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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.)

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: Preterm prelabor rupture of membranes (PPROM) is a common complication after fetal surgeries. The aim of this study was to assess risk factors for and outcomes after PPROM following cord occlusion (CO) in monochorionic diamniotic (MCDA) pregnancies., Methods: This was a retrospective cohort study of 188 consecutive MCDA pregnancies treated by bipolar or laser CO, either primarily because of discordant malformation (dMF) or severe selective fetal growth restriction (sFGR), or secondarily when complete bichorionization was not possible in case of twin-to-twin transfusion syndrome (TTTS) or sFGR. Intentional septostomy was performed when needed. The procedure-related PPROM was defined as rupture of membranes <32 weeks' gestation (PROM <32 weeks). Selected pre-, intra-, and early postoperative variables were analyzed by univariate and binomial logistic regression to determine they are correlated to PROM <32 weeks after CO., Results: Between 2006 and 2017, 188 cases underwent CO. Diagnosis was TTTS in 28.2% (n = 53), severe sFGR in 49.5% (n = 93), and dMF in 22.3% (n = 42). PROM <32 weeks occurred in 21.3% (n = 40), resulting in worse perinatal outcomes, as preterm birth <32 weeks occurred in 80.7% (vs. 8.3%, p = 0.000), procedure-to-delivery interval was 47.5 days (vs. 125, p = 0.000), gestational age (GA) at birth 30.0 weeks (vs. 37.7 weeks, p = 0.000), and survival 65.0% (vs. 91.1%, p = 0.000). In univariate analysis, indication, anterior placenta, cervical length, GA at surgery, operation time, amniodistention and drainage fluid volumes, chorioamniotic membrane separation, and septostomy were selected as relevant factors to be included in the regression model. In a multivariate analysis, TTTS was the only factor associated to PROM <32 weeks (OR 3.5 CI 95% 1.5-7.9)., Conclusions: PROM <32 weeks after CO increases the risk of preterm delivery. In this cohort, the membrane rupture was more likely when CO was done in the context of TTTS., (© 2021 S. Karger AG, Basel.)

Objective: The aim of the study was to assess the diagnostic yield of 2 different next-generation sequencing (NGS) approaches: gene panel and "solo" clinical exome sequencing (solo-CES), in fetuses with structural anomalies and normal chromosomal microarray analysis (CMA), in the absence of a known familial mutation., Methodology: Gene panels encompassing from 2 to 140 genes, were applied mainly in persistent nuchal fold/fetal hydrops and in large hyperechogenic kidneys. Solo-CES, which entails sequencing the fetus alone and only interpreting the Online Mendelian Inheritance in Man genes, was performed in multisystem or recurrent structural anomalies., Results: During the study period (2015-2020), 153 NGS studies were performed in 148 structurally abnormal fetuses with a normal CMA. The overall diagnostic yield accounted for 35% (53/153) of samples and 36% (53/148) of the fetuses. Diagnostic yield with the gene panels was 31% (15/49), similar to 37% (38/104) in solo-CES., Conclusions: A monogenic disease was established as the underlying cause in 35% of selected fetal structural anomalies by gene panels and solo-CES., (© 2021 The Author(s). Published by 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.)

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.)

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.)

Objectives: The aim of this study was to derive longitudinal reference values of fetal growth (estimated fetal weight [EFW] and abdominal circumference [AC]) during the third trimester and to develop coefficients for conditional growth assessment., Patients and Methods: A prospective cohort study was conducted involving consecutive singleton pregnancies in a low-risk population for a routine third-trimester scan at 30+0-34+6 weeks and follow-up at 37+0-38+6 weeks for an additional ultrasound. Statistical analysis was based on multilevel modeling using MLwiN software. Unconditional centiles were calculated from z-values at each gestational age, and conditional centiles were calculated from z-values at a given measurement (30-34 weeks) and the expected measurement (37-38 weeks)., Results: At 30-34 weeks, 8 and 9.3% of the fetuses had an unconditional EFW below the 10th and above the 90th centile, respectively. At 37-38 weeks, these figures were 10.3 and 9.3%, respectively. Regarding the unconditional AC, at the first scan, 8.9 and 9.6% had values below the 10th and above the 90th centile, while at the second scan 10.5 and 10.5% had values below the 10th and above the 90th centile, respectively. The proportion with a conditional EFW below the 10th and above the 90th centile was 10.2 and 9.4% at the second scan, respectively. For conditional AC, these figures were 10.7 and 10.3%, respectively., Conclusion: We have produced reference centiles for EFW and AC growth during the third trimester as a useful tool for quantifying growth., (© 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.)

