INDIAMAN-20 (INstant DIAgnosis of 20 Major ANomalies) protocol: application of IOTA diagnostic strategy to fetal anomalies.

OBJECTIVES: To compile a list of instant diagnoses of major fetal anomalies, and to present their sonographic descriptors and test them in a retrospective series of fetuses with congenital anomalies managed at our center. METHODS: The first step was to identify major anomalies that meet the following criteria: (1) can be diagnosed directly and unequivocally on the basis of a set of descriptors evident on a single sonographic view; (2) are among those more commonly diagnosed in utero; (3) represent major lethal or life-threatening malformations or anomalies for which no or only palliative surgery can be performed. For each of these anomalies, a sonographic descriptor was produced. The second step was to test the descriptors of the instant diagnoses in all cases with these anomalies evaluated since January 2000 in our Fetal Medicine Unit, retrieved from our electronic database. For each congenital anomaly-sonographic descriptor pair we then evaluated the presence vs absence of an unequivocal relationship between anomaly and descriptor, assessing: whether a particular descriptor in a set reference plane identified unequivocally the anomaly, i.e. the same descriptor could not be found in any other malformation; and whether a particular anomaly presented the corresponding descriptor in all cases. Finally, we evaluated whether the sonographic descriptors could be applied in all trimesters or only selectively, considering the natural history of the 20 instant diagnoses. RESULTS: Of the 20 instant diagnoses, five involved the central/peripheral nervous system (exencephaly/anencephaly, alobar/semilobar holoprosencephaly, cephalocele, open spinal dysraphism, complete agenesis of corpus callosum), five involved the heart (hypoplastic left heart syndrome, complete atrioventricular septal defect, severe Ebstein's anomaly, critical aortic stenosis, transposition of the great arteries), five involved the abdominal wall (left-sided congenital diaphragmatic hernia, exomphalos, gastroschisis, body-stalk anomaly) or gastrointestinal tract (duodenal atresia), and five involved the remaining systems (three urinary (autosomal recessive polycystic kidney disease, multicystic dysplastic kidney, lower urinary tract obstruction), two skeletal (transverse limb defect, radial ray defect)). All of the descriptors were found to identify unequivocally the related malformations, whereas four of the malformations were not associated with their reference descriptors in every case. For example, congenital diaphragmatic hernia (left-sided) presented without the stomach in the thorax in 42/93 (45.2%) cases. Due to the natural history of the condition, not all signs were recognizable in the first trimester, some becoming evident only from the second trimester onwards. CONCLUSION: We have defined sonographic descriptors that enable an unequivocal instant diagnosis for a list of 20 major congenital anomalies: the 'INDIAMAN-20' (INstant DIAgnosis of Major ANomalies) protocol. We believe that using this approach may facilitate focused training of less experienced operators and that it may be incorporated into artificial intelligence and deep learning protocols, further boosting the instant prenatal recognition of these lethal or life-threatening malformations. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Antenatal corticosteroids and perinatal outcome in late fetal growth restriction: analysis of prospective cohort.

OBJECTIVE: To evaluate the role of antenatal administration of corticosteroids for fetal lung maturation on the short-term perinatal outcome of pregnancy complicated by late fetal growth restriction (FGR). METHODS: This cohort study was a secondary analysis of a multicenter prospective observational study, the TRUFFLE-2 feasibility study, conducted between 2017 and 2018 in 33 European perinatal centers. The study included women with a singleton pregnancy from 32 + 0 to 36 + 6 weeks of gestation with a fetus considered at risk for FGR, defined as estimated fetal weight (EFW) and/or fetal abdominal circumference < 10th percentile, or umbilicocerebral ratio (UCR) ≥ 95th percentile or a drop of more than 40 percentile points in abdominal circumference measurement from the 20-week scan. For the purposes of the current study, we identified women who received a single course of steroids to improve fetal lung maturation before delivery. Each exposed pregnancy was matched with one that did not receive antenatal corticosteroids (ACS) (control), based on gestational age at delivery and birth weight. The primary adverse outcome was a composite of abnormal condition at birth, major neonatal morbidity or perinatal death. RESULTS: A total of 86 pregnancies that received ACS were matched to 86 controls. The two groups were similar with respect to gestational age (33.1 vs 33.3 weeks), EFW (1673 vs 1634 g) and UCR (0.68 vs 0.62) at inclusion, and gestational age at delivery (35.5 vs 35.9 weeks) and birth weight (1925 vs 1948 g). No significant differences were observed between the exposed and non-exposed groups in the incidence of composite adverse outcome (28% vs 24%; P = 0.73) or any of its elements. CONCLUSION: The present data do not show a beneficial effect of steroids on short-term outcome of fetuses with late FGR. © 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.

