The Effect of Age, Hypertension, and Overweight on Arterial Stiffness Assessed Using Carotid Wall Echo-Tracking in Childhood and Adolescence.

Arterial stiffness represents an independent predictor of the risk of subsequent cardiovascular events. Early identification of high-risk individuals is necessary for effective prevention and targeted interventions. Carotid wall echo-tracking is a modern method for an accurate evaluation of the structural and functional properties of carotid arteries. This study aimed to assess age and sex-specific reference values of the echo-tracking parameters of carotid stiffness in 400 healthy children and adolescents and to evaluate the potential early effect of elevated blood pressure and overweight in 69 overweight normotensives, 45 white coat hypertensives, and 44 essential hypertensives. Stiffness index ß, pressure-strain elastic modulus (Ep), arterial compliance (AC), and pulse wave velocity ß (PWV ß) were evaluated using Aloka ProSound F75. Both white coat and essential hypertension were associated with impaired carotid wall properties with the greatest effect on Ep, followed by PWV ß, index ß, and AC. The excess weight showed a weaker effect on Ep and PWV ß. This is the first study to compare the effects of white coat and essential hypertension on carotid arterial stiffness assessed using the echo-tracking technique in childhood and adolescence with direct application of pediatric reference values specific to age and sex.

Enhancing Solubility and Bioefficacy of Stilbenes by Liposomal Encapsulation-The Case of Macasiamenene F.

Stilbenes in food and medicinal plants have been described as potent antiphlogistic and antioxidant compounds, and therefore, they present an interesting potential for the development of dietary supplements. Among them, macasiamenene F (MF) has recently been shown to be an effective anti-inflammatory and cytoprotective agent that dampens peripheral and CNS inflammation in vitro. Nevertheless, this promising molecule, like other stilbenes and a large percentage of drugs under development, faces poor water solubility, which results in trickier in vivo administration and low bioavailability. With the aim of improving MF solubility and developing a form optimized for in vivo administration, eight types of conventional liposomal nanocarriers and one type of PEGylated liposomes were formulated and characterized. In order to select the appropriate form of MF encapsulation, the safety of MF liposomal formulations was evaluated on THP-1 and THP-1-XBlue-MD2-CD14 monocytes, BV-2 microglia, and primary cortical neurons in culture. Furthermore, the cellular uptake of liposomes and the effect of encapsulation on MF anti-inflammatory effectiveness were evaluated on THP-1-XBlue-MD2-CD14 monocytes and BV-2 microglia. MF (5 mol %) encapsulated in PEGylated liposomes with an average size of 160 nm and polydispersity index of 0.122 was stable, safe, and the most promising form of MF encapsulation keeping its cytoprotective and anti-inflammatory properties.

Pregnancy Termination and Postnatal Major Congenital Heart Defect Prevalence After Introduction of Prenatal Cardiac Screening.

