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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: 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 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]

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]

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]

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]

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]

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]

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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]

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]

Objectives: To compare the performance of third-trimester screening, based on estimated fetal weight centile (EFWc) vs a combined model including maternal baseline characteristics, fetoplacental ultrasound and maternal biochemical markers, for the prediction of small-for-gestational-age (SGA) neonates and late-onset fetal growth restriction (FGR).Methods: This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester (32 + 0 to 36 + 6 weeks' gestation) evaluation. Maternal baseline characteristics, mean arterial pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently delivered a SGA neonate (n = 175), defined as birth weight < 10th centile according to customized standards, and in a control group (n = 875). Among SGA cases, those with birth weight < 3rd centile and/or abnormal uterine artery pulsatility index (UtA-PI) and/or abnormal cerebroplacental ratio (CPR) were classified as FGR. Logistic regression predictive models were developed for SGA and FGR, and their performance was compared with that obtained using EFWc alone.Results: In SGA cases, EFWc, CPR Z-score and maternal serum concentrations of unconjugated estriol and PlGF were significantly lower, while mean UtA-PI Z-score and lipocalin-2 and inhibin A concentrations were significantly higher, compared with controls. Using EFWc alone, 52% (area under receiver-operating characteristics curve (AUC), 0.82 (95% CI, 0.77-0.85)) of SGA and 64% (AUC, 0.86 (95% CI, 0.81-0.91)) of FGR cases were predicted at a 10% false-positive rate. A combined screening model including a-priori risk (maternal characteristics), EFWc, UtA-PI, PlGF and estriol (with lipocalin-2 for SGA) achieved a detection rate of 61% (AUC, 0.86 (95% CI, 0.83-0.89)) for SGA cases and 77% (AUC, 0.92 (95% CI, 0.88-0.95)) for FGR. The combined model for the prediction of SGA and FGR performed significantly better than did using EFWc alone (P < 0.001 and P = 0.002, respectively).Conclusions: A multivariable integrative model of maternal characteristics, fetoplacental ultrasound and maternal biochemical markers modestly improved the detection of SGA and FGR cases at 32-36 weeks' gestation when compared with screening based on EFWc alone. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential value of third-trimester combined screening for the prediction of adverse perinatal outcome (APO) in the general population and among small-for-gestational-age (SGA) fetuses.Methods: This was a nested case-control study within a prospective cohort of 1590 singleton gestations undergoing third-trimester evaluation (32 + 0 to 36 + 6 weeks' gestation). Maternal baseline characteristics, mean arterial blood pressure, fetoplacental ultrasound and circulating biochemical markers (placental growth factor (PlGF), lipocalin-2, unconjugated estriol and inhibin A) were assessed in all women who subsequently had an APO (n = 148) and in a control group without perinatal complications (n = 902). APO was defined as the occurrence of stillbirth, umbilical artery cord blood pH < 7.15, 5-min Apgar score < 7 or emergency operative delivery for fetal distress. Logistic regression models were developed for the prediction of APO in the general population and among SGA cases (defined as customized birth weight < 10th centile).Results: The prevalence of APO was 9.3% in the general population and 27.4% among SGA cases. In the general population, a combined screening model including a-priori risk (maternal characteristics), estimated fetal weight (EFW) centile, umbilical artery pulsatility index (UA-PI), estriol and PlGF achieved a detection rate for APO of 26% (area under receiver-operating characteristics curve (AUC), 0.59 (95% CI, 0.54-0.65)), at a 10% false-positive rate (FPR). Among SGA cases, a model including a-priori risk, EFW centile, UA-PI, cerebroplacental ratio, estriol and PlGF predicted 62% of APO (AUC, 0.86 (95% CI, 0.80-0.92)) at a FPR of 10%.Conclusions: The use of fetal ultrasound and maternal biochemical markers at 32-36 weeks provides a poor prediction of APO in the general population. Although it remains limited, the performance of the screening model is improved when applied to fetuses with suboptimal fetal growth. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To identify different cardiac phenotypes among cases of fetal growth restriction (FGR).Methods: Echocardiography was performed in 126 cases with FGR (birth weight < 10th centile) and 64 appropriate-for-gestational-age (AGA) fetuses. Principal component and cluster analyses were performed to identify different cardiac phenotypes among FGR cases.Results: Three different cardiac phenotypes were identified among the FGR group: globular in 54% of cases, elongated in 29% of cases and hypertrophic in 17% of cases. Those with a globular heart had the lowest median left-ventricular sphericity index (controls, 1.78 (interquartile range (IQR), 1.62-1.97); FGR elongated, 1.92 (IQR, 1.78-2.09); FGR globular, 1.44 (IQR, 1.36-1.52); FGR hypertrophic, 1.65 (IQR, 1.42-1.77); P = 0.001). FGR cases with an elongated left ventricle had nearly normal cardiac dimensions. FGR cases with a hypertrophic phenotype had the highest median left-ventricular wall thickness (controls, 1.22 (IQR, 1.10-1.67) mm/kg; FGR elongated, 1.52 (IQR, 1.28-1.86) mm/kg; FGR globular, 1.65 (IQR, 1.39-1.99) mm/kg; FGR hypertrophic, 3.68 (IQR, 3.45-4.71) mm/kg; P = 0.001) and cardiac dimensions. Globular and elongated phenotypes showed a fetoplacental profile of late-onset FGR, while the hypertrophic phenotype showed signs of early-onset FGR. The hypertrophic group also had the poorest perinatal results, having the lowest birth-weight centile, gestational age at delivery and Apgar score and the highest postnatal blood pressure and aorta intima-media thickness.Conclusions: FGR induces at least three different cardiac phenotypes, with early-onset FGR cases being associated with a hypertrophic response and worse perinatal outcomes. This cardiac phenotypic classification may improve identification of FGR cases with the highest perinatal and long-term cardiovascular risks. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT: 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]

