Prediction of large-for-gestational age at 36 weeks' gestation: two-dimensional ultrasound vs three-dimensional ultrasound vs magnetic resonance imaging.

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 ≥ 95th 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 ≥ 90th percentile at the routine third-trimester ultrasound examination, obesity (prepregnancy body mass index ≥ 30 kg/m2) or excessive weight gain during pregnancy. The outcome was the diagnostic performance of each modality in the prediction of birth weight ≥ 95th 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 ≥ 95th 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 ≥ 95th 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.

Timing of induction of labor in suspected macrosomia: retrospective cohort study, systematic review and meta-analysis.

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 ≥ 90th 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); I2 = 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); I2 = 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.

Effect of cannula insertion site during fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm prelabor rupture of membranes.

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.

Observed-to-expected lung-area-to-head-circumference ratio on ultrasound examination vs total fetal lung volume on magnetic resonance imaging in prediction of survival in fetuses with left-sided diaphragmatic hernia.

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.

Prevalence of and risk factors for failure of fetal magnetic resonance imaging due to maternal claustrophobia or malaise.

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.

Magnetic resonance scoring system for assessment of adnexal masses: added value of diffusion-weighted imaging including apparent diffusion coefficient map.

OBJECTIVES: To validate prospectively the ADNEX magnetic resonance (MR) scoring system to assess adnexal masses and to evaluate a new, modified ADNEX MR scoring system that incorporates diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping. METHODS: Between January 2015 and September 2018, 323 consecutive women with adnexal masses diagnosed on transvaginal ultrasound (TVS) underwent standardized MR imaging (MRI) including diffusion and dynamic contrast-enhanced sequences. Of these, 131 underwent subsequent surgery. For interpretation of the MRI examinations, we applied the five-category ADNEX MR scoring system, along with a modified scoring system including DWI with ADC mapping. For both scoring systems, a score was given for all adnexal masses. Histological diagnosis was considered as the gold standard and lesions were classified as benign or malignant. The difference between the predictive values for diagnosing malignancy of the classical and modified scoring systems was assessed on the basis of the areas under the receiver-operating-characteristics (AUC) curves. The sensitivity and specificity for diagnosing malignancy of each score were also calculated. RESULTS: Among the 131 women with adnexal mass(es) diagnosed on TVS who underwent MRI and subsequent surgery, the surgery revealed 161 adnexal masses in 126 women; five women had no mass. Histological examination confirmed 161 adnexal masses, of which all had been detected on MRI: 32 malignant tumors, 15 borderline tumors, which were classified as part of the malignant group (n = 47), and 114 benign lesions. The AUC for prediction of a malignant lesion was 0.938 (95% CI, 0.902-0.975) using the classical ADNEX MR scoring system and 0.974 (95% CI, 0.953-0.996) using the modified scoring system. Pairwise comparison of these AUCs revealed a significant difference (P = 0.0032). The sensitivity and specificity for diagnosing malignancy with an ADNEX MR score of 4 or more were 95.5% and 86.6%, respectively, using the classic scoring system, and 95.7% and 93.3%, respectively, using the modified scoring system. CONCLUSION: DWI with ADC mapping could be integrated into the ADNEX MR scoring system to improve specificity, thereby potentially optimizing clinical management by avoiding unnecessary surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of a targeted cell-free DNA prenatal test for 22q11.2 deletion in a large clinical cohort.

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.

Prenatal stomach position predicts gastrointestinal morbidity at 2 years in fetuses with left-sided congenital diaphragmatic hernia.

