Prenatal Cardiac Ultrasound Markers of Outcomes in Ebstein's Anomaly: An International Multicenter Case Series.

This study aimed to analyze prenatal cardiac ultrasound markers of outcome in fetuses with Ebstein's anomaly (EA). From a retrospective database, 35 fetuses diagnosed with EA at fetal medicine centers in Brazil, Italy, and Poland were retrieved. The primary outcome was perinatal mortality. We analyzed prenatal cardiac ultrasound markers of outcomes and perinatal follow-up. Gestational age at diagnosis, extracardiac fetal anomalies, spontaneous fetal demise, and gestational age at each event were recorded. In postnatal survivors, data on cardiac surgery and short-term postoperative outcomes were collected. Our study included a cohort of 35 fetuses with EA (mean gestational age of 29.4 weeks), in which 6 fetuses were excluded due to termination of pregnancy (3), pregnancy still ongoing (2), and missed follow-up (1). Of the remaining 29 cases, severe tricuspid regurgitation and absence of anterograde pulmonary flow (pulmonary atresia) were observed in 88%. Significant cardiomegaly accounts for 58% of these data with a mean cardiothoracic ratio of 0.59. The cardiovascular profile (CVS) score ≤ 6 in six patients with one survival (4 fetal deaths, one stillbirth, and one survival). All fetuses with CVS score of 5 had intrauterine demise. Seventeen fetuses were born alive (53.1% of 29 cases). Of the remaining fetuses, one (1%) fetal was a stillbirth, six (20%) fetuses were neonatal deaths, and five (17%) fetuses were fetal deaths. Of the nineteen patients who underwent surgery to correct the cardiac defect, 17 survived after surgery. Among the survivors, biventricular cardiac repair was performed using the cone technique (da Silva's approach) in the majority of cases. We observed 2 abnormal karyotypes among in the remaining 29 fetuses. One of the patients with abnormal karyotype was a fetus with ascites and large for gestational age. The other patient with abnormal karyotype underwent cardiac surgery and progressed to neonatal death. Nine patients (25%) had extracardiac anomalies (genitourinary anomalies and single umbilical artery), being that 2 of them are alive and 4 died (2 had fetal and 2 neonatal death). Fetal EA is associated with high mortality. The most common prenatal marker associated with non-survival was CVP score ≤ 6. Fetuses that survived and underwent postnatal corrective surgery are significantly favorable outcomes.

A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause.

OBJECTIVE: The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status. METHODS: Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status. RESULTS: One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding (p < .005), easy bruising (p = .028), fissures (p = .008), petechiae/splinter hemorrhages (p < .001), and bleeding/blistering or open sores (p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum (p = .013) and the perianal region (p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population (p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population (p = .047). CONCLUSIONS: Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.

Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

OBJECTIVE: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability. DATA SOURCES: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023. STUDY ELIGIBILITY CRITERIA: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation). METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029). RESULTS: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases. CONCLUSION: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making.

A national survey on current practice of ultrasound in labor ward.

OBJECTIVES: Use of ultrasonography has been suggested as an accurate adjunct to clinical evaluation of fetal position and station during labor. There are no available reports concerning its actual use in delivery wards. The aim of this survey was to evaluate the current practice regarding the use of ultrasonography during labor. METHODS: A questionnaire was sent to members of the Italian Society of Ultrasound in Obstetrics and Gynecology employed in delivery wards. The qFeuestionnaire was made up of 22 questions evaluating participant characteristics and the current use of ultrasound in labor in their hospital of employment. The answers were grouped according to participant characteristics. RESULTS: A total of 200 participants replied. Ultrasound was considered useful before an operative vaginal delivery by 59.6 % of respondents, while 51.8 and 52.5 % considered it useful in the management of prolonged first and second stages of labor, respectively. The major indication for ultrasound use during labor was the assessment of fetal occiput position. The major difficulties in its application were the perceived lack of training and the complexity of the ultrasound equipment use. Participants that reported fewer difficulties were those employed in hospitals with a higher number of deliveries or having delivery units with more years of experience using ultrasound in labor, or those who had attended specific training courses. CONCLUSIONS: The results indicate that, despite the reported evidence of a higher accuracy of ultrasound compared to clinical evaluation in assessing fetal position and station, its use is still limited, even amongst maternal-fetal medicine practitioners specialized in ultrasonography.

