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Objectives: Large-for-gestational age (LGA) is associated with several adverse maternal and neonatal outcomes. Although many studies have found that early induction of labor (IOL) in case of a LGA fetus reduces the incidence of shoulder dystocia, no current guidelines recommend this particular clinical strategy, owing to concerns about increased rates of Cesarean delivery (CD) and neonatal complications. The purpose of this study was to assess whether the timing of IOL in LGA fetuses affected maternal and neonatal outcomes in a single center, and to combine these results with evidence reported in the literature., Methods: This study comprised two parts. The first part was a retrospective cohort study that included consecutive patients with a singleton pregnancy and an estimated fetal weight ≥ 90 th percentile on ultrasound between 35 + 0 and 39 + 0 weeks' gestation, who were eligible for normal vaginal delivery. The second part of the study was a systematic review of the literature and meta-analysis, including the results of our cohort study as well as those of previous studies that compared IOL with expectant management in patients with a LGA fetus. The perinatal outcomes of the study were CD, operative vaginal delivery, shoulder dystocia, brachial plexus palsy, anal sphincter injury, postpartum hemorrhage, Apgar score, umbilical artery pH, admission to the neonatal intensive care unit, use of continuous positive airway pressure, intracranial hemorrhage, need for phototherapy and bone fracture., Results: Of the 547 patients included in this retrospective cohort study, 329 (60.1%) underwent IOL and 218 (39.9%) experienced spontaneous labor. Following covariate balancing, the odds of CD were significantly higher in the IOL group compared with the spontaneous-labor group. This difference only became apparent beyond 40 weeks' gestation (hazard ratio, 1.90; P = 0.030). The difference between the IOL and spontaneous-labor groups for the rate of shoulder dystocia was not statistically significant (hazard ratio, 1.57; P = 0.200). Seventeen studies, in addition to our own results, were included in the systematic review and meta-analysis, giving a total population of 111 300 participants. Although there was no significant difference in the rate of CD between IOL and expectant management after pooling the results of included studies, the risk for shoulder dystocia was significantly lower in the IOL group (odds ratio (OR), 0.64 (95% CI, 0.42-0.98); I 2  = 19% from 12 studies) when considering only IOL performed before 40 + 0 weeks. When the studies in which IOL was carried out exclusively before 40 + 0 weeks were removed from the analysis, the risk for CD in the remaining studies was significantly higher in the IOL group (OR, 1.46 (95% CI, 1.02-2.09); I 2  = 56%). There were no statistically significant differences between the IOL and expectant-management groups for the remaining perinatal outcomes. Nulliparity, history of CD and low Bishop score, but not method of induction, were independent risk factors for intrapartum CD in patients that underwent IOL for LGA., Conclusions: The timing of IOL in patients with suspected macrosomia significantly impacts on perinatal adverse outcomes. IOL has no impact on rates of shoulder dystocia but increases the odds of CD when considered irrespective of gestational age; in contrast, IOL may decrease the risk of shoulder dystocia without increasing the risk of other adverse maternal outcomes, in particular CD, when performed before 40 + 0 weeks (GRADE: low/very low). © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To assess and compare the value of antenatally determined observed-to-expected (O/E) lung-area-to-head-circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left-sided congenital diaphragmatic hernia (CDH)., Methods: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E-LHR and one MRI scan for measurement of O/E-TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left-sided CDH with intrathoracic herniation of the liver, receiver-operating-characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E-TFLV and O/E-LHR in the prediction of postnatal survival., Results: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7-39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0-39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6-37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3-37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left-sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133-0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141-0.628), P = 0.001), and higher with increasing O/E-TFLV (OR, 1.123 (95% CI, 1.079-1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055-1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368-16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left-sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E-TFLV and O/E-LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056)., Conclusions: In fetuses with left-sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E-TFLV on MRI examination and O/E-LHR on ultrasound examination was similar in one center (Mannheim), but O/E-TFLV had better predictive value compared to O/E-LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left-sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Twin pregnancy is associated with higher risks of adverse perinatal outcomes for both the mother and the babies. Among the many challenges in the follow-up of twin pregnancies, the mode of delivery is the last but not the least decision to be made, with the main influencing factors being amnionicity and fetal presentation. The aim of the study was to compare perinatal outcomes in two European centers using different protocols for twin birth in case of non-cephalic second twin; the Italian patients being delivered mainly by cesarean section with those in Belgium being routinely offered the choice of vaginal delivery (VD)., Methods: This was a dual center international retrospective observational study. The population included 843 women with a twin pregnancy ≥ 32 weeks (dichorionic or monochorionic diamniotic pregnancies) and a known pregnancy outcome. The population was stratified according to chorionicity. Demographic and pregnancy data were reported per pregnancy, whereas neonatal outcomes were reported per fetus. We used multiple logistic regression models to adjust for possible confounding variables and to compute the adjusted odds ratio (adjOR) for each maternal or neonatal outcome., Results: The observed rate of cesarean delivery was significantly higher in the Italian cohort: 85% for dichorionic pregnancies and 94.4% for the monochorionic vs 45.2% and 54.4% respectively in the Belgian center ( p -value < 0.001). We found that Belgian cohort showed significantly higher rates of NICU admission, respiratory distress at birth and Apgar score of < 7 after 5 min. Despite these differences, the composite severe adverse outcome was similar between the two groups., Conclusion: In this study, neither the presentation of the second twin nor the chorionicity affected maternal and severe neonatal outcomes, regardless of the mode of delivery in two tertiary care centers, but VD was associated to a poorer short-term neonatal outcome.