OBJECTIVE: The long-term morbidity associated with isolated left-sided congenital diaphragmatic hernia (CDH) has been described previously. However, antenatal criteria impacting gastrointestinal morbidity (GIM) are not yet defined. The objective of this study was to evaluate the effect of fetal stomach position on the risk of GIM at 2 years of age in children with left-sided CDH. METHODS: This was a retrospective, observational multicenter cohort study of data obtained from January 2010 to January 2014, that included patients whose fetus had isolated left-sided CDH, with or without fetal endoscopic tracheal occlusion (FETO). Prenatal maternal, fetal and pediatric data were collected. Fetal stomach position was evaluated a posteriori by two observers, using ultrasound images at the level of the four-chamber view of the heart that had been obtained to calculate the observed-to-expected lung-area-to-head-circumference ratio (O/E-LHR). Fetal stomach position was graded as follows: Grade 1, stomach not visualized; Grade 2, stomach visualized anteriorly, next to the apex of the heart, with no structure in between the stomach and the sternum; Grade 3, stomach visualized alongside the left ventricle of the heart, and abdominal structures anteriorly; or Grade 4, as Grade 3 but with stomach posterior to the level of the atrioventricular heart valves. The primary outcome was GIM at 2 years of age, assessed in a composite manner, including the occurrence of gastroesophageal reflux disease, need for gastrostomy, duration of parenteral and enteral nutrition and persistence of oral aversion. Regression analysis was performed in order to investigate the effect of O/E-LHR, stomach position and FETO on various GIM outcome variables. RESULTS: Forty-seven patients with fetal left-sided CDH were included in the analysis. Thirteen (27.7%) infants did not meet the criterion of exclusive oral feeding at 2 years of age. Fetal stomach position grade was associated significantly and independently with the duration of parenteral nutrition (odds ratio (OR), 19.86; P = 0.031) and persistence of oral aversion at 2 years (OR, 3.40; P = 0.006). On multivariate analysis, O/E-LHR was predictive of the need for prosthetic patch repair, but not for GIM. FETO did not seem to affect the risk of GIM at 2 years. CONCLUSION: In isolated left-sided CDH, fetal stomach position is the only factor that is predictive of GIM at 2 years of age. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Postmortem fetal imaging: prospective blinded comparison of two-dimensional ultrasound with magnetic resonance imaging.

OBJECTIVE: To compare the diagnostic rate and accuracy of 3-Tesla (T) postmortem magnetic resonance imaging (PM-MRI) and postmortem ultrasound (PM-US) in an unselected fetal population. METHODS: We performed prospectively, in a blinded manner, 3-T PM-MRI and PM-US on 160 unselected fetuses at 13-41 weeks of gestation. All imaging was reported according to a prespecified template, for five anatomical regions: brain, thorax, heart, abdomen and spine. The rates of non-diagnostic results for PM-US and PM-MRI were compared and, for results that were diagnostic, we calculated sensitivity, specificity and concordance rates for each anatomical region, using conventional autopsy as the reference standard. RESULTS: 3-T PM-MRI performed significantly better than did PM-US overall and in particular for fetuses ≥ 20 weeks' gestation. Specifically, the non-diagnostic rates for PM-MRI vs PM-US were 4.4% vs 26.9% (7/160 vs 43/160; P < 0.001) for the brain, 5.2% vs 17.4% (8/155 vs 27/155; P < 0.001) for the thorax, 3.8% vs 30.6% (6/157 vs 48/157; P < 0.001) for the heart and 3.2% vs 23.6% (5/157 vs 37/157; P < 0.001) for the abdomen. For the spine, both techniques showed an equally low non-diagnostic rate. When both postmortem imaging techniques were diagnostic, they had similar accuracy, with no difference in sensitivity or specificity, and similar concordance with autopsy (PM-US, 79.5-96.5%; PM-MRI, 81.6-99.1%). CONCLUSIONS: PM-MRI performed significantly better than PM-US in this unselected population, due mainly to a lower non-diagnostic rate. PM-MRI should remain the first-line imaging investigation for perinatal autopsy, but PM-US could be considered if MRI is not available, albeit with a higher non-diagnostic rate. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Postmortem examination of human fetuses: comparison of two-dimensional ultrasound with invasive autopsy.

