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Introduction: We investigated whether structured maternal lifestyle interventions based on Mediterranean diet or stress reduction influence fetal-infant neurodevelopment detected by detailed fetal neurosonography and Ages and Stages Questionnaires 3rd edition (ASQ) at 12 months old., Methods: This was a secondary analysis of a randomized clinical trial (2017-2020), including 1,221 singleton pregnancies at high risk for small-for-gestational age. Participants were randomized into three groups at 19-23 weeks' gestation: Mediterranean diet intervention, stress reduction program, or usual care. A detailed neurosonography was performed on 881 participants at mean (SD) 33.4 (1.1) weeks' gestation. Neurosonographic measurements were done offline. ASQ was performed on 276 infants at 1 year of corrected age., Results: Biparietal diameter was similar among study groups. Mediterranean diet group fetuses had deeper insula (26.80 [1.68] versus 26.63 [1.75], mm, p = 0.02) and longer corpus callosum (42.98 [2.44] versus 42.62 [2.27], mm, p = 0.04), with a lower rate of suboptimal score infants in ASQ problem-solving domain (6.2 vs. 16.3%, p = 0.03). Stress reduction group fetuses had deeper insula (26.90 [1.75] versus 26.63 [1.75], mm, p = 0.04) and lower rates of suboptimal score infants in ASQ fine motor domain (4.3 vs. 12.8%, p = 0.04), compared to usual care group fetuses., Conclusion: Maternal structured intervention during pregnancy of the trial has the potential to modify offspring's neurodevelopment., (© 2024 S. Karger AG, Basel.)

Background: Acute leukemia is the most common pediatric cancer, with an incidence peak at 2-5 years of age. Despite the medical advances improving survival rates, children suffer from significant side effects of treatments as well as its high social and economic impact. The frequent prenatal origin of this developmental disease follows the two-hit carcinogenesis model established in the 70s: a first hit in prenatal life with the creation of genetic fusion lesions or aneuploidy in hematopoietic progenitor/stem cells, and usually a second hit in the pediatric age that converts the preleukemic clone into clinical leukemia. Previous research has mostly focused on postnatal environmental factors triggering the second hit., Summary: There is scarce evidence on prenatal risk factors associated with the first hit. Mainly retrospective case-control studies suggested several environmental and lifestyle determinants as risk factors. If these associations could be confirmed, interventions focused on modifying prenatal factors might influence the subsequent risk of leukemia during childhood and reveal unexplored research avenues for the future. In this review, we aim to comprehensively summarize the currently available evidence on prenatal risk factors for the development of childhood leukemia. According to the findings of this review, parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Other factors such as socioeconomic status, consumption of caffeinated beverages, and smoking consumption have been suggested with inconclusive evidence. Additionally, investigating the association between prenatal factors and genetic lesions associated with childhood leukemia at birth is crucial. Prospective studies evaluating the link between lifestyle factors and genetic alterations could provide indirect evidence supporting new research avenues for leukemia prevention. Maternal diet and lifestyle factors are modifiable determinants associated with adverse perinatal outcomes that could be also related to preleukemic lesions., Key Messages: Parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Dedicating efforts to studying maternal lifestyle during pregnancy and its association with genetic lesions leading to childhood leukemia could lead to novel prevention strategies., (© 2024 S. Karger AG, Basel.)

Introduction: The aim of this study was to develop a pipeline using state-of-the-art deep learning methods to automatically delineate and measure several of the most important brain structures in fetal brain ultrasound (US) images., Methods: The dataset was composed of 5,331 images of the fetal brain acquired during the routine mid-trimester US scan. Our proposed pipeline automatically performs the following three steps: brain plane classification (transventricular, transthalamic, or transcerebellar plane); brain structures delineation (9 different structures); and automatic measurement (from the structure delineations). The methods were trained on a subset of 4,331 images and each step was evaluated on the remaining 1,000 images., Results: Plane classification reached 98.6% average class accuracy. Brain structure delineation obtained an average pixel accuracy higher than 96% and a Jaccard index higher than 70%. Automatic measurements get an absolute error below 3.5% for the four standard head biometries (head circumference, biparietal diameter, occipitofrontal diameter, and cephalic index), 9% for transcerebellar diameter, 12% for cavum septi pellucidi ratio, and 26% for Sylvian fissure operculization degree., Conclusions: The proposed pipeline shows the potential of deep learning methods to delineate fetal head and brain structures and obtain automatic measures of each anatomical standard plane acquired during routine fetal US examination., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Cytomegalovirus (CMV) is a major cause of childhood disabilities, and consensus recommendations emphasize the importance of hygienic measures to reduce perinatal infection. Our study aimed to evaluate the level of awareness about CMV among health professionals and pregnant women., Methods: We submitted a 20-item online survey regarding CMV perinatal infection to all obstetricians and midwives in Catalonia (Spain) and a 7-item lay version of the questionnaire to 700 pregnant women. Levels of knowledge were compared among groups., Results: Of the 1,449 health professionals approached, 338 surveys were answered. 72% of professionals considered CMV a relevant problem. 47% of obstetricians and 28% of midwives (p ≤ 0.001) routinely informed pregnant women, and less than half knew the risk of fetal transmission. We observed significant differences in knowledge between obstetricians and midwives concerning the risks of recurrent infections, risk of transmission, and risk of severe infection (60.7% vs. 45.6%, p = 0.006 and 50.6% vs. 22.5%, p ≤ 0.001); and regarding maternal and neonatal symptoms and newborn sequelae (23% vs. 8.8%, p ≤ 0.001). Of the 700 women approached, we obtained a response rate of 72%. Only 23% had previously heard about CMV, 22% identified transmission routes, and 15% preventive measures. Compared to women without risk factors for CMV infection, women at greater risk had heard more about CMV (mothers of children <3 years: 36% vs. 20%, p < 0.001; occupational exposure: 43% vs. 20%, p ≤ 0.001) and had received more information (mothers of children <3 years: 18% vs. 9.5%, p ≤ 0.001; occupational exposure: 23% vs. 9.3%, p = 0.001)., Conclusion: Health care professionals have limited knowledge about CMV and may fail to enforce preventive measures. While pregnant women have limited awareness about CMV infection, they recognize the need for information. Health campaigns should be promoted to enhance awareness about this perinatal infection., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objective: To construct valid reference standards reflecting optimal cerebroplacental ratio and to explore its physiological determinants., Methods: A cohort of 391 low-risk pregnancies of singleton pregnancies of nonmalformed fetuses without maternal medical conditions and with normal perinatal outcomes was created. Doppler measurements of the middle cerebral artery and umbilical artery were performed at 24-42 weeks. Reference standards were produced, and the influence of physiological determinants was explored by nonparametric quantile regression. The derived standards were validated in a cohort of 200 low-risk pregnancies., Results: Maternal body mass index was significantly associated with the 5th centile of the cerebroplacental ratio. For each additional unit of body mass index, the 5th centile was on average 0.014 lower. The derived 5th, 10th, and 50th centiles selected in the validation cohort were 5, 9.5, and 51% of the measurements., Conclusions: This study provides methodologically sound prescriptive standards and suggests that maternal body mass index is a determinant of a cutoff commonly used for decision-making., (© 2020 S. Karger AG, Basel.)