Purpose: To evaluate the impact of the timing of MRI on the prediction of survival and morbidity in patients with CDH, and whether serial measurements have a beneficial value., Methods: This retrospective cohort study was conducted in two perinatal centers, in Germany and Italy. It included 354 patients with isolated CDH having at least one fetal MRI. The severity was assessed with the observed-to-expected total fetal lung volume (o/e TFLV) measured by two experienced double-blinded operators. The cohort was divided into three groups according to the gestational age (GA) at which the MRI was performed (< 27, 27-32, and  > 32 weeks' gestation [WG]). The accuracy for the prediction of survival at discharge and morbidity was analyzed with receiver operating characteristic (ROC) curves. Multiple logistic regression analyses and propensity score matching examined the population for balance. The effect of repeated MRI was evaluated in ninety-seven cases., Results: There were no significant differences in the prediction of survival when the o/e TFLV was measured before 27, between 27 and 32, and after 32 WG (area under the curve [AUC]: 0.77, 0.79, and 0.77, respectively). After adjustment for confounding factors, it was seen, that GA at MRI was not associated with survival at discharge, but the risk of mortality was higher with an intrathoracic liver position (adjusted odds ratio [aOR]: 0.30, 95% confidence interval [95%CI] 0.12-0.78), lower GA at birth (aOR 1.48, 95%CI 1.24-1.78) and lower o/e TFLV (aOR 1.13, 95%CI 1.06-1.20). ROC curves showed comparable prediction accuracy for the different timepoints in pregnancy for pulmonary hypertension, the need of extracorporeal membrane oxygenation, and feeding aids. Serial measurements revealed no difference in change rate of the o/e TFLV according to survival., Conclusion: The timing of MRI does not affect the prediction of survival rate or morbidity as the o/e TFLV does not change during pregnancy. Clinicians could choose any gestational age starting mid second trimester for the assessment of severity and counseling., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the performance of prenatal screening for common autosomal trisomies in twin pregnancies through the use of rolling-circle replication (RCR)-cfDNA as a first-tier test., Method: Prospective multicenter study. Women who underwent prenatal screening for trisomy (T) 21, 18 and 13 between January 2019 and March 2022 in twin pregnancies were included. Patients were included in two centers. The primary endpoint was the rate of no-call results in women who received prenatal screening for common autosomal trisomies by RCR-cfDNA at the first attempt, compared to that in prospectively collected samples from 16,382 singleton pregnancies. The secondary endpoints were the performance indices of the RCR-cfDNA., Results: 862 twin pregnancies underwent screening for T21, T18 and T13 by RCR-cfDNA testing at 10-33 weeks' gestation. The RCR-cfDNA tests provided a no-call result from the first sample obtained from the patients in 107 (0.7%) singleton and 17 (2.0%) twin pregnancies. Multivariable regression analysis demonstrated that significant independent predictors of test failure were twin pregnancy and in vitro fertilization conception. All cases of T21 (n = 20/862; 2.3%), T18 (n = 4/862; 0.5%) and T13 (n = 1/862; 0.1%) were correctly detected by RCR-cfDNA (respectively, 20, 4 and 1 cases). Sensitivity was 100% (95% CI, 83.1%-100%), 100% (95% CI 39.8%-100%) and 100% (95% CI 2.5%-100%) for T21, T18 and T13, respectively, in twin pregnancies., Conclusion: The RCR-cfDNA test appears to have good accuracy with a low rate of no-call results in a cohort of twin pregnancies for the detection of the most frequent autosomal trisomies., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: To simulate the outcomes of Boulvain's trial by using magnetic resonance imaging (MRI) for estimated fetal weight (EFW) as a second-line confirmatory imaging., Study Design: Data derived from the Boulvain's trial and the study PREMACRO (PREdict MACROsomia) were used to simulate a 1000-patient trial. Boulvain's trial compared induction of labor (IOL) to expectant management in suspected macrosomia, whereas PREMACRO study compared the performance of ultrasound-EFW (US-EFW) and MRI-EFW in the prediction of birthweight. The primary outcome was the incidence of significant shoulder dystocia (SD). Cesarean delivery (CD), hyperbilirubinemia (HB), and IOL at < 39 weeks of gestation (WG) were selected as secondary outcomes. A subgroup analysis of the Boulvain's trial was performed to estimate the incidence of the primary and secondary outcomes in the true positive and false positive groups for the two study arms. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for the prediction of macrosomia by MRI-EFW at 36 WG were calculated, and a decision tree was constructed for each outcome., Results: The PPV of US-EFW for the prediction of macrosomia in the PREMACRO trial was 56.3 %. MRI-EFW was superior to US-EFW as a predictive tool resulting in lower rates of induction for false-positive cases. Repeating Boulvain's trial using MRI-EFW as a second-line test would result in similar rates of SD (relative risk [RR]:0.36), CD (RR:0.84), and neonatal HB (RR:2.6), as in the original trial. Increasing the sensitivity and specificity of MRI-EFW resulted in a similar relative risk for SD as in Boulvain's trial, but with reduced rates of IOL < 39 WG, and improved the RR of CD in favor of IOL. We found an inverse relationship between IOL rate and incidence of SD for both US-EFW and MRI-EFW, although overall rates of IOL, CD, and neonatal HB would be lower with MRI-derived estimates of fetal weight., Conclusion: The superior accuracy of MRI-EFW over US-EFW for the diagnosis of macrosomia could result in lower rates of IOL without compromising the relative advantages of the intervention but fails to demonstrate a significant benefit to justify a replication of the original trial using MRI-EFW as a second-line test., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Many complications increase with macrosomia, which is defined as birthweight of ≥4000 g. The ability to estimate when the fetus would exceed 4000 g could help to guide decisions surrounding the optimal timing of delivery. To the best of our knowledge, there is no available tool to perform this estimation independent of the currently available growth charts., Objective: This study aimed to develop ultrasound- and magnetic resonance imaging-based models to estimate at which gestational age the birthweight would exceed 4000 g, evaluate their predictive performance, and assess the effect of each model in reducing adverse outcomes in a prospectively collected cohort., Study Design: This study was a subgroup analysis of women who were recruited for the estimation of fetal weight by ultrasound and magnetic resonance imaging at 36 0/7 to 36 6/7 weeks of gestation. Primigravid women who were eligible for normal vaginal delivery were selected. Multiparous patients, patients with preeclampsia spectrum, patients with elective cesarean delivery, and patients with contraindications for normal vaginal delivery were excluded. Of note, 2 linear models were built for the magnetic resonance imaging- and ultrasound-based models to predict a birthweight of ≥4000 g. Moreover, 2 formulas were created to predict the gestational age at which birthweight will reach 4000 g (predicted gestational age); one was based on the magnetic resonance imaging model, and the second one was based on the ultrasound model. This study compared the adverse birth outcomes, such as intrapartum cesarean delivery, operative vaginal delivery, anal sphincter injury, postpartum hemorrhage, shoulder dystocia, brachial plexus injury, Apgar score of <7 at 5 minutes of life, neonatal intensive care unit admission, and intracranial hemorrhage in the group of patients who delivered after the predicted gestational age according to the magnetic resonance imaging-based or the ultrasound-based models with those who delivered before the predicted gestational age by each model, respectively., Results: Of 2378 patients, 732 (30.8%) were eligible for inclusion in the current study. The median gestational age at birth was 39.86 weeks of gestation (interquartile range, 39.00-40.57), the median birthweight was 3340 g (interquartile range, 3080-3650), and 63 patients (8.6%) had a birthweight of ≥4000 g. Prepregnancy body mass index, geographic origin, gestational age at birth, and fetal body volume were retained for the optimal magnetic resonance imaging-based model, whereas maternal age, gestational diabetes mellitus, diabetes mellitus type 1 or 2, geographic origin, fetal gender, gestational age at birth, and estimated fetal weight were retained for the optimal ultrasound-based model. The performance of the first model was significantly better than the second model (area under the curve: 0.98 vs 0.89, respectively; P<.001). The group of patients who delivered after the predicted gestational age by the first model (n=40) had a higher risk of cesarean delivery, postpartum hemorrhage, and shoulder dystocia (adjusted odds ratio: 3.15, 4.50, and 9.67, respectively) than the group who delivered before this limit. Similarly, the group who delivered after the predicted gestational age by the second model (n=25) had a higher risk of cesarean delivery and postpartum hemorrhage (adjusted odds ratio: 5.27 and 6.74, respectively) than the group who delivered before this limit., Conclusion: The clinical use of magnetic resonance imaging- and ultrasound-based models, which predict a gestational age at which birthweight will exceed 4000 g, may reduce macrosomia-related adverse outcomes in a primigravid population. The magnetic resonance imaging-based model is better for the identification of the highest-risk patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare the diagnostic performance of postmortem ultrasound (PMUS), 9.4 T magnetic resonance imaging (MRI) and microfocus computed tomography (micro-CT) for the examination of early gestation fetuses., Method: Eight unselected fetuses (10-15 weeks gestational age) underwent at least 2 of the 3 listed imaging examinations. Six fetuses underwent 9.4 T MRI, four underwent micro-CT and six underwent PMUS. All operators were blinded to clinical history. All imaging was reported according to a prespecified template assessing 36 anatomical structures, later grouped into five regions: brain, thorax, heart, abdomen and genito-urinary., Results: More anatomical structures were seen on 9.4 T MRI and micro-CT than with PMUS, with a combined frequency of identified structures of 91.9% and 69.7% versus 54.5% and 59.6 (p < 0.001; p < 0.05) respectively according to comparison groups. In comparison with 9.4 T MRI, more structures were seen on micro-CT (90.2% vs. 83.3%, p < 0.05). Anatomical structures were described as abnormal on PMUS in 2.7%, 9.4 T MRI in 6.1% and micro-CT 7.7% of all structures observed. However, the accuracy test could not be calculated because conventional autopsy was performed on 6 fetuses of that only one structure was abnormal., Conclusion: Micro-CT appears to offer the greatest potential as an imaging adjunct or non-invasive alternative for conventional autopsies in early gestation fetuses., (© 2024 John Wiley & Sons Ltd.)

