Objective
The aim of this study was to determine the relationship between the ratio of biparietal diameter to nasal bone length and gestational weeks at the second trimester of pregnancy.
Methods
We evaluated consecutively fetuses referred to our facility between 15 and 22 weeks’ gestation for perinatal sonography and amniocentesis because of an increased risk of aneuploidy. Anatomically normal and euploid 505 fetuses were included in the study. A detailed structural survey, biometric measurements, and measurement of the nasal bone were obtained before the amniocentesis procedure. The distribution of fetal nasal bone length between 15-22 gestational weeks was established and their percentiles were calculated. The ratio of biparietal diameter to nasal bone length was calculated for each case.
Results
The mean nasal bone length for 15 to 22 week`s gestation was 3.21±0.41, 3.45±0.52, 3.81±0.58, 4.17±0.68, 4.42±0.66, 4.89±0.89, 5.35±0.90 and 5.84±1.02 mm respectively. A significant positive correlation was also found between the nasal bone length and the gestational week (Nasal bone length = -2,485+0,370xGestational week (r2=0,50; p<0,001)). The mean biparietal diameter/nasal bone length ratio was 9,94±1,56 and did not progressively increase with advancing gestational age.
Conclusion
The ratio of biparietal diameter to nasal bone length remained constant at 15-22 gestational weeks.
Keywords
Nasal bone length, gestational week, the ratio of biparietal diameter to nasal bone length
Introduction
Nasal bone begins to develop as two separate structures from neural crest cells at sixth gestational week. Both structures ossify through intramembranous ossification. It can be seen by ultrasonography after the 10th gestational week (1,2). The experience of physician using ultrasonography, device quality, the appropriateness of the plan examined, oligohydramnios, obesity, fetus position and gestational week may affect examination quality(3).
It was shown in previous studies that detecting non-existence or hypoplasia of nasal bone is an effective method for scanning chromosomal anomalies (4,5). Langdon Down stated in 1866 that nasal bone shortness is a common characteristics of patients with Trisomia 21 and then this syndrome is named after him later (6). It was reported that 60% of fetuses with non-existence or hypoplasia of nasal bone in between 14th and 25th gestational weeks had Trisomia 21 and that the rate of hypoplasia occurrence in those with euploid was 1.4%.2 Cicero et al. defined in their studies performed on 1046 pregnants between 15th and 22nd gestational week that the nasal bone hypoplasia is the nasal bone length (NBL) below 2.5 mm. Nasal bone hypoplasia rates were 61.8% in fetuses with Trisomia, 3.3% in fetuses with chromosomal anomalies and 1.2% in normal fetuses (7). Bunduki et al. reported in their study performed on pregnants between 16th and 24th gestational weeks that nasal bone hypoplasia is the NBL below 5th percentile and specified the sensitivity for Trisomia 21 as 59.1% (8).
Determining non-existence or hypoplasia of nasal bone is accepted as an effective method today for scanning chromosomal anomalies. While it is required to know nasal bone lengths as to weeks in order to detect nasal hypoplasia, other non-changing rates supporting this finding are also required (4).
In this study, nasal bone length and the change of rate of biparietal diameter to nasal bone length (BPD/NBL) according to gestation gestational week for fetuses with normal karyotype and no anomaly were researched and the relationship between them were analyzed.
Methods
The study was performed on 584 pregnants who were examined by perinatal ultrasonography and than had karyotype analysis in between 01.01.2006 and 01.07.2010. Last menstruation date for pregnancy week, head-back distance at first trimester for those with unknown menstruation date or biparietal diameter measurements at second trimester were based on. Those with structural defect or karyotype anomaly, multiple pregnancies, those who gave stillbirth, those with early membrane rupture and intrauterine growth retardation and with systemic disease were excluded from the study. The study group was formed of 505 single pregnancies with normal karyotype analysis and not having congenital anomaly that were chosen prospectively in between their 15th and 22nd gestational weeks. 79 pregnancies were excluded from the study. The reason for excluding them was that structural anomaly was found in 34 of these pregnancies, chromosomal anomaly was found in 33 of them (also there was structural anomaly in 12 fetuses) and missed abortus found in one of them, and also five pregnants due to systemic diseases were excluded from the study and six pregnants due to not having follow-up.
Ultrasonographic measurements were performed via General Electric Voluson 730 (USA) ultrasonography device with a transabdominal approach (2-7 MHz) by a single operator. Biometric evaluation of the fetus was performed. Fetal biometry and nasal bone measurements were obtained before amniocentesis. BPD measurement was performed by taking the distance from posterior edge of frontal parietal bone to interior surface of posterior parietal bone on cranium axial plan where thalamus, cavum septum pellucidum and third ventricle are seen together. Nasal bone was imaged with low brightness adjustment and 45 or 135 degree angle within the area where maxilla and frontal bone are limited in the plan where jaw and lips of fetus are displayed on midsagittal facial profile. Measurements were done as the maximum length between upmost and lowermost ends of nasal bone. The average value was obtained by performing these measurements twice. BPD/NBL rate was calculated for each fetus. Lengths and rates were compared with gestational week.
