| 1. Pandya PP, Brizot ML, Kuhn P, Snijders RJ, Nicolaides KH. First-trimester fetal nuchal translucency thickness and risk for trisomies. Obstetrics & Gynecology. 84(3):420-3, 1994 Sep. |
Review/Other-Dx |
560 fetuses |
To define the relation between fetal nuchal translucency thickness at 10-13 weeks' gestation and the risk for fetal trisomies and pregnancy outcome. |
The incidence of trisomies 21, 18, or 13 was 18% (102 of 560 cases) and was significantly associated with both maternal age (r = 0.97) and fetal nuchal translucency thickness (r = 0.75). In 383 fetuses with nuchal translucency of 3 mm, the observed number of fetal trisomies was 23, in contrast to the frequency of 6.0 expected on the basis of maternal age. In 177 fetuses with nuchal translucency of 4 mm or more, 79 cases were observed, compared with 2.7 expected on the basis of maternal age. In fetuses with nuchal translucency of 4 mm or more and normal karyotype, there was a high association with other defects and the prognosis was often poor, whereas the translucency resolved for those with 3 mm and the pregnancy outcome was usually normal. |
4 |
| 2. . Practice Bulletin No. 163 Summary: Screening for Fetal Aneuploidy. Obstetrics & Gynecology. 127(5):979-81, 2016 May. |
Review/Other-Dx |
N/A |
To provide current information regarding the available screening test options for fetal aneuploidy and to review their benefits, accuracy, and limitations. |
N/A |
4 |
| 3. Pandya PP, Kondylios A, Hilbert L, Snijders RJ, Nicolaides KH. Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency. Ultrasound in Obstetrics & Gynecology. 5(1):15-9, 1995 Jan. |
Review/Other-Dx |
1015 fetuses |
To report the findings of fetal karyotype and pregnancy outcome in an expanded series of 1015 fetuses with nuchal translucency thickness > or = to 3mm. |
The observed numbers of trisomies 21, 18 and 13 in fetuses with nuchal translucency thicknesses of 3 mm, 4 mm, 5 mm and > or = 6 mm were approximately 3 times, 18 times, 28 times and 36 times higher than the respective numbers expected on the basis of maternal age. The incidences of Turner syndrome and triploidy were 9-fold and 8-fold higher but the incidence of other sex chromosome aneuploidies was similar to that of an unselected population of women undergoing first-trimester fetal karyotyping for maternal age. In the chromosomally normal group, the incidence of structural defects, mainly cardiac, diaphragmatic, renal and abdominal wall, was approximately 4%, which is higher than would be expected in an unselected population. The rates of fetal loss in the groups with nuchal translucency thickness of 3 mm and 4 mm were 2% and 4%, respectively, which is similar to the 2.3% rate of fetal loss observed in a group of fetuses with normal nuchal translucency thickness undergoing chorion villus sampling. For fetal nuchal translucency thickness of > or = 5 mm, the rate of fetal loss was 13%. |
4 |
| 4. Rottem S, Bronshtein M, Thaler I, Brandes JM. First trimester transvaginal sonographic diagnosis of fetal anomalies. Lancet. 1(8635):444-5, 1989 Feb 25. |
Observational-Dx |
N/A |
To describe the transvaginal diagnosis of fetal anomalies during the first trimester. |
No abstract available. |
4 |
| 5. Nicolaides KH, Azar G, Byrne D, Mansur C, Marks K. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ. 304(6831):867-9, 1992 Apr 04. |
Observational-Dx |
827 Fetuses |
To examine the significance of fetal nuchal translucency at 10-14 weeks' gestation in the prediction of abnormal fetal karyotype. |
The incidence of chromosomal defects was 3% (28 of 827 cases). In the 51 (6%) fetuses with nuchal translucency 3-8 mm thick the incidence of chromosomal defects was 35% (18 cases). In contrast, only 10 of the remaining 776 (1%) fetuses were chromosomally abnormal. |
4 |
| 6. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet. 352(9125):343-6, 1998 Aug 01. |
Observational-Dx |
96127 women |
To investigate assessment of risk of trisomy 21 by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation. |
The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8.3%) of 95476 normal pregnancies, 268 (82-2%) of 326 with trisomy 21, and 253 (77.9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases. |
4 |
| 7. Malone FD, D'Alton ME, Society for Maternal-Fetal Medicine. First-trimester sonographic screening for Down syndrome. [Review] [62 refs]. Obstetrics & Gynecology. 102(5 Pt 1):1066-79, 2003 Nov. |
Review/Other-Dx |
N/A |
To provide an objective assessment of the literature describing nuchal translucency, as well as some adjunct first-trimester sonographic techniques, such as ductus venosus flow and nasal bone studies. Additionally, a detailed description of practical problems that might limit the implementation of this form of screening is presented. |
No results stated in abstract. |
4 |
| 8. Comstock CH, Malone FD, Ball RH, et al. Is there a nuchal translucency millimeter measurement above which there is no added benefit from first trimester serum screening?. American Journal of Obstetrics & Gynecology. 195(3):843-7, 2006 Sep. |
Observational-Dx |
36120 patients |
To evaluate whether there is a nuchal translucency (NT) measurement, independent of gestational age, above which immediate diagnostic testing should be offered without waiting for first trimester serum markers. |
Thirty-two patients (0.09%) had NT =4.0 mm; the lowest combined first trimester trisomy 21 risk assessment in euploid cases was 1 in 8 and among aneuploidy cases was 7 in 8. One hundred twenty-eight patients (0.3%) had simple NT =3.0 mm: the lowest combined first trimester trisomy 21 risk assessment of any patient in this group was 1 in 1479 and the lowest risk assessment among aneuploid cases was 1 in 2. Ten patients (8%) had first trimester trisomy 21 risk assessments lowered to less that 1:200 and none of these 10 cases had an abnormal outcome. |
4 |
| 9. Spencer K, Nicolaides KH. Screening for trisomy 21 in twins using first trimester ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years experience. Bjog. 2003;110(3):276-280. |
Observational-Dx |
230 twin pregnancies |
To evaluate the performance of screening for fetal trisomy 21 in the first trimester of twin pregnancies by a combination of maternal serum biochemistry and ultrasonography. |
Overall, 97.4% of the women with twins (224/230) accepted first trimester screening. The rate of detection of trisomy 21 was 75% (3/4). Fetal death at presentation was found in 3.4% of fetuses (16/460). Of women who accepted screening, 4.3% (10/230) presented too late for fetal nuchal translucency measurement and 10.0% of women (23/230) presented too early. A risk for trisomy 21 was calculated for each fetus based on the individual fetal nuchal translucency thickness and the maternal biochemistry. The false positive rate among those eligible for first trimester screening was 9.0% (19/206) of pregnancies and 6.9% of fetuses (28/412). Uptake of invasive testing was 59% (10/17) with chorionic villus sampling in eight cases and amniocentesis in two. No fetal loss occurred within 28 days of chorionic villus sampling and no loss occurred after amniocentesis. One case of trisomy 21 was identified for every three invasive procedures. |
3 |
| 10. Cleary-Goldman J, Berkowitz RL. First trimester screening for Down syndrome in multiple pregnancy. [Review] [59 refs]. Seminars in Perinatology. 29(6):395-400, 2005 Dec. |
Review/Other-Dx |
N/A |
To review the advantages of first trimester screening for Down syndrome in patients with a multiple gestation. |
No results stated in abstract. |
4 |
| 11. Sebire NJ, Snijders RJ, Hughes K, Sepulveda W, Nicolaides KH. Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. Br J Obstet Gynaecol. 1996;103(10):999-1003. |
Review/Other-Dx |
22,518 pregnant women |
To determine the prevalence of increased fetal nuchal translucency thickness in twin pregnancies and to evaluate screening for trisomy 21 by a combination of translucency thickness and maternal age. |
In the 448 twin pregnancies the nuchal translucency thickness was above the 95th centile of the normal range (for crown-rump length in singletons) in 65/896 fetuses (7.3%), including 7/8 (88%) with trisomy 21. Increased translucency was also present in four fetuses with other chromosomal abnormalities. In the chromosomally normal twin pregnancies the prevalence of increased nuchal translucency was higher in fetuses from monochorionic (8.4%; 16/190) than in those with dichorionic pregnancies (5.4%; 37/688). The minimum estimated risk for trisomy 21, based on maternal age and fetal nuchal translucency thickness, was 1 in 300 in 19.5% (175/896) of the twins including all eight of those with trisomy 21. |
