Cord blood cardiovascular biomarkers in tetralogy of fallot and D-transposition of great arteries.

Previous reports suggest that cord blood biomarkers could serve as a prognostic tool for conotruncal congenital heart defects (CHD). We aimed to describe the cord blood profile of different cardiovascular biomarkers in a prospective series of fetuses with tetralogy of Fallot (ToF) and D-transposition of great arteries (D-TGA) and to explore their correlation with fetal echocardiography and perinatal outcome. Methods: A prospective cohort study (2014-2019), including fetuses with isolated ToF and D-TGA and healthy controls, was conducted at two tertiary referral centers for CHD in Barcelona. Obstetric ultrasound and fetal echocardiography were performed in the third trimester and cord blood was obtained at delivery. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factorß (TGFß), placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. Results: Thirty-four fetuses with conotruncal-CHD (22 ToF and 12 D-TGA) and 36 controls were included. ToF-fetuses showed markedly increased cord blood TGFß (24.9 ng/ml (15.6-45.3) vs. normal heart 15.7 ng/ml (7.2-24.3) vs. D-TGA 12.6 ng/ml (8.7-37.9); P = 0.012). These results remained statistically significant even after adjusting for maternal body mass index, birth weight and mode of delivery. TGFß levels showed a negative correlation with the pulmonary valve diameter z-score at fetal echocardiography (r = -0.576, P = 0.039). No other differences were found in the rest of cord blood biomarkers among the study populations. Likewise, no other significant correlations were identified between cardiovascular biomarkers, fetal echocardiography and perinatal outcome. Conclusions: This study newly describes increased cord blood TGFß concentrations in ToF compared to D-TGA and normal fetuses. We also demonstrate that TGFß levels correlate with the severity of right ventricle outflow obstruction. These novel findings open a window of research opportunities on new prognostic and potential preventive strategies.

Lethal Congenital Contracture Syndrome 11: A Case Report and Literature Review.

Lethal congenital contracture syndrome 11 (LCCS11) is caused by homozygous or compound heterozygous variants in the GLDN gene on chromosome 15q21. GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report a fetus with ultrasound alterations detected at 28 weeks of gestation. The fetus exhibited hydrops, short long bones, fixed limb joints, absent fetal movements, and polyhydramnios. The pregnancy was terminated and postmortem studies confirmed the prenatal findings: distal arthrogryposis, fetal growth restriction, pulmonary hypoplasia, and retrognathia. The fetus had a normal chromosomal microarray analysis. Exome sequencing revealed two novel compound heterozygous variants in the GLDN associated with LCCS11. This manuscript reports this case and performs a literature review of all published LCCS11 cases.

Feasibility of 4D-Spatio Temporal Image Correlation (STIC) in the Comprehensive Assessment of the Fetal Heart Using FetalHQ®.

Fetal Heart Quantification (FetalHQ®) is a novel speckle tracking software that permits the study of global and regional ventricular shape and function from a 2D four-chamber-view loop. The 4D-Spatio Temporal Image Correlation (STIC) modality enables the offline analysis of optimized and perfectly aligned cardiac planes. We aimed to evaluate the feasibility and reproducibility of 4D-STIC speckle tracking echocardiography (STE) using FetalHQ® and to compare it to 2D STE. We conducted a prospective study including 31 low-risk singleton pregnancies between 20 and 40 weeks of gestation. Four-chamber view volumes and 2D clips were acquired with an apex pointing at 45° and with a frame rate higher than 60 Hz. Morphometric and functional echocardiography was performed by FetalHQ®. Intra- and interobserver reproducibility were evaluated by the intraclass correlation coefficient (ICC). Our results showed excellent reproducibility (ICC > 0.900) for morphometric evaluation (biventricular area, longitudinal and transverse diameters). Reproducibility was also good (ICC > 0.800) for functional evaluation (biventricular strain, Fractional Area Change, left ventricle volumes, ejection fraction and cardiac output). On the contrary, the study of the sphericity index and shortening fraction of the different ventricular segments showed lower reproducibility (ICC < 0.800). To conclude, 4D-STIC is feasible, reproducible and comparable to 2D echocardiography for the assessment of cardiac morphometry and function.

