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Background: Because the data from previous experiments on the fetal effects of carbon dioxide (CO2) amniodistention in endoscopic fetal surgery are conflicting, we set out to evaluate the fetal acid-base status during CO2 amniodistention, with or without maternal hyperventilation, using a sheep model for endoscopic surgery.Methods: We assigned 26 pregnant ewes undergoing amniodistention with CO2 (4-5 mmHg intraamniotic pressure) to one of the following three groups: group I had fetal surgery + no maternal hyperventilation (n = 10); group II had fetal surgery + maternal hyperventilation (n = 10); group III had no fetal surgery + maternal hyperventilation (n = 6). Hyperventilation kept CO2 at 29-31 mmHg; in its absence, pCO2 ranged from 38 to 41. Fetal surgery consisted of fetoscopic tracheal clipping. Maternal blood pressure (mean, 98/69 mmHg) and heart rate (mean, 72 bpm) were kept at values comparable to human pregnancy. Fetal and maternal blood gas measurements were taken every 15 min during 1 h of amniodistention.Results: The ranges for baseline mean fetal pCO2 (mmHg) and pH were 51-55 and 7.24-7.25, respectively, in all study groups. After 1 h of amniodistention, mean +/- SEM values of fetal pCO2 and pH were 88 +/- 3 and 7.06 +/- 0.03 in group I, 69 +/- 4 and 7.13 +/- 0.02 in group II, and 71 +/- 5 and 7.14 +/- 0.04 in group III, respectively. Therefore, maternal hyperventilation attenuated but could not prevent significant fetal hypercarbia and acidosis. Fetal surgical manipulation had no effect on these observations.Conclusion: CO2 amniodistention should not be considered for clinical practice until ways of preventing its effects on the fetal acid-base status can be demonstrated. [ABSTRACT FROM AUTHOR]

Monochorionic (MC) twins represent a significant proportion of perinatal morbidity and mortality. Overall, 1 of 3 MC twin pregnancies will develop complications in relation to the MC placenta and the presence of interfetal placental anastomoses. From a clinical standpoint, these complications can be grouped into four main types of clinical problems: chronic transfusion, acute transfusion, growth discordance, and discordant malformation. Differential diagnosis of MC twin complications is still challenging due to frequent overlap of their clinical signs and the complex relationships between them. Clinical experience demonstrates that most instances of wrong management derive from failure to comply with a basic set of rules for diagnosis and management. In this review, we propose a simplified approach to the understanding of MC twin pregnancy, its potential complications, and the key concepts allowing adequate differential diagnosis and targeted management. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: There is paucity of data on the capacity of fetal membranes to repair surgical defects following trauma. We aimed at developing an in vitro model using monolayers of human amnion epithelial cells to study fetal membrane healing. Methods: Term (n = 6) and preterm (n = 3) fetal membranes were collected at caesarean section. The amnion was digested twice in a trypsin solution. Amniocytes were seeded (250,000-750,000/ml) and incubated at 37°C and 5% CO2 and 21 or 5% O2. A microsurgical injury was made centrally in the monolayers and the cultures were incubated for 48 h. Every 6 h, slides were fixed and immunohistochemical staining was performed to quantify proliferation at the site of the defect and centrally in the monolayer. The closure rate was evaluated by measuring the defect size every 6 h. Results: The closure rate of the defects was higher in preterm versus term cultures. Proliferation was significantly higher in the defect zone versus the peripheral zone, and also higher in the preterm group. Conclusion: We describe a new model for the study of fetal membrane healing and observed gestational age-dependent repair capacity of the amnion. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

References 1 Paules C, Miranda J, Policiano C, Crovetto F, Youssef L, Hahner N, Nakaki A, Crispi F, Gratacós E, Eixarch E. Fetal neurosonography detects differences in cortical development and corpus callosum in late-onset small fetuses. First of all, we did not recommend "universal" targeted neurosonography in this population, although we believe that, in selected cases, it may be a suitable tool to detect subtle brain differences, identify small fetuses and counsel parents on the potentially higher risker of neurobehavioral problems. We appreciate the interest of D'Antonio and colleagues in our work on the use of fetal neurosonography in late-onset small fetuses1, and would like to comment on some of the points that they have raised. [Extracted from the article]

The article focuses on the application of percutaneous fetal endoscoping left-handed congenetial in severe left-handed, "Diaphragmatic Hernia" in the treatment of such music. the article talks about the regarding varioys aspect of search. The values and design of the country's live change will allow prospectives of people. The article examines the concept of aerial trip.

Objective To assess the incidence of parenchymal lesions on early and late neonatal brain scans and its association with the presence or absence of intermittent absent or reversed end-diastolic umbilical artery flow velocity (A/REDV) in monochorionic twins complicated by selective intrauterine growth restriction (IUGR), as compared to dichorionic twins and monochorionic twins without selective IUGR. Methods This was a prospective cohort study involving 42 monochorionic twins diagnosed with selective IUGR and managed expectantly. The presence or absence of intermittent A/REDV was recorded in all cases. This study group was compared to dichorionic twins (n = 29) and monochorionic twins without selective IUGR (n = 32) delivered at 26-34 weeks during the study period. All infants underwent an early neonatal brain scan (at or before the fourth day of postnatal life) and at least one follow-up scan during the first 28 days of postnatal life. Perinatal outcome and the incidence of neurological damage were compared between the study groups. Results The incidence of intrauterine fetal death (IUD) and periventricular leukomalacia was significantly increased in monochorionic twins complicated with selective IUGR, as compared with the other study groups. Intermittent A/REDV was observed in 22/42 (52.4%) twin pairs, and was always present in the growth- restricted twin. The incidence of IUD (overall 9/44 (20.5%) vs. 0/40, P < 0.001; smaller twin 6/22 (27.3%) vs. 0/20, P < 0.05) and parenchymal brain damage (overall 7/35 (20.0%) vs. 2/40 (5.0%), P = 0.07; larger twin 7/19(36.8%) vs. 1/20(5.0%), P < 0.05) was significantly higher in pregnancies with intermittent A/REDV than in those without intermittent A/REDV. Brain damage usually occurred in the larger twin, irrespective of whether the smaller twin was liveborn or not. Conclusions The presence of intermittent A/REDV in monochorionic twins with selective IUGR identifies a subgroup with an elevated risk of intrauterine demise of the smaller twin and neurological damage in the larger twin; this latter finding is not restricted to cases with IUD of the cotwin. [ABSTRACT FROM AUTHOR]

Objective To evaluate the incidence and clinical relevance of intermittent absent and/or reversed diastolic flow on umbilical artery Doppler in different groups of monochorionic twin pregnancies. Methods This was a prospective study involving three groups of monochorionic pregnancies: Group 1: controls followed fortnightly from the first trimester (n = 80); Group 2: cases with selective intrauterine growth restriction (n = 40); and Group 3: cases with severe twin-twin transfusion syndrome (n = 50). The presence and persistence over time of intermittent absent and/or reversed end- diastolic flow on umbilical artery Doppler was recorded. Placentas were examined and placental sharing and the presence of large arterioarterial anastomoses (AAA) was assessed. Perinatal outcome was recorded in all cases. Results Intermittent absent and/or reversed diastolic flow was present in 5% (4/80) of cases in Group 1, 45% (18/40) in Group 2 and 2% (1/50) in Group 3 (P < 0.0001, Group 2 vs. 1 and 3). Placental examination was performed in 76.4% (130/170) of cases and sharing was 58% for Group 1, 81% for Group 2 and 73% for Group 3 (P < 0.0001, Groups 2 and 3 vs. 1). Large AAA were identified in all examined cases with intermittent flow (18/18) and in 3.6% (4/112) of those without. The in-utero mortality rate was 0% in Group 1 and in Group 2 fetuses without intermittent flow. However, it was 19.4% in Group 2 cases with intermittent diastolic flow. Conclusions Intermittent absent and/or reversed end-diastolic flow may be considered to be a characteristic sign of monochorionic pregnancy, and seems to result from the existence of large AAA. Its incidence is significantly increased in the context of selective intrauterine growth restriction, indicating a high risk for poor pregnancy outcome in these cases. [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the impact of fetoscopic laser coagulation of placental anastomoses in severe twin–twin transfusion syndrome on fetal Doppler indices and umbilical vein blood flow volume as calculated with Doppler and two-dimensional ultrasound. Methods Thirty-two cases of second-trimester severe twin–twin transfusion undergoing laser therapy were examined with serial ultrasound before and 1, 3 and 5 days after therapy. Pulsatility indices in the umbilical artery and ductus venosus were measured. Blood volume flow at the level of the intra-abdominal umbilical vein was calculated by means of Doppler and two-dimensional ultrasound. The development of hydropic signs in donors was recorded. Perinatal outcome in terms of neonatal survival was recorded for all cases. Results In recipients, ductus venosus pulsatility index decreased progressively after therapy and, by day 5, median pulsatility index was significantly lower than that before therapy (0.97 vs. 0.82, P < 0.0001). Umbilical vein blood flow volume in recipient twins showed no significant variations before and after laser. In donors, umbilical artery pulsatility index decreased significantly by the first day following therapy (2.1 vs. 1.6, P < 0.0001). Previously absent or reverse umbilical end-diastolic flow reappeared after therapy in 46% (7/15) of donors. Ductus venosus pulsatility index in donors increased significantly by day 1 after therapy (0.99 vs. 1.35, P < 0.0001) but, over days 3 and 5, it returned towards preoperative values. Umbilical vein flow volume measurements (mL/min/kg) in the donor increased by approximately 50% the day after treatment (151 vs. 232, P < 0.0001) and remained elevated. Umbilical vein flow volume before laser therapy was significantly lower in donors compared to recipients (151 vs. 260, P < 0.0001), but the difference was non-significant after treatment (240 vs. 267). One or more hydropic signs developed in eight (25%) donors during the 5... [ABSTRACT FROM AUTHOR]

