- Email: [email protected]
Absence of nasal bone and detection of trisomy 21
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
Absence of nasal bone and detection of trisomy 21 Sir—Simona Cicero and colleagues (Nov 17, p 1665)1 describe how they estimated the potential effect of nasalbone screening on the detection of trisomy 21. They state “In each case, the estimated risk for trisomy 21 by maternal age and fetal nuchal translucency thickness was multiplied by the appropriate likelihood ratio for the presence or absence of the nasal bone”. Cuckle2 describes the correct method. In Bayesian terms it is the prior odds that are multiplied by the likelihood ratio to calculate the posterior odds. The posterior odds are then converted to reach the posterior risk. There is great confusion about whether the prior odds or prior risk should be used.3,4 Although there is little difference in the results at the risk levels normally dealt with, the effect can be critical if there is a precise cut-off risk for action. It will be helpful if the correct method is clarified. David J R Hutchon Memorial Hospital, Darlington DL3 6HX, UK (e-mail: [email protected]) 1
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Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet 2001; 358: 1665–67. Cuckle H. Calculating correct Down’s syndrome risks. Br J Obstet Gynaecol 1999; 106: 371–72. Hutchon DJR. Trisomy 21: 91% detection rate using second-trimester ultrasound markers. Ultrasound Obstet Gynecol 2001; 18: 83. Devore GR. Trisomy 21: 91% detection rate using second-trimester ultrasound markers. Ultrasound Obstet Gynecol 2001; 18: 83–84.
Sir—We agree with Simona Cicero and colleagues1 that examination of the fetal nasal bone is likely to improve screening for trisomy 21, and with Howard Cuckle,2 in his Nov 17 Commentary, that screening should now move from the second to the first trimester of pregnancy. From September 2001, to November 2001, we included examination of the fetal nose in our routine screening for trisomy by measurement of fetal nuchal translucency at 11–14 weeks.3 The nose was successfully examined in all 880 fetuses that were screened. The nasal bone was present in 875 and absent in five (0·5%). For 593 fetuses, the
maternal age was younger than 35 years and the nasal bone was absent in three. In 20 of the 593 fetuses, nuchal translucency was increased and the estimated risk of trisomy 21 was more than one per 250; in 18 of these 20 cases, including two with absent nasal bone, chorionic villous sampling was done and the fetal karyotype was normal in all cases. For 287 fetuses the maternal age was 35 years or older. Although in 212 of these 287 cases fetal nuchal translucency was normal and the estimated risk of trisomy 21 was less than one per 250, 249 elected to have fetal karyotyping because of anxiety related to older maternal age.4 There were four chromosomal abnormalities, including three with trisomy 21 and one with trisomy 18. In the three cases of trisomy 21, one had increased nuchal translucency and absent nasal bone, one had increased nuchal translucency and present nasal bone, and one had normal nuchal translucency and absent nasal bone. In the trisomy 18 fetus, nuchal translucency was increased and the nasal bone was present. Our preliminary findings are compatible with those of Cicero and colleagues in that examination of the fetal nose can be easily incorporated in routine screening by nuchal translucency and the nose can be examined in all cases attempted; the incidence of absent nasal bone is about 0·5%; and the sensitivity of screening for trisomy 21 by nuchal translucency is likely to be improved by examination of the nasal bone, since in some cases the nasal bone may be absent and the nuchal translucency normal, whereas in others the nasal bone may be present and the nuchal translucency increased. However, as for the nuchal translucency scan, sonographers undertaking risk assessment by examination of the fetal nasal bone must receive appropriate training and certification of their competence by the Fetal Medicine Foundation.5 *Giovanni Monni, Maria Angelica Zoppi, Rosa Maria Ibba Department of Obstetrics and Gynaecology, Prenatal and Preimplantation Genetic Diagnosis, Fetal Therapy, Ospedale Microcitemico, Via Jenner, 09121 Cagliari, Italy (e-mail: [email protected])
THE LANCET • Vol 359 • April 13, 2002 • www.thelancet.com
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Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet 2001; 358: 1665–67. Cuckle H. Time for total shift to firsttrimester screening for Down’s syndrome. Lancet 2001; 358: 1658–59. Zoppi MA, Ibba RM, Floris M, Monni G. Fetal nuchal translucency screening in 12495 pregnancies in Sardinia. Ultrasound Obstet Gynecol 2001; 18: 649–510. Zoppi MA, Ibba RM, Putzolu M, Floris M, Monni G. Nuchal translucency and the acceptance of prenatal chromosomal diagnosis in women aged 35 and older. Obstet Gynecol 2001; 97: 916–20. Monni G, Ibba RM, Zoppi MA. Antenatal screening for Down’s syndrome. Lancet 1997; 350: 1631.