Brain Oxygen Perfusion and Oxidative Stress Biomarkers in Fetuses with Congenital Heart Disease-A Retrospective, Case-Control Pilot Study.

Fetuses with congenital heart disease (CHD) have circulatory changes that may lead to predictable blood flow disturbances that may affect normal brain development. Hypoxemia and hypoperfusion may alter the redox balance leading to oxidative stress (OS), that can be assessed measuring stable end-products. OS biomarkers (OSB) were measured in amniotic fluid in fetuses with (n = 41) and without CHD (n = 44) and analyzed according to aortic flow, expected cyanosis after birth, and a CHD classification derived from this. Birth head circumference (HC) was used as a neurodevelopment biomarker. CHD fetuses had higher levels of ortho-Tyrosine (o-Tyr) than controls (p = 0.0003). There were no differences in o-Tyr levels considering aortic flow obstruction (p = 0.617). Fetuses with expected extreme cyanosis presented the highest levels of o-Tyr (p = 0.003). Among groups of CHD, fetuses without aortic obstruction and extreme cyanosis had the highest levels of o-Tyr (p = 0.005). CHD patients had lower HC than controls (p = 0.023), without correlation with OSB. Patients with HC < 10th percentile, presented high levels of o-Tyr (p = 0.024). Fetuses with CHD showed increased OSB and lower HC when compared to controls, especially those with expected extreme cyanosis. Our results suggest that increased levels of OSB are more influenced by the effect of low oxygenation than by aortic flow obstruction. Future studies with larger sample size are needed to further investigate the role of OSB as an early predictor of neurodevelopmental problems in CHD survivors.

Prescriptive standards of echocardiographic morphometric and functional parameters in uncomplicated monochorionic diamniotic fetuses.

OBJECTIVE: To create prescriptive standards of cardiac morphometric and functional parameters in a cohort of uncomplicated monochorionic diamniotic (MCDA) twins. METHOD: Fetal echocardiography was performed in a cohort of uncomplicated monochorionic twin fetuses scanned longitudinally, including comprehensive morphometric and functional parameters, using 2-D imaging, M-mode and conventional Doppler. A multilevel polynomial hierarchical model adjusted by gestational age and estimated fetal weight was used to fit each cardiac parameter. RESULTS: The global heart dimensions including the atrial and ventricular areas, the ventricles dimensions and myocardial wall thicknesses and most of the functional parameters, such as the longitudinal myocardial motion and the biventricular cardiac output showed a positive quadratic increment throughout pregnancy. On the other hand, the left ejection fraction, shortening fraction and right fractional area change decreased with gestational age. Scatterplots for the main structural and functional parameters and ratios by gestational age, with mean, 5th, 10th, 90th, and 95th percentiles are provided. Regression equations by estimated fetal weight are also created. CONCLUSION: We provide specific comprehensive echocardiographic prescriptive standards for uncomplicated MCDA twin fetuses following current standardized methodology. The implementation of these charts will potentially help to better identify abnormal cardiovascular parameters associated to monochorionic complications.

Segmentation of the placenta and its vascular tree in Doppler ultrasound for fetal surgery planning.

PURPOSE: Twin-to-twin transfusion syndrome (TTTS) is a serious condition that occurs in about 10-15% of monochorionic twin pregnancies. In most instances, the blood flow is unevenly distributed throughout the placenta anastomoses leading to the death of both fetuses if no surgical procedure is performed. Fetoscopic laser coagulation is the optimal therapy to considerably improve co-twin prognosis by clogging the abnormal anastomoses. Notwithstanding progress in recent years, TTTS surgery is highly risky. Computer-assisted planning of the intervention can thus improve the outcome. METHODS: In this work, we implement a GPU-accelerated random walker (RW) algorithm to detect the placenta, both umbilical cord insertions and the placental vasculature from Doppler ultrasound (US). Placenta and background seeds are manually initialized in 10-20 slices (out of 245). Vessels are automatically initialized in the same slices by means of Otsu thresholding. The RW finds the boundaries of the placenta and reconstructs the vasculature. RESULTS: We evaluate our semiautomatic method in 5 monochorionic and 24 singleton pregnancies. Although satisfactory performance is achieved on placenta segmentation (Dice ≥ 84.0%), some vascular connections are still neglected due to the presence of US reverberation artifacts (Dice ≥ 56.9%). We also compared inter-user variability and obtained Dice coefficients of ≥ 76.8% and ≥ 97.42% for placenta and vasculature, respectively. After a 3-min manual initialization, our GPU approach speeds the computation 10.6 times compared to the CPU. CONCLUSIONS: Our semiautomatic method provides a near real-time user experience and requires short training without compromising the segmentation accuracy. A powerful approach is thus presented to rapidly plan the fetoscope insertion point ahead of TTTS surgery.