Abstract Objective To evaluate the incidence, characteristics, and impact on perinatal outcome of the development of hydropic signs in the donor fetus after laser coagulation for severe twin–twin transfusion syndrome in the second trimester. Methods Forty cases of second-trimester severe twin–twin transfusion underwent fetoscopic laser coagulation of placental anastomoses and were followed up with serial ultrasound up to 14 days after therapy. Ultrasound scans were performed just before, and on days 1, 3, 5 and 14 after therapy, and fetuses were monitored for the presence of hydropic signs (skin edema, pleural effusion, ascites and pericardial effusion). Response to therapy and perinatal outcome in terms of neonatal survival were recorded for all cases. Results Four recipients (10%) and three donors (7.5%) died over the first 72 h after therapy. During the study period, two recipients (5.5%) developed frank hydrops fetalis, and eventually died in utero . Ten donors (27.0%) developed one or more hydropic signs. In nine (90%), signs were mild or moderate and transient (mean, 3.2 days), while in one case hydrops worsened and the fetus eventually died. No donors with transient hydrops died in utero , and two died postnatally due to extreme prematurity. Gestational age at procedure and deepest amniotic fluid vertical pocket were similar between hydropic and non-hydropic donors. Discrepancy in estimated fetal weight at procedure was significantly lower in donors developing hydrops (9.6 (SD, 6.4) vs. 17.8 (14.4)%,P = 0.018). In pregnancies with hydropic donors, gestational age at delivery (33.1 (3.4) vs. 29.7 (3.5) weeks,P = 0.015) and birth weight for recipient (2392 (423) vs. 1631 (576) g, P < 0.001) and donor (1908 (774) vs. 1281 (583) g,P = 0.021) were significantly higher. The development of transient hydrops had no influence on neonatal survival at 28 days nor on the rate of clinical resolution of intertwin transfusion. Conclusions Transient... [ABSTRACT FROM AUTHOR]

The article comments on the study which examines the risks of predicting neurological outcome associated with preterm intrauterine growth restriction (IUGR). The author argues that preterm uterine growth compromises the risks between irreversible neurological damage and risks of prematurity. According to the author, the study will help in the clarification of optimal issues related to delivery.

No abstract available [ABSTRACT FROM AUTHOR]

