Trimester-specific diagnostic accuracy of ultrasound for detection of placenta accreta spectrum: systematic review and meta-analysis.

BACKGROUND: This study aimed to assess the diagnostic accuracy of ultrasound for detecting placenta accreta spectrum (PAS) during the first trimester of pregnancy and compare it with the accuracy of second and third trimester ultrasound in pregnancies at risk for PAS. METHODS: PubMed, Embase, and Web of Science, databases were searched to identify relevant studies published from inception until March 10th, 2023. Inclusion criteria were all studies, including cohort, case-control, or cross-sectional studies, that evaluated the diagnostic accuracy of first trimester ultrasound performed prior to 14 weeks (first trimester) or after 14 weeks of gestation (second/third trimester) for diagnosis of PAS in pregnancies with clinical risk factors. The primary outcome was to assess the diagnostic accuracy of ultrasound in detecting PAS in the first trimester, and to compare it with the accuracy of ultrasound in the second and third trimesters. The secondary outcome was to evaluate the diagnostic accuracy of each ultrasonographic marker individually across the trimesters of pregnancy. Reference standard was PAS confirmed at pathological or surgical examination. The potential of ultrasound and different ultrasound signs to detect PAS was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and positive (LR+) and negative (LR-) likelihood ratios. RESULTS: A total of 37 studies including 5,764 pregnancies at risk of PAS, with 1,348 cases of confirmed PAS, were included in our analysis. The meta-analysis yielded a sensitivity of 86% (95% CI: 78%, 92%) and specificity of 63% (95% CI: 55%, 70%) during the 1st trimester, while the sensitivity was 88% (95% CI: 84%, 91%) and specificity was 92% (95% CI: 85%, 96%) during the 2nd/3rd trimester. Regarding ultrasonographic markers examined in the 1st trimester, lower uterine hypervascularity exhibited the highest sensitivity of 97% (95% CI: 19%, 100%), and uterovesical interface irregularity demonstrated the highest specificity of 99% (95% CI: 96%, 100%). However, in the 2nd/3rd trimester, loss of clear zone had the highest sensitivity of 80% (95% CI: 72%, 86%), while uterovesical interface irregularity exhibited the highest specificity of 99% (95% CI: 97%, 100%). CONCLUSION: First trimester ultrasound has similar accuracy to second and third trimester ultrasound for the diagnosis of PAS. Routine first trimester ultrasound screening for patients at high risk of PAS may improve detection rates and allow earlier referral to tertiary care centers for pregnancy management. This article is protected by copyright. All rights reserved.

Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Midline structures and cortical development in fetuses with late growth restriction according to Doppler status: prospective study.

OBJECTIVE: Fetuses with late growth restriction (FGR) have a higher risk of sub-optimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structures and cortical development in fetuses with late growth restriction according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. METHODS: Prospective cross-sectional study including fetuses with late FGR undergoing neurosonography between 32 and 34 weeks of gestation. Midline structures (corpus callosum (CC) and cerebellar vermis (CV) length) and cortical development, including the depth of Sylvian (SF), parieto-occipital (POF) and calcarine (CF) were compared between FGR, small (SGA) and appropriate for gestational age (AGA) fetuses, defined upon the Delphi criteria. Sub-group analysis according to the severity of FGR (normal vs abnormal fetal Dopplers) was also performed. Univariate analysis was used to analyze the data. RESULTS: 52 FGR with normal, 60 with abnormal Dopplers, 64 SGA and 100 AGA fetuses were included in the analysis. SGA and FGR fetuses showed significant differences in absolute values of CC (median (interquartile range) control 43.47 (28.9-56.05), vs SGA 41.85 (27.82-51.79), vs FGR ND 38.54 (29.12-50.53), vs FGR AD 31.72 (23.8-40.19) K= 26.68; p<0.0001), CV (control 24.85 (17.55-29.21), SGA K=16.71; p=0.0008), SF (control 14.52 (10.65-16.76) vs SGA 12.71 (9.8-15.10) vs FGR ND 11.93 (9.12-13.43) VS FGR A 8.30 (6.72-10.33) K=75.82; p<0.0001), POF (control 8.56 (6.31-11.09) vs SGA 8.11 (5.58-10.43) vs FGR ND 7.81 (6.14-9.29) vs FGR AD 6.56 (4.22-7.99), K=45.06; p<0.0001) and CF ( control 9.27 (6.70-11.45) vs SGA 8.23 (5.67-10.65) vs FGR ND 7.68 (5.22-9.41) vs FGR AD 6.26 (4.48-7.19) K=46.14; p<0.0001) when compared to AGA controls with a progressive reduction across groups. When neurosonographic variables were corrected for fetal HC values, significant difference in the length of CC, SF, POF and CF but CV were observed only in FGR fetuses with abnormal Doppler when compared to AGA controls. CONCLUSIONS: Late onset small fetuses showed shorter CC length and a delayed cortical development when compared to control. After controlling for HC size these differences remain significant only in FGR fetuses with abnormal Dopplers. These findings support the existence of a link between brain development and impaired placental function. This article is protected by copyright. All rights reserved.