Prenatal identification of a pathogenic maternal FGFR1 variant in two consecutive pregnancies with fetal forebrain malformations.

OBJECTIVE: Holoprosencephaly (HPE) is the most common aberration of forebrain development, and it leads to a wide spectrum of developmental and craniofacial anomalies. HPE etiology is highly heterogeneous and includes both chromosomal abnormalities and single-gene defects. METHODS: Here, we report an FGFR1 heterozygous variant detected by prenatal exome sequencing and inherited from the asymptomatic mother, in association with recurrent neurological abnormalities in the HPE spectrum in two consecutive pregnancies. RESULTS: Individuals with germline pathogenic variants in FGFR1 (MIM: 136350) show extensive phenotypic variability, which ranges from asymptomatic carriers to hypogonadotropic hypogonadism, arhinencephaly, Kallmann's syndrome with associated features such as cleft lip and palate, skeletal anomalies, isolated HPE, and Hartsfield syndrome. CONCLUSION: The presented case supports the role of exome sequencing in prenatal diagnosis when fetal midline structural anomalies are suggestive of a genetic etiology, as early as the first trimester of gestation. The profound heterogeneity of FGFR1 allelic disorders needs to be considered when planning prenatal screening even in asymptomatic carriers.

Effects of uterine Doppler on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVE: To investigate midbrain growth, including corpus callusum (CC), cerebellar vermis (CV) and cortical development in late fetal growth restriction (FGR) depending on uterine artery (UtA) Pulsatility Index (PI) values. METHODS: This was a prospective study including singleton fetuses with late FGR characterized by abnormal cerebral placental ratio (CPR). According to UtA PI values, the FGR fetuses were subdivided into normal ≤95th centile) and abnormal (>95th centile). Neurosonography was performed at 33-44 weeks of gestations to assess CC and CV lengths and the depth of Sylvian fissure (SF), parieto-occipital (POF) and calcarine fissures (CF). Neurosonographic variables were normalized for fetal head circumference size. RESULTS: The study cohort included 60 fetuses with late FGR, 39 with normal UtA PI and 21 with abnormal PI values. The latter group showed significant differences in CC (median (interquartile range) normal 35.9 (28.49-45.53) vs abnormal UtA PI 25.31(19.76-35.13) mm; p < 0.0022), CV (normal 25.78 (18.19-29.35) abnormal UtA PI 17.03 (14.07-24.16)mm; p = 0.0067); SF (normal 10.58 (8.99-11.97)vs abnormal UtA PI 7.44 (6.23-8.46) mm; p < 0.0001), POF (normal 6.85 (6.35-8.14) vs abnormal UtA PI 4.82 (3.46-7.75) mm; p < = 0.0184) and CF (normal 04.157 (2.85-5.41) vs abnormal UtA PI 2.33 (2.49-4.01)); p < 0.0382). CONCLUSIONS: Late onset FGR fetuses with abnormal UtA PI showed shorter CC and CV length and delayed cortical development compared to those with normal uterine PI. These findings support the existence of a link between abnormal brain development and changes in utero placental circulation.

Counseling in fetal medicine: Congenital cytomegalovirus infection.

Although the clinical work-up of CMV in pregnancy has gradually become more accurate, counseling for CMV is still challenging. Despite the potential feasibility of universal prenatal serological screening, its introduction in prenatal diagnosis continues to raise concerns related to its real cost-effectiveness. Contextually, anticipating the confirmation of fetal infection earlier in pregnancy is one of the most pressing issues to reduce the parental psychological burden. Amniocentesis is still the gold standard and recent data have demonstrated that it could be performed before 20 weeks of gestation, provided that at least 8 weeks have elapsed from the presumed date of maternal seroconversion. New approaches, such as chorionic villus sampling (CVS) and virome DNA, even if not yet validated as confirmation of fetal infection, have been studied alternatively to amniocentesis to reduce the time-interval from maternal seroconversion and the amniocentesis results. Risk stratification for sensorineural hearing loss (SNHL) and long-term sequelae should be provided according to the prognostic predictors. Nevertheless, in the era of valacyclovir, maternal high-dose therapy, mainly for first trimester infections, can reduce the risk of vertical transmission and increase the likelihood of asymptomatic newborns, but it is still unclear whether valacyclovir continues to exert a beneficial effect on fetuses with positive amniocentesis. This review provides updated evidence-based key counseling points with GRADE recommendations.