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.

Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Incidence, clinical features and perinatal outcome in anomalous fetuses with late-onset growth restriction: cohort study.

OBJECTIVE: To describe the incidence, clinical features and perinatal outcome of late-onset fetal growth restriction (FGR) associated with genetic syndrome or aneuploidy, structural malformation or congenital infection. METHODS: This was a retrospective multicenter cohort study of patients who attended one of four tertiary maternity hospitals in Italy. We included consecutive singleton pregnancies between 32 + 0 and 36 + 6 weeks' gestation with either fetal abdominal circumference (AC) or estimated fetal weight < 10th percentile for gestational age or a reduction in AC of > 50 percentiles from the measurement at an ultrasound scan performed between 18 and 32 weeks. The study group consisted of pregnancies with late-onset FGR and a genetic syndrome or aneuploidy, structural malformation or congenital infection (anomalous late-onset FGR). The presence of congenital anomalies was ascertained postnatally in neonates with abnormal findings on antenatal investigation or detected after birth. The control group consisted of pregnancies with structurally and genetically normal fetuses with late-onset FGR. Composite adverse perinatal outcome was defined as the presence of at least one of stillbirth, 5-min Apgar score < 7, admission to the neonatal intensive care unit (NICU), need for respiratory support at birth, neonatal jaundice and neonatal hypoglycemia. The primary aims of the study were to assess the incidence and clinical features of anomalous late-onset FGR, and to compare the perinatal outcome of such cases with that of fetuses with non-anomalous late-onset FGR. RESULTS: Overall, 1246 pregnancies complicated by late-onset FGR were included in the study, of which 120 (9.6%) were allocated to the anomalous late-onset FGR group. Of these, 11 (9.2%) had a genetic syndrome or aneuploidy, 105 (87.5%) had an isolated structural malformation, and four (3.3%) had a congenital infection. The most frequent structural defects associated with late-onset anomalous FGR were genitourinary malformations (28/105 (26.7%)) and limb malformation (21/105 (20.0%)). Compared with the non-anomalous late-onset FGR group, fetuses with anomalous late-onset FGR had an increased incidence of composite adverse perinatal outcome (35.9% vs 58.3%; P < 0.01). Newborns with anomalous, compared to those with non-anomalous, late-onset FGR showed a higher frequency of need for respiratory support at birth (25.8% vs 9.0%; P < 0.01), intubation (10.0% vs 1.1%; P < 0.01), NICU admission (43.3% vs 22.6%; P < 0.01) and longer hospital stay (median, 24 days (range, 4-250 days) vs 11 days (range, 2-59 days); P < 0.01). CONCLUSIONS: Most pregnancies complicated by anomalous late-onset FGR have structural malformations rather than genetic abnormality or infection. Fetuses with anomalous late-onset FGR have an increased incidence of complications at birth and NICU admission and a longer hospital stay compared with fetuses with isolated late-onset FGR. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

External validation of a simple risk score based on the ASPRE trial algorithm for preterm pre-eclampsia considering maternal characteristics in nulliparous pregnant women: a multicentre retrospective cohort study.

OBJECTIVE: To validate the performance of a first-trimester simple risk score based on the ASPRE trial algorithm for pre-eclampsia. DESIGN: Multicentre retrospective cohort analysis. SETTING: Four Italian hospitals. POPULATION: Unselected nulliparous women at 11-13 weeks of gestation from January 2014 through to January 2018. METHODS: Model performance was evaluated based on discrimination and calibration. MAIN OUTCOME MEASURES: Delivery before 37 weeks of gestation with a diagnosis of pre-eclampsia. RESULTS: Based on 73 preterm pre-eclampsia cases and 7546 controls (including 101 cases of late pre-eclampsia), the area under the receiver operating characteristics curve was 0.659 (95% CI 0.579-0.726). The sensitivity was 32.9% (95% CI 22.1-43.7) at a false-positive rate of 8.8%. The positive likelihood ratio was 3.74 (95% CI 2.67-5.23), the positive predictive value was 3.49% (95% CI 2.12-4.86%) and the negative predictive value was 99.3% (95% CI 99.1-99.5%). The sensitivity and positive likelihood ratio were approximately 40% lower than in the original study. The calibration analysis showed a good agreement between observed and expected risks (P = 0.037). Comparison with the Fetal Medicine Foundation (FMF) algorithm yielded a difference in the area under the curve of 0.084 (P = 0.007). CONCLUSIONS: In our Italian population, the simple risk score had a lower performance than expected for the prediction of preterm pre-eclampsia in nulliparous women. The FMF algorithm applied to the same data set resulted in a better prediction. TWEETABLE ABSTRACT: Simple risk score predicts preterm pre-eclampsia in Italy.

Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis.

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.

Comparative analysis of 2-year outcomes in GRIT and TRUFFLE trials.

OBJECTIVE: To explore the effect on perinatal outcome of different fetal monitoring strategies for early-onset fetal growth restriction (FGR). METHODS: This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age. RESULTS: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P < 0.01). The rate of survival without impairment at 2 years was lowest in pregnancies that underwent immediate delivery (70% (95% CI, 61-78%)) or delayed delivery with monitoring by CTG (69% (95% CI, 57-82%)), increased in those monitored using cCTG only in both GRIT (80% (95% CI, 68-91%)) and TRUFFLE (77% (95% CI, 70-84%)), and was highest in pregnancies monitored using cCTG and DV Doppler (84% (95% CI, 80-89%)) (P < 0.01 for trend). CONCLUSIONS: This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early-onset FGR is a combination of cCTG and DV Doppler assessment. TRIAL REGISTRATION: GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Análisis comparativo de los resultados a los 2 años de edad en los ensayos GRIT y TRUFFLE OBJETIVO: Examinar el efecto sobre el resultado perinatal de diferentes estrategias de monitoreo del feto para la restricción del crecimiento fetal (RCF) de inicio precoz. MÉTODOS: Este estudio realizó un análisis de cohortes de datos de participantes individuales en dos ensayos multicéntricos europeos de métodos de monitoreo fetal para la RCF: el Estudio de Intervención en la Restricción del Crecimiento (GRIT, por sus siglas en inglés) y el Ensayo Europeo de Flujo Umbilical y Fetal (TRUFFLE, por sus siglas en inglés). Se incluyeron todas las mujeres de GRIT (n = 238) y de TRUFFLE (n = 503) que habían sido asignadas al azar entre 26 y 32 semanas de gestación. Las mujeres se agruparon según el método de intervención y monitoreo: parto inmediato (GRIT) o parto diferido con monitoreo mediante cardiotocografía convencional (CTG) (GRIT), solo CTG digital (cCTG, por sus siglas en inglés) (GRIT y TRUFFLE) o cCTG y Doppler del conducto de Arancio (DV) (TRUFFLE). La medida de resultado primaria fue la supervivencia sin deterioro del desarrollo neurológico a los dos años de edad. RESULTADOS: La edad gestacional al momento del parto y el peso al nacer fueron similares en ambos estudios. La tasa de mortalidad fetal fue similar entre los grupos de GRIT y TRUFFLE, pero la muerte neonatal y tardía fue más frecuente en el grupo de GRIT (18% vs 6%; P < 0,01). La tasa de supervivencia sin deterioro a los dos años fue más baja en los embarazos que se sometieron a un parto inmediato (70% (IC 95%, 61-78%)) o a un parto tardío con monitoreo mediante CTG (69% (IC 95%, 57-82%)), más alta en los monitoreados solo mediante cCTG en GRIT (80% (IC 95%, 68-91%)) y TRUFFLE (77% (IC 95%, 70-84%)), y mayor aun en los embarazos monitoreados mediante cCTG y Doppler DV (84% (IC 95%, 80-89%)) (P < 0,01 para tendencia). CONCLUSIONES: Este análisis apoya la hipótesis de que el método óptimo para el monitoreo fetal en los embarazos complicados por RCF de inicio precoz es una combinación de cCTG y evaluación Doppler DV. INSCRIPCIÓN DEL ENSAYO: GRIT ISRCTN41358726 y TRUFFLE ISRCTN56204499. © 2019 Los autores. Ultrasonido en Obstetricia y Ginecología publicado por John Wiley & Sons Ltd. en nombre de la Sociedad Internacional de Ultrasonido en Obstetricia y Ginecología.

Quality assessment of fetal middle cerebral and umbilical artery Doppler images using an objective scale within an international randomized controlled trial.

