Long-term outcome of peripheral T-cell lymphomas: Ten-year follow-up of the International Prospective T-cell Project.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs.

Reference ranges for fetal brain structures using magnetic resonance imaging: systematic review.

OBJECTIVE: To evaluate the methodology of studies reporting reference ranges for fetal brain structures on magnetic resonance imaging (MRI). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to 31 December 2020 to identify studies investigating biometry and growth of the fetal brain and reporting reference ranges for brain structures using MRI. The primary aim was to evaluate the methodology of these studies. A list of 26 quality criteria divided into three domains, including 'study design', 'statistical and reporting methods' and 'specific aspects relevant to MRI', was developed and applied to evaluate the methodological appropriateness of each of the included studies. The overall quality score of a study, ranging between 0 and 26, was defined as the sum of scores awarded for each quality criterion and expressed as a percentage (the lower the percentage, the higher the risk of bias). RESULTS: Fifteen studies were included in this systematic review. The overall mean quality score of the studies evaluated was 48.7%. When focusing on each domain, the mean quality score was 42.0% for 'study design', 59.4% for 'statistical and reporting methods' and 33.3% for 'specific aspects relevant to MRI'. For the 'study design' domain, sample size calculation and consecutive enrolment of women were the items found to be at the highest risk of bias. For the 'statistical and reporting methods' domain, the presence of regression equations for mean and SD for each measurement, the number of measurements taken for each variable and the presence of postnatal assessment information were the items found to be at the highest risk of bias. For the 'specific aspects relevant to MRI' domain, whole fetal brain assessment was not performed in any of the included studies and was therefore considered to be the item at the highest risk of bias. CONCLUSIONS: Most of the previously published studies reporting fetal brain reference ranges on MRI are highly heterogeneous and have low-to-moderate quality in terms of methodology, which is similar to the findings reported for ultrasound studies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Counseling in maternal-fetal medicine: SARS-CoV-2 infection in pregnancy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic coronavirus that crossed species to infect humans, causing coronavirus disease 2019 (COVID-19). Despite a potentially higher risk of pregnant women acquiring SARS-CoV-2 infection compared with the non-pregnant population (particularly in some ethnic minorities), no additional specific recommendations to avoid exposure are needed in pregnancy. The most common clinical symptoms and laboratory signs of SARS-CoV-2 infection in pregnancy are fever, cough, lymphopenia and elevated C-reactive protein levels. Pregnancy is associated with a higher risk of severe SARS-CoV-2 infection compared with the non-pregnant population, including pneumonia, admission to the intensive care unit and death, even after adjusting for potential risk factors for severe outcomes. The risk of miscarriage does not appear to be increased in women with SARS-CoV-2 infection. Evidence with regards to preterm birth and perinatal mortality is conflicting, but these risks are generally higher only in symptomatic, hospitalized women. The risk of vertical transmission, defined as the transmission of SARS-CoV-2 from the mother to the fetus or the newborn, is generally low. Fetal invasive procedures are considered to be generally safe in pregnant women with SARS-CoV-2 infection, although the evidence is still limited. In pregnant women with COVID-19, use of steroids should not be avoided if clinically indicated; the preferred regimen is a 2-day course of dexamethasone followed by an 8-day course of methylprednisolone. Non-steroidal anti-inflammatory drugs may be used if there are no contraindications. Hospitalized pregnant women with severe COVID-19 should undergo thromboprophylaxis throughout the duration of hospitalization and at least until discharge, preferably with low molecular weight heparin. Hospitalized women who have recovered from a period of serious or critical illness with COVID-19 should be offered a fetal growth scan about 14 days after recovery from their illness. In asymptomatic or mildly symptomatic women who have tested positive for SARS-CoV-2 infection at full term (i.e. ≥ 39 weeks of gestation), induction of labor might be reasonable. To date, there is no clear consensus on the optimal timing of delivery for critically ill women. In women with no or few symptoms, management of labor should follow routine evidence-based guidelines. Regardless of COVID-19 status, mothers and their infants should remain together and breastfeeding, skin-to-skin contact, kangaroo mother care and rooming-in throughout the day and night should be practiced, while applying necessary infection prevention and control measures. Many pregnant women have already undergone vaccination, mostly in the USA where the first reports show no significant difference in pregnancy outcomes in pregnant women receiving SARS-CoV-2 vaccination during pregnancy compared with the background risk. Vaccine-generated antibodies were present in the umbilical cord blood and breast milk samples of pregnant and lactating women who received the mRNA COVID-19 vaccine. Based on the available limited data on the safety of the COVID-19 vaccine in pregnancy, it seems reasonable to offer the option of vaccination to pregnant women after accurate counseling on the potential risk of a severe course of the disease and the unknown risk of fetal exposure to the vaccine. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Biological insight into the extracellular vesicles in women with and without gestational diabetes.

PURPOSE: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, with increasing prevalence worldwide and still unclear pathogenic mechanisms. Extracellular vesicles (EVs) are emerging as potential biomarkers of disease-specific pathways in metabolic disorders, but their potential role in GDM is not fully understood. Therefore, the main aim of this study was to evaluate the link between EVs and hyperglycaemia during pregnancy. METHODS: We assessed 50 GDM women and 50 controls at the third trimester of pregnancy in whom we collected demographic characteristics and clinical and anthropometric parameters. In addition, the circulating total EVs (tEVs) and their subpopulations were assessed using flow cytometry. RESULTS: The levels of tEVs and EVs subtypes, expressed as median and interquartile range, were not significantly different between two groups; however, adipocyte-derived EVs (aEVs) concentration, expressed as percentage, was higher in controls than in GDM women (p = 0.045). In addition, a significant correlation was observed between aEVs (%) and third trimester total cholesterol (p = 0.022) within the GDM group. Furthermore, a significant correlation between endothelial-derived EVs (eEVs) and platelet-derived EVs (pEVs) within both groups was found, as well as a significant relation between aEVs and pEVs. CONCLUSIONS: These data, although preliminary, represent the starting point for further studies to determine the role of circulating EVs in GDM.