The coronavirus disease 2019 (COVID-19) pandemic has represented a major impact to health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. The mother and fetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-fetal medicine practice have suffered profound changes to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists in order to correctly diagnose the disease, classify the severity, distinguish specific signs of COVID-19 from those of obstetric complications, and take the most appropriate management decisions. In this review we present in a highly concise manner an evidence-based protocol for the management of COVID-19 in pregnancy. We briefly contemplate all relevant aspects that we believe a specialist in obstetrics and maternal medicine should know, ranging from basic concepts about the disease and protection measures in the obstetric setting to more specific aspects related to maternal-fetal management and childbirth., (© 2020 S. Karger AG, Basel.)

The heart is a central organ in the fetal adaptation to an adverse environment. Fetal cardiac changes may persist postnatally and increase the risk of cardiovascular disease in adulthood. Knowledge about fetal cardiac structural as well as functional remodeling has radically improved over the last few years. As it occurs in postnatal life, the fetal heart remodels - changing its structure and shape - to adapt to an insult. Several conditions have been reported to be associated with fetal cardiac remodeling including intrauterine growth restriction, diabetes, exposure to antiretroviral drugs, conception by assisted reproductive technologies, pulmonary stenosis, and other congenital heart diseases. Here we summarized the main observable patterns of cardiac remodeling, i.e., globular shape, hypertrophy without dilation, and hypertrophy with cardiomegaly. We discuss the potential pathophysiology behind different types of remodeling. Defining precisely the distinct patterns of fetal cardiac remodeling is critical for advancing in the understanding of fetal cardiovascular programming and its consequences on adult health, and potentially for the design of preventive strategies that might have an impact on long-term cardiovascular health., (© 2020 S. Karger AG, Basel.)

Objective: There is a need for standardized reference values for cardiac dimensions in prenatal life. The objective of the present study was to construct nomograms for fetal cardiac dimensions using a well-defined echocardiographic methodology in a low-risk population., Methods: This is a prospective cohort study including 602 low-risk singleton pregnancies undergoing a standardized fetal echocardiography to accurately assess fetal cardiac, ventricular, and atrial dimensions. Parametric regressions were tested to model each measurement against gestational age from 18 to 41 weeks of gestation., Results: Nomograms were constructed for fetal cardiac dimensions (transverse and longitudinal diameters and areas) of the whole heart, atria, and ventricles, as well as myocardial wall thicknesses. All dimensions showed a progressive increase with gestational age. The best model for most parameters was a second-degree linear polynomial. Fetal cardiac, ventricular, and atrial diameters and areas were successfully obtained in 98.6% of the fetuses, while myocardial wall thicknesses could be obtained in 96.5% of the population. The results showed excellent interobserver and intraobserver reproducibility (intraclass correlation coefficient, ICC > 0.811 and ICC > 0.957, respectively)., Conclusions: We provide standardized and comprehensively evaluated reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. These no mograms would enable the early identification of different patterns of fetal cardiac remodeling., (© 2019 S. Karger AG, Basel.)

