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.

Diagnostic yield of exome sequencing in prenatal agenesis of corpus callosum: systematic review and meta-analysis.

OBJECTIVES: To determine the incremental diagnostic yield of exome sequencing (ES) after negative chromosomal microarray analysis (CMA) in cases of prenatally diagnosed agenesis of the corpus callosum (ACC) and to identify the associated genes and variants. METHODS: A systematic search was performed to identify relevant studies published up until June 2022 using four databases: PubMed, SCOPUS, Web of Science and The Cochrane Library. Studies in English reporting on the diagnostic yield of ES following negative CMA in prenatally diagnosed partial or complete ACC were included. Authors of cohort studies were contacted for individual participant data and extended cohorts were provided for two of them. The increase in diagnostic yield with ES for pathogenic/likely pathogenic (P/LP) variants was assessed in all cases of ACC, isolated ACC, ACC with other cranial anomalies and ACC with extracranial anomalies. To identify all reported genetic variants, the systematic review included all ACC cases; however, for the meta-analysis, only studies with ≥ three ACC cases were included. Meta-analysis of proportions was employed using a random-effects model. Quality assessment of the included studies was performed using modified Standards for Reporting of Diagnostic Accuracy criteria. RESULTS: A total of 28 studies, encompassing 288 prenatally diagnosed ACC cases that underwent ES following negative CMA, met the inclusion criteria of the systematic review. We classified 116 genetic variants in 83 genes associated with prenatal ACC with a full phenotypic description. There were 15 studies, encompassing 268 cases, that reported on ≥ three ACC cases and were included in the meta-analysis. Of all the included cases, 43% had a P/LP variant on ES. The highest yield was for ACC with extracranial anomalies (55% (95% CI, 35-73%)), followed by ACC with other cranial anomalies (43% (95% CI, 30-57%)) and isolated ACC (32% (95% CI, 18-51%)). CONCLUSIONS: ES demonstrated an incremental diagnostic yield in cases of prenatally diagnosed ACC following negative CMA. While the greatest diagnostic yield was observed in ACC with extracranial anomalies and ACC with other central nervous system anomalies, ES should also be considered in cases of isolated ACC. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal 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.

Nipple-sparing mastectomy with different approaches: surgical incisions, complications, and cosmetic results. Preliminary results of 100 consecutive patients at a single center.

Nipple- and areola-sparing mastectomy is a novel surgical approach that preserves the nipple-areolar complex. Patients with moderate and/or severe breast ptosis are usually not eligible for this surgical approach. In this study, we aimed to demonstrate the feasibility of nonconventional surgical approaches for nipple-sparing mastectomy. One hundred consecutive patients diagnosed with primary breast cancer (BC) were enrolled in this study. Clinical and pathological data such as body mass index, smoking status, breast ptosis, complications, and aesthetic satisfaction (Breast-Q test) were collected. According to different types of breast ptosis, surgical procedures were classified as (a) hemi-periareolar, (b) round block, (c) vertical pattern, and (d) wise pattern skin incisions. We performed statistical analysis to assess the correlation with complications, degree of ptosis, and breast-Q scores. Among the 117 surgical procedures performed in 100 patients with BC, no significant associations are verified considering clinical and pathological data, complications, pre- and postsurgery satisfactions, and other parameters. Different surgical approaches represent the evolution of "classic" nipple-sparing mastectomy, thus meeting the cosmetic and oncological results. These procedures are safe and also indicated in cases conventionally considered as not eligible for nipple-areola preservation.

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

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

Outcome of monochorionic twin pregnancy with selective intrauterine growth restriction according to umbilical artery Doppler flow pattern of smaller twin: systematic review and meta-analysis.