Outcome of fetuses with congenital cytomegalovirus infection and normal ultrasound at diagnosis: systematic review and meta-analysis.

OBJECTIVE: To report the outcome of fetuses with congenital cytomegalovirus (CMV) infection and normal ultrasound at the time of diagnosis, and to evaluate the rate of an additional anomaly detected only on magnetic resonance imaging (MRI). METHODS: Medline, EMBASE, CINAHL and Cochrane databases were searched for studies reporting on the outcome of fetuses with congenital CMV infection. Inclusion criteria were fetuses with confirmed CMV infection and normal ultrasound assessment at the time of the initial evaluation. The outcomes observed were an anomaly detected on a follow-up ultrasound scan, an anomaly detected on prenatal MRI but missed on ultrasound, an anomaly detected on postnatal assessment but missed prenatally, perinatal mortality, symptomatic infection at birth, neurodevelopmental outcome and hearing and visual deficits. Neurodevelopmental outcome was assessed only in cases of isolated CMV infection confirmed at birth. Subgroup analysis was performed according to the trimester in which maternal infection occurred. Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Twenty-six studies were included, comprising 2603 fetuses with congenital CMV infection, of which 1178 (45.3%) had normal ultrasound at the time of diagnosis and were included in the analysis. The overall rate of an associated central nervous system (CNS) anomaly detected on a follow-up ultrasound scan was 4.4% (95% CI, 1.4-8.8%) (32/523; 15 studies), while the rates of those detected exclusively on prenatal MRI or on postnatal imaging were 5.8% (95% CI, 1.9-11.5%) (19/357; 11 studies) and 3.2% (95% CI, 0.3-9.0%) (50/660; 17 studies), respectively. The rate of an associated extra-CNS anomaly detected on a follow-up ultrasound scan was 2.9% (95% CI, 0.8-6.3%) (19/523; 15 studies), while the rates of those detected exclusively on MRI or on postnatal imaging were 0% (95% CI, 0.0-1.7%) (0/357; 11 studies) and 0.9% (95% CI, 0.3-1.8%) (4/660; 17 studies), respectively. Intrauterine death and perinatal death each occurred in 0.7% (95% CI, 0.3-1.4%) (2/824; 23 studies) of cases. In cases without an associated anomaly detected pre- or postnatally, symptomatic infection was found in 1.5% (95% CI, 0.7-2.7%) (6/548; 19 studies) of infants, the overall rate of a neurodevelopmental anomaly was 3.1% (95% CI, 1.6-5.1%) (16/550; 19 studies), and hearing problems affected 6.5% (95% CI, 3.8-10.0%) (36/550; 19 studies) of children. Subanalyses according to the trimester in which maternal infection occurred were affected by the very small number of included cases and lack of comparison of the observed outcomes in the original studies. Compared with fetuses infected in the second or third trimester, those infected in the first trimester had a relatively higher risk of having an additional anomaly detected on follow-up ultrasound or MRI, abnormal neurodevelopmental outcome and hearing problems. CONCLUSIONS: In fetuses with congenital CMV infection in which no anomalies are detected on prenatal ultrasound or MRI, the risk of adverse postnatal outcome is lower than that reported previously in the published literature when not considering the role of antenatal imaging assessment. The results from this review also highlight the potential role of MRI, even in fetuses with no anomalies detected on ultrasound, as an anomaly can be detected exclusively on MRI in about 6% of cases. The findings from this study could enhance prenatal counseling of pregnancies with congenital CMV infection with normal prenatal imaging. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Risk factors, histopathology and diagnostic accuracy in posterior placenta accreta spectrum disorders: systematic review and meta-analysis.

OBJECTIVE: To elucidate the risk factors, histopathological correlations and diagnostic accuracy of prenatal imaging in pregnancies complicated by posterior placenta accreta spectrum (PAS) disorders. METHODS: MEDLINE, EMBASE and CINAHL were searched for studies reporting on women with posterior PAS. Inclusion criteria were women with posterior PAS confirmed either at surgery or on histopathological analysis. The outcomes explored were risk factors for posterior PAS, histopathological correlation and the diagnostic accuracy of ultrasound and magnetic resonance imaging (MRI) in detecting posterior PAS. Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Twenty studies were included. Placenta previa was present in 92.8% (107/114; 17 studies) of pregnancies complicated by posterior PAS, while 76.1% (53/88; 11 studies) of women had had prior uterine surgery, mainly a Cesarean section (CS) or curettage and 82.5% (66/77; 10 studies) were multiparous. When considering histopathological analysis in women affected by posterior PAS, 77.5% (34/44; 11 studies) had placenta accreta, 19.5% (8/44; 11 studies) had placenta increta and 9.3% (2/44; 11 studies) had placenta percreta. Of the cases of posterior PAS disorder, 52.4% (31/63; 12 studies) were detected prenatally on ultrasound, while 46.7% (32/63; 12 studies) were diagnosed only at birth. When exploring the distribution of the classic ultrasound signs of PAS, placental lacunae were present in 39.0% (12/30; seven studies), loss of the clear zone in 41.1% (13/30; seven studies) and bladder-wall interruption in 16.6% (4/30; seven studies) of women, while none of the included cases showed hypervascularization at the bladder-wall interface. When assessing the role of MRI in detecting posterior PAS, 73.5% (26/32; 11 studies) of cases were detected on prenatal MRI, while 26.5% (6/32; 11 studies) were discovered only at the time of CS. CONCLUSIONS: Placenta previa, prior uterine surgery and multiparity represent the most commonly reported risk factors for posterior PAS. Ultrasound had a very low diagnostic accuracy in detecting these disorders prenatally. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Cardiovascular events following pregnancy complicated by pre-eclampsia with emphasis on comparison between early- and late-onset forms: systematic review and meta-analysis.

