Diagnostic accuracy of cell-free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies. METHODS: Medline, Embase and Cochrane databases were searched. The inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model. RESULTS: Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies. CONCLUSION: cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.

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

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

Rate of reinfections after SARS-CoV-2 primary infection in the population of an Italian province: a cohort study.

BACKGROUND: Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections are rare, but no information are available on minors and after 12 months of follow-up. METHODS: This retrospective cohort study included all the population of an Italian Province, diagnosed with a SARS-CoV-2 infection from March 2020 to May 2021. The primary outcome was the incidence of a reinfection, defined as a new positive polymerase chain reaction (PCR) test occurring ≥90 days after complete resolution of the first infection, and data were retrieved from the official datasets (coronavirus disease 2019 [COVID-19], demographic, hospital and co-pay exemption) of the Local Health Unit (LHU) of Pescara. RESULTS: After an average of 201 days of follow-up (max. 414), we recorded 24 reinfections ≥90 days after the resolution of the first 7173 infections (0.33%). Four reinfections required hospitalization, one was lethal. Most of the reinfections (n = 13) occurred 6-9 months after the resolution of the first infection; no new infection was detected 12 or more months later and among the 832 minors. CONCLUSIONS: This study confirms previous findings on a low risk of SARS-CoV-2 reinfection. If confirmed, these findings suggest that more targeted restriction policies can be applied to the subjects that recovered after a first infection.

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.

Levels of Polychlorinated Dibenzo-p-Dioxins/Furans and Polychlorinated Biphenyls in Free-Range Hen Eggs in Central Italy and Estimated Human Dietary Exposure.

ABSTRACT: The aim of the present study was to evaluate the contamination levels of some classes of persistent organic pollutants in free-range hen eggs and to estimate the related human dietary exposure in a site of national interest, characterized by a serious state of environmental pollution in the Bussi sul Tirino area in central Italy. For these purposes, 17 samples of free-range hen eggs collected in home-producing farms located in the site of national interest territory were analyzed for 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), 12 dioxin-like polychlorinated biphenyls (dl-PCBs), and 6 non-dioxin-like PCBs (ndl-PCBs). Dietary exposure was assessed assuming a standard consumption of eggs per week. The concentration of ∑PCDD/Fs plus dl-PCBs ranged from 0.463 to 8.028 pg toxic equivalent g-1 fat, whereas the mean contamination level of the ∑ndl-PCBs ranged from 0.234 to 7.741 ng toxic equivalent g-1 fat. PCDD/Fs and PCBs contamination levels were lower than maximum values established by the Commission Regulation (European Union) 1259/2011, except for one sample. The estimated weekly intake, calculated to evaluate the contribution in terms of the monitored pollutants of the locally produced eggs to the diet, was lower than the tolerable weekly intake established by the European Food Safety Authority.

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.

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.

Endovascular Treatment of Ruptured Intracranial Blister Aneurysms: A Systematic Review and Meta-analysis.

BACKGROUND: Endovascular treatment of blister aneurysms is a promising approach, even though they are vascular lesions challenging to treat due to their angioarchitectural characteristics. PURPOSE: Our aim was to investigate clinical and radiologic outcomes after endovascular treatment of ruptured blister aneurysms. DATA SOURCES: PubMed, Ovid MEDLINE, Ovid EMBASE, Scopus, and the Web of Science were screened. STUDY SELECTION: We performed a comprehensive review of the literature from 2010 to 2019 reporting series of patients with blister aneurysms treated with an endovascular approach. DATA ANALYSIS: Event rates were pooled across studies using a random effects meta-analysis. DATA SYNTHESIS: A total of 32 studies reporting on 684 patients (707 aneurysms) were included. Stent placement, stent-assisted coiling, and flow diversion were the most commonly described treatments (282, 256, and 155 patients, respectively). The long-term complete occlusion rate was 76.9% (95% CI, 69.2%-83.9%). The perioperative complication rate was 8.9%, and clinical outcome at final follow-up was mRS <2 in 76.6% (95% CI, 68.2%-84.2%) of patients. The mortality rate was 4.7% (95% CI, 2.30%-7.80%). Among the different techniques, stent-assisted coiling is the one that had the higher rate of immediate occlusion (63.4%); however, the occlusion rate at the final follow-up was comparable among the different techniques. LIMITATIONS: Different techniques were described and data were reported in a nonhomogeneous way, possibly representing a bias in the present study. CONCLUSIONS: This study suggests that endovascular treatment of blister aneurysms is associated with good long-term occlusion rates and reasonable complication and mortality rates. There is no consensus on the best endovascular techniques in blister aneurysm management.

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.

Tobacco vs. electronic cigarettes: absence of harm reduction after six years of follow-up.

