation is certain. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.

OBJECTIVE: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. METHODS: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. RESULTS: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. CONCLUSIONS: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

sFlt-1/PlGF ratio and timing of delivery in early-onset fetal growth restriction with antegrade umbilical artery flow.

OBJECTIVE: To analyze the value of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio in predicting the time to delivery in early-onset fetal growth restriction (FGR) with preserved antegrade umbilical artery (UA) flow at diagnosis. METHODS: This was a prospective observational single-center cohort study of pregnancies with early-onset (< 32 + 0 weeks) FGR and antegrade UA flow, in which maternal serum sFlt-1/PlGF ratio was determined at diagnosis. FGR was defined as estimated fetal weight < 3rd centile or < 10th centile with UA pulsatility index > 95th centile, fetal middle cerebral artery pulsatility index < 5th centile or cerebroplacental ratio < 5th centile. The previously described sFlt-1/PlGF ratio cut-off value of 85 for facilitating the diagnosis of pre-eclampsia was assessed in the prediction of the need to deliver in < 1 week and ≥ 4 weeks. RESULTS: In total, 120 cases were included. There were 116 (96.7%) liveborn neonates and 108 (90.0%) perinatal survivors. Median (interquartile range (IQR)) gestational age at diagnosis of early-onset FGR was 27.1 (25.7-29.4) weeks. Median (IQR) sFlt-1/PlGF ratio at diagnosis was 196 (84-474). Ninety (75.0%) cases had a sFlt-1/PlGF ratio ≥ 85. Among pregnancies with a liveborn neonate, median (IQR) interval to delivery in the groups with sFlt-1/PlGF ratio < 85 and ≥ 85 was 41 (22-54) days and 11 (4-20) days, respectively (P < 0.01). The probability of having to deliver within 1 week after diagnosis was 0% and 35.6% in those with sFlt-1/PlGF ratio < 85 and ≥ 85, respectively (P = 0.03), and the probability of delaying delivery for ≥ 4 weeks was 72.4% and 19.5%, respectively (P < 0.01). CONCLUSION: sFlt-1/PlGF ratio < 85 at diagnosis of early-onset FGR with antegrade UA flow identifies a group of pregnancies in which the need to deliver within 1 week is very low and the interval to delivery is expected to be prolonged for ≥ 4 weeks in > 70% of cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Longitudinal change of sFlt-1/PlGF ratio in singleton pregnancy with early-onset fetal growth restriction.

OBJECTIVE: To describe the evolution of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) ratio in the last 5 weeks prior to delivery in singleton pregnancy complicated by early-onset fetal growth restriction (FGR), with or without pre-eclampsia (PE). METHODS: This was a prospective observational cohort study of early-onset FGR cases that underwent serial assessment of maternal serum sFlt-1/PlGF ratio from diagnosis to delivery. Measurements were made at weekly intervals and within the last 48 h before birth. Absolute values and percentage increase between time intervals were computed, and previously described cut-off values of 38 (suspicion of PE), 85 (aids diagnosis of PE) and 655 (high risk for imminent delivery) were used for analysis of the sFlt-1/PlGF ratio. We compared findings between cases with early-onset FGR only (n = 37) and those that additionally developed PE (n = 36). RESULTS: Overall perinatal survival was 63/73 (86.3%). A sFlt-1/PlGF ratio above 38 was observed 4 weeks before delivery in most FGR-only and FGR with PE cases (73% and 100%, respectively), but absolute values of sFlt-1/PlGF were significantly higher in FGR cases with PE. Extremely elevated values of the ratio (≥ 655) within the last 48 h before delivery were found in 65% of cases of FGR with PE, but in only 8% of isolated FGR cases (P < 0.001). CONCLUSION: Elevated sFlt-1/PlGF was observed in most early-onset FGR pregnancies from 4 weeks before delivery, and values were even higher if there was concurrent PE. However, serial measurements of the ratio were of limited value, being useful only to anticipate the need for imminent delivery in cases of FGR with PE when sFlt-1/PlGF values ≥ 655 were reached. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maternal serum sFlt-1/PlGF ratio in twin pregnancies with and without pre-eclampsia in comparison with singleton pregnancies.