Objectives: To determine the longitudinal behavior of fetal biometric measures and cerebroplacental hemodynamics throughout gestation in fetuses with congenital heart disease (CHD).Methods: Fetal biometry and Doppler hemodynamics (uterine artery (UtA), umbilical artery (UA) and fetal middle cerebral artery (MCA)) were measured serially in a cohort of consecutive fetuses diagnosed with CHD. Evaluations were made at various time points, from diagnosis (20-25 weeks) to delivery, with at least two measurements per fetus that were at least 2 weeks apart. Fetuses were classified into three groups according to the pattern of blood supply to the brain (placental vs systemic) that would be expected on the basis of the type of CHD. All parameters were transformed into Z-scores. A linear mixed model to analyze repeated measurements was constructed for each parameter to assess its behavior throughout gestation.Results: Four hundred and forty-four ultrasound examinations were performed in 119 CHD fetuses, with a median of two measurements per fetus. The fetuses presented a small head at diagnosis (biparietal diameter (BPD) Z-score, -1.32 ± 0.99; head circumference (HC) Z-score, -0.79 ± 1.02), which remained small throughout gestation. UtA and UA pulsatility indices (PI) showed a significant increase towards the end of pregnancy, whereas no significant changes were observed in MCA-PI or cerebroplacental ratio (CPR) with gestational age. Both MCA and CPR presented significant differences in longitudinal behavior between CHD groups, while BPD and HC did not.Conclusions: CHD fetuses have a relatively small head from the second trimester of pregnancy, regardless of the type of CHD anomaly, and increasing resistance in the UtA and UA as pregnancy progresses, suggestive of increasing degree of placental impairment. Our findings indicate the early onset of mechanisms that could lead to poorer neurodevelopment later in life. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To validate the performance of a previously constructed first-trimester predictive model for pre-eclampsia (PE) in routine care of an unselected population.Methods: A validation cohort of 4621 consecutive women attending their routine first-trimester ultrasound examination was used to test a prediction model for PE that had been developed previously in 5170 women. The prediction model included maternal factors, uterine artery Doppler, blood pressure and pregnancy-associated plasma protein-A. Model performance was evaluated using receiver-operating characteristics (ROC) curve analysis and ROC curves from both cohorts were compared unpaired.Results: Among the 4203 women included in the final analysis, 169 (4.0%) developed PE, including 141 (3.4%) cases of late-onset PE and 28 (0.7%) cases of early-onset PE. For early-onset PE, the model showed an area under the ROC curve of 0.94 (95% CI, 0.88-0.99), which did not differ significantly (P = 0.37) from that obtained in the construction cohort (0.88 (95% CI, 0.78-0.99)). For late-onset PE, the final model showed an area under the ROC curve of 0.72 (95% CI, 0.66-0.77), which did not differ significantly (P = 0.49) from that obtained in the construction cohort (0.75 (95% CI, 0.67-0.82)).Conclusion: The prediction model for PE achieved a similar performance to that obtained in the construction cohort when tested on a subsequent cohort of women, confirming its validity as a predictive model for PE. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [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]

