Search Results (50)

Chromosomal defects are a significant cause of perinatal death and childhood disability, occurring in 3.6–6.0 per 1000 births in unscreened populations. Common chromosomal defects include trisomy 21, 18, and 13, triploidy, and sex chromosome abnormalities. Screening for these defects began in the mid-1960s with the advent of amniocentesis, and various methods have since been developed to improve screening performance. Initial screening was based solely on maternal and gestational age, a method incorporated later into all subsequent screening methods giving an a priori background risk. This a priori background risk, which is further refined by maternal serum biochemistry, results of ultrasound examinations, and most recently, results of non-invasive prenatal testing by cell-free DNA in maternal blood. This paper will describe methods of screening for all chromosomal defects and their performance. Unlike most reviews, this paper covers not only screening tests for Down syndrome, but also screening methods for the other most common and less common chromosomal defects. Full article

Background/Objectives: Non-invasive prenatal testing (NIPT) has become a widely used method for screening common fetal aneuploidies due to its high sensitivity and specificity compared to traditional screening methods. With various NIPT technologies available, such as whole-genome sequencing (WGS), single nucleotide polymorphisms (SNPs), microarray, and rolling circle amplification (RCA), understanding the accuracy and reliability of each method is critical for clinical decision-making. However, comprehensive evaluations comparing the performance of these NIPT methods, especially in terms of predictive values for trisomy detection, remain limited. A systematic review of the difference in accuracy of the different NIPT methods used for common aneuploidy screening. Methods: A systematic review of former clinical studies using different NIPT methods, such as whole-genome sequencing (WGS), a targeted method of single nucleotide polymorphisms (SNPs), microarray and rolling circle amplification (RCA). We collected data from the PubMed, Embase, Web of Science, Scopus, clinicaltrials.gov, and Cochrane library from the last 20 years, between 2003 January and 2023 October, without any language, search filter or publication type restrictions. Results: Two authors selected twenty articles including twenty-one studies to perform the systematic review. In these studies, altogether 92,164 pregnant women were tested by genomics-based non-invasive prenatal testing (NIPT). We extracted data on true positive, false positive, false negative, and true negative values from each study, and calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) from them. We collected data regarding trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) detection from all studies. Conclusions: As a conclusion, for the detection of common fetal trisomies, different methods of NIPT perform similarly in terms of clinical sensitivity, specificity and NPV. However, the tests utilizing SNP and RCA had lower PPV values than other NIPT methods. Our research indicates all NIPT methods showed greater sensitivity for the detection of T21, above 97%, than traditional screening tests. For T18 detection, the targeted method with the microarray had a lower sensitivity compared to other tests. The SNP and the microarray-based test had high PPV, whilst the other tests, utilizing WGS, and the test with RCA had quite low PPV. Regarding T13 detection, all of the tests performed similarly in terms of clinical sensitivity, specificity, PPV, and NPV (with one exception—one of the tests using WGS had lower PPV). According to these results, there was no significant difference between the methods of NIPT, such as WGS, SNPs, microarray, and RCA, used to detect common trisomies, but the variation in PPV underlines the importance of invasive tests to derive positive NIPT results. We suggest that NIPT combined with US screening for structural abnormalities could further improve the utility of the non-invasive tests in pregnancy. This is the first independent systematic review into the efficacy of the different NIPT methods. Full article