Objective: To assess whether the cannula insertion site on the maternal abdomen during fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was associated with preterm prelabor rupture of membranes (PPROM) before balloon removal., Methods: This was a multicenter retrospective study of consecutive pregnancies with isolated left- or right-sided CDH that underwent FETO in four centers between January 2009 and January 2021. The site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups to calculate an average treatment effect (ATE) by inverse probability of treatment weighting. Logistic regression and Cox proportional hazard regression including the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM before balloon removal., Results: A total of 294 patients were included. The mean ± SD gestational age at PPROM was 33.45 ± 2.01 weeks and the mean rate of PPROM before balloon removal was 25.9% (76/294). Gestational age at FETO was later in the below-umbilicus group (mean ± SD, 29.47 ± 1.29 weeks vs 29.00 ± 1.25 weeks; P = 0.002) and the duration of FETO was longer in the above-umbilicus group (median, 14.49 min (interquartile range (IQR), 8.00-21.00 min) vs 11.00 min (IQR, 7.00-14.49 min); P = 0.002). After balancing for possible confounding factors, trocar entry point below the umbilicus did not increase the risk of PPROM before balloon removal (adjusted odds ratio, 1.56 (95% CI, 0.89-2.74); P = 0.120) and had no effect on the timing of PPROM before balloon removal (adjusted hazard ratio, 1.56 (95% CI, 0.95-2.55); P = 0.080)., Conclusion: There was no evidence that uterine entry site for FETO was correlated with the risk of PPROM before balloon removal. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To compare the performance of two-dimensional ultrasound (2D-US), three-dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) at 36 weeks' gestation in predicting the delivery of a large-for-gestational-age (LGA) neonate, defined as birth weight ≥ 95 th percentile, in patients at high and low risk for macrosomia., Methods: This was a secondary analysis of a prospective observational study conducted between January 2017 and February 2019. Women with a singleton pregnancy at 36 weeks' gestation underwent 2D-US, 3D-US and MRI within 15 min for estimation of fetal weight. Weight estimations and birth weight were plotted on a growth curve to obtain percentiles for comparison. Participants were considered high risk if they had at least one of the following risk factors: diabetes mellitus, estimated fetal weight ≥ 90 th percentile at the routine third-trimester ultrasound examination, obesity (prepregnancy body mass index ≥ 30 kg/m 2 ) or excessive weight gain during pregnancy. The outcome was the diagnostic performance of each modality in the prediction of birth weight ≥ 95 th percentile, expressed as the area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity and positive and negative predictive values., Results: A total of 965 women were included, of whom 533 (55.23%) were high risk and 432 (44.77%) were low risk. In the low-risk group, the AUCs for birth weight ≥ 95 th percentile were 0.982 for MRI, 0.964 for 2D-US and 0.962 for 3D-US; pairwise comparisons were non-significant. In the high-risk group, the AUCs were 0.959 for MRI, 0.909 for 2D-US and 0.894 for 3D-US. A statistically significant difference was noted between MRI and both 2D-US (P = 0.002) and 3D-US (P = 0.002), but not between 2D-US and 3D-US (P = 0.503). In the high-risk group, MRI had the highest sensitivity (65.79%) compared with 2D-US (36.84%, P = 0.002) and 3D-US (21.05%, P < 0.001), whereas 3D-US had the highest specificity (98.99%) compared with 2D-US (96.77%, P = 0.005) and MRI (96.97%, P = 0.004)., Conclusions: At 36 weeks' gestation, MRI has better performance compared with 2D-US and 3D-US in predicting birth weight ≥ 95 th percentile in patients at high risk for macrosomia, whereas the performance of 2D-US and 3D-US is comparable. For low-risk patients, the three modalities perform similarly. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: The treatment of fetuses with a congenital diaphragmatic hernia is challenging, but there is evidence that fetoscopic endoluminal tracheal occlusion has a benefit over expectant care. In addition, standardization and expertism have a great impact on survival and are probably crucial in centers that rely on expectant management with extracorporeal membrane oxygenation after birth., Objective: This study aimed to examine the survival and morbidity rates of fetuses with a severe isolated left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion vs expectant management in high-volume centers., Study Design: This was a multicenter, retrospective study that included all consecutive fetuses with severe isolated left-sided congenital diaphragmatic hernia who were expectantly managed in a German center or who underwent fetoscopic endoluminal tracheal occlusion in 3 other European centers (Belgium, France, and Italy). Severe congenital diaphragmatic hernia was defined as having an observed to expected total fetal lung volume ≤35% with intrathoracic position of the liver diagnosed with magnetic resonance imaging. All magnetic resonance images were centralized, and lung volumes were measured by 2 experienced operators who were blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect of the management strategy in the 2 groups on the short- and long-term outcomes., Results: A total of 147 patients who were managed expectantly and 47 patients who underwent fetoscopic endoluminal tracheal occlusion were analyzed. Fetuses who were managed expectantly had lower observed to expected total fetal lung volumes (20.6%±7.5% vs 23.7%±6.8%; P=.013), higher gestational age at delivery (median weeks of gestation, 37.4; interquartile range, 36.6-38.00 vs 35.1; interquartile range, 33.1-37.2; P<.001), and more frequent use of extracorporeal membrane oxygenation (55.8% vs 4.3%; P<.001) than the fetuses who underwent fetoscopic endoluminal tracheal occlusion. The survival rates at discharge and at 2 years of age in the expectant management group were higher than the survival rates of the fetoscopic endoluminal tracheal occlusion group (74.3% vs 44.7%; P=.001 and 72.8% vs 42.5%; P=.001, respectively). After adjustment for maternal age, gestational age at birth, observed to expected total fetal lung volume, and birth weight Z-score, the odds ratios were 4.65 (95% confidence interval, 1.9-11.9; P=.001) and 4.37 (95% confidence interval, 1.8-11.0; P=.001), respectively., Conclusion: Fetuses with a severe isolated left-sided congenital diaphragmatic hernia had a higher survival rate when treated in an experienced center in Germany with antenatal expectant management and frequent use of extracorporeal membrane oxygenation during the postnatal period than fetuses who were treated with fetoscopic endoluminal tracheal occlusion in 3 centers in Belgium, France, and Italy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the influence of the test-to-delivery interval (TDI) on the performance of ultrasound (US) and magnetic resonance imaging (MRI) for predicting birthweight (BW)., Study Design: This is a secondary analysis of a prospective, single center, blinded cohort study that compared MRI and US for the prediction of BW ≥ 95th percentile in singleton pregnancies. Patients that were included in the initial study underwent US and MRI for estimation of fetal weight between 36 + 0/7 and 36 + 6/7 weeks of gestation (WG). The primary outcome of the current study was to report the changes of US and MRI sensitivity and specificity in the prediction of BW > 95th percentile, BW > 90th percentile, BW < 10th percentile, and BW < 5th percentile, according to the TDI. The secondary outcome was to represent the performance of both tools in the prediction of BW > 90th percentile when TDI is<2 weeks, between 2 and 4 weeks, and>4 weeks. Receiver operating characteristic (ROC) curves were constructed accordingly., Results: 2378 patients were eligible for final analysis. For the prediction of BW > 95th or 90th percentile, the sensitivity of MRI remains high until 2 weeks, and it decreases slowly between 2 and 4 weeks, in contrast to the sensitivity of US which decreases rapidly 2 weeks after examination (p < 0.001). For the prediction of BW < 10th or 5th percentile, the sensitivity of both tools decreases in parallel between 1 and 2 weeks. The specificities of both tools remain high from examination till delivery. These findings are reproducible with the use of the antenatal customized and the postnatal national growth charts., Conclusion: The performance of MRI in the prediction of BW, especially in large-for-gestational age, is maximal when delivery occurs within two weeks of the examination, decreasing slightly thereafter, in contrast with the performance of US which decreases drastically over time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To determine the learning curve of fetal postmortem ultrasound (PMUS) and evaluate the evolution of its diagnostic performance over the past 8 years., Methods: PMUS was performed by two fetal medicine specialists and two experts on 100 unselected fetuses of 12-38 weeks of gestation in a prospective, double-blind manner. 21 pre-defined internal structures were analyzed consecutively by the trainee alone and the expert, with a comparison of diagnosis and immediate feedback. The learning curves for examination duration, non-recognition of structures and final diagnoses were computed using cumulative summation analysis. Secondly, the expert PMUS diagnostic accuracy using autopsy as the gold standard was compared to the previously published data., Results: The trainees reached expert level of PMUS at 28-36 cases for examination duration (12.1 ± 5.2 min), non-diagnostic rate (6.5%, 137/2100), and abnormality diagnosis. In a group of 33 fetuses ≥20 weeks who had an autopsy, the experts PMUS performance was improved after 8 years with a reduction of all organs non-diagnostic rate (6.5 %VS 11.4%, p < 0.01) and higher sensitivity for the heart (100% VS 40.9%, p < 0.01) and the abdomen (100%VS 56.5%, p < 0.05)., Conclusion: PMUS offers a short learning curve for fetal medicine specialists and on-going improvement of diagnostic accuracy over time., (© 2023 John Wiley & Sons Ltd.)

