Occurrence Of Down Syndrome Research Articles

SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (β-hCG) levels (p < 0.05). This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and β-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Down Syndrome: Insights and Analysis

Normally, there are 23 pairs of chromosomes found in human beings. But in some conditions, a mother has a fetus with an additional chromosome at T21(21st position) which is said to be the fetus with Trisomy-21 (Down Syndrome). There are many factors of Down Syndrome - nasal bone absence, short nasal bone, thick amniotic fluid (greater than 3 mm), fetal heart rate (FHR), Crown Lump Length, short arm, and thighs’ bones; are screened during 10-14th (First Trimester) and 15-22nd week (Second Trimester) of pregnancy. These screenings are very crucial tasks as invasive methods, hence ultrasound imaging technique comes into the picture as a non-invasive methods. With this article, we put a glance at various reasons of occurrence of Down Syndrome and comment on some analysis of societal impact of Down Syndrome. Further, we should focus on how a fetus can be diagnosed with Down Syndrome during the early age of her mother’s pregnancy using Computerized techniques such as machine learning and deep learning approaches?

Analisis Studi Kasus Mengenai Usia Ibu dan Gambaran Fisik Penderita Sindrom Down

Down syndrome or trisomy 21 is the most common genetic disorder among other genetic disorders. The definition of Down syndrome is a chromosomal abnormality in which there is an extra copy of chromosome 21 due to non-disjunction, mosaicism or the rarest occurrence is translocation. The age of the mother when pregnant is one of the factors causing Down syndrome, the older the mother's age, the greater the chance of Down syndrome. The development of Down syndrome children is different from other normal children, so special care and parenting are needed. The purpose of this research is to analyze through case studies of Down syndrome patients aspects of birth occurrence, aspects of child growth and development, and aspects of the physical description of Down syndrome patients. The results of this study indicate that many factors can influence the occurrence of Down syndrome, namely genetic factors, radiation factors, and the age of the mother. If Down syndrome children receive a form of therapy, health care, and supportive parenting and environment. Then Down syndrome children can adapt well such as how to communicate and interact.

Prevalence of Bruxism in Down Syndrome Patients: A Systematic Review and Metanalysis.

Bruxism is a parafunctional activity characterized by grinding or clenching of teeth and is a common oral health concern in individuals with Down syndrome (DS). Understanding the prevalence of bruxism in this population is crucial for developing effective management strategies. This systematic review and meta-analysis is aimed to investigate the prevalence of bruxism among individuals with DS and explore its association with other oral health issues; METHODS: A comprehensive search was conducted across multiple electronic databases to identify relevant studies. Cross-sectional and observational studies were included. Data on bruxism prevalence and associated factors were extracted, and a meta-analysis was performed using both fixed and random-effects models of MedCalc software. Heterogeneity among studies was assessed using I2 statistics. New Castle - Ottawa scale was used to evaluate methodological quality of the included studies RESULTS: Eight studies met the predefined inclusion criteria and were included in the analysis. Seven studies used a questionnaire to assess bruxism. The pooled proportion estimate for occurrence of Down's syndrome across the included studies was found to be 0.33 (95% CI: 0.22-0.45) as per the RE model and 0.35(95% CI: 0.31-0.450) as per FE model in the quantitative analysis. All studies exhibited good methodological quality CONCLUSION: This systematic review and meta-analysis provide evidence of a significant prevalence of bruxism among individuals with Down syndrome. The findings highlight the association of bruxism with other oral health issues and specific chromosomal abnormalities. Comprehensive oral health assessments, including diagnostic procedures like PSG, are essential for addressing the unique oral health needs of individuals with DS. Further studies are recommended with a valid tool for the diagnosis. Early interventions and management strategies need to be tailored to this population, considering the multifaceted nature of oral health concerns in individuals with DS.

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

Aurora kinase genetic polymorphisms: an association study in Down syndrome and spontaneous abortion.

