Noninvasive prenatal screening in twin pregnancies with cell-free DNA using the IONA test: a prospective multicenter study.

BACKGROUND: In singleton pregnancies, studies investigating cell-free DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies. OBJECTIVE: In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance. STUDY DESIGN: This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020. RESULTS: A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%-36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n=13; 95% confidence interval, 75-100), 0% for trisomy 18 (n=1; 95% confidence interval, 0-98), and 100% for trisomy 13 (n=1; 95% confidence interval, 3-100). The corresponding false-positive rates were 0% (95% confidence interval, 0-0.39), 0.10% (95% confidence interval, 0-0.58), and 0% (95% confidence interval, 0-0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n=74; 95% confidence interval, 90-99) and the false-positive rate was 0.09% (n=5598; 95% confidence interval, 0.03-0.19). The corresponding values for trisomy 18 were 82% (n=22; 95% confidence interval, 66-93) and 0.08% (n=4869; 95% confidence interval, 0.02-0.18), respectively. There were 5 cases of trisomy 13 and 3881 non-trisomy 13 pregnancies, resulting in a computed average detection rate of 80% and a false-positive rate of 0.13%. CONCLUSION: This large multicenter study confirms that cell-free DNA testing is the most accurate screening test for trisomy 21 in twin pregnancies, with screening performance similar to that in singletons and very low failure rates (0.31%). The predictive accuracy for trisomies 18 and 13 may be less. However, given the low false-positive rate, offering first-line screening with cell-free DNA to women with twin pregnancy is appropriate in our view and should be considered a primary screening test for trisomy 21 in twins.

Terminology in early pregnancy loss: what women hear and what clinicians write.

OBJECTIVE: The Royal College of Obstetricians and Gynaecologists recommends that patient-focused terminology be used in early pregnancy care. The objective of the study was to evaluate whether inappropriate terminology is continuing to be used in Scottish gynaecology services. METHODS: A case note review (1259 records) and a patient survey (648 replies) assessed usage of four inappropriate terms ('abortion', 'blighted ovum', 'incompetent cervix' and 'pregnancy failure') in 18 Scottish hospitals providing secondary care to women with early pregnancy loss. RESULTS: Women reported hearing 'abortion' in 4.2% of hospital episodes (95% CI 2.9-6.0), but the term was used in 9.9% (95% CI 8.4-11.7) of hospital records. CONCLUSION: In order to meet national recommendations on terminology for early pregnancy loss, clinicians should not only say 'miscarriage' but also write it.

Are national recommendations regarding examination and disposal of products of miscarriage being followed? A need for revised guidelines?

BACKGROUND: National guidance documents advise that tissue obtained from treatment of miscarriage should be submitted for histological examination to exclude trophoblastic disease and ectopic pregnancy, and require sensitive disposal of human tissue. The aim of this study was to determine the extent to which health professionals have adopted these recommendations. METHODS AND RESULTS: Fifteen Scottish Obstetric and Gynaecology services participated in an audit of early pregnancy loss care. Three audit tools were used. In a case note review, 484 women completed medical or surgical treatment for miscarriage. 71% of records contained evidence of histological examination of tissue. Documentation of discussion of disposal of tissue with the woman was found in 29% of records. In a patient survey, 648 women with threatened or confirmed miscarriage returned questionnaires. Active treatment occurred in 134 cases. Only 55%, 50.9% and 47.4% reported being 'informed', 'consented' and 'involved', respectively, with decisions about tissue disposal. In a staff survey, a postal questionnaire was administered to 224 gynaecologists, with 144 replies. Self reported practice as 'seldom' or 'occasional' for sending tissue for histological examination was 34% for surgical evacuation and 57% for medical management. Reporting of 'seldom' or 'occasional' discussion of disposal of tissue with the woman was 42% and 49% for surgical and medical treatment, respectively. CONCLUSIONS: National guidance on these issues was found to be contentious and implementation was variable. Wide consultation with stakeholders is needed prior to the publication of revised guidance.