Down Syndrome Pregnancies Research Articles

Retracted: Study on the Effect of B‐Ultrasound NT Scan in Early Pregnancy Combined with Serum Screening in Early and Middle Pregnancy for Down Syndrome

Retracted: Study on the Effect of B‐Ultrasound NT Scan in Early Pregnancy Combined with Serum Screening in Early and Middle Pregnancy for Down Syndrome

Study on the Effect of B-Ultrasound NT Scan in Early Pregnancy Combined with Serum Screening in Early and Middle Pregnancy for Down Syndrome.

Objective Down syndrome (DS), also known as trisomy 21 syndrome, is a common and most harmful congenital chromosomal genetic disease. This study is aimed at exploring the effect of B-ultrasound NT scan in early pregnancy combined with serum screening in early and middle pregnancy for Down syndrome. Methods A total of 168 pregnant women who were diagnosed and treated in the obstetric clinic of our hospital from January 2019 to December 2021 were selected as the research objects. B-ultrasound NT scanning and serum detection in the early and middle trimester of pregnancy were performed, respectively. The accuracy of single detection and combined detection was analyzed and compared with the results of amniotic fluid cell chromosome examination as the gold standard. Results There were 4 cases of DS and 165 cases of non-DS. The serum PAPP-A, AFP, and UE levels in DS group were lower than those in non-DS group. β-HCG level and NT value were higher than those in non-DS group (all p < 0.05). Among 168 pregnant women, 5 cases were diagnosed as abnormal by ultrasonography, and 1 case was diagnosed as normal. By serological test, 20 cases with high risk of DS were diagnosed in 4 cases, and 148 cases with low risk of DS were diagnosed in 2 cases. Among 168 cases examined by serology combined with ultrasound, 10 cases with high risk of DS were found, and 4 cases were diagnosed; 158 cases had low risk of DS, and 0 cases were diagnosed. The negative predictive value, specificity, and coincidence rate of DS screening by the three methods were higher, and the positive predictive value and coincidence rate of combined screening were the highest (p < 0.05). The screening risk of Down syndrome was correlated with pregnancy outcome. The abnormal pregnancy rate in high-risk group was significantly higher than that in low-risk group, and the difference was statistically significant (p < 0.05). ROC curve showed that the sensitivity, specificity, and AUC of the combined detection were greater than those of serology and NT. Conclusion The application of B-ultrasound NT scan in early pregnancy combined with early and mid-term serum comprehensive screening in the screening of Down's infants is helpful to improve the diagnostic coincidence rate and reduce the occurrence of misdiagnosis.

Down syndrome among primiparae at older maternal age: A test of the relaxed filter hypothesis.

Down syndrome (DS) ranks as one of the most common birth defects in the United States. The relaxed filter hypothesis (RFH) asserts that mothers with no previous children but nearing reproductive senescence reduce fetal selectivity against DS pregnancies in the first trimester given the high probability of having no offspring at all if the DS pregnancy is not carried to term. We test the parity prediction of RFH-specifically, that pregnancies to older mothers with no previous live births show an elevated prevalence of DS above values expected from the separate contributions of older maternal age and primiparity. We retrieved maternal age and parity information on 2,748 DS cases (live, stillborn, or terminated due to anomaly) from the Paris Birth Defects Registry, 1983-2015. We used two waves of the Enquête Fertility Survey (n = 5,460) and counts of stillbirths to calculate total prevalence of DS by maternal age and parity. Primiparous mothers 35+ years show the greatest prevalence of any parity group (9.78 cases per 1,000 deliveries). Tests for additive interaction of primiparity and older maternal age reject the null (relative excess risk due to interaction = 1.01; 95% confidence interval: 0.33, 1.69; null value on additive scale is 0). Relaxed selection may account for 10% of the increase in the prevalence, among older primiparous mothers, of DS detected during or after the 11th week. Future work may hold implications for understanding, among older mothers, the strength of this maternal screen against other defects.