Objective: The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT., Methods: Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists., Results: The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k = 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k = 0.766, k = 0.756, and k = 0.785, respectively) with a high interobserver agreement., Conclusion: WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT., Clinical Relevance Statement: Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases., Key Points: Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective., Methods: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications. Temporal trends and between-site/device consistency were explored. Proportions of run standard deviations exceeding pre-specified caps of 0.4%, 0.4% and 0.6% were computed., Results: Overall, 661 RCA runs between April 2019 and July 30, 2022 tested 39,756 samples. In the first 24, subsequent 9, and final 7 months, proportions of capped chromosome 21 runs dropped from 39% to 22% to 6.0%; for chromosome 18, rates were 76%, 36%, and 4.0%. Few chromosome 13 runs were capped using the original 0.60%, but capping at 0.50%, rates were 28%, 16%, and 7.6%. Final rates occurred after reformulated reagents and imaging software modifications were fully implemented across all devices. Revised detection and false positive rates are estimated at 98.4% and 0.3%, respectively. After repeat testing, failure rates may be as low as 0.3%., Conclusion: Current RCA-based screening performance estimates are equivalent to those reported for other methods, but with a lower test failure rate after repeat testing., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. G Palomaki and G Lambert-Messerlian have received authorship royalty from UptoDate and a previous research grant to Women & Infants Hospital for an international collaborative study of the Vanadis cfDNA technology's clinical validity (published: Clin Chem, 2022).

Purpose: To investigate the role of chest computed tomography (CT) scan in the prediction of admission of pregnant women with COVID-19 into intensive care unit (ICU)., Methods: This was a single-center retrospective case-control study. We included pregnant women diagnosed with COVID-19 by reverse transcriptase polymerase chain reaction between February 2020 and July 2021, requiring hospital admission due to symptoms, who also had a CT chest scan at presentation. Patients admitted to the ICU (case group) were compared with patients who did not require ICU admission (control group). The CT scans were reported by an experienced radiologist, blinded to the patient's course and outcome, aided by an artificial intelligence software. Total CT scan score, chest CT severity score (CT-SS), total lung volume (TLV), infected lung volume (ILV), and infected-to-total lung volume ratio (ILV/TLV) were calculated. Receiver operating characteristic curves were constructed to test the sensitivity and specificity of each parameter., Results: 8/28 patients (28.6%) required ICU admission. These also had lower TLV, higher ILV, and ILV/TLV. The area under the curve (AUC) for these three parameters was 0.789, 0.775, and 0.763, respectively. TLV, ILV, and ILV/TLV had good sensitivity (62.5%, 87.5%, and 87.5%, respectively) and specificity (84.2%, 70%, and 73.7%, respectively) for predicting ICU admission at the following selected thresholds: 2255 mL, 319 mL, and 14%, respectively. The performance of CT-SS, CT scan score, and ILV/TLV in predicting ICU admission was comparable., Conclusion: TLV, ILV, and ILV/TLV as measured by an artificial intelligence software on chest CT, may predict ICU admission in hospitalized pregnant women, symptomatic for COVID-19.