Effects of umbilical vein flow on midbrain growth and cortical development in late onset fetal growth restricted fetuses: a prospective cross-sectional study.

OBJECTIVES: To investigate midbrain growth, including corpus callusum (CC) and cerebellar vermis (CV) and cortical development in late fetal growth restricted (FGR) subclassified according to the umbilical vein blood flow (UVBF) values. METHODS: This was a prospective study on singleton fetuses late FGR with abnormal placental cerebral ratio (PCR). FGR fetuses were further subdivided into normal (≥fifth centile) and abnormal (

Fetal brain development in pregnancies complicated by gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) carries an increased risk of neurocognitive impairment in offsprings. However, the contribution of maternal hyperglycemia in affecting fetal brain development is not fully elucidated yet. The aim of this study was to evaluate fetal brain and sulci development in pregnancies complicated by GDM. METHODS: Prospective observational study including 100 singleton pregnancies complicated by GDM and 100 matched controls. All fetuses underwent neurosonography at 29-34 weeks of gestation, including the assessment of the length of the corpus callosum (CC), cerebellar vermis (CV), Sylvian (SF), parieto-occipital (POF) and calcarine fissures (CF). Sub-group analysis according to the specific treatment regimen adopted (n 67 diet vs. 33 insulin therapy) was also performed. RESULTS: Fetuses from mothers with GDM under insulin therapy had a smaller CC (35.54 mm) compared to both controls (40 mm; p<0.001) and women with GDM under diet (39.26 mm; p=0.022) while there was no difference in the HC between the groups. Likewise, when corrected for HC, CV depth was smaller in fetuses with GDM both under insulin therapy (7.03 mm) and diet (7.05 mm,) compared to controls (7.36 mm; p=0.013). Finally, when assessing the sulci development of the brain SF (p≤0.0001), POF (p≤0.0001) and CF (p≤0.0001) were significantly smaller in fetuses with maternal GDM. Post-hoc analysis showed that fetuses of GDM mothers requiring insulin therapy had significantly lower values of SF (p=0.032), POF (p=0.016) and CF (p=0.001). CONCLUSIONS: Pregnancies complicated by GDM showed a peculiar pattern of fetal brain growth and cortical development and these changes, which are more evident in those requiring insulin supplementation.

Effects of gender on fetal cortical development: a secondary analysis of a prospective cross-sectional study.

OBJECTIVES: The primary objective was to evaluate the effects of fetal sex on fetal cortical development in low-risk pregnancies. Secondary objective was the evaluate the impact of gestational age. METHODS: This was a secondary analysis of a prospective cross-sectional study on low-risk fetuses undergoing fetal neurosonography between 19 and 34 weeks of gestation. The depth of Sylvian Fissure (SF), Parieto Occipital Fissure (POF) and Calcarine Fissure (CF) were evaluated and related to fetal sex. Neurosonographic variables were normalized for fetal head circumference and expressed as multiple of the median (MoM). RESULTS: A total of 344 fetuses were considered (173 male, 171 female). The baseline characteristic of the two groups were similar except a higher birthweight present in male fetuses (p=0.044). The depth SF (p=0.023) CF (p=0.014) and POF (p=0.046) showed significantly higher values in male fetuses when all the gestational age range was considered. However, when data were controlled for gestational age, these differences resulted significant only after 28 weeks. CONCLUSIONS: Differences in cortical development related to gender occur after 28 weeks of gestation with an increase depth of SF, POF and CF in male fetuses.

Validation of an automated software (Smartpelvic™) in assessing hiatal area from three dimensional transperineal pelvic volumes of pregnant women: comparison with manual analysis.

OBJECTIVES: The aim of this investigation was to evaluate the agreement between a manual and an automatic technique in assessing levator hiatus area (LHA) during pregnancy from three-dimensional (3D) pelvic floor volumes obtained by trans-perineal ultrasound (TPUS). METHODS: 3D volumes were acquired during rest, maximum pelvic floor contraction and Valsalva maneuver from 66 pregnant women. Manual selection of LHA and automatic software (Smart Pelvic™) were applied on TPUS volume starting from a C-plane view. To evaluate intra- and inter-observer variability measurements of LHA were performed twice by the same operator and once by a second sonographer. Reference hiatal contours obtained manually by the first operator were compared with the automated ones. Reproducibility was evaluated by intraclass correlation coefficients (ICC) and Bland-Altman plots. RESULTS: LHA measurement, using automatic software, achieved excellent intra-observer and inter-observer reproducibility in pregnant women both at rest and after dynamic analysis (ICC>0.9). Further, an excellent agreement resulted between manual selection of the LHA and automatic imaging (ICC>0.9). The average time taken to obtain LHA manually was significantly longer when compared to the automatic analysis (p≤0.0001). CONCLUSIONS: Smart pelvic software resulted from a reliable method for automatically measuring the LHA, showing high reproducibility and accuracy.