The role of fetal growth restriction in the association between Down syndrome and perinatal mortality

Objective: Down syndrome (DS) is associated with significant risk of perinatal mortality. We hypothesize that this association is primarily mediated through the effects of fetal growth restriction (FGR).Methods: This was a retrospective cohort analysis using the US Natality Database from 2011 to 2013. Analysis was limited to singleton nonanomalous pregnancies or confirmed DS pregnancies without severe structural anomalies between 24 and 42 w in gestation. The risk of stillbirth (SB) associated with DS was estimated using both Cox proportional Hazard (HR) regression and accelerated failure time (AFT) methods. The risk of neonatal mortality was estimated using logistic regression analyses. Mediation analysis was then performed to estimate the effect of small for gestational age (SGA), defined as birthweight ≤10th percentile for gestational age, on perinatal mortality associated with DS. All regression models were selected using backward stepwise elimination method. The final regression models included adjustment for maternal age, hypertension, and diabetes.Results: The final cohort included 2446 DS cases among 9,804,718 births. The overall SB rate was 223.6/1000 births in DS group and 4.7/1000 births without DS (p < .001, adjusted hazard ratio (aHR): 58.25; 95% CI [53.44,63.49]). Based on the AFT model, DS survival-to-delivery rate is 4.3 times lower (TR: 0.23; 95% CI [0.22,0.24]). Thirty-five percentage of the effect of DS on stillbirth was mediated through SGA (% mediation:35.1%; 95% CI [33.7,36.4]). The rate of neonatal mortality among DS was 69.0/1000 births compared with 2.8/1000 births without DS (p < .001, adjusted odds ratio (aOR): 27.16; 95% CI: [22.63,32.60]). Only 11.6% of the effect of DS on neonatal deaths was mediated through SGA (%mediation:11.6%; 95% CI [8.4,10.6]).Conclusion: Over one-third of overall stillbirths were mediated through SGA. Routine surveillance of fetal growth and standard SGA surveillance protocols may reduce the risk of perinatal mortality in DS pregnancies. Conversely, it is important to point out that these surveillance strategies may not be effective two-third of the cases not affected by growth restriction.

Maternal plasma metabolic fingerprint indicative for fetal Down syndrome

The objective of the study was to perform maternal plasma metabolic fingerprinting to evaluate differences in plasma metabolites between healthy and Down syndrome (DS) pregnancies and to indicate novel non-invasive markers for DS prenatal diagnostics. This was a case-control study of pregnancies between 15th and 18th gestational week. LC-MS-based metabolic fingerprinting of plasma samples was performed. Levels of five metabolites were significantly lower in the plasma of DS pregnancies. The majority of the statistically significant metabolites may be connected with fetal brain and central nervous system development (eg, fatty acid amides). According to the receiver operating characteristic (ROC), the combination of linoleamide and piperine has the highest diagnostic potential: area under the curve (AUC)=0.878, sensitivity of 100%, and specificity of 73.3%. The study indicates disturbances in maternal metabolic pathways evoked by fetal DS. Novel potential maternal plasma metabolomic markers for non-invasive prenatal diagnostics of fetal DS are proposed.

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.

Who is and isn't having babies with Down syndrome in western Sydney: a ten year hospital cohort study

Screening for Down syndrome (DS) is a key component of antenatal care, recommended to be universally offered to women irrespective of age or background. Despite this, the diagnosis of DS is often not made until the neonatal period. To retrospectively describe and compare the differences in populations with an antenatal diagnosis (AD) and neonatal diagnosis (ND) of DS and to explore why an antenatal diagnosis was not made. The cohorts were women cared for at Westmead Hospital whose pregnancy received a diagnosis of DS between 2006 and 2015. The demographic variables of the AD and ND cohorts were examined and reasons why an antenatal diagnosis was not made in the ND cohort were analysed. There were 127 diagnoses of DS in the 10-year period, of which 41% were in the ND cohort (n=52) and 59% in the AD (n=75). Declaring a religious affiliation rather than Nil Religion was significantly more common in the ND cohort (88.5%) and especially the ND sub-cohort who declined DS screening/testing (95.8%) than the AD cohort (72%, P<0.05). Women who were not offered screening were significantly younger (P<0.001) than those who were, with 69% and 20% being ≤30years, respectively. The proportion of DS pregnancies diagnosed in the antenatal period in western Sydney could be increased by ensuring younger women are not falsely reassured that DS screening is unnecessary for them. While religious affiliation may be a factor when women decline screening, ensuring appropriate counselling remains important.

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part II-women's perspectives.