Prediction of Perinatal Mortality in Ebstein's Anomaly Diagnosed in the Second Trimester of Pregnancy.

OBJECTIVES: Firstly, to describe the outcome of a series of fetuses with Ebstein's anomaly (EA) and, secondly, to study the utility of different second-trimester echocardiographic parameters to predict fetal and neonatal mortality. METHODS: 39 fetuses with EA diagnosed between 18 and 28 weeks of gestation were included. Fetal echocardiography included the cardiothoracic ratio (CTR); right atrial (RA) area index; displacement of the tricuspid valve (TV); tricuspid regurgitation; pulmonary artery; and ductus arteriosus flow characteristics. Additionally, 2 novel parameters were obtained: the relative RA area ratio (RA area/cardiac area) and the TV displacement index (TVDI, TV displacement distance/longi-tudinal diameter of the left ventricle). Correlation between the echocardiographic variables and the primary outcome of perinatal mortality or survival at 1 year of life was evaluated. RESULTS: From the initial cohort, 8 cases were excluded due to complex congenital heart defects. Termination of pregnancy (TOP) was performed in 15 cases, and fetal death was diagnosed in 3 cases. In the live-born cohort of 13 patients, 4 died in the neonatal period, yielding a perinatal survival rate of 29 and 56%, respectively, after excluding TOP cases. Compared with survivors, nonsurvivors showed a significantly higher CTR (56.7 ± 16.2 vs. 42.6 ± 8.6; p = 0.04), relative RA area ratio (0.39 ± 0.13 vs. 0.25 ± 0.05; p = 0.01), and TVDI (0.62 ± 0.17 vs. 0.44 ± 0.12; p = 0.03) at diagnosis. The best model to predict perinatal mortality was obtained by using a scoring system which included the relative RA area ratio and TVDI (AUC 0.905 [95% CI 0.732-1.000]). CONCLUSIONS: Fetuses with a relative RA area ratio ≥0.29 and TVDI ≥0.65 at the second trimester have the highest risk of dying in the perinatal stage.

TTTS-GPS: Patient-specific preoperative planning and simulation platform for twin-to-twin transfusion syndrome fetal surgery.

Twin-to-twin transfusion syndrome (TTTS) is a serious condition that may occur in pregnancies when two or more fetuses share the same placenta. It is characterized by abnormal vascular connections in the placenta that cause blood to flow unevenly between the babies. If left untreated, perinatal mortality occurs in 90% of cases, whilst neurological injuries are still present in TTTS survivors. Minimally invasive fetoscopic laser surgery is the standard and optimal treatment for this condition, but is technically challenging and can lead to complications. Acquiring and maintaining the required surgical skills need consistent practice, and a steep learning curve. An accurate preoperative planning is thus vital for complex TTTS cases. To this end, we propose the first TTTS fetal surgery planning and simulation platform. The soft tissue of the mother, the uterus, the umbilical cords, the placenta and its vascular tree are segmented and registered automatically from magnetic resonance imaging and 3D ultrasound using computer vision and deep learning techniques. The proposed state-of-the-art technology is integrated into a flexible C++ and MITK-based application to provide a full exploration of the intrauterine environment by simulating the fetoscope camera as well as the laser ablation, determining the correct entry point, training doctors' movements and trajectory ahead of operation, which allows improving upon current practice. A comprehensive usability study is reported. Experienced surgeons rated highly our TTTS planner and simulator, thus being a potential tool to be implemented in real and complex TTTS surgeries.