OBJECTIVE: To explore the outcome of monochorionic twin pregnancies affected by selective intrauterine growth restriction (sIUGR) according to the umbilical artery Doppler pattern of the smaller twin. METHODS: An electronic search of MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases (2000-2016) was performed. sIUGR was defined as the presence of one twin with an estimated fetal weight and/or abdominal circumference < 10th or < 5th percentile and classified according to the umbilical artery Doppler flow pattern of the smaller twin (Type I: persistently positive; Type II: persistently absent/reversed; Type III: intermittently absent/reversed). Primary outcomes were perinatal mortality, intrauterine death, neonatal death and double fetal loss. Secondary outcomes were neonatal morbidity, including abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, admission to neonatal intensive care unit and respiratory distress syndrome, deterioration of fetal status, gestational age at delivery and degree of birth-weight discordance. A composite adverse outcome, defined as the presence of any mortality or abnormal brain findings, was also assessed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was used to compute the summary odds ratios (ORs), mean differences (MD) and proportions for the different outcomes. RESULTS: Thirteen studies (610 pregnancies) were included. The risk of perinatal mortality was higher in twins affected by Type II compared with Type I sIUGR (OR, 4.1 (95% CI, 1.6-10.3)), whereas there was no difference among the other variants of growth restriction. Risk of abnormal postnatal brain imaging was significantly higher in twins affected by either Type II (OR, 4.9 (95% CI, 1.9-12.9)) or Type III (OR, 8.2 (95% CI, 2.0-33.1)) sIUGR compared with Type I sIUGR. The risk for neonatal intensive care unit admission was higher in Type II compared with Type I sIUGR (OR, 18.3 (95% CI, 1.0-339.7)). Twin pregnancies affected by Type I sIUGR were delivered at a significantly later gestational age compared with Type II (MD, 2.8 (95% CI, 1.83-3.86) weeks) and Type III (MD, 2.1 (95% CI, 0.97-3.19) weeks). The degree of birth-weight discordance was higher in Type II compared with Type I (MD, 21.6% (95% CI, 9.9-33.2%)) and Type III (MD, 9.3% (95% CI, 3.8-14.9%)) sIUGR. CONCLUSION: Monochorionic twin pregnancies affected by Type II sIUGR are at a higher risk of perinatal mortality and morbidity compared with Type I. The likelihood of an abnormal outcome is usually not significantly different between sIUGR Types II and III, although the latter has an unpredictable clinical course. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Early prediction of twin-to-twin transfusion syndrome: systematic review and meta-analysis.

OBJECTIVE: To assess the role of first- and early second-trimester markers in the prediction of twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies. METHODS: Electronic databases MEDLINE, EMBASE and ClinicalTrials.gov were searched from inception to April 2014, using the MeSH term 'fetofetal transfusion' in combination with phrases 'predictive value', 'sensitivity', 'specificity', 'false positive', 'false negative', 'screening', 'accuracy' and 'ROC'. Study quality was assessed using the PRISMA guidelines and QUADAS-2 tool. A meta-analysis was planned for the following predictive factors: intertwin nuchal translucency (NT) discrepancy; NT > 95th percentile in at least one twin; intertwin crown-rump length (CRL) discrepancy as a percentage of the larger CRL; abnormal ductus venosus (DV) flow in at least one twin. The outcome assessed was TTTS, defined according to the presence of a twin oligohydramnios-polyhydramnios sequence. The diagnostic performance of the predictive factors was evaluated for each included study. RESULTS: The electronic search identified 152 records, of which 23 were assessed in full for eligibility. We identified 13 eligible studies that reported the predictive accuracy of ultrasound parameters, measured before 16 weeks, for the development of TTTS, including a total of 1991 pregnancies, of which 323 developed TTTS. An increased risk of TTTS was associated with: intertwin NT discrepancy (positive likelihood ratio (LR+), 1.92 (95% CI, 1.25-2.96); negative likelihood ratio (LR-), 0.65 (95% CI, 0.50-0.84)); NT > 95th percentile (LR+, 2.63 (95% CI, 1.51-4.58); LR-, 0.85 (95% CI, 0.75-0.96)); CRL discrepancy > 10% (LR+, 1.80 (95% CI, 1.05-3.07); LR-, 0.92 (95% CI, 0.81-1.05)); abnormal DV flow (LR+, 4.77 (95% CI, 1.33-17.04; LR-, 0.49 (95% CI, 0.17-1.41)). The highest sensitivities were observed for intertwin NT discrepancy (52.8% (95% CI, 43.8-61.7%)) and abnormal DV flow (50.0% (95% CI, 33.4-66.6%)). CONCLUSION: Monochorionic twin pregnancies with intertwin NT discrepancy, NT > 95th percentile, intertwin CRL discrepancy > 10% or abnormal DV flow on first-trimester ultrasound examination are at significantly increased risk of developing TTTS. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of ultrasound in predicting birth-weight discordance in twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic performance of ultrasound in predicting birth-weight (BW) discordance in twin pregnancy. METHODS: Electronic databases PubMed, EMBASE and CINAHL were searched using combinations of MeSH terms 'birth weight', 'discordance', 'twins' and 'ultrasound'. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios for the predictive accuracy of sonographically estimated fetal-weight (EFW) discordance and abdominal-circumference (AC) discordance in predicting BW discordance were computed using hierarchical summary receiver-operating characteristics curves. RESULTS: Twenty studies (including 5826 twin pregnancies) were included. EFW discordance ≥ 20% had a sensitivity of 65.4% and specificity of 90.8% in predicting BW discordance ≥ 20%. The predictive performance of ultrasound performed within 1 month, 2 weeks and 3 days before birth was 61.4%, 72.3% and 78.9%, respectively. EFW discordance ≥ 25% had a sensitivity of 57.7% and specificity of 95.2% in predicting BW discordance ≥ 25%. The sensitivity of EFW discordance ≥ 25% detected within 1 month, 2 weeks and 3 days before birth was 60.0%, 75.0% and 60.3%, respectively, while the corresponding values for specificity were 97.7%, 96.2% and 87.3%, respectively. In view of the different cut-offs reported among studies, it was not possible to perform comprehensive data synthesis for each AC discordance cut-off. The optimal diagnostic performance of AC discordance was for prediction of BW discordance ≥ 25%, with a sensitivity of 70.8% and specificity of 86.4%. CONCLUSION: Ultrasound EFW discordance has an overall moderate accuracy in predicting BW discordance in twin pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Outcome of fetal ovarian cysts diagnosed on prenatal ultrasound examination: systematic review and meta-analysis.