STUDY QUESTION Do spontaneously conceived (SC) fetuses from subfertile couples show the same signs of cardiac remodeling as those observed after IVF treatments? SUMMARY ANSWER As opposed to fetuses from IVF, SC fetuses from subfertile couples do not show cardiac remodeling and present a similar cardiac structure and function to those of SC fetuses from fertile couples. WHAT IS KNOWN ALREADY Subjects conceived by IVF present signs of cardiac remodeling and suboptimal function in utero and during childhood, including larger atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation as compared to SC individuals from fertile couples. There are no previous publications investigating the independent cardiac programming effects of infertility in SC fetuses from subfertile couples (with time-to-pregnancy (TTP) over 12 months). STUDY DESIGN, SIZE, DURATION A prospective cohort study of 289 singleton pregnancies exposed and not exposed to subfertility recruited from 2019 to 2021, including 96 SC pregnancies from fertile couples (TTP under 12 months), 97 SC from subfertile couples (TTP over 12 months), and 96 from IVF after fresh embryo transfer. Fetal echocardiography was performed in all pregnancies. Epidemiological data and perinatal outcomes were collected in all pregnancies. The overall attrition rate was 15.7%. PARTICIPANTS/MATERIALS, SETTING, METHODS SC from subfertile couples and IVF pregnancies were identified as eligible at pregnancy diagnosis, and eligible SC pregnancies from fertile couples who attended our maternal-fetal unit were invited to participate at third trimester, being matched to the other groups by maternal age. Fetal echocardiography was performed at 29–34 weeks of pregnancy to assess cardiac structure and function, and results were adjusted by parental age, maternal smoking status, child's birth order, birthweight centile, gestational age, and estimated fetal weight at scan. MAIN RESULTS AND THE ROLE OF CHANCE Parental age, ethnicity, BMI, and smoking exposure, median gestational age and estimated fetal weight were similar in all study groups. There were no significant differences in infertility duration or etiology between the subfertile and the IVF populations (TTP: subfertile median 35 months (interquartile range 20–48) versus IVF: 47 (25–61); P -value = 0.051). While both fertile and subfertile SC groups presented similar fetal cardiac results, IVF fetuses showed larger atria (right atria-to-heart ratio: IVF mean 18.9% (SD 3.4) versus subfertile 17.8% (3.5) versus fertile 17.6% (3.3); adjusted P -value < 0.001), more globular ventricles (right ventricular sphericity index: IVF 1.56 (0.25) versus subfertile 1.72 (0.26) versus fertile 1.72 (0.26); <0.001), and thicker myocardial walls (relative wall thickness: IVF 0.86 (0.22) versus subfertile 0.64 (0.13) versus fertile 0.64 (0.18); <0.001). Whereas SC fetuses from fertile and subfertile couples had preserved cardiac function, IVF fetuses showed signs of suboptimal systolic and diastolic function, with reduced tricuspid ring displacement (IVF 7.26 mm (1.07) versus subfertile 8.04 mm (1.18) versus fertile 7.89 mm (1.51); <0.001) and increased left myocardial performance index (IVF 0.49 (0.08) versus subfertile 0.45 (0.09) versus fertile 0.45 (0.10); <0.001). A sub-analysis including only unexplained infertility cases in subfertile SC and IVF groups showed similar results. LIMITATIONS, REASONS FOR CAUTION The fetal cardiac changes reported here are subclinical, and most of the cardiovascular parameters were within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with long-term cardiovascular disease remains to be demonstrated. WIDER IMPLICATIONS OF THE FINDINGS Subfertility per se does not seem to be associated to fetal cardiac remodeling, which has been previously described in IVF fetuses. Future studies are warranted to further investigate other factors related to the observed fetal cardiac changes associated with ART. STUDY FUNDING/COMPETING INTEREST(S) This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI16/00861, PI17/00675, PI18/00073, INT21/00027)—co-funded by the European Union, Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant no 1531. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective: To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non‐invasive hemodynamic assessment. Methods: This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109–117 days' gestation. The study was designed to collect in‐utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1–3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3–24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre‐ and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. Results: Compared with in‐utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06–1.50) vs 0.38 (IQR, 0.31–0.50) vs 0.36 (IQR, 0.29–0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41–0.67) vs 0.29 (IQR, 0.22–0.33) vs 0.36 (IQR, 0.22–0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18–22 cm/s) vs 39 cm/s (IQR, 31–43 cm/s) vs 43 cm/s (IQR, 34–54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35–54 mmHg), 72 mmHg (IQR, 61–77 mmHg) and 58 mmHg (IQR, 50–64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142–156 bpm) vs 188 bpm (IQR, 171–209 bpm) vs 175 bpm (IQR, 165–190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34–41%) in utero, 38% (IQR, 30–40%) at 30 min and 37% (IQR, 33–40%) at 180 min (P = 0.807 for extreme timepoints). Conclusions: Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short‐term evaluation, cardiac structure and function were preserved. However, the system resulted in non‐physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Fetuses conceived by assisted reproductive technology (ART) and those that are small-for-gestational age (SGA) show cardiovascular remodeling in utero; however, these two conditions are often associated. We aimed to evaluate the differential effect of ART and SGA on fetal cardiac remodeling.Methods: This was a prospective cohort study of term singleton pregnancies seen at our department between April 2011 and September 2013. The cohort was divided according to fetal growth and mode of conception into the following four groups: 102 appropriate-for-gestational-age (AGA) fetuses conceived spontaneously (controls), 72 AGA fetuses conceived by ART (ART-AGA), 31 SGA fetuses conceived by ART (ART-SGA) and 28 SGA fetuses conceived naturally (Spont-SGA). SGA was defined as birth weight < 10th centile. Fetal echocardiography was performed at 28-32 weeks to assess cardiac dimensions, geometry and function.Results: ART fetuses had dilated atria (mean left atrium-to-heart area ratio: controls, 15 ± 2.7%; ART-AGA, 18 ± 4.1%; Spont-SGA, 14 ± 3.7%) and more globular ventricles (left ventricular sphericity index: controls, 1.77 ± 0.2; ART-AGA, 1.68 ± 0.2; Spont-SGA, 1.72 ± 0.2), with normally sized hearts. In contrast, SGA fetuses had enlarged hearts (cardiothoracic ratio: controls, 24 ± 3%; ART-AGA, 24 ± 4%; Spont-SGA, 29 ± 6%), preserved atrial size, more globular and concentric hypertrophic ventricles (left ventricle relative wall thickness: controls, 0.48 ± 0.17; ART-AGA, 0.54 ± 0.13; Spont-SGA, 0.63 ± 0.23). Both ART and SGA fetuses had decreased longitudinal motion (tricuspid annular ring displacement: controls, 6.5 ± 0.8 mm; ART-AGA, 5.5 ± 0.7 mm; Spont-SGA, 5.9 ± 0.6 mm) and impaired relaxation (left isovolumetric relaxation time: controls, 47.0 ± 7.3 ms; ART-AGA, 50.0 ± 7.9 ms; Spont-SGA, 49.5 ± 9.3 ms). ART-SGA fetuses presented a combination of features from both ART and SGA groups.Conclusion: SGA and conception with ART were associated with distinct patterns of fetal cardiac remodeling, supporting the concept that they are independent causes of cardiac programming. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection. Methods: This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal–fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non‐isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin–eosin‐stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0–3) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions. Results: Thirty‐five CMV‐infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non‐isolated CNS finding (22.6 vs 24.4 weeks; P = 0.10). In fetuses with a non‐isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10/18 (56%) vs 1/8 (13%); P = 0.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non‐isolated halo sign (21/26 (81%)) and those without a periventricular echogenic halo (2/3 (67%); P = 0.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white‐matter necrosis or cortical injury. On the other hand, 25/26 fetuses with a non‐isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non‐isolated halo, histological brain lesions did not progress with gestational age, although white‐matter necrosis was more frequent, albeit non‐significantly, in fetuses diagnosed in the second vs the third trimester (10/15 (67%) vs 3/11 (27%); P = 0.06). Conclusions: In CMV‐infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white‐matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow‐up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. Methods: This was a retrospective case–control study of consecutive pregnancies with a CMV‐infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low‐risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV‐DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto‐occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non‐parametric trend analysis. Results: Twenty‐four CMV‐infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV‐infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9–9.9) mm vs 3.9 (IQR, 2.6–5.3) mm; left side, 7.5 (IQR, 6.0–10.9) mm vs 4.2 (IQR, 3.2–5.3) mm), significantly decreased parieto‐occipital sulcus depth (right side, 12.6 (IQR, 11.3–13.5) mm vs 15.9 (IQR, 13.5–17.3) mm; left side, 12.3 (IQR, 10.6–13.5) mm vs 16.0 (IQR, 13.3–17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4–16.3) mm vs 17.5 (IQR, 16.1–18.7) mm; left side, 14.6 (IQR, 14.1–15.6) mm vs 16.7 (IQR, 15.6–18.9) mm) (P < 0.001 for all). Compared with controls, CMV‐infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8–45.8°) vs 48.9° (IQR, 38.4–64.7°); left side, 40.9° (IQR, 34.2–45.8°) vs 48.2° (IQR, 41.9–60.7°)) and lower (right side, 41.6° (IQR, 34.4–49.2°) vs 48.9° (IQR, 40.6–60.9°); left side, 42.2° (IQR, 38.8–46.9°) vs 48.9° (IQR, 39.5–57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV‐infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto‐occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small‐for‐gestational age as a confounding factor. Conclusions: Unaffected and mildly affected CMV‐infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non‐severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore fetal cortical brain development by neurosonography in fetuses conceived by assisted reproductive technology (ART), including frozen and fresh embryo transfer (ET), compared with those conceived spontaneously (SC), and to investigate its association with infant neurobehavior at 12 months of age.Methods: This was a prospective cohort study of 210 singleton pregnancies, including 70 SC pregnancies, 70 conceived by in-vitro fertilization (IVF) following frozen ET and 70 conceived by IVF after fresh ET. Fetal neurosonography was performed at 32 ± 2 gestational weeks to assess cortical development. Sulci depths were measured offline and normalized by biparietal diameter (BPD). Ages and Stages Questionnaires (ASQ) were completed postnatally, at 12 ± 1 months of corrected age. Neurosonographic findings were adjusted by regression analysis for maternal age, ethnicity, parity, fetal sex and fetal-weight centile and gestational age at scan, and ASQ scores were adjusted for maternal age, ethnicity, parity, educational level and employment status, gestational age at birth, breastfeeding, infant sex and infant age at the ASQ evaluation.Results: Overall, in comparison to the SC fetuses, fetuses conceived by ART showed statistically significant differences in cortical development, with reduced parieto-occipital sulci depth adjusted for BPD (mean ± SD: fresh ET, 12.5 ± 2.5 vs frozen ET, 13.4 ± 2.6 vs SC, 13.4 ± 2.6, P < 0.001), cingulate sulci depth adjusted for BPD (median (interquartile range (IQR)): fresh ET, 5.8 (4.2-7.4) vs frozen ET, 5.8 (4.1-7.5) vs SC, 6.5 (4.8-7.8), P = 0.001) and calcarine sulci depth adjusted for BPD (median (IQR): fresh ET, 13.5 (10.1-16.1) vs frozen ET, 14.5 (12.1-15.8) vs SC, 16.4 (14.3-17.9), P < 0.001), together with lower Sylvian fissure grading score. Changes in cortical development were more pronounced in the fresh ET than in the frozen ET group. ART infants showed lower ASQ scores as compared to SC infants, particularly in the fresh ET group (mean ± SD global ASQ Z-score: fresh ET, -0.3 ± 0.4 vs frozen ET, -0.2 ± 0.4 vs SC, 0 ± 0.4, P < 0.001).Conclusions: Fetuses conceived by ART show a distinctive pattern of cortical development and suboptimal infant neurodevelopment, with more pronounced changes in those conceived following fresh ET. These findings support the existence of in-utero brain reorganization associated with ART and warrant follow-up studies to assess its long-term persistence. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prevalence of and perinatal outcome associated with increased nuchal translucency thickness (NT) > 99(th) percentile in dichorionic and monochorionic twins with normal karyotype. Methods: Two hundred and six consecutive twin pregnancies (166 dichorionic and 40 monochorionic) underwent an NT scan during a 4-year period. In those with NT > 99(th) percentile and normal karyotype, we performed first- and second-trimester anomaly scans, fetal echocardiography at 14-16 and 20-22 weeks, maternal serology and, in monochorionic pregnancies, serial ultrasound examinations every other week. Perinatal outcome was recorded. Results: There were 10 (4.95%) pregnancies in which one of the fetuses had NT > 99(th) percentile and normal karyotype, including five fetuses (1.5%) in dichorionic and five (6.25%) in monochorionic pregnancies. During the same period the prevalence of NT > 99(th) percentile and normal karyotype in singleton pregnancies studied in our center was 2.6%. Among the 10 twins affected, six (60%) were diagnosed with structural abnormalities (three dichorionic and three monochorionic), and two intrauterine fetal demises occurred (one dichorionic and one monochorionic). Thus, the perinatal outcome was normal in only two of the pregnancies, one dichorionic and one monochorionic. Conclusions: The prevalence of NT > 99(th) percentile in dichorionic twins with a normal karyotype is similar to that in singletons. In monochorionic twins we confirmed previous studies reporting an increased prevalence compared with singletons. NT > 99(th) percentile with a normal karyotype in twins was associated with a high rate of fetal abnormalities and/or fetal demise (overall 80%) irrespective of chorionicity. [ABSTRACT FROM AUTHOR]

Aim: To construct normal reference values for Doppler parameters in 2 anatomical segments of the fetal anterior cerebral artery (ACA) throughout pregnancy. Methods: The ACA was evaluated in 373 normally growing fetuses from 20 to 40 weeks of gestation. The first segment of the ACA (ACA-S1) was recorded just after its origin from the internal carotid artery in the same plane as the middle cerebral artery (MCA). The second segment (ACA-S2) was recorded distal to the outlet of the anterior communicating artery. Results: The ACA pulsatility index (PI) behaved similarly in both segments, with a constant increase until 28 weeks followed by a decrease until the end of pregnancy [ACA-S1 PI = 3.49 - 0.37 x gestational age (GA) - (0.0063 x GA(2)), SD = 0.6 - 0.061 x GA - (0.001 x GA(2)); ACA-S2 PI = 1.54 - 0.22 x GA - (0.0037 x GA(2)), SD = 0.206 + (0.0037 x GA)]. Peak systolic velocities in both segments showed a constant increase from 20 to 40 weeks of gestation. No significant differences were found between the 2 segments with regard to any Doppler parameter. However, the angle of insonation and the time spent on examination were significantly lower and reproducibility was better for ACA-S1. Conclusion: Despite showing similar Doppler values, ACA-S1 has a higher reliability than ACA-S2 and can be recorded in the same anatomical projection as the MCA. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the operative and perinatal aspects of fetal endoscopic tracheal occlusion (FETO) as treatment for severe congenital diaphragmatic hernia (CDH). In this study, the researchers observe that the survival rate in fetuses with left CDH treated with FETO increased from 24.1% to 49.1% while in right CDH the survival increased from 0% to 35.3%. Result of the study finds that FETO in severe CDH is a substantial improvement in survival.