Sir—The findings of Simona Cicero and colleagues1 are in agreement with the observed clinical features of Down’s syndrome children, and has been corroborated by radiographic necropsy studies of fetuses with trisomy 21. In a radiographic study on the pattern of malformations in the axial skeleton of aborted fetuses with trisomy 21, Keeling and colleagues2 reported absence or hypoplasia of the nasal bones in 19 of 31 fetuses. A second analysis of the material showed that absent nasal bones were noted in eight fetuses with gestational age 14–25 weeks (mean gestational age 19 weeks; I Kjaer, personal communication). In another study, absent ossification of the nasal bones was seen in a quarter of trisomy 21 fetuses, irrespective of gestational age.3 The demonstration of the absence of the nasal bones adds to the “minor” phenotypic markers that can be seen on ultrasonography and suggest Down’s syndrome. Absence of the nasal bones may not, however, be indicative only of Down’s syndrome or other aneuploidies, but also of fragile X syndrome. We have published the results of an investigation of six fetuses with fragile X full mutation with gestational age 12–14 weeks.4 In five fetuses the nasal bone was absent on radiographs. A DNA analysis done on cells from a chorionic villus sample or an amniocentesis can exclude or verify this possibility, although it will add to
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For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
Absence of nasal bone and detection of trisomy 21 Sir—Simona Cicero and colleagues (Nov 17, p 1665)1 describe how they estimated the potential effect of nasalbone screening on the detection of trisomy 21. They state “In each case, the estimated risk for trisomy 21 by maternal age and fetal nuchal translucency thickness was multiplied by the appropriate likelihood ratio for the presence or absence of the nasal bone”. Cuckle2 describes the correct method. In Bayesian terms it is the prior odds that are multiplied by the likelihood ratio to calculate the posterior odds. The posterior odds are then converted to reach the posterior risk. There is great confusion about whether the prior odds or prior risk should be used.3,4 Although there is little difference in the results at the risk levels normally dealt with, the effect can be critical if there is a precise cut-off risk for action. It will be helpful if the correct method is clarified. David J R Hutchon Memorial Hospital, Darlington DL3 6HX, UK (e-mail: [email protected]) 1
2
3
4
Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet 2001; 358: 1665–67. Cuckle H. Calculating correct Down’s syndrome risks. Br J Obstet Gynaecol 1999; 106: 371–72. Hutchon DJR. Trisomy 21: 91% detection rate using second-trimester ultrasound markers. Ultrasound Obstet Gynecol 2001; 18: 83. Devore GR. Trisomy 21: 91% detection rate using second-trimester ultrasound markers. Ultrasound Obstet Gynecol 2001; 18: 83–84.
