Evaluation of pre-test counselling offered for non-invasive prenatal testing (NIPT) as a primary screening tool.

The increasing popularity and expansion of non-invasive prenatal testing (NIPT) to screen for rare conditions beyond common trisomies prompts evaluation of pre-test counselling currently offered. We conducted a prospective survey to assess women's knowledge of NIPT in those who had undergone NIPT (study group) and those who were planning to have NIPT (control group). Out of the 189 questionnaires analysed, the study group did not show a higher knowledge score compared to the control group (P = 0.097). 44% misunderstood that NIPT can identify more conditions than invasive testing, 69.8% were unaware of the recommended need for nuchal translucency measurement and 52.6% were unaware of the possibility of incidental findings. 31% even considered discussing termination of pregnancy as one of the next steps if NIPT shows high risk for Down syndrome. This study shows that current pre-test counselling is inadequate. Service providers should address these knowledge gaps and assist women to make informed choices.Impact StatementWhat is already known on this subject? Pre-test counselling for non-invasive prenatal testing (NIPT) should be conducted to assist women in making an informed consent.What do the results of this study add? Our results show that a significant proportion of women are unaware of the limitations of NIPT.What are the implications of these findings for clinical practice and/or further research? Service providers should improve their pre-test counselling focusing on areas of knowledge deficiencies and misunderstanding on NIPT identified in this study.

Prenatal presentation in two fetuses with features of Beckwith Wiedemann syndrome-An unexpected diagnosis of androgenetic chimera and its clinical implications.

Beckwith Wiedemann Syndrome (BWS, OMIM 130650) is an imprinting disorder that may present antenatally with a constellation of sonographic features namely polyhydramnios, macrosomia, macroglossia, omphalocele, placental mesenchymal dysplasia, cardiomegaly, nephromegaly, fetal hydrops, and other rare anomalies. Paternal uniparental disomy in chromosome 11p15 imprinting region accounts for 20% of all BWS, and 8% among those were due to genome-wide paternal uniparental disomy (GWpUPD). GWpUPD is a rare condition and usually results in prenatal lethality. The 31 liveborns reported in the literature demonstrate female predominance in surviving GWpUPD. Here, we reported two prenatal cases which initially presented with features suggestive of BWS, which subsequently were confirmed to have GWpUPD. Further trio SNP genotyping analysis using SNP-based chromosomal microarray revealed androgenetic biparental chimera as the underlying cause. Finally, we highlighted the importance of recognizing GWpUPD as a possible cause in a fetus presenting with BWS phenotype, as it carried a different disease prognosis, tumor predisposition, manifestations of other imprinting disorders, and possibility in unmasking autosomal recessive disorders from the paternal alleles.

First Case Report of Maternal Mosaic Tetrasomy 9p Incidentally Detected on Non-Invasive Prenatal Testing.

Tetrasomy 9p (ORPHA:3390) is a rare syndrome, hallmarked by growth retardation; psychomotor delay; mild to moderate intellectual disability; and a spectrum of skeletal, cardiac, renal and urogenital defects. Here we present a Chinese female with good past health who conceived her pregnancy naturally. Non-invasive prenatal testing (NIPT) showed multiple chromosomal aberrations were consistently detected in two sampling times, which included elevation in DNA from chromosome 9p. Amniocentesis was performed and sent for chromosomal microarray, which was normal. Maternal karyotype revealed that mos 47,XX,+dic(9;9)(q21.1;q21.1)(24)/46,XX(9) presents mosaic tetrasomy for the short arm of chromosome 9p and is related to the NIPT results showing elevation in DNA from chromosome 9p. The pregnancy was uneventful, and the patient was delivered at term. Maternal samples were obtained at two different time points after delivery showed the same multiple chromosomal aberrations detected during pregnancy. This is a first report on an unusual case of mosaic isodicentric tetrasomy 9p in a healthy adult with normal intellect. With widespread adoption of NIPT for screening fetal aneuploidy and genome-wide copy number changes, a rise in incidental detection of maternal rare genetic syndrome will bring challenges in our current approach to genetic counselling and prenatal diagnosis.

Neonatal outcome and mode of delivery in the presence of nuchal cord loops: implications on patient counselling and the mode of delivery.