Objectives: To construct gestational age (GA)-based reference ranges for the uterine artery (UtA) mean pulsatility index (PI) at 11-41 weeks of pregnancy. Methods: A prospective cross-sectional observational study was carried out of 20 consecutive singleton pregnancies for each completed gestational week at 11-41 weeks. UtAs were examined by color and pulsed Doppler imaging, and the mean PI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded. Polynomials were fitted by means of least-square regression to estimate the relationship between the mean UtA-PI and GA. Results: A total of 620 women were included. A second-degree polynomial (Log(e) mean UtA-PI = 1.39 - 0.012 x GA + GA(2) x 0.0000198, with GA measured in days), after a natural logarithmic transformation, was selected to model our data. There was a significant decrease in the mean UtA-PI between 11 weeks (mean PI, 1.79; 95(th) centile, 2.70) and 34 weeks (mean PI, 0.70; 95(th) centile, 0.99). It then became more stable up until 41 weeks (mean PI, 0.65; 95(th) centile, 0.89). Conclusions: The mean UtA-PI shows a progressive decrease until the late stages of pregnancy. Reference ranges for mean UtA-PI may have clinical value in screening for placenta-associated diseases in the early stages of pregnancy, and in evaluating patients with pregnancy-induced hypertension and/or small-for-gestational age fetuses during the third trimester. [ABSTRACT FROM AUTHOR]

Objective: To standardize the evaluation of regional fetal brain blood perfusion, using power Doppler ultrasound (PDU) to estimate the fractional moving blood volume (FMBV) and to evaluate the reproducibility of this estimation. Methods: Brain blood perfusion was evaluated in 35 normally grown fetuses at 28-30 weeks of gestation, using PDU. The following cerebral regions were included in the PDU color box: anterior sagittal, complete sagittal, basal ganglia, and cerebellar. Ten consecutive good-quality images of each anatomical plane were recorded and the delimitation of the region of interest (ROI) was performed off-line. FMBV was quantified in the ROI of all images and the mean considered as the final value. Differences between regions, variability, reproducibility and agreement between observers were assessed. Results: Power Doppler images of the described anatomical planes were obtained in all cases, regardless of fetal position. The median time for the acquisition of the images was 7 (range 4-12) min. Mean (range) FMBV values were: anterior sagittal, 16.5 (10.7-22.8)%, inter-patient coefficient of variation (CV) 0.22; complete sagittal, 13.5 (8.8-16.1)%, CV 0.27; basal ganglia, 18.3 (10.7-27.6)%, CV 0.27; and cerebellar, 6.6 (3.0-11.0)%, CV 0.38. There were statistically significant differences in FMBV between cerebellar and complete sagittal ROIs with the frontal and basal ganglia regions. Reproducibility analyses showed an intraclass correlation coefficient of 0.91 (95% CI 0.67-0.97) and an interclass correlation coefficient of 0.87 (95% CI 0.70-0.94). Interobserver agreement showed a mean difference between observers of -0.2 (SD 2.7) with 95% limits of agreement -5.6 to 5.2. Conclusions: When the regions of interest are well defined, the FMBV estimate offers a method to quantify blood flow perfusion in different fetal cerebral areas. There appear to be regional differences in FMBV within the fetal brain. [ABSTRACT FROM AUTHOR]

Objective: To estimate changes in umbilical blood flow (UBF) and Doppler indices in pregnancies complicated by twin-to-twin transfusion syndrome (TTS) treated with either laser therapy or amniodrainage, and to evaluate the influence of the presence of hemodynamic deterioration prior to therapy, as determined by the Quintero stages of severity. Methods: Forty-eight cases of TTS were included, and further classified into severity Stages I or II (absence of critically abnormal Dopplers (CAD), n = 22) and Stages III or IV (presence of CAD or hydrops fetalis, n = 26). In Stages I-II, 14 cases were treated with laser and eight with amniodrainage, and in Stages III-IV, 17 were treated with laser and nine with amniodrainage. Differences in the UBF, umbilical artery pulstility index (UA-PI) and ductus venosus pulsatility index (DV-PI) were estimated for both groups of severity before and after both treatments. Eleven normal monochorionic pregnancies were evaluated as controls. Results: In recipients, UBF was significantly higher with respect to controls regardless of the stage, while donors had a significant decrease in UBF, but only in Stages III-IV. After laser treatment no changes were observed in fetuses in Stages I-II. In Stages III-IV, recipients showed a significant reduction in the DV-PI (mean DV-PI 1.31 +/- 0.18 vs. 1.05 +/- 0.22; P = 0.005) whereas donors showed a significant increase in the UBF (mean UBF 134 +/- 36 mL/min vs. 195 +/- 25 mL/min; P < 0.001) and in the DV-PI (mean DV-PI 0.99 +/- 0.26 vs. 1.36 +/- 0.42; P = 0.002), and a reduction in the UA-PI (mean UA-PI 1.86 +/- 0.41 vs. 1.58 +/- 0.30; P = 0.01). After amniodrainage only donor fetuses in Stages III-IV showed an increase in UA-PI (mean UA-PI 1.54 +/- 0.35 vs. 1.72 +/- 0.40; P = 0.015). No other changes were observed in any of the parameters studied. Conclusion: Laser therapy induces consistent hemodynamic variations in TTS mainly manifested in Stages III-IV. [ABSTRACT FROM AUTHOR]

Objective: To evaluate corpus callosum (CC) size by neurosonography (NSG) in fetuses with an isolated major congenital heart defect (CHD) and explore the association of CC size with the expected pattern of in‐utero oxygen supply to the brain. Methods: A total of 56 fetuses with postnatally confirmed isolated major CHD and 56 gestational‐age‐matched controls were included. Fetuses with CHD were stratified into two categories according to the main expected pattern of cerebral arterial oxygen supply: Class A, moderately to severely reduced oxygen supply (left outflow tract obstruction and transposition of the great arteries) and Class B, near normal or mildly impaired oxygenated blood supply to the brain (other CHD). Transvaginal NSG was performed at 32–36 weeks in all fetuses to evaluate CC length, CC total area and areas of CC subdivisions in the midsagittal plane. Results: CHD fetuses had a significantly smaller CC area as compared to controls (7.91 ± 1.30 vs 9.01 ± 1.44 mm2; P < 0.001), which was more pronounced in the most posterior part of the CC. There was a significant linear trend for reduced CC total area across the three clinical groups, with CHD Class‐A cases showing more prominent changes (controls, 9.01 ± 1.44 vs CHD Class B, 8.18 ± 1.21 vs CHD Class A, 7.53 ± 1.33 mm2; P < 0.05). Conclusions: Fetuses with major CHD had a smaller CC compared with controls, and the difference was more marked in the CHD subgroup with expected poorer brain oxygenation. Sonographic CC size could be a clinically feasible marker of abnormal white matter development in CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

To evaluate neuroprotective effects of docosahexaenoic acid (DHA), melatonin (MEL) and sialic acid (SA) or lactoferrin (LF) in an I in vitro i neurosphere model of fetal growth restriction (FGR). Finally, the I in vivo i administration of DHA and MEL, and not LF, presented a significant increase in the oligodendrocyte differentiation in comparison to untreated FGR neurospheres (4.7% in untreated FGR vs. [Extracted from the article]

The customised 95th centile of the UA was higher, and the customised 5th centile of the CPR was lower than only GA-adjusted standards. The 5th centile of the CPR and the 95th centile of the UA PI were modelled by quantile regression. To determine the effect of maternal and fetal physiological characteristics on the 95th/5th centile of the umbilical artery (UA) and cerebroplacental ratio (CPR) Doppler, measured at 37+ weeks; and to evaluate its clinical impact on the classification of term small for gestational age babies. [Extracted from the article]

