Frontal lobe growth is impaired in fetuses with congenital heart disease.

OBJECTIVES: The primary objective of this study was to assess whether fetuses with congenital heart disease (CHD) have smaller frontal brain areas compared with normal controls. The secondary objective was to evaluate whether there are any differences in frontal brain area between cases with different types of CHD, grouped according to their impact on hemodynamics. METHODS: This was a retrospective cross-sectional study, including 421 normal fetuses and 101 fetuses with isolated CHD evaluated between 20 and 39 gestational weeks at our fetal medicine and surgery unit in the period January 2016-December 2019. The study group was subdivided, according to the CHD hemodynamics, as follows: (1) hypoplastic left heart syndrome and other forms of functionally univentricular heart defect; (2) transposition of the great arteries; (3) conotruncal defects and other CHDs with large shunts; (4) right ventricular outflow tract obstruction, without a hypoplastic right ventricle; (5) left outflow tract obstruction; (6) others. The transventricular axial view of the fetal head was used as the reference view, on which the frontal lobe anteroposterior diameter (FAPD) and the occipitofrontal diameter (OFD) were measured, assuming the former to be representative of the area of the frontal lobes. The FAPD/OFD ratio was then calculated as FAPD/OFD × 100. These two variables (FAPD and FAPD/OFD ratio) were then evaluated and compared between the study and control groups. Adjustment for gestational age, both via multiple linear regression and by using a-posteriori matching based on the propensity score, was employed. RESULTS: In normal fetuses, FAPD showed a linear positive correlation with gestational age. In fetuses with CHD, the FAPD was shorter than in normal fetuses from the 20th gestational week onwards, with the difference increasing after 30 gestational weeks. FAPD/OFD ratio was significantly smaller in fetuses with CHD than in normal fetuses (P < 0.0001) at all gestational ages, with no apparent differences among the various CHD categories, all of which had smaller FAPD/OFD ratio compared with controls. CONCLUSIONS: Fetuses with CHD have a shorter FAPD and a smaller FAPD/OFD ratio compared with normal fetuses. This impaired growth of the frontal area of the brain seems to occur in all types of CHD, regardless of their impact on hemodynamics. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Redundancy of foramen ovale flap may mimic fetal aortic coarctation.

OBJECTIVES: To assess the relationship between presence of a redundant foramen ovale flap (RFOF), in the absence of a clearly restrictive foramen ovale, and ventricular disproportion, in three groups of fetuses: (1) those with a final diagnosis of aortic coarctation (CoA); (2) those referred for suspicion of ventricular disproportion and/or CoA which did not develop CoA postnatally; and (3) normal fetuses. METHODS: This was a retrospective study including 73 fetuses: 12 with a final diagnosis of isolated CoA; 30 referred for suspicion of ventricular disproportion and/or CoA, which did not develop CoA postnatally; and 31 normal fetuses. Four-dimensional volume datasets and clips were assessed offline. Maximum diameters of the FOF (FOFD), left atrium (LAD), right atrium, left and right ventricles and, when available, aortic isthmus, were measured, as were areas of the FOF (FOFA), left atrium (LAA) and right atrium. The left/right ratios for all segments of the heart, as well as the FOFD/LAD ratio and FOFA/LAA ratio, were calculated. Regression analysis was performed to assess the relationship between RFOF and ventricular disproportion and means were compared by ANOVA. RESULTS: Repeatability was fair, with all variables having an intraclass correlation coefficient ≥ 83%. In the pooled group of fetuses with no CoA found at birth (normal fetuses plus those with ventricular disproportion (n = 61)), there was a significant linear correlation between redundancy of the FOF and degree of ventricular disproportion (P < 0.01 and P < 0.05 for diameter and area ratios, respectively). Categorizing the FOF redundancy, FOFD/LAD ratio ≥ 0.65 was significantly associated with ventricular disproportion (P = 0.006). Based on the degree of FOF prominence, we described four categories of redundancy, ranging from no redundancy/ventricular disproportion (Stage 0) to severe redundancy/ventricular disproportion with transient obstruction of the foramen ovale or mitral orifice (Stage III). Comparing cases without neonatal evidence of coarctation but FOFD/LAD ratio ≥ 0.65 vs those with neonatal evidence of coarctation, there was no statistically significant difference in the degree of ventricular disproportion or in the Z-score of the aortic isthmus maximum diameter. CONCLUSIONS: This study demonstrates that: (1) there is an association between RFOF and ventricular disproportion, independent of the association with a restrictive foramen ovale, and (2) the presence of a RFOF may mimic CoA. In fact, it causes both ventricular disproportion and a significant reduction in the diameter of the aortic isthmus, associated in some cases also with reversed isthmic flow. Future prospective studies are needed to evaluate whether focusing the sonologist's attention on the appearance of the foramen ovale may reduce the rate of false-positive diagnosis of CoA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Early fetal hydropic changes are associated with moderate dilatation of the brain ventricular system: A clue to a possible link between cervical lymphatic engorgement and ventricular dilatation?