OBJECTIVE: To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst. METHODS: The electronic databases MEDLINE and EMBASE were searched using keywords and word variants for 'ovarian cysts', 'ultrasound' and 'outcome'. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale. RESULTS: Thirty-four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0-61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10-0.23)) and in cysts measuring ≥ 40 mm vs < 40 mm (OR, 0.03 (95% CI, 0.01-0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9-71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with < 40 mm (OR, 30.8 (95% CI, 8.6-110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with < 40 mm (OR, 64.4 (95% CI, 23.6-175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5-24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8-64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4-19.7%) and 12.8% (95% CI, 3.8-26.0%), respectively, and 21.8% (95% CI, 0.9-40.0%) had surgery after birth. CONCLUSION: Size and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cervical length at mid-gestation in screening for preterm birth in twin pregnancy.

OBJECTIVE: Short cervical length (CL) in mid-gestation is considered predictive of spontaneous preterm birth (PTB). The medical literature suggests 20 mm as the cut-off for high risk in twin pregnancies. Our objective was to assess the predictive value of CL for spontaneous PTB < 32 weeks' gestation in twin pregnancies and to calculate the cut-off point with the best sensitivity and specificity. METHODS: This was a single-center retrospective cohort study of women in whom CL had been measured by transvaginal ultrasound at 18-23 weeks' gestation. Pregnancies complicated by twin-to-twin transfusion syndrome, those requiring intrauterine therapy or those with indicated PTB were excluded. The predictive value of CL for PTB < 32 weeks was assessed. The distribution of CL measurements and the optimal cut-off in patients with PTB were calculated and logistic regression analysis was performed to assess the association between pregnancy characteristics and PTB. RESULTS: A total of 940 twin pregnancies were included. CL showed an area under the receiver-operating characteristics curve of 0.65 (95% CI, 0.58-0.71) for the prediction of PTB < 32 weeks. The optimal cut-off value for predicting PTB was 36 mm (sensitivity, 64.1%; specificity, 62.8%; positive predictive value, 13.5%; negative predictive value, 95.1%; accuracy, 62.9%). The relative risk of PTB with CL ≤ 36 mm was 2.35 (95% CI, 1.53-3.60; P < 0.001). After adjusting for confounders in logistic regression analysis, only CL (adjusted odds ratio (aOR), 0.94 (95% CI, 0.90-0.99); P = 0.03), and not monochorionicity (aOR 4.14 (95% CI, 0.89-19.25); P = 0.07), was independently associated with PTB. More than one-third (36%) of PTB cases delivering < 32 weeks had a normal CL in mid-gestation. This proportion rose to 85% when considering the 20-mm cut-off suggested by the medical literature. CONCLUSIONS: This study shows that, despite the weak independent association, CL assessed in mid-gestation is a poor predictor of PTB < 32 weeks' gestation in asymptomatic twin pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Intertwin discrepancy in middle cerebral artery peak systolic velocity and third-trimester fetal growth restriction in monochorionic-diamniotic twin pregnancy.