Placental lakes vs lacunae: spot the differences.

Sonographic sonolucencies are anechoic areas surrounded by tissue of normal echogenicity, commonly found in the placental parenchyma during the second and third trimesters of pregnancy. The ultrasound appearance of lakes and lacunae derives from the low echogenicity of villous-free areas within the placental parenchyma, filled with maternal blood of varying velocities. In normal placentation, lakes usually start appearing as soon as maternal blood begins to flow freely within the intervillous space at the end of the first trimester, whereas, in accreta placentation, lacunae develop progressively during the second trimester. Larger lakes are found mainly in areas of lower villous density under the fetal plate or in the marginal areas, but can also be found in the center of a lobule above the entry of a spiral artery. Lakes of variable size, position and shape are of no clinical significance, except if they transform into echogenic cystic lesions, which have been associated with poor fetal growth and placental malperfusion. Lacunae are formed by the distortion of one or more placental lobules developing inside a uterine scar, resulting from high-volume, high-velocity flows from the radial/arcuate arteries, and are associated with a high probability of placenta accreta spectrum at birth. They often present with ultrasound signs of uterine remodeling following scarring. Lakes and lacunae can coexist within the same placenta and both will change in size and shape as pregnancy advances. Better understanding of the etiopathology of placental sonolucent spaces and associated morphological changes is necessary to identify patients at risk of subsequent complications during pregnancy and/or at delivery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Selective fetal growth restriction in dichorionic diamniotic twin pregnancy: systematic review and meta-analysis of pregnancy and perinatal outcomes.

OBJECTIVE: Most of the published literature on selective fetal growth restriction (sFGR) has focused on monochorionic twin pregnancies. The aim of this systematic review was to report on the outcome of dichorionic diamniotic (DCDA) twin pregnancies complicated by sFGR. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched. The inclusion criteria were DCDA twin pregnancies complicated by sFGR. The outcomes explored were intrauterine death (IUD), neonatal death and perinatal death (PND), survival of at least one and both twins, preterm birth (PTB) (either spontaneous or iatrogenic) prior to 37, 34, 32 and 28 weeks' gestation, pre-eclampsia (PE) or gestational hypertension, neurological, respiratory and infectious morbidity, Apgar score < 7 at 5 min, necrotizing enterocolitis, retinopathy of prematurity and admission to the neonatal intensive care unit (NICU). A composite outcome of neonatal morbidity, defined as the occurrence of respiratory, neurological or infectious morbidity, was also evaluated. Random-effects meta-analysis was used to analyze the data, and results are reported as pooled proportion or odds ratio (OR) with 95% CI. RESULTS: Thirteen studies reporting on 1339 pregnancies with sFGR and 6316 pregnancies without sFGR were included. IUD occurred in 2.6% (95% CI, 1.1-4.7%) of fetuses from DCDA pregnancies with sFGR and 0.6% (95% CI, 0.3-9.7%) of those from DCDA pregnancies without sFGR, while the respective values for PND were 5.2% (95% CI, 3.5-7.3%) and 1.7% (95% CI, 0.1-5.7%). Spontaneous or iatrogenic PTB before 37 weeks complicated 84.1% (95% CI, 55.6-99.2%) of pregnancies with sFGR and 69.1% (95% CI, 45.4-88.4%) of those without sFGR. The respective values for PTB before 34, 32 and 28 weeks were 18.4% (95% CI, 4.4-38.9%), 13.0% (95% CI, 9.5-17.1%) and 1.5% (95% CI, 0.6-2.3%) in pregnancies with sFGR and 10.2% (95% CI, 3.1-20.7%), 7.8% (95% CI, 6.8-9.0%) and 1.8% (95% CI, 1.3-2.4%) in those without sFGR. PE or gestational hypertension complicated 19.9% (95% CI, 12.4-28.6%) of pregnancies with sFGR and 12.8% (95% CI, 10.4-15.4%) of