Objectives: Fetal right ventricular (RV) function assessment is challenging due to the RV geometry and limitations of in utero assessment. Postnatally, 2D echocardiographic RV fractional area change (FAC) is used to assess RV global systolic function by calculating the percentage of change in RV area from systole to diastole. Reports on FAC are scarce in prenatal life, and nomograms throughout pregnancy are not available. Our aims were (1) to study prenatal RV FAC feasibility and reproducibility and (2) to construct nomograms for RV FAC and end-diastolic (ED) and end-systolic (ES) RV areas from 18 to 41 weeks of gestation., Methods: Prospective cohort study including 602 low-risk singleton pregnancies undergoing a fetal echocardiography from 18 to 41 weeks of gestation. RV ED and ES areas were measured following standard recommendations for ventricular dimensions and establishing strict landmarks to identify the different phases of the cardiac cycle. RV FAC was calculated as: ([ED area - ES area]/ED area) × 100. RV FAC intra- and inter-observer reproducibility was evaluated in 45 fetuses by calculating the intraclass correlation coefficient (ICC). Parametric regressions were tested to model each parameter against gestational age (GA) and estimated fetal weight (EFW)., Results: RV areas and FAC were successfully obtained in ∼99% of fetuses with acceptable reproducibility throughout gestation (RV ED area inter-observer ICC [95% CI] 0.96 [0.93-0.98], RV ES area 0.97 [0.94-0.98], and FAC 0.69 [0.44-0.83]). Nomograms were constructed for RV ED and ES areas and FAC. RV areas showed a quadratic and logarithmic increase with GA and EFW, respectively. In contrast, RV FAC showed a slight quadratic decrease throughout gestation (mean RV FAC ranged from 36% at 18 weeks of gestation [10-90th centiles: 25-47%, respectively] to 29% at 41 weeks [10-90th centiles: 18-40%, respectively]). The best models for RV areas and FAC were a second-degree polynomial., Conclusions: RV FAC is a feasible and reproducible parameter to assess RV global systolic function in fetal life. We provide reference ranges adjusted by GA and EFW that can be used as normal references for the assessment of RV function in prenatal conditions., (© 2019 S. Karger AG, Basel.)

Background: A midtrimester cervical length (CL) <25 mm is associated with spontaneous preterm birth (sPTB). However, as CL ≥25 mm is not enough to exclude recurrence in high-risk patients, follow-up CL measurement later in pregnancy has been proposed., Objectives: To evaluate whether CL measurement at 26±1 weeks in asymptomatic high-risk patients improves the prediction of sPTB recurrence., Methods: A retrospective cohort of high-risk women because of previous sPTB was analyzed. Patients with a CL ≥25 mm at 20±1 weeks and subsequent CL measurement at 26±1 weeks were included. The exclusion criteria were incomplete follow-up, any treatment before CL assessments, and medically indicated preterm birth. The association and predictive performance of CL at 26±1 weeks for sPTB was studied., Results: Of 131 patients with a CL measurement at 26±1 weeks, 19 and 4.6% presented sPTB before 37 and 34 weeks, respectively. The rate of sPTB before 37 weeks was higher in women with a CL <25 mm (37.5 vs. 16.5%, RR 2.3 [1.07-4.8], p = 0.045), although the detection rate of CL at 26±1 weeks to predict sPTB before 37 weeks was 24% (95% CI 10-46%). The performance did not improve regardless of the selected cutoff., Conclusions: In asymptomatic high-risk patients, CL <25 mm at 26±1 weeks is associated with higher risk of sPTB. However, the prediction of recurrence by CL was low and did not improve, regardless of the selected cutoff., (© 2017 S. Karger AG, Basel.)

Objective: To develop a model combining clinical and sonographic features to predict the risk of cesarean delivery after the induction of labor (IOL)., Methods: We designed a prospective observational study involving women admitted for IOL. The main outcome was defined as cesarean delivery due to failed IOL or arrest of labor. Several clinical and ultrasonographic variables were collected. Seventy percent of the sample was used to build the predictive model, using stepwise logistic regression, while the remaining sample was used for validation. The final model was estimated and calibrated using all participants., Results: We analyzed 477 pregnancies. The main outcome occurred in 102/477 (21.4%) women. The final model included previous vaginal delivery (odds ratio [OR] 0.088; 95% confidence interval [CI] 0.04-0.21), height (OR 0.904; 95% CI 0.87-0.94), body mass index before delivery (OR 1.084; 95% CI 1.02-1.15), ultrasonographic estimated fetal weight (OR 3.965; 95% CI 2.18-7.22), and ultrasonographic cervical length (OR 1.065; 95% CI 1.04-1.09) as predictors. Area under the receiver operating characteristics curve was 0.826 (95% CI 0.78-0.87). For a 5% false-positive rate, the sensitivity, specificity, and positive and negative likelihood ratios were 44.1%, 94.9%, 8.7, and 0.59, respectively., Conclusion: Our model combining clinical and ultrasonographic features might offer individualized counseling regarding risk of cesarean delivery to women who are candidates for IOL., (© 2018 S. Karger AG, Basel.)

Objectives: To perform a longitudinal assessment comparison between estimated fetal weight (EFW) and abdominal circumference (AC) in the prediction of late fetal growth restriction (FGR) as opposed to small for gestational age (SGA)., Patients and Methods: A cohort of unselected singleton pregnancies scanned at 32±2 and 37±1 weeks was created. Longitudinal growth assessment by calculating the conditional AC and conditional EFW was performed, and both parameters were compared for their prediction capacity for late FGR and SGA. Conditional standards set an expected size (EFW or AC) given a first measurement performed earlier. A declining growth was defined as a conditional growth of <10th centile., Results: A total of 938 pregnancies were included. As expected, declining growth between 32±2 and 37±1 weeks was associated with late FGR and SGA, but the predictive capacity of both conditional AC and conditional EFW was comparably poor, with detection rates of 28% at a 10% rate of false positives for late FGR., Conclusions: Longitudinal assessment of fetal growth during the third trimester has a low predictive capacity for late FGR, with no differences between conditional AC and conditional EFW., (© 2018 S. Karger AG, Basel.)

Introduction: The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored., Materials and Methods: IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus., Results: IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure., Conclusions: IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR., (© 2017 S. Karger AG, Basel.)