OBJECTIVE: To assess the diagnostic accuracy of postmortem ultrasound performed by operators blinded to prenatal findings and to invasive autopsy results in fetuses at different gestational ages and to investigate the effect of various parameters on its diagnostic success. METHODS: We performed postmortem two-dimensional ultrasound examination, blinded to clinical details, on 163 fetuses at 13-42 weeks' gestation. Logistic regression analysis was used to investigate the effect of: (i) gestational age at postmortem ultrasound, (ii) presence of maceration and (iii) mode of death, on whether the exam succeeded or failed to reach a diagnosis. In 123 cases in which invasive autopsy was available, the diagnostic accuracy of ultrasound in detecting major organ abnormalities was evaluated, using invasive autopsy as the gold standard. RESULTS: For the fetal brain, postmortem ultrasound exam was non-diagnostic in significantly more fetuses with maceration (39.5%; 17/43) vs those without maceration (20.0%; 24/120) (P = 0.013). For the fetal thorax, the exam was non-diagnostic in 34.1% (15/44) of fetuses < 20 weeks of gestation and in 10.9% (13/119) of fetuses ≥ 20 weeks (P < 0.001). For the heart and abdominal organs, there was no association between non-diagnostic postmortem ultrasound and the variables tested. For fetuses < 20 weeks, specificity of postmortem ultrasound examination was 83.3% for detection of anomalies of the brain, 68.6% for the thorax and 77.4% for the heart. For fetuses ≥ 20 weeks, sensitivity and specificity were, respectively, 61.9% and 74.2% for detection of anomalies of the brain, 29.5% and 87.0% for the thorax and 65.0% and 83.1% for the heart. For the fetal abdominal organs, sensitivity was 60.7% and specificity 75.8%, and postmortem ultrasound was particularly useful for detection of abnormalities of the kidneys, irrespective of gestational age. CONCLUSION: Although maceration may lead to failure of postmortem ultrasound examination in some cases, this technique achieves diagnostically acceptable levels of accuracy for fetal brain and abdominal organs, compared with conventional autopsy. It may therefore play a role as a first-line examination before other virtual autopsy techniques are indicated. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal prediction of postnatal large-for-dates neonates using a simplified MRI method: comparison with conventional 2D ultrasound estimates.

OBJECTIVE: To evaluate the performance of a simple semi-automated method for estimation of fetal weight (EFW) using magnetic resonance imaging (MRI) as compared with two-dimensional (2D) ultrasound (US) for the prediction of large-for-dates neonates. METHODS: Data of two groups of women with singleton pregnancy between March 2011 and May 2016 were retrieved from our database and evaluated retrospectively: the first group included women who underwent US-EFW and MRI-EFW within 48 h before delivery and the second group included women who had these evaluations between 35 + 0 weeks and 37 + 6 weeks of gestation, more than 48 h before delivery. US-EFW was based on Hadlock et al. and MRI-EFW on the formula described by Baker et al. For MRI-EFW, planimetric measurement of the fetal body volume (FBV) was performed using a semi-automated method and the time required for measurement was noted. Outcome measure was the performance of MRI-EFW vs US-EFW in the prediction of large-for-dates neonates, both ≤ 48 h and > 48 h before delivery. Receiver-operating characteristics (ROC) curves for each method were compared using the DeLong method. RESULTS: Of the 270 women included in the first group, 48 (17.8%) newborns had birth weight ≥ 90th centile and 30 (11.1%) ≥ 95th centile. The second group included 83 women, and nine (10.8%) newborns had birth weight ≥ 95th centile. Median time needed for FBV planimetric measurements in all 353 fetuses was 3.5 (range, 1.5-5.5) min. The area under the ROC curve (AUC) for prediction of large-for-dates neonates by prenatal MRI performed within 48 h before delivery was significantly higher than that by US (for birth weight ≥ 90th centile, difference between AUCs = 0.085, standard error (SE) = 0.020, P < 0.001; for birth weight ≥ 95th centile, difference between AUCs = 0.036, SE = 0.014, P = 0.01). Similarly, MRI-EFW was better than US-EFW in predicting birth weight ≥ 95th centile when both examinations were performed > 48 h prior to delivery (difference between AUCs = 0.077, SE = 0.039, P = 0.045). CONCLUSION: MRI planimetry using our purpose-designed semi-automated method is not time-consuming. The predictive performance of MRI-EFW performed immediately prior to or remote from delivery is significantly better than that of US-EFW for the prediction of large-for-dates neonates. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prediction and prevention of small-for-gestational-age neonates: evidence from SPREE and ASPRE.