PURPOSE: To review and compare the foetal outcomes and mode of delivery in patients with nuchal cord for single loop, double loops, and multiple loops. METHODS: A retrospective study of 4,404 singleton term pregnancies which underwent spontaneous labour was conducted. The patients were classified into five groups: without nuchal cord, nuchal cord of any turns, nuchal cord for 1 turn, nuchal cord for 2 turns and nuchal cord for 3 turns or above. The perinatal outcomes and mode of delivery were then compared. RESULTS: Nuchal cord of any turns was not shown to be associated with intrauterine death, neonatal death, Apgar score <7 at 1 and 5 min. Only nuchal cord for three turns or more were associated with higher incidence of meconium-stained liquor, neonatal unit admission, suspected foetal distress during labour and emergency caesarean section. CONCLUSIONS: Only nuchal cord for 3 turns or more was associated with higher incidence of suspected foetal distress. However, the Apgar scores were not affected. Therefore, nuchal cord of any turns was not associated with adverse foetal outcomes. Prenatal ultrasound scan for nuchal cord is, therefore, unnecessary and there should be no differences in management of nuchal cord of any turns.

Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.

OBJECTIVE: To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service. METHODS: Five cases with secondary findings were reviewed. RESULTS: In Case 1, NIPT revealed a large duplication in chromosome 18p, which was supported by arrayCGH of amniocyte DNA, with final karyotype showing mosaic tetrasomy 18p. In Case 2, a deletion in the proximal long arm of chromosome 18 of maternal origin was suspected and confirmed by arrayCGH of maternal white cell DNA. In Case 3, NIPT was negative for trisomies 21 and 18. In-depth analysis for deletions/duplications was requested when fetal structural anomalies were detected at routine scan. A deletion in the proximal long arm of chromosome 3 was found and confirmed by karyotyping. In Case 4, NIPT correctly predicted confined placental mosaicism with triple trisomy involving chromosomes X, 7 and 21. In Case 5, NIPT correctly detected a previously unknown maternal mosaicism for 45X. CONCLUSION: Non-invasive prenatal testing is able to detect a wide range of fetal, placental and maternal chromosomal abnormalities. This has important implications on patient counseling when an abnormality is detected by NIPT.

Scan the fetal heart by real-time three-dimensional echocardiography with live xPlane imaging.

OBJECTIVE: To describe the methodology of live xPlane imaging in the visualization of the fetal heart in detail. METHODS: Fifty-one consecutive pregnant women with singleton pregnancies were imaged to display four screening sections of the fetal heart, the four-chamber view, the left outflow tract view (LVOT), the right outflow tract view (RVOT), and the three-vessel and trachea view (3VT), using live xPlane imaging. The methodology of how to visualize the screening planes was described in detail. We used two methods to image the fetal heart with live xPlane imaging: one uses the four-chamber view as the starting plane and the other uses the longitudinal view of fetal upper thorax as the starting plane. RESULTS: When using the four-chamber view as the starting plane, the visualization rate of LVOT, RVOT, and 3VT was 94.1% (48/51), 100% (51/51), and 98.0% (50/51), respectively. When using the longitudinal view as the starting plane, the visualization rate of four-chamber view, LVOT, RVOT, and 3VT was 100% (51/51), 100% (51/51), 41.2% (21/51), and 100% (51/51), respectively. CONCLUSIONS: Live xPlane imaging can be used to visualize the screening views of the fetal heart, and potentially may be a useful tool for the assessment and diagnosis of fetal congenital heart diseases.

Serum placental growth factor and fms-like tyrosine kinase 1 during first trimester in Chinese women with pre-eclampsia--a case-control study.

OBJECTIVE: To investigate the association between first trimester maternal placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels with subsequent development of pre-eclampsia (PE). METHODS: This is a matched case-control study using stored serum samples collected from non-smoking Chinese women with singleton pregnancies who underwent first trimester screening for aneuploidy. Each case that developed PE was matched with a control whose maternal age, weight, gestational age and date of blood collection were within ± 2 years, ± 5 kg, ± 1 day, and ± 2 weeks of the index case, respectively. Non-parametric paired test was used to compare the PlGF and sFlt-1 levels. PlGF and sFlt-1 were transformed to their equivalent multiple of the median (MoM) using the matched control as the expected median value. The 95% confidence interval (CI) of the estimated median PlGF and sFlt-1 MoM in those with PE was determined. RESULTS: The median PlGF level in the 27 study cases with PE was lower than that of the matched controls (42.9 pg/ml versus 59.8 pg/ml; p = 0.001). The median PIGF MoM was 0.71 (95% CI 0.63-0.92). There was no statistically significant difference in sFlt-1 levels between those with PE and their matched control (p = 0.648). The median sFlt-1 MoM was 1.01 (95% CI 0.65-1.3). CONCLUSIONS: Women who developed PE had lower serum PlGF levels but normal sFlt-1 levels in the first trimester.