OBJECTIVES: To assess the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) for the prediction of late selective intrauterine growth restriction (sIUGR) at birth and birth weight discrepancy of > 25% (BW-25) in otherwise uncomplicated monochorionic-diamniotic (MCDA) twin pregnancies. METHODS: This was a cohort study including all MCDA pregnancies followed in a tertiary fetal medicine unit between 2008 and 2013. Exclusion criteria were referral after first trimester, abnormal karyotype, structural anomalies, twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence and sIUGR detected before 28 weeks. MCA-PSV values of both twins measured in the second trimester (18-24 weeks) and early third trimester (26-32 weeks) were converted in multiples of the median (MoM). sIUGR was defined as birth weight < 5(th) centile. The relationship between MCA-PSV discrepancy, sIUGR and BW-25 was assessed by logistic regression analysis. Receiver-operating characteristics (ROC) curves were used to ascertain the predictive value of MCA-PSV discrepancy for such complications. RESULTS: In total, 136 MCDA twin pregnancies were included in the analysis. Thirty (22.1%) were complicated with sIUGR at birth and 12 (8.8%) were complicated with BW-25. Logistic regression analysis identified MCA-PSV discrepancy as an independent predictor for sIUGR. ROC curves identified third-trimester MCA-PSV discrepancy as the best predictor for both sIUGR (area under ROC curve (AUC), 0.73 (95% CI, 0.62-0.85)) and BW-25 (AUC, 0.79 (95% CI, 0.65-0.93)). The optimal cut-off point for MCA-PSV discrepancy was 0.30 MoM (sensitivity, 70% and specificity, 69% for sIUGR; sensitivity, 83% and specificity, 72% for BW-25). CONCLUSION: In MCDA twin pregnancies, MCA-PSV discrepancy is associated with both sIUGR at birth and BW discordance. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.

AIM: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. METHODS: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. RESULTS: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. CONCLUSION: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.

Crown-rump length discordance and adverse perinatal outcome in twin pregnancies: systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to explore the relationship between crown-rump length (CRL) discordance detected at 11-14 weeks of gestation and adverse outcome in twin pregnancy and to assess its predictive accuracy. METHODS: A protocol designed a priori following MOOSE guidelines and recommended for systematic review and meta-analysis was used. The outcomes observed were: total fetal and perinatal loss, fetal loss at <24 weeks, fetal loss at ≥ 24 weeks, birth-weight (BW) discordance, preterm delivery (PTD) at < 34 weeks and fetal anomalies. The analysis was performed for all twins and for dichorionic (DC) and monochorionic (MC) twins separately. RESULTS: A total of 2008 articles were identified and 17 studies were included in the systematic review. Twin pregnancies with CRL discordance ≥ 10% were at significantly higher risk of perinatal loss (RR, 2.80; 95% CI, 1.25-6.27; P = 0.012), fetal loss at ≥ 24 weeks (RR, 4.07; 95% CI, 1.47-11.23; P = 0.006), BW discordance (RR, 2.24; 95% CI, 1.89-2.64; P < 0.001) and PTD at < 34 weeks (RR, 1.49; 95% CI, 1.23-1.80; P < 0.001) but not of fetal loss at < 24 weeks (P = 0.130). A meta-analysis of fetal anomalies was not possible because fewer than two studies explored this outcome. However, when used alone to screen for adverse pregnancy outcome, the predictive accuracy of CRL discordance was low for each of the outcomes explored. CONCLUSION: CRL discordance is associated with an increased risk of adverse pregnancy outcome. However, the accuracy of CRL discordance in predicting adverse outcome is poor and thus limits its routine use in clinical practice.

Neurodevelopmental outcome in isolated mild fetal ventriculomegaly: systematic review and meta-analysis.