Importance: Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of pregnancy (TOP), and outcomes among children born alive with CHDs. Objective: To examine the prenatal and postnatal incidence of major CHDs (ie, necessitating intervention within the first year of life), detection rate trends, rates of TOP, and the association of cardiac screening with postnatal outcomes. Design, Settings, and Participants: In this cross-sectional study, 3827 fetuses with antenatally diagnosed major CHDs in the Czech Republic (population 10.7 million) between 1991 and 2021 were prospectively evaluated with known outcomes and associated comorbidities. Prenatal and postnatal prevalence of CHD in an unselected population was assessed by comparison with a retrospective analysis of all children born alive with major CHDs in the same period (5454 children), using national data registry. Data analysis was conducted from January 1991 to December 2021. Main Outcomes and Measures: Prenatal detection and postnatal prevalence of major CHDs and rate of TOPs in a setting with a centralized health care system over 31 years. Results: A total of 3 300 068 children were born alive during the study period. Major CHD was diagnosed in 3827 fetuses, of whom 1646 (43.0%) were born, 2069 (54.1%) resulted in TOP, and 112 (2.9%) died prenatally. The prenatal detection rate increased from 6.2% in 1991 to 82.8% in 2021 (P < .001). Termination of pregnancy decreased from 70% in 1991 to 43% (P < .001) in 2021. Of 627 fetuses diagnosed in the first trimester (introduced in 2007), 460 were terminated (73.3%). Since 2007, of 2066 fetuses diagnosed in the second trimester, 880 (42.6%) were terminated, resulting in an odds ratio of 3.6 (95% CI, 2.8-4.6; P < .001) for TOP in the first trimester compared with the second trimester. Postnatal prevalence of major CHDs declined from 0.21% to 0.14% (P < .001). The total incidence (combining prenatal detection of terminated fetuses with postnatal prevalence) of major CHD remained at 0.23% during the study period. Conclusions and Relevance: In this cross-sectional study, the total incidence of major CHD did not change significantly during the 31-year study period. The prenatal detection of major CHD approached 83% in the current era. Postnatal prevalence of major CHD decreased significantly due to early TOPs and intrauterine deaths. The introduction of first trimester screening resulted in a higher termination rate in the first trimester but did not revert the overall decreasing trend of termination for CHDs in general.

Sensitivity of Papilledema as a Sign of Increased Intracranial Pressure.

Our study evaluates the sensitivity of papilledema as a sign of high intracranial pressure in children. Patients younger than 18 years old, diagnosed with increased ICP, and who had received dilated fundus examination between 2019 and 2021 were retrospectively reviewed. Factors including the patient's age, sex, aetiology, duration of signs or symptoms, intracranial pressure (ICP), and presence of papilledema were evaluated. We included 39 patients in this study, whose mean age was 6.7 years. The 31 patients without papilledema had a mean age of 5.7 years, and 8 patients (20%) with papilledema had a mean age of 10.4 (p < 0.037). The mean duration of signs or symptoms was nine weeks in patients without papilledema and seven weeks in those with papilledema (p = 0.410). The leading causes of increased ICP with papilledema were supratentorial tumor (12.5%), infratentorial tumor (33.3%), and hydrocephalus (20%) (p = 0.479). Papilledema was statistically significantly more common in older patients. We found no statistical significance between sex, diagnosis, and symptoms. The relatively low incidence of papilledema (20%) in our study shows that papilledema's absence does not ensure the absence of increased ICP, especially in younger patients.

Circulating Serum Cystatin C as an Independent Risk Biomarker for Vascular Endothelial Dysfunction in Patients with COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Observational Study.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a new clinical entity that has emerged in the context of the COVID-19 pandemic. Despite the less severe course of the disease, varying degrees of cardiovascular events may occur in MIS-C; however, data on vascular changes occurring in MIS-C are still lacking. Endothelial dysfunction (ED) is thought to be one of the key risk factors contributing to MIS-C. BACKGROUND: We conducted a prospective observational study. We investigated possible manifestations of cardiac and endothelial involvement in MIS-C after the treatment of the acute stage and potential predictive biomarkers in patients with MIS-C. METHODS: Twenty-seven consecutive pediatric subjects (≥9 years), at least three months post-treated MIS-C of varying severity, in a stable condition, and twenty-three age- and sex-matched healthy individuals (HI), were enrolled. A combined non-invasive diagnostic approach was used to assess endothelial function as well as markers of organ damage using cardiac examination and measurement of the reactive hyperemia index (RHI), by recording the post- to pre-occlusion pulsatile volume changes and biomarkers related to ED and cardiac disease. RESULTS: MIS-C patients exhibited a significantly lower RHI (indicative of more severe ED) than those in HI (1.32 vs. 1.80; p = 0.001). The cutoff of RHI ≤ 1.4 was independently associated with a higher cardiovascular risk. Age and biomarkers significantly correlated with RHI, while serum cystatin C (Cys C) levels were independently associated with a diminished RHI, suggesting Cys C as a surrogate marker of ED in MIS-C. CONCLUSIONS: Patients after MIS-C display evidence of ED, as shown by a diminished RHI and altered endothelial biomarkers. Cys C was identified as an independent indicator for the development of cardiovascular disease. The combination of these factors has the potential to better predict the cardiovascular consequences of MIS-C. Our study suggests that ED may be implicated in the pathophysiology of this disease.