Patient data were analyzed by SPSS 11.5 software (SPSS Inc., Chicago, IL, USA). Pearson Correlation test, Regression analyzes and descriptive statistical analyses were performed. One-way variance analysis (One-way Anova) and Post Hoc comparison test were performed by Tukey’s HSD method. Results were evaluated evaluated at p<0.05 significance level within 95% confidence interval.
Results
505 pregnants complying with research criteria were included into our study. Age range of these pregnants was 18-47, and the mean age was 34.41±5.10. Gestational week range was 15- 22 for the study, and mean gestation week was found as 17.84±1.80. Mean NBL was 4.12±0.94 mm and BPD was 39.93±5.94 mm.
It was found in our study that NBL increased linearly with gestational week (GW) and this correlation was significant. The regression equation between NBL and GW was found as NBL = -2.485 + 0.370 x GW (r2=0.50; p<0.001) by linear regression analysis (Diagram 1). NBL measurements according to gestational week within 95% confidence interval are given in Table 1 and percentile distributions are given in Table 2. The regression equation between NBL and BPD was found as NBL = -0.529 + 0.116 x BPD (r2=0.54; p<0.001) by linear regression analysis (Diagram 2). It was seen that nasal bone length displayed most correlation with BPD in between 15th and 22nd gestational weeks.
It was observed in our study that nasal bone length displayed diversity significantly among groups formed according to the gestational weeks. However, BPD/NBL rate did not change significantly (P>0.05) and mean BPD/NBL rate was 9.94±1.56 (Diagram 3). When 11, 12 and 13 were taken as the limit value of BPD/NBL for scanning, false positivity rates were found as 21.8%, 10.5% and 4.2%, respectively.
Discussion
In our study, it was found that nasal bone length increases linearly with gestational week (r2=0.50) and it was averagely 4.12±0.94 mm. Guis et al. reported in their study that mean nasal bone length was between 4 and 12 mm and it displayed an increase linear with gestational week (r2=0.68).9 Sonek et al. measured nasal bone length in 3537 pregnancies in between 11th and 40th gestational weeks and reported that this length displayed a positive correlation with gestational week (r2=0.77) (10). Bunduki et al. found mean nasal bone length as 6.9±1.29 mm in their study performed on 1631 fetuses between 16th and 24th gestational weeks and stated that there was a linear increase with gestational week.8 Yayla et al., Naraphut et al., and Sutthibenjakul et al. Reported that nasal bone length increased linearly with gestational week (3,11,12).
The relation level between NBL and GW (r2=0,43) found in the study of by Jung et al. On 3019 fetuses in between 16th and 28th gestational week was similar to our study (13). Nasal bone length was shorter in our study than found in other national studies. It is considered that this is caused by high risky pregnancies forming the study group, and technical, ethnical and racial differences (Table 3). In fact, Zelop et al. reported that nasal bone length may vary among ethnical origin and races.14 Also we could not compare properly the studies of Yayla et al. and Yalinkaya et al. performed on NBL in our study.3,15 The reason was that both study groups (polyclinic patients without karyotype anomaly risk) and studied gestational weeks (11-39 GW) and (11-41 GW) were different and mean NBL and percentile values according to gestational weeks were not analyzed in these studies.
Bromley et al. measured nasal bone length of 239 fetuses with high risk in between 15th and 20th gestational week and found that the rate of BPD/NBL did not change with gestational week and only one limit value could be used. Mean BPD/NBL rate in fetuses with normal karyotype was reported as 8.1±1.4 while it was 11.3±2.0 in fetuses with Trisomia 21 and the difference was significant. Also, it was reported that false positivity rates were 22%, 11.5% and %2 respectively when BPD/NBL rates were 9, 10, 11 and 12.4 Obido et al. found the sensitivity of scanning Down syndrome as 59% and false positivity as 15% when BPD/NBL rate was ≥11.16 Tran et al. also stated that BPD/NBL rate was a significant and independent marker for Down syndrome (17). In our study, we found mean BPD/NBL rate as 9.94±1.56 and that it was not changing with gestational week similar to other studies. When BPD/NBL limit value for scanning was taken 11, 12, and 13, false positivity rate was found as 21.8%, 10.5% and 4.2% and these rates were found high according to the literature.