Background/Objectives: Prevalence of umbilical cord cysts is largely unknown, mainly due to small dimensions and to the fact that only placental and fetal insertion of the umbilical cord are usually assessed. Older studies report a total prevalence of about 3%, regardless of the size. To date, no correlation between the gestational age, the size of the cyst at the moment of diagnosis and pregnancy prognosis can be made. Methods: We managed a case of a large umbilical cyst diagnosed in the first trimester. As our experience with this pathology was limited, we performed a systematic review in order to find out the optimal management. Results: We report a case of a large umbilical cord cyst that ended in fetal demise at 13 weeks in the absence of any chromosomal and structural anomalies. Our results differ from what was expected from our literature review. Sixteen papers were included in our analysis. According to the selected papers, single cysts are more frequent than multiple cysts (79% single cysts). The mean value of the maximum diameter of the cyst was 32 mm, and there was no difference in number considering the localization of the cyst. Considering the cases in which genetic testing was performed, there were 22.76% modified results. The most frequent genetic disorder was trisomy 18 (53.57% from the modified results). Conclusions: Large umbilical cord cysts are correlated with uncertain prognosis. We made the conclusion that large umbilical cord cystic lesions might have an unfavorable prognosis. Although there are case series that have shown an unproblematic evolution of the pregnancy, large umbilical cysts could be associated with increased risk of fetal anomalies and intrauterine fetal death. Full article

Chromosomal abnormalities of the embryo are the most common cause of first-trimester pregnancy loss. In this single-center study, we assessed the frequency and the spectrum of chromosomal abnormalities in miscarriages for each year of maternal age from 23 to 44. Cytogenetic data were obtained by conventional karyotyping of 7118 miscarriages in women with naturally conceived pregnancies. Chromosomal abnormalities were identified in 67.25% of miscarriages. The total incidence of chromosomal abnormalities increased with maternal aging; however, its average change for a one-year increase in maternal age differed between age spans, equaling 0.704% in the span from 23 to 37 years and 2.095% in the span from 38 to 44 years. At the age of 38 years, the incidence rate surged sharply by 14.79% up to 79.01% and then increased progressively up to 94% in 44-year-old women. The spectrum of chromosomal abnormalities in miscarriages was the same for each year of maternal age from 23 to 44 years. However, the proportions of particular chromosomal abnormalities differed between karyotypically abnormal miscarriages in younger and older women. The proportions of trisomy 16, polyploidy, monosomy X, mosaic aneuploidies, and structural rearrangements decreased with increasing maternal age. In contrast, the proportions of multiple aneuploidies and regular trisomies 13, 15, 18, 21, and 22 showed an upward trend with maternal aging. To summarize, despite the increase in the total incidence of chromosomal abnormalities in miscarriages with maternal aging, the rate of change differs for younger and older women, being three times lower in the former than in the latter. Moreover, the proportion of some abnormalities in karyotypically abnormal miscarriages shows a steady growth, whereas the proportion of others becomes increasingly low with maternal aging, most probably due to the age-dependent prevalence of different molecular and cellular defects. Full article

Objective: To assess the prenatal course and early postnatal outcomes of fetuses diagnosed with tricuspid atresia and to identify predictors of survival. Methods: This was a retrospective study of 25 fetuses diagnosed with tricuspid atresia in a single tertiary referral center, evaluating prenatal echocardiographic features and postnatal outcomes. Results: A total of 4 of 29 initially diagnosed fetuses were excluded due to changes in diagnosis or loss to follow-up, leaving 25 fetuses for analysis. Of these, 16 (64%) had concordant VA alignment, 8 (32%) had discordant VA connections, and 1 had a double-outlet left ventricle (DOLV). Pulmonary stenosis was observed in 13 fetuses, and 10 (40%) had extracardiac anomalies. Genetic testing, performed in 5 cases, identified a chromosomal anomaly in one case (trisomy 18). Overall, three pregnancies were terminated due to severe associated anomalies. Among the 22 liveborn infants, survival at 12 months was 72%. Restrictive ventricular septal defect (VSD) and the high ductus venosus pulsatility index were significantly associated with lower survival (p = 0.021 and p = 0.034, respectively). Conclusions: Tricuspid atresia can be accurately diagnosed in utero with a thorough echocardiographic evaluation. Restrictive VSD and outflow tract obstructions are critical determinants of early survival, while abnormal DV Doppler patterns may serve as additional markers for adverse outcomes. More extensive studies are needed to validate these findings and improve prognostic counseling. Full article