OBJECTIVE: In singleton pregnancies, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and the sFlt-1/PlGF ratio have shown utility as a diagnostic test for pre-eclampsia (PE). The objective of this study was to characterize the maternal serum levels of sFlt-1, PlGF and sFlt-1/PlGF ratio in normal and pre-eclamptic twin pregnancies. METHODS: In a European multicenter case-control study, 49 women with a twin pregnancy were enrolled, including 31 uneventful and 18 pre-eclamptic pregnancies. sFlt-1 and PlGF were measured and receiver-operating characteristics (ROC) analysis was performed. The median sFlt-1 and PlGF serum concentrations and sFlt-1/PlGF ratio were compared with those of a singleton cohort, matched for gestational age, with PE (n = 54) and with an uncomplicated pregnancy outcome (n = 238). RESULTS: In twin pregnancies with PE, sFlt-1 levels and the sFlt-1/PlGF ratio were increased and PlGF levels were decreased as compared with those of twin gestations with an uneventful pregnancy outcome (20 011.50 ± 2330.35 pg/mL vs 4503.00 ± 2012.05 pg/mL (P ≤ 0.001), 164.22 ± 31.35 vs 13.29 ± 319.64 (P ≤ 0.001), and 138.80 ± 20.04 pg/mL vs 403.00 ± 193.10 pg/mL (P ≤ 0.001), respectively). The sFlt-1/PlGF ratio did not differ between twin pregnancies with PE and singleton pregnancies with PE. In twin pregnancies with an uneventful outcome, sFlt-1 levels and sFlt-1/PlGF ratio were increased, but no differences in PlGF concentration were found when compared with that of singleton controls. ROC analysis determined 53 as an optimal cut-off of the sFlt-1/PlGF ratio for diagnosing PE in twin gestations, yielding a sensitivity of 94.4% and a specificity of 74.2%. The cut-off values established for singleton pregnancies, of 33 and 85, led to sensitivities of 100% and 83.3%, and specificities of 67.7% and 80.6%, when used to detect PE in twin pregnancies. CONCLUSIONS: Significant differences in the serum marker levels in singleton vs twin pregnancies were detected. Reference ranges of sFlt-1, PlGF and their ratio in singleton pregnancies are therefore not transferable to twin pregnancies.

Uterine artery Doppler and sFlt-1/PlGF ratio: prognostic value in early-onset pre-eclampsia.

OBJECTIVE: To evaluate the performance of the mean uterine artery pulsatility index (UtA-PI) and the automated measurement of the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio for the prognostic assessment of both maternal and perinatal outcomes, and the time-to-delivery interval in early-onset (≤ 34 + 0 weeks) pre-eclampsia (PE) cases with attempted expectant management. METHODS: Fifty-one singleton pregnancies with early-onset PE were enrolled in the study. Mean UtA-PI and sFlt/PlGF ratio were measured at diagnosis. The association of each marker and their combinations with adverse maternal and perinatal outcomes was assessed by univariable comparisons and multivariable logistic regression analysis and time-to-delivery interval by survival analysis. RESULTS: Twenty-six (51%) had adverse maternal outcome and 14 (27%) had adverse perinatal outcome. At the time of onset of PE, only gestational age was significantly related to maternal complications. Gestational age at onset, mean UtA-PI and sFlt-1/PlGF ratio were significantly associated with perinatal complications, their combination reaching a sensitivity of 64% with 95% specificity, and an area under the receiver-operating characteristics curve of 0.89 (95% CI, 0.79-0.99). Regarding the time until delivery, 92% (12/13) of cases with sFlt-1/PlGF ratio > 655 and 39% (15/38) of cases with a ratio ≤ 655 delivered within the first 48 h, 8% (1/13) and 19% (7/38), respectively, delivered between 48 h and 7 days and 0% (0/13) and 42% (16/38), respectively, delivered after 7 days. CONCLUSION: Mean UtA-PI and sFlt-1/PlGF ratio in combination with gestational age are useful for the prognostic assessment of perinatal complications at the time of diagnosis of early-onset PE, but this combination has limited value for the prediction of maternal complications. Moreover, sFlt-1/PlGF ratio > 655 is closely related to the need to deliver within 48 h. [[ArtCopyrightmsg]].

Prediction of coarctation of the aorta in the second half of pregnancy.

