General Obstetrics and Gynecology: Obstetrics
Nasal bone in first-trimester screening for trisomy 21

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Objective

This study was undertaken to investigate the impact of incorporating assessment of the nasal bone into first-trimester combined screening by fetal nuchal translucency (NT) thickness and maternal serum biochemistry.

Study design

In this prospective combined screening study for trisomy 21, the fetal nasal bone was also examined and classified as present or absent. A multivariate approach was used to calculate patient-specific risks for trisomy 21 and the detection rate (DR) and false-positive rate (FPR) were estimated. We examined 2 screening strategies; first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free ß-hCG and PAPP-A, followed by second-stage assessment of nasal bone only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first-stage.

Results

The nasal bone was absent in 113 (0.6%) of the 20,165 chromosomally or phenotypically normal fetuses and in 87 (62.1%) of the 140 fetuses with trisomy 21. With combined first-trimester NT and serum screening, the DR of 90% was achieved at a FPR of 5%. Inclusion of the nasal bone, either in all cases or in about 10% of the total in the 2-stage approach, halved the FPR to 2.5%.

Conclusion

Inclusion of the nasal bone in first-trimester combined screening for trisomy 21 achieves a DR of 90% for a FPR of 2.5%.

Section snippets

Methods

The fetal nasal bone was examined and classified as present or absent in women attending the Fetal Medicine Centre, London (between October 2001 and October 2004) for screening for trisomy 21 by a combination of fetal NT and maternal serum free ß-hCG and PAPP-A at 11 to 13+6 weeks.16, 21, 22 The study was approved by the IRB of King's College Hospital and informed written consent was obtained from all women.

Serum free ß-hCG and PAPP-A were measured using the Kryptor analyser (Brahms AG, Berlin,

Statistical analysis

Patient-specific risks for trisomy 21 were calculated by a multivariate approach. Essentially, the maternal age related risk was multiplied with each likelihood ratio (LR) derived from the fetal NT and maternal weight-adjusted serum free β-hCG and PAPP-A. The maximum and minimum LR allowed were 0.185 and 509 for NT, 0.014 and 62 for each free β-hCG and PAPP-A and 0.05 and 1000 for the combined sonographic and biochemical markers. In addition, we used the positive and negative LRs for trisomy 21

Results

Screening for trisomy 21 was carried out in 21,074 singleton pregnancies with live fetuses at 11 to 13+6 (median 12) weeks. Fetal NT and maternal serum free ß-hCG and PAPP-A were successfully measured in all cases. Pregnancy outcome, including karyotype results or the birth of a phenotypically normal infant, was obtained from 20,418 (96.9%) cases. Excluded from further analysis were 656 cases, because the fetal karyotype was not known and they resulted in spontaneous fetal loss (n = 185) or

Comment

The findings of this prospective study confirm the high association between absent nasal bone at the 11 to 13+6 weeks scan and trisomy 21, as well as other major chromosomal defects. Furthermore, the data demonstrate that examination of the nasal bone can be combined with maternal serum biochemistry and fetal NT thickness in first-trimester screening for trisomy 21 to achieve a detection rate of 90%, with a halving in the FPR from about 5% to 2.5%.

The main contributors to the finding of absent

References (27)

  • S. Cicero et al.

    Likelihood ratio for Trisomy 21 in fetuses with absent nasal bone at the 11-14 weeks scan

    Ultrasound Obstet Gynecol

    (2004)
  • F. Orlandi et al.

    Measurement of nasal bone length at 11-14 weeks of pregnancy and its potential role in Down syndrome risk assessment

    Ultrasound Obstet Gynecol

    (2003)
  • L. Otano et al.

    Association between first trimester absence of fetal nasal bone on ultrasound and Down's syndrome

    Prenat Diagn

    (2002)

    • Cited by (0)

    Supported by a grant from the Fetal Medicine Foundation (Charity No: 1037116) and is part of the PhD Thesis of Dr S Cicero, University of Tor Vergata, Rome, Italy.

    Reprints not available from the authors.

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