ObjectiveTo evaluate preferences and decision‐making among high‐risk pregnant women offered a choice between Non‐Invasive Prenatal Testing (NIPT), invasive testing or no further testing.MethodsNationwide implementation study (TRIDENT) offering NIPT as contingent screening test for women at increased risk for fetal aneuploidy based on first‐trimester combined testing (>1:200) or medical history. A questionnaire was completed after counseling assessing knowledge, attitudes and participation following the Multidimensional Measure of Informed Choice.ResultsA total of 1091/1253 (87%) women completed the questionnaire. Of these, 1053 (96.5%) underwent NIPT, 37 (3.4%) invasive testing and 1 (0.1%) declined testing. 91.7% preferred NIPT because of test safety. Overall, 77.9% made an informed choice, 89.8% had sufficient knowledge and 90.5% had positive attitudes towards NIPT. Women with intermediate (odds ratio (OR) = 3.51[1.70–7.22], p < 0.001) or high educational level (OR = 4.36[2.22–8.54], p < 0.001) and women with adequate health literacy (OR = 2.60[1.36–4.95], p = 0.004) were more likely to make an informed choice. Informed choice was associated with less decisional conflict and less anxiety (p < 0.001). Intention to terminate the pregnancy for Down syndrome was higher among women undergoing invasive testing (86.5%) compared to those undergoing NIPT (58.4%) (p < 0.001).ConclusionsThe majority of women had sufficient knowledge and made an informed choice. Continuous attention for counseling is required, especially for low‐educated and less health‐literate women. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Down Syndrome Screening: Evidence that Test Results Differ According to Phenotype

AbstractThe purpose of the present study was to examine screening marker levels in Down syndrome (DS) pregnancies with and without cardiac defects and in euploid pregnancies. Retrospective series in two centers with one or more markers—ultrasound nuchal translucency (NT), first trimester maternal serum pregnancy associated plasma protein (PAPP-A), free-β human chorionic gonadotrophin (free β-hCG), and second trimester serum α-fetoprotein (AFP), unconjugated estriol (uE3), hCG, and free-β hCG. Levels were expressed as multiples of the gestation-specific median (MoM). Differences were assessed by the Wilcoxon rank sum test and 95 % confidence intervals. There were 318 DS pregnancies including 53 (17 %) with cardiac defects. Median NT was higher in cardiac defects (1.82 compared with 1.62 MoM), but not statistically significant (P = 0.17). Median free β-hCG was significantly highly reduced in the first trimester (1.14 and 2.17 MoM; P &lt; 0.005) and similarly but nonsignificantly in the second trimester (1.59 and 2.32 MoM; P = 0.14). PAPP-A was reduced and AFP increased nonsignificantly with no material differences for uE3 and hCG. The results on NT and free β-hCG were consistent with a series of 62 euploid pregnancies with cardiac defects screened in one of the centers. The distribution of some markers differs in DS pregnancies with cardiac defects. Depending on the screening protocol, this may affect the phenotype of DS births.

Impact of prenatal screening and diagnostic testing on trends in Down syndrome births and terminations in Western Australia 1980 to 2013.

To assess how prenatal screening and diagnostic testing have impacted the diagnosis, termination and birth prevalence of Down syndrome in Western Australia (1980-2013). We analysed trends in termination rates and birth prevalence of Down syndrome using aggregated data (1980-2013). We modelled the expected live-birth rate and prevalence of Down syndrome and compared different eras of screening and diagnosis with respect to the impact on live-birth rate and prevalence of Down syndrome. Between 1980 and 2013, the rate of Down syndrome pregnancies increased, corresponding to a greater proportion of babies born to older women. Following the introduction of screening in 1994, the rate of live-born infants with Down syndrome reduced significantly (p = 0.001). The rate of terminations of pregnancy for Down syndrome remained stable over this period. In the absence of termination, the Down syndrome live-birth rate would have risen from 1.1 per 1000 to 2.17 per 1000 between 1980 and 2013. Prenatal testing in Western Australia has reduced the birth prevalence of Down syndrome despite an increased rate of Down syndrome pregnancies. Most women for whom a prenatal diagnosis of fetal Down syndrome is made, chose to terminate the pregnancy (93%), and this proportion has not changed over the study period.

Oral Abstracts of the ISPD 19th International Conference on Prenatal Diagnosis and Therapy, Washington, DC, USA, 12-15 July 2015.