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 whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery.Design: Multicentre, randomised, double-blind, placebo-controlled trial.Setting: Twelve tertiary care centres in Spain.Population: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm.Methods: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first.Main Outcome Measures: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality.Results: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion.Conclusions: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery.Tweetable Abstract: Maintenance progesterone in 258 women after arrested PTL showed no benefit. [ABSTRACT FROM AUTHOR]

Objectives: Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well-documented. We evaluated longitudinally the association between cardiovascular remodeling in small-for-gestational-age (SGA) fetuses and at 6 months of age.Methods: A cohort of 80 SGA fetuses (defined by estimated fetal and birth weights < 10(th) centile) delivered > 34 weeks' gestation was compared with 80 normally grown age-matched control fetuses, with follow-up at 6 months of corrected age (i.e. 6 months from estimated date of delivery according to first-trimester crown-rump length). Cardiovascular evaluation included a comprehensive echocardiographic assessment in both fetuses and infants and blood pressure and aortic intima-media thickness (aIMT) measurement in infants. Parameters were adjusted by linear regression analysis for gender, gestational age at delivery, pre-eclampsia, prenatal glucocorticoid exposure, Cesarean delivery, admission to neonatal intensive care unit and body surface area.Results: Both pre- and postnatally, when compared with controls, the SGA group showed a more globular cardiac shape (left sphericity index: controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007) postnatally), as well as signs of systolic longitudinal dysfunction (systolic annular peak velocity (S'): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4 cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs 6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P < 0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P < 0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001).Conclusions: Primary cardiovascular changes are already present in the SGA fetus and persist at 6 months of age. These data support prenatal cardiovascular remodeling as a mechanistic pathway of increased risk later in life in cases of SGA, regardless of Doppler abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence of chorioamniotic membrane separation (CMS) after fetoscopy in monochorionic diamniotic (MCDA) twins and its impact on pregnancy outcome.Methods: The study group comprised a consecutive series of 338 women with an MCDA pregnancy complicated by twin-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR) treated with selective laser photocoagulation of communicating vessels (SLPCV) or cord occlusion (CO). Data obtained included cervical length, gestational age at procedure, type and duration of surgery and placental location. The incidence of CMS, the rates of miscarriage and preterm prelabor rupture of membranes (PPROM), gestational age at delivery and neonatal survival were recorded.Results: Of the study population of MCDA pregnancies, 270 (79.9%) had TTTS and 68 (20.1%) had sIUGR. SLPCV was performed in 252 (74.6%) cases and CO in 86 (25.4%). Postoperative CMS was observed in 70 (20.7%) cases. Patients with CMS had higher rates of miscarriage (14.3% vs 7.1%; P = 0.049), PPROM before 32 weeks (43.3% vs 13.7%; P < 0.001) and preterm delivery before 32 weeks (53.3% vs 26.1%; P < 0.001) and a lower rate of neonatal survival of at least one twin (81.7% vs 93.6%; P = 0.003). Multivariate analysis showed that gestational age at surgery was the only independent predictor, with the highest proportion of CMS occurring in cases that underwent surgery before 18 weeks' gestation (odds ratio, 2.941 (95% CI, 1.640-5.275); P < 0.001). There was no influence of cervical length, placental location, duration of surgery or type of surgery on the risk of CMS.Conclusions: CMS complicated one-fifth of all MCDA pregnancies that underwent fetoscopy. It appeared to be more common in those who underwent surgery before 18 weeks' gestation and was associated with poorer outcomes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Fetuses with congenital heart disease (CHD) show evidence of abnormal brain development before birth, which is thought to contribute to adverse neurodevelopment during childhood. Our aim was to evaluate whether brain development in late pregnancy can be predicted by fetal brain Doppler, head biometry and the clinical form of CHD at the time of diagnosis.Methods: This was a prospective cohort study including 58 fetuses with CHD, diagnosed at 20-24 weeks' gestation, and 58 normal control fetuses. At the time of diagnosis, we recorded fetal head circumference (HC), biparietal diameter, middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and brain perfusion by fractional moving blood volume. We classified cases into one of two clinical types defined by the expected levels (high or low) of placental (well-oxygenated) blood perfusion, according to the anatomical defect. All fetuses underwent subsequent 3T-magnetic resonance imaging (MRI) at 36-38 weeks' gestation.Results: Abnormal prenatal brain development was defined by a composite score including any of the following findings on MRI: total brain volume <  10(th) centile, parietoccipital or cingulate fissure depth <  10(th) centile or abnormal metabolic profile in the frontal lobe. Logistic regression analysis demonstrated that MCA-PI (odds ratio (OR), 12.7; P = 0.01), CPR (OR, 8.7; P = 0.02) and HC (OR, 6.2; P = 0.02) were independent predictors of abnormal neurodevelopment; however, the clinical type of CHD was not.Conclusions: Fetal brain Doppler and head biometry at the time of CHD diagnosis are independent predictors of abnormal brain development at birth, and could be used in future algorithms to improve counseling and targeted interventions. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