Objectives: In fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity.Methods: This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non-severe LCDH, defined as observed-to-expected lung-to-head ratio (o/e-LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e-LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z-scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2 .Results: Observations for 70 non-severe LCDH cases were available. Fifty-four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA-PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62-9.70)), independently of o/e-LHR (OR, 0.87 (95% CI, 0.79-0.97)). An IPA-PI Z-score cut-off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA-PI to o/e-LHR improved significantly the model's performance (Nagelkerke R2 , 46% for o/e-LHR + IPA-PI vs 28% for o/e-LHR (P < 0.002)), with a detection rate of 81% at a 10% false-positive rate. IPA-PI was associated with PHT (OR, 2.20 (95% CI, 1.01-4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10-3.40)), independently of lung size.Conclusions: In fetuses with mild or moderate LCDH, IPA-PI was associated with mortality and morbidity, independently of lung size. A model combining o/e-LHR with IPA-PI identified up to four in five cases that eventually died, despite being considered to have non-severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Study Question: Do fetuses from frozen embryo transfer (FET) present signs of cardiac remodeling and suboptimal function similar to those observed in fetuses from fresh embryo transfer (ET)?Summary Answer: Fetuses from both fresh ET and FET present signs of fetal cardiac remodeling and suboptimal function, with more pronounced changes after fresh ET as compared to FET.What Is Known Already: Our group and others have previously demonstrated that fetuses and children conceived by ARTs present cardiac remodeling and suboptimal function. These fetuses show dilated atria, more globular and thicker ventricles, reduced longitudinal motion, and impaired relaxation. Cardiac changes were already present in utero and persisted after birth. Most of the ART fetuses included in previous publications were from fresh ET. However, singletons from FET have different perinatal outcomes compared to those from fresh ET. There are no previous studies comparing cardiac morphology and function between fetuses following fresh and FET.Study Design, Size, Duration: This is a prospective cohort study of 300 singleton pregnancies recruited from 2017 to 2020, including 100 spontaneously conceived (SC) pregnancies, 100 fetuses conceived by IVF with FET, and 100 fetuses conceived by IVF with fresh ET. Fetal structural and functional echocardiography was performed in all pregnancies.Participants/materials, Setting, Methods: Pregnancies conceived by IVF were recruited from a single assisted reproduction center, ensuring homogeneity in IVF stimulation protocols, endometrial preparation for FET, laboratory procedures, and embryo culture conditions. SC pregnancies from fertile couples were selected from the general population and matched to IVF pregnancies by maternal age. Epidemiological and perinatal outcomes were collected in all cases. Fetal echocardiography was performed at 28-33 weeks of pregnancy to assess cardiac structure and function in all pregnancies. All echocardiographic comparisons were adjusted by maternal age, nulliparity, birthweight centile, preeclampsia, and prematurity.Main Results and the Role Of Chance: Parental age, ethnicity, body mass index and smoking were similar among the study groups. Median gestational age at echocardiography and estimated fetal weight were similar in all study groups. Both fresh ET and FET groups showed similar fetal echocardiographic changes, with more pronounced features in the fresh ET as compared to FET pregnancies. Fetuses conceived by IVF showed larger atria (right atria-to-heart ratio: fresh ET mean 18.1% (SD 3.2) vs FET 18.0% (3.9) vs SC 17.3% (3.2); linear tendency P-value <0.001), more globular ventricles (right ventricular sphericity index: fresh ET 1.62 (0.29) vs FET 1.61 (0.25) vs SC 1.68 (0.26); <0.001) and thicker myocardial walls (relative wall thickness: fresh ET 0.79 (0.21) vs FET 0.74 (0.22) vs SC 0.65 (0.25); <0.001) as compared to SC pregnancies. Both fresh ET and FET groups also had signs of suboptimal systolic and diastolic function, with reduced tricuspid annular systolic peak velocity (fresh ET 7.17 cm/s (1.22) vs FET 7.41 cm/s (1.19) vs SC 7.58 cm/s (1.32); <0.001) and increased left myocardial performance index (fresh ET 0.53 (0.08) vs FET 0.53 (0.08) vs SC 0.50 (0.09); <0.001) as compared to SC pregnancies.Limitations, Reasons For Caution: The cardiac changes reported here are subclinical, with most cardiovascular indexes lying within normal ranges. Although echocardiographic changes are recognized as potential cardiovascular risk factors, their association with the long-term cardiovascular disease remains to be proven. The observed milder fetal cardiac features in FET fetuses cannot condition the choice of this technique and must be considered together with the global perinatal results related to these gestations.Wider Implications Of the Findings: The identification of cardiac remodeling in fetuses conceived by IVF with fresh ET and FET represents an opportunity for early detection. Future studies are warranted to study the potential long-term consequences of these findings.Study Funding/competing Interest(s): This project has been partially funded with support from the Erasmus + Programme of the European Union (Framework Agreement number: 2013-0040). This publication reflects the views only of the author, and the Commission cannot be held responsible for any use, which may be made of the information contained therein. Additionally, the research leading to these results has received funding from 'la Caixa' Foundation under grant agreement LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI15/00130, PI17/00675, PI18/00073) integrated into the Plan Nacional de I + D+I and cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa', Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and AGAUR 2017 SGR grant n° 1531. The authors declare no conflicts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective: To construct nomograms for fetal cardiac, ventricular and atrial relative size and geometry parameters from 18 to 41 weeks' gestation using a low-risk population of singleton pregnancies.Methods: This was a prospective cohort study of 602 low-risk singleton pregnancies undergoing comprehensive fetal echocardiography, from 18 to 41 weeks of gestation, to assess fetal cardiac, atrial and ventricular relative size and sphericity, ventricular dominance, wall asymmetry and relative wall thickness. Intra- and interobserver measurement reproducibility was evaluated using intraclass correlation coefficients (ICC). In order to construct reference ranges across pregnancy, parametric regressions were tested to model each measurement against gestational age and estimated fetal weight. The measurements evaluated were: cardiothoracic ratio; atrial-to-heart area ratios; ventricular-to-heart area ratios; cardiac, ventricular and atrial sphericity indices; right-to-left basal and midventricular ratios; septal-to-free wall thickness ratios; and relative wall thickness.Results: Fetal cardiac, ventricular and atrial morphometry for assessing relative size and geometry could be successfully performed in > 95% of the population, with moderate-to-excellent interobserver reproducibility (ICC, 0.623-0.907) and good-to-excellent intraobserver reproducibility (ICC, 0.787-0.938). Cardiothoracic ratio and ventricular right-to-left ratio showed a modest increase throughout gestation. Atrial-to-heart and ventricular-to-heart area ratios, atrial sphericity indices and septal-to-free wall thickness ratios were constant with gestational age. Left and right ventricular basal sphericity indices showed a tendency to decrease at the end of gestation, while left and right midventricular sphericity indices tended to decrease in the second trimester. The cardiac sphericity index and left and right relative wall thickness showed a modest decrease with gestational age. Nomograms across gestation were constructed for all echocardiographic parameters described.Conclusions: The assessment of cardiac, ventricular and atrial relative size and geometry is feasible and reproducible in the fetus. We provide standardized reference ranges for these parameters throughout gestation, enabling the accurate assessment of cardiac remodeling patterns during fetal life. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To explore whether neurosonography can detect differences in cortical development and corpus callosal length in late-onset small fetuses subclassified into small-for-gestational age (SGA) or growth restricted (FGR).Methods: This was a prospective cohort study in singleton pregnancies, including normally grown fetuses (birth weight between the 10th and 90th centiles) and late-onset small fetuses (estimated fetal weight < 10th centile, diagnosed after 32 weeks of gestation and confirmed by birth weight < 10th centile). Small fetuses were subclassified into SGA (birth weight between the 3rd and 9th centiles and normal fetoplacental Doppler) and FGR (birth weight < 3rd centile and/or abnormal cerebroplacental ratio and/or abnormal uterine artery Doppler). Neurosonography was performed at 33 ± 1 weeks of gestation to assess the depth of the insula, Sylvian fissure and parieto-occipital sulcus in the axial views and corpus callosal length in the midsagittal plane. Measurements were performed offline using Alma Workstation software and were adjusted by biparietal diameter or cephalic index. Linear regression analysis was used to assess the association between the neurosonographic variables and study group, adjusting for confounding factors such as gender, gestational age at neurosonography, nulliparity and pre-eclampsia.Results: In total, 318 fetuses were included, of which 97 were normally grown and 221 were late-onset small fetuses that were further subdivided into late-onset SGA (n = 67) or late-onset FGR (n = 154). Compared to controls, both SGA and FGR cases showed significantly increased insular depth adjusted for biparietal diameter (median (interquartile range), controls 0.329 (0.312-0.342) vs SGA 0.339 (0.321-0.347) vs FGR 0.336 (0.325-0.349); P = 0.006). A linear tendency to reduced Sylvian fissure depth adjusted for biparietal diameter was also observed across the study groups (mean ± SD, controls 0.148 ± 0.021 vs SGA 0.142 ± 0.025 vs FGR 0.139 ± 0.022; P = 0.003). However, differences were significant only between the FGR and control groups. Corpus callosal length adjusted for cephalic index was significantly reduced in FGR cases compared with both controls and SGA cases, while there was no difference between SGA cases and controls (median (interquartile range), controls 0.500 (0.478-0.531) vs SGA 0.502 (0.487-0.526) vs FGR 0.475 (0.447-0.508); P = 0.005). No differences were found in parieto-occipital sulcus depth between the three study groups.Conclusion: Neurosonography seems to be a sensitive tool to detect subtle structural differences in brain development in late-onset small fetuses. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: Fetal cardiac function can be evaluated using a variety of parameters. Among these, cardiac cycle time‐related parameters, such as filling time fraction (FTF) and ejection time fraction (ETF), are promising but rarely studied. We aimed to report the feasibility and reproducibility of fetal FTF and ETF measurements using pulsed‐wave Doppler, to provide reference ranges for fetal FTF and ETF, after evaluating their relationship with heart rate (HR), gestational age (GA) and estimated fetal weight (EFW), and to evaluate their potential clinical utility in selected fetal conditions. Methods: This study included a low‐risk prospective cohort of singleton pregnancies and a high‐risk population of fetuses with severe twin–twin transfusion syndrome (TTTS), aortic stenosis (AoS) or aortic coarctation (CoA), from 18 to 41 weeks' gestation. Left ventricular (LV) and right ventricular inflow and outflow pulsed‐wave Doppler signals were analyzed, using valve clicks as landmarks. FTF was calculated as: (filling time/cycle time) × 100. ETF was calculated as: (ejection time/cycle time) × 100. Intraclass correlation coefficients (ICC) were used to evaluate the intra‐ and interobserver reproducibility of FTF and ETF measurements in low‐risk fetuses. The relationships of FTF and ETF with HR, GA and EFW were evaluated using multivariate regression analysis. Reference ranges for FTF and ETF were then constructed using the low‐risk population. Z‐scores of FTF and ETF in the high‐risk fetuses were calculated and analyzed. Results: In total, 602 low‐risk singleton pregnancies and 54 high‐risk fetuses (nine pairs of monochorionic twins with severe TTTS, 16 fetuses with AoS and 20 fetuses with CoA) were included. Adequate Doppler traces for FTF and ETF could be obtained in 95% of low‐risk cases. Intraobserver reproducibility was good to excellent (ICC, 0.831–0.905) and interobserver reproducibility was good (ICC, 0.801–0.837) for measurements of all timing parameters analyzed. Multivariate analysis of FTF and ETF in relation to HR, GA and EFW in low‐risk fetuses identified HR as the only variable predictive of FTF, while ETF was dependent on both HR and GA. FTF increased with decreasing HR in low‐risk fetuses, while ETF showed the opposite behavior, decreasing with decreasing HR. Most recipient twins with severe TTTS showed reduced FTF and preserved ETF. AoS was associated with decreased FTF and increased ETF in the LV, with seemingly different patterns associated with univentricular vs biventricular postnatal outcome. The majority of fetuses with CoA had FTF and ETF within the normal range in both ventricles. Conclusions: Measurement of FTF and ETF using pulsed‐wave Doppler is feasible and reproducible in the fetus. The presented reference ranges account for associations of FTF with HR and of ETF with HR and GA. These time fractions are potentially useful for clinical monitoring of cardiac function in severe TTTS, AoS and other fetal conditions overloading the heart. © 2020 International Society of Ultrasound in Obstetrics and Gynecology [ABSTRACT FROM AUTHOR]

