DOI 10.1515/jpm-2013-0141 J. Perinat. Med. 2014; 42(2): 255–259
Short communication Edward Araujo Júnior*, Claudio Rodrigues Pires, Wellington P. Martins, Luciano Marcondes Machado Nardozza and Sebastião Marques Zanforlin Filho
Reference values of nuchal translucency thickness in a Brazilian population sample: experience from a single center Abstract Objective: To determine the reference values of nuchal translucency (NT) thickness at 11–14 weeks of gestation in a sample of the Brazilian population. Methods: A retrospective cross-sectional study was carried out with singleton gestations and fetuses with a crownrump length (CRL) of 45–84 mm. NT thickness was performed according to the guidelines of the Fetal Medicine Foundation (FMF), London, UK. To evaluate the correlation between NT thickness and gestational age (GA), polynomial equations were calculated, with determination coefficient (R2) adjustments, as proposed by Altman-Chitty. Results: A total of 1420 pregnancies were assessed. The mean of the gestational age was 12.69 ± 0.78 weeks. The mean maternal age was 28.78 ± 6.81 years. The mean NT thickness (mm) for the CRL intervals of 4550; 5055; 5560; 6065; 6570; 7075; 7580; 8085 was 1.30 ± 0.74; 1.34 ± 0.60; 1.48 ± 0.48; 1.56 ± 0.68; 1.71 ± 0.67; 1.78 ± 0.69; 1.67 ± 0.43; 1.67 ± 0.58; respectively. The following second-order equation best represented the correlation between NT thickness and GA: NT = –1.2570+0.0765 × GA– 0.0005 × GA2 (R2 = 0.05). Conclusion: The reference values for NT thickness were determined for a sample of the Brazilian population. Further studies are required to evaluate the real need for including these values in first-trimester screening for chromosomal defects in Brazil. Keywords: Brazilian population; crown-rump length; nuchal translucency; reference values. *Corresponding author: Edward Araujo Júnior, Referral Center for Teaching of Diagnostic Imaging; and Department of Obstetrics, São Paulo Federal University, Rua Carlos Weber, 956, apto. 113 Visage, Alto da Lapa, São Paulo-SP, Brazil, CEP 05303-000, Tel./Fax: +55-11-37965944, E-mail: [email protected]
Claudio Rodrigues Pires and Sebastião Marques Zanforlin Filho: Referral Center for Teaching of Diagnostic Imaging São Paulo-SP, Brazil Wellington P. Martins: Department of Obstetrics and Gynecology, School of Medicine of Ribeirão Preto – São Paulo University, Ribeirão Preto-SP, Brazil; and Ultrasonography and Retraining Medical School of Ribeirao Preto, Ribeirão Preto-SP, Brazil Luciano Marcondes Machado Nardozza: Department of Obstetrics, São Paulo Federal University, São Paulo-SP, Brazil
Introduction Nuchal translucency (NT) is the sonography finding of accumulated fluid in the neck of fetuses at 11–14 weeks of gestation. Some studies carried out in the 1990s showed a strong association between increased NT thickness and chromosomal defects [12, 13]. It is well known the need to correct biochemical markers, such as the free fraction of β-HCG and pregnancyassociated plasma protein-A (PAPP-A), in addition to ultrasound markers, like NT measurement in the first trimester for Down syndrome, in different ethnical groups [3]. Reference curves were described for NT thickness at 11–14 weeks of gestation in different world groups [4, 7], but the great majority are homogeneous populations, which hinders evaluating the real effect in measuring NT thickness. In the census conducted in the year 2000, for a total of 168,200,000 inhabitants, the Brazilian population comprised 53.7% white; 7.7% black and 38.6% of miscegenated individuals (white, black and indigenous). It is the largest miscegenated population in the world [10]. There is one single study that assessed NT thickness in a sample of the Brazilian population; however, no reference values were determined for this parameter [2]. The objective of this study was to establish the reference values for NT thickness at 11–14 weeks of gestation in a representative sample of the Brazilian population.