Background: Chromosomal numerical and structural alterations are significant causes of various developmental disorders in foetuses. Non-invasive prenatal testing (NIPT) has emerged as an effective screening tool for detecting common aneuploidies, aiding in the identification of individuals who may require further diagnostic work-up. Methods: This retrospective, monocentric observational study evaluates the usage patterns, test choices, turnaround times (TAT), and outcomes of NIPT between 2013 and 2023 on a sample of 2431 pregnant women at a special hospital offering outpatient services and comprehensive gynaecological/obstetric inpatient care. We analysed the trends in NIPT usage, high-risk results, prior screening procedures, as well as factors such as age, gestational age and in vitro fertilisation (IVF) status. NIPT was performed using cell-free foetal DNA (cffDNA) extracted from maternal plasma, followed by library construction, sequencing and result analysis. The sequencing results were aligned with reference genomes, and z-scores were calculated to assess the likelihood of aneuploidy. Statistical significance was set at p < 0.05. Results: The average age of women undergoing NIPT decreased from 36.1 years in 2013 to 33.01 years in 2023 (p = 0.0287), and mean TAT dropped from 12.44 days in 2013 to 7.08 days in 2023 (p = 0.0121), with the most substantial reduction occurring between 2013 and 2019. The study identified a stable rate of women who underwent IVF seeking prenatal testing, with no statistically significant difference between the first half and the second half of the analysed period (p = 0.2659). Among high-risk results, there were 39 chromosomal abnormalities detected, most of them belonging to trisomy 21 (59%). Conclusions: Our findings demonstrate the increasing efficiency and accessibility of NIPT in prenatal care in Croatia, while the significant reduction in TAT and the decreasing age of women undergoing NIPT reflect enhanced operational practices and broader acceptance. Introducing NIPT into the public healthcare system in the Republic of Croatia could improve equitable access to advanced prenatal care and enhance pregnancy outcomes. Future advancements in technology and genetic counselling will further enhance its role, requiring careful attention to ethical and regulatory considerations. Full article

Background/Objective: Balanced reciprocal translocations are structural chromosomal anomalies that involve a mutual exchange of segments between two non-homologous chromosomes with a consequent 50–80% risk of conceiving fetuses with unbalanced chromosomal anomalies. This study describes a 37-year-old woman, at 13 + 5 weeks of gestation, who is a balanced reciprocal translocation 46,XX,t(9;18)(q34;q11.2) carrier, with a high-risk non-invasive prenatal screening test, NIPT, for chromosome 18 aneuploidy. Methods: The highlighted aneuploidy was characterized with cytogenetic, FISH and SNP-array techniques. Results: Cytogenetic analysis, performed on flask-cultured amniocytes, indicated a 48,XX,+2mar karyotype on 50 metaphases. SNP array analysis showed a 15.3 Mb duplication of chromosome 18p (arr[hg19]18p11.32-p11.21(12,842-15,303,932)x4), consistent with a partial tetrasomy 18p, and a 926 kbp duplication of chromosome 9q (arr[GRCh37]9q34.3(140,118,286-141,044,489)x3), consistent with partial trisomy 9q. FISH analysis with a 9q34.3 probe was performed on flask-cultured amniocytes’ metaphases, highlighting the presence of a third signal on one of the two marker chromosomes (18p11.32-p11.21). Conclusions: The evidence of such partial aneuploidies suggests that different mutational events may be possible at meiotic segregation or probably post-meiotic segregation. The results obtained highlight the high sensitivity of the screening test, NIPT, with massive parallel sequencing, and the usefulness of cytogenetics, cytogenomics and molecular biology techniques, in synergy, to characterize and confirm positive NIPT results. Full article