OBJECTIVE: To elucidate whether pre-eclampsia (PE) and the gestational age at onset of the disease (early- vs late-onset PE) have an impact on the risk of long-term maternal cardiovascular complications. METHODS: MEDLINE, EMBASE and Scopus databases were searched until 15 April 2020 for studies evaluating the incidence of cardiovascular events in women with a history of PE, utilizing combinations of the relevant MeSH terms, keywords and word variants for 'pre-eclampsia', 'cardiovascular disease' and 'outcome'. Inclusion criteria were cohort or case-control design, inclusion of women with a diagnosis of PE at the time of the first pregnancy, and sufficient data to compare each outcome in women with a history of PE vs women with previous normal pregnancy and/or in women with a history of early- vs late-onset PE. The primary outcome was a composite score of maternal cardiovascular morbidity and mortality, including cardiovascular death, major cardiovascular and cerebrovascular events, hypertension, need for antihypertensive therapy, Type-2 diabetes mellitus, dyslipidemia and metabolic syndrome. Secondary outcomes were the individual components of the primary outcome analyzed separately. Data were combined using a random-effects generic inverse variance approach. MOOSE guidelines and the PRISMA statement were followed. RESULTS: Seventy-three studies were included. Women with a history of PE, compared to those with previous normotensive pregnancy, had a higher risk of composite adverse cardiovascular outcome (odds ratio (OR), 2.05 (95% CI, 1.9-2.3)), cardiovascular death (OR, 2.18 (95% CI, 1.8-2.7)), major cardiovascular events (OR, 1.80 (95% CI, 1.6-2.0)), hypertension (OR, 3.93 (95% CI, 3.1-5.0)), need for antihypertensive medication (OR, 4.44 (95% CI, 2.4-8.2)), dyslipidemia (OR, 1.32 (95% CI, 1.3-1.4)), Type-2 diabetes (OR, 2.14 (95% CI, 1.5-3.0)), abnormal renal function (OR, 3.37 (95% CI, 2.3-5.0)) and metabolic syndrome (OR, 4.30 (95% CI, 2.6-7.1)). Importantly, the strength of the associations persisted when considering the interval (< 1, 1-10 or > 10 years) from PE to the occurrence of these outcomes. When stratifying the analysis according to gestational age at onset of PE, women with previous early-onset PE, compared to those with previous late-onset PE, were at higher risk of composite adverse cardiovascular outcome (OR, 1.75 (95% CI, 1.0-3.0)), major cardiovascular events (OR, 5.63 (95% CI, 1.5-21.4)), hypertension (OR, 1.48 (95% CI, 1.3-1.7)), dyslipidemia (OR, 1.51 (95% CI, 1.3-1.8)), abnormal renal function (OR, 1.52 (95% CI, 1.1-2.2)) and metabolic syndrome (OR, 1.66 (95% CI, 1.1-2.5). CONCLUSIONS: Both early- and late-onset PE represent risk factors for maternal adverse cardiovascular events later in life. Early-onset PE is associated with a higher burden of cardiovascular morbidity and mortality compared to late-onset PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Risk of fetal loss following amniocentesis or chorionic villus sampling in twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure-related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure-related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head-to-head meta-analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta-analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls. RESULTS: Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head-to-head meta-analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4-3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9-4.6%) in those not undergoing amniocentesis. Head-to-head meta-analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0-6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3-4.2%) in those not undergoing CVS. CONCLUSION: The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Riesgo de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas en un embarazo de gemelos: revisión sistemática y metaanálisis OBJETIVO: Evaluar la tasa de pérdida del feto tras una amniocentesis o una biopsia de vellosidades coriónicas (BVC) en un embarazo de gemelos. MÉTODOS: Se hizo una búsqueda en las bases de datos MEDLINE, EMBASE y Cochrane de estudios que habían reportado complicaciones relacionadas con el procedimiento después de una amniocentesis o una BVC en un embarazo de gemelos. El resultado primario fue la tasa de pérdida del feto relacionada con el procedimiento. Los resultados secundarios fueron la pérdida del feto producida antes de las 24 semanas de gestación y la pérdida del feto producida dentro de las 4 semanas posteriores al procedimiento. Se utilizaron metaanálisis cara a cara para comparar cada resultado directamente, entre las mujeres que se sometieron a una amniocentesis y las que no se sometieron a ella, y entre las mujeres que se sometieron a una BVC y las que no se sometieron a ella, así como para calcular las diferencias de riesgo (DR) combinadas entre las mujeres expuestas y las no expuestas a cada procedimiento agresivo. Además, se utilizaron los metaanálisis de proporciones para estimar las tasas combinadas de cada uno de los tres resultados en las mujeres que se sometieron a amniocentesis o a BVC y en los controles. RESULTADOS: Se incluyeron 16 estudios (3.419 embarazos de gemelos sometidos a un procedimiento agresivo y 2.517 no sometidos). Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos sometidos y no sometidos a amniocentesis mostraron un mayor riesgo de pérdida general del feto en total en los sometidos a amniocentesis (Razón de Momios (RM), 1,46 (P=0,04); DR, 0,013 (P=0,04)), mientras que no hubo diferencias en el riesgo de pérdida del feto antes de las 24 semanas de gestación (RM, 1,59 (P=0,06); DR, 0,010 (P=0,11)) ni en el de las 4 semanas posteriores al procedimiento (RM, 1,38 (P=0,3); DR, 0,003 (P=0,8)). En general, la tasa conjunta de pérdida del feto fue del 2,4% (IC 95%, 1,4-3,6%) en los embarazos de gemelos sometidos a amniocentesis, en comparación con el 2,4% (IC 95%, 0,9-4,6%) en los que no se sometieron a amniocentesis. Los metaanálisis cara a cara que compararon directamente los embarazos de gemelos que se sometieron y que no se sometieron a una BVC no mostraron diferencias significativas ni en la pérdida del feto en total (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)) ni en la pérdida del feto antes de las 24 semanas de gestación (RM, 1,61 (P=0,5); DR, 0,003 (P=0,8)). En general, la tasa combinada de pérdida del feto fue del 2,0% (IC 95%, 0,0-6,5%) de los embarazos de gemelos sometidos a BVC, comparada con el 1,8% (IC 95%, 0,3-4,2%) de los que no se sometieron a BVC. CONCLUSIÓN: El riesgo de pérdida del feto tras la amniocentesis y la BVC en gemelos es menor que lo reportado en el pasado y la tasa de pérdida del feto antes de las 24 semanas de gestación, o dentro de las 4 semanas posteriores al procedimiento, no difiere de la del riesgo de contexto en los embarazos de gemelos que no se someten a pruebas prenatales agresivas. Estos datos pueden servir de guía para el asesoramiento prenatal de los embarazos de gemelos que se someten a procedimientos agresivos.