Placental site in the second trimester of pregnancy and its association with subsequent obstetric outcome.

OBJECTIVE: To determine if placental location in the second trimester of pregnancy is associated with adverse pregnancy outcomes. METHODS: We performed a retrospective study on 16 236 patients having ultrasound examination at 14 to 23 weeks of gestation between 2000 and 2007. The placental location was classified into one of four groups: 'central', 'fundal', 'lateral' and 'covering Os'. Obstetric outcomes of non-central placenta were compared to those with 'central' placenta. RESULTS: Women with a 'fundal' placenta were at increased risk of developing pre-eclampsia (PET) (odds ratios (OR) = 2.27; 95% confidence intervals (CI), 1.31-3.93), a preterm delivery before 34 weeks (OR = 2.23; 95% CI, 1.18-4.22), a non-vertex presentation (OR = 3.48; 95% CI, 2.49-4.86), undergoing a manual removal of placenta (MROP) following a vaginal delivery (OR = 7.1; 95% CI, 4.24-11.85) and small for gestational age (SGA) (OR = 1.35; 95% CI, 1.03-1.79). Women with a 'lateral' placenta were at increased risk of developing PET (OR = 2.04; 95% CI, 1.28-3.25), spontaneous preterm delivery before 34 weeks (OR = 2.04; 95% CI, 1.04-3.98), MROP (OR = 6.75; 95% CI, 4.4-10.33) and SGA (OR = 1.82; 95% CI, 1.48-2.23). Five women with a 'cover Os' placenta had an increased risk of postpartum haemorrhage (>1000 mL) (OR = 6.18; 95% CI 2.29-16.65) if they had a vaginal delivery. CONCLUSION: Non-central placental location in the second trimester is associated with an increase risk of adverse obstetric outcome.

Assessment of sonographer nuchal translucency measurement performance--central tendency and dispersion.

OBJECTIVE: To assess center and sonographer nuchal translucency (NT) measurements that were performed as part of routine prenatal screening for Down syndrome. METHODS: Sonographers were assessed for measures of central tendency and dispersion by comparing them with expected population median and dispersion parameters. NT measurements were converted to multiples of the expected NT values according to CRL (NTMoM) and transformed to their log(10) equivalent (log(10) NTMoM). Central tendency and measurement were assessed by checking whether the median of the NTMoM distribution and SD of the log(10) NTMoM distributions were, respectively, within 5% or 10% of the expected median of 1 and SD of 0.1. Assessment was performed using both the Center specific and Fetal Medicine Foundation (FMF) reference NT for Crown rump length (CRL). RESULTS: The median NT MoM was 0.95 MoM using the FMF reference and 1.01 MoM when assessed using our center specific reference median. The difference between the center and FMF derived NT MoMs was statistically significantly (p < 0.0001). NTMoM medians increased over time at a rate of 0.0099 MoM per year while log(10) NT MoM measurement dispersement was similar to the 0.1 value expected and decreased by 0.0048 per year. CONCLUSION: Centers should routinely monitor the quality of NT measurements used to estimate Down syndrome screening risk and should provide individualized feedback to sonographers of their measures of central tendency and dispersion to ensure consistent and improved performance. NT reference medians adopted from other populations should be assessed and validated against a centers own measurement distribution.