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256 Araujo Júnior et al., Nuchal translucency thickness in Brazilian population
Methods A retrospective cross-sectional study was conducted from June 2006 to March 2013, with pregnant women referred for first-trimester screening at 11–14 weeks of gestation. The study was approved by the Research Ethics Committee of the Referral Center for Teaching of Diagnostic Imaging (CETRUS). The inclusion criteria were singleton pregnancies, absence of fetal malformations and crown-rump length (CRL) of 45–84 mm. The pregnant women were referred from diverse public healthcare units of the metropolitan region of São Paulo-SP city, Brazil. All exams were performed transabdominally and supervised and audited by three physicians (CFAP, CRP and SMZF) certified by the Fetal Medicine Foundation (FMF). To assess NT thickness, the guidelines established by the FMF were followed: (1) CRL of 45–84 mm; mid-sagittal plan; image magnification so that the fetal head and trunk occupy at least 75% of the screen; calipers calibrated to 0.1 mm; fetus in neutral position; distinction between fetal skin and amniotic membrane; maximum thickness measurement of the anechoic space between skin and subcutaneous tissue that covers the spine [11]. Three NT measurements were taken and their mean was considered for analysis. The data were transferred to an Excel 2007 spreadsheet (Microsoft Corporation, Redmond, WA, USA) and analyzed by the software PASW (version 18.0, SPSS Incorporated, Chicago, IL, USA), and GraphPad (version 5.0, GraphPad Software, San Diego, CA, USA). Polynomial regressions were calculated to determine the reference values for NT thickness of the CRL, and the adjustments were made by the determination coefficient (R2). The 1st, 5th, 50th, 95th and 99th percentiles were determined for each CRL, according to Altman and Chitty [1].
Results From June 2006 to March 2013, a total of 1457 pregnant women were referred to the service for first-trimester screening. Thirty-seven were excluded (success rate of 97.4%) due to several factors, including inappropriate fetal position, obesity and previous surgical scars. Therefore, a total of 1420 pregnant women were considered for final statistical analysis. The mean maternal age was 28.78 ± 6.81 years. The mean gestational age was 12.69 ± 0.78 weeks. The mean CRL was 64.93 ± 10.75 mm. Figure 1 shows the distribution of NT thickness for CRL for 1st and 99th percentiles. The mean NT thickness (mm) in the CRL intervals of 4550; 5055; 5560; 6065; 6570; 7075; 7580; 8085 are shown in Table 1. A second-order equation had the best adjustment for correlating NT thickness and gestational age, as follows: NT = –1.2570+0.0765 GA – 0.0005 × GA2 (R2 = 0.05). The additional formulas for 1st, 5th, 95th and 99th percentiles were, respectively:
NT = –1.1529+0.0406 CRL –0.0002 × CRL2; NT = –1.1833+ 0.0511 × CRL –0.0003 × CRL2; NT = –1.3307+0.1020 × CRL –0.0007 × CRL2; NT = –1.3611+0.1125 × CRL –0.0007 × CRL2. Table 2 presents the means and 1st, 5th, 95th and 99th percentiles for NT thickness and CRL of 45–84 mm.