Background and Objectives: Down syndrome (DS) is the most common chromosomal disorder in the world. It is caused by the imbalance of the chromosomal constitution of 21 by free trisomy, translocation or mosaicism. Children and adolescents with Down syndrome have immune dysregulation and are more susceptible to infections. This study aims to evaluate hospitalizations of children and adolescents with DS in the pediatric ward of Botucatu Clinics Hospital (HCFMB) and to classify the population of children included in the study according to age, diagnosis, outpatient follow-up, length of stay and need for the intensive care unit (ICU). Thus, it will be possible to improve care for these children, aiming to reduce these hospitalizations. Materials and Methods: This study was an observational, cross-sectional study, with retrospective data collected from the last nine years of hospitalization, from January 2013 to December 2021, from children and adolescents with DS in the pediatric ward, emergency room, and the ICU of HCFMB. Children hospitalized in this period in the pediatric ward and ICU, in the age range of 30 days to 15 years, were included in this study. The evaluation of comorbidities that culminated in the need for hospitalization in this population can be the focus of actions to improve the diagnoses and conducts for this population, which can prevent worsening illness and hospitalizations in future populations. Results: In this analysis, 80 children with DS were evaluated, with a total of 283 hospitalizations. The most prevalent age group was 1 to 3 years, and the main cause was due to problems in the respiratory system (99 cases). Among the respiratory causes, the main cause of hospitalization was due to pneumonia in 50% of cases, followed by acute respiratory failure in 14%. The average hospitalization time was 8 days, and in 49 hospitalizations, the children required the ICU. The main cause of hospitalization in the ICU was due to respiratory causes (36%), followed by cardiac malformations (14%). During the ICU hospitalizations, there were 13 deaths, and we observed a higher prevalence of heart conditions and, in some cases, positive urine cultures in these children. Conclusions: The Hospital serves as a reference for pediatric hospitalizations within its region and beyond, owing to its specialized capabilities. The main causes of hospitalization were those related to the respiratory system and cardiac malformations. Roughly one-third of the children required admission to the intensive care unit. Full article

Cleft lip and/or palate are prevalent congenital anomalies. Early and accurate diagnosis allows proper case management. The Objective: This retrospective cohort study aimed to investigate the association between cleft lip and palate and other congenital anomalies. Methods: This study analyzed 17 pregnancies prenatally diagnosed with cleft lip and palate. The investigations consisted of ultrasound examination, fetal karyotyping through amniocentesis, and family tree analysis. In the presence of an abnormal fetal karyotype, the parental karyotype was also indicated. Results: Of the 17 cases identified, 9 (52.94%) were syndromic and 8 (47.06%) were non-syndromic. The genetic syndromes identified in association with cleft lip and palate in this study included translocation syndrome (one case), Patau syndrome, trisomy 13 (seven cases), and Edwards syndrome, mosaic trisomy 18 (one case). Conclusions: A comprehensive approach ensures a thorough assessment and accurate diagnosis. Early detection and a multidisciplinary approach allow appropriate case management. Full article

Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers’ demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent “big data”. Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies. Full article

Background: This study’s aim was to determine whether diminished oocyte reserve (DOR) increases the risk of having a fetus with trisomy 13, 18, or 21 at 10 weeks as evaluated by non-invasive prenatal testing (NIPT) and to evaluate the confounding effect of advanced age. Methods: NIPT was undertaken in all pregnancies conceived through natural treatment or assisted reproductive technology that reached 10 weeks from conception with a viable fetus from one infertility center. Data were stratified according to serum anti-Mullerian hormone (AMH) < 1 ng/mL and ≥1 ng/mL. Results: No woman < 39 or with AMH ≥ 1 ng/mL showed trisomy 13, 18, or 21 by NIPT. Only women ≥ age 39 with DOR had one of these trisomies. Conclusions: Hopefully these data, coupled with other factors, e.g., etiology of infertility, age, insurance, or financial circumstances, and personal views of pregnancy termination, will aid patients with DOR when choosing treatment options, including natural conception, IVF-ET, IVF with pre-implantation genetic testing for aneuploidy, or transfer of fertilized donor eggs. Full article