OBJECTIVE: To determine which combination of cardiac parameters provides the best prediction of postnatal coarctation of the aorta (CoAo) in fetuses with cardiac asymmetry. METHODS: We selected all cases of disproportion of the ventricles and great vessels prenatally diagnosed between 2003 and 2010 at the Hospital Universitario '12 de Octubre', Madrid, Spain. Only appropriate-for-gestational age liveborn fetuses with isolated cardiac asymmetry and with complete postnatal follow-up were included in the study. Eighty-five cases were retrieved and analyzed. Logistic regression analysis was used to select the best predictors of CoAo. Optimal cut-offs for these parameters were identified and the corresponding likelihood ratios used to calculate the post-test probability of CoAo in each fetus. RESULTS: CoAo was confirmed in 41/85 neonates (48%). The parameters selected by logistic regression and their cut-off values were: gestational age at diagnosis ≤ 28 weeks, Z-score of diameter of the ascending aorta ≤ -1.5, pulmonary valve/aortic valve diameters ratio ≥ 1.6 and Z-score of the aortic isthmus diameter in the three vessels and trachea view ≤ -2. We divided the study group into two subgroups: Group A, in whom the diagnosis was made at ≤ 28 weeks' gestation (80% CoAo (32/40)); and Group B, in whom the diagnosis was made at > 28 weeks (20% CoAo (9/45)). The mean post-test probabilities of CoAo were higher in fetuses with CoAo than in normal fetuses in both subgroups (Group A, 82 vs 55%; P = 0.002 and Group B, 51 vs 20%; P < 0.001). In addition, a rate of growth of the aortic valve of ≤ 0.24 mm/week provided 80% sensitivity and 100% specificity for predicting CoAo in Group A. CONCLUSIONS: We have derived a multiparametric scoring system, combining size-based cardiac parameters and gestational age at diagnosis, which may improve the accuracy of fetal echocardiography for the stratification of the risk of CoAo. The objectivity and simplicity of its components may allow its implementation in fetal cardiology units.

Uterine artery Doppler and sFlt-1/PlGF ratio: usefulness in diagnosis of pre-eclampsia.

OBJECTIVE: To evaluate the usefulness of the mean pulsatility index of the uterine arteries (mPI-UtA) and automated measurement of the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio on suspicion or at diagnosis of pre-eclampsia (PE). METHODS: Patients with singleton pregnancies with PE (n = 60) diagnosed according to current recommendations, or with suspected PE (n = 32) defined by (1) blood pressure (BP) ≥ 160/100 mmHg, (2) BP ≥ 140/90 mmHg or proteinuria, together with suggestive clinical symptoms or (3) intrauterine growth restriction (IUGR) at < 34 + 0 weeks, were enrolled and mPI-UtA and the sFlt-1/PlGF ratio were measured. Values > 95(th) centile were considered abnormal. All cases were classified according to occurrence of PE and/or IUGR and subclassified, depending on gestational age at delivery, as early (< 34 + 0 weeks) or late (≥ 34 + 0 weeks). RESULTS: PE was confirmed in 72 cases, in which 32 early deliveries occurred. Isolated IUGR was diagnosed in nine early cases and one late case, while the remaining 10 cases were late deliveries without PE or IUGR. In pregnancies in which PE and IUGR were excluded, mPI-UtA was abnormal in 40% but the sFlt-1/PlGF ratio was normal in 100%. In early PE, mPI-UtA at diagnosis was abnormal in 100% of cases with IUGR and in 91% without IUGR, while sFlt-1/PlGF was abnormal in 100% and 96%, respectively. In late PE, mPI-UtA was abnormal in 50% and 37% of cases with and without IUGR while the sFlt-1/PlGF ratio was abnormal in 50% and 26%, respectively. CONCLUSION: Abnormal mPI-UtA and sFlt-1/PlGF ratio are common in early PE. In late PE, mPI-UtA is normal in most cases and thus not diagnostically useful. The sFlt-1/PlGF ratio shows high specificity but low sensitivity to confirm PE when suspected.

Predictive value of sequential models of uterine artery Doppler in pregnancies at high risk for pre-eclampsia.