those without sFGR. Composite morbidity occurred in 28.2% (95% CI, 7.8-55.1%) of fetuses from pregnancies with sFGR and 13.9% (95% CI, 6.5-23.5%) of those from pregnancies without sFGR. When stratified according to the sFGR status within a twin pair, composite morbidity occurred in 39.0% (95% CI, 11.1-71.5%) of growth-restricted fetuses and 29.9% (95% CI, 3.5-65.0%) of appropriately grown fetuses (OR, 1.9 (95% CI, 1.7-3.1)), while the respective values for PND were 3.0% (95% CI, 1.8-4.5%) and 1.6% (95% CI, 0.9-2.6%) (OR, 2.1 (95% CI, 1.0-4.1)). On risk analysis, DCDA pregnancies complicated by sFGR had a significantly higher risk of IUD (OR, 5.2 (95% CI, 3.2-8.6)) and composite morbidity or admission to the NICU (OR, 3.2 (95% CI, 1.9-5.6)) compared to those without sFGR, while there was no difference in the risk of PTB before 34 weeks (P = 0.220) or PE/gestational hypertension (P = 0.210). CONCLUSIONS: DCDA twin pregnancies complicated by sFGR are at high risk of perinatal morbidity and mortality. The findings of this systematic review are relevant for counseling and management of complicated DCDA twin pregnancies, in which twin-specific, rather than singleton, outcome data should be used. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Urological complications in women undergoing Cesarean section for placenta accreta spectrum disorders: systematic review and meta-analysis.

OBJECTIVE: To report on the occurrence of urological complications in women undergoing Cesarean section for placenta accreta spectrum disorders (PAS). METHODS: MEDLINE, EMBASE and the Cochrane databases were searched electronically up to 1 November 2022. Studies reporting on the urological outcome of women undergoing Cesarean section for PAS were included. Two independent reviewers performed data extraction using a predefined protocol and assessed the risk of bias using the Newcastle-Ottawa scale for observational studies, with disagreements resolved by consensus.The primary outcome was the overall occurrence of urological complications. Secondary outcomes were the occurrence of any cystotomy, intentional cystotomy, unintentional cystotomy, ureteral damage, ureteral fistula and vesicovaginal fistula. All outcomes were explored in the overall population of women undergoing surgery for PAS. In addition, we performed subgroup analyses according to the type of surgery (Cesarean hysterectomy, or conservative surgery or management), severity of PAS at histopathology (placenta accreta/increta and placenta percreta), type of intervention (planned vs emergency) and number of cases per year. Random-effects meta-analyses of proportions were used to analyze the data. RESULTS: There were 62 studies included in the systematic review and 56 were included in the meta-analysis. Urological complications occurred in 15.2% (95% CI, 12.9-17.7%) of cases. Cystotomy complicated 13.5% (95% CI, 9.7-17.9%) of surgical operations. Intentional cystotomy was required in 7.7% (95% CI, 6.5-9.1%) of cases, while unintentional cystotomy occurred in 7.2% (95% CI, 6.0-8.5%) of cases. Urological complications occurred in 19.4% (95% CI, 16.3-22.7%) of cases undergoing hysterectomy and 12.2% (95% CI, 7.5-17.8%) of those undergoing conservative treatment. In the subgroup analyses, urological complications occurred in 9.4% (95% CI, 5.4-14.4%) of women with placenta accreta/increta and 38.5% (95% CI, 21.6-57.0%) of those described as having placenta percreta, and included mainly cystotomy (5.5% (95% CI, 0.6-15.1%) and 22.0% (95% CI, 5.4-45.5%), respectively). Urological complications occurred in 15.4% (95% CI, 8.1-24.6%) of cases undergoing a planned procedure and 24.6% (95% CI, 13.0-38.5%) of those undergoing an emergency intervention. In subanalysis of studies reporting on ≥ 12 cases per year, the incidence of urological complication was similar to that reported in the primary analysis. CONCLUSIONS: Women undergoing surgery for PAS are at high risk of urological complication, mainly cystotomy. The incidence of these complications was particularly high in women described as having placenta percreta at birth and in those undergoing emergency surgical intervention. The high heterogeneity between the included studies highlights the need for a standardized protocol for the diagnosis of PAS to identify prenatal imaging signs associated with the increased risk of urological morbidity at delivery. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Outcome following laser surgery of twin-twin transfusion syndrome complicated by selective fetal growth restriction: systematic review and meta-analysis.