Ectrodactyly-ectodermal dysplasia-clefting syndrome. Prenatal prospective ultrasound diagnosis.

OBJECTIVE: Prenatal diagnosis of the Ectrodactyly-Ectodermal dysplasia-clefting (EEC) syndrome has been based upon the detection of ectrodactyly, in association with facial clefting and/or positive family history. Our aim is to describe other ultrasonographic features indicating the presuntive diagnosis, regardless of genetic diagnosis, especially in cases of negative family history. MATERIALS AND METHODS: A case report and a review of the literature was assessed. RESULTS: Our case report showed a singleton foetus "lobster claw" deformities of hands and feet. Paternal history revealed bilateral agenesia of two fingers. Through literature, 15 case reports of prenatal diagnosis of EEC syndrome were found, 14 of which were eligible for our systematic review. The 33% of cases (5/15) had a familiar history of EEC, thus, we found one case of consanguinity of parents. Anomalies EEC-related were recognized in the 40% of cases (6/15). An association with genitourinary anomalies was found in 30% (5/15) of them. CONCLUSIONS: A strong suspicion of final diagnosis of EEC may be done in the presence of ectrodactyly, facial clefting and urinary malformation especially in cases of negative family history. More attention should be given to a genetic counseling, especially to understand a possible relation to other genetic syndromes.

Modeling fetal cavum septum pellucidi width by quantile regression at 18-34 weeks of gestation: A prospective cross-sectional study.

OBJECTIVE: Develop charts for cavum septum pellucidi (CSP) following a standardized methodology and using quantile regression. The secondary objective was to assess the influence of fetal gender on the generated reference curves. METHODS: In a cross-sectional prospective study 453 low-risk singleton pregnancies were evaluated at a gestational age interval between 18 and 34 weeks. The width of CSP were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). Differences between sex were evaluated. RESULTS: The measurement of CSP significantly increased with gestation and HC. Linear models better described the changes of CSP with GA and HC. The fits of CSP width with GA and HC were not significantly different. Male fetuses showed significantly higher CSP width when compared to female fetuses (u = 2.973; p = 0.005). CONCLUSIONS: We generated prospective nomograms of fetal CSP development using quantile regression and following a strict standardized methodology. These new charts may be useful to better identify abnormal cases at higher risk of associated anomalies. Further our findings underline the potential effect of gender in developing fetal brain.

Modeling fetal cortical development by quantile regression for gestational age and head circumference: a prospective cross sectional study.

OBJECTIVES: To develop charts for fetal brain cortical structures following a proposed standardized methodology and using quantile regression. METHODS: Prospective cross-sectional study including 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. The depth of Sylvian (SF), Parieto-occipital (POF) and Calcarine fissures (CF) were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). RESULTS: The measurements of SF, POF and CF depth significantly increased with gestation. Linear models better described the changes of cortical variables with GA and HC. When the fit of sulci depth with GA and HC were compared, a close relationship was highlighted for the latter variable. CONCLUSIONS: We provided prospective charts of fetal cortical development using quantile regression and following a strict standardized methodology These new charts may help in better identifying cases at higher risk of abnormal cortical neurodevelopment.

Evaluation of an artificial intelligent algorithm (Heartassist™) to automatically assess the quality of second trimester cardiac views: a prospective study.

