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.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 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.

Technique for precaval and laterocaval nodes excision at extraperitoneal paraaortic lymphadenectomy.

STUDY OBJECTIVE: To describe our technique for excision of the pre-caval and laterocaval nodes using an extraperitoneal approach. This technique was developed to make the dissection and excision of the less accessible nodes in an easier and safer way by minimizing the risk of great vessels injury and bleeding. DESIGN: Step-by-step description of the surgical procedure using video (Canadian Task Force classification III). SETTING: The procedure was performed at a teaching hospital, Hospital Universitario Donostia (Spain). PATIENTS: A 52-year-old woman with a body mass index of 33 underwent endoscopic extraperitoneal paraaortic lymphadenectomy for advanced high grade cervical adenocarcinoma FIGO IIB. INTERVENTIONS: The patient underwent an endoscopic extraperitoneal para-aortic lymphadenectomy. An anatomical dissection is being performed being the upper limit of the dissection the left renal vein. Focus of the video involves the challenging dissection of the right nodes. MEASUREMENTS AND MAIN RESULTS: Firstly we complete a dissection of all the anatomical aortic limits until the renal vein and exeresis of aortic nodes. A plane just above the cava vein is carefully developed by pushing all the lymph nodes to the roof of the dissection. Special care must be taken close to the aortic bifurcation due to the perforating vessels that can be found more frequently in this location. Once all this space is dissected, nodes attached to the roof are easily pushed down. It is useful to use a clip in the upper part, close to the renal vein, to prevent lymphorrhea. Nodes are excised in four blocks, supramesenteric and inframesenteric aortic and precaval nodes. The proximity to the peritoneal roof and the chance for a peritoneal hole and loss of pneumoperitoneum can be less problematic if the right dissection is performed at the end of the procedure. CONCLUSION: A complete para-aortic retroperitoneal dissection can be achieved with this extraperitoneal approach. Benefits of this technique are based on the absence of the bowel or other intraperitoneal structures invading the operative field given the barrier-free nature of the retroperitoneal space. Despite the challenge of the access to the right nodes in a retroperitoneal paraaortic lymphadenectomy they can be successfully excised reaching the renal vein including obese patients.

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.

Perioperative complications of lung transplantation in patients with emphysema and fibrosis: experience from 1992-2002.

UNLABELLED: Our objective was to describe the incidence of perioperative complications of lung transplantation among patients with emphysema and fibrosis and the morbidity and mortality risk factors. MATERIALS AND METHODS: We performed a retrospective study of 111 lung transplant patients engrafted from 1992 to 2002 for emphysema (n = 65) or lung fibrosis (n = 46). This descriptive study included the most frequent complications during the perioperative period in the intensive care unit. RESULTS: The most frequent intraoperative complications were reperfusion syndrome, hemodynamic instability, and cardiac arrhythmias. Among patients with emphysema, the follow-up of postoperative complications proved statistically significant on univariate analysis for an association of patient mortality with prolonged intubation (P = .005), rejection (P = .0001), hemorrhage (P = .0001), sepsis (P = .0001), renal failure (P = .001), and implantation response (P = .014). Mortality among these patients was 16.9%. Mechanical ventilation for over 48 hours and postoperative hemorrhage were the variables with the greatest predictive value for mortality in the postoperative period. Among patients with fibrosis, the complication-related mortality were reperfusion syndrome (P = .039), implantation response (P = .039), renal failure (P = .013), rejection (P = .016), and sepsis (P < .001). The mortality rate was 23.9% with sepsis (P = .000) being the most frequent cause of death in the immediate postoperative period. CONCLUSIONS: The most frequent intraoperative complications were reperfusion syndrome and hemodynamic instability. The most frequent postoperative complications were implantation response, sepsis, prolonged intubation, hemorrhage, and renal failure.

[Risk factors for acute respiratory failure after liver transplantation]. / Factores pronósticos de insuficiencia respiratoria aguda en el postoperatorio del trasplante hepático.

OBJECTIVES: To study the risk factors for acute respiratory failure during recovery after liver transplantation. PATIENTS AND METHODS: We prospectively studied 340 consecutive liver transplant operations. Patient data was grouped according to whether acute respiratory failure developed (group I) or not (group II). Acute respiratory failure was defined by the need for mechanical ventilation longer than 5 days after transplantation or by the need for an inspired oxygen fraction of over 50% for 72 hours. We evaluated demographic characteristics, stage of liver disease before the transplant, comorbidity, immunosuppressant treatment administered, and complications during and after surgery. RESULTS: Sixty-six patients were placed in group I and 274 in group II. Univariate analysis showed significant differences between the groups for age, sex, Child-Pugh functional stage, preoperative renal failure, type of immunosuppression, and postoperative complications such as atrial fibrillation, pleural effusion, pulmonary edema, ascites, postoperative acute renal failure, brain dysfunction, early graft dysfunction, and respiratory infection. Multivariate analysis by logistic regression, taking the development or not of acute respiratory failure as the dependent variable, gave a model with 6 variables that accounted for 94% of the cases. The variables entering into the model, with their respective odds ratios (OR) were female sex (OR, 5.5), stage C liver function (OR, 3.9), pulmonary edema (OR, 16.3), postoperative acute renal failure (OR, 9), cerebral dysfunction (OR, 4.5), and respiratory infection (OR, 62). CONCLUSIONS: The development of acute respiratory failure after liver transplantation is affected by the following factors: female sex, Child-Pugh class, pulmonary edema, postoperative acute renal failure, cerebral dysfunction, and respiratory infection.

[Headache caused by cerebral angiopathy during labor with epidural analgesia]. / Cefalea por angiopatía cerebral durante el trabajo de parto con analgesia epidural.

A 29-year-old woman presented projectile vomiting followed by frontal headache, immediately upon receiving epidural analgesia for labor. The clinical picture persisted until expulsion. Although no leaking of spinal fluid into the needle or epidural catheter had been observed, post-dural puncture headache was diagnosed. The postpartum persistence of symptoms and the patient's generally worsening condition indicated the need for more thorough physical examination, which revealed signs of neurological involvement. Those findings and imaging studies (computed tomography of the brain, transcranial Doppler and magnetic resonance angiography) established a final diagnosis of postpartum cerebral angiopathy. Although epidural analgesia is increasingly requested by women entering labor, it is not a risk-free procedure. We describe a relatively unknown clinical entity, postpartum cerebral angiopathy, that developed during epidural analgesia for labor and that was initially believed to be a complication of the analgesic technique.

[Lung transplantation for pulmonary fibrosis: perioperative morbidity and mortality]. / Trasplante pulmonar en la fibrosis: morbi-mortalidad perioperatoria.

Lung transplantation has become a valid therapeutic option for patients with pulmonary fibrosis in terminal stage, and the number of such interventions has increased exponentially in recent years. We undertook a retrospective study of 46 pulmonary fibrosis patients who received lung transplants from 1992 through 2002 with the aim of describing the most common intra- and early postoperative complications in the recovery unit. We also aimed to analyze the impact of each complication on mortality during the study period. The most frequent complications during surgery were reperfusion syndrome (47.5%), hemodynamic instability (41%), arrhythmias (23.9%), and pulmonary hypertension (15%), with exitus secondary to reperfusion syndrome. The most common postoperative complications were infection (56.5%), reimplantation response (45.7%), and kidney failure (19.6%). Overall mortality during the study period was 23.9%. The following complications were statistically significant in the univariate analysis of the relation with mortality: reperfusion syndrome (p=0.039), reimplantation response (p=0.039), kidney failure (p=0.013), rejection (p=0.016), and sepsis (p<0.001). The only complication that remained significant in the multivariate analysis was sepsis (p<0.001). In spite of the considerable progress made, intra- and postoperative complications continue to be a real threat for the transplanted lung patient. Sepsis was the strongest predictor of poor prognosis in the early recovery period.