Objective: To report our 10-year experience of protocol-based management of small-for-gestational-age (SGA) fetuses, based on standardized clinical and Doppler criteria, in late-pregnancy cases.Methods: A retrospective cohort was constructed of consecutive singleton pregnancies referred for late-onset (> 32 weeks) SGA (defined as estimated fetal weight (EFW) < 10th centile) that were classified as fetal growth restriction (FGR) or low-risk SGA, based on the severity of smallness (EFW < 3rd centile) and the presence of Doppler abnormalities (uterine artery pulsatility index (UtA-PI) ≥ 95th centile or cerebroplacental ratio (CPR) < 5th centile). Low-risk SGA pregnancies were followed at 2-week intervals and delivered electively at 40 weeks. FGR pregnancies were followed at 1-week intervals, or more frequently if there were signs of fetal deterioration, and were delivered electively after 37 + 0 weeks' gestation. The occurrence of stillbirth and composite adverse outcome (CAO; defined as neonatal death, metabolic acidosis, need for endotracheal intubation or need for admission to the neonatal intensive care unit) was analyzed in low-risk SGA and FGR pregnancies.Results: A total of 1197 pregnancies with EFW < 10th centile were identified and classified at diagnosis as low-risk SGA (n = 619; 51.7%) or FGR (n = 578; 48.3%). Of these, 160 were delivered before 37 weeks' gestation; for obstetric reasons in 93 (58.1%) cases, severe pre-eclampsia in 33 (20.6%), FGR with severe hypoxia in 47 (29.4%) and stillbirth in four (2.5%) (indications are non-exclusive). During follow-up, 52/574 (9.1%) low-risk SGA pregnancies were reclassified as FGR, whereas 22/463 (4.8%) FGR pregnancies were reclassified as low-risk SGA. Overall, there were no stillbirths in the low-risk SGA group and four in the FGR group, all of which occurred before 37 weeks. There were no instances of neonatal death in pregnancies delivered ≥ 37 weeks. The risk of CAO was higher in those meeting antenatal criteria for FGR at 37 weeks than in those classified as low-risk SGA (32/493 (6.5%) vs 15/544 (2.8%); odds ratio, 2.5 (95% CI, 1.3-4.6)). In FGR pregnancies, the adjusted odds ratio (95% CI) for CAO was 6.3 (1.8-21.1) in those with EFW < 3rd centile, while it was 3.2 (1.5-6.8) and 4.2 (1.9-8.9) in those with UtA-PI ≥ 95th centile and CPR < 5th centile, respectively, as compared to FGR pregnancies without each of these criteria.Conclusion: Protocol-based risk stratification with different management and monitoring schemes for late pregnancy with a suspected SGA baby, based on clinical and Doppler criteria, enables identification and tailored assessment of high-risk FGR, while allowing expectant management with safe perinatal outcome for low-risk SGA fetuses. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation.Methods: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively.Results: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct.Conclusions: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To describe placental histopathological findings in a large cohort of pregnancies complicated by pre-eclampsia (PE) and/or small-for-gestational age (SGA), and to investigate their association with fetoplacental Doppler parameters.Methods: This was a prospective observational study of normotensive pregnancies with SGA (defined as birth weight < 10th centile) (n = 184), PE pregnancies with a normally grown fetus (n = 102), pregnancies with both PE and SGA (n = 120) and uncomplicated pregnancies (n = 202). Uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) artery pulsatility indices (PI) were assessed. The cerebroplacental ratio (CPR) was calculated by dividing MCA-PI by UA-PI. Doppler parameters were considered abnormal when UtA-PI or UA-PI was > 95th centile or MCA-PI or CPR was < 5th centile. Placental lesions were categorized as vascular (maternal or fetal side), immunoinflammatory or other, according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Comparison between the study groups was performed using univariate and multiple regression analysis, and logistic regression was used to determine the relationship between abnormal Doppler parameters and placental lesions.Results: Maternal-side vascular lesions were significantly more common in PE pregnancies with SGA than in the other groups (PE + SGA, 73% vs PE, 46% vs SGA, 38% vs controls, 31%; P = 0.01) and included mainly two types of lesion: developmental (PE + SGA, 13% vs PE, 5% vs SGA, 3% vs controls, 1.5%; P < 0.001) and malperfusion (PE + SGA, 70% vs PE, 39% vs SGA, 32% vs controls, 25%; P = 0.001). In contrast, the incidence of fetal-side developmental lesions was significantly higher in normotensive SGA pregnancies than in controls and PE pregnancies (PE + SGA, 0% vs PE, 3% vs SGA, 8% vs controls, 2%; P = 0.001). All cases displayed a lower prevalence of infectious lesions than did controls, with the highest prevalence of immune lesions observed in pregnancies with both PE and SGA (PE + SGA, 18% vs PE, 8% vs SGA, 10% vs controls, 9%; P = 0.001). All fetoplacental Doppler parameters evaluated were associated with maternal-side vascular lesions, mainly malperfusion (mean UtA-PI: odds ratio (OR), 2.45 (95% CI, 1.51-3.97); UA-PI: OR, 2.05 (95% CI, 1.02-4.47); MCA-PI: OR, 2.75 (95% CI, 1.40-5.42); CPR: OR, 1.75 (95% CI, 1.04-2.95)). This association was evident mainly in the normotensive SGA group, being non-significant in controls or PE pregnancies without SGA. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups.Conclusions: PE and SGA are associated with different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs fetal). Fetoplacental Doppler findings show an association with placental malperfusion lesions on the maternal side, supporting the use of abnormal Doppler as a surrogate for placental insufficiency. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between the cervical consistency index (CCI) and the risk of Cesarean delivery after planned induction of labor (IOL) at term.Methods: This was a prospective observational study of women with a term singleton pregnancy admitted for IOL due to maternal or fetal indication. Ultrasonographic images were obtained before IOL and CCI was calculated offline once recruitment was completed. The main outcome was defined as Cesarean delivery due to failed IOL or arrest of labor. Cesarean deliveries indicated due to maternal or fetal compromise (Van Dillen's grade 1 or 2) were excluded from analysis. Univariate statistical analysis was performed using Fisher's exact test and Student's t-test for categorical and continuous variables, respectively. Multivariate analysis was performed using logistic regression, including CCI and other variables related to the main outcome. Intraclass correlation coefficients were used to estimate intra- and interobserver agreement.Results: Of 510 women admitted for IOL during the study period and for whom image quality was adequate, 46 were excluded due to emergency Cesarean delivery leaving 464 pregnancies for analysis. Cesarean section due to failed IOL or arrest of labor was performed in 100/464 (21.6%) pregnancies. The mean CCI of women who underwent Cesarean delivery was not significantly different from that in those who had vaginal delivery after IOL (70.1 ± 12.3% vs 70.0 ± 13.1%; P = 0.94). Multivariate analysis also showed absence of statistical association between CCI and Cesarean delivery for failed IOL or arrest of labor. Intraclass correlation coefficients for intra- and interobserver agreement were 0.81 (95% CI, 0.66-0.89) and 0.86 (95% CI, 0.75-0.92), respectively.Conclusion: CCI does not seem to be associated with the risk of Cesarean delivery after IOL. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the transgenerational transmission of small-for-gestational age (SGA).Methods: This was a cohort study of a random sample of 2043 offspring delivered between 1975 and 1993 at Hospital Sant Joan de Déu in Barcelona. Exclusion criteria were multiple pregnancy, aneuploidy or genetic syndrome, major birth defects, severe mental disease and macrosomia. Eligible individuals were contacted and those with at least one offspring were included in the study. Participants were classified according to the presence of SGA (defined as birth weight < 10th percentile) at birth. Multiple regression analysis was used to determine the presence of SGA or placenta-mediated disease (defined as the presence of SGA, pre-eclampsia, gestational hypertension and/or placental abruption) in the following generation.Results: Of 623 individuals who agreed to participate, 152 (72 born SGA and 80 born appropriate-for-gestational age (AGA)) were reported to have at least one child. Descendants of SGA individuals presented with a lower birth-weight percentile (median, 26 (interquartile range (IQR), 7-52) vs 43 (IQR, 19-75); P < 0.001) and a higher prevalence of SGA (40.3% vs 16.3%; P = 0.001) and placenta-mediated disease (43.1% vs 17.5%; P = 0.001) than did the offspring of AGA individuals. After adjustment for confounding variables, parental SGA background was associated with an almost three-fold increased risk of subsequent SGA or any placenta-mediated disease in the following generation. This association was stronger in SGA mothers than in SGA fathers.Conclusions: Our data provide evidence suggesting a transgenerational transmission of SGA, highlighting the importance of public health strategies for preventing intrauterine growth impairment. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To perform a comprehensive assessment of the placental aging process in small term fetuses classified as being small-for-gestational age (SGA) or having fetal growth restriction (FGR) through analysis of senescence and apoptosis markers.Methods: This was a prospective nested case-control study of singleton pregnancies delivered at term, including 21 control pregnancies with normally grown fetuses and 36 with a small fetus classified as SGA (birth weight between the 3rd and 9th percentiles and normal fetoplacental Doppler; n = 18) or FGR (birth weight < 3rd percentile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler; n = 18). Telomerase activity, telomere length (quantified by comparing the amount of amplification product for the telomere sequence (T) to that of a single copy of the gene 36B4 (S)) and RNA expression of senescence (Sirtuins 1, 3 and 6) and apoptosis (p53, p21, BAX and Caspases 3 and 9) markers (analyzed using the 2-ΔΔCt method) were determined in placental samples collected at birth and compared between the three groups.Results: Compared to pregnancies with a normally grown fetus, both SGA and FGR pregnancies presented signs of accelerated placental aging, including lower telomerase activity (mean ± SD, 12.8 ± 6.6% in controls vs 7.98 ± 4.2% in SGA vs 7.79 ± 4.6% in FGR; P = 0.008), shorter telomeres (mean ± SD T/S ratio, 1.20 ± 0.6 in controls vs 1.08 ± 0.9 in SGA vs 0.66 ± 0.5 in FGR; P = 0.047) and reduced Sirtuin-1 RNA expression (mean ± SD 2-ΔΔCt , 1.55 ± 0.8 in controls vs 0.91 ± 0.8 in SGA vs 0.63 ± 0.5 in FGR; P = 0.001) together with increased p53 RNA expression (median (interquartile range) 2-ΔΔCt , 1.07 (0.3-3.3) in controls vs 5.39 (0.6-15) in SGA vs 3.75 (0.9-7.8) in FGR; P = 0.040). FGR cases presented signs of apoptosis, with increased Caspase-3 RNA levels (median (interquartile range) 2-ΔΔCt , 0.94 (0.7-1.7) in controls vs 3.98 (0.9-31) in FGR; P = 0.031) and Caspase-9 RNA levels (median (interquartile range) 2-ΔΔCt , 1.21 (0.6-4.0) in controls vs 3.87 (1.5-9.0) in FGR; P = 0.037) compared with controls. In addition, Sirtuin-1 RNA expression, telomerase activity, telomere length and Caspase-3 activity showed significant linear trends across groups as severity of the condition increased.Conclusions: Accelerated placental aging was observed in both clinical forms of late-onset fetal smallness (SGA and FGR), supporting a common pathophysiology and challenging the concept of SGA fetuses being constitutionally small. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies (ART) in children at 3 years of age.Design: A cohort study of children conceived by ART.Setting: Maternal-Fetal Medicine Unit, Hospital Clinic Barcelona, Spain.Population Sample: Eighty singleton pregnancies conceived by ART and 80 spontaneously conceived (controls) followed from fetal life up to childhood.Methods: Cardiovascular evaluation was performed at 3 years of corrected age, including echocardiography, carotid intima-media (cIMT) by ultrasound, and blood pressure.Main Outcome Measures: Postnatal persistence of cardiovascular changes in children conceived by ART.Results: Compared with controls, children conceived by ART showed larger atria (right atrial area: control 4.9 cm2 (0.9) versus ART 5.5 cm2 (0.9), P < 0.001), more globular ventricles (right ventricular sphericity index: control mean 1.8 (SD 0.5) versus ART 1.6 (0.2), P < 0.001), and signs of systolic (tricuspid annular plane systolic excursion: control 18 mm (2) versus ART 16 mm (3), P < 0.001) and diastolic dysfunction (isovolumic relaxation time: control 68 ms (12) versus ART 79 ms (12), P < 0.001). ART children also presented increased systolic blood pressure (control 90 mmHg (6) versus ART 94 mmHg (5), P < 0.003) and cIMT (control 0.52 μm (0.14) versus ART 0.60 μm (0.16), P < 0.001) as compared with those spontaneously conceived.Conclusions: Cardiovascular changes previously reported in ART fetuses persist postnatally at 3 years of age. These results underscore the importance of future studies for assessing the long-term cardiovascular health associated with ART.Tweetable Abstract: Cardiovascular changes described in fetuses conceived by ART, persist in children at 3 years of age. [ABSTRACT FROM AUTHOR]