Introduction: To evaluate the largest vertical pocket (LVP) of amniotic fluid as a time-dependent factor to predict perinatal mortality in women with early preterm premature rupture of membranes (EPPROM)., Material and Methods: Observational cohort study of singleton pregnancies with EPPROM <24 weeks. Termination of pregnancy (TOP) was considered if the LVP was <2 cm at 7 days. The maternal and neonatal characteristics of ongoing pregnancies were recorded. Prediction of perinatal mortality was estimated based on the influence of the LVP as a time-dependent factor after adjustment for maternal age, prior invasive procedure, and gestational age at EPPROM., Results: Of 104 women, 39 requested TOP. Neonatal survival to discharge was 40%, increasing to 74% if pregnancies achieved 24 weeks. LVP at admission <1 cm, latency to delivery, and gestational age at delivery were independent predictors of perinatal mortality. When evaluating the LVP at different time points of gestation, the highest perinatal mortality risk was established at 2 weeks (odds ratio 14.67, p < 0.001) after membrane rupture, being 5.75 (p = 0.05) the week after and 10.93 (p = 0.037) beyond 2 weeks of EPPROM., Discussion: When LVP measurement, gestational age at EPPROM, maternal age, and prior invasive procedure were considered, we found that the worst prognosis related to perinatal mortality was at 2 weeks after EPPROM., (© 2017 S. Karger AG, Basel.)

Objective: To assess cardiovascular function and damage in term small-for-gestational-age (SGA) and intrauterine growth-restricted (IUGR) fetuses by echocardiography and biomarkers in cord blood., Methods: This was a cohort study including 60 normal fetuses and 47 term small fetuses subclassified as small for gestational age (SGA) with estimated fetal weight (EFW) between the 3rd and 9th centiles and normal fetoplacental Doppler (n = 14) or intrauterine growth restriction (IUGR, n = 33) if EFW <3rd centile or EFW <10th centile together with cerebroplacental ratio <5th and/or mean uterine artery pulsatility index >95th centile. Fetal echocardiography included left myocardial performance index (MPI) and annular plane systolic excursion. Fetal B-type natriuretic peptide (BNP), troponin-I, heart-type fatty acid-binding proteins (H-FABP), and homocysteine concentrations were measured in cord blood collected at delivery., Results: Both SGA and IUGR cases presented echocardiographic signs of systolic and diastolic dysfunction with increased MPI (mean controls 0.43 [SD 0.12], SGA 0.47 [0.03], and IUGR 0.57 [0.08], p < 0.01) and decreased mitral annular plane systolic excursion (controls 6.0 mm [1.0], SGA 5.5 mm [0.6], and IUGR 4.9 mm [0.8], p = 0 01). IUGR fetuses presented increased levels of cord blood BNP (controls 17.2 pg/mL [11.5], SGA 22.4 pg/mL [10.7], and IUGR 31.2 pg/mL [26.8], p < 0.01). Troponin I was increased in both SGA and IUGR cases (controls 0.004 ng/mL [0.007], SGA 0.012 ng/mL [0.02], and IUGR 0.018 ng/mL [0.05], p < 0.01). H-FABP and homocysteine showed similar values among groups., Conclusions: Cardiac dysfunction and cell damage is a common feature of term SGA and IUGR fetuses despite of the severity criteria for perinatal outcome. Further research is needed to evaluate the potential long-term consequences on their cardiovascular system., (© 2017 S. Karger AG, Basel.)

Objective: To create antenatal gender-specific reference growth charts in uncomplicated monochorionic diamniotic twins., Materials and Methods: This is a prospective longitudinal study in which uncomplicated monochorionic (MC) twin pregnancies were included from 23 + 4 weeks of gestation onwards. Estimated fetal weight (EFW) and biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) were evaluated in both fetuses every 2 weeks using standardized methodology. Maternal and fetal complications were excluded. Charts were fitted for each biometric parameter and EFW in relation to gestational age and fetal gender using multilevel mixed models., Results: The final analysis included a total of 456 ultrasound examinations in 62 MC twins, with a mean of 7 scans per pregnancy (range 5-8). The mean as well as 5th and 95th percentiles of each biometric parameter and EFW were adjusted in relation to gender and gestational age between 24 and 37 weeks of gestation. Male fetuses have higher reference values than females, and the disparity is larger in the upper centiles of the distribution., Discussion: We provide gender-specific reference growth charts for MC twins. We suggest that these charts will improve prenatal MC twin assessment and surveillance, with a more accurate classification of normal or growth-restricted fetuses adjusted per sex., (© 2017 S. Karger AG, Basel.)

Objective: To study whether knowledge of cervical length (CL) is useful in reducing the length of hospital stay in women admitted because of threatened preterm labor., Methods: We performed a single-center, parallel, randomized trial at the Hospital Clínic of Barcelona. Inclusion criteria were single pregnancy, gestational age (GA) between 24+0 and 35+6 weeks, Bishop score <6, no parturition within 24-48 h after admission, and no clinical signs of chorioamnionitis, vaginal bleeding, or nonreassuring fetal status. CL measurement was performed 24-48 h after admission. In the control group, the patient and the physician in charge were blinded. In the study group, this information was given; if CL was >25 mm, early discharge within 12-24 h from randomization was recommended. Length of hospital stay was the main outcome., Results: After randomization, 149 patients had complete follow-up (control group, n = 74; study group, n = 75). The mean (SD) length of stay was significantly shorter - 3.0 (2.2) vs. 4.0 (2.0) days (p = 0.004) - in the study group, with a higher proportion of women remaining hospitalized ≤3 days (relative risk [95% confidence interval] 0.43 [0.26-0.70]), with no differences in GA at delivery or preterm birth rate., Conclusions: Knowledge of CL in women admitted because of threatened preterm labor is useful in reducing length of stay, with no impact on GA at delivery or preterm birth rate., (© 2017 S. Karger AG, Basel.)