Background: The estimation of fetal weight by fetal magnetic resonance imaging is a simple and rapid method with a high sensitivity in predicting birthweight in comparison with ultrasound. Several national and international growth charts are currently in use, but there is substantial heterogeneity among these charts due to variations in the selected populations from which they were derived, in methodologies, and in statistical analysis of data., Objective: This study aimed to compare the performance of magnetic resonance imaging and ultrasound for the prediction of birthweight using 3 commonly used fetal growth charts: the INTERGROWTH-21 st Project, World Health Organization, and Fetal Medicine Foundation charts., Study Design: Data derived from a prospective, single-center, blinded cohort study that compared the performance of magnetic resonance imaging and ultrasound between 36 +0/7 and 36 +6/7 weeks of gestation for the prediction of birthweight ≥95th percentile were reanalyzed. Estimated fetal weight was categorized as above or below the 5th, 10th, 90th, and 95th percentile according to the 3 growth charts. Birthweight was similarly categorized according to the birthweight standards of each chart. The performances of ultrasound and magnetic resonance imaging for the prediction of birthweight <5th, <10th, >90th, and >95th percentile using the different growth charts were compared. Data were analyzed with R software, version 4.1.2. The comparison of sensitivity and specificity was done using McNemar and exact binomial tests. P values <.05 were considered statistically significant., Results: A total of 2378 women were eligible for final analysis. Ultrasound and magnetic resonance imaging were performed at a median gestational age of 36 +3/7 weeks, delivery occurred at a median gestational age of 39 +3/7 weeks, and median birthweight was 3380 g. The incidences of birthweight <5th and <10th percentiles were highest with the Fetal Medicine Foundation chart and lowest with the INTERGROWTH-21 st chart, whereas the incidences of birthweight >90th and >95th percentiles were lowest with the Fetal Medicine Foundation chart and highest with the INTERGROWTH-21 st chart. The sensitivity of magnetic resonance imaging with an estimated fetal weight >95th percentile in the prediction of birthweight >95th percentile was significantly higher than that of ultrasound across the 3 growth charts; however, its specificity was slightly lower than that of ultrasound. In contrast, the sensitivity of magnetic resonance imaging with an estimated fetal weight <10th percentile for predicting birthweight <10th percentile was significantly lower than that of ultrasound in the INTERGROWTH-21 st and Fetal Medicine Foundation charts, whereas the specificity and positive predictive value of magnetic resonance imaging were significantly higher than those of ultrasound for all 3 charts. Findings for the prediction of birthweight >90th percentile were close to those of birthweight >95th percentile, and findings for the prediction of birthweight <5th percentile were close to those of birthweight <10th percentile., Conclusion: The sensitivity of magnetic resonance imaging is superior to that of ultrasound for the prediction of large for gestational age fetuses and inferior to that of ultrasound for the prediction of small for gestational age fetuses across the 3 different growth charts. The reverse is true for the specificity of magnetic resonance imaging in comparison with that of ultrasound., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The occurrence of COVID-19 during the pregnancy can cause several negative maternal and neonatal outcomes. Nasopharyngeal viral load is associated with inflammatory markers and might influence the disease severity in non-pregnant patients, but there are no data about the relationship between viral load and perinatal outcomes in pregnant patients., Objective: To investigate the hypothesis that nasopharyngeal SARS-CoV-2 load (estimated with real-time polymerase chain reaction delta cycle (ΔCt), measured in hospital clinical laboratories) is associated with perinatal outcomes, when COVID-19 is diagnosed in the third trimester of pregnancy., Study Design: International, retrospective, observational, multi-center, cohort study enrolling 390 women (393 neonates, three pairs of twins), analyzed with multivariate generalized linear models with skewed distributions (gamma) and identity link. The analyses were conducted for the whole population and then followed by a subgroup analysis according to the clinical severity of maternal COVID-19., Results: The estimated viral load in maternal nasopharynx is not significantly associated with gestational age at birth (adjusted B: -0.008 (95%CI: -0.04; 0.02); p = 0.889), birth weight (adjusted B: 4.29 (95%CI: -25; 35); p = 0.889), weight Z-score (adjusted B: -0.01 (95%CI: -0.03; 1); p = 0.336), 5' Apgar scores (adjusted B: -0. -9.8e -4 (95%CI: -0.01; 0.01); p = 0.889), prematurity (adjusted OR: -0.97 (95%CI: 0.93; 1.03); p = 0.766) and the small for gestational age status (adjusted OR: 1.03 (95%CI: 0.99; 1.07); p = 0.351). Similar results were obtained in subgroup analyses according to COVID-19 clinical severity., Conclusions: The estimated maternal nasopharyngeal viral load in pregnant women affected by COVID-19 during the third trimester is not associated with main perinatal outcomes., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the prevalence of and risk factors for failure of fetal magnetic resonance imaging (MRI) due to maternal claustrophobia or malaise., Methods: This retrospective cohort study included pregnant women who underwent fetal MRI for clinical indications or research purposes between January 2012 and December 2019 at a single center. One group included patients who completed the entire examination and the other group inlcuded patients who interrupted their MRI examination due to claustrophobia/malaise. We estimated the rate of MRI failure due to maternal claustrophobia/malaise and compared maternal and clinical variables between the two groups. Multiple logistic regression analysis was performed to identify independent risk factors for claustrophobia/malaise during MRI examination in pregnancy., Results: Among 3413 patients who agreed to undergo fetal MRI, the prevalence of failure because of claustrophobia or malaise was 2.1%. The rate of claustrophobia/malaise in patients who underwent MRI for a clinical indication was lower compared to that in patients who underwent MRI for research purposes only (0.6% (4/696) vs 2.4% (65/2678); P = 0.003). Fetal MRI performed for research purposes only (adjusted odds ratio (aOR), 0.05 (95% CI, 0.01-0.48); P = 0.003), higher maternal age (aOR, 1.07 (95% CI, 1.02-1.12); P = 0.003) and later gestational age at the time of fetal MRI (aOR, 1.46 (95% CI, 1.16-2.04); P = 0.008) were independent risk factors for claustrophobia/malaise. Shorter fetal MRI duration (aOR, 0.77 (95% CI, 0.63-0.88); P = 0.001) was also associated with claustrophobia/malaise during the procedure. Body mass index, ethnic origin, multiple pregnancy, being parous and size of the magnetic bore were not associated with MRI failure due to claustrophobia/malaise., Conclusion: The rate of fetal MRI failure due to claustrophobia or malaise was found to be low, particularly when the examination was performed for a clinical indication, and should not be considered a common problem in the pregnant population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: The lockdown caused by the COVID-19 pandemic has imposed some restrictions on hospital activities, requiring medical staff to find efficient alternatives to ensure adequate medical care for patients., Objective: This study aimed to investigate the experience of pregnant women who delivered during the first wave of COVID-19, and to evaluate the impact of COVID-19-related restrictions., Study Design: This was a retrospective multicenter study. All pregnant women who delivered a live infant between March 20, 2020 and June 20, 2020 were evaluated using a 35-item survey at 1 year following delivery. Each patient was contacted via 3 modalities. Patients who reported that their prenatal follow-up was interrupted were compared with those who reported that their prenatal follow-up was unchanged. Among 1096 patients who delivered a live infant across the 3 participating centers during the study period, 389 responses were needed for an estimated margin of error of 4%., Results: A total of 469 of 1096 (42.8%) patients answered the survey, of whom 151 (32.2%) reported that the follow-up of their pregnancy was interrupted (exposed group) and 318 (67.8%) reported that their follow-up was maintained as normal (unexposed group). The rate of presentation to the emergency department was higher in the exposed group than in the unexposed group ( P =.001). The level of dissatisfaction was also higher in the exposed group, and patients in this group would have postponed their pregnancy if they had known about the pandemic in advance ( P <.001 and P =.001, respectively)., Conclusion: Interruption and modification of antenatal follow-up in pregnant women is associated with patient dissatisfaction and increased presentation to the emergency department., (© 2022 The Authors.)

To compare region of interest (ROI)-apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) measurements and Ki-67 proliferation index before and after neoadjuvant chemotherapy (NACT) for breast cancer. 55 women were enrolled in this prospective single-center study, with a final population of 47 women (49 cases of invasive breast cancer). ROI-ADC measurements were obtained on MRI before and after NACT and were compared to histological findings, including the Ki-67 index in the whole study population and in subgroups of "pathologic complete response" (pCR) and non-pCR. Nineteen percent of women experienced pCR. There was a significant inverse correlation between Ki-67 index and ROI-ADC before NACT (r = - 0.443, p = 0.001) and after NACT (r = - 0.614, p < 0.001). The mean Ki-67 index decreased from 45.8% before NACT to 18.0% after NACT (p < 0.001), whereas the mean ROI-ADC increased from 0.883 × 10 -3 mm 2 /s before NACT to 1.533 × 10 -3 mm 2 /s after NACT (p < 0.001). The model for the prediction of Ki67 index variations included patient age, hormonal receptor status, human epidermal growth factor receptor 2 status, Scarff-Bloom-Richardson grade 2, and ROI-ADC variations (p = 0.006). After NACT, a significant increase in breast cancer ROI-ADC on diffusion-weighted imaging was observed and a significant decrease in the Ki-67 index was predicted. Clinical trial registration number: clinicaltrial.gov NCT02798484, date: 14/06/2016., (© 2023. The Author(s).)

Background: The aim of this study was to evaluate the performance of magnetic resonance imaging (MRI) in the diagnosis of acute appendicitis in pregnant women., Methods: The study was conducted in 2 referral centers in Brussels, Belgium, between March 1st 2009 and January 31st 2017. Pregnant women who presented with abdominal pain and underwent MRI were included. Baseline characteristics, clinical, laboratory, and ultrasound test results were extracted retrospectively from the electronic medical charts. MRI exams were prospectively reevaluated by an experienced radiologist blinded to patient outcome and MRI findings. Visualization of the appendix and assessment of gastrointestinal, genitourinary, and vascular systems were recorded. The diagnosis of acute appendicitis was confirmed by pathology exam., Results: In total, 85 patients were included. The appendix was identified in all patients on MRI and acute appendicitis was suspected in 7. The diagnosis was confirmed in 6 patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI were 100% (95% confidence interval [95% CI]: 54.1%-100%), 98.7% (95% CI: 93.2-99.9%), 85.7% (95% CI: 46.1-97.7%), and 100%, respectively. In contrast, the sensitivity, specificity, PPV, and NPV of the combination of clinical exam, laboratory findings and/or ultrasound were 100% (95% CI: 54.1%-100%), 62% (95% CI: 50.4-72.7%), 16.7% (95% CI: 13.1-20.96%), and 100%, respectively., Conclusion: MRI is reliable in confirming or excluding acute appendicitis during pregnancy, with a rate of visualization of the appendix approaching 100%. Efforts should be focused on the implementation of MRI as a first-line imaging exam in the workup of suspected acute appendicitis during pregnancy.

Background: Medical literature supports planned cesarean delivery for breech presentation at term because of observed reductions in neonatal morbidity and mortality compared with vaginal breech delivery., Objective: This study aimed to compare perinatal outcomes of singleton pregnancies with breech presentation at term according to the different delivery protocols of 2 teaching hospitals, where vaginal breech delivery (protocol 1) or cesarean delivery (protocol 2) is routinely offered, respectively., Study Design: A retrospective matched cohort study was conducted between January 2015 and May 2021. A total of 1079 women were eligible for analysis. After matching for possible confounding factors, the final analysis was performed on 257 patients in each group. The primary outcomes were a composite of adverse obstetrical outcomes and a composite of neonatal adverse outcomes., Results: Overall, 1079 women were eligible for analysis. After matching for possible confounding factors, the final analysis was performed on 257 patients in each group. The composite of adverse obstetrical outcomes was similar in the 2 groups (24.1% vs 24.5%; P =1.000); however, the composite of neonatal adverse outcomes was significantly higher for protocol 1 (17.9% vs 1.2%; P <.001). No neonatal death or birth trauma was reported in either group. The rates of neonatal intensive care unit admission (4.3% vs 0.4%; P =.004), respiratory distress at birth (17.5% vs 1.2%; P <.001), and Apgar scores of <7 after 5 minutes (5.8% vs 0.4%; P <.001) were significantly higher for protocol 1., Conclusion: Short-term, nonsevere adverse neonatal outcomes were significantly increased in the protocol 1 group. These must be balanced against the possible negative effects of cesarean delivery on long-term infant and maternal health., (© 2022 The Authors.)