Outcome of twin-twin transfusion syndrome according to Quintero stage of disease: systematic review and meta-analysis.

OBJECTIVES: To report the outcome of pregnancies complicated by twin-twin transfusion syndrome (TTTS) according to Quintero stage. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies reporting the outcome of pregnancies complicated by TTTS stratified according to Quintero stage (I-V). The primary outcome was fetal survival rate according to Quintero stage. Secondary outcomes were gestational age at birth, preterm birth (PTB) before 34, 32 and 28 weeks' gestation and neonatal morbidity. Outcomes are reported according to the different management options (expectant management, laser therapy or amnioreduction) for pregnancies with Stage-I TTTS. Only cases treated with laser therapy were considered for those with Stages-II-IV TTTS and only cases managed expectantly were considered for those with Stage-V TTTS. Random-effects head-to-head meta-analysis was used to analyze the extracted data. RESULTS: Twenty-six studies (2699 twin pregnancies) were included. Overall, 610 (22.6%) pregnancies were diagnosed with Quintero stage-I TTTS, 692 (25.6%) were Stage II, 1146 (42.5%) were Stage III, 247 (9.2%) were Stage IV and four (0.1%) were Stage V. Survival of at least one twin occurred in 86.9% (95% CI, 84.0-89.7%) (456/552) of pregnancies with Stage-I, in 85% (95% CI, 79.1-90.1%) (514/590) of those with Stage-II, in 81.5% (95% CI, 76.6-86.0%) (875/1040) of those with Stage-III, in 82.8% (95% CI, 73.6-90.4%) (172/205) of those with Stage-IV and in 54.6% (95% CI, 24.8-82.6%) (5/9) of those with Stage-V TTTS. The rate of a pregnancy with no survivor was 11.8% (95% CI, 8.4-15.8%) (69/564) in those with Stage-I, 15.0% (95% CI, 9.9-20.9%) (76/590) in those with Stage-II, 18.6% (95% CI, 14.2-23.4%) (165/1040) in those with Stage-III, 17.2% (95% CI, 9.6-26.4%) (33/205) in those with Stage-IV and in 45.4% (95% CI, 17.4-75.2%) (4/9) in those with Stage-V TTTS. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS. Overall, the incidence of PTB and neonatal morbidity increased as the severity of TTTS increased, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of pregnancies with Stage-I TTTS according to the type of intervention, the rate of fetal survival of at least one twin was 84.9% (95% CI, 70.4-95.1%) (94/112) in cases managed expectantly, 86.7% (95% CI, 82.6-90.4%) (249/285) in those undergoing laser therapy and 92.2% (95% CI, 84.2-97.6%) (56/60) in those after amnioreduction, while the rate of double survival was 67.9% (95% CI, 57.0-77.9%) (73/108), 69.7% (95% CI, 61.6-77.1%) (203/285) and 80.8% (95% CI, 62.0-94.2%) (49/60), respectively. CONCLUSIONS: Overall survival in monochorionic diamniotic pregnancies affected by TTTS is higher for earlier Quintero stages (I and II), but fetal survival rates are moderately high even in those with Stage-III or -IV TTTS when treated with laser therapy. Gestational age at birth was similar in pregnancies with Stages-I-III TTTS, and gradually decreased in those with Stages-IV and -V TTTS treated with laser and expectant management, respectively. In pregnancies affected by Stage-I TTTS, amnioreduction was associated with slightly higher survival compared with laser therapy and expectant management, although these findings may be confirmed only by future head-to-head randomized trials. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado del síndrome de transfusión feto-fetal según el estadio de Quintero de la enfermedad: revisión sistemática y metaanálisis OBJETIVOS: Informar sobre el resultado de los embarazos complicados por el síndrome de transfusión feto-fetal (TTTS, por sus siglas en inglés) según el estadio de Quintero. MÉTODOS: Se hicieron búsquedas en las bases de datos de MEDLINE, EMBASE y CINAHL de estudios que hubieran informado sobre el resultado de embarazos complicados por TTTS, estratificados según el estadio de Quintero (I-V). El resultado primario fue la tasa de supervivencia fetal según el estadio de Quintero. Los resultados secundarios fueron la edad gestacional al nacer, el parto pretérmino (PPT) antes de las 34, 32 y 28 semanas de gestación y la morbilidad neonatal. Los resultados se reportan de acuerdo con las diferentes opciones de tratamiento (expectante, terapia de láser o amniorreducción) para los embarazos con TTTS en Estadio I. Sólo se consideraron los casos tratados con terapia de láser para aquellos con TTTS de las Etapas II-IV y sólo se consideraron los casos tratados de manera expectante para aquellos con TTTS de la Etapa V. Para analizar los datos extraídos se utilizó un metaanálisis directo de efectos aleatorios. RESULTADOS: Se incluyeron veintiséis estudios (2699 embarazos de gemelos). En total, 610 (22,6%) embarazos fueron diagnosticados con TTTS de Estadio I de Quintero, 692 (25,6%) de Estadio II, 1146 (42,5%) de Estadio III, 247 (9,2%) de Estadio IV y cuatro (0,1%) de Estadio V. La supervivencia de al menos un gemelo se produjo en el 86,9% (IC 95%, 84,0-89,7%) (456/552) de los embarazos en Estadio I, en el 85% (IC 95%, 79,1-90,1%) (514/590) de aquellos en Estadio II, en el 81,5% (IC 95%, 76,6-86,0%) (875/1040) de aquellos en Estadio-III, en el 82,8% (IC 95%, 73,6-90,4%) (172/205) de aquellos en Estadio-IV y en el 54,6% (IC 95%, 24,8-82,6%) (5/9) de aquellos en Estadio-V de TTTS. La tasa de embarazos sin supervivientes fue del 11,8% (IC 95%, 8,4-15,8%) (69/564) de aquellos en Estadio-I, 15,0% (IC 95%, 9,9-20,9%) (76/590) de aquellos en Estadio-II, 18,6% (IC 95%, 14,2-23,4%) (165/1040) de aquellos en Estadio-III, 17,2% (IC 95%, 9,6-26,4%) (33/205) de aquellos en Estadio-IV y en el 45,4% (IC 95%, 17,4-75,2%) (4/9) de aquellos en Estadio-V de TTTS. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V. En general, la incidencia de PPT y la morbilidad neonatal aumentaron a medida que se incrementó la gravedad del TTTS, pero los datos sobre estos dos resultados se vieron limitados por el pequeño tamaño de la muestra de los estudios incluidos. Al estratificar el análisis de los embarazos con TTTS en Estadio I según el tipo de tratamiento, la tasa de supervivencia fetal de al menos un gemelo fue del 84,9% (IC 95%, 70,4-95,1%) (94/112) en los casos tratados de forma expectante, del 86,7% (IC 95%, 82,6-90.4%) (249/285) en los sometidos a terapia láser y del 92,2% (IC 95%, 84,2-97,6%) (56/60) en los sometidos a amniorreducción, mientras que la tasa de supervivencia doble fue del 67,9% (IC 95%, 57,0-77,9%) (73/108), del 69,7% (IC 95%, 61,6-77,1%) (203/285) y del 80,8% (IC 95%, 62,0-94,2%) (49/60), respectivamente. CONCLUSIONES: La supervivencia en general en los embarazos biamnióticos monocoriónicos afectados por TTTS es mayor en los estadios tempranos de Quintero (I y II), pero las tasas de supervivencia fetal son moderadamente altas incluso en aquellos con TTTS en estadios III o IV cuando se tratan con terapia láser. La edad gestacional al nacer fue similar en los embarazos con TTTS en los Estadios I-III, y disminuyó gradualmente en aquellos con TTTS en los Estadios IV y V tratados con láser y tratamiento expectante, respectivamente. En los embarazos afectados por TTTS en Estadio I, la amniorreducción estuvo asociada con una supervivencia ligeramente mayor en comparación con la terapia de láser y el tratamiento expectante, aunque estos hallazgos solo pueden confirmarse mediante futuros estudios aleatorizados directos. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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.