OBJECTIVE: The published literature reports mostly on the outcome of twin pregnancies complicated by twin-twin transfusion syndrome (TTTS) without considering whether the pregnancy is also complicated by another pathology, such as selective fetal growth restriction (sFGR). The aim of this systematic review was to report on the outcome of monochorionic diamniotic (MCDA) twin pregnancies undergoing laser surgery for TTTS that were complicated by sFGR and those not complicated by sFGR. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. The inclusion criteria were studies reporting on MCDA twin pregnancies with TTTS undergoing laser therapy that were complicated by sFGR and those not complicated by sFGR. The primary outcome was the overall fetal loss following laser surgery, defined as miscarriage and intrauterine death. The secondary outcomes included fetal loss within 24 h after laser surgery, survival at birth, preterm birth (PTB) prior to 32 weeks of gestation, PTB prior to 28 weeks, composite neonatal morbidity, neurological and respiratory morbidity, and survival free from neurological impairment. All outcomes were explored in the overall population of twin pregnancies complicated by sFGR vs those not complicated by sFGR in the setting of TTTS and in the donor and recipient twins separately. Random-effects meta-analysis was used to combine data and the results are reported as pooled odds ratios (OR) with 95% CI. RESULTS: Five studies (1710 MCDA twin pregnancies) were included in the qualitative synthesis and four in the meta-analysis. The overall risk of fetal loss after laser surgery was significantly higher in MCDA twin pregnancies with TTTS complicated by sFGR (20.90% vs 14.42%), with a pooled OR of 1.6 (95% CI, 1.3-1.9) (P < 0.001). The risk of fetal loss was significantly higher in MCDA twin pregnancies with TTTS and sFGR for the donor but not for the recipient twin. The rate of live twins was 79.1% (95% CI, 72.6-84.9%) in TTTS pregnancies with sFGR and 85.6% (95% CI, 81.0-89.6%) in those without sFGR (pooled OR, 0.6 (95% CI, 0.5-0.8)) (P < 0.001). There was no significant difference in the risk of PTB prior to 32 weeks of gestation (P = 0.308) or prior to 28 weeks (P = 0.310). Assessment of short- and long-term morbidity was affected by the small number of cases. There was no significant difference in the risk of composite (P = 0.506) or respiratory (P = 0.531) morbidity between twins complicated by TTTS with vs those without sFGR, while the risk of neurological morbidity was significantly higher in those with TTTS and sFGR (pooled OR, 1.8 (95% CI, 1.1-2.9)) (P = 0.034). The risk of neurological morbidity was significantly higher for the donor twin (pooled OR, 2.4 (95% CI, 1.1-5.2)) (P = 0.029) but not for the recipient twin (P = 0.361). Survival free from neurological impairment was observed in 70.8% (95% CI, 45.0-91.0%) of twin pregnancies with TTTS complicated by sFGR and in 75.8% (95% CI, 51.9-93.3%) of those not complicated by sFGR, with no difference between the two groups. CONCLUSIONS: sFGR in MCDA pregnancies with TTTS represents an additional risk factor for fetal loss following laser surgery. The findings of this meta-analysis may be useful for individualized risk assessment of twin pregnancy complicated by TTTS and tailored counseling of the parents prior to laser surgery. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcome of monochorionic triamniotic triplet pregnancy: multicenter cohort study.