Objective: To characterize the proteome profile of women with threatened preterm labor (PTL) below 34;0 weeks with and without microbial invasion of the amniotic cavity (MIAC) using mass spectrometry in the amniotic fluid (AF) and Western blot analysis in the cervical mucus and the vaginal fluid., Subjects and Methods: In the discovery phase, a case-control study including 8 women with MIAC and 7 without matched for gestational age at sampling was performed. Proteomic profile characterization was done using the LTQ VELOS Orbitrap mass spectrometer in the AF. In the validation phase, a selection of the proteins differentially expressed by mass spectrometry in the genital samples of a prospective cohort of 109 women was validated by Western blot analysis., Results: In the discovery phase, the mass spectrometry analysis identified a total of 444 proteins. Sixteen were chosen for validation, being involved in defense (calgranulin A, B, C, C-reactive protein), cytoskeletal remodeling (alpha-actinin-4 [ACTN-4], plastin-2, α2-antiplasmin, vitronectin), metabolism (cystatin-β, glucose 6 phosphate isomerase, glutathione S-transferase, prostaglandin D2 synthase, corticosteroid-binding globulin), and vascular (α1-antichymotrypsin, hemopexin, endosialin) pathways. In the validation phase, cervical ACTN-4 was the only significantly upregulated protein in women with MIAC with an odds ratio of 6.8 (p = 0.002)., Conclusions: Cervical ACTN-4 was significantly upregulated in the group of women with PTL with MIAC., (© 2017 S. Karger AG, Basel.)

Background: Prenatal detection of excessive growth remains inaccurate. Most strategies rely on a single cross-sectional evaluation of fetal size during the third trimester., Objectives: To compare second- to third-trimester longitudinal growth assessment with cross-sectional evaluation at the third trimester in the prediction of largeness for gestational age (LGA) and macrosomia., Methods: A cohort of 2,696 unselected singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks was created. Abdominal circumference (AC) measurements were transformed to z values according to the INTERGROWTH-21st standards. Longitudinal growth assessment was performed by calculation of z velocity and conditional growth. Both methods were compared to cross-sectional assessment at 32 ± 2 weeks. Predictive performance for LGA and macrosomia was determined by receiver operating characteristic curve analysis., Result: A total of 188 (7%) newborns qualified for LGA and 182 (6.8%) for macrosomia. The areas under the curve (AUCs) for 32-week AC z score, AC z velocity, and conditional AC were 0.78, 0.61, and 0.55, respectively, for the prediction of LGA, and 0.75, 0.61, and 0.55, respectively, for the prediction of macrosomia. Both AUCs of AC z velocity and conditional AC were significantly lower (p < 0.001) than the AUC of cross-sectional AC z scores., Conclusions: In the general population, second- to third-trimester longitudinal assessment of fetal growth is inferior to third-trimester cross-sectional evaluation of size in the prediction of LGA and macrosomia., (© 2017 S. Karger AG, Basel.)

Objective: To evaluate left myocardial performance index (MPI) and time intervals in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser surgery., Methods: Fifty-one fetal pairs with TTTS and 47 uncomplicated monochorionic twin pairs were included. Left ventricular isovolumetric contraction time (ICT), ejection time (ET), and isovolumetric relaxation time (IRT) were measured using conventional Doppler., Results: Recipients showed prolonged ICT (46 ± 12 vs. 31 ± 8 vs. 30 ± 5 ms; p < 0.001) and IRT (51 ± 9 vs. 43 ± 8 vs. 43 ± 5 ms; p < 0.001) and higher MPI (0.57 ± 0.12 vs. 0.47 ± 0.09 vs. 0.44 ± 0.05; p < 0.001) than donors and controls. Donors showed shorter ET than recipients and controls (157 ± 12 vs. 169 ± 10 vs. 168 ± 10 ms; p < 0.001) and higher MPI than controls (0.47 ± 0.09 vs. 0.44 ± 0.05; p = 0.006). Preoperative MPI changes were observed in all TTTS stages. Time intervals partially improved after surgery., Conclusion: Donor and recipient twins had higher MPI due to different changes in the time intervals, possibly reflecting the state of hypovolemia in the donor and hypervolemia and pressure overload in the recipient., (© 2018 S. Karger AG, Basel.)

Perinatal maternal smoking exposure (PMSE) is one of the major environmental risk factors encountered by the fetus. PMSE is usually associated with adverse pregnancy outcomes that may manifest at different stages of life. Nevertheless, fetal growth restriction is the most common smoking-induced side effect. PMSE induces changes in the maternal multiple organ systems. These alterations may affect placentation, which subsequently affects fetal growth. It is worthy to note, however, that the extent of maternal smoking-induced changes depends mainly on the maternal level of susceptibility. Hence, the perinatal pregnancy outcomes vary depending on the interaction between the triad: the maternal, fetal, and placental modifications, making it more complex. In this review, we try to unveil the effect of smoking-induced maternal changes on the maternal immune, endocrine, and metabolic pathways and their impact on fetal growth., (© 2017 S. Karger AG, Basel.)