Background: In recent years, preimplantation genetic testing for aneuploidies (PGT-A) has become widespread in assisted reproduction. However, contrary to expectations, PGT-A does not significantly improve the clinical outcomes of assisted reproductive technologies. One of the underlying reasons is the discordance between the PGT-A results and the true chromosomal constitution of the blastocyst. In this case series, we re-examined the PGT-A results in trophectoderm (TE) re-biopsies and in the two isolated blastocyst compartments—the TE and the inner cell mass (ICM). Methods: This study enrolled 23 human blastocysts from 17 couples who were referred for assisted reproduction. The blastocysts were unsuitable for uterine transfer due to the chromosomal imbalance revealed by PGT-A using array comparative genomic hybridization (aCGH) (n = 11) or next-generation sequencing (NGS) (n = 12). The re-examination of the PGT results involved two steps: (1) a TE re-biopsy with subsequent aCGH and (2) blastocyst separation into the TE and the ICM with a subsequent cell-by-cell analysis of each isolated compartment by fluorescence in situ hybridization (FISH) with the DNA probes to chromosomes 13, 16, 18, 21, and 22 as well as to the PGT-A detected imbalanced chromosomes. Results: In 8 out of 23 cases, the PGT-A results were concordant with both the re-biopsy and the isolated TE and ICM analyses. The latter included the diagnoses of full non-mosaic aneuploidies (five cases of trisomies and two cases of monosomies). In one case, the results of PGT-A, aCGH on the TE re-biopsy, and FISH on the isolated TE showed Xp tetrasomy, which contrasted with the FISH results on the isolated ICM, where this chromosomal pathology was not detected. This case was classified as a confined mosaicism. In 4 out of 23 cases, the results were partially discordant. The latter included one case of trisomy 12, which was detected as non-mosaic by PGT-A and the re-biopsy and as mosaic by FISH on the isolated TE and ICM. This case was classified as a true mosaicism with a false negative PGT-A result. In 11 out of 23 cases, the re-examination results were not concordant with the PGT-A results. In one of these discordant cases, non-mosaic tetraploidy was detected by FISH in the isolated TE and ICM, whereas the PGT-A and the TE re-biopsy failed to detect any abnormality, which advocated for their false negative result. In two cases, the re-examination did not confirm full aneuploidies. In eight cases, full or partial mosaic aneuploidies as well as chaotic mosacism were not confirmed in the isolated TE nor the isolated ICM. Thus, in 47.8% of cases, the PGT-A results did not reflect the true chromosomal constitution of a blastocyst. Conclusions: The PGT results may have different prognostic value in the characterization of the chromosomal constitution of a blastocyst. The detected non-mosaic aneuploidies have the highest prognostic value. In stark contrast, most PGT-identified mosaic aneuploidies fail to characterize the true chromosomal constitution of a blastocyst. Once detected, a differential diagnosis is needed. Full article

Genome-wide prenatal cell-free DNA (cfDNA) screening can be used to screen for a wide range of fetal chromosomal anomalies in pregnant patients. In this study, we describe our clinical experience with a genome-wide cfDNA assay in screening for common trisomies, sex chromosomal aneuploidies (SCAs), rare autosomal aneuploidies (RAAs), and copy-number variations (CNVs) in about 6000 patients over a three-year period at our hospital’s Prenatal Diagnostic Unit in Spain. Overall, 204 (3.3%) patients had a high-risk call, which included 76 trisomy 21, 21 trisomy 18, 7 trisomy 13, 29 SCAs, 31 RAAs, 31 CNVs, and 9 cases with multiple anomalies. The diagnostic outcomes were obtained for the high-risk cases when available, allowing for the calculation of positive predictive values (PPVs). Calculated PPVs were 95.9% for trisomy 21, 77.8% for trisomy 18, 66.7% for trisomy 13, 10.7% for RAAs, and 10.7% for CNVs. Pregnancy and birth outcomes were also collected for the majority of RAA and CNV cases. Adverse perinatal outcomes for some of these cases included preeclampsia, fetal growth restriction, preterm birth, reduced birth weight, and major congenital structural abnormalities. In conclusion, our study showed strong performance for genome-wide cfDNA screening in a large cohort of pregnancy patients in Spain. Full article