Background: The ovarian-adnexal reporting and data system-magnetic resonance imaging (O-RADS-MRI) score decreases the incidence of indeterminate adnexal masses from 18% to 31% with ultrasound till 10.8% to 12.5% with MRI. Further improvement of this score may be useful to improve patients' management., Purpose: To evaluate the added value of quantitative diffusion-weighted imaging (DWI) in the diagnosis of adnexal masses classified according to the O-RADS-MRI score., Study Type: Prospective cohort study with retrospective DWI analysis., Population: Among 402 recruited patients, surgery was done only in 163 women (median-age: 51 years) with 201 indeterminate adnexal masses, which were included in the final analysis., Field Strength/sequence: Standardized MRI (1.5 and 3-T) including diffusion and dynamic contrast-enhanced sequences (diffusion-weighted single-shot spin-echo echo-planar imaging) were used., Assessment: Two radiologists classified the adnexal masses according to O-RADS-MRI and they were blinded to the pathology report. Two methods of quantitative analysis were applied using region-of-interest apparent-diffusion-coefficient (ROI-ADC) and whole-lesion ADC-histogram (WL-ADC)., Statistical Tests: Fisher's exact and Mann-Whitney-U tests were used to compare variables among malignant and benign lesions. Receiver-operating-characteristic (ROC) curves were constructed to examine the sensitivity/specificity of each parameter. ROI-ADC and WL-ADC of lesions with O-RADS-MRI score-4 were plotted to identify thresholds of malignant lesions. The improvement of the O-RADS-MRI score after adding these thresholds was assessed by two ROC-curves. A P < 0.05 was considered to be statistically significant., Results: Fifty-eight of the 201 lesions (28.9%) were malignant. The ROI-ADC and the WL-ADC means of malignant lesions were significantly lower than those of benign lesions. Forty-two lesions (20.9%) had an O-RADS-MRI score-4. In this subgroup, 76% of lesions with ROI-ADC < 1.7 × 10 -3  mm 2 /sec and WL-ADC < 2.6 × 10 -3  mm 2 /sec were malignant, whereas only 11.8% with ROI-ADC ≥ 1.7 × 10 -3  mm 2 /sec or a WL-ADC ≥ 2.6 × 10 -3  mm 2 /sec were malignant. The overall performance of the O-RADS-MRI score combined with these thresholds was improved., Data Conclusion: Integrating ADC-thresholds in O-RADS-MRI score-4 may discriminate low-to-intermediate and intermediate-to-high malignancy risk groups., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: To describe the outcomes of sickle-cell disease in pregnancy according to the different treatments adopted before and during pregnancy and to propose a systematic approach to treat sickle-cell disease (SCD) during pregnancy., Methods: A retrospective descriptive study compared pregnancy outcomes among women with SCD who stopped hydroxyurea (HU) once pregnant (Group 1), were never treated before and during pregnancy (Group 2) or were treated by HU before conception who received prophylactic transfusion during pregnancy (Group 3). For each group we recorded the population's characteristics and the transfusion-related, obstetrical, perinatal and SCD complications., Results: We found 11 patients for group 1 (9/11 with at least 3 painful crises during the 12 months before conception), 4 for group 2 (3/4 with no sickle-cell complications during the year before pregnancy) and 2 for group 3 (one with previous multiorgan failure (MOF), one with previous stroke). No transfusion-related complication occurred. Group 1 and 2 developed SCD complications and a high number of acute transfusions and hospital admissions. Group 3 showed none of these complications, but one patient developed preeclampsia and preterm birth. Several obstetrical and perinatal complications occurred in group 1., Conclusion: Not treating sickle-cell during pregnancy increases maternal and perinatal morbidity, even in mildly affected women. All sickle-cell pregnancies should be treated, according to the treatment adopted before but also to patient's SCD-history. We propose chronic transfusion to women with previous stroke or MOF or already under transfusion program, and HU for severely and mildly affected patients, respectively from the second and third trimesters. Additional prospective studies are needed to validate the results of the proposed protocol.

Objective: The aim of the study was to assess DWI with ROI-ADC and WL-ADC measurements in early response after NAC in breast cancer., Methods: Between January 2016 and December 2019, 55 women were enrolled in this prospective single-center study. MRI was performed at three time points for each patient: before treatment (MRI 1: DW and DCE MRI), after one cycle of NAC (MRI 2: noncontrast DW MRI), and after completion of NAC before surgery (MRI 3: DW and DCE MRI). ROI-ADC and WL-ADC measurements were obtained on MRI and were compared to histology findings and to the RCB class. Patients were categorized as having pCR or non-pCR., Results: Among 48 patients, 9 experienced pCR. An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 88.9% and a specificity of 63.4% in predicting pCR, whereas WL-ADC did not predict pCR. An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 83.3% and a specificity of 64.9% in predicting radiologic complete response. An increase of WL-ADC between MRI 1 and 2 of more than 25.5% had a sensitivity of 83.3% and a specificity of 75.5% in predicting radiologic complete response., Conclusion: After one cycle of NAC, a significant increase in breast tumor ROI-ADC at DWI predicted complete pathologic and radiologic responses., Key Points: • An increase of WL-ADC between MRI 1 and 2 of more than 25.5% had a sensitivity of 83.3% and a specificity of 75.5% in predicting radiologic complete response. • An increase of ROI-ADC between MRI 1 and 2 of more than 47.5% had a sensitivity of 88.9% and a specificity of 63.4% in predicting pCR, and a sensitivity of 83.3% and a specificity of 64.9% in predicting radiologic complete response. • A significant increase in breast tumor ROI-ADC at DWI predicted complete pathologic and radiologic responses., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: To compare the outcomes of a cohort of monochorionic pregnancies with selective fetal growth restriction (sFGR) diagnosed according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) definition published in 2015 with a cohort considered as sFGR according to new expert consensus-based diagnostic parameters published in 2019., Methods: This was a retrospective study, conducted between January 1st 2010 and July 30th 2019. We reviewed the medical records of all the monochorionic pregnancies followed in our center including perinatal outcomes. Pregnancies complicated by fetal anomalies, infection, twin-twin transfusion syndrome, twin anaemia-polycythemia sequence and twin reversed arterial perfusion sequence were excluded. Patients were grouped according to the 2015 ISUOG definition into: normal (Group 1), sFGR (Group 2), and monochorionic pregnancies with abnormal growth that did not fulfill the full criteria for sFGR (Group 3). After the initial classifications were made, an additional group, was created, including all pregnancies reclassified as sFGR according to the 2019 expert consensus parameters (Group 4)., Results: During the study period, 291 monochorionic pregnancies were followed in our center, 132 of whom were eligible for inclusion in the final analysis. The prevalence of sFGR increased from 17.4% to 26.5% after applying the expert consensus-based parameters to the study population. Compared to group 1, group 2 had higher rates of emergency cesarean, neonatal intensive care admissions, invasive and noninvasive ventilation, surfactant use, metabolic disorders and lower gestational ages at birth. In contrast, the neonatal outcomes of Groups 1 and 4 were not significantly different., Conclusion: When the 2019 consensus-based diagnostic parameters for sFGR were applied to our study population, the number of sFGR cases increased by over 50%, without any improvements in perinatal outcomes. Larger prospective studies are needed to examine the potential clinical implications of these new parameters for sFGR in monochorionic pregnancies.