Nausea and vomiting in health-related quality of life among Chinese pregnant women.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) is the most common pregnancy complication affecting women during the first trimester of pregnancy. The cause of NVP remains unknown and factors associated with the occurrence of NVP are contradictory. There is currently little information on its effects of NVP in general and specifically in the Chinese population. AIMS: To assess the prevalence of NVP with different degree of severity and identify their relationship with health-related quality of life (HRQoL) and to determine its association with the sociodemographic and obstetric factors. METHODS: In a prospective cross-sectional study, 396 women who attended the antenatal clinic between 10 and 14 weeks of gestation were invited to complete a structured questionnaire covering maternal characteristics, severity of NVP and their HRQoL. The status of NVP and HRQoL was measured by the frequency of symptoms and the Medical Outcomes Study Short-Form-36 (SF-36) respectively. Logistic regression analysis was performed to delineate the factors associated with NVP. RESULTS: The prevalence of NVP was 90.9%. Almost all domains and dimensions of SF-36 were affected by the presence of NVP and its severity. Factors associated with the presence and severity of NVP were non-smoking, younger age and history of NVP in previous pregnancy. CONCLUSIONS: The various degrees of severity of NVP significantly impair both physical and mental HRQoL in Hong Kong Chinese women. Awareness and care should be given to women with symptoms of nausea or retching alone, as well as vomiting.

Massive subchorionic thrombohematoma: a series of 10 cases.

A retrospective audit identified 10 cases of massive idiopathic subchorionic thrombohematoma. The incidence was 1:3,133. Only six of these pregnancies resulted in a livebirth and only two reached term. In eight cases there were ultrasound abnormalities, including two cases of placentomegaly both of which resulted in a pregnancy loss. There was one placental abruption. Seven of the women were nulliparous. Massive subchorionic thrombohematoma is associated with poor pregnancy outcome. Ultrasound findings of placentomegaly might be a bad prognostic sign.

Outcome of induction of labour using maternal characteristics, ultrasound assessment and biochemical state of the cervix.

OBJECTIVE: To assess pre-induction sonographic, digital examination and biochemical changes in the cervix to predict induction outcome. METHODS: Transvaginal and abdominal scans were performed in 460 women at 37-41 weeks of gestation to determine cervical length (CL), posterior cervical angle (PCA) and foetal occipital position. The Bishop Score (BS) and the absence/presence of phosphorylated form of insulin-like growth factor-binding protein-1 (phIGFBP-1) in cervical secretions were assessed. Independent parameters significantly associated with a vaginal delivery were identified. RESULTS: A total of 340 (73.9%) women achieved a vaginal delivery following induction. Multivariate analysis indicated that significant independent predictors of vaginal delivery were CL (adjusted odds ratio [AOR]: 0.59, 95% confidence interval [CI]: 0.45-0.79), PCA (AOR: 1.89, 95% CI: 1.09-3.28) and multiparae (AOR: 10.02, 95% CI: 5.10-19.69). For a specificity of 75%, the sensitivity for prediction of vaginal delivery using the BS, the CL and the multivariate model using the identified significant independent predictors were 37.1, 46.8 and 68%, respectively. CONCLUSION: The combination of sonographic assessment of the cervix and maternal characteristics was superior to the either BS or CL alone in the prediction of the induction outcome. Inclusion of the absence/presence of phIGFBP-1 did not further improve induction outcome.

Effect of long-term storage on placental growth factor and fms-like tyrosine kinase 1 measurements in samples from pregnant women.

OBJECTIVE: To assess the effect of storage time on the stability of placental growth factor (PlGF) and fms-like tyrosine kinase 1 (sFlt-1) levels in frozen serum samples from pregnant women. METHODS: This is a matched case-control study using fresh and stored serum samples collected at 6, 12, 18, 24, 30 and 36 months prior to the collection of the fresh samples and frozen at -80°C. Forty-eight samples from each of the seven time-groups were matched for non-smoking Chinese, maternal weight, singleton-term pregnancy without major obstetric complications and extracted for PlGF and sFlt-1 assays. Multivariate analysis was performed to assess residual effects of the case-matching procedure. ANOVA was used to assess the effects of storage time. RESULTS: Multivariate analysis of the 336 samples indicated that log(10)PlGF was positively correlated with parity (p=0.014) and gestational age (p=0.029), while log(10)sFlt-1 was inversely correlated with parity (p=0.018). After correcting for the residual effect of gestation and parity, ANOVA showed no significant difference in PlGF and sFlt-1 levels between the fresh samples and all stored samples (p=0.410 and p=0.158, respectively). CONCLUSIONS: Serum PlGF and sFlt-1 levels are stable for at least 3 years when stored at -80°C. Parity is an independent factor of PlGF and sFlt-1 levels. PlGF levels are lower and sFlt-1 levels are higher in nulliparous women compared to multiparous.