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.)

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., (© 2016 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.)

Objective: Congenital high airway obstruction syndrome (CHAOS) normally has a dire prognosis due to laryngeal atresia and association with other anomalies. However, rare cases with an isolated tracheal membrane have been described. We assessed systematically the larynx and vocal cords in fetuses with CHAOS, with the goal of identifying such cases and attempting fetoscopic deobstruction., Methods: Between 2008 and 2012, 7 cases of CHAOS were referred to our institution. The ultrasonographic aspect of the larynx and trachea was assessed. We report the ultrasound findings, necropsy findings of 6 cases and perinatal outcome in 1 case undergoing therapy., Results: In 6 cases, laryngeal atresia was presumed by ultrasound and confirmed by necropsy after termination of pregnancy. In 1 case, normal appearance of the vocal cords led to suspicion of a possible isolated tracheal web completely occluding the trachea. Fetoscopy confirmed the finding, thus the membrane was perforated. Lung size normalized and hydrops resolved. A normal fetus was delivered at term, requiring no respiratory support. At 9 months of age, the infant showed a normal laryngoscopy and was developing well., Conclusions: Systematic ultrasound assessment of the vocal cords can be performed in fetuses with CHAOS. We report the first case of long-term intact survival after fetoscopic airway deobstruction., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To compare the outcomes of twin-to-twin transfusion syndrome (TTTS) cases treated with fetoscopic laser coagulation of vascular anastomoses before 25 + 6 weeks of gestation and between 26 and 28 weeks of gestation., Material and Methods: 28 consecutive cases of TTTS at Quintero stages II-IV treated with laser therapy between 26 + 0 and 28 + 6 weeks of gestation were compared with 324 cases treated between 15 + 0 and 25 + 6 weeks during a 3-year period in two centers. The following data were recorded and compared: duration of the fetoscopy, rate of complications (preterm labor before 28 weeks and before 32 weeks, chorioamnionitis, twin anemia-polycythemia syndrome and recurrent TTTS), gestational age at delivery and neonatal survival rate., Results: The study groups were similar as regards Quintero staging and the frequency of anterior placental location (50.0 vs. 47.8%, p = 0.85 in late and conventional laser, respectively). There were no significant differences in the duration of surgery (29 vs. 30, p = 0.27, respectively) and in the rates of any of the complications evaluated. Gestational age at delivery (33 vs. 33.3 weeks, p = 0.69) and neonatal survival of at least one fetus (92.3 vs. 88.6%, p = 0.24) were also similar., Conclusion: Fetoscopic laser coagulation for TTTS performed between 26 + 0 and 28 + 6 weeks of gestation was associated with similar outcomes as those observed in cases treated before 26 weeks., (Copyright © 2011 S. Karger AG, Basel.)

Prostaglandin E(1) analogues, gemeprost and misoprostol, are the most widely used drugs for medical termination of pregnancy within the first two trimesters of pregnancy. Gemeprost has been reported to be associated with acute cardiovascular accidents in a few cases, but no adverse cardiovascular events have been reported with misoprostol. For this reason, misoprostol has been considered a potentially safer drug and is widely recommended as a first-choice drug in combination with mifepristone. We report a case of a 32-year-old woman with active smoking and obesity, who developed an episode of transient acute coronary artery vasospasm following the administration of intravaginal misoprostol. This report illustrates that misoprostol can also be associated with acute coronary events, although it remains to be evaluated whether the risk is similar or lower to gemeprost., (Copyright 2010 S. Karger AG, Basel.)

Introduction: To describe an animal model of growth restriction based on selective ligature of uteroplacental vessels in the pregnant rabbit., Material and Methods: Two experimental protocols (+21 and +25 days of gestation) with three groups were defined: controls, mild (20-30%) and severe (40-50%) uteroplacental vessel ligature. Fetuses were delivered 120 h after the procedure by cesarean section. Biometrical measurements were carried out. Brains were obtained and glial response and cell proliferation were studied by S100beta and Ki-67 immunohistochemistry., Results: Mortality rate and biometrical restriction increased across experimental groups according to the time and severity of the procedure. S100beta expression was significantly higher in the severe reduction group at 25 days. Ki-67 expression was significantly higher in the mild reduction group at 21 days and in the severe reduction group at 25 days., Discussion: Selective ligature of uteroplacental vessels in the pregnant rabbit results in a gradual model of growth restriction in terms of mortality, biometrical restriction and histological brain changes.