OBJECTIVE: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. METHODS: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin-to-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. RESULTS: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow-up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity-related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). CONCLUSION: Monochorionicity-related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Modified Delphi study of ultrasound signs associated with placenta accreta spectrum.

OBJECTIVE: To determine, by expert consensus through a modified Delphi process, the role of standardized and new ultrasound signs in the prenatal evaluation of patients at high risk of placenta accreta spectrum (PAS). METHODS: A systematic review of articles providing information on ultrasound imaging signs or markers associated with PAS was performed before the development of questionnaires for the first round of the Delphi process. Only peer-reviewed original research studies in the English language describing one or more new ultrasound sign(s) for the prenatal evaluation of PAS were included. A three-round consensus-building Delphi method was then conducted under the guidance of a steering group, which included nine experts who invited an international panel of experts in obstetric ultrasound imaging in the evaluation of patients at high risk for PAS. Consensus was defined as agreement of ≥ 70% between participants. RESULTS: The systematic review identified 15 articles describing eight new ultrasound signs for the prenatal evaluation of PAS. A total of 35 external experts were approached, of whom 31 agreed and participated in the first round. Thirty external experts (97%) and seven experts from the steering group completed all three Delphi rounds. A consensus was reached that a prior history of at least one Cesarean delivery, myomectomy or PAS should be an indication for detailed PAS ultrasound assessment. The panelists also reached a consensus that seven of the 11 conventional signs of PAS should be included in the examination of high-risk patients and the routine mid-gestation scan report: (1) loss of the 'clear zone', (2) myometrial thinning, (3) bladder-wall interruption, (4) placental bulge, (5) uterovesical hypervascularity, (6) placental lacunae and (7) bridging vessels. A consensus was not reached for any of the eight new signs identified by the systematic review. With respect to other ultrasound features that are not specific to PAS but increase the probability of PAS at birth, the panelists reached a consensus for the finding of anterior placenta previa or placenta previa with cervical involvement. The experts were also asked to determine which PAS signs should be quantified and consensus was reached only for the quantification of placental lacunae using an existing score. For predicting surgical outcome in patients with a high probability of PAS at delivery, a consensus was obtained for loss of the clear zone, bladder-wall interruption, presence of placental lacunae and presence of placenta previa involving the cervix. CONCLUSIONS: We have confirmed the continued importance of seven established standardized ultrasound signs of PAS, highlighted the role of transvaginal ultrasound in evaluating the placental position and anatomy of the cervix, and identified new ultrasound signs that may become useful in the future prenatal evaluation and management of patients at high risk for PAS at birth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Role of fetal magnetic resonance imaging in fetuses with congenital cytomegalovirus infection: multicenter study.