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]

The objective of this study was to evaluate the feasibility, efficacy and safety of bipolar coagulation using endoscopic forceps of diameters of 2.7 mm and less in animal models mimicking in-utero conditions. Forceps of 2.2, 2.3, 2.5 and 2.7 mm were tested in rabbits (n = 36). Vessel pairs were dissected and coagulated in a fluid environment under endoscopic vision at 15 and 25 W. The main outcome measure was the perforation rate. In fetal lambs (n = 25), umbilical cords were coagulated under sono-endoscopic control with power settings from 10 to 35 W. Main outcome measures were the duration of coagulation, perforation rate, change in the temperature of the amniotic fluid and efficacy of vessel occlusion rate. At 20-25 W, all cords were coagulated successfully without any perforation using 2.3, 2.5 or 2.7 mm forceps. Coagulation with the 2. 2 mm forceps was associated with a high perforation rate, although the design rather than the diameter of the forceps may have influenced this outcome. Bipolar coagulation with forceps between 2. 3 and 2.7 mm and appropriate power settings achieves efficacious and safe coagulation in animal models for umbilical cord occlusion. [ABSTRACT FROM AUTHOR]

Conclusions Our preliminary data demonstrates than fetuses with isolated CHD have increased levels of the protein oxidation biomarker o-Tyr in amniotic fluid. The aim of this study is to evaluate protein OS biomarkers in amniotic fluid in fetuses with isolated major CHD. Recent evidence suggests that oxidative stress (OS) plays an important role in the pathogenesis of congenital heart defect (CHD). [Extracted from the article]

Objective: Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI.Methods: A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler.Results: Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001).Conclusions: Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed. [ABSTRACT FROM AUTHOR]