The use of maternal age alone to identify pregnant mothers at risk of a fetus with Down's syndrome has recently been supplemented by maternal serum screening using biochemical markers such as alpha-protein, human chorionic gonadotrophin and oestriol. These tests have been reported to increase the sensitivity of antenatal detection of such fetuses from 35% to 67% with a false positive rate of 5%. However, these maternal serum markers may be affected by maternal weight, the smoking history of mothers and diabetes mellitus. Furthermore, such sensitivities are achieved only when gestational age is assessed accurately by ultrasound. Many further studies need to be carried out before the introduction of maternal serum screening into routine obstetric practice in Singapore. These include studies on the incidence of Down's syndrome in the local population, studies on the distribution of these serum markers in the second trimester of pregnancy, sensitivities and positive predictive values of such a test in the local population as well as the socio-economic implications of implementing such a screening test in the local obstetric population.
The association between hypoechoic hepatomegaly in the third trimester and transient abnormal myelopoiesis (TAM) was reported previously in six fetuses with trisomy 21 (T21). We report a series of three cases of T21 in which hypoechoic liver (HL) was found in the second trimester but without evidence of TAM on both hematological and histological examination. We postulate that the hypo-echogenicity may be due to liver congestion secondary to hemodynamic disturbances seen in T21 fetuses. All three cases had negative first trimester Down syndrome screening and one case was detected solely because of the isolated finding of HL. HL per se may be associated with T21 and more positive cases are required to support this association.
Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35-100.00%); 100.00% sensitivity for T18 (71.51-100.00%); and 100.00% sensitivity for T13 analyses (66.37-100.00%). The specificities were >99% for each trisomy (99.7% (99.01-99.97%) for T21; 99.5% (98.62-99.85%) for T18; 99.7% (99.03-99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.
Depending on the severity of their disabilities, children with Down syndrome (DS) and with cerebral palsy (CP) may remain pre-symbolic for prolonged periods of time. When interacting with pre-symbolic children, communication partners have a role in identifying which of their behaviours are communicative, to be able to respond to those behaviours and maintain reciprocal interaction. To date, most research on these children's communication development has been conducted within the context of mother-child interaction. Seldom have they been observed interacting with other family members, and in interactions other than dyadic, despite these interactions also occurring daily.
We studied 253 women with a pregnancy complicated by a birth defect and 506 controls to determine the frequency and type of prenatal tests and the types of defects detected antenatally. Most women had at least one ultrasound examination, but the frequency of other screening tests was low. Only 38 (15%) of defects were detected antenatally (37 by ultrasound). Birth prevalence is unlikely to be affected by pregnancy termination.
The chromosome in situ suppression hybridization or chromosome painting technic was applied to confirm and eliminate the markers involving chromosome 21 segments using a chromosome 21 DNA library. The library ATCCLL21SNO2 was amplified, directly biotinylated using the polymerase chain reaction. The results demonstrated a translocation of chromosome 21 material on chromosome 2 and X and eliminate the origin of the marker. Thus, the technique provides an important tool to complement the conventional G-banding technic.
Limited data are available on the survival of patients with Down syndrome and congenital heart disease (CHD) from middle-income countries. This retrospective cohort study was performed to determine the trends in the prevalence and survival of such patients born from January 2006 to December 2015 in Malaysia. Among 754 patients with Down syndrome, 414 (55%) had CHD, and no significant trend was observed during the 10 years. Of these 414 patients, 30% had lesions that closed spontaneously, 35% underwent surgery/intervention, 9% died before surgery/intervention, and 10% were treated with comfort care. The overall mortality rate was 23%, the median age at death was 7.6 months, and no significant changes occurred over time. The early and late post-surgery/intervention mortality rates were 0.7% and 9.0%, respectively. Most deaths were of non-cardiac causes. The overall 1-, 5-, and 10-year survival rates were 85.5%, 74.6%, and 72.9%, respectively. Patients with severe lesions, persistent pulmonary hypertension of the newborn, atrioventricular septal defect, and pulmonary hypertension had low survival at 1 year of age.Conclusion: The prevalence of CHD in patients with Down syndrome is similar between Malaysia and high-income countries. The lower survival rate is attributed to limited expertise and resources which limit timely surgery. What is Known: • The survival of patients with Down syndrome with congenital heart disease (CHD) has improved in high-income countries. However, little is known about the survival of patients with Down syndrome with CHD from middle-income countries. • In the Caucasian population, atrioventricular septal defect is the most common type of CHD associated with Down syndrome. What is New: • In middle-income countries, the prevalence of CHD is the same as in high-income countries, but with a lower survival rate. • In the Asian population, ventricular septal defect is the most common type of CHD in patients with Down syndrome.
Neurodevelopmental disorders are defined as a set of abnormal brain developmental conditions marked by the early childhood onset of cognitive, behavioral, and functional deficits leading to memory and learning problems, emotional instability, and impulsivity. Autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, fragile X syndrome, and Down's syndrome are a few known examples of neurodevelopmental disorders. Although they are relatively common in both developed and developing countries, very little is currently known about their underlying molecular mechanisms. Both genetic and environmental factors are known to increase the risk of neurodevelopmental disorders. Current diagnostic and screening tests for neurodevelopmental disorders are not reliable; hence, individuals with neurodevelopmental disorders are often diagnosed in the later stages. This negatively affects their prognosis and quality of life, prompting the need for a better diagnostic biomarker. Recent studies on microRNAs and their altered regulation in diseases have shed some light on the possible role they could play in the development of the central nervous system. This review attempts to elucidate our current understanding of the role that microRNAs play in neurodevelopmental disorders with the hope of utilizing them as potential biomarkers in the future.