Aneuploidies, such as Down syndrome (DS), are the leading cause of pregnancy loss. Abnormalities in aurora kinase proteins result in genomic instability and aneuploidy, mainly in tumors. Thus, polymorphisms in Aurora kinase genes could influence the occurrence of DS and spontaneous abortion. A case-control study was conducted including 124 mothers of DS children (DSM) and 219 control mothers (CM) to investigate DS risk according to AURKA and AURKC polymorphisms. Genotyping was performed using TaqMan real-time PCR. The minor allele frequency (MAF) observed in AURKA rs2273535 was, respectively, 0.23 in DSM and 0.20 in CM, whereas the frequency of the AURKC rs758099 T allele was 0.32 in case and 0.33 in control mothers. Statistical analysis showed no significant difference in the distribution of genotypes and allele frequencies between DSM and CM. According to previous history of spontaneous abortion, the AURKA rs2273535 genotypes (TT+AT vs. AA: OR 2.54, 95% CI 1.13-5.71, p=0.02; AT vs. AA: OR 2.39, 95% CI 1.03-5.51, p=0.04; T vs. A: OR 2.08, 95% CI 1.12-3.90, p=0.02) and AURKC rs758099 (TT vs. CC: OR 4.34, 95% CI 1.03-18.02, p=0.04; TT+CT vs. CC: OR 2.52, 95% CI 1.02-6.23, p=0.04; T vs. C: OR 2.03, 95% CI 1.09-3.80, p=0.02) were observed as risk factors for spontaneous abortion in case mothers. Our study suggests a possible relationship between AURKA/AURKC variants and increased risk of spontaneous abortion within Down syndrome mothers.

Down Syndrome in Brazil: Occurrence and Associated Factors.

Background: Down syndrome is the most frequent genetic cause of intellectual disability, with an estimated birth prevalence of 14 per 10,000 live births. In Brazil, statistical data on the occurrence of babies born with Down syndrome remain unclear. We aimed to estimate the occurrence of Down syndrome between 2012 and 2018, and to observe its association with maternal, gestational, paternal characteristics, and newborn vitality. Methods: A retrospective study was carried out using secondary data included in the Certificate of Live Birth in a state located in the southeastern region of Brazil. Data analysis was performed in the software Stata 14.1. Pearson’s chi-square test for bivariate analysis, and logistic regression for multivariate analysis were performed, with a 95% confidence interval (CI) and a significance of 5%. Results: We observed that 157 cases of Down syndrome were reported among 386,571 live births, representing an incidence of 4 in 10,000 live births. Down syndrome was associated with maternal age ≥ 35 years, paternal age ≥ 30 years, the performance of six or more prenatal consultations, prematurity, and low birth weight (p < 0.05). Conclusions: Women aged 35 and over were more likely to have children born with Down syndrome. In addition, there is an association of Down syndrome with premature birth, low birth weight, and the number of prenatal consultations (≥6).

The demographic data and the high frequency of chromosome/chromatid breaks as biomarkers for genome integrity have a role in predicting the susceptibility to have Down syndrome in a cohort of Egyptian young-aged mothers

BackgroundDown syndrome (DS) is a common numerical chromosome disorder that has its burden on both family and community. The well-known risk factor for chromosome 21 nondisjunction is advanced maternal age which failed to explain the occurrence of Down syndrome born to mothers less than 35 years. This study aimed to assess the effect of demographic data (consanguinity, residency area, and socioeconomic state) and chromosome/chromatid breaks as biomarkers for genome integrity on the susceptibility of young mothers to have a child with Down syndrome.ResultsFifty mothers with a history of at least one DS pregnancy before the age of 35 were compared to 50 control mothers. There was a significant increase in DS births in consanguineous parents (46%) compared to 20% in non-consanguineous ones (OR = 3.40; 95% CI = 1.4–8.20, P = 0.006). Young mothers with DS children were more likely to be from rural areas (60%) than urban areas (40%) (OR = 2.66; 95%, CI = 1.18–5.98, P = 0.017) and of a low socioeconomic status (62%) rather than a high socioeconomic status (38%) (OR = 3.80; 95%, CI = 1.65–8.74, P = 0.001).Chromosome/chromatid breaks were detected in 76% of DS young mothers and 32% of control mothers (P < 0.001). There was an odds ratio of chromatid breaks of 8.50 (3.411–21.17) and chromosome breaks of 3.93 (1.40–11.05) with significant difference between the studied groups (P < 0.001 and P = 0.009 respectively).ConclusionIn addition to advanced maternal age, consanguinity, residency in rural areas, and low socioeconomic status could be considered as possible risk factors for Down syndrome. The high frequency of chromosome/chromatid breaks in young mothers with a previous history of DS children highlights the impact of genome integrity on the tendency to chromosome 21 nondisjunction. These findings are valuable in predicting having a Down syndrome baby and providing proper genetic counseling for high-risk families.