4 |
| 12. Nicolaides KH.. Screening for fetal aneuploidies at 11 to 13 weeks. [Review]. Prenatal Diagnosis. 31(1):7-15, 2011 Jan. |
Review/Other-Dx |
N/A |
To evaluate the different methods of screening for fetal aneuploidies. |
No results stated in abstract |
4 |
| 13. Vandecruys H, Faiola S, Auer M, Sebire N, Nicolaides KH. Screening for trisomy 21 in monochorionic twins by measurement of fetal nuchal translucency thickness. Ultrasound Obstet Gynecol. 2005;25(6):551-553. |
Observational-Dx |
769 twin pregnancies |
To determine whether in screening for trisomy 21 by measurement of fetal nuchal translucency (NT) thickness in monochorionic twin pregnancies it is preferable to use the higher, smaller or average NT. |
The median maternal age was 33 (range, 16–45) years, the CRL was 62 (range, 45–84) mm and gestational age was 12 (range, 11 to 13 + 6) weeks. Either the fetal karyotype was normal, or phenotypically normal babies were born, in 761 cases. The karyotype was abnormal in eight cases, including six with trisomy 21. The estimated risk using the higher, smaller and average NT was 1 in 300 or more in 6 (100%), 4 (66.7%) and 6 (100%) of the trisomy 21 pregnancies and in 148 (19.4%), 57 (7.5%) and 106 (13.9%) of the normal pregnancies. For a detection rate of 100%, the false positive rates using the higher, smaller and average NT would be 5.1%, 45.9% and 4.2%, respectively. |
3 |
| 14. Cuckle H, Platt LD, Thornburg LL, et al. Nuchal Translucency Quality Review (NTQR) program: first one and half million results. Ultrasound in Obstetrics & Gynecology. 45(2):199-204, 2015 Feb. |
Review/Other-Dx |
1.5 million scans |
To evaluate the performance of first-trimester nuchal translucency (NT) measurement by providers (physician-sonologists and sonographers) within the Nuchal Translucency Quality Review (NTQR) program. |
Among the first 1.5 million scans in the NTQR program, performed between 2005 and 2011, there were 1 485 944 with CRL in the range 41-84 mm, from 4710 providers at 2150 ultrasound units. Among the 3463 providers with at least 30 scans in total, the median of the providers' median NT-MoMs was 0.913. Only 1901 (55%) had a median NT-MoM within the expected range; there were 89 above 1.1 MoM, 1046 at 0.8-0.9 MoM, 344 at 0.7-0.8 MoM and 83 below 0.7 MoM. There was a small increase in the median NT-MoM according to providers' length of time in the NTQR program and number of scans entered annually. On average, physician-sonologists had a higher median NT-MoM than did sonographers, as did those already credentialed before joining the program. The median provider SD was 0.093 and the median slope was 13.5%. SD correlated negatively with the median NT-MoM (r = -0.34) and positively with the slope (r = 0.22) |
4 |
| 15. D'Alton ME, Cleary-Goldman J, Lambert-Messerlian G, et al. Maintaining quality assurance for sonographic nuchal translucency measurement: lessons from the FASTER Trial. Ultrasound in Obstetrics & Gynecology. 33(2):142-6, 2009 Feb. |
Observational-Dx |
37,018 patients |
To evaluate nuchal translucency measurement quality assurance techniques in a large-scale study. |
Detailed quality assessment was available for 37 018 patients. Nuchal translucency measurement was successful in 96.3% of women. Local reviewers rejected 0.8% of images, and the single central physician reviewer rejected a further 2.9%. Multivariate analysis indicated that higher body mass index, earlier gestational age and transvaginal probe use were predictors of failure of nuchal translucency measurement and central image rejection (P = 0.001). Epidemiological monitoring identified a drift in measurements over time. |
3 |
| 16. Kagan KO, Cicero S, Staboulidou I, Wright D, Nicolaides KH. Fetal nasal bone in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation. Ultrasound in Obstetrics & Gynecology. 33(3):259-64, 2009 Mar. |
Observational-Dx |
21,141 singleton pregnancies |
To investigate the performance of first-trimester screening for aneuploidies by including assessment of the fetal nasal bone in the combined test of maternal age, fetal nuchal translucency (NT) thickness, fetal heart rate (FHR) and serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). |
The nasal bone was absent in 2.6% of the euploid fetuses, 59.8% with trisomy 21, 52.8% with trisomy 18, 45.0% with trisomy 13 and in none of the fetuses with Turner syndrome. Respective figures for an absent nasal bone in the validation population, which contained fewer Black women, were 0.6%, 62.6%, 55.3%, 35.3% and 41.7%. In a screening policy based on maternal age, fetal NT, FHR, serum free beta-hCG and PAPP-A, for a fixed risk cut-off of 1 : 100, the false-positive rate was 3.0%. The standardized detection rates were 91% for trisomy 21 and 100% for trisomy 18, trisomy 13 and Turner syndrome, respectively. Assessment of the nasal bone in all pregnancies reduced the false-positive rate to 2.5% without changing the detection rate. A detection rate of 93% was achieved with the two-stage strategy at a false-positive rate of 2.4% in which it was necessary to assess the nasal bone in only 15% of the total population. In the validation dataset, screening by the combined test and using a risk cut-off of 1 : 100 detected 90% of the cases with trisomy 21 for a false-positive rate of 4%. Inclusion of the nasal bone increased the detection rate to 92% for a false-positive rate of 2.9%. Contingent screening detected 92% of cases for a false-positive rate of 2.9%. |
3 |
| 17. Alldred SK, Takwoingi Y, Guo B, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening. [Review]. Cochrane Database of Systematic Reviews. 3:CD012600, 2017 Mar 15. |
Meta-analysis |
126 Studies |
To estimate and compare the accuracy of first trimester ultrasound markers alone, and in combination with first trimester serum tests for the detection of Down's syndrome. |
We included 126 studies (152 publications) involving 1,604,040 fetuses (including 8454 Down's syndrome cases). Studies were generally good quality, although differential verification was common with invasive testing of only high-risk pregnancies. Sixty test combinations were evaluated formed from combinations of 11 different ultrasound markers (nuchal translucency (NT), nasal bone, ductus venosus Doppler, maxillary bone length, fetal heart rate, aberrant right subclavian artery, frontomaxillary facial angle, presence of mitral gap, tricuspid regurgitation, tricuspid blood flow and iliac angle 90 degrees); 12 serum tests (inhibin A, alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (ßhCG), total hCG, pregnancy-associated plasma protein A (PAPP-A), unconjugated oestriol (uE3), disintegrin and metalloprotease 12 (ADAM 12), placental growth factor (PlGF), placental growth hormone (PGH), invasive trophoblast antigen (ITA) (synonymous with hyperglycosylated hCG), growth hormone binding protein (GHBP) and placental protein 13 (PP13)); and maternal age. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free ßhCG.Comparisons of the 10 most frequently evaluated test strategies showed that a combined NT, PAPP-A, free ßhCG and maternal age test strategy significantly outperformed ultrasound markers alone (with or without maternal age) except nasal bone, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). In both direct and indirect comparisons, the combined NT, PAPP-A, free ßhCG and maternal age test strategy showed superior diagnostic accuracy to an NT and maternal age test strategy (P < 0.0001). Based on the indirect comparison of all available studies for the two tests, the sensitivity (95% confidence interval) estimated at a 5% FPR for the combined NT, PAPP-A, free ßhCG and maternal age test strategy (69 studies; 1,173,853 fetuses including 6010 with Down's syndrome) was 87% (86 to 89) and for the NT and maternal age test strategy (50 studies; 530,874 fetuses including 2701 Down's syndrome pregnancies) was 71% (66 to 75). Combinations of NT with other ultrasound markers, PAPP-A and free ßhCG were evaluated in one or two studies and showed sensitivities of more than 90% and specificities of more than 95%.High-risk populations (defined before screening was done, mainly due to advanced maternal age of 35 years or more, or previous pregnancies affected with Down's syndrome) showed lower detection rates compared to routine screening populations at a 5% FPR. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under-ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting test sensitivity. Conversely, for the NT, PAPP-A, free ßhCG and maternal age test strategy, detection rates and false positive rates increased with maternal age in the five studies that provided data separately for the subset of women aged 35 years or more. |