Fully automatic 3D reconstruction of the placenta and its peripheral vasculature in intrauterine fetal MRI.

Recent advances in fetal magnetic resonance imaging (MRI) open the door to improved detection and characterization of fetal and placental abnormalities. Since interpreting MRI data can be complex and ambiguous, there is a need for robust computational methods able to quantify placental anatomy (including its vasculature) and function. In this work, we propose a novel fully-automated method to segment the placenta and its peripheral blood vessels from fetal MRI. First, a super-resolution reconstruction of the uterus is generated by combining axial, sagittal and coronal views. The placenta is then segmented using 3D Gabor filters, texture features and Support Vector Machines. A uterus edge-based instance selection is proposed to identify the support vectors defining the placenta boundary. Subsequently, peripheral blood vessels are extracted through a curvature-based corner detector. Our approach is validated on a rich set of 44 control and pathological cases: singleton and (normal / monochorionic) twin pregnancies between 25-37 weeks of gestation. Dice coefficients of 0.82 â€¯±â€¯ 0.02 and 0.81 â€¯±â€¯ 0.08 are achieved for placenta and its vasculature segmentation, respectively. A comparative analysis with state of the art convolutional neural networks (CNN), namely, 3D U-Net, V-Net, DeepMedic, Holistic3D Net, HighRes3D Net and Dense V-Net is also conducted for placenta localization, with our method outperforming all CNN approaches. Results suggest that our methodology can aid the diagnosis and surgical planning of severe fetal disorders.

Segmentation and classification in MRI and US fetal imaging: Recent trends and future prospects.

Fetal imaging is a burgeoning topic. New advancements in both magnetic resonance imaging and (3D) ultrasound currently allow doctors to diagnose fetal structural abnormalities such as those involved in twin-to-twin transfusion syndrome, gestational diabetes mellitus, pulmonary sequestration and hypoplasia, congenital heart disease, diaphragmatic hernia, ventriculomegaly, etc. Considering the continued breakthroughs in utero image analysis and (3D) reconstruction models, it is now possible to gain more insight into the ongoing development of the fetus. Best prenatal diagnosis performances rely on the conscious preparation of the clinicians in terms of fetal anatomy knowledge. Therefore, fetal imaging will likely span and increase its prevalence in the forthcoming years. This review covers state-of-the-art segmentation and classification methodologies for the whole fetus and, more specifically, the fetal brain, lungs, liver, heart and placenta in magnetic resonance imaging and (3D) ultrasound for the first time. Potential applications of the aforementioned methods into clinical settings are also inspected. Finally, improvements in existing approaches as well as most promising avenues to new areas of research are briefly outlined.

Fetal MRI Synthesis via Balanced Auto-Encoder Based Generative Adversarial Networks.

Machine learning approaches for image analysis require large amounts of training imaging data. As an alternative, the use of realistic synthetic data reduces the high cost associated to medical image acquisition, as well as avoiding confidentiality and privacy issues, and consequently allows the creation of public data repositories for scientific purposes. Within the context of fetal imaging, we adopt an auto-encoder based Generative Adversarial Network for synthetic fetal MRI generation. The proposed architecture features a balanced power of the discriminator against the generator during training, provides an approximate convergence measure, and enables fast and robust training to generate high-quality fetal MRI in axial, sagittal and coronal planes. We demonstrate the feasibility of the proposed approach quantitatively and qualitatively by segmenting relevant fetal structures to assess the anatomical fidelity of the simulation, and performing a clinical verisimilitude study distinguishing the simulated data from the real images. The results obtained so far are promising, which makes further investigation on this new topic worthwhile.

Study protocol for a randomised controlled trial: treatment of early intrauterine growth restriction with low molecular weight heparin (TRACIP).