OBJECTIVES: The aim of this study was to evaluate the agreement between visual and automatic methods in assessing the adequacy of fetal cardiac views obtained during second trimester ultrasonographic examination. METHODS: In a prospective observational study frames of the four-chamber view left and right outflow tracts, and three-vessel trachea view were obtained from 120 consecutive singleton low-risk women undergoing second trimester ultrasound at 19-23 weeks of gestation. For each frame, the quality assessment was performed by an expert sonographer and by an artificial intelligence software (Heartassist™). The Cohen's κ coefficient was used to evaluate the agreement rates between both techniques. RESULTS: The number and percentage of images considered adequate visually by the expert or with Heartassist™ were similar with a percentage >87 % for all the cardiac views considered. The Cohen's κ coefficient values were for the four-chamber view 0.827 (95 % CI 0.662-0.992), 0.814 (95 % CI 0.638-0.990) for left ventricle outflow tract, 0.838 (95 % CI 0.683-0.992) and three vessel trachea view 0.866 (95 % CI 0.717-0.999), indicating a good agreement between the two techniques. CONCLUSIONS: Heartassist™ allows to obtain the automatic evaluation of fetal cardiac views, reached the same accuracy of expert visual assessment and has the potential to be applied in the evaluation of fetal heart during second trimester ultrasonographic screening of fetal anomalies.

Induction of Labor in Women with Previous Cesarean Section and Unfavorable Cervix: A Retrospective Cohort Study.

Background: The efficacy and safety of a cervical ripening balloon (CRB) in women with a previous cesarean section (CS) and unfavorable Bishop score are still controversial. Methods: A retrospective cohort study was performed across six tertiary hospitals from 2015 to 2019. Women with one previous transverse CS, singleton cephalic term pregnancy and BS < 6 were included if submitted to labor induction with a CRB. The main outcome was the rate of vaginal birth after cesarean (VBAC) after CRB ripening. Secondary outcomes were abnormal composite fetal and maternal outcomes. Results: Of the 265 women included, 57.3% had successful vaginal birth. Augmentation improved vaginal delivery (32.2% vs. 21.2%). Intrapartum analgesia was associated with an increased VBAC rate (58.6% vs. 34.5%). Maternal BMI ≥30 and age ≥40 years increased emergency CS rate (11.8% vs. 28.3% and 7.2 vs. 15.9%). Composite adverse maternal outcome occurred in 4.8% of CRB group women and increased to 17.6% when associated with oxytocin. Uterine rupture occurred in one case (0.4%) in the CRB-oxytocin group. Poorer fetal outcome occurred after emergency CS, if compared to successful VBAC (12.4% vs. 3.3%). Conclusions: In women with a previous CS and unfavorable Bishop score, induction of labor with a CRB can be considered safe and effective.

The role of ultrasound in the diagnosis and management of postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of death or severe morbidity for the mother after delivery. As a consequence healthcare staff working in the delivery room should be trained to perform a prompt diagnosis and adequate management of PPH. Uneventful outcome is induced correct identification of the underlying cause of hemorrhage. Ultrasound is a promising technique for the prompt diagnosis of PPH etiology. Indeed, it is easily available, with relatively low cost, not using ionizing radiation, and can be used in different settings including the labor room, the operating theater and at the bedside of an affected women. In order to be effective Obstetricians should have an adequate knowledge of postpartum ultrasonography. In this article, we will review the sonographic findings occurring in PPH, in the differential diagnosis of the underlying cause of hemorrhage, that include retained placenta, morbidly adherent placenta, rupture of the uterus uterine, vascular anomalies of the uterine arteries and uterine inversion. We will also provide an algorithm to manage PPH according to the ultrasonographic findings.

Prognostic Value of Amniotic Fluid Viral Load to Predict Adverse Outcome in Pregnancies Complicated by Congenital Cytomegalovirus Infection: A Multicenter Study.

INTRODUCTION: The aim of the study was to report the prognostic value of cytomegalovirus (CMV) viral load in the amniotic fluid (AF) in predicting the outcome of infected pregnancies. METHODS: Multicenter retrospective study involving 11 Italian referral centers from 2012 to 2021 was conducted. Inclusion criteria were fetuses with confirmed congenital CMV infection. The primary outcome was the prognostic value accuracy of CMV quantitative polymerase chain reaction (qPCR) in AF in predicting the risk of additional anomalies detected either at follow-up ultrasound or fetal magnetic resonance imaging (MRI). The secondary outcome was prediction of postnatal clinical symptoms related to CMV infection. Multivariate logistic regression and area under the curve (AUC) analyses were used to analyze the data. RESULTS: 104 fetuses were included. Associated anomalies detected at follow-up ultrasound or fetal MRI were detected in 14.4% of cases (15/104). Mean AF CMV viral load was significantly higher in fetuses with additional anomalies compared to those without additional anomalies at follow-up ultrasound or fetal MRI (3,346,634.27 ± 402,582.95 vs. 761,934 ± 222513,2 p < 0.001). At multivariate logistic regression analysis, CMV AF viral load was independently associated with the presence of additional anomalies at follow-up ultrasound or MRI, with an OR of 1.07 (p = 0.010), while maternal age (p = 0.24), trimester at maternal infection (p = 0.97), and type of infection (primary vs. non-primary) (p = 0.12) were not. CMV AF viral load had AUC of 0.755 for the occurrence of anomalies due to CMV infection, with an optimal cut-off point of >1,310,520 copies/mL, a sensitivity of 66.7%, a specificity of 84.3%, and a positive likelihood ratio of 4.24. Once excluding fetuses with anomalies at ultrasound or MRI, the diagnostic performance of qPCR in identifying fetuses with symptomatic infection after birth was low, with an AUC of 0.586. CONCLUSION: CMV viral load at second trimester amniocentesis has a moderate accuracy for the occurrence of CMV-related anomalies in fetuses with congenital infection and normal ultrasound at the initial diagnosis. Conversely, prediction of symptomatic infection is low.