The aim of this study is to assess whether early cervical lymphatic obstruction is associated with a sonographically detectable dilatation of the ventricular system in the 1st trimester of pregnancy. In particular, the objective is to assess whether fetuses with non-immune hydrops fetalis (NIHF), cystic hygroma, or enlarged nuchal translucency (NT) have a greater atrial width/biparietal diameter (AW/BPD) ratio than normal at time of the combined first trimester screening scan. This retrospective study included 96 first trimester fetuses (33 normal and 63 with various degree of cervical lymphatic engorgement). Inclusion criteria were CRL in the 45-84 mm range and availability of one or more three-dimensional volume datasets of the fetal head, acquired from the BPD plane. Each three-dimensional volume dataset was opened and multiplanar correlation employed to align the three orthogonal planes. The ratio between the atrial width and the BPD (AW/BPD ratio) was used to evaluate the possible presence of increased amount of cerebrospinal fluid. Abnormal cases were placed into 4 categories: 1) enlarged non-septated NT 2.5-3.9 mm, no hydrops; 2) grossly enlarged non-septated NT / edema >3.9 mm; 3) cystic hygroma and/ or NIHF; 4) major anomalies with NT <2.5 mm. Presence of dilatation of the laterocervical jugular lymphatic sacs, karyotype and presence of congenital anomalies were also recorded. The One-way ANOVA test was used to compare means. Intra- and inter-observer variability were also assessed. The AW/BPD ratio was found to be significantly higher in fetuses with grossly enlarged NT/nuchal edema and NIHF/septated cystic hygroma than in normal (p <0.05 and p <0.01, respectively). Also, the AW/BPD ratio was significantly higher in NIHF/septated cystic hygroma than in enlarged NT 2.5-3.9 mm (p <0.05). In case of enlarged NT (2.5-3.9 mm), the AW/BPD ratio is significantly higher in presence of JLS (p <0.01). At the end of the first trimester, presence of cervical lymphatic engorgement, in terms of grossly enlarged NT, nuchal edema, septated cystic hygroma, and NIHF, is statistically associated with a moderate dilatation of the ventricular system. Of note, among fetuses with moderately enlarged NT, those with evidence of dilatation of the JLS show a statistically significant increase in the AW/BPD ratio.

Hindbrain morphometry and choroid plexus position in differential diagnosis of posterior fossa cystic malformations.