Karyotyping of Lymphocytes and Epithelial Cells of Distinct Embryonic Origin Does Not Help to Predict the Turner Syndrome Features.

BACKGROUND: In Turner syndrome (TS), fluorescent in situ hybridization (FISH) karyotyping offers an alternative to classical karyotyping. OBJECTIVE: We tested the added value of FISH karyotyping from lymphocytes (mesodermal origin), buccal cells (ectodermal origin), and a rear-tongue smear (endodermal origin) to determine the 45,X cell line fraction and its impact on patient phenotype. DESIGN AND PATIENTS: Classical karyotyping and three FISH assays were done in 153 girls and women previously diagnosed with TS in four university hospitals. The 45,X cell line fraction was determined for each method and correlated with the major phenotypic signs. RESULTS: Classical karyotyping identified 45,X/46,XX mosaicism in 77/153 subjects (50%), 45,X monosomy in 52/153 (34%), and other karyotypes in 24/153 (16%). FISH from lymphocytes verified 45,X in 47/52 original cases, whereas 4/52 had 45,X/46,XX and 1/52 45,X/47,XYY mosaicism. The 45,X cell line fraction was higher in FISH from lymphocytes compared to classical karyotyping (median 86.4% vs. 70.0%; p < 0.001), while there was no difference for FISH from buccal or rear-tongue smear cells. The mean 45,X cell line fraction was more abundant in patients with several of the characteristic phenotypic signs compared to patients without them (p < 0.01), but the predictive power was insufficient. CONCLUSION: FISH analysis confirmed the findings of classical karyotyping; only a few 45,X monosomy cases were reclassified as mosaics. The 45,X cell line fraction did not show clinically meaningful prediction of the phenotype. FISH analysis of buccal or rear-tongue epithelial cells may be a non-inferior, less invasive alternative to classical karyotyping.

Nationwide observational study of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Czech Republic.

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management.

Screening for congenital defects and genetic diseases of the fetus at University Hospital in Olomouc and sending/ reporting to the National register of reproductive health in the Czech Republic.

OBJECTIVE: The aim of the study was to analyze the results of the screening for congenital defects (CD) and genetic diseases (GD) of the fetus in the Fetal Medicine Centre at the Department of Obstetrics and Gynecology, University Hospital in Olomouc. MATERIALS AND METHODS: Prospective cohort study. In the period from 1 January 2020 to 31 December 2021, a total of 14,460 health services were performed on 4,916 pregnant women. Within the screening of CD and GD of the fetus, 501 pregnant women were found to have an abnormality requiring further clinical management, 170 of them were diagnosed with a CD of the fetus and in 20 cases a GD of the fetus was diagnosed by a laboratory genetic examination. All diagnosed fetal CD and GD were sent/ reported according to the valid methodology of the National health information system (NHIS) to the National register of reproductive health (NRRH) to the CD Module. RESULTS: An increased calculated individual risk of genetic fetal disease was diagnosed in the first trimester of pregnancy in 10.7% of fetuses (319/ 2,968), and in the second trimester in 0.9% of fetuses (27/ 2,948). Nuchal translucency (NT) > 3.5 mm was diagnosed in 0.9% of fetuses by ultrasound examination in the first trimester of pregnancy (26/ 2,968). In fetal CD and GD screening, 501 pregnant women were found to have an abnormality requiring further clinical management, 72.1% of women (361/ 501) had an increased risk of genetic fetal disease, and diagnostic examination of the fetal genetic material obtained by invasive procedure (chorionic villus sampling or amniocentesis) was indicated. A total of 31.3% of them (113/ 361) refused the invasive procedure and 2.5% (9/ 361) did not attend the planned procedure; the invasive procedure was performed in 66.2% (239/ 361). CONCLUSION: Comparing the results of CD and GD fetal screening in our medical facility with other specialized medical facilities in the Czech Republic is currently difficult to do, but information from the NRRH could allow objective and transparent comparisons in the future.