OBJECTIVE: To investigate the role of fetal brain magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses with congenital cytomegalovirus (CMV) infection and normal neurosonography. METHODS: This was a multicenter, retrospective cohort study of patients examined between 2012 and 2021 in 11 referral fetal medicine centers in Italy. Inclusion criteria were fetuses with congenital CMV infection diagnosed by polymerase chain reaction analysis of amniotic fluid, pregnancies that underwent detailed multiplanar ultrasound assessment of the fetal brain as recommended by the International Society of Ultrasound in Obstetrics and Gynecology, maternal age ≥ 18 years, normal fetal karyotype and MRI performed within 3 weeks after the last ultrasound examination. The primary outcome was the rate of central nervous system (CNS) anomalies detected exclusively on MRI and confirmed after birth or autopsy in fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography at diagnosis. Additional CNS anomalies were classified into anomalies of the ventricular and the periventricular zone, intracranial calcifications in the basal ganglia or germinal matrix, destructive encephalopathy in the white matter, malformations of cortical development, midline anomalies, posterior fossa anomalies and complex brain anomalies. We evaluated the relationship between the incidence of structural CNS malformations diagnosed exclusively on fetal MRI and a number of maternal and gestational characteristics. Univariate and multivariate logistic regression analyses were used to identify and adjust for potential independent predictors of the MRI diagnosis of fetal anomalies. RESULTS: The analysis included 95 fetuses with a prenatal diagnosis of congenital CMV infection and normal neurosonography referred for prenatal MRI. The rate of structural anomalies detected exclusively at fetal MRI was 10.5% (10/95). When considering the type of anomaly, malformations of cortical development were detected on MRI in 40.0% (4/10) of fetuses, destructive encephalopathy in 20.0% (2/10), intracranial calcifications in the germinal matrix in 10.0% (1/10) and complex CNS anomalies in 30.0% (3/10). On multivariate logistic regression analysis, only CMV viral load in the amniotic fluid, expressed as a continuous variable (odds ratio (OR), 1.16 (95% CI, 1.02-1.21); P = 0.02) or categorical variable (> 100 000 copies/mL) (OR, 12.0 (95% CI, 1.2-124.7); P = 0.04), was independently associated with the likelihood of detecting fetal anomalies on MRI. Associated anomalies were detected exclusively at birth and missed by both prenatal neurosonography and fetal MRI in 3.8% (3/80) of fetuses with congenital CMV infection. CONCLUSIONS: Fetal brain MRI can detect additional anomalies in a significant proportion of fetuses with congenital CMV infection and negative neurosonography. Viral load in the amniotic fluid was an independent predictor of the risk of associated anomalies in these fetuses. The findings of this study support a longitudinal evaluation using fetal MRI in congenital CMV infection, even in cases with negative neurosonography at diagnosis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Pregnancy and perinatal outcomes of early vs late selective termination in dichorionic twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To evaluate outcomes of dichorionic twin pregnancies undergoing early vs late selective termination of pregnancy (ST). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to March 2022. The primary outcome of this study was pregnancy loss prior to 24 weeks' gestation. The secondary outcomes included preterm birth (PTB) before 37, 34, and 32 weeks, preterm prelabor rupture of membranes (PPROM), gestational age (GA) at delivery, Cesarean delivery, mean birth weight, 5-min Apgar score < 7, overall neonatal morbidity and neonatal survival. Only prospective or retrospective studies reporting data on the outcome of early (before 18 weeks) vs late (at or after 18 weeks) ST in dichorionic twin pregnancies were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale for cohort studies. Random-effects head-to-head meta-analysis was used to analyze the data. RESULTS: Seven studies reporting on 649 dichorionic twin pregnancies were included in this systematic review. The risk of pregnancy loss prior to 24 weeks was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST (1% vs 8%; odds ratio (OR), 0.25 (95% CI, 0.10-0.65); P = 0.004). The risk of PTB was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST when considering PTB before 37 weeks (19% vs 45%; OR, 0.36 (95% CI, 0.23-0.57); P < 0.00001), before 34 weeks (4% vs 19%; OR, 0.24 (95% CI, 0.11-0.54); P = 0.0005) and before 32 weeks (4% vs 20%; OR, 0.21 (95% CI, 0.05-0.85); P = 0.03). The mean birth weight was significantly greater in the early-ST group (mean difference (MD), 392.2 g (95% CI, 59.1-726.7 g); P = 0.02), as was the mean GA at delivery (MD, 2.47 weeks (95% CI, 0.04-4.91 weeks); P = 0.049). There was no significant difference between dichorionic twin pregnancies undergoing early compared with late ST in terms of PPROM (P = 0.27), Cesarean delivery (P = 0.38), 5-min Apgar score < 7 (P = 0.35) and neonatal survival of the non-reduced twin (P = 0.54). CONCLUSIONS: The risk of pregnancy loss prior to 24 weeks and the rate of PTB before 37, 34 and 32 weeks were significantly higher in dichorionic twin pregnancies undergoing late vs early ST, thus highlighting the importance of early diagnosis of fetal anomalies in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Effectiveness and safety of prenatal valacyclovir for congenital cytomegalovirus infection: systematic review and meta-analysis.