OBJECTIVE: To evaluate the performance of models described previously for the prediction of pre-eclampsia (PE), based on the sequential evaluation of uterine artery resistance at 11-13 weeks and 19-22 weeks, in a high-risk population. METHODS: This was a prospective study in 135 women with singleton pregnancies and at least one of the following high-risk conditions: PE and/or intrauterine growth restriction in a previous pregnancy, chronic hypertension, pregestational diabetes, renal disease, body mass index > 30 kg/m(2) , autoimmune disease (systemic lupus erythematosus, antiphospholipid syndrome or rheumatoid arthritis) and thrombophilia. Mean uterine artery pulsatility index (mUtA-PI) at 11-13 and at 19-22 weeks' gestation was measured and analyzed according to quantitative and semi-quantitative models, to predict late PE (resulting in delivery ≥ 34 weeks) and early PE (delivery < 34 weeks). RESULTS: Late PE developed in 21 (15.6%) pregnancies and early PE in six (4.4%). Using mUtA-PI, the detection rates of late and early PE for a false-positive rate of 10% were 14.3% and 33.3%, respectively, at 11-13 weeks, and 19.0% and 66.7%, respectively, at 19-22 weeks. Using a semi-quantitative approach, the group of pregnant women with mUtA-PI ≥ 90(th) percentile at both 11-13 and 19-22 weeks had a greater risk for early PE (odds ratio, 21.4 (95% CI, 2.5-184.7)) compared with the group with mUtA-PI < 90(th) percentile at both periods. Using a quantitative approach, there was relative worsening in the mUtA-PI (multiples of the median) from the first to the second trimester in all cases of early PE. CONCLUSION: The application of semi-quantitative and especially quantitative models to evaluate sequential changes in uterine artery Doppler findings between the first and second trimesters could be of additional value in assessing high-risk women regarding their true risk of developing early PE.

Pulmonary atresia/critical stenosis with intact ventricular septum: prediction of outcome in the second trimester of pregnancy.

OBJECTIVES: To determine which cardiac parameters provide the best prediction of postnatal outcome--biventricular (BV) versus non-BV--in fetuses with pulmonary atresia/critical stenosis with intact ventricular septum (PA/CS-IVS). METHODS: We searched our database for cases of PA/CS-IVS prenatally diagnosed in 2001-2009. Only fetuses diagnosed ≤28 weeks were included. Data of 16 fetuses (nine PA, seven CS) were retrieved and analyzed. Receiver-operating characteristics curves were constructed to assess the sensitivity and specificity of cardiac features for predicting postnatal outcome. RESULTS: Twelve fetuses had a BV outcome and four had non-BV repair. Cut-off values yielding the best results for a non-BV outcome were a tricuspid valve/mitral valve ratio ≤0.83, a pulmonary valve/aortic valve ratio ≤0.75, tricuspid inflow duration/cardiac cycle length ≤36.5%, and a right ventricle/left ventricle length ratio ≤0.64. If 3/4 markers are present, this predicts a non-BV outcome with sensitivity of 100% and specificity of 92%, and both are 100% if all the four criteria are fulfilled. CONCLUSIONS: The postnatal outcome of fetuses with PA-CS/IVS can be predicted in the second trimester at the first echocardiography by a four-criterion scoring system. This is clinically relevant since it allows early selection of candidates for fetal intervention and early and precise parental counseling.

Tetralogy of Fallot: prediction of outcome in the mid-second trimester of pregnancy.

OBJECTIVE: To evaluate the usefulness of fetal echocardiography in the mid-second trimester in predicting postnatal outcome of tetralogy of Fallot (ToF), focusing on the need for early intervention (EI) and surgery type: pulmonary valve-sparing surgery (PVSS) versus placement of transannular patch (TAP). METHODS: Assessment of cardiac morphological and functional parameters in 23 live-born fetuses with isolated ToF was performed at 19 to 22 and 34 to 38 weeks. Comparisons were made between outcome groups (EI vs non-EI and PVSS vs TAP). EI was considered as requirement either of palliative procedure or corrective surgery before three months. RESULTS: Overall survival was 96%. EI was required in 32% of cases and TAP in 50%. At 19 to 22 weeks, a pulmonary valve peak systolic velocity (PVPSV) ≥87.5 cm/s predicted EI with 100% sensitivity and 93.3% specificity (p < 0.01). At 34 to 38 weeks, the size of the pulmonary valve, pulmonary valve/aortic valve and main pulmonary artery/ascending aorta were significantly different, but the PVPSV again yielded the best performance: all cases undergoing EI and/or TAP were selected using cut-off of ≥144.5 cm/s. CONCLUSION: The postnatal outcome of fetuses with ToF may be established using PVPSV from the mid-second trimester. This may be useful in providing the most appropriate perinatal management and accurate parental counselling.

Hypoplastic left heart syndrome diagnosed in fetal life: associated findings, pregnancy outcome and results of palliative surgery.