Discussion In this study we determined the reference values of NT thickness in a sample of the Brazilian population, aiming to evaluate the influence of the ethnic factor in measuring this ultrasound marker, which could interfere in calculating the risk of chromosomal abnormalities in the first trimester of gestation. Some previous studies showed the need to correct biochemical and ultrasonographic markers in first-trimester screening for the ethnicity of the population assessed [3, 14]. The Brazilian population, according to the year 2000 census, has approximately 65,000,000 miscegenated people, comprising the largest miscegenated population of the world [10]. Hence, it is crucial to determine the reference values for NT thickness in a sample that represents this population. Brizot et al. [2] assessed 2996 single gestations at 10–14 weeks, and identified 22 cases of chromosomal defects. The NT thickness was above 99th percentile in 12 (54.5%) out of 22 fetuses with chromosomal defects, but the study did not establish the reference values for NT thickness. Several studies have determined reference values for NT thickness in different populations; however these investigations addressed European [10, 15] and Asian populations [4, 7], which are predominantly homogeneous, hindering checking the ethnic factor in NT thickness. An increase in NT thickness was observed in our study, tending to stabilize at CRL of 70 mm or greater. Comparing with studies carried out with other populations, both visual analyses of dispersion graphs and of means was very similar in European [8, 15] and Asian individuals [7, 8]. Two other studies with great samples were developed in a homogeneous population in Europe. Wøjdemann et al. [16] developed a study in a Danish population to develop and apply a quality control system in Down syndrome screening by means of the fetal NT thickness in 9236 pregnancies. They observed a good inter-observer reproducibility of fetal NT thickness measurement after a learning curve. However, the measurements of fetal NTs were realized in multiples of the median (MoMs), making it impossible the compare their reference values
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Araujo Júnior et al., Nuchal translucency thickness in Brazilian population 257
8.0 7.5 7.0 6.5 6.0 5.5
NT (mm)
5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 40
50
60
70
80
90
CRL (mm)
Figure 1 Scatter plot of nuchal translucency thickness for crown-rump length. 50th percentile = solid line; 5th and 95th percentiles = dashed lines; 1st and 99th percentiles = dotted lines.
with ours. In another study, Merz et al. [9] developed a new approach for calculating the risk of chromosomal abnormalities in the screening of first trimester in a German population. They used a database of 70,030 normal pregnancies. They used to determinate a new approach the maternal age, CRL 45–84 mm, NT thickness measurement, and maternal serum markers (pregnancy associated plasma protein A – PAPP-A and free human chorionic gonadotrofin – β-hCG). They used the FMF UK program to validate the new approach. They Table 1 Means, standard deviation and maximum and minimum values for nuchal translucency thickness for crown-rump length. CRL (mm)
≥ 45 and
Short communication Edward Araujo Júnior*, Claudio Rodrigues Pires, Wellington P. Martins, Luciano Marcondes Machado Nardozza and Sebastião Marques Zanforlin Filho
Reference values of nuchal translucency thickness in a Brazilian population sample: experience from a single center Abstract Objective: To determine the reference values of nuchal translucency (NT) thickness at 11–14 weeks of gestation in a sample of the Brazilian population. Methods: A retrospective cross-sectional study was carried out with singleton gestations and fetuses with a crownrump length (CRL) of 45–84 mm. NT thickness was performed according to the guidelines of the Fetal Medicine Foundation (FMF), London, UK. To evaluate the correlation between NT thickness and gestational age (GA), polynomial equations were calculated, with determination coefficient (R2) adjustments, as proposed by Altman-Chitty. Results: A total of 1420 pregnancies were assessed. The mean of the gestational age was 12.69 ± 0.78 weeks. The mean maternal age was 28.78 ± 6.81 years. The mean NT thickness (mm) for the CRL intervals of 4550; 5055; 5560; 6065; 6570; 7075; 7580; 8085 was 1.30 ± 0.74; 1.34 ± 0.60; 1.48 ± 0.48; 1.56 ± 0.68; 1.71 ± 0.67; 1.78 ± 0.69; 1.67 ± 0.43; 1.67 ± 0.58; respectively. The following second-order equation