OBJECTIVE: To assess the differential diagnostic significance of a series of quantitative and qualitative variables of the cerebellar vermis in fetuses with posterior fossa cystic malformation, including Dandy-Walker malformation (DWM), vermian hypoplasia (VH) and Blake's pouch cyst (BPC). METHODS: This was a retrospective study of confirmed cases of DWM, VH and BPC, diagnosed at the Fetal Medicine and Surgery Unit of the Federico II University between January 2005 and June 2013 or the Fetal Medicine and Surgery Unit of G. Gaslini Hospital between July 2013 and September 2017. All included cases had good-quality three-dimensional (3D) volume datasets of the posterior fossa, acquired by transvaginal ultrasound through the posterior fontanelle. The midsagittal view of the posterior fossa was the reference view for the study. We assessed brainstem-tentorium angle and brainstem-vermis angle (BVA), as well as craniocaudal (CCVD) and anteroposterior (APVD) vermian diameters and vermian area (VA), which were normalized by biparietal diameter (BPD) to take into account gestational age (CCVD/BPD × 100, APVD/BPD × 100 and VA/BPD × 100, respectively). Finally, the position of the fourth ventricular choroid plexus (4VCP) was defined as normal ('up') or abnormal ('down'), relative to the roof/cyst inlet of the fourth ventricle. RESULTS: We analyzed 67 fetuses with posterior fossa malformations (24 cases of DWM, 13 of VH and 30 of BPC). The mean gestational age at diagnosis was 23.6 weeks. Regardless of gestational age, the BVA differed significantly between the three groups, and the VA/BPD was able to differentiate between VH and BPC. In differentiating between VH and BPC, the greatest areas under the receiver-operating characteristics curve were those for VA/BPD ratio. The 4VCP position was down in all cases of DWM and VH, while it was up in all cases of BPC. CONCLUSIONS: Our data support the concept that VA/BPD ratio and 4VCP position may be used to differentiate between DWM, VH and BPC in the fetus. In our series, the position of the 4VCP had the highest accuracy, but a larger number of VH cases should be evaluated to confirm that an up position of the 4VCP indicates BPC while a down position indicates DWM or VH. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis of total and partial anomalous pulmonary venous connection: multicenter cohort study and meta-analysis.

OBJECTIVES: The aims of this study were to review systematically literature on and describe the sonographic features and associated anomalies of total (TAPVC) and partial (PAPVC) anomalous pulmonary venous connection and scimitar syndrome (SS). METHODS: A retrospective cohort study was carried out of cases of TAPVC, PAPVC and SS that underwent comprehensive ultrasound examination, seen over a 20-year period at two tertiary referral centers. Assessed variables included TAPVC subtype, gestational age at diagnosis, area behind the left atrium, ventricular disproportion, vertical vein, pulmonary venous obstruction, mode of diagnosis, association with cardiac and extracardiac conditions, and pregnancy and fetoneonatal outcomes. The outcome was considered favorable if the individual was alive and well (no functional impairment from surgery or cardiac or extracardiac conditions). Cases associated with right isomerism were excluded from the analysis, as TAPVC in these cases was only one of several major cardiac anomalies affecting sonographic signs. A systematic review was performed in order to obtain a synthesis of characteristics associated with TAPVC, PAPVC and SS. The literature search of PubMed and EMBASE (1970-2016) included reviews, case series and case reports. A meta-analysis was conducted only for TAPVC. Random-effects models were used to obtain pooled estimates of the frequencies of clinical characteristics and sonographic features. RESULTS: For TAPVC, a total of 15 studies involving 71 patients (including 13 from the current cohort study) were included in the systematic review and meta-analysis. The pooled estimate for the association of TAPVC with congenital heart disease was 28.3% (95% CI, 18.1-41.3%) and with extracardiac anomalies it was 18.5% (95% CI, 10.5-30.6%). Of TAPVC cases, obstructed venous return was observed in 34.1% (95% CI, 22.7-47.7%), a favorable outcome in 43.8% (95% CI, 24.0-65.8%), ventricular disproportion in 59.2% (95% CI, 45.1-72.0%), increased area behind the left atrium in 58.1% (95% CI, 41.1-73.5%) and a vertical vein in 59.3% (95% CI, 41.1-75.3%). Diagnosis was established by using color or power Doppler in 84.9% (95% CI, 67.3-93.9%) of cases. For SS, there were only three studies describing eight cases, to which the current study added another five. Ventricular disproportion was present in three out of nine SS cases for which data were available, but for two of these, there was a concurrent heart anomaly. Color Doppler was used for all SS diagnoses, and four-dimensional echocardiography was useful in two out of six cases in which it was used. Outcome for SS cases was generally good. For PAPVC, there were only five studies describing five cases, to which the current study added another two. Major cardiac anomalies were associated in four out of seven of these cases, and extracardiac anomalies in three out of six cases for which data were available. CONCLUSIONS: TAPVC can be associated with other cardiac and extracardiac anomalies in a significant percentage of cases. Leading sonographic signs are ventricular disproportion, increased area behind the left atrium and the finding of a vertical vein. Color/power Doppler is the key mode for diagnosis of TAPVC. Obstructed venous return can be expected in roughly one-third of cases of TAPVC and outcome is favorable in less than half of cases. Data for SS and PAPVC are too few to synthesize. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Assessment of fetal optic chiasm: an echoanatomic and reproducibility study.