Perinatal outcome of pregnancies complicated by placental chorioangioma: systematic review and meta-analysis.

OBJECTIVE: To report the perinatal outcome of singleton pregnancies complicated by placental chorioangioma diagnosed on prenatal ultrasound. METHODS: MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched for studies reporting the outcome of pregnancies complicated by placental chorioangioma. Inclusion criteria were singleton pregnancy diagnosed with placental chorioangioma on prenatal ultrasound, with no other associated structural anomaly. The primary outcome was perinatal mortality. Secondary outcomes included associated non-structural anomalies detected on prenatal ultrasound (including fetal hydrops, anemia, polyhydramnios, signs of hyperdynamic circulation and small-for-gestational-age (SGA) fetus), SGA at birth, composite neonatal morbidity and preterm birth. Outcome was assessed separately in pregnancies undergoing and those not undergoing fetal therapy. Subanalyses were performed according to the presence of hydrops and the size of the tumor in all pregnancies diagnosed with chorioangioma. Random-effects meta-analyses of proportions were used to analyze the data. RESULTS: Twenty-eight studies (161 pregnancies) were included. In pregnancies complicated by chorioangioma that did not undergo intervention, intrauterine death occurred in 8.2% (95% CI, 3.8-15.0%), while neonatal death and perinatal death occurred in 3.8% (95% CI, 1.0-8.1%) and 11.1% (95% CI, 5.0-19.4%), respectively. SGA at birth was present in 24.0% (95% CI, 13.5-36.5%) of cases, while preterm birth < 37 weeks complicated 34.1% (95% CI, 21.1-48.3%) of pregnancies. Composite neonatal morbidity occurred in 12.0% (95% CI, 4.5-22.3%) of cases. On ultrasound, signs of fetal hyperdynamic circulation were present in 21.0% (95% CI, 9.6-35.3%) of cases, while peak systolic velocity in the fetal middle cerebral artery was increased in 20.6% (95% CI, 10.9-32.3%). Subanalysis according to the size of chorioangioma, including both pregnancies that did and those that did not undergo intervention, showed a progressive increase in the occurrence of most of the outcomes explored with increasing size of the tumor. Furthermore, the prevalence of adverse perinatal outcome was high in pregnancies complicated by chorioangioma presenting with fetal hydrops. There was no randomized controlled trial comparing intervention vs expectant management in pregnancies complicated by chorioangioma with signs of fetal compromise (hydrops or hyperdynamic circulation). Overall, perinatal mortality occurred in 31.2% (95% CI, 18.1-46.1%) of fetuses undergoing in-utero therapy, and 57.3% (95% CI, 39.2-74.4%) had resolution of hydrops or hyperdynamic circulation after treatment. CONCLUSIONS: Placental chorioangioma is associated with adverse perinatal outcome. The size of the mass and presence of fetal hydrops are likely to be the main determinants of perinatal outcome in affected pregnancies. 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.