OBJECTIVES: To determine the quality of Doppler images of the fetal middle cerebral artery (MCA) and umbilical artery (UA) using an objective scale, and to determine the reliability of this scale, within a multicenter randomized controlled trial (Revealed versus concealed criteria for placental insufficiency in unselected obstetric population in late pregnancy (Ratio37)). METHODS: The Ratio37 trial is an ongoing randomized, open-label, multicenter controlled study of women with a low-risk pregnancy recruited at 20 weeks. Doppler measurements of the fetal MCA and UA were performed at 37 weeks. Twenty patients from each of the six participating centers were selected randomly, with two images evaluated per patient (one each for the MCA and UA). The quality of a total of 240 images was evaluated by six experts, scored on an objective scale of six items. Inter- and intrarater reliability was assessed using the Fleiss-modified kappa statistic for ordinal scales. RESULTS: On average, 89.2% of MCA images and 85.0% of UA images were rated as being of perfect (score of 6) or almost perfect (score of 5) quality. Kappa values for intrarater reliability of quality assessment were 0.90 (95% CI, 0.88-0.92) and 0.90 (95% CI, 0.88-0.93) for the MCA and UA, respectively. The corresponding inter-rater reliability values were 0.85 (95% CI, 0.81-0.89) and 0.84 (95% CI, 0.80-0.89), respectively. CONCLUSION: The quality of MCA and UA Doppler ultrasound images can be evaluated reliably using an objective scale. Over 85% of images, which were obtained by operators from a broad range of clinical practices within a multicenter study, were rated as being of perfect or almost perfect quality. Intra- and inter-rater reliability of quality assessment was very good. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Interobserver agreement in MRI assessment of severity of placenta accreta spectrum disorders.

OBJECTIVE: To evaluate the level of agreement in the prenatal magnetic resonance imaging (MRI) assessment of the presence and severity of placenta accreta spectrum (PAS) disorders between examiners with expertise in the diagnosis and management of these conditions. METHODS: This was a secondary analysis of a prospective study including women with placenta previa or low-lying placenta and at least one prior Cesarean delivery or uterine surgery, who underwent MRI assessment at a regional referral center for PAS disorders in Italy, between 2007 and 2017. The MRI scans were retrieved from the hospital electronic database and assessed by four examiners, who are considered to be experts in the diagnosis and surgical management of PAS disorders. The examiners were blinded to the ultrasound diagnosis, histopathological findings and clinical data of the patients. Each examiner was asked to assess 20 features on the MRI scans, including the presence, depth and topography of placental invasion. Depth of invasion was defined as the degree of adhesion and invasion of the placenta into the myometrium and uterine serosa (placenta accreta, increta or percreta) and the histopathological examination of the removed uterus was considered the reference standard. Topography of the placental invasion was defined as the site of placental invasion within the uterus in relation to the posterior bladder wall (posterior upper bladder wall and uterine body, posterior lower bladder wall and lower uterine segment and cervix or no visible bladder invasion) and the site of invasion at surgery was considered the reference standard. The degree of interrater agreement (IRA) was evaluated by calculating both the percentage of observed agreement among raters and the Fleiss kappa (κ) value. RESULTS: Forty-six women were included in the study. The median gestational age at MRI was 33.8 (interquartile range, 33.1-34.0) weeks. A final diagnosis of placenta accreta, increta and percreta was made in 15.2%, 17.4% and 50.0% patients, respectively. There was excellent agreement between the four examiners in the assessment of the overall presence of a PAS disorder (IRA, 92.1% (95% CI, 86.8-94.0%); κ, 0.90 (95% CI, 0.89-1.00)). However, there was significant heterogeneity in IRA when assessing the different MRI signs suggestive of a PAS disorder. There was excellent agreement between the examiners in the identification of the depth of placental invasion on MRI (IRA, 98.9% (95% CI, 96.8-100.0%); κ, 0.95 (95% CI, 0.89-1.00)). However, agreement in assessing the topography of placental invasion was only moderate (IRA, 72.8% (95% CI, 72.7-72.9%); κ, 0.56 (95% CI, 0.54-0.66)). More importantly, when assessing parametrial invasion, which is one of the most significant prognostic factors in women affected by PAS, the agreement was substantial and moderate in judging the presence of invasion in the coronal (IRA, 86.6% (95% CI, 86.5-86.7%); κ, 0.69 (95% CI, 0.59-0.71)) and axial (IRA, 78.6% (95% CI, 78.5-78.7%); κ, 0.56 (95% CI, 0.33-0.60)) planes, respectively. Likewise, interobserver agreement in judging the presence and the number of newly formed vessels in the parametrial tissue was moderate (IRA, 88.0% (95% CI, 88.0-88.1%); κ, 0.59 (95% CI, 0.45-0.68)) and fair (IRA, 66.7% (95% CI, 66.6-66.7%); κ, 0.22 (95% CI, 0.12-0.37)), respectively. CONCLUSIONS: MRI has excellent interobserver agreement in detecting the presence and depth of placental invasion, while agreement between the examiners is lower when assessing the topography of invasion. The findings of this study highlight the need for a standardized MRI staging system for PAS disorders, in order to facilitate objective correlation between prenatal imaging, pregnancy outcome and surgical management of these patients. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Intracervical lakes as sonographic marker of placenta accreta spectrum disorder in patients with placenta previa or low-lying placenta.