Good |
| 18. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. Electronic address: pubs@smfm.org.. #36: Prenatal aneuploidy screening using cell-free DNA. American Journal of Obstetrics & Gynecology. 212(6):711-6, 2015 Jun. |
Review/Other-Dx |
N/A |
To aid clinicians in their day-to-day practice of counseling patients regarding prenatal aneuploidy testing options with cell-free DNA screening, which includes how it compares to current testing methods, potential benefits and harms, and its limitations and caveats. |
N/A |
4 |
| 19. American College of Radiology. ACR-ACOG-AIUM-SMFM-SRU Practice Parameter for the Performance of Standard Diagnostic Obstetrical Ultrasound. Available at: https://www.acr.org/-/media/ACR/Files/Practice-Parameters/us-ob.pdf |
Review/Other-Dx |
N/A |
To promote the safe and effective use of diagnostic and therapeutic radiology by describing the key elements of standard ultrasound examinations in the first, second, and third trimesters of pregnancy. |
No abstract available. |
4 |
| 20. AIUM practice guideline for the performance of fetal echocardiography. J Ultrasound Med. 2013;32(6):1067-1082. |
Review/Other-Dx |
N/A |
To provide practice guidelines for the performance of fetal echocardiography. |
No results stated in abstract. |
4 |
| 21. Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Norton ME, Biggio JR, Kuller JA, Blackwell SC. The role of ultrasound in women who undergo cell-free DNA screening. American Journal of Obstetrics & Gynecology. 216(3):B2-B7, 2017 Mar. |
Review/Other-Dx |
N/A |
To review the current data on the role of ultrasound in women who have undergone or are considering cell-free DNA screening. |
No results stated in abstract. |
4 |
| 22. Malone FD, Ball RH, Nyberg DA, et al. First-trimester septated cystic hygroma: prevalence, natural history, and pediatric outcome. Obstetrics & Gynecology. 106(2):288-94, 2005 Aug. |
Observational-Dx |
134 cases |
To estimate prevalence, natural history, and outcome of septated cystic hygroma in the first trimester in the general obstetric population, and to differentiate this finding from simple increased nuchal translucency. |
There were 134 cases of cystic hygroma (2 lost to follow-up) among 38,167 screened patients (1 in 285). Chromosomal abnormalities were diagnosed in 67 (51%), including 25 trisomy-21, 19 Turner syndrome, 13 trisomy-18, and 10 others. Major structural fetal malformations (primarily cardiac and skeletal) were diagnosed in 22 of the remaining 65 cases (34%). There were 5 cases (8%) of fetal death and 15 cases of elective pregnancy termination without evidence of abnormality. One of 23 (4%) normal survivors was diagnosed with cerebral palsy and developmental delay. Overall, survival with normal pediatric outcome was confirmed in 17% of cases (22 of 132). Compared with simple increased nuchal translucency, cystic hygroma has 5-fold, 12-fold, and 6-fold increased risk of aneuploidy, cardiac malformation, and perinatal death, respectively. |
4 |
| 23. Nicolaides KH, Heath V, Cicero S. Increased fetal nuchal translucency at 11-14 weeks. [Review] [47 refs]. Prenatal Diagnosis. 22(4):308-15, 2002 Apr. |
Review/Other-Dx |
N/A |
To review increased fetal NT thickness at 11–14-weeks. |
No results stated in abstract. |
4 |
| 24. Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. New England Journal of Medicine. 353(19):2001-11, 2005 Nov 10. |
Observational-Dx |
38,167 patients |
To conduct the First- and Second-Trimester Evaluation of Risk (FASTER) Trial with the goal of providing direct comparative data on currently available screening approaches to Down's syndrome from a large population followed prospectively. |
First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. |
3 |
| 25. Van Mieghem T, Hindryckx A, Van Calsteren K. Early fetal anatomy screening: who, what, when and why?. [Review]. Current Opinion in Obstetrics & Gynecology. 27(2):143-50, 2015 Apr. |
Review/Other-Dx |
N/A |
To review the potential benefits and downsides of early anatomy screening. |
No results stated in abstract. |
4 |
| 26. Rossi AC, Prefumo F. Accuracy of ultrasonography at 11-14 weeks of gestation for detection of fetal structural anomalies: a systematic review. [Review]. Obstet Gynecol. 122(6):1160-7, 2013 Dec. |
Meta-analysis |
19 articles |
To review the literature concerning the efficacy of early ultrasonography (at 11-14 weeks of gestation) to identify fetal malformations. |
From 1,203 articles, 19 were included. Overall, we pooled 78,002 fetuses undergoing ultrasonography at 11-14 weeks, of which 996 were malformed, leading to prevalence of malformation of 12 per 1,000. The overall detection rate was 472 of 957 (51%). The highest detection rate was achieved for neck anomalies (92%), whereas limbs (34%), face (34%), and genitourinary anomalies (34%) were associated with the lowest detection rate. At 14 weeks of gestation or less, fetal echocardiography detected 53% of congenital heart disease compared with 43% by complete scan (P=.040). The use of Doppler did not improve the detection rate for congenital heart defects (52% compared with 44%, respectively; P=.11). Multiple defects were identified more frequently than isolated malformations (60% compared with 44%; P=.005). The detection rate was higher combining transabdominal and transvaginal techniques (62%) than either abdominal (51%) or transvaginal (34%; P<.001). Detection rate was higher in women at high risk (65%) than unselected population (50% P=.001). |
Inadequate |
| 27. Makrydimas G, Sotiriadis A, Ioannidis JP. Screening performance of first-trimester nuchal translucency for major cardiac defects: a meta-analysis. American Journal of Obstetrics & Gynecology. 189(5):1330-5, 2003 Nov. |
Meta-analysis |
8 independent studies with 58,492 pregnant women |
To evaluate the screening performance of increased first-trimester nuchal translucency for the detection of major congenital heart defects. |
Eight independent studies with 58,492 pregnant women were analyzed. There was significant heterogeneity among the studies. Nuchal translucency above the 99th percentile had a sensitivity of 31% and specificity of 98.7% (random effects calculations), with a positive likelihood ratio of 24. Summary receiver-operating characteristic estimates were consistent with these values. The ability of nuchal translucency measurements above this threshold to detect cardiac malformations varied nonsignificantly (P=.64) for different congenital heart defects types (sensitivity range, 25%-55%). |
Good |
| 28. Cicero S, Bindra R, Rembouskos G, Tripsanas C, Nicolaides KH. Fetal nasal bone length in chromosomally normal and abnormal fetuses at 11-14 weeks of gestation. Journal of Maternal-Fetal & Neonatal Medicine. 11(6):400-2, 2002 Jun. |
Observational-Dx |
1092 fetuses |
To determine the value of measuring fetal nasal bone length at 11-14 weeks of gestation in screening for chromosomal defects. |
The median gestation was 12 (11-14) weeks. The fetal profile was successfully examined in all cases. The fetal karyotype was normal in 955 pregnancies and abnormal in 137, including 79 cases of trisomy 21. In the chromosomally normal group, the fetal nasal bone length increased significantly with crown-rump length (CRL) from a mean of 1.3 mm at a CRL of 45 mm to 2.1 mm at a CRL of 84 mm. In 54 of the 79 (68.4%) cases of trisomy 21, the nasal bone was absent. In the 25 cases with present nasal bone, the nasal bone length for the CRL was not significantly different from normal. Similarly, there were no significant differences from normal in the nasal bone length of fetuses with other chromosomal defects. |
4 |
| 29. Braithwaite JM, Economides DL. The measurement of nuchal translucency with transabdominal and transvaginal sonography--success rates, repeatability and levels of agreement. British Journal of Radiology. 68(811):720-3, 1995 Jul. |
Observational-Dx |
242 Patients |
To assess the abilities of transabdominal sonography (TAS) and transvaginal sonography (TVS) to measure nuchal translucency (NT) and to establish the levels of agreement between the two scan mode measures. |