Value of first-trimester ultrasound in prediction of third-trimester sonographic stage of placenta accreta spectrum disorder and surgical outcome.

OBJECTIVES: To explore whether early first-trimester ultrasound can predict the third-trimester sonographic stage of placenta accreta spectrum (PAS) disorder and to elucidate whether combining first-trimester ultrasound findings with the sonographic stage of PAS disorder can stratify the risk of adverse surgical outcome in women at risk for PAS disorder. METHODS: This was a retrospective analysis of prospectively collected data from women with placenta previa, and at least one previous Cesarean delivery (CD) or uterine surgery, for whom early first-trimester (5-7 weeks' gestation) ultrasound images could be retrieved. The relationship between the position of the gestational sac and the prior CD scar was assessed using three sonographic markers for first-trimester assessment of Cesarean scar (CS) pregnancy, reported by Calí et al. (crossover sign (COS)), Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS) and Timor-Tritsch et al. (position of the center of the gestational sac below vs above the midline of the uterus), by two different examiners blinded to the final diagnosis and clinical outcome. The primary aim of the study was to explore the association between first-trimester ultrasound findings and the stage of PAS disorder on third-trimester ultrasound. Our secondary aim was to elucidate whether the combination of first-trimester ultrasound findings and sonographic stage of PAS disorder can predict surgical outcome. Logistic regression analysis and area under the receiver-operating-characteristics curve (AUC) were used to analyze the data. RESULTS: One hundred and eighty-seven women with vasa previa were included. In this cohort, 79.6% (95% CI, 67.1-88.2%) of women classified as COS-1, 94.4% (95% CI, 84.9-98.1%) of those with gestational-sac implantation in the niche of the prior CS and 100% (95% CI, 93.4-100%) of those with gestational sac located below the uterine midline, on first-trimester ultrasound, were affected by the severest form of PAS disorder (PAS3) on third-trimester ultrasound. On multivariate logistic regression analysis, COS-1 (odds ratio (OR), 7.9 (95% CI, 4.0-15.5); P < 0.001), implantation of the gestational sac in the niche (OR, 29.1 (95% CI, 8.1-104); P < 0.001) and location of the gestational sac below the midline of the uterus (OR, 38.1 (95% CI, 12.0-121); P < 0.001) were associated independently with PAS3, whereas parity (P = 0.4) and the number of prior CDs (P = 0.5) were not. When translating these figures into diagnostic models, first-trimester diagnosis of COS-1 (AUC, 0.94 (95% CI, 0.91-0.97)), pregnancy implantation in the niche (AUC, 0.92 (95% CI, 0.89-0.96)) and gestational sac below the uterine midline (AUC, 0.92 (95% CI, 0.88-0.96)) had a high predictive accuracy for PAS3. There was an adverse surgical outcome in 22/187 pregnancies and it was more common in women with, compared to those without, COS-1 (P < 0.001), gestational-sac implantation in the niche (P < 0.001) and gestational-sac position below the uterine midline (P < 0.001). On multivariate logistic regression analysis, third-trimester ultrasound diagnosis of PAS3 (OR, 4.3 (95% CI, 2.1-17.3)) and first-trimester diagnosis of COS-1 (OR, 7.9 (95% CI, 4.0-15.5); P < 0.001), pregnancy implantation in the niche (OR, 29.1 (95% CI, 8.1-79.0); P < 0.001) and position of the sac below the uterine midline (OR, 6.6 (95% CI, 3.9-16.2); P < 0.001) were associated independently with adverse surgical outcome. When combining the sonographic coordinates of the three first-trimester imaging markers, we identified an area we call high-risk-for-PAS triangle, which may enable an easy visual perception and application of the three methods to prognosticate the risk for CS pregnancy and PAS disorder, although it requires validation in large prospective studies. CONCLUSIONS: Early first-trimester sonographic assessment of pregnancies with previous CD can predict reliably ultrasound stage of PAS disorder. Combination of findings on first-trimester ultrasound with second- and third-trimester ultrasound examination can stratify the surgical risk in women affected by a PAS disorder. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Role of interventional radiology in pregnancy complicated by placenta accreta spectrum disorder: systematic review and meta-analysis.

OBJECTIVE: To evaluate the potential benefit of interventional radiology (IR) in improving the outcome of women undergoing surgery for a placenta accreta spectrum (PAS) disorder. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for studies comparing outcomes of women with a prenatal diagnosis of PAS who underwent an IR procedure before surgery vs those who did not, using a robust collection of terms relating to PAS. The primary outcome was intraoperative estimated blood loss (EBL). Secondary outcomes were the number of transfused units of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets and cryoprecipitate, operation time, length of hospital stay, EBL ≥ 2.5 L, PRBC transfused ≥ 5 units, surgical complications, bladder or ureteral injury, relaparotomy, infection, disseminated intravascular coagulation, and complications related to endovascular catheter placement. Only studies reporting on the incidence of, or the mean difference in, the observed outcomes in women affected by a PAS disorder who had vs those who did not have an IR procedure before surgery were considered for inclusion. All outcomes were explored in the overall population of women with a prenatally diagnosed PAS disorder and in those undergoing hysterectomy. Quality assessment of each included study was performed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. The GRADE methodology was used to assess the quality of the body of retrieved evidence. RESULTS: Fifteen studies (958 women with PAS) were included. In women who underwent IR before surgery, compared with those who did not, mean EBL (mean difference (MD), -1.02 L; 95% CI, -1.60 to -0.43 L; P < 0.001) and the risk of EBL ≥ 2.5 L (odds ratio (OR), 0.18; 95% CI, 0.04-0.78; P = 0.02) were significantly lower. There was no significant difference between the two groups in the other outcomes explored. On subgroup analysis of pregnancies complicated by PAS undergoing hysterectomy, EBL (MD, -0.68 L; 95% CI, -1.24 to -0.12 L; P = 0.02) and the number of transfused FFP units (MD, -1.66; 95% CI, -2.71 to -0.61; P = 0.02) were significantly lower in women who had an endovascular IR procedure compared with controls. Furthermore, women undergoing IR had a significantly lower risk of EBL ≥ 2.5 L (OR, 0.10; 95% CI, 0.02-0.47; P = 0.004). Overall, complications related to the placement of an endovascular catheter occurred in 5.3% (95% CI, 2.6-8.9; I2 , 65.3%) of pregnancies undergoing IR. Overall quality of evidence, as assessed by GRADE, was very low. CONCLUSIONS: The current available data provide encouraging evidence that IR procedures may be associated with lower EBL and need for transfusion in pregnancies undergoing surgery for a PAS disorder. However, given the overall very low quality of the evidence, further large studies are needed in order to confirm the beneficial role of IR in improving the outcome of these women. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