Bi-stream CNN Down Syndrome screening model based on genotyping array

BackgroundHuman Down syndrome (DS) is usually caused by genomic micro-duplications and dosage imbalances of human chromosome 21. It is associated with many genomic and phenotype abnormalities. Even though human DS occurs about 1 per 1,000 births worldwide, which is a very high rate, researchers haven’t found any effective method to cure DS. Currently, the most efficient ways of human DS prevention are screening and early detection.MethodsIn this study, we used deep learning techniques and analyzed a set of Illumina genotyping array data. We built a bi-stream convolutional neural networks model to screen/predict the occurrence of DS. Firstly, we built image input data by converting the intensities of each SNP site into chromosome SNP maps. Next, we proposed a bi-stream convolutional neural network (CNN) architecture with nine layers and two branch models. We further merged two CNN branch models into one model in the fourth convolutional layer, and output the prediction in the last layer.ResultsOur bi-stream CNN model achieved 99.3% average accuracies, and very low false-positive and false-negative rates, which was necessary for further applications in disease prediction and medical practice. We further visualized the feature maps and learned filters from intermediate convolutional layers, which showed the genomic patterns and correlated SNPs variations in human DS genomes. We also compared our methods with other CNN and traditional machine learning models. We further analyzed and discussed the characteristics and strengths of our bi-stream CNN model.ConclusionsOur bi-stream model used two branch CNN models to learn the local genome features and regional patterns among adjacent genes and SNP sites from two chromosomes simultaneously. It achieved the best performance in all evaluating metrics when compared with two single-stream CNN models and three traditional machine-learning algorithms. The visualized feature maps also provided opportunities to study the genomic markers and pathway components associated with Human DS, which provided insights for gene therapy and genomic medicine developments.

No-fistula vs. fistula type anorectal malformation: Outcome comparative study

IntroductionAnorectal malformation (ARM) is a congenital defect that exists in varying presentations and no-fistula type (NFT) ARM is a rare high-type category. We aim to report our experience with management of this anomaly and its outcome, compared to the more common fistula-type (FT) ARM. MethodsA retrospective review of medical records of patients diagnosed with high ARM and 3years and older, for the period between September 2000 and January 2015 was conducted. Demographic, anatomic, and outcome data were obtained for each group and compared. Quality of life data were collected using the Krickenbeck classification and assessed as documented at clinic visits as well as phone interviews. ResultsThere were 100 patients managed for ARM during that period and were 3years or older. Sixteen of them were NFT (16%). For comparison purposes each NFT patient was matched with 3 FT patients.We have analyzed data on 44 patients with FT (44 males), and 16 with NFT (12 males and 4 females). The occurrence of Down syndrome in NFT patients was 56.2% compared to 0% in the FT patients (p=<0.0001). Quality of Life data showed no significant differences between the two groups with p-values of 0.39, 1.0, and 1.0 for Voluntary Bowel Movement, Soiling, and Constipation respectively. ConclusionNFT ARM represents a significant number at our population (16%). There is a strong association between NFT ARM and Down syndrome. NFT ARM has similar outcomes compared to the FT ARM. Type of studyClinical research paper. Level of evidenceLevel III.

DNA (cytosine-5)-methyltransferase 3B (DNMT 3B) polymorphism and risk of Down syndrome offspring.

Down syndrome (DS) is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)-methyltransferase 3B (DNMT3B – EC 2.1.1.37) de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS infants (MDS) and 212 control mothers (CM) through PCR-RFLP. The observed genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC = 0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T = 0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed, and both DNMT 3B rs2424913 genotype (χ2 = 4.53; DF = 1; P = 0.03) and allelic (χ2 = 4.90; DF = 1; P = 0.03) frequencies show significant differences between MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of bearing a DS child (OR = 0.69; 95% CI: 0.50–0.96; P = 0.03), and the risk is diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95% CI: 0.31–0.96; P = 0.04). Our results suggest that women harboring the single nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Fetopathological examination for the fetuses with Down syndrome in Tunisia: Epidemiological study and associated malformations

BackgroundFor Down syndrome (DS), traditional epidemiological studies to determine the prevalence, cause, and clinical significance of the syndrome have been conducted over the last 100 years. In Tunisia, the current work is the first in-depth study in epidemiology of DS from fetopathological data. Aim of the studyThe aim of this epidemiological study was to determine the impact of some feto-maternal characteristics in occurrence of DS and to search the frequency of associated congenital malformations with this syndrome. MethodsOur retrospective study was realized for 144 fetuses with DS among 9321 autopsied fetuses in embryo-fetopathological service between 1994 and 2011. ResultsIn our study, the majority of mothers (72.91%) were 35 years and older, with a statistically significant difference (p<10−6, OR=16.7, CI=8.7–32.4). The abnormalities of extremities (31%) were the most common fetal abnormalities followed by facial (23.51%) and digestive abnormalities (19.63%). ConclusionOne of the main conclusions of this research is that the most common risk factor for DS is maternal age. On the other hand, the type and the frequency of associated congenital anomalies with DS are still controversial.