OBJECTIVES: The TRIDENT study (Trial by Dutch laboratories for Evaluation of Non-Invasive Prenatal Testing) evaluates the implementation of non-invasive prenatal testing (NIPT) in the Dutch healthcare system. Here we report on the preferences and experiences of pregnant women at high risk for fetal aneuploidy who were offered a choice between NIPT, invasive testing or no follow-up test. METHODS: A nationwide prospective cohort study among pregnant women at high risk for fetal aneuploidy because of first trimester screening results (risk ≥1:200) or medical history. Questionnaires were administered to the women, to be completed after counselling and after receiving the test-results, at seven (of the eight) prenatal diagnostic centers in the Netherlands. The questionnaires addressed: women's preference for follow-up testing, intention to terminate the pregnancy, attitudes, knowledge, decisional conflict, anxiety and satisfaction. RESULTS: Pre- and post-test questionnaires were completed by n = 1,106 (86% response) and n = 686 (67% response) women, respectively. Preliminary analyses show that the majority of respondents (92%) preferred NIPT, 5% invasive testing, 2% were unsure, and 1% declined testing. The main reason to prefer NIPT was safety for the child (92%). Of the 60 women preferring invasive testing, 52% did so because of test-accuracy, 25% desired more rapid test-results, 5% because it provides more information, and 18% reported other reasons. Most women (92%) felt that they made a well-informed decision, and 75% reported that this decision was easy to make. Intention to terminate the pregnancy for Down syndrome was lower among women preferring NIPT (58%) compared to women preferring invasive testing (87%). Women were highly satisfied with NIPT. However, 64% perceived the waiting time for NIPT results (mean: 11 days (range 5-32)) as too long, while 3% in retrospect would have preferred a different follow-up test, mostly to avoid the long waiting time. CONCLUSIONS: Most pregnant women in our study felt they could make an informed decision. The majority of women prefer NIPT, mainly because it has no miscarriage risk. Reducing turnaround time for test-results is our next challenge in meeting women's needs.

Genomic Testing and Genomic Care: Are They Talking to Each Other?

The principle of basing medical decisions on the concept of risk is not new. Table 1 shows comparative information on medical management guidance in a number of relatively common scenarios such as the use of statins in hypercholesterolaemia, treatment of hypertension, prevention of sudden death in hypertrophic cardiomyopathy, prevention of berry aneurysm rupture in autosomal dominant polycystic kidney disease, screening for Down Syndrome in pregnancy and the management of familial breast cancer susceptibility (Table 1).

Shotgun metabolomic profiles in maternal urine identify potential mass spectral markers of abnormal fetal biochemistry - dihydrouracil and progesterone in the metabolism of Down syndrome.

In Down syndrome (DS) in particular, the precise cellular mechanisms linking genotype to phenotype is not straightforward despite a clear mapping of the genetic cause. Metabolomic profiling might be more revealing in understanding molecular-cellular mechanisms of inborn errors of metabolism/syndromes than genomics alone and also result in new prenatal screening approaches. The urinary metabolome of 122 maternal urine from women with and without an aneuploid pregnancy (predominantly Down syndrome) were compared by both zwitterionic hydrophilic interaction chromatography (ZIC-HILIC) and reversed-phase liquid chromatography (RPLC) coupled to hybrid ion trap time of flight mass spectral analysis. ZIC-HILIC mass spectrometry resolved 10-fold more unique molecular ions than RPLC mass spectrometry, of which molecules corresponding to ions of m/z 114.07 and m/z 314.20 showed maternal urinary level changes that significantly coincided with the presence of a DS fetus. The ion of m/z 314.20 was identified as progesterone and m/z 114.07 as dihydrouracil. A metabolomics profiling-based maternal urinary screening test modelled from this separation data would detect approximately 87 and 60.87% (using HILIC-MS and RPLC-MS, respectively) of all DS pregnancies between 9 and 23 weeks of gestation with no false positives.

Knowledge of Down’s syndrome Screening amongst Patients and Health Care Professionals in Sri Lanka