Background: Following the adoption of the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) diagnosis by the World Health Organization (WHO) in 2014, many investigators have tried to identify independent risk factors for antenatal insulin therapy (AIT). The purpose of the current study is to build and validate a score that stratifies patients according to their need for AIT., Methods: All pregnant women diagnosed with GDM according to the IADPSG definition were included. Group 1 comprised patients of 2018, and group 2 comprised patients of 2019. Each group was divided into two subgroups: subgroup A comprised patients diagnosed according to the 75-g oral glucose tolerance test (OGTT), and subgroup B comprised patients diagnosed according to fasting plasma glucose (FPG)., Results: A total of 1298 patients were included; 19.3% of those diagnosed by OGTT and 40.9% by FPG required AIT. The risk for AIT was stratified as low, moderate, and high. Brugmann FPG score comprised six risk factors and Brugmann OGTT score 12. Higher scores were associated with higher risk for AIT. The use of these scores in the two subgroups of group 2 showed no statistical differences compared to group 1., Conclusions: Both Brugmann FPG and OGTT scores may be useful to stratify patients with GDM according to their need for AIT. Future studies should be conducted to prospectively validate these scores, and to examine whether or not using oral anti-hyperglycemic agents in a high-risk group may decrease the need for AIT.

Background and Objective: Orofacial clefts are the most commonly diagnosed birth defects of the face during pregnancy. They can be either syndromic or non-syndromic. The objective of this study was to calculate the incidence of non-syndromic cleft lip with or without cleft palate (CL/CP) and isolated cleft palate (CP) in patients with a positive family history of non-syndromic oral clefts, and to identify the familial risk factors of oral cleft development in these patients., Methods: This was a retrospective study that included all patients with a positive family history of non-syndromic oral clefts, followed up in the department of fetal medicine in Brugmann University Hospital, Brussels, Belgium, between 1 January 2009 and 31 December 2019., Results: Over the study period, the incidence of non-syndromic oral clefts was 10.81/10,000 pregnancies. Seventy-three (0.15%) women had a positive family history of oral clefts, and had 86 pregnancies during this period. The incidence of oral clefts in this group was 9.3% (86-fold increase). This incidence varied depending on many factors, including the type of oral clefts in the family, the degree of relation of the fetus or baby to the family member who has the cleft, and the number of siblings with oral clefts., Conclusion: The offspring of pregnant patients with a positive family history of oral clefts are at risk for recurrence. The incidence is very high when there are 3 or more siblings with oral clefts, when the father or mother has the anomaly, or when there is bilateral CL/CP in the family history.

Objective: To evaluate various signal intensity ratios in isolated congenital diaphragmatic hernia (CDH) and to compare their potential in predicting survival with that of the observed-to-expected (O/E) ratio of total fetal lung volume (TFLV) using magnetic resonance imaging (MRI) measurements. Our second objective was to evaluate the impact of operator's experience in comparing the prediction of postnatal survival by O/E-TFLV., Methods: In 75 conservatively managed CDH fetuses and in 50 who underwent fetoscopic endoluminal tracheal occlusion (FETO), the fetal lung-to-amniotic fluid, lung-to-liver, lung-to-muscle, lung-to-spinal fluid signal intensity ratios, respectively LAFSIR, LLSIR, LMSIR, and LSFSIR, were measured, as was O/E-TFLV. Receiver operating characteristic (ROC) curves were constructed and used to compare the various signal intensity ratios with O/E-TFLV in the prediction of postnatal survival. In 72 MRI lung volumes assessed by the referring radiologists in Paris and Lille and secondarily by our expert radiologist in Brussels (M.M.C.) using the same MRI examinations, ROC curves were constructed and used to compare the value of O/E-TFLV determined by the two centers in the prediction of postnatal survival., Results: In the total cohort of CDH fetuses, O/E-TFLV and LLSIR were predictive of postnatal survival whereas in the conservatively managed group O/E-TFLV, LLSIR, and LMSIR predicted postnatal survival. O/E-TFLV predicted postnatal survival far better than the signal intensity ratios: area under the ROC curve for prediction by O/E-TFLV in the total cohort was 0.866 ( p  < .001; standard error = 0.031). The area under the ROC curve for prediction of postnatal survival using O/E-TFLV by MRI evaluated at the referral centers was 0.640 ( p  = 102; standard error = 0.085), and with O/E-TFLV reevaluated by M.M.C., it was 0.872 ( p  < .001; standard error = 0.061). Pairwise comparison showed a significant difference between the areas under the ROC curves (difference = 0.187, p  = .012; standard error = 0.075)., Conclusion: In fetuses with CDH with/without FETO, LLSIR was significantly correlated with the prediction of postnatal survival. However, measurement of O/E-TFLV was far better in predicting postnatal outcome. Operator experience in measurement of lung volumes using MRI seem to play a role in the predictive value of the technique.

Background: Large-for-gestational-age fetuses are at increased risk of perinatal morbidity and mortality. Magnetic resonance imaging seems to be more accurate than ultrasound in the prediction of macrosomia; however, there is no well-powered study comparing magnetic resonance imaging with ultrasound in routine pregnancies., Objective: This study aimed to prospectively compare estimates of fetal weight based on 2-dimensional ultrasound and magnetic resonance imaging with actual birthweights in routine pregnancies., Study Design: From May 2016 to February 2019, women received counseling at the 36-week clinic. Written informed consent was obtained for this Ethics Committee-approved study. In this prospective, single-center, blinded study, pregnant women with singleton pregnancies between 36 0/7 and 36 6/7 weeks' gestation underwent both standard evaluation of estimated fetal weight with ultrasound according to Hadlock et al and magnetic resonance imaging according to the formula developed by Baker et al, based on the measurement of the fetal body volume. Participants and clinicians were aware of the results of the ultrasound but blinded to the magnetic resonance imaging estimates. Birthweight percentile was considered as the gold standard for the ultrasound and magnetic resonance imaging-derived percentiles. The primary outcome was the area under the receiver operating characteristic curve for the prediction of large-for-gestation-age neonates with birthweights of ≥95th percentile. Secondary outcomes included the comparative prediction of large-for-gestation-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles for gestational age and maternal and perinatal complications., Results: Of 2914 women who were initially approached, results from 2378 were available for analysis. Total fetal body volume measurements were possible for all fetuses, and the time required to perform the planimetric measurements by magnetic resonance imaging was 3.0 minutes (range, 1.3-5.6). The area under the receiver operating characteristic curve for the prediction of a birthweight of ≥95th percentile was 0.985 using prenatal magnetic resonance imaging and 0.900 using ultrasound (difference=0.085, P<.001; standard error, 0.020). For a fixed false-positive rate of 5%, magnetic resonance imaging for the estimation of fetal weight detected 80.0% (71.1-87.2) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 59.1% (49.0-68.5) of birthweight of ≥95th percentile. The positive predictive value was 42.6% (37.8-47.7) for the estimation of fetal weight using magnetic resonance imaging and 35.4% (30.1-41.1) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.0% (98.6-99.3) for the estimation of fetal weight using magnetic resonance imaging and 98.0% (97.6-98.4) for the estimation of fetal weight using ultrasound. For a fixed false-positive rate of 10%, magnetic resonance imaging for the estimation of fetal weight detected 92.4% (85.5-96.7) of birthweight of ≥95th percentile, whereas ultrasound for the estimation of fetal weight detected 76.2% (66.9-84.0) of birthweight of ≥95th percentile. The positive predictive value was 29.9% (27.2-32.8) for the estimation of fetal weight using magnetic resonance imaging and 26.2% (23.2-29.4) for the estimation of fetal weight using ultrasound, and the negative predictive value was 99.6 (99.2-99.8) for the estimation of fetal weight using magnetic resonance imaging and 98.8 (98.4-99.2) for the estimation of fetal weight using ultrasound. The area under the receiver operating characteristic curves for the prediction of large-for-gestational-age neonates with birthweights of ≥90th, 97th, and 99th percentiles and small-for-gestational-age neonates with birthweights of ≤10th, 5th, and 3rd percentiles was significantly larger in prenatal magnetic resonance imaging than in ultrasound (P<.05 for all)., Conclusion: At 36 weeks' gestation, magnetic resonance imaging for the estimation of fetal weight performed significantly better than ultrasound for the estimation of fetal weight in the prediction of large-for-gestational-age neonates with birthweights of ≥95th percentile for gestational age and all other recognized cutoffs for large-for-gestational-age and small-for-gestational-age neonates (P<.05 for all)., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Since the lockdown caused by the COVID-19 pandemic, restrictions on hospitals' activity forced healthcare practitioners to innovate in order to provide continuity of care to patients. The aim of this study was to evaluate the efficiency of a newly established protocol for medical abortion and to measure the level of satisfaction of the patients who experienced abortion at home., Methods: This retrospective study compared all the patients who had an early medical abortion at up to 9 weeks of gestation during the two drastically different periods between December 2018 and March 2021 ("hospital" and "home" groups). We evaluated the expulsion of the gestational sac as a primary outcome. The rates of infection, hemorrhage, retained trophoblastic material and need for surgical management were also assessed. A survey was also used to measure the satisfaction and acceptability of the method., Results: The rate of expulsion of pregnancy was not significantly different between the two groups: 92.9% in hospital versus 99% at home. Early retained trophoblastic material and surgical interventions were higher in the hospital group. No significant difference was observed for the remaining outcomes. Moreover, the level of acceptability was similar in both groups, though patients felt safer in the "hospital" group., Conclusion: Switching an early medical abortion protocol from expulsion of pregnancy in hospital to expulsion of pregnancy at home is effective and acceptable to women, and may be associated with decreased rate of retained trophoblastic material. Further larger studies are needed to test the long-term result of this protocol., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-to-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. In the current retrospective study, we determined the incidence of MC pregnancy complications in a tertiary care centre during a 10-year period. Single foetal death (FD) beyond 14 weeks' gestation was significantly higher when complicated by either TTTS, TAPS or selective foetal growth restriction (21.4%, 16.7% and 9.1% versus 1.6%, p <.001, p =.02 and p =.04, respectively). We also demonstrated that twins' weight discordance >20% is an independent risk factor for single or double FD after LPC. Consequently, prior to LPC, patients should be counselled that early diagnosis of TTTS, advanced Quintero stages and weight discordances >20% are potential risk factors for FD. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.Impact Statement What is already known on this subject? Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. What the results of this study add? The results of the current study determined the incidence of MC pregnancy complications in a tertiary care centre in Brussels, and identified that twins' weight discordance >20% is an independent risk factor for single or double foetal death after LPC. What the implications are of these findings for clinical practice and/or further research? Prior to laser coagulation, patients should be counselled that early diagnosis of TTTS, Quintero stages 3 or 4 and weight discordances >20% are potential risk factors for foetal demise. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.

