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 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.

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).

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.

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.

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.

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.

Impact of prenatal diagnosis of transposition of the great arteries on postnatal outcome.

OBJECTIVE: To assess the impact of prenatal diagnosis of transposition of the great arteries (TGA) on postnatal outcome. METHODS: Hundred and fifty-four patients with either simple (n = 101) or complex forms (n = 53) of TGA, diagnosed prenatally (G1, n = 88) or postnatally (G2, n = 66), who were admitted and underwent surgical correction in our centre between 1998 and 2014, were analysed. RESULTS: Prostaglandin E1 (PgE1) infusion and balloon atrial septostomy (BAS) were performed in the first 48 h after birth more commonly in G1. The hospital mortality rate for the whole group was 7.1%, higher for complex forms (13.2%) than for simple TGA (3.9%), (p = 0.034). The overall mortality rate was similar in G1 and G2. The mortality for simple TGA was higher when PgE1 infusion and BAS were implemented after the first 48 h (p = 0.001). All deaths in G2 occurred in patients first receiving PgE1 and BAS beyond 48 h. PgE1 was initiated in the first 48 h in most patients (83%) with simple TGA postnatally diagnosed. CONCLUSIONS: Adequate measures in the first 48 h after birth are essential to reduce the early mortality in TGA, especially in the simple form. This can be provided by prenatal diagnosis or by early neonatal clinical suspicion and prompt measures.

Fetal intervention in right outflow tract obstructive disease: selection of candidates and results.

Objectives. To describe the process of selection of candidates for fetal cardiac intervention (FCI) in fetuses diagnosed with pulmonary atresia-critical stenosis with intact ventricular septum (PA/CS-IVS) and report our own experience with FCI for such disease. Methods. We searched our database for cases of PA/CS-IVS prenatally diagnosed in 2003-2012. Data of 38 fetuses were retrieved and analyzed. FCI were offered to 6 patients (2 refused). In the remaining it was not offered due to the presence of either favourable prognostic echocardiographic markers (n = 20) or poor prognostic indicators (n = 12). Results. The outcome of fetuses with PA/CS-IVS was accurately predicted with multiparametric scoring systems. Pulmonary valvuloplasty was technically successful in all 4 fetuses. The growth of the fetal right heart and hemodynamic parameters showed a Gaussian-like behaviour with an improvement in the first weeks and slow worsening as pregnancy advanced, probably indicating a restenosis. Conclusions. The most likely type of circulation after birth may be predicted in the second trimester of pregnancy by means of combining cardiac dimensions and functional parameters. Fetal pulmonary valvuloplasty in midgestation is technically feasible and in well-selected cases may improve right heart growth, fetal hemodynamics, and postnatal outcome.