A measurement of NT was obtained in 92% and 90% of fetuses using TAS and TVS, respectively, and in 100% of fetuses by combination of the scan modes. Failure to measure NT with TAS was due to inability to obtain mid-sagittal views because of unfavourable fetal lie or poor resolution, especially in patients with high body mass indexes. Although there was generally good correlation between the two scan mode measurements, a significant overmeasuring of NT was observed with TAS (mean difference +/- SD: 0.10 +/- 0.29 mm, p < 0.01). The repeatability coefficients were 0.40 mm and 0.22 mm for TAS and TVS, respectively. |
3 |
| 30. Malone FD, Ball RH, Nyberg DA, et al. First-trimester nasal bone evaluation for aneuploidy in the general population. Obstetrics & Gynecology. 104(6):1222-8, 2004 Dec. |
Observational-Dx |
38,189 patients |
To evaluate the role of fetal nasal bone imaging at 10 3/7 to 13 6/7 weeks as a screening tool for aneuploidy, in a prospective multicenter trial. |
A total of 38,189 patients completed first trimester NT screening, of whom 6,324 also underwent nasal bone sonography. An acceptable nasal image was obtained in 4,801 cases (76%), with nasal bones described as present in 4,779 (99.5%), and absent in 22 (0.5%). There were 11 identified cases of trisomy-21 in the population of 6,324 patients. In 9 of the 11 cases (82%) the nasal bones were described as present, and 2 cases were described as unable to determine. The only other aneuploidies were 2 cases of trisomy-18, in 1 of which the nasal bones were described as absent, and in 1 present. Absence of nasal bones had sensitivity for aneuploidy of 7.7%, false-positive rate 0.3%, and positive predictive value 4.5%. |
4 |
| 31. Sonek J, Nicolaides K. Additional first-trimester ultrasound markers. [Review]. Clinics in Laboratory Medicine. 30(3):573-92, 2010 Sep. |
Review/Other-Dx |
N/A |
To review additional first-trimester ultrasound markers |
No results stated in abstract. |
4 |
| 32. Kagan KO, Valencia C, Livanos P, Wright D, Nicolaides KH. Tricuspid regurgitation in screening for trisomies 21, 18 and 13 and Turner syndrome at 11+0 to 13+6 weeks of gestation. Ultrasound in Obstetrics & Gynecology. 33(1):18-22, 2009 Jan. |
Observational-Dx |
19,614 singleton pregnancies |
To investigate the performance of first-trimester screening for aneuploidies by including assessment of tricuspid blood flow in the combined test of maternal age, fetal nuchal translucency (NT) thickness, fetal heart rate (FHR) and serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A). |
Tricuspid regurgitation was observed in 0.9% of the euploid fetuses and 55.7%, 33.3% and 30% of the fetuses with trisomies 21, 18 and 13, respectively, and in 37.5% of those with Turner syndrome. In a screening policy based on maternal age, fetal NT, FHR, serum free beta-hCG and PAPP-A, for a fixed false positive rate of 3% the standardized detection rates were 91% for trisomy 21 and 100% for trisomy 18, trisomy 13 and Turner syndrome. Assessment of tricuspid flow in all pregnancies would increase the detection rate of trisomy 21 to 96%, and the detection rates of trisomy 18, trisomy 13 and Turner syndrome would be 92%, 100% and 100%, respectively. The same detection rates were achieved with the two-stage strategy-in which it was necessary to assess tricuspid flow in only 15% of the total population-at a false positive rate of 2.4%. |
4 |
| 33. Scala C, Morlando M, Familiari A, et al. Fetal Tricuspid Regurgitation in the First Trimester as a Screening Marker for Congenital Heart Defects: Systematic Review and Meta-Analysis. [Review]. Fetal Diagnosis & Therapy. 42(1):1-8, 2017. |
Meta-analysis |
4 studies |
to establish the predictive accuracy of tricuspid regurgitation (TR) for congenital heart defects CHD |
A total of 452 articles were identified; 60 were assessed with respect to their eligibility for inclusion and a total of 4 studies were included in the study. TR was associated with an increased risk of CHD (RR: 9.6, 95% CI 2.8-33.5; I2: 92.7%). The strength of association between TR and CHD persisted when considering fetuses at risk for CHD, such as those with increased nuchal translucency (RR: 7.2, 95% CI 5.2-9.8; I2: 0%), while TR did not show any association with CHD when detected in a population at low risk for cardiac defects (RR: 9.3, 95% CI 0.8-111.8; I2: 93%). The overall diagnostic performance of TR in detecting CHD was poor in detecting CHD (sROC: 0.684, SE: 0.61) with a sensitivity of 35.2% (95% CI 26.9-44.1) and a specificity of 98.6% (95% CI 98.5-98.7). Detection of TR at the 11-14 weeks' scan showed a positive likelihood ratio of 7.2 (95% CI 5.3-9.8) in detecting CHD when applied to a population at risk for CHD such as fetuses with an increased nuchal translucency. |
Good |
| 34. Maiz N, Valencia C, Kagan KO, Wright D, Nicolaides KH. Ductus venosus Doppler in screening for trisomies 21, 18 and 13 and Turner syndrome at 11-13 weeks of gestation. Ultrasound in Obstetrics & Gynecology. 33(5):512-7, 2009 May. |
Observational-Dx |
19,614 fetuses |
To investigate the performance of first-trimester screening for aneuploidies by including assessment of ductus venosus flow in the combined test of maternal age, fetal nuchal translucency thickness, fetal heart rate, and serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. |
Reversed a-wave was observed in 3.2% of the euploid fetuses, and in 66.4%, 58.3%, 55.0% and 75.0% of fetuses with trisomies 21, 18 and 13 and Turner syndrome, respectively. Inclusion of ductus venosus flow in all pregnancies would detect 96%, 92%, 100% and 100% of trisomies 21, 18 and 13 and Turner syndrome, respectively, at a false-positive rate of 3%. The same detection rates were achieved with the two-stage strategy at a false-positive rate of 2.6%, in which it was necessary to assess the ductus venosus in only 15% of the total population. |
4 |
| 35. Bilardo CM, Muller MA, Zikulnig L, Schipper M, Hecher K. Ductus venosus studies in fetuses at high risk for chromosomal or heart abnormalities: relationship with nuchal translucency measurement and fetal outcome. Ultrasound in Obstetrics & Gynecology. 17(4):288-94, 2001 Apr. |
Observational-Dx |
186 fetuses |
To investigate, in a high-risk group of fetuses, the role of ductus venosus Doppler velocimetry as a prognostic factor, in addition to nuchal translucency measurement, for predicting chromosomal anomalies and, where the karyotype was normal, for predicting fetal outcome. |
Nuchal translucency measurement was increased in 112 fetuses. The outcome of pregnancy was normal in 130 fetuses. Fifty-six fetuses had an adverse outcome (46 chromosomal anomalies, three intrauterine deaths, six structural anomalies and one developmental disorder). The sensitivity of an abnormal ductus venosus pulsatility index or of absent or reversed flow during the a-wave was 65% for chromosomal anomalies and 68% for an adverse outcome. The specificity was 79%. There was a significant correlation between nuchal translucency and ductus venosus pulsatility index. In chromosomally normal fetuses with an enlarged nuchal translucency an abnormal ductus venosus flow was associated with a nearly nine-fold increase in adverse outcome (odds ratio 11.7). |
4 |
| 36. Maiz N, Plasencia W, Dagklis T, Faros E, Nicolaides K. Ductus venosus Doppler in fetuses with cardiac defects and increased nuchal translucency thickness. Ultrasound in Obstetrics & Gynecology. 31(3):256-60, 2008 Mar. |
Observational-Dx |
191 fetuses |
To examine the possible role of Doppler ultrasound assessment of ductus venosus blood flow in screening for major cardiac defects in chromosomally normal fetuses with increased nuchal translucency (NT) thickness at 11 + 0 to 13 + 6 weeks' gestation. |
Major cardiac defects were diagnosed in 16 (8.4%) of the 191 chromosomally normal fetuses. Reversed or absent flow in the ductus venosus during atrial contraction was observed in 11 of the 16 (68.8%) fetuses with cardiac defects and in 40 of the 175 (22.9%) with no cardiac defects. Multivariate analysis demonstrated that the prevalence of an abnormal A-wave in the ductus venosus in fetuses without major cardiac defects increased with fetal NT thickness (odds ratio (OR), 1.463; 95% CI, 1.183-1.809; P < 0.0001) but in those with cardiac defects it did not change significantly with NT thickness (OR, 2.054; 95% CI, 0.573-7.360; P = 0.269). The likelihood ratio for a major cardiac defect when the ductus venosus flow was abnormal decreased with fetal NT thickness from 4.58 at NT 3.5 mm to 2.47 for NT 5.5 mm, and the likelihood ratio when the ductus venosus flow was normal increased from 0.37 at NT 3.5 mm to 0.43 for NT 5.5 mm. |