OBJECTIVE: To evaluate the diagnostic accuracy of a new ultrasound sign, intracervical lakes (ICL), in predicting the presence of placenta accreta spectrum (PAS) disorder and delivery outcome in patients with placenta previa or low-lying placenta. METHODS: This was a retrospective multicenter study of women with placenta previa or low-lying placenta at ≥ 26 weeks' gestation, who were referred to three Italian tertiary units from January 2015 to September 2018. The presence of ICL, defined as tortuous anechoic spaces within the cervix which appeared to be hypervascular on color Doppler, was evaluated on ultrasound images obtained at the time of referral. The primary aim was to explore the diagnostic accuracy of ICL in detecting the presence and depth of PAS disorder. The secondary aim was to explore the accuracy of this sign in predicting total estimated blood loss, antepartum bleeding, major postpartum hemorrhage at the time of Cesarean section and need for Cesarean hysterectomy. The diagnostic accuracy of ICL in combination with typical sonographic signs of PAS disorder, was assessed by computing summary estimates of sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and diagnostic odds ratios (DOR). RESULTS: A total of 332 women with placenta previa or low-lying placenta were included in the analysis, with a median maternal age of 33.0 (interquartile range, 29.0-37.0) years. ICL were noted in 15.1% of patients. On logistic regression analysis, the presence of ICL was associated independently with major postpartum hemorrhage (odds ratio (OR), 3.3 (95% CI, 1.6-6.5); P < 0.001), Cesarean hysterectomy (OR, 7.0 (95% CI, 2.1-23.9); P < 0.001) and placenta percreta (OR, 2.8 (95% CI, 1.3-5.8); P ≤ 0.01), but not with the presence of any PAS disorder (OR, 1.6 (95% CI, 0.7-3.5); P = 0.2). Compared with the group of patients without ultrasound signs of PAS disorder, the presence of at least one typical sonographic sign of PAS disorder in combination with ICL had a DOR of 217.2 (95% CI, 27.7-1703.4; P < 0.001) for placenta percreta and of 687.4 (95% CI, 121.4-3893.0; P < 0.001) for Cesarean hysterectomy. CONCLUSION: ICL may represent a marker of deep villus invasion in women with suspected PAS disorder on antenatal sonography and anticipate the occurrence of severe maternal morbidity. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Los espacios intracervicales como marcador ecográfico de trastornos del espectro de la placenta acreta en pacientes con placenta previa o placenta baja OBJETIVO: Evaluar la precisión del diagnóstico de un nuevo indicio de ultrasonido, los espacios intracervicales (EIC), para predecir la presencia de trastornos del espectro de la placenta acreta (EPA) y el resultado del parto en pacientes con placenta previa o placenta baja. MÉTODOS: Este fue un estudio multicéntrico retrospectivo de mujeres con placenta previa o placenta baja a ≥ 26 semanas de gestación, que se remitieron a tres unidades terciarias italianas desde enero de 2015 a septiembre de 2018. Se evaluó la presencia de EIC, definida como espacios anecoicos tortuosos dentro del cuello uterino que parecían ser hipervasculares en el Doppler a color, en imágenes de ecografías obtenidas en el momento de la remisión. El objetivo principal fue estudiar la precisión del diagnóstico mediante EIC en la detección de la presencia y la profundidad de un trastorno del EPA. El objetivo secundario fue explorar la precisión de este indicador para predecir la pérdida total estimada de sangre, la hemorragia antes del parto, la hemorragia puerperal importante en el momento de la cesárea y la necesidad de una histerectomía por cesárea. La precisión diagnóstica de EIC, en combinación con los indicios ecográficos típicos de los trastornos del EPA, se evaluó calculando estimaciones estadísticas descriptivas de la sensibilidad, la especificidad, los valores predictivos positivos y negativos, los cocientes de verosimilitud positivos y negativos y las razones de momios del diagnóstico (RMD). RESULTADOS: En el análisis se incluyó un total de 332 mujeres con placenta previa o placenta baja, con una mediana de la edad materna de 33,0 años (rango intercuartil, 29,0-37,0). Se observaron EIC en el 15,1% de las pacientes. En el análisis de regresión logística, la presencia de EIC se asoció de forma independiente con la hemorragia puerperal grave (razón de momios (RM), 3,3 (IC 95%, 1,6-6,5); P<0,001), la histerectomía por cesárea (RM, 7,0 (IC 95%, 2,1-23,9); P<0,001) y la placenta percreta (RM, 2,8 (IC 95%, 1,3-5,8); P≤0,01), pero no con la presencia de ningún trastorno del EPA (RM, 1,6 (IC 95%, 0,7-3,5); P=0,2). En comparación con el grupo de pacientes sin indicios de ultrasonido de algún trastorno del EPA, la presencia de al menos un indicio ecográfico típico de trastorno del EPA en combinación con EIC tuvo una RMD de 217,2 (IC 95%, 27,7-1703,4; P<0,001) para la placenta percreta y de 687,4 (IC 95%, 121,4-3893,0; P<0,001) para la histerectomía por cesárea. CONCLUSIÓN: Los EIC pueden representar un marcador de invasión profunda de las vellosidades en mujeres con sospecha de algún trastorno del EPA basado en la ecografía prenatal y anticipar la presencia de una morbilidad materna grave.

