Aneuploidy In Twin Pregnancies Research Articles

Cell-free DNA screening in twin pregnancies.

Cell-free DNA (cfDNA) screening for fetal aneuploidies is clinically available and exhibits better performance than conventional serum screening tests. However, data on the clinical performance of cfDNA screening in twin pregnancies are limited. In this review, we summarized the clinical performance and evaluated the feasibility of cfDNA screening in twin pregnancies based on recent studies and recommendations. The performance of cfDNA screening for trisomy 21 in twin pregnancies is similar to that in singleton pregnancies. Specifically, cfDNA screening has a higher detection rate and lower false-positive rate compared with conventional serum screening. Consequently, recent international guidelines from several academic communities have recommended that cfDNA screening for aneuploidy in twin pregnancies could be considered. Moreover, twin pregnancies can present with specific conditions, such as different zygosities and vanishing twins; therefore, individualized counseling and management are required. Further clinical studies with more twin pregnancies are required for a more accurate analysis.

Clinical application of non-invasive prenatal testing for twin pregnancies

To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies. A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated. Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction (P < 0.05). It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

Prevalence of common aneuploidy in twin pregnancies

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

1057: Noninvasive prenatal screening for fetal aneuploidy in twin pregnancies: A clinical laboratory experience

1057: Noninvasive prenatal screening for fetal aneuploidy in twin pregnancies: A clinical laboratory experience

Cell-free DNA fetal fraction in twin gestations in single-nucleotide polymorphism-based noninvasive prenatal screening.

ObjectivesThe performance of noninvasive prenatal screening (NIPS) for fetal aneuploidy in twin pregnancies is dependent on the amount of placentally derived cell‐free DNA, the “fetal fraction (FF),” present in maternal plasma. We report FF values in monozygotic (MZ) and dizygotic (DZ) pregnancies.MethodsWe reviewed FF in pregnancies at 10 to 20 completed weeks gestational age based on single‐nucleotide polymorphism (SNP)‐based NIPS where zygosity was routinely established in twin pregnancies. The cohort included 121 446 (96.3%) singleton, 1454 (1.2%) MZ, and 3161 (2.5%) DZ pregnancies. For DZ twins, individual FFs were measured.ResultsCombined FF for DZ and MZ fetuses were 35% and 26% greater than singletons, respectively. The individual FF contributions from each fetus in DZ twins were, on average, 32% less than singletons. FF in DZ twin pairs were moderately correlated (Pearson correlation coefficient.66). When a threshold of 2.8% FF was applied to define uninterpretable results, 1.7% (2102/121 446) of singletons, 0.8% (11/1454) of MZ pairs, and 5.6% (178/3161) of DZ pairs were uninterpretable.ConclusionFor optimal aneuploidy NIPS in twin pregnancies, zygosity should be established and in DZ twins FF for both fetuses should be determined to identify those cases where results can be reliably interpreted.

Non-invasive prenatal screening for fetal aneuploidy in twin pregnancies by cell-free DNA analysis

Objective: To evaluate the efficacy of Cell-free DNA (cfDNA) based non-invasive prenatal testing (NIPS) in detecting fetal chromosomal aneuploidies among twin pregnancies. Materials and Methods:&nbsp;A cohort of 384 women with twin pregnancies were recruited for chromosomal aneuploidies testing through NIPS. cfDNA was extracted from maternal blood serum and sequenced by massively parallel sequencing (MPS). Result: Two cases of trisomy 21 (T21), one case of trisomy 13 (T13), and two cases of sex chromosomal aneuploidies (SCA) in twin pregnancies were correctly identified through MPS and confirmed their discordant fetal karyotypes (one normal and the other trisomy) by karyotyping; 378 twin pregnancies cases with negative NIPS results were confirmed through postnatal phone follow-up. NIPS detection rate and positive predictive value for T21, T13, and SCA were 100%, respectively, in twin pregnancies; sensitivity and specificity towards T21 and T13 in twin pregnancies were both 100%. Conclusion: cfDNA based NIPS for fetal chromosomal aneuploidy have shown a satisfactory clinical performance in twin pregnancies.