Conclusion
Consequently, we found in our study that nasal bone length increased linearly with gestational week. However, we found that BPD/NBL rate was not changing with gestational week and this rate was 9.9±1.5. We observed that it could be pathological with 4% false positivity when BPD/NBL rate was 13 and above. We considered that fetuses might need more advanced analyses in diagnosis with this measurement and above, and the diagnoses in cases with anomaly should be compared with current diagnoses in order to do that and secondary studies are needed to examine them, and the related rate could be used securely only by these studies.
References
1) Sonek JD, Cicero S, Neiger R and Nicolaides KH .Nasal bone assessment in prenatal screening for trisomy 21.Am J Obstet Gynecol 2006;195:1219-30.
2) Sandikcioglu M, Molsted K and Kjaer I.The prenatal development of the human nasal and vomeral bones.J Craniofac Genet Dev Biol 1994;14:124–34.
3) Yayla M, Göynümer G, Uysal Ö.Fetal Nasal Bone Lenght Nomogram.Perinatoloji Dergisi 2006;14:77-82.
4) Bromley B, Lieberman E, Shipp TD, Benacerraf B.Fetal nose bone length: a marker for Down syndrome in the second trimester.J Ultrasound Med 2002;21:1387-94.
5) Gianferrari EA, Benn PA, Dries L, Brault K, Egan JF, Zelop, CM.Absent or shortened nasal bone length and the detection of Down Syndrome in second-trimester fetuses.Obstet Gynecol 2007;109:371-5.
6) Down LJ .Observations on an ethnic classification of idiots. Clinical Lectures and Reports.London Hospital 1866;3:259–62.
7) Cicero S, Sonek JD, McKenna DS, Croom CS, Johnson L and Nicolaides KH. Nasal bone hypoplasia in fetuses with Trisomy 21 at 15-22 weeks' gestation .Ultrasound Obstet Gynecol 2003;21:15–8.
8) Bunduki V, Ruano R, Miguelez J, Yoshizaki CT, Kahhale S, Zugaib M.Fetal nasal bone length: reference range and clinical application in ultrasound screening for trisomy 21.Ultrasound Obstet Gynecol 2003;21:156-60.
9) Guis F, Ville Y, Vincent Y, Doumerc S, Pons J, Frydman R.Ultrasound evaluation of the length of the fetal nasal bones throughout gestation.Ultrasound Obstet Gynecol 1995;5:304–7.
10) Sonek JD, Mckenna D, Webb D, Croom C, Nicolaides KH .Nasal bone length throughout gestation: normal ranges based on 3537 fetal ultrasound.Ultrasound Obstet Gynecol 2003;21:152-5.
11) Naraphut B, Uerpairojkit B, Chaithongwatthana S, Tannirandorn Y, Tanawattanacharoen S, Manotaya S, Charoenvidhya D.Nasal bone hypoplasia in trisomy 21 at 15 to 24 weeks' gestation in a high risk Thai population. J Med Assoc Thai 2006;89:911-7.
12) Sutthibenjakul S, Suntharasaj T, Suwanrath C, Kor-anantakul O, Geater A .A Thai reference for normal fetal nasal bone length at 15 to 23 weeks' gestation.J Ultrasound Med 2009;28:49-53.
13) Jung E, Won HS, Lee PR, Kim A.Ultrasonographic measurement of fetal nasal bone length in the second trimester in Korean population.Prenat Diagn 2007;27:154-7.
14) Zelop CM, Milewski E, Brault K, Benn P, Borgida AF, Egan JF.Variation of fetal nasal bone length in second-trimester fetuses according to race and ethnicity .J Ultrasound Med 2005;24:1487-9.
15) Yalınkaya A, Güzel Aİ, Uysal E, Kangal K, Kaya Z .The Fetal Nose Bone Nomogram According To Gestational Weeks.Perinatoloji Dergisi 2009;17:100-3.
16) Odibo AO, Sehdev HM, Sproat L, Parra C, Odibo L, Dunn L, et al .Evaluating the efficiency of using second-trimester nasal bone hypoplasia as a single or a combined marker for fetal aneuploidy.J Ultrasound Med 2006; 25: 437-41.
17) Tran LT, Carr DB, Mitsumori LM, Uhrich SB, Shields LE .Second-trimester biparental diameter/nasal bone length ratio is an independent predictor of trisomy 21.J Ultrasound Med 2005;24:805-10.
|
File/Dsecription |
|
Diagram 1. Bromley et al. measured nasal b |
|
Diagram 2. Nasal bone length according to biparietal
diameter. |
|
Diagram 3. The relationship of BPD/NBL rate with gestational
week. |
|
Table 1. NBL measurements according to gestational week within 95% confidence interval. |
|
Table 2. NBL distribution according to gestational week. |
|
Table 3. 5th percentile values of current study and other studies between 15th and 22nd GW. |