OBJECTIVE: Information on the long-term safety of electronic cigarettes (e-cig) is still limited. We report the results after six years of follow-up of the first observational study assessing e-cig long-term effectiveness and safety. PATIENTS AND METHODS: Participants were adults who smoked ≥1 tobacco cigarette/day (tobacco smokers); or used any type of e-cig inhaling ≥50 puffs weekly (e-cig users); or used both (dual users). Participants were contacted directly or by phone and/or internet interviews. Hospital discharge abstract data and carbon monoxide level tests were also used. RESULTS: Data were available for 228 e-cig users (all ex-smokers), 469 tobacco smokers, 215 dual users. A possibly smoking-related disease (PSRD) was recorded in 90 subjects (9.9%); 11 deceased (1.2%). No differences were observed across groups in PSRD rates, with minor changes in self-reported health. Among e-cig users, 64.0% remained tobacco abstinent. Dual users and tobacco smokers did not significantly differ in the rate of cessation of tobacco (38.6% vs. 33.9%, respectively) and all products (23.7% vs. 26.4%). A comparable decrease in daily cigarettes was also observed. 39.5% of the sample switched at least once (tobacco smokers: 15.1%; dual users: 83.3%). CONCLUSIONS: After six years, no evidence of harm reduction was found among e-cig or dual users. The complete switch to e-cig might support tobacco quitters remain abstinent, but the use of e-cig in addition to tobacco did not improve smoking cessation or reduction.

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.

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.

Costs of irritable bowel syndrome in European countries with universal healthcare coverage: a meta-analysis.

OBJECTIVE: To provide an overall estimate of the direct, indirect and total costs of irritable bowel syndrome (IBS) for the adult population of the European countries with universal healthcare coverage. MATERIALS AND METHODS: We searched MedLine and Scopus databases (up to September 2018) to identify the European studies that evaluated the economic impact of IBS. Mean annual direct, indirect and total per-capita IBS costs were estimated using random-effect single-group meta-analyses of continuous data. All analyses were stratified by payer category (governments, insurance, societal), and the results were expressed as summary mean and 95% CI. RESULTS: A total of 24 studies were included in the meta-analyses. Only two studies evaluated IBS costs in Italy. The pooled summary of direct IBS per-capita cost, obtained from 23 European datasets (n=15,157), was €1837/year (95% CI: 1480-2195), with large differences across payers (from €1183 to €3358, in countries with publicly-funded and insurance-based health systems, respectively). The mean indirect cost, extracted from 13 datasets (n=3978), was €2314/year (95% CI: 1811-2817), again with wide differences across payers. Finally, the meta-analysis estimating the total annual cost, based upon 11 European datasets (n=2757), yielded a summary estimate of €2889/year (95% CI: 2318-3460) per patient, ranging from €1602 (insurance-based health systems) to €3909 (studies adopting a societal perspective). CONCLUSIONS: Considering a conservative estimate of 2,736,700 Italian adults affected by the syndrome, the minimum costs due to IBS in Italy - likely underestimated - range from 6 to 8 billion euro per year. Given the substantial economic burden for patients, healthcare systems and society, IBS should be included among the priorities of the public health agenda.

Prenatal ultrasound staging system for placenta accreta spectrum disorders.