Objective: Fetal aortic valvuloplasty (FAV) may avoid progression of critical aortic stenosis (CAS) to hypoplastic left ventricle, improving the options for biventricular circulation (BVC). We describe the results of FAV in 2 referral centers in Spain., Methods: We analyzed all FAVs performed in the period 2007-2015. The selection of candidates, the technique, and postnatal management were made following an agreed protocol. A descriptive analysis of survival, type of circulation after birth, and complications was made, considering all deaths in the first 48 h after FAV as FAV-related., Results: FAV was performed in 28 fetuses at a median gestational age (GA) of 23 weeks (range, 20-32). FAV was technically successful in 22 (78.6%), of whom 11 were born alive and with intention to treat. Eight (72.7%) resulted in BVC and 3 (27.3%) in univentricular circulation. The rate of FAV-related deaths was 32%. These patients underwent FAV earlier than live-born fetuses (median GA at FAV 22 weeks [range, 20.0-25.0] vs. 24.5 weeks [range, 21.0-32.0], respectively, p = 0.031)., Conclusions: A significant proportion of fetuses with CAS who undergo technically successful FAV have BVC postnatally. However, FAV implies a high risk of fetal death, which highly depends on the GA at which this intervention is required., (© 2017 S. Karger AG, Basel.)

Introduction: Chronic reduction of oxygen and nutrient delivery to the fetus has been related to neurodevelopmental problems. Placental underperfusion induces a significant reduction in oxygen and nutrient delivery, whereas maternal undernutrition causes mainly nutrient deficiency. A comparison of the neurodevelopmental effects of both situations in pregnant rabbits was performed., Materials and Methods: The placental underperfusion model was induced after uteroplacental vessel ligation at 25 days of pregnancy. The undernutrition model was induced after a reduction of 70% of the basal maternal intake at 22 days of pregnancy. Neurobehavioral tests were applied in the derived offspring at the neonatal period and over the long term. Structural brain differences were evaluated by brain networks obtained from diffusion magnetic resonance imaging., Results: Birth weight was significantly lower in both cases. However, stillbirth was only increased in the placental underperfusion model. Cases from both models presented poorer neurobehavioral performance and network infrastructure, being more pronounced in the placental underperfusion model., Discussion: Prenatal insults during the last third of gestation resulted in functional and structural disturbances. The degree of neurodevelopmental impairment and its association with structural brain reorganization seemed to be related to the type of the prenatal insult, showing stronger effects in the placental underperfusion model., (© 2017 S. Karger AG, Basel.)

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., (© 2015 S. Karger AG, Basel.)

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., (© 2015 S. Karger AG, Basel.)

Objective: To evaluate in normally growing fetuses at routine 32-36 weeks scan the performance of maternal angiogenic factors, Doppler and ultrasound indices in predicting smallness for gestational age (SGA) at birth., Methods: A cohort of 1,000 singleton pregnancies with normal estimated fetal weight (EFW, ≥10th centile) at 32-36 weeks scan was included. At inclusion, Doppler indices (mean uterine artery pulsatility index [mUtA-PI], cerebroplacental ratio and normalized umbilical vein blood flow by EFW (ml/min/kg) were evaluated, and blood samples were collected and frozen. Nested in this cohort, maternal circulating placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by enzyme-linked immunosorbent assay in all cases with a birth weight <10th centile by customized standards and in an equivalent number of controls (birth weight ≥10th centile)., Results: 160 cases were included (80 SGA and 80 controls). EFW (2,128 vs. 2,279 g, p < 0.001), mUtA-PI z-values (-0.25 vs. -0.65, p = 0.034) and sFlt-1/PlGF ratio (11.10 vs. 6.74, p < 0.005) were lower in SGA. The combination of sFlt-1/PlGF ratio and EFW resulted in a 66.3% detection rate for subsequent SGA, with 20% of false-positives. Fetal Doppler indices were not predictive of SGA., Conclusions: In normally growing fetuses, maternal angiogenic factors add to ultrasound parameters in predicting subsequent SGA at birth. This supports further research to investigate composite scores in order to improve the definition and identification of fetal growth restriction., (© 2015 S. Karger AG, Basel.)

Objective: To describe perinatal outcomes achieved with cord occlusion (CO) in monochorionic twins with severe selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery Doppler in the IUGR twin (types II and III)., Methods: We studied a consecutive series of 90 cases of sIUGR with abnormal Doppler treated with CO of the IUGR fetus. Abnormal Doppler was defined as continuous (type II, n = 41) or intermittent (type III, n = 49) absent/reversed end-diastolic flow. All cases presented at least one of the following severity criteria: gestational age (GA) <22 weeks, inter-twin estimated weight discordance >35%, reversed end-diastolic umbilical artery flow or ductus venosus pulsatility index >95th centile. We prospectively recorded pregnancy course and perinatal outcome., Results: Median GA at surgery was 20.6 weeks and mean duration 22.4 min. Miscarriage (<24 weeks) occurred in 3.3% (3/90) and preterm delivery <32 weeks in 7.1% (6/84) of continuing pregnancies. GA at delivery was 36.4 weeks and neonatal survival of the larger twin was achieved in 93.3%., Conclusion: In a consecutive series studied by an experienced team, CO in monochorionic twins with severe sIUGR type II or III was associated with delivery >32 weeks in 92.9% and neonatal survival of the normal twin in 93.3% of pregnancies., (© 2015 S. Karger AG, Basel.)