Prenatal findings and delineation of de novo concurrent partial trisomy 7q(7q31.2 --> qter) and partial monosomy 6q(6q26 --> qter) by high-resolution array CGH.

OBJECTIVE: We investigated the application of microarray-based comparative genomic hybridization (array CGH) on a fetus showing hemivertebrae and intra-abdominal mass at 15 weeks. METHODS: Conventional karyotyping and high-resolution array CGH techniques using 244K CGH microarray were performed to investigate the possibility of genomic imbalance on the opted chorionic villus sample. RESULTS: G-banded fetal chromosome analysis showed 46,XY,der(6)t(6;7)(q26;q31.2)pat. Whole genome scan by array CGH fine mapped the origin of the aberrant chromosomes to be a partial single copy gain of 42.5 Mb from chromosome region 7:116266547 --> qter and concurrent partial single copy loss of 8.1 Mb from chromosome region 6:162756975 --> qter. Pathological examination of the abortus showed gastrointestinal malformations, hemivertebrae with scoliosis, clinodactyly and club feet. CONCLUSIONS: Prenatal and perinatal findings of concurrent trisomy 7q and monosomy 6q were unique. This study demonstrated array CGH can interrogate the entire genome at a resolution and rapidity unattainable by conventional cytogenetic techniques and may have wide application in prenatal diagnosis.

Study on the applicability of frontomaxillary facial angle in the first-trimester trisomy 21 fetuses in Chinese population.

OBJECTIVE: To evaluate the measurement of frontomaxillary facial (FMF) angle at 11 weeks to 13 weeks, 6 days in a Chinese population and its applicability in the screening for fetal trisomy 21. METHOD: In a retrospective study, the stored images for the measurement of fetal nuchal translucency (NT) thickness in a Chinese population from August 2003 to March 2007 were reviewed for the comparison of the FMF angle between 22 trisomy 21 fetuses (study group) with 220 randomly selected normal fetuses with satisfactory images (control group). RESULTS: No association between FMF angle and NT, nasal bone length, or fetal heart rate was shown (P > 0.05). But the FMF angle was significantly greater in the trisomy 21 fetuses (89.7 vs 82.8, P < 0.001). The intraobserver and interobserver agreement were assessed in 9.5% (n = 21) normal cases. Mean (SD) differences of two observers were -0.83 (2.69) degrees (P > 0.05). For each observer, mean (SD) differences between the two paired measurements were -0.98 (3.11) degrees and 0.93 (1.80) degrees , respectively (P > 0.05). CONCLUSION: Our results indicated that measurement of the FMF angle in the first trimester can be incorporated into the screening of trisomy 21 in the Chinese population, and its application is not affected by intraobserver and interobserver variability.

Gastroschisis associated with an intra-abdominal umbilical vein varix: a report of 2 cases.

We describe 2 cases of gastroschisis which were found to be associated with an intra-abdominal umbilical vein varix.

First trimester measurements of nasal bone length using three-dimensional ultrasound.

OBJECTIVES: To investigate the feasibility and reproducibility of measurements of nasal bone length using a three-dimensional (3D) ultrasound in the first trimester. METHODS: In a prospective study, 118 consecutive pregnant women attending for Down syndrome screening at 11-13 + 6 weeks were recruited. They had successful fetal nasal bone measurement by two-dimensional (2D) ultrasound by four operators. Three-dimensional volumes were recorded in the mid-sagittal plane of fetal profile by the fifth operator and examined using multiplanar techniques. Another independent investigator randomly compared his measurements with one of the four operators. RESULTS: In the subsequent 3D examination, the nasal bone length could be examined in 94 cases (79.7%). The mean difference between the 2D and 3D measurements was 0.19 mm [95% confidence interval (CI) 0.08 to 0.31] (P < 0.05). Limits of agreement were -0.73 to 1.11. The mean differences between these two observers were 0.66 mm (95% CI -0.47 to 0.86) (P < 0.05). CONCLUSIONS: There was significant intermethod difference between the results obtained by 2D and 3D, as well as substantial interobserver variation in 3D measurement of fetal nasal bone length in the first trimester. Independent 3D measurement of nasal bone offers no additional advantages over 2D sonography.

