Table 9.7First-trimester screening for Down’s syndrome using nasal bone evaluation – additional studies

StudyWeingertner et al. (2006)779Ramos-Corp et al. (2006)774Orlandi et al. (2005)780Kozlowski et al. (2006)775Zoppi et al. (2003)776Viora et al. (2003)777
Type of studyProspective cohortProspective cohortprospective cohortProspective cohortProspective cohortProspective cohort
Year of publication200620062005200620032003
Period2002–20042003–2004Not specified2002–20042001–20022001–2002
Setting1 reference centre, France1 fetal medicine unit, Spain1 fetal medicine unit, Italy1 prenatal centre, Germany1 prenatal diagnosis unit, Italy1 prenatal diagnosis unit, Italy
Study populationBoth unselected and selected (single reference centre)Selected (single centre, only 45% participated)Selected (details not specified)Selected (single centre, 46% > 35 years)Selected (single centre)Selected (referred women)
ExclusionsAdequately describedNot describedNot describedAdequately describedAdequately describedAdequately described
Test conductedNT with or without NBNBCombined test with or without NBCombined test with or without NBNBNB
Monitoring of test qualityAdequateAdequateAdequateAdequateAdequateNot described
Validated reference standardYes (prenatal karyotype, pregnancy records)Yes (karyotype, pregnancy records)Yes (prenatal karyotype, pregnancy records)Yes (prenatal karyotype, pregnancy records)Incomplete info. for 35% of study populationYes (prenatal karyotype, pregnancy records)
Sample size (% of study population)2044 (91.5%); Selected – 33%; Unselected – 67%1800 (45%)2411 (% not specified)2973 (92.4%)3503 (64.6%)1906 (% not specified)
Maternal ageMedian 32 years, range 16–47 yearsMean 30.09 years (SD 5.37 years), range 15–46 yearsMean 30.5 years (SD 4.115 years)Median 34 years, range 14–46 yearsMedian 32 years, range 15–48 yearsMedian 32.2 years, range 18–47 years
Successful NB image (% of sample size)1260 (61.6%)1682 (93.4%)2411 (100%)3194/3218 (99.3% of study population)5525/5532 (99.8% of study population)1752 (91.9% of sample size)
Number of cases (prevalence)DS: 30 (1.47%); T 18: 14 (0.68%); others: 35 (1.71%)DS: 7 (0.39%); others: 3 (0.17%)DS: 15 (0.62%)DS: 18 (0.60%); others: 22 (0.74%)DS: 27 (0.77%); others: 13 (0.37%)DS: 10 (0.57%); others: 9 (0.51%)
  1. Observed performance for DS (risk 1: 250 (NT), ≤ 0.60 MoM (NB)) (95% CI):
    NT: ST 88% (86–90%); FPR 23% (21–26%)
    NT + NB: ST 100%; FPR 5% (3–6%)
  2. Performance of only NB:
    ST 32%; FPR 10%; LR+ 4.4 (2.0–9.4)
Observed performance of NB for DS (95% CI):
ST 33.3% (4.3–77.7%); FPR 1.13%; SP 98.9% (98.5–99.4%); PPV 9.5% (1.2–30.4%); NPV 99.7% (99.4–99.9%)
  1. Observed performance of NB for DS (95% CI):
    ST 53.3% (26.6–78.7%); SP 99.5% (99.3–99.8%); PPV 47.1% (23.3–70.8%); LR+ 142 (63–318); LR− 0.47 (0.27–0.80)
  2. Estimated performance (risk 1: 250):
    Combined: DR 87%; FPR 4.3%
    Combined + NB: DR 90%; FPR:2.5%
Estimated performance for DS (risk cut-off 1: 300):
Combined: DR 94.4%; FPR 5.5%
Combined + NB: DR 77.8%; FPR 2.8%
Observed performance of NB for DS:
DR 70%; FPR missing value
Observed performance of NB for DS:
DR 60%
FPR: 1.4
CommentsThe population was low-risk and mainly unselected (67%) but not representative. Feasibility of NB measurement was low (62%), but its inclusion improved the screening performance for DS detection.The population was low-risk but not representative (only 45% opted for the test).Details about study population (low-risk or high-risk) and exclusions were not specified. The estimated performance of adding NB into the combined test was evaluated from modelling using data from the author’s previous studies.The study population was high risk. This study compared the two algorithms of Fetal Medicine Foundation – Old algorithm using combined test vs New algorithm which allows inclusion of NB and some refinements in distribution of first-trimester parameters.The population was low risk/unselected but follow-up was not available for 35% (1922/5532) of pregnancies. Moreover, the reported data were inadequate for calculating FPR and other screening parameters.The population was high risk referred to the centre for chorionic villus sampling, amniocentesis or NT measurement. The results are given for absent NB. If hypoplastic NB (< 10th centile) is added, the DR becomes 80% with FPR 3.7%.

DR = detection rate; DS = Down’s syndrome; FPR = false positive rate; MoM = multiples of the median; NB = nasal bone; NPV = negative predictive value; NT = nuchal translucency; PPV = positive predictive value; SD = standard deviation; SP = specificity; ST = sensitivity; T 18 = trisomy 18.

From: 9, Screening for fetal anomalies

Cover of Antenatal Care
Antenatal Care: Routine Care for the Healthy Pregnant Woman.
NICE Clinical Guidelines, No. 62.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2008 Mar.
Copyright © 2008, National Collaborating Centre for Women’s and Children’s Health.

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