OBJECTIVES: Our aims were: (1) to perform an echoanatomic correlation study, in order to confirm that the structure identified as the optic chiasm (OC) on ultrasound (US) is indeed this anatomical structure; (2) to assess and compare the reproducibility of two- (2D) and three-(3D) dimensional US in measurement of the OC in normal fetuses; and (3) to assess whether the spatial orientation of the OC changes with increasing gestational age. METHODS: For the echoanatomic study, the OC was studied in a neonatal specimen, deceased at 29 + 4 weeks, by passing a suture around the OC and visualizing the supposed OC structure on US while pulling gently on the suture. The reproducibility study included 39 women with normal pregnancy at 20-33 weeks undergoing routine obstetric US examination. After the routine exam, the OC was visualized on 2D-US, and a 2D image and 3D volume dataset were stored for offline measurement. On the 2D images, the diameters of the OC decussation and the optic tract proximal to the transducer were measured. For the 3D volume dataset, multiplanar image correlation with volume contrast imaging (VCI) was used to measure both these diameters and the chiasmocallosal angle (CCA). Two operators each took two sets of measurements of the diameters on 2D- and 3D-US, and intra- and interoperator variability were analyzed using Cronbach's alpha intraclass correlation coefficient (ICC), while a single operator took two sets of CCA measurements for assessment of intraoperator variability. Differences in CCA with increasing gestational age were also analyzed by regression, and CCA measurements were divided into three groups according to gestational age and their means compared by one-way ANOVA. RESULTS: During the echoanatomic experiment, when the sling suture was pulled, the hyperechoic X-shaped structure just below the circle of Willis identified on 2D-US as the OC was displaced slightly and was eventually cut by the sling, confirming its identity as the OC. Intraoperator variability was low and almost identical for the two operators and the two imaging modalities for measurement of the decussation (ICC for 2D-US: 0.96 vs 0.95; 3D-US: 0.95 vs 0.96), but less so for the optic tract (ICC for 2D-US: 0.95 vs 0.91; 3D-US: 0.94 vs 0.83). Interoperator variability was low for the decussation (2D-US: 0.92; 3D-US: 0.92), but higher for the optic tracts (ICC for 2D-US: 0.80; 3D-US: 0.78). The difference between the mean measurement of the two operators was not statistically significantly different for the decussation, but it was for the optic tracts (P = 0.04). The CCA increased steadily between 20 and 30 gestational weeks and plateaued thereafter, at least until 33 weeks. CONCLUSIONS: The hyperechoic structure evident on 2D- and 3D-US, just below the circle of Willis, is indeed the OC. 2D-US is apparently as good as 3D-US for visualization of the OC. However, only measurement of the decussation showed low intra- and interoperator variability, whereas measurement of the optic tract is of questionable variability. As gestation advances between 20 and 30 weeks, the OC becomes more oblique in orientation. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effects of recombinant follicle-stimulating hormone on bone turnover markers in infertile women undergoing in vitro fertilization procedure.

CONTEXT: There is experimental but limited clinical evidence that FSH may have direct effects on bone. OBJECTIVE: The aim of the study was to evaluate the effects of acute FSH stimulation on bone turnover in premenopausal women. DESIGN AND SETTING: We conducted a prospective study at a referral center. PATIENTS: Twenty-nine infertile women (age range, 30-40 yr) undergoing an in vitro fertilization procedure were included in the study. INTERVENTIONS: Pharmacological suppression of endogenous gonadotropin and estradiol (E2) production by GnRH analog (leuprolide 1 mg/d s.c.) was followed by stimulation with recombinant FSH (rFSH; starting dose, 375 IU/d s.c.). MAIN OUTCOME MEASURES: We measured serum osteocalcin, C-telopeptides of type-1 collagen (ß-CTX), FSH, and E2 at the beginning of leuprolide administration (T0), at the beginning of rFSH administration (T1), and 3 d (T2) and 10 d (T3) after the first dose of rFSH. RESULTS: At T1, the suppression of FSH and E2 secretion, as an effect of leuprolide administration, led to a significant increase in serum ß-CTX values vs. T0 (P < 0.001). After the administration of rFSH, a rapid increase in serum FSH was observed, whereas serum E2 values increased more slowly. At T2, the increase in serum FSH values above our reference range for early follicular phase (with E2 in the reference range) did not induce any significant change in median serum ß-CTX values as compared to T1. At T3 (when both FSH and E2 were high), serum ß-CTX values decreased significantly vs. T1 (P < 0.001). Osteocalcin did not change significantly throughout the study period. CONCLUSIONS: Our model suggests that FSH does not acutely exert relevant direct effects on bone metabolism in premenopausal women.

[External cephalic version for breech presentation at term: an effective procedure to reduce the caesarean section rate]. / La versione cefalica esterna nel feto in presentazione podalica: una manovra efficace per ridurre il numero di tagli cesarei.

AIM: Although term breech presentation is a relatively rare condition (3-5% of all births), it continues to be an important indication for caesarean section and has contributed to its increased use. Risk of complications may be increased for both mother and foetus in such a situation. Vaginal delivery of a breech presenting foetus is complex and may involve many difficulties, so today there is a general consensus that planned caesarean section is better than planned vaginal birth for the foetus in breech presentation at term. External cephalic version is one of the most effective procedures in modern obstetrics. It involves the external manipulation of the foetus from the breech into the cephalic presentation. A successful manoeuvre can decrease costs by avoiding operative deliveries and decreasing maternal morbidity. The aim of the present study is to evaluate the effectiveness of this obstetric manoeuvre to increase the proportion of vertex presentation among foetuses that were formerly in the breech position near term, so as to reduce the caesarean section rate. The safety of the version is also showed. METHODS: From 1999 to 2002, 89 women with foetal breech presentation underwent external cephalic version at the Department of Obstetrics and Gynaecology of the Brescia University. The gestational age was 36.8+/-0.8 weeks. The following variables have been taken into consideration: breech variety, placental location, foetal back position, parity, amount of amniotic fluid and gestational age. Every attempt was performed with a prior use of an intravenous drip of Ritodrine, and foetal heart rate was monitored continuously with cardiotocogram. RESULTS: The success rate of the procedure was 42.7% (n=38). No maternal or foetal complication or side effects occurred, both during and after the manoeuvre, except a transient foetal bradycardia that resolved spontaneously. Only one spontaneous reversion of the foetus occurred before delivery. Of all the women that underwent a successful version, 84.2% (n=32) had a non complicated vaginal delivery. Five women (15.8%) had a caesarean section. There was no significant interaction between the variables assessed. CONCLUSION: The external cephalic version is a safe and effective manoeuvre reducing the risks of vaginal breech delivery and the rate of caesarean section.