Ultrasound screening for fetal structural abnormalities performed by trained midwives in the second trimester in a low-risk population--an appraisal.

OBJECTIVE: To determine the performance of trained midwives in second trimester ultrasound screening for fetal structural abnormalities in a low-risk population. DESIGN: Retrospective study. SETTING: University Department of Obstetrics and Gynecology. POPULATION: About 13,882 women with singleton pregnancies. METHODS: The findings of routine second trimester anomaly scan performed by midwives were reviewed. Reasons for referral to maternal fetal medicine (MFM) specialists for further assessment were analyzed. MAIN OUTCOME MEASURES: The detection, false positive and false alarm rates for fetal anomalies. RESULTS: One hundred and eighty-nine pregnancies with unknown outcome were excluded from the final analysis. Overall, 617 (4.51%) women were referred to MFM specialists for further assessment, of which 470 (70.2%) were for soft markers alone and 147 (23.8%) for suspected fetal structural abnormalities. In these 13,693 fetuses with known outcome, malformed fetuses were present in 185, a prevalence of 1.35%. Of these, 115 were detected during the second trimester scan and two were detected in the third trimester. The remaining 68 malformed fetuses, most of which had minor anomalies, were identified after birth. The detection rate for a malformed fetus in second trimester scan was 62.2% (115/185) (95% CI 55.2-69.2). There were four cases of false positives and 33 cases of false alarm. CONCLUSIONS: Experienced midwives with proper training can detect the majority of major structural abnormalities. Continuous audit and quality control plays a significant role in optimizing the fetal structural examination.

First trimester combined screening for Trisomy 21 in Hong Kong: outcome of the first 10,000 cases.

OBJECTIVE: To examine the effectiveness of first trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency, maternal serum levels of free beta-hCG and PAPP-A in a predominantly Chinese population in Hong Kong. METHODS: Consecutive women who underwent the combined screening for T21 between 11 and 13 + 6 weeks of gestation between 2003 and 2007 were recruited. Risk of T21 was calculated using Fetal Medicine Foundation algorithm and karyotyping was advised when the risk was 1:300 or above. All women were followed up for pregnancy and fetal outcome. RESULTS: 10,363 fetuses underwent screening. 99% of the women were Chinese and 27.4% were at or above 35 years old. 618 fetuses were screened positive (5.9%), which included 31 cases of T21, 14 cases of T18, 7 cases of T13, 10 cases of 45XO and 7 cases of other chromosomal abnormalities. Among the 9745 screened negative fetuses all but 50 (0.5%) had a known outcome, which included three T21 and four other chromosomal abnormalities. All were subsequently identified at the morphology scan except for one case of T21. The detection rate and false positive rates for T21 were 91.2% and 5.4%, respectively and the positive predictive value for all chromosomal abnormalities was 1 in 9. CONCLUSIONS: Combined screening for T21 is highly effective among Chinese women. Training, quality control, regular auditing and follow up are essential to maintain screening standards.

Fetal nasal bone status in Chinese women undergoing first-trimester screening for trisomy 21.

OBJECTIVE: The objective of the study was to determine the likelihood ratio for trisomy 21 in Chinese fetuses with absent nasal bone (NB) at 11-14 weeks of gestation. STUDY DESIGN: The NB was classified as present or absent in 8101 chromosomally/phenotypically normal or trisomy 21 pregnancies. The effect of crown rump length (CRL), nuchal translucency (NT), maternal age, and fetal karyotype on the incidence of absent NB was examined using logistic regression. RESULTS: The NB was successfully examined in 7925 cases (97.8%). The incidence of absent NB in unaffected and trisomy 21 cases were 2.1% (164/7899) and 50% (13/26), respectively. CRL (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.87-0.92), NT (OR, 1.7; 95% CI, 1.4-2.3), and trisomy 21 (OR, 22.3; 95% CI, 8.1-61) were significant independent predictors of likelihood of absent NB. Positive likelihood ratios (LR) for trisomy 21 in Chinese were lower than that of Caucasians for the equivalent CRL and NT measurements. CONCLUSION: Estimated risk for trisomy 21 in Chinese incorporating nasal bone status should use LRs derived in Chinese rather than Caucasians.