4 |
| 37. Pereira S, Ganapathy R, Syngelaki A, Maiz N, Nicolaides KH. Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects. Obstetrics & Gynecology. 117(6):1384-91, 2011 Jun. |
Observational-Dx |
85 cases |
To estimate the potential value of fetal assessment for tricuspid regurgitation at 11-13 weeks of gestation in the prediction of major cardiac defects. |
The study population of euploid fetuses included 85 cases with major cardiac defects and 40,905 with no cardiac defects. Fetal nuchal translucency above the 95th percentile, tricuspid regurgitation, or ductus venosus reversed A-wave was observed in 30 (35.3%), 28 (32.9%), and 24 (28.2%) of the fetuses with cardiac defects, respectively, and in 1,956 (4.8%), 516 (1.3%), and 856 (2.1%) of those without cardiac defects. Any one of the three markers was found in 49 of the fetuses with cardiac defects (57.6%, 95% confidence interval [CI] 47.0-67.6%) and in 3,265 of those without cardiac defects (8.0%, 95% CI 7.7-8.2%). |
4 |
| 38. Pham A, Melchior M. Screening for fetal congenital heart disease. CMAJ Canadian Medical Association Journal. 189(12):E468, 2017 03 27. |
Review/Other-Dx |
N/A |
To review five things to know about screening for fetal congenital heart disease. |
No abstract available. |
4 |
| 39. Syngelaki A, Chelemen T, Dagklis T, Allan L, Nicolaides KH. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11-13 weeks. [Review]. Prenatal Diagnosis. 31(1):90-102, 2011 Jan. |
Observational-Dx |
45,191 Pregnancies |
To examine the performance of the 11–13 weeks scan in detecting non-chromosomal abnormalities. |
Aneuploidies (n = 332) were excluded from the analysis. Fetal abnormalities were observed in 488 (1.1%) of the remaining 44 859 cases; 213 (43.6%) of these were detected at 11–13 weeks. The early scan detected all cases of acrania, alobar holoprosencephaly, exomphalos, gastroschisis, megacystis and body stalk anomaly, 77% of absent hand or foot, 50% of diaphragmatic hernia, 50% of lethal skeletal dysplasias, 60% of polydactyly, 34% of major cardiac defects, 5% of facial clefts and 14% of open spina bifida, but none of agenesis of the corpus callosum, cerebellar or vermian hypoplasia, echogenic lung lesions, bowel obstruction, most renal defects or talipes. Nuchal translucency (NT) was above the 95th percentile in 34% of fetuses with major cardiac defects. |
4 |
| 40. Haak MC, van Vugt JM. Echocardiography in early pregnancy: review of literature. [Review] [51 refs]. Journal of Ultrasound in Medicine. 22(3):271-80, 2003 Mar. |
Review/Other-Dx |
N/A |
To describe the development of echocardiography in early pregnancy with its possibilities and limitations, and to define the indications in which first-trimester echocardiography could be offered. |
In the analyzed articles, an increase in visualization rates of the 4-chamber view and the outflow tracts was shown in the last decade, with visualization rates of greater than 90% at 13 weeks' gestation. The different cardiac defects that are shown in first-trimester fetuses are mainly defects involving the 4-chamber view, indicating that defects solely affecting the outflow tracts are difficult to diagnose in the first trimester of pregnancy. The sonographic assessment of the fetal heart between 14 and 18 weeks' gestation has been described. The literature, however, has not shown clear advantages of performing fetal echocardiography during this period compared with transvaginal sonography at 13 weeks' gestation. |
4 |
| 41. Khalil A, Nicolaides KH. Fetal heart defects: potential and pitfalls of first-trimester detection. [Review]. Seminars In Fetal & Neonatal Medicine. 18(5):251-60, 2013 Oct. |
Review/Other-Dx |
N/A |
To review the advantages and limitations of screening for congenital heart defects in the first trimester. |
No results stated in abstract. |
4 |
| 42. Clur SA, Bilardo CM. Early detection of fetal cardiac abnormalities: how effective is it and how should we manage these patients?. [Review]. Prenatal Diagnosis. 34(13):1235-45, 2014 Dec. |
Review/Other-Dx |
N/A |
To review the detection of major congenital heart defects (CHD) in the first trimester and early second trimester including specific markers that help to identify high-risk groups for early fetal echocardiography (EFEC). |
No results stated in abstract. |
4 |
| 43. Simpson LL, Malone FD, Bianchi DW, et al. Nuchal translucency and the risk of congenital heart disease. Obstetrics & Gynecology. 109(2 Pt 1):376-83, 2007 Feb. |
Observational-Dx |
34,266 euploid fetuses |
To estimate whether nuchal translucency assessment is a useful screening tool for major congenital heart disease (CHD) in the absence of aneuploidy. |
A total of 34,266 euploid fetuses with cardiac outcome data were available for analysis. There were 224 cases of CHD (incidence 6.5 per 1,000), of which 52 (23.2%) were major (incidence 1.5 per 1,000). The incidence of major CHD increased with increasing nuchal translucency: 14.1 per 1,000, 33.5 per 1,000, and 49.5 per 1,000 at 2.0 or more MoM, 2.5 or more MoM, and 3.0 or more MoM cutoffs, respectively. Sensitivity, specificity, and positive predictive values were 15.4%, 98.4%, and 1.4% at 2.0 or more MoM; 13.5%, 99.4%, and 3.3% at 2.5 or more MoM; and 9.6%, 99.7%, and 5.0% at 3.0 or more MoM. Nuchal translucency of 2.5 or more MoM (99th percentile) had a likelihood ratio (95% confidence interval) of 22.5 (11.4-45.5) for major CHD. Based on our data, for every 100 patients referred for fetal echocardiography with a nuchal translucency of 99th percentile or more, three will have a major cardiac anomaly |
4 |
| 44. Liu H, Zhou J, Feng QL, et al. Fetal echocardiography for congenital heart disease diagnosis: a meta-analysis, power analysis and missing data analysis. [Review]. European Journal of Preventive Cardiology. 22(12):1531-47, 2015 Dec. |
Meta-analysis |
42 articles |
To evaluate the potential role of demographic, clinical and ultrasonographic characteristics on diagnostic yields for detecting fetal congenital heart disease (CHD). |
Overall, prenatal ultrasound in the detection of CHD had a moderate sensitivity of 68.1% (95% CI 59.6-75.5) and a favorable specificity of 99.9% (99.7-99.9). Risk level and gestation age were independent predictors of diagnostic performance for detecting CHD (p?=?0.004 vs. p?=?0.002, respectively). The pooled sensitivities significantly increased to varying extents with the following echocardiographic views: 48.7% (34.8-67.2) for four-chamber view (4CV); 58.0% (40.3-73.9) for a combination of 4CV and outflow tract views (OTV); 73.5% (59.2-84.1) for combination of 4CV, OTV and three vessels and trachea view (3VTV); 77.1% (62.0-87.5) for extensive cardiac echocardiography examination (ECEE); and 89.6% (81.0-94.6) for spatiotemporal image correlation (STIC). |
Good |
| 45. Practice Bulletin No. 175: Ultrasound in Pregnancy. Obstet Gynecol. 2016;128(6):e241-e256. |
Review/Other-Dx |
N/A |
To present information and evidence regarding the methodology of, indications for, benefits of, and risks associated with obstetric ultrasonography in specific clinical situations. |
No results stated in abstract. |
4 |
| 46. Maya I, Yacobson S, Kahana S, et al. Cut-off value of nuchal translucency as indication for chromosomal microarray analysis. Ultrasound in Obstetrics & Gynecology. 50(3):332-335, 2017 Sep. |
Observational-Dx |
1588 pregnancies |
To assess different NT cut-off levels as indication for chromosomal microarray analysis (CMA) and to determine whether CMA should be recommended for mildly increased NT of 3.0-3.4 mm |
CMA results were recorded in 1588 pregnancies, among which 770 fetuses had either normal NT with no other finding or isolated increased NT. Of these, 462 had NT = 2.9 mm, 170 had NT of 3.0-3.4 mm and 138 had NT = 3.5 mm. Pathogenic copy number variants were found in 1.7%, 6.5% and 13.8% of cases, respectively. |
4 |
| 47. Ali MM, Chasen ST, Norton ME. Testing for Noonan syndrome after increased nuchal translucency. Prenatal Diagnosis. 37(8):750-753, 2017 Aug. |
Review/Other-Dx |
804 fetuses |
To report the prevalence of Noonan syndrome (NS) in a cohort of fetuses that presented with increased nuchal translucency (NT) thickness in the first trimester of pregnancy. |