OBJECTIVES: To examine the effect of first-trimester screening for pre-eclampsia (PE) on the prediction of delivering a small-for-gestational-age (SGA) neonate and the effect of prophylactic use of aspirin on the prevention of SGA. METHODS: The data for this study were derived from two multicenter studies. In SPREE, we investigated the performance of screening for PE by a combination of maternal characteristics and biomarkers at 11-13 weeks' gestation. In ASPRE, women with a singleton pregnancy identified by combined screening as being at high risk for preterm PE (> 1 in 100) participated in a trial of aspirin (150 mg/day from 11-14 until 36 weeks' gestation) compared to placebo. In this study, we used the data from the ASPRE trial to estimate the effect of aspirin on the incidence of SGA with birth weight < 10th , < 5th and < 3rd percentile for gestational age. We also used the data from SPREE to estimate the proportion of SGA in the pregnancies with a risk for preterm PE of > 1 in 100. RESULTS: In SPREE, screening for preterm PE by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor identified a high-risk group that contained about 46% of SGA neonates < 10th percentile born at < 37 weeks' gestation (preterm) and 56% of those born at < 32 weeks (early); the overall screen-positive rate was 12.2% (2014 of 16 451 pregnancies). In the ASPRE trial, use of aspirin reduced the overall incidence of SGA < 10th percentile by about 40% in babies born at < 37 weeks' gestation and by about 70% in babies born at < 32 weeks; in babies born at ≥ 37 weeks, aspirin did not have a significant effect on incidence of SGA. The aspirin-related decrease in incidence of SGA was mainly due to its incidence decreasing in pregnancies with PE, for which the decrease was about 70% in babies born at < 37 weeks' gestation and about 90% in babies born at < 32 weeks. On the basis of these results, it was estimated that first-trimester screening for preterm PE and use of aspirin in the high-risk group would potentially reduce the incidence of preterm and early SGA by about 20% and 40%, respectively. CONCLUSION: First-trimester screening for PE by the combined test identifies a high proportion of cases of preterm SGA that can be prevented by the prophylactic use of aspirin. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

ASPRE trial: incidence of preterm pre-eclampsia in patients fulfilling ACOG and NICE criteria according to risk by FMF algorithm.