Outcome of twin-to-twin transfusion syndrome in monochorionic monoamniotic twin pregnancy: systematic review and meta-analysis.

OBJECTIVES: To explore the outcome of monochorionic monoamniotic (MCMA) twin pregnancies affected by twin-to-twin transfusion syndrome (TTTS). METHODS: MEDLINE and EMBASE databases were searched for studies reporting the outcome of MCMA twin pregnancies complicated by TTTS. The primary outcome was intrauterine death (IUD); secondary outcomes were miscarriage, single IUD, double IUD, neonatal death (NND), perinatal death (PND), survival of at least one twin, survival of both twins and preterm birth (PTB) before 32 weeks' gestation. Outcomes were assessed in MCMA twins affected by TTTS not undergoing intervention and in those treated with amniodrainage, laser therapy or cord occlusion. Subgroup analysis was performed including cases diagnosed before 24 weeks. Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Fifteen cohort studies, including 888 MCMA twin pregnancies, of which 44 were affected by TTTS, were included in the review. There was no randomized trial comparing the different management options in MCMA twin pregnancies complicated by TTTS. In cases not undergoing intervention, miscarriage occurred in 11.0% of fetuses, while the incidence of IUD, NND and PND was 25.2%, 12.2% and 31.2%, respectively. PTB complicated 50.5% of these pregnancies. In cases treated by laser surgery, the incidence of miscarriage, IUD, NND and PND was 19.6%, 27.4%, 7.4% and 35.9%, respectively, and the incidence of PTB before 32 weeks' gestation was 64.9%. In cases treated with amniodrainage, the incidence of IUD, NND and PND was 31.3%, 13.5% and 45.7% respectively, and PTB complicated 76.2% of these pregnancies. Analysis of cases undergoing cord occlusion was affected by the very small number of included cases. Miscarriage occurred in 19.2%, while there was no case of IUD or NND of the surviving twin. PTB before 32 weeks occurred in 50.0% of these cases. CONCLUSIONS: MCMA twin pregnancies complicated by TTTS are at high risk of perinatal mortality and PTB. Further studies are needed in order to elucidate the optimal type of prenatal treatment in these pregnancies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal mortality, timing of delivery and prenatal management of monoamniotic twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To quantify the rate of perinatal mortality in monochorionic monoamniotic (MCMA) twin pregnancies, according to gestational age, and to ascertain the incidence of mortality in pregnancies managed as inpatients compared with those managed as outpatients. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies on monoamniotic twin pregnancy. The primary outcomes explored were the incidence of intrauterine death (IUD), neonatal death (NND) and perinatal death (PND) in MCMA twins at different gestational-age windows (24-30, 31-32, 33-34, 35-36 and ≥ 37 weeks of gestation). The secondary outcomes were the incidence of IUD, NND and PND in MCMA twins according to the type of fetal monitoring (inpatient vs outpatient), and the incidence of delivery ahead of schedule. Random-effects model meta-analyses were used to analyze the data. RESULTS: Twenty-five studies (1628 non-anomalous twins reaching 24 weeks of gestation) were included. Single and double intrauterine deaths occurred in 2.5% (95% CI, 1.8-3.3%) and 3.8% (95% CI, 2.5-5.3%) of cases, respectively. IUD occurred in 4.3% (95% CI, 2.8-6.2%) of twins at 24-30 weeks, in 1.0% (95% CI, 0.6-1.7%) at 31-32 weeks and in 2.2% (95% CI, 0.9-3.9%) at 33-34 weeks of gestation, while there was no case of IUD, either single or double, from 35 weeks of gestation. In MCMA twin pregnancies managed mainly as inpatients, the incidence of IUD was 3.0% (95% CI, 1.4-5.2%), while the corresponding figure for those managed mainly as outpatients was 7.4% (95% CI, 4.4-11.1%). Finally, 37.8% (95% CI, 28.0-48.2%) of MCMA pregnancies were delivered before the scheduled time, due mainly to spontaneous preterm labor or abnormal cardiotocographic findings. CONCLUSIONS: MCMA twins are at high risk of perinatal loss during the third trimester of pregnancy, with the large majority of such losses occurring as apparently unexpected events. Inpatient management seems to be associated with a lower rate of mortality, although further studies are needed in order to establish the appropriate type and timing of prenatal assessment in these pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound evaluation of left ventricular and aortic fibrosis after pre-eclampsia.