Objective: New tools are required to improve the identification of women who are at increased risk for spontaneous preterm birth (sPTB). Quantitative analysis of tissue texture on ultrasound has been used to extract robust features from the ultrasound image to detect subtle changes in its microstructure. This may be applied to the cervix. The aim of this study was to determine if there is an association between quantitative analysis of cervical texture (CTx) on mid-trimester ultrasound and sPTB < 37 + 0 weeks' gestation.Methods: This was a single-center nested case-control study of a prospective cohort of 677 consecutive women with singleton pregnancy assessed between 19 + 0 and 24 + 6 weeks' gestation. Women at increased risk for sPTB were included unless they received treatment to prevent sPTB. Women who delivered < 37 + 0 weeks (sPTB) were considered as cases and were matched in a 1: 10 ratio with randomly selected contemporary controls who delivered at term. For each woman, one ultrasound image of the cervix was obtained for which quality was assessed, cervical length (CL) measured offline and a region of interest in the midportion of the anterior cervical lip delineated for use in local binary patterns analysis of CTx. A learning algorithm was developed to obtain the combination of CTx features best associated with sPTB based on feature transformation and discriminant analysis regression. The ability of the learning algorithm to predict sPTB was evaluated using a leave-one-out cross-validation technique, which produced a CTx-based score for each participant. Receiver-operating characteristics (ROC) curves were produced and sensitivity, specificity, and positive and negative likelihood ratios were calculated for the optimal cut-off based on the ROC curve. The results were compared with those obtained for CL. Investigators studying the images were blinded to pregnancy outcome at all times.Results: Images from 310 women (27 cases and 283 controls) were of sufficient quality and included in the study. Median CTx-based score was significantly lower in cases compared with controls (-1.01 vs -0.07, P ≤ 0.0001). CTx-based score maintained its significant association with sPTB after adjusting for possible confounders (history of sPTB, conization or Müllerian malformation, and CL < 25 mm). CTx-based score was a better predictor of sPTB (AUC, 0.77; 95% CI, 0.66-0.87) than was CL (AUC, 0.60; 95% CI, 0.47-0.72) (P = 0.03). Median CL was similar for cases and controls (37.7 vs 38.6 mm, P = 0.26), although cases were more likely to have CL < 25 mm (18.5% vs 0.4%, P < 0.001).Conclusion: Quantitative analysis of CTx enables the extraction of information relevant to sPTB from ultrasound images to generate a CTx-based score that is associated independently with sPTB. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effectiveness of mid-trimester sonographic cervical consistency index (CCI) for the prediction of spontaneous preterm birth (sPTB) in low-risk pregnancies and to compare its performance with that of mid-trimester sonographic cervical-length (CL) measurement.Methods: This was a prospective cohort study of women with a singleton pregnancy examined by ultrasound at 19 + 0 to 24 + 6 weeks' gestation. All women underwent transvaginal ultrasound examination of the cervix, but CCI and CL were measured, offline, only in women without a risk factor for sPTB. Staff and participants were blinded to CL and CCI results. CCI was obtained by calculating the ratio between the anteroposterior diameter of the uterine cervix at maximum compression and at rest. The primary outcome was prediction of sPTB before 37 + 0 weeks. Receiver-operating characteristics (ROC) curves were produced and sensitivity and specificity were calculated for the optimal cut-off based on the ROC curve and for the 1st , 5th and 10th centiles of CCI and CL. Intraclass correlation coefficients (ICC) and Bland-Altman plots were used to estimate intra- and interobserver agreement and reliability for measurement of CCI and CL.Results: Of the 749 women who underwent ultrasound examination of the cervix, 532 were included for analysis. The rates of sPTB before 37 + 0 and before 34 + 0 weeks were 4.1% (22/532) and 1.3% (7/532), respectively. The rates of short cervix < 25 mm and ≤ 20 mm were 0.9% (5/532) and 0.4% (2/532), respectively. The area under the ROC curve (AUC) with regard to predicting sPTB before 37 + 0 weeks was 0.84 (95% CI, 0.75-0.93) for CCI compared with 0.68 (95% CI, 0.56-0.81) for CL (P = 0.03). The optimal cut-off based on the ROC curve was 64.6% for CCI (sensitivity, 77.3%; specificity, 82.7%) and that for CL was 37.9 mm (sensitivity, 72.7%; specificity, 61.2%). The AUC with regard to predicting sPTB before 34 + 0 weeks was 0.87 (95% CI, 0.71-1.0) for CCI compared with 0.71 (95% CI, 0.47-0.94) for CL (P = 0.25). The optimal cut-off based on the ROC curve was 63.6% for CCI (sensitivity, 85.7%; specificity, 84.0%) and that for CL was 37.9 mm (sensitivity, 85.7%; specificity, 61.3%). Intraobserver ICC was > 0.90 both for CCI and CL, while interobserver ICC was 0.89 for CCI and 0.90 for CL.Conclusions: Second-trimester CCI is a better predictor of sPTB < 37 weeks in low-risk pregnancies than is CL. External validation is needed as well as studies assessing the value of CCI as a screening tool in unselected and high-risk populations. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication. Methods Hearts and placentas from 16 IUGR-offspring and 14 controls were included to characterize mitochondrial function. Results Enzymatic activities of complexes II, IV and II + III in IUGR-hearts (−11.96 ± 3.16%; −15.58 ± 5.32%; −14.73 ± 4.37%; p < 0.05) and II and II + III in IUGR-placentas (−17.22 ± 3.46%; p < 0.005 and −29.64 ± 4.43%; p < 0.001) significantly decreased. This was accompanied by a not significant reduction in CI-stimulated oxygen consumption and significantly decreased complex II SDHB subunit expression in placenta (−44.12 ± 5.88%; p < 0.001). Levels of mitochondrial content, Coenzyme Q and cellular ATP were conserved. Lipid peroxidation significantly decreased in IUGR-hearts (−39.02 ± 4.35%; p < 0.001), but not significantly increased in IUGR-placentas. Sirtuin3 protein expression significantly increased in IUGR-hearts (84.21 ± 31.58%; p < 0.05) despite conserved anti-oxidant SOD2 protein expression and activity in both tissues. Conclusions IUGR is associated with cardiac and placental mitochondrial CII dysfunction. Up-regulated expression of Sirtuin3 may explain attenuation of cardiac oxidative damage and preserved ATP levels under CII deficiency. General significance These findings may allow the design of dietary interventions to modulate Sirtuin3 expression and consequent regulation of mitochondrial imbalance associated with IUGR and derived cardiovascular remodeling. [ABSTRACT FROM AUTHOR]