OBJECTIVES: To analyze the main prenatal characteristics of hypoplastic left heart syndrome (HLHS), its association with extracardiac anomalies including increased nuchal translucency (NT) and the outcome of affected patients. METHODS: We searched our database for classical forms of HLHS (aortic atresia, mitral and aortic atresia and critical aortic stenosis evolved to a severely hypoplastic left ventricle) prenatally diagnosed between 1998 and 2006. Data on 101 fetuses were retrieved and analyzed. RESULTS: The main reason for referral was suspected heart defect on a routine ultrasound scan (82%). The mean gestational age at diagnosis was 21 weeks. Most cases were detected at < or = 22 weeks (72%), the upper limit for termination of pregnancy (TOP) in our country (Spain). An intact atrial septum was diagnosed in 11 of the 58 fetuses (19%) in which pulmonary vein blood flow was assessed, and this diagnosis was proved to be correct in the six liveborn babies. Most fetuses (68%) had an isolated HLHS. Fourteen fetuses (14%) were chromosomally abnormal and all had associated extracardiac defects. NT was above the 95th centile in 21 of the 74 cases (28%) in which this measurement was available. 79% (58/73) of the cases in which HLHS was detected at < or = 22 weeks were terminated, and no differences in the rate of TOP were found through the study period. Among the 43 continuing pregnancies, seven fetuses died in utero and there were 36 live births; in 12 cases the parents opted for compassionate care and 24 chose to have the infant surgically treated. In the cohort of intention-to-treat cases, the overall survival rate was 36% (9/25). This rate improved from 18% (2/11) in the period 1998-2002 to 50% (7/14) in 2003-2006. There were no survivors in cases with intact atrial septum or when there were associated defects. At follow-up, 2/9 survivors suffered from significant neurological morbidity. CONCLUSIONS: Fetal echocardiography allows an accurate diagnosis of HLHS, which is made in most instances in the first half of pregnancy. Despite the advantage offered by the prenatal detection of HLHS, which provides the opportunity to plan perinatal management, our up-to-date results show that the outlook for these fetuses is still poor, and highlight the importance of presenting these figures when counseling parents with affected fetuses.

Role of uterine artery Doppler in interpreting low PAPP-A values in first-trimester screening for Down syndrome in pregnancies at high risk of impaired placentation.

OBJECTIVES: Low maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) are associated with both increased risk of aneuploidies and impaired trophoblastic invasion, while high uterine artery (UtA) resistance is associated with impaired trophoblastic invasion but not with an increased risk of aneuploidies. The aim of this study was to determine whether high UtA resistance plays a role in explaining low PAPP-A levels in the absence of aneuploidies. METHODS: This was a prospective study of 116 singleton pregnancies at high risk for impaired placentation (having at least one major risk factor: prior history of pre-eclampsia, pregestational diabetes mellitus, chronic hypertension, chronic kidney disease, body mass index >30, autoimmune disorder, thrombophilia or recurrent pregnancy loss), booked for routine assessment of risk for aneuploidies by means of the first-trimester combined screening test (nuchal translucency thickness (NT) + PAPP-A + beta-human chorionic gonadotropin (beta-hCG)). Measurement of NT and the mean UtA pulsatility index (PI) were carried out at the 11 to 13 + 6-week scan. All values were calculated in multiples of the median (MoM) adjusted for gestational age. A cut-off risk of 1/270 at time of sampling was adopted to differentiate high- from low-risk groups for trisomy 21. RESULTS: There were 108 patients deemed to be at low risk for trisomy 21 and eight at high risk. None had chromosomal defects, giving a false-positive rate for trisomy 21 of 6.9%. The greatest differences between patients at low risk and those at high risk for trisomy 21 were found in their PAPP-A (0.98 vs. 0.38 MoM, P < 0.01) and beta-hCG (1.09 vs. 1.77 MoM, P = 0.04) values. Greater NT thickness (1.02 vs. 0.90 MoM) and higher mean UtA-PI (1.05 vs. 0.96 MoM) were recorded in the high-risk group, although the differences did not reach statistical significance (P = 0.19 and 0.40, respectively). After log-transformation there were no significant correlations between mean UtA-PI and NT and between mean UtA-PI and beta-hCG. There was a significant negative linear correlation between mean UtA-PI and PAPP-A (r = -0.331; P < 0.01). After adjusting the PAPP-A values by UtA-PI, the false-positive rate for trisomy 21 decreased to 2.6%. CONCLUSION: Mean UtA-PI at the 11 to 13 + 6-week scan may be an effect-modifier variable for PAPP-A that should be taken into account in the first-trimester combined screening for aneuploidies, at least in pregnancies at high risk for impaired placentation.

Application of a first-trimester prediction model for pre-eclampsia based on uterine arteries and maternal history in high-risk pregnancies.