Objectives: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing as a first-line screening method for major trisomies, performed by two laboratories using different analytical methods: a targeted chromosome-selective method (Harmony ® prenatal Test) versus a home-brew genome-wide (GW) massively parallel sequencing method (HB-cfDNA test), and to evaluate the clinical value of incidental findings for the latter method., Methods: CfDNA testing was performed in 3137 pregnancies with the Harmony ® prenatal Test and in 3373 pregnancies with the HB-cfDNA test. Propensity score analysis was used to match women between both groups for maternal age, weight, gestational age at testing, in vitro fertilization, rate of twin pregnancies and that of aneuploidies. Detection rates for trisomy 21 were compared between the 2 laboratories. For the HB-cfDNA test, cases with rare incidental findings were reported, including their clinical follow-up., Results: The Harmony ® prenatal Test failed at the first attempt in 90 (2.9%) of 3114 women and the HB-cfDNA test in 413 (12.2%) of 3373 women. Postmatched comparisons of the women's characteristics indicate a significantly lower failure rate in the Harmony ® group (2.8%) than in the HB cfDNA group (12.4%; p  < .001). Of the 90 women in whom the Harmony ® prenatal Test failed, 61 had a repeat test, which still failed in 10, and of the 413 women in whom the HB-cfDNA test failed, 379 had a repeat test, which still failed in 110. The total failure rate after one or two attempts was therefore 1.3% (39/3114) for Harmony ® and 4.3% (144/3373) for the HB cfDNA test. After the first or second Harmony ® prenatal Test, a high-risk result was noted in 17 of the 17 cases with trisomy 21, in 5 of the seven cases with trisomy 18, and a no-call in two cases, and in the one case with trisomy 13. The respective numbers for the HB-cfDNA test are 17 of the 18 cases with trisomy 21, and a no-call in one case, 2 of the two cases with trisomy 18, and in 2 of the three cases with trisomy 13, and a no-call in one. Of the 3373 women with the HB-cfDNA test, a rare incidental finding was noted in 28 (0.8%) of the cases, of which only 2 were confirmed on amniocytes (one with microduplication 1q21.1q21.2 and one with a deletion Xp21.1), and in another case a deletion rather than a duplication of the long arm of chromosome 8 was found. In all 28 cases, there was normal clinical follow-up., Conclusions: Comparison of cfDNA testing between these two laboratories showed a four-fold lower failure rate with the Harmony ® prenatal Test, with a similar detection rate for trisomy 21. We showed no clinical relevance of disclosing additional findings beyond common trisomies with the GW HB-cfDNA test.

Objective: 22q11.2 deletion is more common than trisomies 18 and 13 combined, yet no routine approach to prenatal screening for this microdeletion has been established. This study evaluated the clinical sensitivity and specificity of a targeted cell-free DNA (cfDNA) test to screen for fetal 22q11.2 deletion in a large cohort, using blinded analysis of prospectively enrolled pregnancies and stored clinical samples., Methods: In order to ensure that the analysis included a meaningful number of cases with fetal 22q11.2 deletion, maternal plasma samples were obtained by prospective, multicenter enrolment of pregnancies with a fetal cardiac abnormality and from stored clinical samples from a research sample bank. Fetal genetic status, as evaluated by microarray analysis, karyotyping with fluorescence in-situ hybridization or a comparable test, was available for all cases. Samples were processed as described previously for the Harmony prenatal test, with the addition of DANSR (Digital Analysis of Selected Regions) assays targeting the 3.0-Mb region of 22q11.2 associated with 22q11.2 deletion syndrome. Operators were blinded to fetal genetic status. Sensitivity and specificity of the cfDNA test for 22q11.2 deletion were calculated based on concordance between the cfDNA result and fetal genotype., Results: The final study group consisted of 735 clinical samples, including 358 from prospectively enrolled pregnancies and 377 stored clinical samples. Of 46 maternal plasma samples from pregnancies with a 22q11.2 deletion, ranging in size from 1.25 to 3.25 Mb, 32 had a cfDNA result indicating a high probability of 22q11.2 deletion (sensitivity, 69.6% (95% CI, 55.2-80.9%)). All 689 maternal plasma samples without a 22q11.2 deletion were classified correctly by the cfDNA test as having no evidence of a 22q11.2 deletion (specificity, 100% (95% CI, 99.5-100%))., Conclusions: The results of this large-scale prospective clinical evaluation of the sensitivity and specificity of a targeted cfDNA test for fetal 22q11.2 deletion demonstrate that this test can detect the common and smaller, nested 22q11.2 deletions with a low (0-0.5%) false-positive rate. Although the positive predictive value (PPV) observed in this study population was 100%, the expected PPV in the general pregnant population is estimated to be 12.2% at 99.5% specificity and 41.1% at 99.9% specificity. The use of this cfDNA test to screen for 22q11.2 deletion could enhance identification of pregnancies at risk for 22q11.2 deletion syndrome without significantly increasing the likelihood of maternal anxiety and unnecessary invasive procedures related to a false-positive result. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible.