Objectives: Some genetic causes of heterotaxy have been identified in a small number of heterotaxy familial cases or animal models. However, knowledge on the genetic causes of heterotaxy in the fetal population remains scarce. Here, we aimed to investigate the clinical characteristics and genetic spectrum of a fetal cohort with heterotaxy. Methods: We retrospectively investigated all fetuses with a prenatal diagnosis of heterotaxy at a single center between October 2015 and November 2020. These cases were studied using the genetic testing data acquired from a combination of copy number variation sequencing (CNV-seq) and whole-exome sequencing (WES), and their clinical phenotypes were also reviewed. Result: A total of 72 fetuses diagnosed with heterotaxy and complete clinical and genetic results were enrolled in our research. Of the 72 fetuses, 18 (25%) and 54 (75%) had left and right isomerism, respectively. Consistent with the results of a previous study, intracardiac anomalies were more severe in patients with right atrial isomerism than in those with left atrial isomerism (LAI) and mainly manifested as atrial situs inversus, bilateral right atrial appendages, abnormal pulmonary venous connection, single ventricles or single atria, and pulmonary stenosis or atresia. In 18 fetuses diagnosed with LAI, the main intracardiac anomalies were bilateral left atrial appendages. Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease. Conclusion: Thus, diagnostic genetic variants contributed to a substantial fraction in the etiology of fetal heterotaxy. PCD mutations accounted for approximately 6.9% of heterotaxy cases in our fetal cohort. WES was identified as an effective tool to detect genetic causes prenatally in heterotaxy patients.
Objectives: Noncompaction Cardiomyopathy (NCCM) has been classified as primary genetic cardiomyopathy and has gained increasing clinical awareness; however, little is known about NCCM in the fetal population. We aimed to investigate the clinical characteristics and genetic spectrum of a fetal population with NCCM. Methods: We retrospectively reviewed all fetuses with a prenatal diagnosis of NCCM at a single center between October 2010 and December 2019. These cases were investigated for gestational age at diagnosis, gender, left or biventricular involvement, associated cardiac phenotypes, outcomes, and genetic testing data. Results: We identified 37 fetuses with NCCM out of 49,898 fetuses, indicating that the incidence of NCCM in the fetal population was 0.07%. Of the 37 fetuses, 26 were male, ten were female and one was of unknown gender. NCCM involvement biventricle is the most common ( n = 16, 43%), followed by confined to the left ventricle ( n = 14, 38%). Nineteen (51%) had additional congenital heart defects, with right-sided lesions being the most common ( n = 14, 74%), followed by ventricular septal defects ( n = 10, 53%). Hydrops fetalis was present in 12 cases (32%), of which four were atypical (pericardial effusion only). Sequencing analysis was performed at autopsy ( n = 19) or postnatally ( n = 1) on 20 fetuses. Of the 20 fetuses undergoing copy number variation sequencing and whole-exome sequencing, nine (47%) had positive genetic results, including one with a pathogenic copy number variant and eight with pathogenic/likely pathogenic variants. Non-sarcomere gene mutations accounted for the vast majority ( n = 7). In contrast, sarcomere gene mutations occurred in only one case (TPM1), and no mutations were identified in the three most common sarcomere genes (MYH7, TTN, and MYBPC3) of pediatric and adult patients. Pathogenic/likely pathogenic variants were significantly more frequent in fetuses with congenital heart defects than those without congenital heart defects. Conclusions: Our data demonstrate that fetal NCCM is a unique entity. Compared with pediatric and adult NCCM, fetal NCCM is more prone to biventricle involvement, more likely to be complicated with congenital heart defects, and has a distinct genetic spectrum.
To assess cardiac twist in dilated cardiomyopathy (DCM) patients using echocardiography velocity vector imaging (VVI) and to explore the clinical application value of VVI in evaluating cardiac twist.Thirty-three normal subjects and 30 DCM patients were enrolled. Echocardiographs of parasternal left ventricle basal, papillary muscle level and apical short axis plane, apical four-, two-chamber plane were obtained respectively. Systolic maximal rotation degree, peak rotation velocity, circumferential strain (CS), time to peak rotation velocity (TPRV), peak un-rotation velocity of end diastole and end isovolumic relaxation period in subendocardium were measured by VVI software.(1) In the normal group, left ventricle performed systolic wring motion with counterclockwise rotation at the apex and clockwise rotation at the base as seen from the apex, while with transient counterclockwise rotation at the base and clockwise rotation at the apex in isovolumic relaxation period. The papillary level rotation form was not constant For the dominant rotation action of the apex, the whole cardiac twist form was counterclockwise. (2) Compared with the control group, 4 DCM patients cardiac twist pattern changed: two showed both counterclockwise rotation of the base and the apex, one represented both clockwise rotation of the base and the apex, another performed the base rotated counterclockwise and the apex rotated clockwise. (3) All rotation and twist parameters of other 26 DCM patients decreased, especially at the apical level: LVtw:7.34 degrees +/- 3.65 degrees vs. 17.01 degrees +/- 4.81 degrees, LVtor: (0.09 +/- 0.04) degrees/mm vs. (0.23 +/- 0.06) degrees/mm, torsion rate: (60.23 +/- 23.67) degrees/s vs. (148.24 +/- 56.23) degrees/s, untwisting rate (0.37 +/- 0.19) degrees/m vs. (0.59 +/- 0.33%)/m, basal CS: (-8.09 +/- 2.73)% vs. (-19.49 +/- 5.51)% (P = 0.013), apical CS: (-8.94 +/- 5.90)% vs. (-27.49 +/- 9.53)% (P = 0.000), basal rotation angle: (-3.60 +/- 2.38) vs. (-6.28 +/- 3.05) (P = 0.014), apical rotation angle: (5.80 +/- 3.55) degrees vs. (11.02 +/- 3.33) degrees (P = 0.001). (4) The apical TPRV in DCM group were longer than the control group represented rotational dyssynchrony in DCM patients (400.26 ms +/- 70.15 ms vs 328.13 ms +/- 66.95 ms, P = 0.008). LVtw correlated positively well with EF (r = 0.489, P < 0.05).(1) Cardiac twist function was diffusely impaired in DCM patients and it contributed to the global cardiac dysfunction. (2) Cardiac twist pattern changed in some of DCM patients. (3) VVI can objectively reflect cardiac twist function in DCM patients.
More than 4.5 million children have been conceived by in vitro fertilization (IVF). Interestingly, singleton IVF offspring born at term have an increased incidence of low birth weight. The mechanism responsible for the lower birth weight is unknown, but alterations in placental function are possible. Hence, the goal of our study was to examine placental growth and function in mice generated in vivo or in vitro. To assess placental function, blastocysts were generated by IVF or produced by natural mating (control group); both IVF and control blastocysts were transferred to pseudopregnant recipients. Placental weights did not differ at embryonic d 15.5 (E15.5) but were increased at E18.5 in the IVF group (25.4%, P < 0.001) compared with control. Proliferation was increased in IVF placentae, whereas overall placental gross morphology and apoptosis were not affected. Both fetal weights (16.4% lower at E15.5 and 8.8% lower at E18.5, P < 0.05) and fetal to placental ratios were lower (P < 0.001) in the IVF compared with the control group at both time points, whereas birth weights did not differ. At E18.5, the mRNA for selected glucose, system A amino acid transporters, and imprinted genes were down-regulated in IVF placentae. GLUT3 protein level was decreased in the IVF group (P < 0.05). Importantly, intrajugular injections of 14C-methyl-d-glucose or 14C-MeAIB tracers (n = 6 litters per group) showed that placental transport of glucose and amino acids were 24.8% (not significant) and 58.1% (P < 0.05) lower in the IVF group. Fetal accumulation of glucose was not different, but amino acid accumulation was significantly (36 %) lower in IVF fetuses (P < 0.05). We conclude that IVF alters both fetal and placental growth and, importantly, decreases placental transport efficiency in mice conceived by IVF.
It is hypothesized that diminished cerebral vascular resistance or the "brain sparing effect" is associated with fetuses with complex congenital heart defects (CHD) and may affect their neurodevelopmental outcome. An alternative explanation is that it is related to the location, cardiac output, pressure, and resistance in left heart obstructive CHDs. We sought to determine the effects of various left and right heart obstructive defects on the cerebral and placental hemodynamics and to evaluate the utility of these variables for the assessment and prognosis of CHDs.A total of 290 fetal echocardiograms were reviewed, including 91 fetuses with CHD and 199 normal ones. The CHD fetuses were divided into four groups, that is, left-sided obstructive lesions (LSOL), hypoplastic left heart syndrome (HLHS), right-sided obstructive lesions (RSOL), and hypoplastic right heart syndrome (HRHS). The pulsatility index of middle cerebral artery (MCA-PI) and umbilical artery (UA-PI) were measured by pulse-wave Doppler, and their Z scores were also derived. Cerebroplacental ratio (CPR) was calculated as: CPR=MCA-PI/UA-PI.There was no significant difference in MCA-PI between the 4 CHD and normal control groups (P>.05). However, MCA-PI and Z score decreased in aortic stenosis but not in interrupted aortic arch or coarctation subgroups, whereas they increased in pulmonary atresia but not pulmonary stenosis or tetralogy of Fallot subgroups compared with normal group (P<.05). There was no significant difference in CPR between any study group or subgroup and normal control group.Our study suggests MCA-PI is lower in aortic stenosis and high in pulmonary atresia but not significantly different in other LSOL, HLHS, RSOL, and HRHS. MCA-PI regulation in CHD is probably more associated with left and right outflow obstruction, location of the obstruction, and hemodynamics rather than "brain sparing effect" or preferential shunting of blood to the fetal brain, heart, and adrenals in the stressed fetus (eg, IUGR). CPR may not be a sensitive measure for the effect of CHDs and their severity on cerebral and placental circulation.