Occurrence of Congenital Heart Disease among Children with Down syndrome: What is the Influence of Maternal Age?

Abstract Background: The occurrence of Down syndrome is strongly dependent on maternal age and incidence varies at various maternal ages. This incidence may differ from one country to another according to the social and environmental factors predominant in such countries. The study aims to document the prevalence of congenital heart defects in patients with Down syndrome, identify the association between maternal age and occurrence of congenital heart disease among these subjects Methods: The study was prospective, cross-sectional and consecutive, involving subjects from two centers which were; a tertiary hospital, a private hospital which is a major cardiology center. Children with clinical features of Down syndrome had transthoracic echocardiography done by a cardiologist. Results: A total of 195 patients with Down syndrome were studied ages between1day to 12years. The mean age + SD were 241.03 + 529.71days and male to female ratio of 1.04:1. The mother’s age range was from 19 to 44years with a mean age + SD of 32.36 + 5.43 years. Up to 16.9% had structurally normal heart. The most common heart defect was atrioventricular septal defect 24.1%. There was no significant association between maternal age and occurrence of congenital heart defects in the subjects. Conclusion: The incidence of congenital heart disease is high among subjects with Down syndrome. Atrioventricular defects were the commonest cardiac defect among the subjects. The incidence of congenital heart defect in the subjects was decreasing from maternal age 36 years and above. Routine cardiac evaluation including echocardiography is recommended for all patients with Down syndrome.

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India.

BACKGROUND:Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not.OBJECTIVE:We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism.RESULTS:The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864).CONCLUSION:Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.

Betaine–homocysteine methyltransferase 742G&gt;A polymorphism and risk of down syndrome offspring in a Brazilian population

Down syndrome (DS) is the most common form of mental retardation of genetic etiology. Several polymorphisms in genes involved with the folic acid cycle have been associated to the risk of bearing a DS child; however, the results are controversial. Betaine-homocysteine methyltransferase (BHMT) is a key enzyme of folate pathway, and catalyzes the remethylation of homocysteine into methionine. Recent studies suggest that the polymorphism BHMT 742G>A may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 94 mothers of DS infants (DSM) and 134 control mothers (CM) for this polymorphism through PCR-RFLP, and found significant differences for both BHMT 742G>A genotype (P=0.04) and allele (P=0.03) frequencies between DSM and CM. The observed genotypic frequencies were GG=0.45; GA=0.45 and AA=0.10 in CM, and GG=0.54; GA=0.38 and AA=0.02 in DSM. Allelic frequencies were G=0.68 and A=0.32 in CM and G=0.78 and A=0.22 in DSM. The presence of the mutant BHMT 742 A allele decreases 40% the risk of bearing a DS child (OR=0.61; 95% CI: 0.40-0.93; P=0.03), and the risk is diminished up to >80% in association with the homozygous genotype (OR=0.17; 95% CI: 0.04-0.80; P=0.01). Our results indicate that women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Impact of parental ages and other characteristics at childbearing on congenital anomalies

BACKGROUND While it is widely known that maternal age at childbearing plays a role in the occurrence of Down syndrome, less is known about the effects of maternal age on other major congenital anomalies. Information on the possible effects of other maternal characteristics and of the age of the father is even scarcer. OBJECTIVE We present new results on the associations between parental ages and other maternal characteristics on the one hand, and congenital anomalies on the other, using linked data from three Czech registries on mothers, newborns, and malformations, for the period 2000-2007. METHODS As the variables are in a categorical format, binary logistic regression is used in order to investigate the relationship between the presence/absence of a congenital anomaly for each of the 11 types of anomalies considered, and for the set of predictors. RESULTS This research confirms that the age of the mother has an impact on the incidence of Down syndrome and other chromosomal anomalies. Paternal age is not associated with chromosomal anomalies, and, in this Czech population, has a rather slight effect on some of the congenital anomalies examined. Another finding of the present study is that various other maternal characteristics may affect the incidence of congenital malformations. CONCLUSIONS Based on a large dataset, this study concludes that the ages of both parents can be associated with congenital anomalies of the child, and that maternal characteristics other than age have also to be considered. COMMENTS Risk factors can be tentatively proposed if they are based on a plausible and suitably tested explanatory mechanism. Unfortunately, in the majority of individual cases of congenital anomaly, the cause of the condition is unknown, and is suspected to result from an interaction of multiple environmental and genetic factors. © 2013 Jitka Rychtařikova et al.