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.

Interstitial Pregnancy: From Medical to Surgical Approach-Report of Three Cases.

BACKGROUND: Interstitial pregnancy is a rare form of ectopic pregnancy that usually leads to uterine rupture resulting in sudden life-threatening haemorrhage, need for blood transfusion, and admission to intensive care unit. Mortality rate is 6-7 times higher than that in classical ectopic pregnancy. Uterine rupture has been typically reported to occur at more advanced gestational ages compared to tubal pregnancy although several recent reports have shown a high risk of rupture before 12 weeks of gestation. CASES PRESENTATION: We report three cases of women affected by interstitial pregnancy, with different clinical symptoms, and managed to be treated with surgery or medical therapy. An emergency laparotomy was performed in the first case by the general surgeon, while in the second case laparoscopy was made by a gynecologist; last case shows the success of systemic administration of methotrexate. CONCLUSION: Interstitial pregnancy is still a challenging condition to diagnose and treat; early diagnosis may help to choose the proper management.

Outcome of fetuses with congenital parvovirus B19 infection: systematic review and meta-analysis.

OBJECTIVE: To explore the outcome of fetuses affected by congenital parvovirus B19 (PB19) infection, with or without signs of hydrops on ultrasound. METHODS: PubMed, EMBASE and CINAHL databases were searched for studies reporting on prenatal diagnosis and outcome of fetal PB19 infection. The outcomes explored were miscarriage, perinatal death (PND), intrauterine death, neonatal death, spontaneous resolution of hydrops or fetal anemia, need for intrauterine transfusion (IUT), resolution of hydrops or anemia after transfusion, fetal loss following transfusion, abnormal brain scan after birth and abnormal neurodevelopmental outcome. Outcomes were reported according to the presence or absence of signs of hydrops on ultrasound. A subgroup analysis was performed including hydropic and non-hydropic fetuses diagnosed at < 20 weeks and ≥ 20 weeks of gestation. Meta-analyses of proportions and meta-analyses using individual-data random-effects logistic regression were performed to analyze the data. RESULTS: Thirty-five observational studies were included, involving 611 fetuses affected by PB19 infection. The risks of miscarriage (odds ratio (OR), 11.5; 95% CI, 2.7-49.7) and PND (OR, 4.2; 95% CI, 1.6-11.0) were higher in fetuses with PB19 infection presenting, compared with those not presenting, signs of hydrops on ultrasound. In fetuses affected by hydrops, spontaneous resolution of the infection, defined as disappearance of hydrops without need for IUT, occurred in 5.2% (95% CI, 2.5-8.8%) of cases whereas, in the group of fetuses not affected by hydrops, infection resolved in 49.6% (95% CI, 20.7-78.6%) of cases. IUT was performed in 78.7% (95% CI, 66.4-88.8%) of hydropic and in 29.6% (95% CI, 6.0-61.6%) of non-hydropic fetuses affected by congenital PB19 infection and resolution of the infection after IUT occurred in 55.1% (95% CI, 34.0-75.3%) and in 100% (95% CI, 57.3-100%) of cases, respectively. The risk of fetal loss after IUT was higher in fetuses affected compared with those not affected by hydrops (OR, 9.8; 95% CI, 2.8-34.6). The prevalence of abnormal brain imaging was 9.8% (95% CI, 2.5-21.0%) in fetuses affected and 0.0% (95% CI, 0.0-7.0%) in those not affected by hydrops, whilst the corresponding figures for abnormal neurodevelopmental outcome were 9.5% (95% CI, 2.6-20.2) and 0.0% (95% CI, 0.0-7.5), respectively; however, statistical power to assess these outcomes was inadequate due to the small number of included cases. CONCLUSIONS: Hydrops is the main determinant of mortality and adverse perinatal outcome in fetuses with PB19 infection. Perinatal outcome in non-hydropic fetuses is generally favorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Influence of prenatal diagnosis of abnormally invasive placenta on maternal outcome: systematic review and meta-analysis.

OBJECTIVE: To ascertain the impact of prenatal diagnosis on surgical outcome of women affected by abnormally invasive placenta (AIP). METHODS: MEDLINE, EMBASE, CINAHL and Cochrane databases were searched. Observed outcomes included: gestational age at birth (weeks), amount of blood loss (L), units of red blood cells (RBC), platelets (PLT) and fresh frozen plasma (FFP) transfused, length of stay in hospital and the intensive care unit (ICU) (days), urinary tract injury and infection. Only studies reporting the occurrence of any of the explored outcomes in women with a prenatal compared with an intrapartum diagnosis of AIP were considered eligible for inclusion. Random-effect head-to-head meta-analyses were used to analyze the data. RESULTS: Thirteen studies were included. Women with a prenatal diagnosis of AIP had less blood loss during surgery (mean difference (MD), -0.87; 95% CI, -1.5 to -0.23), had fewer units of RBC (MD, -1.45; 95% CI, -2.9 to -0.04) and FFP (MD, -1.73; 95% CI, -3.3 to -0.2) transfused, and delivered earlier (MD, 1.33 weeks; 95% CI, -2.23 to -0.43) compared with those with an intrapartum diagnosis. The risk of admission to an ICU and length of in-hospital and in-ICU stay were not different between the groups. Prenatal diagnosis of AIP was associated with a higher risk of urinary-tract injury (odds ratio, 2.5; 95% CI, 1.3-4.6), mainly due to the higher prevalence of placenta percreta in the group with AIP diagnosed prenatally. CONCLUSION: Prenatal diagnosis of AIP is associated with reduced hemorrhagic morbidity compared with cases in which such anomalies are detected at delivery. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of first-trimester ultrasound in detecting abnormally invasive placenta in high-risk women with placenta previa.