OBJECTIVES: The finding of fetal ventriculomegaly is variably associated with other fetal abnormalities and, even when isolated, is thought to be linked to abnormal neurodevelopmental outcome. The aim of this study was to undertake a systematic review and meta-analysis of the current literature to assess the prevalence of neurodevelopmental delay in cases of isolated mild fetal ventriculomegaly, as well as the false-negative rate of prenatal imaging for the diagnosis of associated abnormalities in patients referred for isolated mild ventriculomegaly. METHODS: Studies that assessed neurodevelopmental outcome in isolated ventriculomegaly were identified from a search of scientific databases. Studies that did not check for karyotype or that excluded cases of bilateral ventriculomegaly were not included in the analysis. Ventriculomegaly was defined as mild when the width of the ventricular atrium was between 10 and 15 mm. Cases in which an associated abnormality (abnormal karyotype, structural abnormality or fetal infection) was observed either before or after birth were not considered as part of the isolated group. Neurodevelopmental delay was defined as an abnormal quotient score, according to the test used. RESULTS: The search yielded 961 possible citations; of these, 904 were excluded by review of the title or abstract as they did not meet the selection criteria. Full manuscripts were retrieved for 57 studies, and 20 were included in the review with a total of 699 cases of isolated mild ventriculomegaly. The overall prevalence of neurodevelopmental delay was 7.9% (95% CI, 4.7-11.1%). Of the 20 studies included in the systematic review, nine reported data on postnatal imaging, showing a prevalence of previously undiagnosed findings of 7.4% (95% CI, 3.1-11.8%). CONCLUSIONS: The false-negative rate of prenatal imaging is 7.4% in apparently isolated fetal ventriculomegaly of ≤ 15 mm. The incidence of neurodevelopmental delay in truly isolated ventriculomegaly of ≤ 15 mm is 7.9%. As the latter rate is similar to that noted in the general population, large prospective cohort studies assessing the prevalence of childhood disability, rather than subtle neurodevelopmental delay, are required.

Multichromophoric electrochromic polymers: colour tuning of conjugated polymers through the side chain functionalization approach.

Organic electrochromic materials have gained constantly increasing interest over the years with respect to their inorganic counterpart due to essentially two distinctive characteristics: their processability through solution based low cost processes and their wide colour palette. Such characteristic features enabled their application in displays, smart windows, electronic paper and ophthalmic lenses. Alongside the established concept of donor-acceptor polymers, side chain functionalized multichromophoric polymers are gaining attention as a highly performing and synthetically feasible alternative, particularly relevant to applications requiring a complete colourlessness in one of the accessible redox states of the material. The primary aim of the present article is to review all the results involving the tuning of the native electrochromic properties of simple conjugated polymers through the introduction of a discrete electrochromic molecule as a side chain substituent.

Fetal weight estimation in gestational diabetic pregnancies: comparison between conventional and three-dimensional fractional thigh volume methods using gestation-adjusted projection.

OBJECTIVES: To evaluate the accuracy of gestation-adjusted birth-weight estimation using a three-dimensional (3D) fractional thigh volume (TVol) method in pregnant women with gestational diabetes mellitus (GDM), and to compare it with the conventional two-dimensional method of Hadlock et al. METHODS: Pregnant women with GDM were referred at 34 to 36 + 6 weeks' gestation for ultrasound examination. Estimated fetal weight (EFW) was obtained using both the Hadlock and the TVol methods. Using a gestation-adjusted projection method, predicted birth weight was compared to actual birth weight at delivery. RESULTS: Based on 125 pregnancies, the TVol method with gestation-adjusted projection had a mean (± SD) percentage error in estimating birth weight of -0.01 ± 5.0 (95% CI, -0.96 to 0.98)% while the method of Hadlock with gestation-adjusted projection had an error of 1.28 ± 9.1 (95% CI, -0.33 to 2.87)%. The mean percentage error of the two methods was significantly different (P = 0.039), while the random error was not (P = 1.0). For the prediction of macrosomia (birth weight ≥ 4000 g, n = 19), sensitivity was 84 and 63% for the TVol and Hadlock methods, respectively (95% CI for difference -2 to 44%, P = 0.22) and specificity was 96 and 89% for the TVol and Hadlock methods, respectively (95% CI for difference 5-9%, P = 0.01). CONCLUSIONS: In women with GDM, a new method of estimating birth weight based on 3D-TVol measurements performed at 34 + 0 to 36 + 6 weeks' gestation and gestation-adjusted projection of estimated fetal weight, is more accurate than the standard method based on Hadlock's formula in predicting birth weight. The TVol method has comparable sensitivity but higher specificity than the Hadlock method in predicting neonatal macrosomia.