Haplotype analysis of the X chromosome in patients with Turner syndrome in order to verify the possible effect of imprinting on selected symptoms.

AIMS: Turner syndrome is the only chromosome monosomy that is postnatally compatible with life. The reported incidence of TS is 1 in 2500 liveborn girls. The phenotype of these girls is highly variable, with cardiac abnormalities being life-threatening defects. The aim of the study was to reveal the possible influence of the parental origin of the X chromosome in these patients on a selected phenotype that is associated with Turner syndrome. Selected symptoms and parameters were: a bicuspid aortic valve, aortic coarctation, lymphoedema, pterygium colli, coeliac disease, thyroiditis, otitis media, diabetes mellitus 2, renal abnormalities, spontaneous puberty, and IVF. METHODS: The X chromosome haplotype was determined for a group of 45,X patients verified by native FISH. A molecular diagnostic method based on the detection of different lengths of X chromosome-linked STR markers using the Argus X-12 QS kit was used to determine the X haplotype. RESULTS: Our results, analysed by Fisher's exact (factorial) test, suggest independence between the maternal/paternal origin of the inherited X chromosome and the presence of the anomalies that were studied (P=1 to P=0.34). CONCLUSION: In the group of 45,X patients, who were precisely selected by means of the native FISH method, no correlation was demonstrated with the parental origin of the X chromosome and the observed symptom.

Area of the right atrium of the fetal heart and its significance in fetuses with tricuspid regurgitation.

OBJECTIVES: The first aim was to develop a nomogram for the area of the right atrium (ARA) of the fetal heart in uncomplicated singleton pregnancies. The second aim was to assess diagnostic indices of ARA to distinguish between tricuspid regurgitation (TR) with and without concomitant congenital heart defect (CDH). METHODS: The study was conducted between 2014 and 2019. Fetal echocardiography was performed on fetuses with and without TR. For the first aim, ARA was measured in 460 fetuses without proven structural and chromosomal abnormalities, and for the second aim, ARA was measured in 1077 fetuses with TR. RESULTS: A nomogram for the ARA of fetuses with normal hearts was developed. TR was observed in 4.5% (1077/23,771) of euploid fetuses; 4.3% (1020/23,771) of fetuses had TR without a concomitant CHD, and 0.2% (57/23,771) fetuses had TR with a concomitant CHD. No significant differences in ARAs were found between fetuses with normal hearts without TR (n = 22,694) and fetuses with TR without CHD (n = 1020; p = .751). Fetuses with TR and CHDs had different ARA than fetuses with normal hearts without TR and fetuses with TR without CHD (p < .0005 in both cases). CONCLUSIONS: ARA seems to be an auxiliary marker to distinguish the presence of CHD in fetuses with TR.

MLPA analysis of 32 foetuses with a congenital heart defect and 1 foetus with renal defects - pilot study. The significant frequency rate of presented pathological CNV.