A total of 804 fetuses had an NT measurement of =3 mm, with a median NT thickness of 3.6 mm. Of these, 302 had karyotyping by CVS or amniocentesis, 200 (66.23%) with normal results. Of fetuses with a normal karyotype, 39 with a median NT thickness of 4.0 mm had a NS gene sequencing panel done, and 161 fetuses with a mean NT thickness of 4.3 mm were not tested for NS (p = 0.05). Of the 39 fetuses who were tested for NS, four (10.3%) had variants consistent with this diagnosis. |
4 |
| 48. Grande M, Jansen FA, Blumenfeld YJ, et al. Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis. [Review]. Ultrasound in Obstetrics & Gynecology. 46(6):650-8, 2015 Dec. |
Review/Other-Dx |
17 Studies |
To estimate the incremental yield of detecting copy number variants (CNVs) by genomic microarray over karyotyping in fetuses with increased nuchal translucency (NT) diagnosed by first-trimester ultrasound. |
Seventeen studies met the inclusion criteria for analysis. Meta-analysis indicated an incremental yield of 5.0% (95% CI, 2.0-8.0%) for the detection of CNVs using microarray when pooling results. Stratified analysis of microarray results demonstrated a 4.0% (95% CI, 2.0-7.0%) incremental yield in cases of isolated NT and 7.0% (95% CI, 2.0-12.0%) when other malformations were present. The most common pathogenic CNVs reported were 22q11.2 deletion, 22q11.2 duplication, 10q26.12q26.3 deletion and 12q21q22 deletion. The pooled prevalence for variants of uncertain significance was 1%. |
4 |
| 49. Borenstein M, Persico N, Kagan KO, Gazzoni A, Nicolaides KH. Frontomaxillary facial angle in screening for trisomy 21 at 11 + 0 to 13 + 6 weeks. Ultrasound in Obstetrics & Gynecology. 32(1):5-11, 2008 Jul. |
Observational-Dx |
890 fetuses |
To examine whether in trisomy 21 fetuses fetal nuchal translucency (NT) thickness and maternal serum free ss-human chorionic gonadotropin (ss-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are independent of the frontomaxillary facial (FMF) angle, and to estimate the performance of a first-trimester screening test for trisomy 21 that includes measurement of the FMF angle. |
The FMF angle was measured in 782 euploid and 108 trisomy 21 fetuses. In the euploid fetuses the mean FMF angle decreased linearly with CRL from 83.5 degrees at a crown-rump length (CRL) of 45 mm to 76.4 degrees at a CRL of 84 mm. In the euploid fetuses the mean delta FMF angle was 0.0 (SD, 4.264) degrees and the respective values in the trisomy 21 fetuses were 7.172 (SD, 4.092) degrees . Incorporating the FMF angle in first-trimester combined screening increased the estimated DR from 90 to 94% at an FPR of 5% and from 85 to 92% at an FPR of 3%. In two-stage screening it would be necessary to measure the FMF angle in 12% of cases and the DRs would be 93 and 91% at FPRs of 5 and 3%, respectively. |
4 |
| 50. Timor-Tritsch IE, Fuchs KM, Monteagudo A, D'alton ME. Performing a fetal anatomy scan at the time of first-trimester screening. Obstetrics & Gynecology. 113(2 Pt 1):402-7, 2009 Feb. |
Review/Other-Dx |
N/A |
To evaluate the accuracy of a fetal anatomy scan at the time of first-trimester screening. |
No results stated in abstract. |
4 |
| 51. Maiz N, Nicolaides KH. Ductus venosus in the first trimester: contribution to screening of chromosomal, cardiac defects and monochorionic twin complications. [Review]. Fetal Diagnosis & Therapy. 28(2):65-71, 2010. |
Review/Other-Dx |
N/A |
To review the contribution of ductus venosus flow in the prediction of chromosomal abnormalities in the first trimester. |
Ductus venosus flow provides an independent contribution in the prediction of chromosomal abnormalities when combined with NT and the maternal serum markers of PAPP-A and free beta-hCG, increasing the detection rate to 96% at a false-positive rate of 2.6%. Abnormal ductus venosus flow increases the risk of cardiac defects in fetuses with NT above the 95th centile, and it may increase the risk in fetuses with normal NT. |
4 |
| 52. Giles W, Bisits A, O'Callaghan S, Gill A, DAMP Study Group. The Doppler assessment in multiple pregnancy randomised controlled trial of ultrasound biometry versus umbilical artery Doppler ultrasound and biometry in twin pregnancy. BJOG: An International Journal of Obstetrics & Gynaecology. 110(6):593-7, 2003 Jun. |
Observational-Dx |
526 twin pregnancies |
To assess the addition value of umbilical artery Doppler ultrasound added to standard ultrasound biometry measurements in the management of twin pregnancies. |
Standard obstetric (mode of delivery, perinatal mortality, hypertension, antenatal admissions and gestation at delivery) and neonatal (5 minute Apgar scores <5, admissions to neonatal nursery and requirements for ventilation) outcomes and statistical analysis was on intention-to-treat. There were no significant differences between the two groups with respect to demography, antenatal, peripartum and neonatal outcomes. There was no difference in the perinatal mortality rate in the no Doppler group (n = 264), which was 11/1000 live births, and the Doppler group (n = 262), which was 9/1000 live births. There were three unexplained intrauterine deaths in the no Doppler group and none in the Doppler group (OR 0.14, 95% CI 0.01-1.31). Two intrauterine deaths in the Doppler group were due to cord prolapse in labour and a fetomaternal haemorrhage, both very unlikely to be influenced by Doppler surveillance. |
3 |
| 53. Matias A, Montenegro N, Blickstein I. Down syndrome screening in multiple pregnancies. [Review] [47 refs]. Obstetrics & Gynecology Clinics of North America. 32(1):81-96, ix, 2005 Mar. |
Review/Other-Dx |
N/A |
To review the risks of down syndrome screening in multiple pregnancies. |
No results stated in abstract. |
4 |
| 54. Prats P, Rodriguez I, Comas C, Puerto B. Systematic review of screening for trisomy 21 in twin pregnancies in first trimester combining nuchal translucency and biochemical markers: a meta-analysis. [Review]. Prenatal Diagnosis. 34(11):1077-83, 2014 Nov. |
Meta-analysis |
9 studies |
To establish the detection rate and false-positive rate of the combined test for the screening of trisomy 21 in twins. |
The combined test in twins had a pooled sensitivity of 0.893 [95% confidence interval (CI) 0.797-0.947] and a pooled specificity of 0.946 (95% CI 0.933-0.957). The performance of the test was good (summary receiver operating characteristic area under the curve: 0.817). In dichorionic twins, sensitivity and specificity were 0.862 (95% CI 0.728-0.936) and 0.952 (95% CI 0.942-0.96), respectively. In monochorionic twins, the sensitivity and specificity were 0.874% (95% CI 0.526-0.977) and 0.954% (95% CI 0.943-0.963), respectively. |
Inadequate |
| 55. Maymon R, Cuckle H, Svirsky R, et al. Nuchal translucency in twins according to mode of assisted conception and chorionicity. Ultrasound Obstet Gynecol. 44(1):38-43, 2014 Jul. |
Observational-Dx |
852 twin pregnancies |
To assess, in a large cohort from a single center, nuchal translucency (NT) in twins following various modes of assisted reproduction technology (ART) as compared with NT in spontaneously-conceived twins and to differentiate results with regard to chorionicity. |
NT values were statistically significantly higher in ART pregnancies as compared with spontaneously-conceived pregnancies (Wilcoxon rank-sum test, P?<?0.05) with medians of 1.073 and 1.038 MoM, respectively, but the proportion with values above the normal 95(th) percentile did not differ (chi-square test, P?=?0.89). Among the ART twins, NT values were significantly higher for those conceived using IVF methods (P?<?0.005), with a median of 1.082 MoM, compared with a median of 1.022 MoM using other methods. However, although a greater proportion exceeded the 95(th) centile (7.3% compared with 4.8%) this difference did not reach statistical significance (P?=?0.17). There were no differences in NT values according to chorionicity (Wilcoxon rank-sum test, P?= 0.75). The standard deviation of log10 NT was similar for all subgroups of twins. The correlation coefficient between fetuses in ART pregnancies was statistically significantly lower than that in spontaneously-conceived pregnancies (P?<?0.05) but no significant differences were found between types of ART or according to chorionicity. |
4 |
| 56. Gonce A, Borrell A, Meler E, et al. Prevalence and perinatal outcome of dichorionic and monochorionic twins with nuchal translucency above the 99(th) percentile and normal karyotype. Ultrasound in Obstetrics & Gynecology. 35(1):14-8, 2010 Jan. |
Observational-Dx |
206 twin pregnancies |
To evaluate the prevalence of and perinatal outcome associated with increased nuchal translucency thickness (NT) > 99(th) percentile in dichorionic and monochorionic twins with normal karyotype. |