OBJECTIVE: Universal screening for cytomegalovirus (CMV) infection in pregnancy is not recommended in most countries. One of the major deterrents is the lack of effective prenatal therapy. The role of valacyclovir therapy in reducing the risk of vertical transmission, symptomatic congenital CMV infection and adverse outcome is controversial. The main aim of this systematic review and meta-analysis was to investigate the safety and effectiveness of prenatal valacyclovir therapy in pregnancies with maternal CMV infection. METHODS: MEDLINE, EMBASE and Cochrane databases and ClinicalTrials.gov were searched. The inclusion criteria were pregnancy with confirmed maternal CMV infection, treated or untreated with valacyclovir. The primary outcome was the incidence of congenital CMV infection confirmed by a positive CMV polymerase chain reaction result of the amniotic fluid. The secondary outcomes were symptomatic and asymptomatic infection, perinatal death, termination of pregnancy, anomalies detected on follow-up ultrasound, on fetal magnetic resonance imaging or at birth, severe and mild-to-moderate symptoms due to congenital CMV infection, neurological, visual and hearing symptoms, and adverse events related to valacyclovir. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) or Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool, as appropriate. Head-to-head meta-analyses were used to compare the risk of each of the explored outcomes according to whether pregnancies with maternal CMV infection were treated with prenatal valacyclovir therapy. RESULTS: Eight studies (620 women) were included. Pregnancies treated with valacyclovir had a significantly lower risk of congenital CMV infection compared with those not receiving valacyclovir (three studies; 325 fetuses; pooled odds ratio (OR), 0.37 (95% CI, 0.21-0.64); I2 = 0%; P < 0.001). When stratifying the analysis according to gestational age at maternal infection, the risk of vertical transmission was significantly lower in pregnancies receiving valacyclovir following first-trimester maternal infection (three studies; 184 fetuses; pooled OR, 0.34 (95% CI, 0.15-0.74); I2 = 20.9%; P = 0.001), while there was no significant difference between the two groups in those acquiring CMV infection in the periconceptional period or in the third trimester of pregnancy. Only one study reported on the risk of vertical transmission in women infected in the second trimester, demonstrating a lower risk of congenital infection in women taking valacyclovir, although this was based on a small number of cases. Pregnancies treated with valacyclovir therapy had an increased likelihood of asymptomatic congenital CMV infection compared with those not receiving valacyclovir (two studies; 132 fetuses; pooled OR, 2.98 (95% CI, 1.18-7.55); I2 = 0%; P = 0.021), while there was no significant difference between the two groups in the risk of perinatal death (P = 0.923), termination of pregnancy (P = 0.089), anomalies detected at follow-up imaging assessment during pregnancy or at birth (P = 0.934) and symptoms due to CMV infection in the newborn (P = 0.092). The occurrence of all adverse events in pregnant individuals taking valacyclovir was 3.17% (95% CI, 1.24-5.93%) (six studies; 210 women), with 1.71% (95% CI, 0.41-3.39%) experiencing acute renal failure, which resolved after discontinuation of the drug. On GRADE assessment, the quality of evidence showing that valacyclovir reduced the risk of congenital CMV infection and adverse perinatal outcome was very low. CONCLUSIONS: Prenatal valacyclovir administration in pregnancies with maternal CMV infection reduces the risk of congenital CMV infection. Further evidence is needed to elucidate whether valacyclovir can affect the course of infection in the fetus and the risk of symptomatic fetal or neonatal infection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.