Attitudes Toward and Uptake of Prenatal Genetic Screening and Testing in Twin Pregnancies

The rate of twinning is rising and since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. This study aimed to explore the attitudes toward and uptake of current prenatal genetic screening and diagnostic testing options for fetal aneuploidy in twin pregnancies. Women being seen for genetic counseling with twin gestations were recruited for participation in a descriptive study with questionnaire (n = 42) and semi-structured phone interview (n = 15). Women were significantly more in favor of screening than diagnostic testing (p = 0.049). Sixty-nine (n = 25) percent elected screening, while one participant had a diagnostic procedure. Women were interested in screening for preparation or reassurance despite having concerns about accuracy and uncertainty. Most women (86%) felt they would make the same decision in a singleton pregnancy. Despite this, 48% cited twin pregnancy as influential to some degree. Information learned from providers, past experiences, and family and friends were also cited as influencing and anchoring factors, suggesting that tailoring prenatal genetic counseling sessions for twins might parallel that of singletons. No significant differences between natural and assisted conception patients were found. Although it did not alter patient decisions, genetic counseling was used as a platform to raise concerns and gather information.

No. 262-Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies.

To provide a Canadian consensus document with recommendations on prenatal screening for and diagnosis of fetal aneuploidy (e.g., Down syndrome and trisomy 18) in twin pregnancies. The process of prenatal screening and diagnosis in twin pregnancies is complex. This document reviews the options available to pregnant women and the challenges specific to screening and diagnosis in a twin pregnancy. Clinicians will be better informed about the accuracy of different screening options in twin pregnancies and about techniques of invasive prenatal diagnosis in twins. PubMed and Cochrane Database were searched for relevant English and French language articles published between 1985 and 2010, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis, twin gestation). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table1). There is a need for specific guidelines for prenatal screening and diagnosis in twins. These guidelines should assist health care providers in the approach to this aspect of prenatal care of women with twin pregnancies. RECOMMENDATIONS.

Performance of non-invasive prenatal screening for fetal aneuploidy in twin pregnancies: a meta-analysis.

The objectives of this study were to review the published studies of non-invasive prenatal screening (NIPS) in twin pregnancies and to evaluate the performance for screening fetal trisomies 21, 18, and 13 in twin pregnancies. Ten eligible studies were included in this meta-analysis. Data analysis, heterogeneity exploring, meta-regression, and subgroup analysis were all conducted with Meta-DiSc 1.4. Quality assessments were carried out with the Quality Assessment Tool for Diagnostic Accuracy Studies. Non-invasive prenatal screening for trisomy 21 screening in twin pregnancies showed a pooled sensitivity of 0.99 (95% CI, 0.92-1.00), a specificity of 1.00 (95% CI, 0.99-1.00), a positive likelihood ratio (LR) of 116.46 (95% CI, 53.84-251.92), a negative LR of 0.11 (95% CI, 0.06-0.22), and a diagnostic odds ratio of 1297.73 (95% CI, 438.06-3844.42). But the difference of detection rates between monozygotic and dichorionic twin pregnancies was uncertain for only a very small number of monochorionic twins available. For trisomy 18 screening, the pooled sensitivity, specificity, positive LR, negative LR, and diagnostic odds ratio were 0.85 (95% CI, 0.55-0.98), 1.00 (95% CI, 0.99-1.00), 86.11 (95% CI, 32.45-228.47), 0.25 (95% CI, 0.11-0.56), and 333.90 (95% CI, 35.15-3171.78), respectively. For trisomy 13 screening, three cases in three studies were all detected accurately. The meta-analysis results from 10 eligible studies demonstrated that NIPS has both high sensitivity and specificity for trisomy 21 screening in twin pregnancies. The results for trisomy 18 screening are less satisfactory than those for trisomy 21. The performance for trisomy 13 screening could not be determined as only three cases were identified. © 2017 John Wiley & Sons, Ltd.

Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies

ObjectiveTo provide a Canadian consensus document with recommendations on prenatal screening for and diagnosis of fetal aneuploidy (e.g., Down syndrome and trisomy 18) in twin pregnancies. OptionsThe process of prenatal screening and diagnosis in twin pregnancies is complex. This document reviews the options available to pregnant women and the challenges specific to screening and diagnosis in a twin pregnancy OutcomesClinicians will be better informed about the accuracy of different screening options in twin pregnancies and about techniques of invasive prenatal diagnosis in twins. EvidencePubMed and Cochrane Database were searched for relevant English and French language articles published between 1985 and 2010, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis, twin gestation). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline. ValuesThe quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Benefits, harms, and costsThere is a need for specific guidelines for prenatal screening and diagnosis in twins These guidelines should assist health care providers in the approach to this aspect of prenatal care of women with twin pregnancies. Summary StatementsFetal nuchal translucency combined with maternal age is an acceptable first trimester screening test for aneuploidies in twin pregnancies. (II-2)First trimester serum screening combined with nuchal translucency may be considered in twin pregnancies It provides some improvement over the performance of screening by nuchal translucency and maternal age by decreasing the false-positive rate. (II-3)Integrated screening with nuchal translucency plus first and second trimester serum screening is an option in twin pregnancies. Further prospective studies are required in this area, since it has not been validated in prospective studies in twins (III)Non-directive counselling is essential when invasive testing is offered (III)When chorionic villus sampling is performed in non-monochorionic multiple pregnancies, a combination of transabdominal and transcervical approaches or a transabdominal only approach appears to provide the best results to minimize the likelihood of sampling errors. (II-2) RecommendationsAll pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies. In addition, they should be offered a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A)Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A)When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over. (II-2B)Chorionicity has a major impact on the prenatal screening process and should be determined by ultrasound in the first trimester of all twin pregnancies (II-2A)

Screening for trisomy 21 in twin pregnancies in the first trimester: an update of the impact of chorionicity on maternal serum markers

To examine the distribution of first-trimester biochemical markers of aneuploidy in twin pregnancies, and to assess whether there are differences in the distributions between monochorionic and dichorionic twins. Maternal serum-free beta-hCG and PAPP-A were measured between 11 + 0 and 13 + 6 weeks as part of a routine first-trimester screening program in conjunction with fetal nuchal translucency (NT) performed at two sites. Data from twin pregnancies were extracted from the fetal databases along with information on the chorionicty. The individual marker concentrations were expressed as weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM using data from singleton pregnancies as the reference. The overall medians were compared to those in singleton pregnancies and between monochorionic and dichorionic twins. Data was available from 1914 sets of twins. Of these, 1214 had information with respect to chorionicity, with 1024 being dichorionic and 190 being monochorionic. The overall median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM amongst twin pregnancies were 2.023 for free beta-hCG (sd log(10) MoM = 0.2611 and 2.121 for PAPP-A (sd log(10) MoM = 0.2255) -- both medians were significantly greater than the medians in singleton pregnancies (1.00 MoM). In the case of monochorionic and dichorionic twins the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected, free beta-hCG MoM's were not significantly different (1.983 v 2.041), however for PAPP-A the median weight corrected, ethnicity corrected, smoking corrected and IVF corrected MoM in monochorionic twins was significantly lower than in dichorionic twins (1.756 v 2.250) whilst the sd log(10) MoM's were not significantly different (0.2185 v 0.2167). Screening in twin pregnancies requires adjustment of the calculated MoM to account for the presence of two fetuses. In general, for free beta-hCG, this should be by dividing the observed corrected MoM by 2.023. For PAPP-A two different factors are required - 2.192 in dichorionic twins and 1.788 in monochorionic twins.

Screening for aneuploidy in twin pregnancies: maternal age- and race-specific risk assessment between 9-14 weeks.

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9-14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9-14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9-14 weeks is 1/285 for Whites and for African-Americans. This is equivalent to the risk for trisomy 21 (1/265) in a 35-year-old woman with a singleton at the same gestational age. The risks for trisomies 18 and 13 also follow similar trends. In counseling women with twin pregnancies at the time of first trimester nuchal translucency screening or chorionic villus sampling, it should be noted that the maternal age-related risk for aneuploidy for a 32-year-old is equivalent to that of a 35-year-old woman with a singleton gestation.

Screening for Aneuploidy in Twin Pregnancies: Maternal Age- and Race-specific Risk Assessment Between 9–14 Weeks

The aim of this study was to calculate the risk for aneuploidy in twin pregnancies between 9–14 weeks utilizing maternal age, race and dizygotic twinning rates. Using previously published risks for aneuploidy in singletons and twins at the time of amniocentesis and at term, we calculated new risk estimates for twins at 9–14 weeks gestation or at the time of chorionic villus sampling. Using these tables, the risk for trisomy 21 in at least one fetus of a twin gestation in a 32-year-old at 9–14 weeks is 1/285 for Whites and for African- Americans. This is equivalent to the risk for trisomy 21 (1/265) in a 35-year-old woman with a singleton at the same gestational age. The risks for trisomies 18 and 13 also follow similar trends. In counseling women with twin pregnancies at the time of first trimester nuchal translucency screening or chorionic villus sampling, it should be noted that the maternal age-related risk for aneuploidy for a 32-year-old is equivalent to that of a 35-year-old woman with a singleton gestation.