Introduction: Recent studies have reported variations of up to 30% between different ultrasound machines for tissue Doppler imaging (TDI), a problem that can significantly impact clinical diagnosis, patient management and research studies. The objective of this study was to assess repeatability and agreement between fetal myocardial peak velocities evaluated by TDI with two different ultrasound systems., Materials and Methods: Systolic (S'), early (E') and late (A') diastolic myocardial peak velocities at mitral and tricuspid annuli as well as at the basal septum were evaluated by spectral TDI in 150 fetuses using two different ultrasound systems: Siemens Antares (Siemens Medical Systems, Malvern, Pa., USA) and Vivid Q (General Electric Healthcare, Horten, Norway). A method comparison study was performed, calculating intraclass correlation coefficients (ICC), and agreement was assessed by Bland-Altman plots., Results: Annular peak velocities showed lower values when measured by Vivid Q compared to values measured by Siemens Antares. ICC ranged from 0.07 (septal S') to 0.33 (right A'), showing very poor repeatability for clinical application. Agreement between the two systems was also poor, with high coefficients of variation for all measurements., Conclusions: Fetal annular peak velocities obtained with different ultrasound systems are not directly comparable. This is consistent with previous data in adults and warrants the need of system-specific reference values, suggesting that the same ultrasound machine should be used for longitudinal follow-up., (© 2015 S. Karger AG, Basel.)

Introduction: The objective of this study was to evaluate placental 11B-hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria., Material and Methods: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR., Results: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA., Discussion: IUGR fetuses had reduced 11B-HSD-2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness., (© 2015 S. Karger AG, Basel.)

Objective: To assess the learning curve for intrapulmonary artery Doppler in fetuses with congenital diaphragmatic hernia (CDH)., Methods: Three fetal medicine fellows with the theoretic knowledge, but without prior experience, in the evaluation of intrapulmonary artery Doppler in CDH fetuses were selected. Each trainee and 1 experienced explorer assessed the intrapulmonary artery in the contralateral lung to the side of the hernia for calculation of 2 Doppler parameters - pulsatility index (PI) and peak early diastolic reversed flow (PEDRF) - in a cohort of 90 consecutive CDH fetuses. The average difference between the 3 trainees and the expert was calculated. A difference below 15% was considered as accurate measurement. The average learning curve was delineated using the cumulative sum analysis (CUSUM)., Results: Among the total 270 intrapulmonary artery Doppler measurements performed by the 3 trainees, the number of failed examinations was 14 (15.6%) and 16 (17.8%) for PI and PEDRF, respectively. The CUSUM plots demonstrate that the learning curve was achieved by 53 and 63 tests performed for calculations of the intrapulmonary artery PI and PEDRF, respectively., Conclusion: Competence in Doppler evaluation of the intrapulmonary artery in CDH fetuses is achieved only after intensive continuous training., (© 2015 S. Karger AG, Basel.)

Objective: To explore corpus callosum (CC) developmental differences by ultrasound in late-onset small fetuses compared with adequate for gestational age (AGA) controls., Study Design: Ninety four small (estimated fetal weight <10th centile) and 71 AGA fetuses were included. Small fetuses were further subdivided into fetal growth restriction (IUGR, n = 64) and small for gestational age (SGA, n = 30) based on poor perinatal outcome factors, that is, birth weight <3rd centile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler. The entire cohort was scanned to assess CC by transvaginal neurosonography obtaining axial, coronal and midsagittal images. CC length, thickness, total area and the areas after a subdivision in 7 portions were evaluated by semiautomatic software. Furthermore, the weekly average growth of the CC in each study group was calculated and compared., Results: Small fetuses showed significantly shorter (small fetuses: 0.49 vs. AGA: 0.52; p < 0.01) and smaller CC (1.83 vs. 2.03; p < 0.01) with smaller splenium (0.47 vs. 0.55; p < 0.01) compared to controls. The CC growth rate was also reduced when compared to controls. Changes were more prominent in small fetuses with abnormal cerebroplacental Doppler suggesting fetal growth restriction., Conclusions: Neurosonographic assessment of CC showed significantly altered callosal development, suggesting in-utero brain reorganization in small fetuses. This data support the potential value of CC assessment by US to monitor brain development in fetuses at risk., (© 2015 S. Karger AG, Basel.)

We report the successful use of fetoscopy to treat a case of severe low urinary tract obstruction (LUTO) secondary to a congenital megalourethra. A second trimester male fetus presented at 21 weeks of gestation with massive dilatation of the penile urethra. In addition, bilateral hydronephrosis, an enlarged and hypertrophic bladder, with progressive oligohydramnios were found, suggesting poor prognosis. Extensive counselling was performed and, after the approval from the local ethics committee and informed consent, patients accepted fetal therapy by fetoscopy. The procedure consisted in fetoscopic identification of the tip of the penis and confirmation of the complete absence of the urethral meatus. Thereafter, under combined endoscopic and ultrasound guidance a perforation of the tip of the penis was performed with contact diode laser, until an opening into the urethra was achieved. After the operation, resolution of the cystic penile dilation, with reduction of the penile size, and normalization of the amniotic fluid volume were observed. The pregnancy continued uneventfully and a normal male infant was born at term at the local hospital. The baby was developing normally with normal renal function at 6 months of age. Our report demonstrates that fetoscopic decompression of a distal urethra obstruction can achieve neonatal survival in the rare event of congenital megalourethra., (© 2015 S. Karger AG, Basel.)

Objective: To explore the value of circulating luteinizing human chorionic gonadotropin receptor (LHCGR) forms for the prediction of preeclampsia (PE) in the first trimester of pregnancy., Methods: Case-control study, based on a cohort of 5,759 pregnancies, including 20 early PE, 20 late PE, and 300 controls. We recorded/measured maternal characteristics, mean arterial pressure (MAP), uterine artery (UtA) Doppler, placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFtl-1), and LHCGR forms (hCG-LHCGR and soluble LHCGR), and their independent predictive values were analyzed by logistic regression., Results: For early PE, the model included black ethnicity, chronic hypertension, previous PE, MAP, UtA Doppler, PlGF, sFlt-1, and LHCGR forms, achieving detection rates (DR) of 83% at 10% of false-positive rates (FPR) [AUC: 0.961 (95% CI: 0.921-1)]. For late PE, the model included body mass index, previous PE, UtA Doppler, PlGF, sFlt-1, and LHCGR forms, with DR of 75% at 10% of FPR [AUC: 0.923 (95% CI: 0.871-0.976)]. In both early and late PE, LHCGR forms improved DR by 6-15%., Conclusions: LHCGR forms improved the prediction for early and late PE. These results should be confirmed in larger prospective studies.