Objective
To explore the echocardiographic features and pregnant outcomes in fetuses with complete closure of the ductus arteriosus (DA).
Methods
The echocardiographic data and follow-up materials were retrospectively reviewed in 28 605 fetuses. Of all the fetuses, 6 fetuses had complete closure of the DA. The echocardiographic features and pregnant outcomes of the 6 fetuses with complete closure of the DA were summarized.
Results
Of all the 6 fetuses, 4 cases were found in the third trimester and 2 cases in the second trimester. There was no the lumen of the DA in the three vessel view on the two dimensional echocardiography, demonstrating the line-like low echogenicity in the DA area. No DA flow signal was found on the color and spectral Doppler imaging. Four cases had dilated right heart.Six cases had thickened wall of the right ventricle (WRV), and hypokinetic motion of the WRV. Moderate to severe tricuspid regurgitation were found in 5 cases and disappeared or reversal a-wave of the ductus venosus were found in 5 cases. The mild pericardial effusion was found in 2 cases. Of all the 6 cases, 4 cases were delivered by cesarean section and the echocardiographic findings were unremarkable at the follow-up of six months.
Conclusions
Intrauterine complete closure of the DA can be accurately diagnosed by fetal echocardiograph in the 2-3 trimesters. If indicated, elective delivery results in good outcome.
Key words:
Echocardiography; Fetus; Ductus arteriosus; Intrauterine closure; Pregnant outcome
Abstract Background Neuropsychiatric symptoms (NPSs) are exhibited in most patients with Alzheimer’s disease (AD), especially the delusional symptoms are commonly seen. Previous studies suggest that vascular changes such as white matter hyperintensities (WMH) have a significant association with specific NPS.The current study comparing the WMH volume in delusional and non-delusional Alzheimer's to explore the relationship between WMH and delusional symptoms in AD patients. Methods In total,80 AD patients divided into delusional group (n = 36) and non-delusional group (n = 44) according to the Neuropsychiatric Inventory(NPI) scale.The WMH volume of these 80 patients was quantitatively calculated.Include the whole Brain WMH volume, Periventricular WMH(PVWMH) volume, Deep WMH volume, bilateral frontal WMH volume, bilateral temporal WMH volume, bilateral parietal WMH volume and bilateral occipital WMH volume. Firstily,Compared the WMH volume between the delusional group and the non-delusional group.Sencondly,The delusional patients were divided into mild, moderate and severe groups according to the NPI. We Compared the different severity of delusional group to explore the role of WMH volume in delusional symptoms. Results There was a significant difference in WMH volume in the left occipital lobe (P < 0.05).In the delusional group, there were significant differences in the total volume of WMH and PVWMH volume (P < 0.05).Posthoc test showed that WMH volume were significantly different between mild and severe delusional symptoms (P < 0.05). Conclusion Left occipital WMH volume may affect the development of delusional symptoms.In AD patients, WMH promote the serious of delusional symptoms.
Abstract Objective: Current studies have suggested that fetal congenital heart diseases (CHDs) are caused by various factors. However, few data is available with respect to the aspect in China. This study aimed to detect associated maternal and fetal factors of fetal CHD in a large sample in China. Study Design: Pregnant women who underwent fetal echocardiography (N=5024) were recruited in our hospital between May 2018 and September 2019. Of these, 875 pregnant women had fetuses with CHD. The maternal sociodemographic and lifestyle characteristics and some fetal factors were obtained. We used forward stepwise logistic regression analysis to assess the associations of fetal CHD with various factors. Results: Among the fetal CHD group (N=875), critical CHDs account for 27%, of which Tetralogy of Fallot is the most (7.1%), followed by coarctation of aorta (4.0%), Double-outlet right ventricle (2.9%). The forward stepwise logistic regression models revealed that gravidity (OR=1.32, 95%CI 1.21-1.43, P=0.000), upper respiratory tract infection during early pregnancy (OR=1.30, 95%CI 1.04-1.63, P=0.021), mental stress during early pregnancy (OR=2.87, 95%CI 1.35-5.92, P=0.006), single umbilical artery (OR=2.46, 95%CI 1.24-4.85, P=0.010), and parental smoking (OR=1.20, 95%CI 1.00-1.45, P=0.048) are positively associated with an increased risk of fetal CHD. Conclusion: We identified two maternal factors and two fetal factors positively associated with fetal CHD.. These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.
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