OBJECTIVE: To assess the value of a prediction model for pre-eclampsia (PE) in the first trimester (Ultrasound Obstet Gynecol 2007;30:742-794) for the prediction of late (>34 weeks) and early (< or =34 weeks) PE in a high-risk population. METHODS: Longitudinal study performed in 152 high-risk pregnancies with at least one high-risk condition: previous PE, hypertension, pregestational diabetes, renal disease, obesity, hyperlipidemia, autoimmune disorders, thrombophilia or recurrent pregnancy loss. Mean uterine artery pulsatility index at 11 to 13 + 6 weeks and a series of maternal variables were combined in order to obtain the estimated 'a posteriori risk for PE' in each woman. This risk for unaffected women was compared with that for patients who subsequently developed late and early PE. The performance of such approach was described by receiver-operating characteristic curves. RESULTS: Late PE developed in 13 (8.6%) pregnancies and early PE in seven (4.6%). The median 'a posteriori risk for PE' in the unaffected, late PE, and early PE groups was 0.62%, 1.22%, and 2.49% (P < 0.01), respectively. For a false-positive rate of 10%, the detection rates of late and early PE were 23.1 and 42.9%, respectively. CONCLUSIONS: This referenced model shows a modest performance when applied to high-risk women.

Prenatal diagnosis of right aortic arch: associated findings, pregnancy outcome, and clinical significance of vascular rings.

OBJECTIVES: To analyze the characteristics and clinical implications of right aortic arch (RAA) detected in fetal life. METHODS: Retrospective study of all cases of RAA diagnosed prenatally in high-risk patients who underwent fetal echocardiography between 2000 and 2007. RESULTS: There were 48 RAA; 18 had vascular ring (Group 1), including 15 RAA with aberrant left subclavian artery and 3 double aortic arch, and 30 had not vascular ring (Group 2), all RAA with mirror-image branching. The prenatal diagnosis was confirmed in 94%. In Group 1 most fetuses had normal heart (89%), and none had 22q11 deletion. There were 16 live births and all infants but one are asymptomatic (mean follow-up of 31 months). In Group 2 almost all fetuses had congenital heart defects (CHDs) (97%), and five were chromosomally abnormal (17%), including four 22q11 deleted. The 1-year survival rate was 69%, which was significantly higher in Group 1 (89% vs 57%, p < 0.05). CONCLUSIONS: RAA can be accurately diagnosed by fetal echocardiography. The outlook for these patients largely depends on the presence of associated defects, mainly CHDs, and their severity. If isolated, aortic arch anomalies are asymptomatic vascular variants in most cases. This information is important to assist parental counseling in pregnancy.

The role of angiogenic biomarkers and uterine artery Doppler in pregnant women with systemic lupus erythematosus or antiphospholipid syndrome.

OBJECTIVE: To evaluate the usefulness of the uterine artery mean pulsatility index (mPI-UtA) and the sFlt-1/PlGF ratio in women with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS) for the prediction of placental dysfunction-related adverse outcomes (AO), namely pre-eclampsia (PE) and intrauterine growth restriction (IUGR), and for differential diagnosis between PE and SLE flares. STUDY DESIGN: Observational prospective cohort study of 57 pregnant women with SLE or APS. MAIN OUTCOME MEASURES: mPI-UtA and sFlt-1/PlGF ratio in maternal serum were obtained at four gestational age periods (11-14, 19-22, 24-29 and 32-34 weeks). Comparisons among pregnancies with normal outcome, SLE flare and AO were performed. RESULTS: Overall, we had 44 ongoing pregnancies (36 with SLE and 8 with APS) of which most (n = 35, 80%) were uncomplicated. The overall rate of AO was 9% (n = 4), that was diagnosed at a mean (SD) gestational age of 34.1 (7.5) weeks. Five SLE patients (14%) suffered a SLE flare. No differences for these markers were found between normal pregnancies and those affected by SLE flare. mUtA-PI values were significantly higher in the AO group when compared with normal and SLE flare groups, at 19-22 weeks (1.52, 0.95 and 0.76) and 32-34 weeks (1.13, 0.68 and 0.65), respectively. The sFlt-1/PlGF ratio was significantly higher in the AO group at 24-29 weeks (191.1, 3.1 and 9.2), respectively. CONCLUSION: Our preliminary results indicate that mPI-UtA and sFlt1/PlGF ratio may be useful to predict AO in women with SLE, and to make the differential diagnosis with a lupus flare.