OBJECTIVE: To report the incidence of preterm pre-eclampsia (PE) in women who are screen positive according to the criteria of the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), and compare the incidence with that in those who are screen positive or screen negative by The Fetal Medicine Foundation (FMF) algorithm. METHODS: This was a secondary analysis of data from the ASPRE study. The study population consisted of women with singleton pregnancy who underwent prospective screening for preterm PE by means of the FMF algorithm, which combines maternal factors and biomarkers at 11-13 weeks' gestation. The incidence of preterm PE in women fulfilling the NICE and ACOG criteria was estimated; in these patients the incidence of preterm PE was then calculated in those who were screen negative relative to those who were screen positive by the FMF algorithm. RESULTS: A total of 34 573 women with singleton pregnancy delivering at ≥ 24 weeks' gestation underwent prospective screening for preterm PE, of which 239 (0.7%) cases developed preterm PE. At least one of the ACOG criteria was fulfilled in 22 287 (64.5%) pregnancies and the incidence of preterm PE was 0.97% (95% CI, 0.85-1.11%); in the subgroup that was screen positive by the FMF algorithm the incidence of preterm PE was 4.80% (95% CI, 4.14-5.55%), and in those that were screen negative it was 0.25% (95% CI, 0.18-0.33%), with a relative incidence in FMF screen negative to FMF screen positive of 0.051 (95% CI, 0.037-0.071). In 1392 (4.0%) pregnancies, at least one of the NICE high-risk criteria was fulfilled, and in this group the incidence of preterm PE was 5.17% (95% CI, 4.13-6.46%); in the subgroups of screen positive and screen negative by the FMF algorithm, the incidence of preterm PE was 8.71% (95% CI, 6.93-10.89%) and 0.65% (95% CI, 0.25-1.67%), respectively, and the relative incidence was 0.075 (95% CI, 0.028-0.205). In 2360 (6.8%) pregnancies fulfilling at least two of the NICE moderate-risk criteria, the incidence of preterm PE was 1.74% (95% CI, 1.28-2.35%); in the subgroups of screen positive and screen negative by the FMF algorithm the incidence was 4.91% (95% CI, 3.54-6.79%) and 0.42% (95% CI, 0.20-0.86%), respectively, and the relative incidence was 0.085 (95% CI, 0.038-0.192). CONCLUSION: In women who are screen positive for preterm PE by the ACOG or NICE criteria but screen negative by the FMF algorithm, the risk of preterm PE is reduced to within or below background levels. The results provide further evidence to support the personalized risk-based screening method that combines maternal factors and biomarkers. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of screening for early, preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery (UtA) pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). METHODS: The data for this study were derived from three previously reported prospective non-intervention screening studies at 11 + 0 to 13 + 6 weeks' gestation in a combined total of 61 174 singleton pregnancies, including 1770 (2.9%) that developed PE. Bayes' theorem was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiples of the median (MoM) values to derive patient-specific risks of delivery with PE at < 37 weeks' gestation. The performance of such screening was estimated. RESULTS: In pregnancies that developed PE, compared to those without PE, the MoM values of UtA-PI and MAP were increased and those of PAPP-A and PlGF were decreased, and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PlGF predicted 90% of early PE, 75% of preterm PE and 41% of term PE, at a screen-positive rate of 10%; inclusion of PAPP-A did not improve the performance of screening. The performance of screening depended on the racial origin of the women; on screening by a combination of maternal factors, MAP, UtA-PI and PlGF and using a risk cut-off of 1 in 100 for PE at < 37 weeks in Caucasian women, the screen-positive rate was 10% and detection rates for early, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut-off in women of Afro-Caribbean racial origin, the screen-positive rate was 34% and detection rates for early, preterm and term PE were 100%, 92% and 75%, respectively. CONCLUSION: Screening by maternal factors and biomarkers at 11-13 weeks' gestation can identify a high proportion of pregnancies that develop early and preterm PE. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

ASPRE trial: performance of screening for preterm pre-eclampsia.

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. METHODS: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185). RESULTS: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797). CONCLUSION: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Performance of screening for aneuploidies by cell-free DNA analysis of maternal blood in twin pregnancies.

OBJECTIVES: To report clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood in screening for trisomies 21, 18 and 13 in twin pregnancies and examine variables that could influence the failure rate of the test. METHODS: cfDNA testing was performed in 515 twin pregnancies at 10-28 weeks' gestation. The failure rate of the test to provide results was compared with that in 1847 singleton pregnancies, and logistic regression analysis was used to determine which factors among maternal and pregnancy characteristics were significant predictors of test failure. RESULTS: Failure rate of the cfDNA test at first sampling was 1.7% in singletons and 5.6% in twins. Of those with a test result, the median fetal fraction in twins was 8.7% (range, 4.1-30.0%), which was lower than that in singletons (11.7% (range, 4.0-38.9%)). Multivariable regression analysis demonstrated that twin pregnancy, higher maternal weight and conception by in-vitro fertilization provided significant independent prediction of test failure. Follow-up was available in 351 (68.2%) of the twin pregnancies and comprised 334 with euploid fetuses, 12 discordant for trisomy 21 and five discordant for trisomy 18. In all 323 euploid cases with a result, the risk score for each trisomy was < 1:10 000. In 11 of the 12 cases with trisomy 21 and in the five with trisomy 18, the cfDNA test gave a high-risk result, but in one case of trisomy 21, the score was < 1:10 000. CONCLUSION: In twin pregnancies screening by cfDNA testing is feasible, but the failure rate is higher and detection rate may be lower than in singletons.