AIMS: The aim of this retrospective study was to determine the detection rate of the pathogenic copy number variants (CNVs) in a cohort of 33 foetuses - 32 with CHD (congenital heart defects) and 1 with kidney defect, after exclusion of common aneuploidies (trisomy 13, 18, 21, and monosomy X) by karyotyping, Multiplex ligation - dependent probe amplification (MLPA) and chromosomal microarray analysis (CMA). We also assess the effectivity of MLPA as a method of the first tier for quick and inexpensive detection of mutations, causing congenital malformations in foetuses. METHODS: MLPA with probe mixes P070, P036 - Telomere 3 and 5, P245 - microdeletions, P250 - DiGeorge syndrome, and P311 - CHD (Congenital heart defects) was performed in 33 samples of amniotic fluid and chorionic villi. CMA was performed in 10 relevant cases. RESULTS: Pathogenic CNVs were found in 5 samples: microdeletions in region 22q11.2 (≈2 Mb) in two foetuses, one distal microdeletion of the 22q11.2 region containing genes LZTR1, CRKL, AIFM3 and SNAP29 (≈416 kb) in the foetus with bilateral renal agenesis, 8p23.1 (3.8 Mb) microdeletion syndrome and microdeletion in area 9q34.3 (1.7 Mb, Kleefstra syndrome). MLPA as an initial screening method revealed unambiguously pathogenic CNVs in 15.2 % of samples. CONCLUSION: Our study suggests that MLPA and CMA are a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease. Determination of the cause of the abnormality is crucial for genetic counselling and further management of the pregnancy.

Major heart defects: the diagnostic evaluations of first-year-olds.

BACKGROUND: Severe or critical congenital heart defects (CHDs) constitute one third of the heart defect cases detected only after birth. These prenatally unrecognised defects usually manifest as cyanotic or acyanotic lesions and are diagnosed postnatally at various times. The aim of the study was to identify their clinical symptoms and determine individual risk periods for CHD manifestation. METHODS: Data were assessed retrospectively based on a cohort of patients born between 2009 and 2018 in a population of 175,153 live births. Occurrence of the first symptoms of CHD was classified into: early neonatal (0-7 days), late neonatal (8-28 days), early infancy (1-6 months), or late infancy (6-12 months). The first symptom for which the child was referred to a paediatric cardiologist was defined as a symptom of CHD. RESULTS: There were 598 major CHDs diagnosed in the studied region, 91% of which were isolated anomalies. A concomitant genetic disorder was diagnosed in 6% of the cases, while 3% presented extracardiac pathology with a normal karyotype. In total, 47% (282/598) of all CHDs were not identified prenatally. Of these, 74% (210/282) were diagnosed as early neonates, 16% (44/282) as late neonates, and 10% (28/282) as infants. The most common symptoms leading to the diagnosis of CHD were heart murmur (51%, 145/282) and cyanosis (26%, 73/282). Diagnosis after discharge from the hospital occurred in 12% (72/598) of all major CHDs. Ventricular septal defect and coarctation of the aorta constituted the majority of delayed diagnoses. CONCLUSIONS: In conclusion, murmur and cyanosis are the most common manifestations of prenatally undetected CHDs. Although most children with major CHDs are diagnosed as neonates, some patients are still discharged from the maternity hospital with an unidentified defect.

Fetal heart rhabdomyomatosis: a single-center experience.

Objectives: The primary aim of the study was to evaluate the prevalence of fetal heart tumors in a single tertiary referral center over a period of 15 years. The secondary aim was to confirm the presence of tuberous sclerosis complex (TSC) through the evaluation of germline mutation in TSC1/TSC2 and assess the outcomes in affected fetuses and newborns.Methods: A retrospective study was conducted between 2003 and 2017. Fetal echocardiography was performed in the second trimester of pregnancy in the study population. The identification of heart tumors and further follow-up were performed by a pediatric cardiologist. Molecular genetic analysis was conducted on fetuses and children in cases where TSC was suspected.Results: In total, 39,018 fetuses were examined between 2003 and 2017. Heart tumors were detected in nine fetuses and were diagnosed as rhabdomyoma in all cases. We identified mutations in one of the TSC1 or TSC2 genes in all cases with multiple rhabdomyomas (8/9). In all born children (5/9), the genetically confirmed diagnosis of TSC was established, and clinically pathological deposits in the brain were found.Conclusion: Fetal heart tumors are usually represented by rhabdomyomas having a good cardiac prognosis. However, rhabdomyoma is usually the first symptom of TSC with a subsequent brain disorder and impaired neurological development.