OBJECTIVES: To develop a prenatal ultrasound staging system for placenta accreta spectrum (PAS) disorders in women with placenta previa and to evaluate its association with surgical outcome, placental invasion and the clinical staging system for PAS disorders proposed by the International Federation of Gynecology and Obstetrics (FIGO). METHODS: This was a secondary retrospective analysis of prospectively collected data from women with placenta previa. We classified women according to the following staging system for PAS disorders, based upon the presence of ultrasound signs of PAS in women with placenta previa: PAS0, placenta previa with no ultrasound signs of invasion or with placental lacunae but no evidence of abnormal uterus-bladder interface; PAS1, presence of at least two of placental lacunae, loss of the clear zone or bladder wall interruption; PAS2, PAS1 plus uterovescical hypervascularity; PAS3, PAS1 or PAS2 plus evidence of increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region. We explored whether this ultrasound staging system correlates with surgical outcome (estimated blood loss (EBL, mL), units of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets (PLT) transfused, operation time (min), surgical complications defined as the occurrence of any damage to the bladder, ureters or bowel, length of hospital stay (days) and admission to intensive care unit (ICU)) and depth of placental invasion. The correlation between the present ultrasound staging system and the clinical grading system proposed by FIGO was assessed. Prenatal and surgical management were not based on the proposed prenatal ultrasound staging system. Linear and multiple regression models were used. RESULTS: Two-hundred and fifty-nine women were included in the analysis. Mean EBL was 516 ± 151 mL in women with PAS0, 609 ± 146 mL in those with PAS1, 950 ± 190 mL in those with PAS2 and 1323 ± 533 mL in those with PAS3, and increased significantly with increasing severity of PAS ultrasound stage. Mean units of PRBC transfused were 0.05 ± 0.21 in PAS0, 0.10 ± 0.45 in PAS1, 1.19 ± 1.11 in PAS2 and 4.48 ± 2.06 in PAS3, and increased significantly with PAS stage. Similarly, there was a progressive increase in the mean units of FFP transfused from PAS1 to PAS3 (0.0 ± 0.0 in PAS1, 0.25 ± 1.0 in PAS2 and 3.63 ± 2.67 in PAS3). Women presenting with PAS3 on ultrasound had significantly more units of PLT transfused (2.37 ± 2.40) compared with those with PAS0 (0.03 ± 0.18), PAS1 (0.0 ± 0.0) or PAS2 (0.0 ± 0.0). Mean operation time was longer in women with PAS3 (184 ± 32 min) compared with those with PAS1 (153 ± 38 min) or PAS2 (161 ± 28 min). Similarly, women with PAS3 had longer hospital stay (7.4 ± 2.1 days) compared with those with PAS0 (3.4 ± 0.6 days), PAS1 (6.4 ± 1.3 days) or PAS2 (5.9 ± 0.8 days). On linear regression analysis, after adjusting for all potential confounders, higher PAS stage was associated independently with a significant increase in EBL (314 (95% CI, 230-399) mL per one-stage increase; P < 0.001), units of PRBC transfused (1.74 (95% CI, 1.33-2.15) per one-stage increase; P < 0.001), units of FFP transfused (1.19 (95% CI, 0.61-1.77) per one-stage increase; P < 0.001), units of PLT transfused (1.03 (95% CI, 0.59-1.47) per one-stage increase; P < 0.001), operation time (38.8 (95% CI, 31.6-46.1) min per one-stage increase; P < 0.001) and length of hospital stay (0.83 (95% CI, 0.46-1.27) days per one-stage increase; P < 0.001). On logistic regression analysis, increased severity of PAS was associated independently with surgical complications (odds ratio, 3.14 (95% CI, 1.36-7.25); P = 0.007), while only PAS3 was associated with admission to the ICU (P < 0.001). All women with PAS0 on ultrasound were classified as having Grade-1 PAS disorder according to the FIGO grading system. Conversely, of the women presenting with PAS1 on ultrasound, 64.1% (95% CI, 48.4-77.3%) were classified as having Grade-3, while 35.9% (95% CI, 22.7-51.6%) were classified as having Grade-4 PAS disorder, according to the FIGO grading system. All women with PAS2 were categorized as having Grade-5 and all those with PAS3 as having Grade-6 PAS disorder according to the FIGO system. CONCLUSION: Ultrasound staging of PAS disorders is feasible and correlates with surgical outcome, depth of invasion and the FIGO clinical grading system. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Cohort study of electronic cigarette use: safety and effectiveness after 4 years of follow-up.

OBJECTIVE: More than a decade after e-cigarette (e-cig) market launch, limited information are available on their safety after 24 months of use. In 2013, we started the first observational study assessing e-cig long-term effectiveness and safety, directly comparing tobacco smokers and e-cig users. Here we report the results after four years of follow-up. PATIENTS AND METHODS: Adults (30-75 years) were included if: smokers of ≥1 tobacco cigarette/day (tobacco smokers); users of any type of e-cig inhaling ≥50 puffs weekly (e-cig users); users of both tobacco and e-cig (dual users). Data were collected by phone and/or internet, and carbon monoxide levels tested in 50% of those declaring tobacco abstinence. Main outcomes were: possibly smoking-related diseases (PSRD; validated through hospital discharge data or visit in 62.6% of the sample); 4-year tobacco abstinence; number of tobacco cigarettes/day. RESULTS: Data were available for 228 e-cig users (all ex-smokers), 471 tobacco smokers, 216 dual users. A PSRD was observed in 73 subjects (8.0%). No differences emerged across groups in PSRD rates, with negligible variations in self-reported health. Of e-cig users, 63.6% remained tobacco abstinent; dual users and tobacco smokers showed non-significantly different rates of tobacco (33.8% vs. 26.8%) and all-product (20.2% vs. 19.4%) cessation, and a similar decrease in cigarettes/day. Almost 40% of the sample switched at least once (tobacco smokers: 17.2%; dual users: 81.9%). CONCLUSIONS: After four years, a scarce, non-significant harm reduction was observed among e-cig or dual users. Given the long-lasting health effects of tobacco smoking, the benefits of e-cig use may start being detectable at the next follow-up (six years). The complete switch to e-cig may help tobacco quitters remain abstinent, but e-cig use in addition to tobacco did not increase the likelihood of smoking cessation or reduction.

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.

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.

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.