Risk assessment for Down syndrome with genetic sonogram in women at risk

To evaluate the algorithms of risk assessment for Down syndrome (DS). Cohort study conducted in women at risk undergoing midtrimester genetic sonogram. Univariate and logistic regression analysis were used to relate findings to the occurrence of DS. The resulting model was validated in an independent population of patients. In a multivariable model adjusted for gestational age and maternal age, nuchal fold thickness (NFT) >or= 5 mm (OR = 4.6, 95% CI 0.9-23.9), presence of renal pelvic dilation (OR = 18.0, 95% CI 2.9-110.5), absent mid-phalanx of the 5th finger (OR = 29.9, 95% CI 6.1-145.8), presence of noncardiac malformations (OR = 20.1, 95% CI 2.6-154.7) or isolated heart defects (OR = 60.2, 95% CI 9.5-382.8), the interactions of gestational age with NFT >or= 5 mm (P = 0.04) and malformations with heart defects (P = 0.03) were significantly associated with DS. Utilizing this model and a risk cutoff point of 1/270, the sensitivity was 83.3% (5/6) with a false positive rate (FPR) of 28.5% (159/558). Genetic sonogram has adequate accuracy to be incorporated into management algorithms for risk assessment of DS in women at risk.

Quantification of Proteolytically Active Pregnancy-Associated Plasma Protein-A with an Assay Based on Quenched Fluorescence

Maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A, pappalysin-1, EC 3.4.24.79) are used to predict the occurrence of Down syndrome. In pregnancy, PAPP-A primarily circulates as a covalent 2:2 complex with the proform of eosinophil major basic protein (proMBP), which inhibits the proteolytic activity of PAPP-A. At term, however, approximately 1% of PAPP-A exists as an active, uncomplexed dimer with proteolytic activity directed specifically toward insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5. No assays have been developed that allow quantification of PAPP-A proteolytic activity. We developed a sensitive and specific immunocapture assay for PAPP-A activity based on intramolecular quenched fluorescence. We used a 26-residue synthetic peptide derived from IGFBP-4 in which specific positions on each side of the PAPP-A cleavage site were substituted with 3-nitrotyrosine and o-aminobenzoic acid. The assay detected the activity of recombinant PAPP-A as well as PAPP-A in serum samples from pregnant women. The limit of detection (mean signal of blank plus 3 SD) of the active PAPP-A subunit was 13 pmol/L, and the intra- and interassay CVs were <10% and <15%, respectively. Interestingly, the fraction of active PAPP-A decreased gradually from week 7 to week 19 of pregnancy. This method allows the measurement of PAPP-A enzymatic activity and because of its specificity it is relevant to the study of the biological function of PAPP-A. The method may also be useful in the diagnosis of pregnancy disorders.

Influence of advanced age of maternal grandmothers on Down syndrome.

BackgroundDown syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%), mosaic trisomy 21 (2–4%) and translocation (3–4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction.MethodsWe investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression.ResultsOut of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%.ConclusionBesides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.

Chromosomal Abnormalities among Offspring of Childhood-Cancer Survivors in Denmark: A Population-Based Study

Ionizing radiation and many cancer drugs have the potential to produce germ-cell mutations that might lead to genetic disease in the next generation. In a population-based study, we identified, from records in the Danish Cancer Registry, 4,676 children treated for cancer. Their 6,441 siblings provided a comparison cohort. The results of a search of the Central Population Register identified 2,630 live-born offspring of the survivors and 5,504 live-born offspring of their siblings. The occurrence of abnormal karyotypes diagnosed in these offspring and also in any pregnancies terminated following prenatal diagnosis of a chromosome abnormality was determined from the Danish Cytogenetic Registry. After exclusion of hereditary cases and inclusion of the prenatal cases, after correction for expected viability, the adjusted proportion of live-born children in survivor families with abnormal karyotypes (5.5/2,631.5 [0.21%]) was the same as that among the comparison sibling families (11.8/5,505.8 [0.21%]). There were no significant differences in the occurrence of Down syndrome (relative risk [RR]=1.07; 95% CI 0.16-5.47) or Turner syndrome (RR=1.32; 95% CI 0.17-7.96) among the children of cancer survivors, compared with the children of their siblings. These reassuring results are of importance to the survivors, to their families, and to genetic counselors.