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., (© 2014 S. Karger AG, Basel.)

Aim: To establish normal ranges of maternal placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and sFlt-1/PlGF ratio at 32-41 weeks' gestation and to evaluate the influence of maternal characteristics, and of fetoplacental Doppler., Material and Methods: Serum levels of PlGF, sFlt-1 and sFlt-1/PlGF ratio were measured in 300 noncomplicated pregnancies (30 at each gestational week between 32 and 41). Quantile regression analysis was used to derive gestational age (GA)-adjusted normal ranges, and to account for characteristics that might influence serum levels. The relationship with Doppler indices was tested, including umbilical artery pulsatility index and middle cerebral artery pulsatility index., Results: PlGF decreased with GA from 32 weeks, while sFlt-1 and sFlt-1/PlGF ratio increased steadily. None of the factors evaluated showed any significant influence on the levels of angiogenic factors. PlGF multiple of the median significantly correlated with mean uterine artery Doppler (R -0.17; p = 0.029)., Conclusions: In normal pregnancies during the third trimester, serum PlGF decreases, sFlt-1 increases and sFlt-1/PlGF ratio increases with GA. Angiogenic factor levels needed no adjustment for factors such as smoking, body mass index, blood pressure or parity.

Small fetuses are defined as those with an ultrasound estimated weight below a threshold, most commonly the 10th centile. The first clinically relevant step is the distinction of 'true' fetal growth restriction (FGR), associated with signs of abnormal fetoplacental function and poorer perinatal outcome, from constitutional small-for-gestational age, with a near-normal perinatal outcome. Nowadays such a distinction should not be based solely on umbilical artery Doppler, since this index detects only early-onset severe forms. FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile, and, possibly in the near future, maternal angiogenic factors. Once the diagnosis is established, differentiating into early- and late-onset FGR is useful mainly for research purposes, because it distinguishes two clear phenotypes with differences in severity, association with preeclampsia, and the natural history of fetal deterioration. As a second clinically relevant step, management of FGR and the decision to deliver aims at an optimal balance between minimizing fetal injury or death versus the risks of iatrogenic preterm delivery. We propose a protocol that integrates current evidence to classify stages of fetal deterioration and establishes follow-up intervals and optimal delivery timings, which may facilitate decisions and reduce practice variability in this complex clinical condition.

Cell-free DNA testing in maternal blood provides the most effective method of screening for trisomy 21, with a reported detection rate of 99% and a false positive rate of less than 0.1%. After many years of research, this method is now commercially available and is carried out in an increasing number of patients, and there is an expanding number of conditions that can be screened for. However, the application of these methods in clinical practice requires a careful analysis. Current first-trimester screening strategies are based on a complex combination of tests, aiming at detecting fetal defects and predicting the risk of main pregnancy complications. It is therefore necessary to define the optimal way of combining cell-free DNA testing with current first-trimester screening methods. In this concise review we describe the basis of cell-free DNA testing and discuss the potential approaches for its implementation in combination with current tests in the first trimester., (© 2014 S. Karger AG, Basel.)

Objectives: We tested the hypothesis whether a texture analysis (TA) algorithm applied to MRI brain images identified different patterns in small for gestational age (SGA) fetuses as compared with adequate for gestational age (AGA)., Study Design: MRI was performed on 83 SGA and 70 AGA at 37 weeks' GA. Texture features were quantified in the frontal lobe, basal ganglia, mesencephalon, cerebellum and cingulum. A classification algorithm based on discriminative models was used to correlate texture features with clinical diagnosis., Results: Region of interest delineation in all areas was achieved in 61 SGA (12 vasodilated) and 52 AGA; this was the sample for TA feature extraction which allowed classifying SGA from AGA with accuracies ranging from 90.9 to 98.9% in SGA versus AGA comparison and from 93.6 to 100% in vasodilated SGA versus AGA comparison., Conclusions: This study demonstrates that TA can detect brain differences in SGA fetuses. This supports the existence of brain microstructural changes in SGA fetuses., (Copyright © 2013 S. Karger AG, Basel.)

This is the first report of fetoscopy to successfully treat a case of bilobar bronchial atresia presenting in the form of a massive right lung tumor causing severe thoracic compression with mediastinal shift, pulmonary hypoplasia and eventually fetal hydrops. The presence of an echolucent tubular structure in the pulmonary hilum was identified as the intrapulmonary continuation of the interrupted main bronchus, and led to the diagnosis of main bronchial atresia. After extensive discussion and counseling, a fetoscopic operation was designed and indicated. The procedure consisted of a fetal tracheoscopy and access to the right main bronchus, which was perforated with a diode laser until a communication with the dead end of the intrapulmonary main bronchus was achieved. After the operation a significant reduction in size was observed, hydrops and mediastinal shift disappeared and O/E LHR increased to 85%. The fetus was born at term and lobectomy of two dysplastic pulmonary lobes was performed. The infant is developing well at 14 months of age. This report demonstrates that fetoscopic airway decompression can achieve fetal survival in the rare event of main bronchus atresia., (Copyright © 2012 S. Karger AG, Basel.)