Assessment of fetal heart aortic and pulmonary valve annulus area by three-dimensional ultrasonography: reference curves and applicability in congenital heart diseases.

OBJECTIVES: To determine reference curves for fetal aortic and pulmonary valve annulus area by three-dimensional ultrasonography using the spatio-temporal image correlation (STIC) in the rendering mode, and to ascertain its applicability in congenital heart disease (CHD). METHODS: We performed a retrospective cross-sectional study of 328 normal fetuses and 42 fetuses with CHD between 20 and 33 weeks 6 days of gestation. The outflow plane view of the great vessels was used to measure the areas of the valvar annuli, and the measurements were performed in systole. A linear regression model adjusted according to the determination coefficient (R2) was utilized to construct the reference intervals. The concordance correlation coefficient (CCC) was used to calculate the reproducibility of the mitral and tricuspid valve areas. RESULTS: The mean ± standard deviation (SD) of the aortic and pulmonary valve annulus areas ranged from 6.6 ± 1.2 to 32.9 ± 1.1 mm2 and 10.7 ± 1.3 to 40.3 ± 1.2 mm2, respectively. We observed a linear relationship and strong positive correlation between the area of the aortic and pulmonary valve annuli with r=0.97 and 0.96, respectively. Good intra (CCC=0.99) and interobserver agreement (CCC=0.98) was observed for the measurement of the aortic valve annulus area. A good intra (CCC=0.99) and interobserver (CCC=0.97) agreement was also observed for the measurement of the pulmonary valve annulus area. The mean ± SD of the difference of the areas of the aortic and pulmonary valve annuli between the normal fetuses and those with CHD were -1.801 ± 1.429 mm2 (p=0.208) and -1.033 ± 1.467 mm2 (p<0.0001), respectively. CONCLUSIONS: The reference curves for the areas of the aortic and pulmonary valve annuli of fetal hearts were determined, and showed good inter and intraobserver reproducibility. The constructed reference curves showed applicability in different types of CHD.

Fetal heart foramen ovale area by three-dimensional ultrasound using stic in the rendering mode: reference range and applicability in congenital heart diseases.

To determine reference values for the foramen ovale (FO) area of fetal hearts by three-dimensional (3D) ultrasound using spatio-temporal image correlation (STIC) method in the rendering mode, as well as applicability in fetuses with congenital heart disease (CHD). A retrospective and prospective study was performed of 242 normal fetuses and 36 fetuses with CHD between 20 and 33 + 6 weeks of gestation. The FO area was determined in the four-chamber view with manual delineation. To determine the reference curve of the FO area as a function of gestational age (GA), a linear regression model was utilized with an adjusted coefficient of determination (R2). For intra- and interobserver reproducibility calculations, the concordance correlation coefficient (CCC) was used. The mean ± standard deviation (SD) of the FO measurement area was 21.2 ± 1.8 and 48.1 ± 1.9 mm2 at 20 and 33 weeks' gestation, respectively. A linear correlation was observed between the FO area and GA (1.924*GA - 17.95; R2 = 0.91). Good intra- (CCC = 0.97) and interobserver (CCC = 0.94) agreement was observed for the FO area measurement. The mean difference in FO area between normal and CHD fetuses was - 14.4 mm2 (p < 0.001). Reference values for the FO area of fetal hearts were determined by 3D ultrasound using STIC in the rendering mode. This method showed good intra- and interobserver reproducibility and could be used to assess different CHD types.