INTRODUCTION: The incidence of intrauterine growth restriction (IUGR) is estimated at about 3% of pregnancies, and it is associated with 30% of all perinatal mortality and severe morbidity with adverse neurodevelopmental and cardiovascular health consequences in adult life. Early onset IUGR represents 20%-30% of all cases and is highly associated with severe placental insufficiency. The existing evidence suggests that low molecular weight heparin (LMWH) has effects beyond its antithrombotic action, improving placental microvessel structure and function of pregnant women with vascular obstetric complications by normalising proangiogenic and antiapoptotic protein levels, cytokines and inflammatory factors. The objective of our study is to demonstrate the effectiveness of LMWH in prolonging gestation in pregnancies with early-onset IUGR. METHODS AND ANALYSIS: This is a multicentre, triple-blind, parallel-arm randomised clinical trial. Singleton pregnancies qualifying for early (20-32 weeks at diagnosis) placental IUGR (according to Delphi criteria) will be randomised to subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or placebo from inclusion at diagnosis to the time of delivery. Analyses will be based on originally assigned groups (intention-to-treat). The primary objective will be analysed by comparing gestational age and prolongation of pregnancy (days) in each group with Student's t-tests for independent samples and by comparing Kaplan-Maier survival curves (from inclusion to delivery, log-rank test). A linear regression model for gestational age at birth will consider the following covariates: gestational age at inclusion (continuous) and pre-eclampsia (binary). ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was approved by the Clinical Research Ethics Committee (CEIC) of Sant Joan de Déu Hospital, on 13 July 2017. The trial is registered in the public registry www.clinicaltrial.gov. according to Science Law 14/2011, and the results will be published in an open access journal. TRIAL REGISTRATION NUMBER: NCT03324139; Pre-results.

Rate and Outcomes of Pulmonary Stenosis and Functional Pulmonary Atresia in Recipient Twins with Twin-Twin Transfusion Syndrome.

OBJECTIVE: To evaluate the rate of pulmonary stenosis and functional pulmonary atresia (PS/PA) in recipient twins prior to fetal surgery for twin-twin transfusion syndrome (TTTS) and their pre- and postnatal outcomes. METHODS: We carried out a prospective study including 260 cases of TTTS. Echocardiography was performed before laser surgery to detect the presence of PS/PA. The outcomes of recipients with and without PS/PA were compared. The need of postnatal cardiac interventions and the survival rate at 6 months of age were also evaluated. RESULTS: PS was observed in 16/260 (6.2%) of recipient twins and PA in 12/260 (4.6%). After fetal surgery, 10/28 (35.7%) recipients died, 9/28 (32.1%) showed in utero regression, and 9/28 (32.1%) had persistence of PS/PA. Postnatally, seven recipients underwent percutaneous balloon pulmonary valvuloplasty, one required surgical valvotomy and one palliative surgery. Pregnancies with recipient twins with PS/PA had lower survival of at least one twin (67.9 vs. 83.6%, p = 0.045) and lower overall survival (57.1 vs. 72.8%, p = 0.015) at 6 months of age. CONCLUSION: PS and PA were observed in 10.8% of recipients. Among these, about one third showed persistence of pulmonary valve pathology after delivery, which stresses the need for strict follow-up.

Effectiveness of ovarian age as the background risk for aneuploidy screening in an unselected pregnant population.

The aim of this study was to assess the performance of first-trimester combined screening when replacing the chronological maternal age by Anti-Müllerian hormone (AMH) and antral follicle count (AFC)-derived ovarian ages, as the background risk in trisomy risk estimation. A total of 639 pregnant women who completed first-trimester combined screening together with AMH and AFC determination were included. Trisomy risks were estimated based on three distinct 'maternal ages' as a-priori risk (chronological age, AMH- and AFC-derived ovarian age). The screening performance was assessed using three different approaches: received operator curve; detection rate and false positive rates for a fixed 1/250 threshold; and detection rates for a fixed 3% false positive rate. A non-significant trend was shown for AMH-derived age for both an increased area under the curve (0.986 versus 0.979) and an increased detection rate (from 83% to 100%) for a 1/250 risk threshold. For a 3% false-positive rate, a non-significant trend for increased detection with the use of both AMH- and AFC-derived ovarian ages was observed (from 67% to 83%). These results indicate that, although ovarian derived ages seem to potentially reflect a more precise background risk for fetal trisomies, the improvement in screening performance is only residual.

Severity of Fetal Brain Abnormalities in Congenital Heart Disease in Relation to the Main Expected Pattern of in utero Brain Blood Supply.