OBJECTIVES: Myocardial fibrosis is associated with adverse clinical outcome in adults. Our aim was to investigate using echocardiographic calibrated integrated backscatter (cIBS) the presence of myocardial and/or aortic fibrosis in asymptomatic women with a history of early-onset (EO) or late-onset (LO) pre-eclampsia (PE). METHODS: Thirty non-pregnant women whose most recent pregnancy was complicated by EO-PE, 30 with previous LO-PE pregnancy and 30 controls who had experienced only uncomplicated pregnancy previously were selected retrospectively from our electronic database and recalled between 6 months and 4 years after delivery. Data regarding gestational age (GA) and mean uterine artery (UtA) pulsatility index (PI) at diagnosis of PE were collected from their medical records. The women underwent cardiovascular assessment, during which the presence of fibrosis was investigated, by means of cIBS, at the basal interventricular septum (cIBSIVS ), the basal posterior wall (cIBSPW ) and the anterior wall of the ascending aorta, 3 cm above the valve (cIBSAO ). These findings were compared between the three patient groups. RESULTS: Using cIBS imaging, we found significant left ventricular (LV) fibrosis in women with a history of EO-PE compared with those with previous LO-PE pregnancy and controls (intergroup ANOVA P < 0.001 for cIBSIVS and P = 0.005 for cIBSPW ), whereas aortic fibrosis did not differ significantly among cases and controls. Stepwise multivariate regression analysis showed that LV fibrosis was associated independently with lower GA and higher mean UtA-PI at diagnosis of PE, while cIBSAO correlated with aortic diameters, stiffness and ventricular-arterial coupling. CONCLUSIONS: Women with a history of EO-PE show LV fibrosis in the short-medium term after delivery compared with women with previous LO-PE pregnancy and controls. LV fibrosis is associated with GA and mean UtA-PI at onset of PE. Larger studies using cardiac magnetic resonance imaging are needed to validate and confirm our findings. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cervical-length measurement in mid-gestation to predict spontaneous preterm birth in asymptomatic triplet pregnancy.