Cytoplasmic Transfer Improves Human Egg Fertilization and Embryo Quality: an Evaluation of Sibling Oocytes in Women with Low Oocyte Quality.

The aim of this study was to evaluate if cytoplasmic transfer can improve fertilization and embryo quality of women with oocytes of low quality. During ICSI, 10-15% of the cytoplasm from a fresh or frozen young donor oocyte was added to the recipient oocyte. According to the embryo quality, we defined group A as patients in which the best embryo was evident after cytoplasmic transfer and group B as patients in which the best embryo was evident after a simple ICSI. We investigated in the period of 2002-2018, 125 in vitro fertilization cycles involving 1011 fertilized oocytes. Five hundred fifty-seven sibling oocytes were fertilized using ICSI only and 454 oocytes with cytoplasmic transfer. Fertilization rates of oocytes were 67.2% in the cytoplasmic transfer and 53.5% in the ICSI groups (P < 0.001). A reduction in fertilization rate was observed with increased women age in the ICSI but not in the cytoplasmic transfer groups. The best embryo quality was found after cytoplasmic transfer in 78 cycles (62.4%) and without cytoplasmic transfer in 40 cycles (32%, P < 0.001). No significant differences were detected between the age, hormonal levels, dose of stimulation drugs, number of transferred embryos, pregnancy rate and abortion rate between A and B groups. Cytoplasmic transfer improves fertilization rates and early embryo development in humans with low oocyte quality. All 28 children resulting from cytoplasmic transfer are healthy.

Congenital fetal heart defect - an agreement between fetal echocardiography and autopsy findings.

AIMS: To determine the frequency of pregnancy terminations due to prenatal congenital heart defect (CHD) and assess the agreement fetal echocardiography (FECHO) and autopsy findings. METHODS: The data were retrospectively assessed between 2008 and 2017 in a population of 116 698 live births. The correlations between the FECHO and autopsy findings were classified into five levels of agreement: complete, partial, altered diagnosis, disagreement, and unfeasible autopsy. RESULTS: Totally, 293 CHDs were identified and 49% of families (143/293) decided to terminate the pregnancy. In 1% (2/143) of cases, the autopsy could not be performed, for the other 99% (141/143), the pathologist confirmed the presence of CHDs. Complete agreement between FECHO and autopsy was achieved in 85% (122/143). In 10% (14/143) of cases, the pathologist found minor findings, which were not described in the FECHO. In 4% (5/143) of cases, the pathologist changed the main diagnosis. CONCLUSION: Altogether, the results indicated that FECHO is a highly sensitive method for the prenatal detection of CHD but is incapable of detecting the complete spectrum of cardiac defects. Autopsies verified the diagnosis, confirmed the overall impairment in the fetus, and provided data for further counselling of the affected family.

Congenital heart defects according to the types of the risk factors - a single center experience.

Objective: The main aim of this study was to compare the prevalence of congenital heart defects (CHDs) between pregnant women with and those without the risk factors. The secondary aim was to determine the influence of the specific risk factors, divided into subgroups, on the development of the CHD. Methods: The presented results were obtained over the course of a 15-year study between years 2002 and 2016. Fetal echocardiography was performed as a planned screening examination during the second trimester of gravidity. A total of 35,831 singleton pregnancies were examined at our center. Risk factors for the development of CHDs were analyzed and divide into the following groups: (i) maternal age ≥35 years; (ii) mother-related risk factors; (iii) pregnancy- and fetus-related risk factors; (iv) pregnancy after in vitro fertilization (IVF); (v) history of CHDs in the first-degree family member; (vi) history of CHDs in the second-degree family member; and (vii) positive genetic family history. Results: The risk factors were identified in 25% (8990/35,831) of pregnancies. In total, CHDs were detected in 1.1% (394/35,831) of fetuses. The prevalence rate of CHDs was higher in the pregnancies with than in those without the risk factors (2.5% [221/8990] versus 0.6% [173/26,841]; p < .0001). The presence of pregnancy- and fetus-related risk factors (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.3-9.7) and pregnancy after IVF (OR, 2.8; 95% CI, 1.5-5.2) were found to be independent risk factors of CHDs. Conclusions: The presence of specific risk factors is related to the increasing prevalence of CHDs. Pregnancy- and fetus-related risk factors and in vitro fertilization were found to be the independent risk factors of CHD.