OBJECTIVE: To ascertain the diagnostic accuracy of ultrasound in detecting abnormally invasive placenta (AIP) during the first trimester of pregnancy (11-14 weeks' gestation) in women at risk for this condition. METHODS: This was a retrospective analysis of data collected prospectively from women at risk for AIP based upon the presence of at least one prior Cesarean section (CS) and/or uterine surgery and placenta previa, who had ultrasound assessment for AIP at the time of the 11-14-week scan. The ultrasound signs explored in the present study were: loss of the clear zone, placental lacunae, bladder wall interruption and uterovesical hypervascularity. The potential of ultrasound and different ultrasound signs to predict the different types of AIP was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and positive (LR+) and negative (LR-) likelihood ratios. RESULTS: One hundred and eighty-eight women with placenta previa and at least one previous CS or uterine surgery were included in the study. All the explored ultrasound signs were associated significantly with the occurrence of AIP. Overall, when at least one ultrasound sign was used to make the diagnosis, ultrasound had a sensitivity of 84.3% (95% CI, 74.7-91.4%), specificity of 61.9% (95% CI, 51.9-71.2%), DOR of 8.6 (95% CI, 4.1-19.3), LR+ of 2.2 (95% CI, 1.7-2.9) and LR- of 0.3 (95% CI, 0.1-0.4) in detecting AIP. Using two ultrasound signs to label a case as positive increased the diagnostic accuracy in terms of specificity, although it did not affect sensitivity. Among the different ultrasound signs, loss of the clear zone had a sensitivity of 84.3% (95% CI, 74.7-91.4%) and a specificity of 81.9% (95% CI, 73.2-88.7%) in detecting AIP, while sensitivities for placental lacunae and bladder wall interruption were 78.3% (95% CI, 67.9-86.6%) and 75.9% (95% CI, 65.3-84.6%), respectively, and specificities were 81.0% (95% CI, 72.1-88.0%) and 99.1% (95% CI, 94.8-100.0%), respectively. The optimal combination of sensitivity and specificity was achieved when at least two imaging signs of AIP were used in the diagnostic algorithm. CONCLUSIONS: AIP can be detected from the first trimester of pregnancy in women at risk for this condition, and ultrasound performed between 11 and 14 weeks' gestation has an overall good diagnostic accuracy for detecting all types of AIP. However, these findings are applicable only to women with placenta previa and prior uterine scar. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Outcome of prenatally diagnosed fetal heterotaxy: systematic review and meta-analysis.

OBJECTIVES: The main aim of this systematic review was to evaluate the prevalence and type of associated anomalies in fetuses with heterotaxy diagnosed prenatally on ultrasound; the perinatal outcome of these fetuses was also studied. METHODS: An electronic search of MEDLINE, EMBASE and CINAHL databases was performed. Only studies reporting the prenatal diagnosis of isomerism were included. Outcomes observed included associated cardiac and extracardiac anomalies, fetal arrhythmia, abnormal karyotype, type of surgical repair and perinatal mortality. The analysis was stratified according to the type of heterotaxy syndrome (left (LAI) or right (RAI) atrial isomerism). Meta-analyses of proportions were used to combine data. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. RESULTS: Sixteen studies (647 fetuses) were included in the analysis. Atrioventricular septal defect was the most common associated major cardiac anomaly found both in fetuses with LAI (pooled proportion (PP), 59.3% (95% CI, 44.0-73.7%)), with obstructive lesions of the right outflow tract occurring in 35.5% of these cases, and in fetuses with RAI (PP, 72.9% (95% CI, 60.4-83.7%)). Fetal arrhythmias occurred in 36.7% (95% CI, 26.9-47.2%) of cases with LAI and were mainly represented by complete atrioventricular block, while this finding was uncommon in cases with RAI (PP, 1.3% (95% CI, 0.2-3.2%)). Abnormal stomach and liver position were found, respectively, in 59.4% (95% CI, 38.1-79.0%) and 32.5% (95% CI, 11.9-57.6%) of cases with LAI, and in 54.5% (95% CI, 38.5-70.1%) and 45.9% (95% CI, 11.3-83.0%) of cases with RAI, while intestinal malrotation was detected in 14.2% (95% CI, 2.5-33.1%) of LAI and 27.1% (95% CI, 7.9-52.0%) of RAI cases. Hydrops developed in 11.8% (95% CI, 2.9-25.6%) of fetuses diagnosed prenatally with LAI. Biventricular repair was accomplished in 78.2% (95% CI, 64.3-89.4%) of cases with LAI, while univentricular repair or palliation was needed in 17.0% (95% CI, 9.7-25.9%); death during or after surgery occurred in 26.8% (95% CI, 4.6-58.7%) of LAI cases. Most children with RAI had univentricular repair and 27.8% (95% CI, 15.5-42.1%) died during or after surgery. CONCLUSIONS: Fetal heterotaxy is associated with a high prevalence of cardiac and extracardiac anomalies. Approximately one quarter of fetuses with heterotaxy died during or after surgery. Abnormal heart rhythm, especially heart block, is common in fetuses with LAI, while this finding is uncommon in RAI. Biventricular repair was common in LAI while univentricular repair was required in the majority of children affected by RAI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.