Association between reduced fetal movements at term and abnormal uterine artery Doppler indices.

OBJECTIVES: To evaluate the association between second-trimester uterine artery (UtA) Doppler pulsatility index (PI) with reduced fetal movements (RFM) and adverse pregnancy outcome at term. METHODS: This was a retrospective cohort study of all singleton pregnancies referred for routine antenatal care at a fetal medicine unit over a 5-year period. UtA Doppler indices were obtained at the time of the routine anomaly scan between 19 and 23 weeks' gestation to assess the risk for pre-eclampsia. All episodes of RFM within 1 month of the expected date of delivery were recorded. Regression and sensitivity analyses were used to assess the relationship between UtA-PI with RFM, small-for-gestational-age (SGA) fetuses and stillbirth after 36 weeks' gestation. RESULTS: Overall, 17, 649 pregnancies were included in the analysis, of which 742 presented with RFM, 1494 gave birth to an SGA newborn and 53 were complicated by stillbirth after 36 weeks' gestation. Logistic regression analysis showed a significant and independent association between UtA-PI and RFM (odds ratio (OR), 5.03 (95% CI, 4.21-6.01); P < 0.001), SGA (OR 2.41 (95% CI, 2.09-2.79); P < 0.001) and stillbirth (OR 1.55 (95% CI, 1.21-1.98); P< 0.001). The association between UtA-PI and SGA was significantly stronger in women presenting with RFM than in the rest of the cohort (P < 0.001). Similarly the association between UtA-PI and RFM was significantly stronger in those pregnancies complicated by stillbirth (P < 0.001). CONCLUSIONS: Compared with normal pregnancies, those complicated by RFM, SGA and stillbirth at term had higher UtA-PI at 19-23 weeks' gestation. These findings support the assertion that RFM at term is independently related to placental dysfunction and subsequent risk for SGA and stillbirth.

The indocyanine green method is equivalent to the 99mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: a concordance and validation study.

AIMS: The aim of this study was to assess concordance between the indocyanine green (ICG) method and (99m)Tc-radiotracer method to identify the sentinel node (SN) in breast cancer. Evidence supports the feasibility and efficacy of the ICG to identify the SN, however this method has not been prospectively compared with the gold-standard radiotracer method in terms of SN detection rate. METHODS: Between June 2011 and January 2013, 134 women with clinically node-negative early breast cancer received subdermal/peritumoral injection of (99m)Tc-labeled tracer for lymphoscintigraphy, followed by intraoperative injection of ICG for fluorescence detection of SNs using an exciting light source combined with a camera. In all patients, SNs were first identified by the fluorescence method (ICG-positive) and removed. A gamma ray-detecting probe was then used to determine whether ICG-positive SNs were hot ((99m)Tc-positive) and to identify and remove any (99m)Tc-positive (ICG-negative) SNs remaining in the axilla. The study was powered to perform an equivalence analysis. RESULTS: The 134 patients provided 246 SNs, detected by one or both methods. 1, 2 and 3 SNs, respectively, were detected, removed and examined in 70 (52.2%), 39 (29.1%) and 17 (12.7%) patients; 4-10 SNs were detected and examined in the remaining 8 patients. The two methods were concordant for 230/246 (93.5%) SNs and discordant for 16 (6.5%) SNs. The ICG method detected 99.6% of all SNs. CONCLUSIONS: Fluorescent lymphangiography with ICG allows easy identification of axillary SNs, at a frequency not inferior to that of radiotracer, and can be used alone to reliably identify SNs.

The effect of metformin on apoptosis in a breast cancer presurgical trial.

BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial. METHODS: Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery. RESULTS: Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2-12; placebo arm: +2%, IQR: 0-8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman's r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2-14 vs +2%, IQR: 0-7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0-6, vs +5%, IQR: 0-15 on placebo, P-interaction=0.1). CONCLUSION: Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status.