Associations between congenital heart defects and genetic and morphological anomalies. The importance of prenatal screening.

AIM: To study congenital heart defects (CHDs), evaluate their relation to extra-cardiac pathologies, and assess the significance of prenatal diagnostics for heart diseases. METHODS: Data from 1999-2017 were analyzed for the incidence of significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children, including, where applicable, autopsy data and genetic evaluation. RESULTS: Among 220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an isolated impairment in 78% (640/819), associated with a genetic impairment in 16% (128/819), and with extra-cardiac malformations without genetic pathology in 6% (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic pathology association was more frequent prenatally [21% (90/435) vs. postnatally: 10% (38/384; P<0.0001)], as was the association between CHD with other extra-cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs. postnatally: 2% (7/384; P<0.0001)]. CONCLUSION: Heart defects are most frequently isolated, with genetic and other extra-cardiac anomalies in about one third of cases, significantly linked to prenatal diagnostics.

Acute lymphoblastic leukemia in a child with Leri-Weill syndrome and complete SHOX gene deletion: A Case Report.

BACKGROUND: Leri-Weill syndrome (LWS) ranks among conditions with short stature homeobox gene (SHOX) haploinsufficiency. Data on possible association of SHOX aberrations with malignant diseases are scarce. METHODS AND RESULTS: We report a unique case of an 8-year-old girl who was successfully treated for acute lymphoblastic leukemia (pre-B ALL, intermediate risk) and was subsequently diagnosed with LWS due to characteristic clinical appearance (short disproportionate stature, Madelung deformity of the wrist) and molecular genetic examination (complete deletion of SHOX). An identical SHOX deletion was identified also in the patient's mother. Leukemic cells of the patient were retrospectively examined by array comparative genomic hybridization (aCGH), which revealed five regions of deletions at chromosome X, including the SHOX gene locus. CONCLUSION: Growth retardation in children with hemato-oncologic malignancies cannot always be attributed to cytotoxic treatment and should be carefully evaluated, especially with regards to growth hormone therapy.

Increased prevalence of bicuspid aortic valve in Turner syndrome links with karyotype: the crucial importance of detailed cardiovascular screening.

BACKGROUND: Bicuspid aortic valve (BAV) represents one of the strongest risk factors for aortic dissection in Turner syndrome (TS). An exact relation between the occurrence of BAV and a particular karyotype has not been established yet. The aim of this study was to determine the association between karyotype and prevalence of BAV. METHODS: Sixty-seven TS patients aged between 6.6 and 32.5 years underwent cardiac magnetic resonance imaging (MRI) study. They were divided into four cytogenetic subgroups-45,X karyotype (n=27); 45,X/46,XX mosaicism (n=17); structural abnormalities of the X chromosome (n=10); and 45,X/structural abnormality of the X chromosome mosaicism (n=13). Prevalence of BAV and odds ratio (OR) compared with the general population in the whole study group, and statistical comparison of prevalences of BAV among the individual subgroups were determined. RESULTS: Prevalence of BAV in the whole study group was established as 28.4% [OR 208.3 (95% CI - 103.8-418.0); p-value<0.0001]. Individuals with 45,X karyotype had the highest prevalence of BAV - 40.7%, p-value<0.0001. Presence of any 45,X cell line in karyotype significantly predisposed to BAV (p-value=0.05). CONCLUSIONS: The 45,X karyotype is associated with the highest prevalence of BAV. Also, the presence of the 45,X cell line in any mosaic karyotype increases the probability of BAV.