best represented the correlation between NT thickness and GA: NT = –1.2570+0.0765 × GA– 0.0005 × GA2 (R2 = 0.05). Conclusion: The reference values for NT thickness were determined for a sample of the Brazilian population. Further studies are required to evaluate the real need for including these values in first-trimester screening for chromosomal defects in Brazil. Keywords: Brazilian population; crown-rump length; nuchal translucency; reference values. *Corresponding author: Edward Araujo Júnior, Referral Center for Teaching of Diagnostic Imaging; and Department of Obstetrics, São Paulo Federal University, Rua Carlos Weber, 956, apto. 113 Visage, Alto da Lapa, São Paulo-SP, Brazil, CEP 05303-000, Tel./Fax: +55-11-37965944, E-mail: [email protected]
Claudio Rodrigues Pires and Sebastião Marques Zanforlin Filho: Referral Center for Teaching of Diagnostic Imaging São Paulo-SP, Brazil Wellington P. Martins: Department of Obstetrics and Gynecology, School of Medicine of Ribeirão Preto – São Paulo University, Ribeirão Preto-SP, Brazil; and Ultrasonography and Retraining Medical School of Ribeirao Preto, Ribeirão Preto-SP, Brazil Luciano Marcondes Machado Nardozza: Department of Obstetrics, São Paulo Federal University, São Paulo-SP, Brazil
Introduction Nuchal translucency (NT) is the sonography finding of accumulated fluid in the neck of fetuses at 11–14 weeks of gestation. Some studies carried out in the 1990s showed a strong association between increased NT thickness and chromosomal defects [12, 13]. It is well known the need to correct biochemical markers, such as the free fraction of β-HCG and pregnancyassociated plasma protein-A (PAPP-A), in addition to ultrasound markers, like NT measurement in the first trimester for Down syndrome, in different ethnical groups [3]. Reference curves were described for NT thickness at 11–14 weeks of gestation in different world groups [4, 7], but the great majority are homogeneous populations, which hinders evaluating the real effect in measuring NT thickness. In the census conducted in the year 2000, for a total of 168,200,000 inhabitants, the Brazilian population comprised 53.7% white; 7.7% black and 38.6% of miscegenated individuals (white, black and indigenous). It is the largest miscegenated population in the world [10]. There is one single study that assessed NT thickness in a sample of the Brazilian population; however, no reference values were determined for this parameter [2]. The objective of this study was to establish the reference values for NT thickness at 11–14 weeks of gestation in a representative sample of the Brazilian population.
Brought to you by | Georgetown University Authenticated Download Date | 5/24/15 6:51 PM
256 Araujo Júnior et al., Nuchal translucency thickness in Brazilian population
Methods A retrospective cross-sectional study was conducted from June 2006 to March 2013, with pregnant women referred for first-trimester screening at 11–14 weeks of gestation. The study was approved by the Research Ethics Committee of the Referral Center for Teaching of Diagnostic Imaging (CETRUS). The inclusion criteria were singleton pregnancies, absence of fetal malformations and crown-rump length (CRL) of 45–84 mm. The pregnant women were referred from diverse public healthcare units of the metropolitan region of São Paulo-SP city, Brazil. All exams were performed transabdominally and supervised and audited by three physicians (CFAP, CRP and SMZF) certified by the Fetal Medicine Foundation (FMF). To assess NT thickness, the guidelines established by the FMF were followed: (1) CRL of 45–84 mm; mid-sagittal plan; image magnification so that the fetal head and trunk occupy at least 75% of the screen; calipers calibrated to 0.1 mm; fetus in neutral position; distinction between fetal skin and amniotic membrane; maximum thickness measurement of the anechoic space between skin and subcutaneous tissue that covers the spine [11]. Three NT measurements were taken and their mean was considered for analysis. The data were transferred to an Excel 2007 spreadsheet (Microsoft Corporation, Redmond, WA, USA) and analyzed by the software PASW (version 18.0, SPSS Incorporated, Chicago, IL, USA), and GraphPad (version 5.0, GraphPad Software, San Diego, CA, USA). Polynomial regressions were calculated to determine the reference values for NT thickness of the CRL, and the adjustments were made by the determination coefficient (R2). The 1st, 5th, 50th, 95th and 99th percentiles were determined for each CRL, according to Altman and Chitty [1].