OBJECTIVE: To assess the predictive value of sonographic cervical-length (CL) measurement in mid-gestation for spontaneous preterm birth (PTB) in asymptomatic triplet pregnancy. METHODS: This was a retrospective study of asymptomatic triplet pregnancies followed at five Italian tertiary referral centers, between 2002 and 2015. CL was measured transvaginally between 18 and 24 weeks' gestation. Pregnancies with medically indicated PTB were excluded. Demographic and pregnancy characteristics of pregnancies complicated by PTB were analyzed and the distributions of CL measurements in these patients were calculated. Logistic regression analysis was performed to assess the association between CL and PTB, adjusted for confounders. Performance of CL measurement in prediction of PTB < 28, < 30 and < 32 weeks of gestation was assessed. RESULTS: A total of 120 triplet pregnancies were included in the final analysis. Median CL was 35 (interquartile range (IQR), 29-40) mm measured at a median gestational age of 20 + 2 (IQR, 20 + 0 to 23 + 4) weeks. Overall, 23 (19.2%), 17 (14.2%) and eight (6.7%) patients had a CL < 25, < 20 and < 15 mm, respectively. Spontaneous PTB < 32 weeks occurred in 41 (34.2%) cases, < 30 weeks in 23 (19.2%) and < 28 weeks in 12 (10%) cases. CL < 15 mm was significantly more frequent in the group of patients who delivered < 28 (P = 0.03) and < 30 (P = 0.01) weeks' gestation, compared with those who delivered after 28 and after 30 weeks, respectively, while CL < 20 mm was more common in triplet pregnancies with delivery < 32 weeks compared with those delivered ≥ 32 weeks (P = 0.03). Logistic regression analysis was possible only for PTB < 32 weeks due to the small number of cases that delivered < 30 and < 28 weeks. After adjustment for confounders, CL was not significantly associated with PTB < 32 weeks (adjusted odds ratio, 0.97; 95% CI, 0.94-1.01). CL measurement had an area under the receiver-operating characteristics curve of 0.41 (95% CI, 0.20-0.62), 0.41 (95% CI, 0.26-0.56) and 0.42 (95% CI, 0.31-0.54) for the prediction of spontaneous PTB < 28, < 30 and < 32 weeks, respectively. CONCLUSION: CL assessed in mid-gestation is a poor predictor of PTB < 28, < 30 and < 32 weeks' gestation in asymptomatic triplet pregnancy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Weight discordance and perinatal mortality in twin pregnancy: systematic review and meta-analysis.

OBJECTIVES: The primary aim of this systematic review was to explore the strength of association between birth-weight (BW) discordance and perinatal mortality in twin pregnancy. The secondary aim was to ascertain the contribution of gestational age and growth restriction in predicting mortality in growth-discordant twins. METHODS: MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched. Only studies reporting on the risk of mortality in twin pregnancies affected compared with those not affected by BW discordance were included. The primary outcomes explored were incidence of intrauterine death (IUD), neonatal death (NND) and perinatal death. Outcome was assessed separately for monochorionic (MC) and dichorionic (DC) twin pregnancies. Analyses were stratified according to BW discordance cut-off (≥ 15%, ≥ 20%, ≥ 25% and ≥ 30%) and selected gestational characteristics, including incidence of IUD or NND before and after 34 weeks' gestation, presence of at least one small-for-gestational age (SGA) fetus in the twin pair and both twins being appropriate-for-gestational age. Risk of mortality in the larger vs smaller twin was also assessed. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportion were used to analyze the data. RESULTS: Twenty-two studies (10 877 twin pregnancies) were included in the analysis. In DC pregnancies, a higher risk of IUD, but not of NND, was observed in twins with BW discordance ≥ 15% (odds ratio (OR) 9.8, 95% CI, 3.9-29.4), ≥ 20% (OR 7.0, 95% CI, 4.15-11.8), ≥ 25% (OR 17.4, 95% CI, 8.3-36.7) and ≥ 30% (OR 22.9, 95% CI, 10.2-51.6) compared with those without weight discordance. For each cut-off of BW discordance explored in DC pregnancies, the smaller twin was at higher risk of mortality compared with the larger one. In MC twin pregnancies, excluding cases affected by twin-twin transfusion syndrome, twins with BW discordance ≥ 20% (OR 2.8, 95% CI, 1.3-5.8) or ≥ 25% (OR 3.2, 95% CI, 1.5-6.7) were at higher risk of IUD, compared with controls. MC pregnancies with ≥ 25% weight discordance were also at increased risk of NND (OR 4.66, 95% CI, 1.8-12.4) compared with those with concordant weight. The risk of IUD was higher when considering discordant pregnancies involving at least one SGA fetus. The overall risk of mortality in MC pregnancies was similar between the smaller and larger twin, except in those with BW discordance ≥ 20%. CONCLUSION: DC and MC twin pregnancies discordant for fetal growth are at higher risk of IUD but not of NND compared with pregnancies with concordant BW. The risk of IUD in BW-discordant DC and MC twins is higher when at least one fetus is SGA. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.