OBJECTIVES: We evaluated the hypothesis that in fetuses with congenital heart disease (CHD) there is a correlation between the expected pattern of in utero brain blood supply and the severity of neurodevelopmental impairment. METHODS: A total of 58 fetuses with CHD and 58 controls underwent a Doppler ultrasound and fetal MRI at 36-38 weeks. Fetuses with CHD were divided into two functional classes: class A with an expected severe reduction in oxygenated brain blood supply (left outflow tract obstruction and transposition of great vessels) and class B with theoretically near-normal or mildly impaired oxygenated brain blood supply (other CHD). Head biometry and cerebroplacental Doppler were assessed by ultrasound, and brain volumetry, cortical development and metabolism by MRI. RESULTS: Both class A and B CHD fetuses had significant differences in head biometry, brain perfusion, cortical development and brain metabolism compared with controls. However, there was a significant linear tendency for head biometry, cerebral Doppler, volumes, cortical sulcation and metabolic ratios across the three clinical groups, with signs of more severe brain alterations in type A CHD fetuses. CONCLUSIONS: All fetuses with CHD showed significant brain developmental changes, but differences were more pronounced in CHD associated with an expected severe reduction in oxygenated blood supply to the brain.

Accuracy of Fetal Echocardiography in the Differential Diagnosis between Truncus Arteriosus and Pulmonary Atresia with Ventricular Septal Defect.

OBJECTIVES: To report on the accuracy of fetal echocardiography in the distinction between truncus arteriosus communis (CAT) and pulmonary atresia with ventricular septal defect (PA-VSD) and to describe the association with extracardiac and chromosomal anomalies. METHODS: This was a retrospective study on 31 fetuses with a single arterial trunk overriding a VSD with a nonidentifiable right ventricle outflow tract with anterograde flow. Data on the type of cardiac defect, gestational age, characteristics of the arterial trunk valve, presence of additional vascular, chromosomal and extracardiac abnormalities and postnatal outcome were obtained. Misdiagnosed cases were reevaluated by four-dimensional spatiotemporal image correlation (4D-STIC) echocardiography. RESULTS: The overall diagnostic accuracy was 81% and increased to 93.5% with 4D-STIC. Chromosomal and extracardiac anomalies were detected in 40 and 27%, respectively. In the PA-VSD group, patent ductus arteriosus and major aortopulmonary collateral arteries (MAPCAs) were present in 70 and 50% of the cases, respectively, coexisting in 1 of 5 cases. MAPCAs were significantly associated with a right aortic arch and with a 22q11 microdeletion in 50% of cases. CONCLUSIONS: A prenatal distinction between CAT and PA-VSD can currently be achieved in most cases. MAPCAs should be actively searched for when PA-VSD is suspected, as they are associated with a higher risk of 22q11 microdeletion and potentially complicate postnatal treatment.

Longitudinal annular displacement by M-mode (MAPSE and TAPSE) in twin-to-twin transfusion syndrome before and after laser surgery.

OBJECTIVE: To evaluate mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser therapy. METHODS: A prospective study in 24 fetal pairs with TTTS evaluated 24 h before and within 48 h after fetoscopy and 13 gestational age-matched normal monochorionic fetal pairs. MAPSE and TAPSE were measured in an apical or basal four-chamber view by placing the M-mode cursor at the lateral valve ring. RESULTS: Mean preoperative MAPSE (controls 3.6 ± 1.3 mm vs. donors 2.7 ± 0.8 mm vs. recipients 2.8 mm ± 0.9; P < 0.001) and TAPSE (controls 4.4 ± 1.5 mm vs. donors 3.3 ± 1 mm vs. recipients 3.6 ± 1.1 mm; P < 0.001) values were significantly reduced in both TTTS fetuses. When subdividing according to TTTS stages, changes were significant in both stage I-II and III-IV subgroups, although differences were more pronounced in the latter. All observations remained unchanged 48 h post-fetoscopy. CONCLUSION: Both recipient and donor fetuses had decreased global longitudinal motion, even in early TTTS stages.

Role of ovarian reserve markers, antimüllerian hormone and antral follicle count, as aneuploidy markers in ongoing pregnancies and miscarriages.