Sir—We agree with Simona Cicero and colleagues1 that examination of the fetal nasal bone is likely to improve screening for trisomy 21, and with Howard Cuckle,2 in his Nov 17 Commentary, that screening should now move from the second to the first trimester of pregnancy. From September 2001, to November 2001, we included examination of the fetal nose in our routine screening for trisomy by measurement of fetal nuchal translucency at 11–14 weeks.3 The nose was successfully examined in all 880 fetuses that were screened. The nasal bone was present in 875 and absent in five (0·5%). For 593 fetuses, the
maternal age was younger than 35 years and the nasal bone was absent in three. In 20 of the 593 fetuses, nuchal translucency was increased and the estimated risk of trisomy 21 was more than one per 250; in 18 of these 20 cases, including two with absent nasal bone, chorionic villous sampling was done and the fetal karyotype was normal in all cases. For 287 fetuses the maternal age was 35 years or older. Although in 212 of these 287 cases fetal nuchal translucency was normal and the estimated risk of trisomy 21 was less than one per 250, 249 elected to have fetal karyotyping because of anxiety related to older maternal age.4 There were four chromosomal abnormalities, including three with trisomy 21 and one with trisomy 18. In the three cases of trisomy 21, one had increased nuchal translucency and absent nasal bone, one had increased nuchal translucency and present nasal bone, and one had normal nuchal translucency and absent nasal bone. In the trisomy 18 fetus, nuchal translucency was increased and the nasal bone was present. Our preliminary findings are compatible with those of Cicero and colleagues in that examination of the fetal nose can be easily incorporated in routine screening by nuchal translucency and the nose can be examined in all cases attempted; the incidence of absent nasal bone is about 0·5%; and the sensitivity of screening for trisomy 21 by nuchal translucency is likely to be improved by examination of the nasal bone, since in some cases the nasal bone may be absent and the nuchal translucency normal, whereas in others the nasal bone may be present and the nuchal translucency increased. However, as for the nuchal translucency scan, sonographers undertaking risk assessment by examination of the fetal nasal bone must receive appropriate training and certification of their competence by the Fetal Medicine Foundation.5 *Giovanni Monni, Maria Angelica Zoppi, Rosa Maria Ibba Department of Obstetrics and Gynaecology, Prenatal and Preimplantation Genetic Diagnosis, Fetal Therapy, Ospedale Microcitemico, Via Jenner, 09121 Cagliari, Italy (e-mail: [email protected])
THE LANCET • Vol 359 • April 13, 2002 • www.thelancet.com
1
2
3
4
5
Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absence of nasal bone in fetuses with trisomy 21 at 11–14 weeks of gestation: an observational study. Lancet 2001; 358: 1665–67. Cuckle H. Time for total shift to firsttrimester screening for Down’s syndrome. Lancet 2001; 358: 1658–59. Zoppi MA, Ibba RM, Floris M, Monni G. Fetal nuchal translucency screening in 12495 pregnancies in Sardinia. Ultrasound Obstet Gynecol 2001; 18: 649–510. Zoppi MA, Ibba RM, Putzolu M, Floris M, Monni G. Nuchal translucency and the acceptance of prenatal chromosomal diagnosis in women aged 35 and older. Obstet Gynecol 2001; 97: 916–20. Monni G, Ibba RM, Zoppi MA. Antenatal screening for Down’s syndrome. Lancet 1997; 350: 1631.
Sir—The findings of Simona Cicero and colleagues1 are in agreement with the observed clinical features of Down’s syndrome children, and has been corroborated by radiographic necropsy studies of fetuses with trisomy 21. In a radiographic study on the pattern of malformations in the axial skeleton of aborted fetuses with trisomy 21, Keeling and colleagues2 reported absence or hypoplasia of the nasal bones in 19 of 31 fetuses. A second analysis of the material showed that absent nasal bones were noted in eight fetuses with gestational age 14–25 weeks (mean gestational age 19 weeks; I Kjaer, personal communication). In another study, absent ossification of the nasal bones was seen in a quarter of trisomy 21 fetuses, irrespective of gestational age.3 The demonstration of the absence of the nasal bones adds to the “minor” phenotypic markers that can be seen on ultrasonography and suggest Down’s syndrome. Absence of the nasal bones may not, however, be indicative only of Down’s syndrome or other aneuploidies, but also of fragile X syndrome. We have published the results of an investigation of six fetuses with fragile X full mutation with gestational age 12–14 weeks.4 In five fetuses the nasal bone was absent on radiographs. A DNA analysis done on cells from a chorionic villus sample or an amniocentesis can exclude or verify this possibility, although it will add to
1343
For personal use. Only reproduce with permission from The Lancet Publishing Group.