Results From June 2006 to March 2013, a total of 1457 pregnant women were referred to the service for first-trimester screening. Thirty-seven were excluded (success rate of 97.4%) due to several factors, including inappropriate fetal position, obesity and previous surgical scars. Therefore, a total of 1420 pregnant women were considered for final statistical analysis. The mean maternal age was 28.78 ± 6.81 years. The mean gestational age was 12.69 ± 0.78 weeks. The mean CRL was 64.93 ± 10.75 mm. Figure 1 shows the distribution of NT thickness for CRL for 1st and 99th percentiles. The mean NT thickness (mm) in the CRL intervals of 4550; 5055; 5560; 6065; 6570; 7075; 7580; 8085 are shown in Table 1. A second-order equation had the best adjustment for correlating NT thickness and gestational age, as follows: NT = –1.2570+0.0765 GA – 0.0005 × GA2 (R2 = 0.05). The additional formulas for 1st, 5th, 95th and 99th percentiles were, respectively:
NT = –1.1529+0.0406 CRL –0.0002 × CRL2; NT = –1.1833+ 0.0511 × CRL –0.0003 × CRL2; NT = –1.3307+0.1020 × CRL –0.0007 × CRL2; NT = –1.3611+0.1125 × CRL –0.0007 × CRL2. Table 2 presents the means and 1st, 5th, 95th and 99th percentiles for NT thickness and CRL of 45–84 mm.
Discussion In this study we determined the reference values of NT thickness in a sample of the Brazilian population, aiming to evaluate the influence of the ethnic factor in measuring this ultrasound marker, which could interfere in calculating the risk of chromosomal abnormalities in the first trimester of gestation. Some previous studies showed the need to correct biochemical and ultrasonographic markers in first-trimester screening for the ethnicity of the population assessed [3, 14]. The Brazilian population, according to the year 2000 census, has approximately 65,000,000 miscegenated people, comprising the largest miscegenated population of the world [10]. Hence, it is crucial to determine the reference values for NT thickness in a sample that represents this population. Brizot et al. [2] assessed 2996 single gestations at 10–14 weeks, and identified 22 cases of chromosomal defects. The NT thickness was above 99th percentile in 12 (54.5%) out of 22 fetuses with chromosomal defects, but the study did not establish the reference values for NT thickness. Several studies have determined reference values for NT thickness in different populations; however these investigations addressed European [10, 15] and Asian populations [4, 7], which are predominantly homogeneous, hindering checking the ethnic factor in NT thickness. An increase in NT thickness was observed in our study, tending to stabilize at CRL of 70 mm or greater. Comparing with studies carried out with other populations, both visual analyses of dispersion graphs and of means was very similar in European [8, 15] and Asian individuals [7, 8]. Two other studies with great samples were developed in a homogeneous population in Europe. Wøjdemann et al. [16] developed a study in a Danish population to develop and apply a quality control system in Down syndrome screening by means of the fetal NT thickness in 9236 pregnancies. They observed a good inter-observer reproducibility of fetal NT thickness measurement after a learning curve. However, the measurements of fetal NTs were realized in multiples of the median (MoMs), making it impossible the compare their reference values
Brought to you by | Georgetown University Authenticated Download Date | 5/24/15 6:51 PM
Araujo Júnior et al., Nuchal translucency thickness in Brazilian population 257
8.0 7.5 7.0 6.5 6.0 5.5
NT (mm)
5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 40
50
60
70
80
90
CRL (mm)
Figure 1 Scatter plot of nuchal translucency thickness for crown-rump length. 50th percentile = solid line; 5th and 95th percentiles = dashed lines; 1st and 99th percentiles = dotted lines.
with ours. In another study, Merz et al. [9] developed a new approach for calculating the risk of chromosomal abnormalities in the screening of first trimester in a German population. They used a database of 70,030 normal pregnancies. They used to determinate a new approach the maternal age, CRL 45–84 mm, NT thickness measurement, and maternal serum markers (pregnancy associated plasma protein A – PAPP-A and free human chorionic gonadotrofin – β-hCG). They used the FMF UK program to validate the new approach. They Table 1 Means, standard deviation and maximum and minimum values for nuchal translucency thickness for crown-rump length. CRL (mm)
≥ 45 and