OBJECTIVE: To assess the role of two ovarian reserve markers, antimüllerian hormone (AMH) and antral follicle count (AFC), as markers of the background risk for fetal trisomy. DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENT(S): Assessment was carried out either in ongoing pregnancies or miscarriages in our center. INTERVENTION(S): AFC was assessed transvaginally during a routine (11-13 weeks) or referral scan. AMH was determined either during the first-trimester maternal serum markers assessment or in cases referred for chorionic villi sampling after the invasive procedure. MAIN OUTCOME MEASURE(S): AMH reference ranges were constructed according to maternal age, and AMH- and AFC-derived ovarian ages were compared among three different cytogenetic groups (normal karyotype, autosomal trisomies, and other chromosomal anomalies) in both ongoing pregnancies and miscarriages. RESULT(S): In autosomal trisomies, the median AFC-derived ovarian age was 3-5 years above the median maternal age. No differences were observed between AMH-derived ovarian age and maternal age. CONCLUSION(S): AFC-derived ovarian biologic age reflects a more precise background risk for fetal aneuploidy that is not observed for AMH-derived age.

Laser ablation of posterior urethral valves by fetal cystoscopy.

OBJECTIVE: To report the results of fetal cystoscopic laser ablation of posterior urethral valves (PUV) in a consecutive series in two referral centers. METHODS: Twenty pregnant women with a presumptive isolated PUV were treated with fetal cystoscopy under local anesthesia. Identification and fulguration of the PUV by one or several firing-contacts with diode laser were attempted. Perinatal and long-term outcomes were prospectively recorded. RESULTS: The median gestational age at procedure was 18.1 weeks (range 15.0-25.6), and median operation time was 24 min (range 15-40). Access to the urethra was achieved in 19/20 (95%) cases, and postoperative, normalization of bladder size and amniotic fluid was observed in 16/20 (80%). Overall, there were 9 (45%) terminations of pregnancy and 11 women (55%) delivered a liveborn baby at a mean gestational age of 37.3 (29.1-40.2) weeks. No infants developed pulmonary hypoplasia and all were alive at 15-110 months. Eight (40% of all fetuses, 72.7% of newborns) had normal renal function and 3 (27.3%) had renal failure awaiting renal transplantation. CONCLUSION: Fetoscopic laser ablation for PUV can achieve bladder decompression and amniotic fluid normalization with a single procedure in selected cases with anyhydramnios. There is still a significant risk of progression to renal failure pre or postnatally.

Proton magnetic resonance spectroscopy assessment of fetal brain metabolism in late-onset 'small for gestational age' versus 'intrauterine growth restriction' fetuses.

OBJECTIVES: We used magnetic resonance spectroscopy (MRS) to evaluate brain metabolic differences in small fetuses near term as compared to appropriate for gestational age (AGA) fetuses. STUDY DESIGN: 71 term small fetuses (estimated fetal weight <10th centile for gestational age with normal umbilical artery Doppler sonography) were subclassified as late intrauterine growth restriction (IUGR) (n = 50) or small for gestational age (SGA) (n = 21), and compared with 65 AGA fetuses. IUGR was defined by either abnormal middle cerebral artery, abnormal uterine artery Doppler sonography or estimated fetal weight <3rd centile. All participants underwent brain magnetic resonance imaging at 37 weeks of gestation, and single-voxel magnetic resonance spectra were obtained from the frontal lobe on a 3-tesla scanner. N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr) and Cho/Cr ratios were calculated and compared between cases and controls. The association of the metabolic ratios with the study groups was tested. RESULTS: After MRS processing and applying quality control criteria, 31 spectra from late-onset IUGR, 11 from SGA and 30 from AGA fetuses were selected for further analysis. Both SGA and late-onset IUGR fetuses showed significantly reduced NAA/Cho levels when compared to AGA fetuses. This decrease followed a linear trend across the three clinical groups that were considered. CONCLUSIONS: Both SGA and late-onset IUGR fetuses showed differences in MRS brain metabolic ratios. The findings suggest that despite near-normal perinatal outcomes, SGA fetuses are not constitutionally small and may represent a form of growth disorder that needs to be clarified.