Introduction: Pediatric cystic kidney disease (CyKD) includes conditions characterized by renal cysts. Despite extensive research in this field, there are no reliable genetics or other biomarkers to estimate the phenotypic consequences. Therefore, CyKD in children heavily relies on clinical and diagnostic testing to predict the long-term outcomes. Aim: A retrospective study aimed to provide a concise overview of this condition and analyze real-life data from a single-center pediatric CyKD cohort followed during a 12-year period. Methods and Materials: Medical records were reviewed for extensive clinical, laboratory, and radiological data, treatment approaches, and long-term outcomes. Results: During the study period, 112 patients received a diagnosis of pediatric CyKD. Male patients were more involved than female (1:0.93). Fifty-six patients had a multicystic dysplastic kidney; twenty-one of them had an autosomal dominant disorder; fifteen had an isolated renal cyst; ten had been diagnosed with autosomal recessive polycystic kidney disease; three had the tuberous sclerosis complex; two patients each had Bardet–Biedl, Joubert syndrome, and nephronophthisis; and one had been diagnosed with the trisomy 13 condition. Genetic testing was performed in 17.9% of the patients, revealing disease-causing mutations in three-quarters (75.0%) of the tested patients. The most commonly presenting symptoms were abdominal distension (21.4%), abdominal pain (15.2%), and oligohydramnios (12.5%). Recurrent urinary tract infections (UTI) were documented in one-quarter of the patients, while 20.5% of them developed hypertension during the long-term follow-up. Antibiotic prophylaxis and antihypertensive treatment were the most employed therapeutic modalities. Seventeen patients progressed to chronic kidney disease (CKD), with thirteen of them eventually reaching end-stage renal disease (ESRD). The time from the initial detection of cysts on an ultrasound (US) to the onset of CKD across the entire cohort was 59.0 (7.0–31124.0) months, whereas the duration from the detection of cysts on an US to the onset of ESRD across the whole cohort was 127.0 (33.0–141.0) months. The median follow-up duration in the cohort was 3.0 (1.0–7.0) years. The patients who progressed to ESRD had clinical symptoms at the time of initial clinical presentation. Conclusion: This study is the first large cohort of patients reported from Croatia. The most common CyKD was the multicystic dysplastic kidney disease. The most common clinical presentation was abdominal distention, abdominal pain, and oliguria. The most common long-term complications were recurrent UTIs, hypertension, CKD, and ESRD. Full article

Down syndrome (DS) is the most common genetic alteration in humans, resulting from the trisomy of chromosome 21. Individuals with DS are characterized by physical traits and limitations related to intellectual functioning and the development of motor skills. People with DS tend to have lower levels of physical activity (PA) than the general population, despite its benefits for health and quality of life, which could be caused by barriers such as the lack of adapted programs or knowledge on how to adapt them. Therefore, this systematic review aimed to examine the impact of physical activity or sports programs on autonomy and quality of life in individuals with DS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to search four databases (Scopus, Web of Science, PubMed, and SportDiscus), adhering to the population, intervention, comparison, and outcome strategy. A total of 13 studies were selected that followed different training programs (combined training, adapted football, technology-based, pulmonary training, gymnastics and dance, water-based, and whole body vibration). Most of the interventions provided benefits for autonomy or quality of life (physical, psychological, cognitive, emotional, and social) in people with DS. In conclusion, the benefits of physical activity and sports programs adapted to people with DS are positive. Full article