There were 10 (4.95%) pregnancies in which one of the fetuses had NT > 99th percentile and normal karyotype, including five fetuses (1.5%) in dichorionic and five (6.25%) in monochorionic pregnancies. During the same period the prevalence of NT > 99th percentile and normal karyotype in singleton pregnancies studied in our center was 2.6%. Among the 10 twins affected, six (60%) were diagnosed with structural abnormalities (three dichorionic and three monochorionic), and two intrauterine fetal demises occurred (one dichorionic and one monochorionic). Thus, the perinatal outcome was normal in only two of the pregnancies, one dichorionic and one monochorionic. |
3 |
| 57. . Practice Bulletin No. 162 Summary: Prenatal Diagnostic Testing for Genetic Disorders. Obstetrics & Gynecology. 127(5):976-8, 2016 May. |
Review/Other-Dx |
N/A |
To review the current status of prenatal genetic diagnostic testing and the evidence supporting its use. |
No results stated in abstract. |
4 |
| 58. Cleary-Goldman J, Rebarber A, Krantz D, Hallahan T, Saltzman D. First-trimester screening with nasal bone in twins. American Journal of Obstetrics & Gynecology. 199(3):283.e1-3, 2008 Sep. |
Observational-Dx |
2,094 twin pregnancies |
To evaluate the Down syndrome detection rate at a 5% screen positive rate in first-trimester screening for twins. |
Two thousand ninety-four twin pregnancies (4188 fetuses) met the inclusion criteria. The addition of nasal bone to nuchal translucency, pregnancy-associated plasma protein-A, and free beta-hCG increased the Down syndrome detection rate from 79-89% at a 5% screen-positive rate. |
4 |
| 59. Simpson LL. Ultrasound in twins: dichorionic and monochorionic. Semin Perinatol. 2013;37(5):348-358. |
Review/Other-Dx |
N/A |
To assess the evidence that supports the use of ultrasound in twin pregnancies. |
The reasons for ultrasound in twins include pregnancy dating, determination of chorionicity, nuchal translucency assessment, anatomical survey, placental evaluation, cervical length assessment, routine fetal growth, and serial surveillance of pregnancies complicated by anomalies, cervical shortening, fetal growth disturbances, and amniotic fluid abnormalities. Twins with monochorionic placentation require heightened scrutiny for monoamnionicity, conjoined twins, twin reversed arterial perfusion (TRAP) syndrome, twin-twin transfusion syndrome, unequal placental sharing with discordant twin growth or selective intrauterine fetal growth restriction (IUGR), twin anemia-polycythemia sequence (TAPS), and single fetal demise |
4 |
| 60. Committee on Practice Bulletins-Obstetrics, Society for Maternal-Fetal Medicine. Practice Bulletin No. 169: Multifetal Gestations: Twin, Triplet, and Higher-Order Multifetal Pregnancies. [Review]. Obstet Gynecol. 128(4):e131-46, 2016 10. |
Review/Other-Dx |
N/A |
To aid practitioners in making decisions about the gestational age at which to consider antenatal corticosteroids and rescue-course timing. |
No results stated in abstract. |
4 |
| 61. Maiz N, Staboulidou I, Leal AM, Minekawa R, Nicolaides KH. Ductus venosus Doppler at 11 to 13 weeks of gestation in the prediction of outcome in twin pregnancies. Obstetrics & Gynecology. 113(4):860-5, 2009 Apr. |
Observational-Dx |
695 twin pregnancies |
To examine the independent contribution of abnormal flow in the ductus venosus at 11 to 13 weeks of gestation in the prediction of adverse pregnancy outcome in relation to chorionicity. |
The prevalence of reversed a-wave in at least one of the fetuses was significantly higher in monochorionic than in dichorionic pregnancies (18.4% compared with 8.3%, P<.001) and in pregnancies complicated by miscarriage (28.6%, P=.005), fetal aneuploidy (70.0%, P<.001), and twin-twin transfusion syndrome (38.5%, P<.001) compared with the pregnancies with two healthy live births (7.7%). Pregnancy outcome was normal in 33 of the 43 (76.7%) dichorionic and in 14 of the 33 (42.4%) monochorionic twins with reversed a-wave in at least one of the fetuses. |
4 |
| 62. Matias A, Montenegro N, Loureiro T, et al. Screening for twin-twin transfusion syndrome at 11-14 weeks of pregnancy: the key role of ductus venosus blood flow assessment. Ultrasound in Obstetrics & Gynecology. 35(2):142-8, 2010 Feb. |
Observational-Dx |
99 twin pregnancies |
To clarify the role of ductus venosus (DV) blood flow assessment in identifying those monochorionic twins more prone to develop twin-twin transfusion syndrome (TTTS). |
Discrepant values of CRL were not predictive of TTTS development. Intertwin NT discrepancy >or= 0.6 mm had a sensitivity of 50.0% and a specificity of 92.0%. The presence of at least one abnormal blood flow waveform in the DV was associated with a relative risk for developing TTTS of 11.86 (95% CI, 3.05-57.45), with a sensitivity of 75.0% and a specificity of 92.0%. The combination of abnormal DV blood flow with NT discrepancy >or= 0.6 mm yielded a relative risk for the development of TTTS of 21 (95% CI, 5.47-98.33). |
4 |
| 63. Lopriore E, Bokenkamp R, Rijlaarsdam M, Sueters M, Vandenbussche FP, Walther FJ. Congenital heart disease in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. Congenit Heart Dis. 2007;2(1):38-43. |
Review/Other-Tx |
101 twin pairs |
To determine the incidence of congenital heart disease (CHD) and right ventricular outflow tract obstruction (RVOTO) in twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery and evaluate the role of increased afterload by determining the difference in blood pressure and endothelin-1 at birth between donor and recipient twins. |
The incidence of CHD in the TTTS group and non-TTTS group was 5.4% (4/74) and 2.3% (2/87) (P = .42), respectively. RVOTO was diagnosed in 1 recipient twin delivered at our center and 2 recipient twins delivered elsewhere. The incidence of RVOTO in recipients was 4% (3/75). Mean systolic blood pressure at birth was similar in donor and recipient twins, respectively, 53 mm Hg vs. 56 mm Hg (P = .42). Mean endothelin-1 level at birth was also similar between donors and recipients, respectively, 14.3 ng/L and 13.2 ng/L (P = .64). |
4 |
| 64. Society for Maternal-Fetal Medicine, Simpson LL. Twin-twin transfusion syndrome.[Erratum appears in Am J Obstet Gynecol. 2013 May;208(5):392]. American Journal of Obstetrics & Gynecology. 208(1):3-18, 2013 Jan. |
Review/Other-Dx |
N/A |
To review the natural history, pathophysiology, diagnosis, and treatment options for twin-twin transfusion syndrome (TTTS). |
TTTS is a serious condition that can complicate 8-10% of twin pregnancies with monochorionic diamniotic (MCDA) placentation. The diagnosis of TTTS requires 2 criteria: (1) the presence of a MCDA pregnancy; and (2) the presence of oligohydramnios (defined as a maximal vertical pocket of <2 cm) in one sac, and of polyhydramnios (a maximal vertical pocket of >8 cm) in the other sac. The Quintero staging system appears to be a useful tool for describing the severity of TTTS in a standardized fashion. Serial sonographic evaluation should be considered for all twins with MCDA placentation, usually beginning at around 16 weeks and continuing about every 2 weeks until delivery. Screening for congenital heart disease is warranted in all monochorionic twins, in particular those complicated by TTTS. Extensive counseling should be provided to patients with pregnancies complicated by TTTS including natural history of the disease, as well as management options and their risks and benefits. The natural history of stage I TTTS is that more than three-fourths of cases remain stable or regress without invasive intervention, with perinatal survival of about 86%. Therefore, many patients with stage I TTTS may often be managed expectantly. |
4 |
| 65. Shah AD, Border WL, Crombleholme TM, Michelfelder EC. Initial fetal cardiovascular profile score predicts recipient twin outcome in twin-twin transfusion syndrome. Journal of the American Society of Echocardiography. 21(10):1105-8, 2008 Oct. |
Observational-Dx |
62 pregnancies |
To assess the relationship between cardiomyopathy and recipient twin (RT) outcome in twin-twin transfusion syndrome (TTTS). |
Overall neonatal survival for all fetuses was 61% (76 of 124). RT survival was 58% (36 of 62). Grouped by CVPS, RT survival was greater (50%) for those with CVPS > or = 9 and even higher (74%) for CVPS of 10. Among the components of the CVPS, atrioventricular valve regurgitation was associated with negative RT outcome. Other factors at presentation were not predictive of RT outcome. |
3 |