Objectives: To define the pattern of fetal echocardiographic changes associated with isolated pulmonary valve stenosis (PS) and to correlate the echocardiographic findings with neonatal outcome and the need for postnatal pulmonary valvuloplasty within the first 12 months postpartum.Methods: This was a prospective cohort study between January 2009 and October 2015 of 16 fetuses with isolated PS and 48 controls matched by gestational age at ultrasound examination (± 2 weeks) evaluated at the Fetal Cardiology Unit at BCNatal (Barcelona). Standard fetal ultrasound and comprehensive echocardiography, which included cardiovascular morphometric parameters, and systolic and diastolic functional and timing measurements, were performed in all cases. Baseline characteristics and perinatal outcome were retrieved from clinical records. Cases were followed up until 12 months of age, and admission to intensive care unit, days of hospitalization, need for prostaglandins and requirement for postnatal surgery were reviewed. Fetal PS cases were analyzed according to the need for postnatal pulmonary valvuloplasty.Results: The study groups were similar in terms of baseline, fetal ultrasound and perinatal characteristics. Median gestational age at diagnosis of PS was 33.4 (range, 20.0-36.5) weeks. Most cases corresponded to mild or moderate PS; only three fetuses had reversed flow in the ductus arteriosus before delivery. Six (37.5%) newborns, including all three with reversed flow in the ductus arteriosus prenatally, required postnatal pulmonary valvuloplasty. Fetuses with PS presented with larger and more globular hearts, with increased myocardial wall thickness in the third trimester. Despite preserved right ventricular (RV) ejection fraction and systolic longitudinal motion, PS cases showed increased right cardiac output and signs of diastolic dysfunction, with higher ductus venosus pulsatility index (0.72 ± 0.32 vs 0.53 ± 0.16, P = 0.004) and tricuspid E/E' ratio (7.52 ± 3.07 vs 5.76 ± 1.79, P = 0.022). In addition, fetuses with PS displayed a compensatory increase in left ventricular (LV) radial and longitudinal motion, as shown by a higher ejection fraction (79.3 ± 8.23% vs 67.6 ± 11.3%, P = 0.003) and mitral annular-plane systolic excursion (5.94 ± 1.38 vs 5.0 ± 1.22 mm, P = 0.035). Finally, fetuses requiring postnatal pulmonary valvuloplasty showed a different pattern of echocardiographic findings from those not requiring valvuloplasty, with a significantly smaller RV and pulmonary valve diameter, reduced tricuspid annular-plane systolic excursion (5.08 ± 1.59 vs 8.07 ± 1.93 mm, P = 0.028), increased LV cardiac output (340 ± 16 vs 176 ± 44 mL/min/kg, P = 0.003) and more pronounced signs of LV diastolic dysfunction (mitral E' velocity, 5.78 ± 0.90 vs 8.16 ± 1.58 cm/s, P = 0.008).Conclusions: Fetuses with PS present with more hypertrophic, larger and more globular hearts in the third trimester of pregnancy, associated with a higher right cardiac output and impaired biventricular relaxation. In addition, signs of increased LV contraction were observed. Our data suggest that RV and LV functional parameters could be useful for predicting the need for postnatal pulmonary valvuloplasty. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross-sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second- to third-trimester longitudinal growth assessment to cross-sectional evaluation in the third trimester for the prediction of small-for-gestational age (SGA) and late FGR in low-risk singleton pregnancy.Methods: This was a prospective cohort study of 2696 unselected consecutive low-risk singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks. For cross-sectional growth assessment, abdominal circumference (AC) measurements were transformed to z-values according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by calculating the AC z-velocity and the second- to third-trimester AC conditional growth centile. Longitudinal assessment was compared with cross-sectional assessment at 32 weeks. Association of cross-sectional and longitudinal evaluations with SGA and late FGR was assessed by logistic regression analysis. Predictive performance was determined by receiver-operating characteristics curve analysis.Result: In total, 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. Neither longitudinal measurement improved the association with SGA or late FGR provided by cross-sectional evaluation of AC z-score at 32 weeks. Areas under the curves of AC z-velocity and conditional AC growth were significantly smaller than those of cross-sectional AC z-scores (P < 0.001), although AC z-velocity performed significantly better than did conditional AC growth (P < 0.001).Conclusion: Longitudinal assessment of fetal growth from the second to third trimester has a low predictive capacity for SGA and late FGR in low-risk singleton pregnancy compared with cross-sectional growth evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: Recent data suggest that singleton fetuses conceived by assisted reproductive technology (ART) present cardiovascular remodeling that may persist postnatally. Twin pregnancies are more frequent in the ART population and are associated with increased adverse perinatal outcomes, such as hypertensive disorders, gestational diabetes and preterm birth. However, it is unknown whether cardiac remodeling is also present in twin pregnancies conceived by ART. Our aim was to assess the presence of fetal cardiac remodeling and dysfunction in twin pregnancies conceived by ART as compared with those conceived spontaneously (SC).Methods: This was a prospective cohort study including 50 dichorionic twin fetuses conceived by ART and 50 SC twin fetuses. The study protocol included collection of baseline/perinatal data and a fetal ultrasound examination at 28-30 weeks' gestation, including assessment of estimated fetal weight, fetoplacental Doppler and fetal echocardiography. Measurements of atrial area, atrial/heart ratio, ventricular sphericity index, free wall thickness, mitral and tricuspid annular plane systolic excursions, and systolic and early diastolic peak velocities were assessed. Multilevel analyses were used to compare perinatal and ultrasonographic parameters. Comparisons of echocardiographic variables were adjusted for parental age, paternal body mass index and incidence of pre-eclampsia.Results: Compared with SC twins, ART twin fetuses showed significant cardiac changes, predominantly affecting the right heart, such as dilated atria (right atrial/heart area: 15.7 ± 3.1 vs 18.4 ± 3.2, P < 0.001), more globular ventricles (right ventricular sphericity index: 1.57 ± 0.25 vs 1.41 ± 0.23, P = 0.001) and thicker myocardial walls (septal wall thickness: 2.57 ± 0.45 mm vs 2.84 ± 0.41 mm, P = 0.034) together with reduced longitudinal motion (tricuspid annular plane systolic excursion: 6.36 ± 0.89 mm vs 5.18 ± 0.93 mm, P < 0.001).Conclusions: ART twin fetuses present signs of cardiac remodeling and dysfunction. These changes are similar to those observed in ART singletons and reinforce the concept of fetal cardiac programing in ART. These results open opportunities for early detection and intervention in infants conceived by ART. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Results Among 1356 pregnancies, the mean (SD) adherence to Mediterranean diet was 7.9 (2.6). To assess the adherence to Mediterranean diet at mid gestation in a cohort of pregnant women in Barcelona, Spain. Mediterranean diet adherence was classified as low (mean 4.1 [0.92]) in 262 pregnancies (19.3%), moderate (mean 8.8 [1.4]) in 972 (71.7%), and high (mean 12.8 [0.9]) in 122 (9.0%) pregnant women. [Extracted from the article]

EP36.08: Effects of Mediterranean diet or mindfulness-based stress reduction during pregnancy on newborns' neurobehaviour: the IMPACT-BCN trial Conclusions Maternal lifestyle interventions during pregnancy based on MedDiet or MBSR program positively affect the newborns' neurobehaviour. To assess whether a Mediterranean diet (MedDiet) or a mindfulness-based stress reduction (MBSR) intervention during pregnancy affects the newborns' neurobehaviour. [Extracted from the article]

Carotid-subclavian artery index (CSAI) is a recently described promising parameter for prenatal diagnosis of coarctation of the aorta (COA). EP17.09: Carotid-subclavian artery index to predict coarctaction of the aorta in the second trimester of gestation Aortic arch diameter at the origin of the left subclavian artery (D1) and distance between left carotid and left subclavian artery (D2) were measured as shown in figure 1 to calculate CSAI (D1/D2). [Extracted from the article]

In CMV-infected fetuses we observed significantly larger lateral ventricle width (lvw), significantly less profound parietooccipital-sulcus (POs) and calcarine-sulcus (Cas), significantly larger Sylvian fissure angle (SFA) (table 1); and significantly lower cortical-grading in temporal-area, parietal-area, parietooccipital-sulcus, and calcarine-sulcus (p < 0.05). Assess cortical maturation by MRI in CMV infected fetuses and establish differences compared to a group of healthy fetuses. [Extracted from the article]