Aim: Different screening strategies have been proposed to detect high risk women during pregnancy for Down syndrome. In order to achieve effective screening, the patient making the choice and the staff offering the test must have a reasonable understanding of all facts relevant to the test. The aim of this study was to assess the existing knowledge and awareness of antenatal Down syndrome screening in patients and obstetric stakeholders across eight major obstetric centres in Sri Lanka. Methods: This was a prospective study carried out between January and June 2013 in eight tertiary care settings in 7 districts representing Northern, Western, Eastern, Southern and central provinces in Sri Lanka. A validated questionnaire was translated from English into Singhalese and Tamil and independently translated back to English and piloted to confirm the accuracy of the translation. This translated questionnaire was distributed among antenatal patients and obstetric unit staff members. Results: A total of 1116 patients and 535 staff members were recruited. Present overall knowledge of Down syndrome among antenatal patients was poor in all 7 districts. Majority of patients were not aware that available options of screening for Down syndrome (Awareness about nuchal translucency-21.6% (95% CI 14.7-30.6%), biochemical screening-26.3% (95% CI 18.7-35.7%) invasive procedures-23.3 (95% CI, 16.1-32.5%). Majority of staff members were also not aware about available screening strategies (Awareness about nuchal translucency-29.3% (95% CI 21.3- 38.9%), biochemical screening-26.9% (95% CI 19.2-36.3%) but their knowledge of diagnostic tests were high (invasive procedures- 59.4% (49.6-68.5%). Moreover, there is no difference in knowledge in different part of the island. Conclusions: Adequate education on available screening methods of Down syndrome for the staff is a timely need so that the means would be available to disseminate knowledge to the wider patient and public populations.

Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21).

Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. Conclusions. miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of 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.

Metabolomic analysis for first-trimester Down syndrome prediction

The objective of the study was to perform first-trimester maternal serum metabolomic analysis and compare the results in aneuploid vs Down syndrome (DS) pregnancies. This was a case-control study of pregnancies between 11+0 and 13+6 weeks. There were 30 DS cases and 60 controls in which first-trimester maternal serum was analyzed. Nuclear magnetic resonance-based metabolomic analysis was performed for DS prediction. Concentrations of 11 metabolites were significantly different in the serum of DS pregnancies. The combination of 3-hydroxyisovalerate, 3-hydroxybuterate, and maternal age had a 51.9% sensitivity at 1.9% false-positive rate for DS detection. One multimarker algorithm had 70% sensitivity at 1.7% false-positive rate. Novel markers such as 3-hydroxybutyrate, involved in brain growth and myelination, and 2-hydroxybutyrate, involved in the defense against oxidative stress, were found to be abnormal. The study reports novel metabolomic markers for the first-trimester prediction of fetal DS. Metabolomics provided insights into the cellular dysfunction in DS.

Micronucleated lymphocytes in parents of Down syndrome children

Down syndrome (DS) is the most common disease due to an autosomal aneuploidy in live born children and also the major known genetic cause of mental retardation. The risk of a DS pregnancy increases substantially with increasing maternal age. However, several women aged less than 35 years at conception have a child with DS. The micronucleus (MN) assay can identify chromosome breakage or chromosome malsegregation and is an ideal biomarker to investigate genomic instability. The aim of the present study was to determine the frequency of peripheral lymphocytes with MN in the parents of DS individuals. The subjects were 17 couples, 1 father and 9 mothers, and 24 couples who had at least one healthy child formed the control group. For each individual we evaluated the frequency of binucleated micronucleated lymphocytes (BNMN%) as number of binucleated lymphocytes containing one or more MN per 1000 binucleated cells. The mean age of DS parents and controls was 32.6 and 29.8 years, respectively. The frequency of MN in DS parents was significantly higher compared to controls. The higher frequency of MN in DS parents suggests a higher predisposition of DS parents to aneuploidy events in this sample.

Prenatal screening for Down syndrome in pregnancies at risk for α‐thalassemia

Prenatal screening for Down syndrome in pregnancies at risk for α‐thalassemia

Sonographic thymic measurements in Down syndrome fetuses

Children with Down syndrome (DS) can have hypoplastic thymuses with an impaired capacity to liberate newly generated T cells. We sought to determine if the size of the thymus in DS fetuses is different from control fetuses. We performed comprehensive prenatal sonographic evaluation that included measurements of the thymus in 874 control fetuses and in 12 DS fetuses. We used graphic comparisons between thymic measurements obtained from the two groups of fetuses and a nested case-control validation study in which DS fetuses were matched for gestational age with control fetuses using a 2-to-1 ratio to make group comparisons. The plot analysis showed that more than two-thirds of DS fetuses had sonographic signs of thymic hypoplasia. The nested case-control study confirmed that the thymus of DS fetuses was statistically smaller than the thymus of control fetuses [DS transverse diameter 12.3 mm, interquartile range (IQR) 6.2 vs. control 18.1 mm, IQR 4.4; p < 0.001 and, DS perimeter 30.9 mm, IQR 20.1 vs. control 48.6 mm, IQR 20.4; p < 0.01]. Our findings suggest that the majority of DS fetuses have smaller thymuses than control. Prenatal measurements of the thymus may be clinically useful in the management of DS pregnancies.