| 66. Sebire NJ, Souka A, Skentou H, Geerts L, Nicolaides KH. Early prediction of severe twin-to-twin transfusion syndrome. Hum Reprod. 2000;15(9):2008-2010. |
Observational-Dx |
303 pregnancies |
To explore the possible association of increased fetal nuchal translucency thickness (NT) in the early prediction of severe twin-to-twin transfusion syndrome (TTS). |
Of 303 pregnancies, there were 16 in which at least one fetus was structurally or chromosomally abnormal and in the remaining 287 ongoing pregnancies there were 43 (15%) which developed severe TTS. The median fetal NT was 1.0 multiples of the median (MOM) and NT was >95th centile in 47 (8.2%) fetuses and in at least one fetus in 37 (12.9%) pregnancies. The prevalence of increased NT in the pregnancies that developed TTS [17.4% (n = 15) of fetuses and 28% (n = 12) of pregnancies] was significantly higher than in the non-TTS group [6.6% (n = 32) and 10.2% (n = 25) respectively; Z: = -3.4, P: < 0.001 and Z: = 3.2, P: < 0.001 respectively], likelihood ratio of increased fetal NT for prediction of TTS = 3.5 [95% confidence interval (CI) 1.9-6.2]. In 153 of the pregnancies, an ultrasound examination was also performed at 15-17 weeks gestation and intertwin membrane folding was seen in 49 (32%) cases; 21 of these (43%) subsequently developed TTS compared to two (1.9%) of the 104 pregnancies without membrane folding (Z: = 6.6, P: < 0.001), likelihood ratio of membrane folding for prediction of TTS = 4.2 (95% CI 3.0-6.0). |
3 |
| 67. Lewi L, Lewi P, Diemert A, et al. The role of ultrasound examination in the first trimester and at 16 weeks' gestation to predict fetal complications in monochorionic diamniotic twin pregnancies. American Journal of Obstetrics & Gynecology. 199(5):493.e1-7, 2008 Nov. |
Observational-Dx |
202 twin pregnancies |
To determine the value of ultrasound examination in the first trimester and at 16 weeks to predict fetal complications in monochorionic diamniotic (MCDA) twin pregnancies, defined as the occurrence of either twin-to-twin transfusion syndrome, severe discordant growth, or intrauterine death. |
Significant predictors in the first trimester were the difference in crown-rump length (odds ratio [OR], 11) and discordant amniotic fluid (OR, 10). At 16 weeks, significant predictors were the difference in abdominal circumference (OR, 29), discordant amniotic fluid (OR, 7), and discordant cord insertions (OR, 3). Risk assessment in the first trimester and at 16 weeks detected 29% and 48% of cases with a complicated fetal outcome, respectively, with a false-positive rate of 3% and 6%, respectively. Combined first-trimester and 16 week assessment identified 58% of fetal complications, with a false-positive rate of 8%. |
3 |
| 68. Stagnati V, Zanardini C, Fichera A, et al. Early prediction of twin-to-twin transfusion syndrome: systematic review and meta-analysis. [Review]. Ultrasound Obstet Gynecol. 49(5):573-582, 2017 May. |
Meta-analysis |
13 Studies |
To assess the role of first- and early second-trimester markers in the prediction of twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies. |
The electronic search identified 152 records, of which 23 were assessed in full for eligibility. We identified 13 eligible studies that reported the predictive accuracy of ultrasound parameters, measured before 16?weeks, for the development of TTTS, including a total of 1991 pregnancies, of which 323 developed TTTS. An increased risk of TTTS was associated with: intertwin NT discrepancy (positive likelihood ratio (LR+), 1.92 (95% CI, 1.25-2.96); negative likelihood ratio (LR-), 0.65 (95% CI, 0.50-0.84)); NT>95th percentile (LR+, 2.63 (95% CI, 1.51-4.58); LR-, 0.85 (95% CI, 0.75-0.96)); CRL discrepancy>10% (LR+, 1.80 (95% CI, 1.05-3.07); LR-, 0.92 (95% CI, 0.81-1.05)); abnormal DV flow (LR+, 4.77 (95% CI, 1.33-17.04; LR-, 0.49 (95% CI, 0.17-1.41)). The highest sensitivities were observed for intertwin NT discrepancy (52.8% (95% CI, 43.8-61.7%)) and abnormal DV flow (50.0% (95% CI, 33.4-66.6%)). |
Good |
| 69. Kagan KO, Gazzoni A, Sepulveda-Gonzalez G, Sotiriadis A, Nicolaides KH. Discordance in nuchal translucency thickness in the prediction of severe twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2007;29:527-32. |
Observational-Dx |
512 monochorionic twin pregnancies |
To examine in monochorionic pregnancies the possible value of intertwin discordance in nuchal translucency (NT) thickness in the prediction of early fetal death or severe twin-twin transfusion syndrome (TTTS). |
In 412 (80.5%) pregnancies there was a normal outcome, in 58 (11.3%) there was severe TTTS requiring endoscopic laser surgery at 18-24 weeks, in 19 (3.7%) there was death of one or both fetuses at 13-18 weeks and in 23 (4.5%) there was fetal death at 21-38 weeks. In the four outcome groups the median discordance in NT was 11%, 22%, 35% and 7%, respectively. Significant prediction of early fetal death and severe TTTS was provided by the discordance in fetal NT, which was not significantly improved by including the discordance in crown-rump length. If the discordance in NT was 20% or more, the false positive rate was 20%, the detection rate of early fetal death was 63% and the detection rate of severe TTTS was 52%. |
3 |
| 70. Glanc P, Nyberg DA, Khati NJ, et al. ACR Appropriateness Criteria® Multiple Gestations. J Am Coll Radiol 2017;14:S476-S89. |
Review/Other-Dx |
N/A |
Evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for ACR Appropriateness Criteria Multiple Gestations. |
No results stated in abstract. |
4 |
| 71. Mackie FL, Hall MJ, Morris RK, Kilby MD. Early prognostic factors of outcomes in monochorionic twin pregnancy: systematic review and meta-analysis. Am J Obstet Gynecol. 219(5):436-446, 2018 11. |
Meta-analysis |
48 Studies |
To assess ability of first-trimester pregnancy-related factors (ultrasound measurements, maternal characteristics, biomarkers) to predict complications in monochorionic twin pregnancies. |
In all, 48 studies were eligible for inclusion. Twenty meta-analyses could be performed. A moderate association was demonstrated in 3 meta-analyses, between: nuchal translucency >95th centile in one/both fetuses and twin-twin transfusion syndrome (odds ratio, 2.29 [95% confidence interval, 1.05–4.96], I2 = 6.6%, 4 studies, 615 pregnancies); crown-rump length discordance =10% and twin-twin transfusion syndrome (odds ratio, 2.43 [95% confidence interval, 1.13–5.21], I2 = 14.1%, 3 studies, 708 pregnancies); and maternal ethnicity and twin-twin transfusion syndrome (odds ratio, 2.12 [95% confidence interval, 1.17–3.83], I2 = 0.0%, 5 studies, 467 pregnancies), but none demonstrated a prognostic ability for any outcome under investigation |
Good |
| 72. American College of Radiology. ACR–SPR Practice Parameter for the Safe and Optimal Performance of Fetal Magnetic Resonance Imaging (MRI). Available at: https://www.acr.org/-/media/ACR/Files/Practice-Parameters/mr-fetal.pdf |
Review/Other-Dx |
N/A |
To promote safe and optimal performance of fetal magnetic resonance imaging (MRI). |
No abstract available. |
4 |
| 73. American College of Radiology. ACR-SPR Practice Parameter for Imaging Pregnant or Potentially Pregnant Patients with Ionizing Radiation. Available at: http://www.acr.org/~/media/ACR/Documents/PGTS/guidelines/Pregnant_Patients.pdf. |
Review/Other-Dx |
N/A |
To assist practitioners in providing appropriate radiologic care for pregnant or potentially pregnant adolescents and women by describing specific training, skills and techniques. |
No abstract available. |
4 |
| 74. American College of Radiology. Manual on Contrast Media. Available at: https://www.acr.org/Clinical-Resources/Contrast-Manual. |
Review/Other-Dx |
N/A |
To assist radiologists in recognizing and managing risks associated with the use of contrast media. |
No abstract available. |
4 |
| 75. Expert Panel on MR Safety, Kanal E, Barkovich AJ, et al. ACR guidance document on MR safe practices: 2013. J Magn Reson Imaging. 37(3):501-30, 2013 Mar. |
Review/Other-Dx |
N/A |
To help guide MR practitioners regarding MR safety issues and provide a basis for them to develop and implement their own MR policies and practices. |
No abstract available. |
4 |
| 76. American College of Radiology. ACR Appropriateness Criteria® Radiation Dose Assessment Introduction. Available at: https://www.acr.org/-/media/ACR/Files/Appropriateness-Criteria/RadiationDoseAssessmentIntro.pdf. |
Review/Other-Dx |
N/A |
To provide evidence-based guidelines on exposure of patients to ionizing radiation. |
No abstract available. |
4 |
