Free Beta-human Chorionic Gonadotropin Research Articles

Effect of Maternal Hepatitis B Carrier Status on First-Trimester Markers of Down Syndrome

Up to 10% of women of reproductive age in our country are carriers of hepatitis B virus. This study examined whether maternal hepatitis B carrier status has any effect on markers used in first-trimester screening for Down syndrome. Records for 2 major Taiwanese hospitals were retrospectively examined to identify women with singleton pregnancies resulting in normal live births from June 2002 through 2008. Maternal hepatitis B data were used to define 3 groups: seronegative women, inactive carrier women, and active carrier women. Women with active or inactive carrier status were significantly older than seronegative women. The results of the study show that maternal hepatitis B carrier status does not influence first-trimester levels of maternal serum free beta-human chorionic gonadotropin (free beta-hCG) multiples of the median (MoM), pregnancy-associated plasma protein A (PAPP-A) MoM, and median fetal nuchal translucency and screening false-positive rate; therefore, correction in the risk calculation algorithm for maternal hepatitis B carrier status is not necessary.

The significance of fetal maxillary length in the first trimester screening for trisomy 21

The present study aims to specify the significance of fetal maxillary length by establishing a nomogram for a Turkish population and by investigating its relationship with the ultrasonographic and biochemical parameters which are commonly used to screen trisomy 21 in the first trimester of pregnancy. The present observational study investigates 1,308 Turkish women who had 11- to 14-week-old singleton healthy pregnancies. Fetal crown-rump length (CRL), nuchal translucency (NT), nasal bone length (NBL) and maxillary length are measured by ultrasonography and maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (HCG) are determined. A positive and significant correlation was detected between the fetal maxillary length and gestational age (r = 0.309, P < 0.001) as was the case with fetal CRL (r = 0.357, P < 0.001) and NBL (r = 0.487, P < 0.001). Although there was a significant and positive correlation between fetal maxillary length and maternal serum PAPP-A levels (r = 0.201, P < 0.001), a significant and negative correlation was found between fetal maxillary length and the maternal serum concentrations of free beta-HCG (r = -0.238, P < 0.001). Fetal maxillary length increased in accordance with the advancing gestational age and increasing CRL. Maternal serum PAPP-A concentrations and fetal CRL and NBL were addressed as independent predictors of fetal maxillary length. The length of fetal maxillary bone is a promising biometrical parameter which can be reliably and efficiently used to screen trisomy 21 in first trimester. Fetal maxillary length is also found to correlate with gestational age, CRL, NBL and PAPP-A significantly. It would be rational to use a combination of nasal and maxillary bone length measurements in case serum concentrations of PAPP-A or beta-HCG cannot be assessed.

Early vaginal bleeding has no impact on markers used in first trimester aneuploidy screening

To assess the impact of early vaginal bleeding on the levels of markers used in first trimester screening for aneuploidy. A retrospective analysis was carried out on the free beta human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency thickness in 49 653 women with a normal singleton fetus who had first trimester combined screening for Down Syndrome in three centres. Median MoMs and the distribution of log MoMs of the two markers were compared in two groups-7470 women who self-reported vaginal bleeding and 42 183 women who reported no vaginal bleeding at any stage prior to the screening test. The overall median MoM free beta-hCG and that in the bleeding and non-bleeding group were 0.9854, 1.0012 and 0.9832, and for PAPP-A were 1.0407, 1.0413 and 1.037. There was no significant difference between the bleeding and non-bleeding group by median test (p = 0.080) or by t-test comparing log MoMs (p = 0.1305) for free beta-hCG and for PAPP-A with median test (p = 0.5071) or by t-test comparing log MoMs (p = 0.1740). For delta nuchal translucency (NT) there was also no significant difference between the bleeding and non-bleeding group (p = 0.055). Vaginal bleeding has little or no impact on first trimester marker levels and no correction is necessary.

Down syndrome maternal serum screening in patients with renal disease

The objective of the study was to determine the value of maternal serum Down syndrome screening in patients affected by renal disease. A study group of 54 pregnant women with renal diseases defined before pregnancy, was compared with a control group of 108 patients matched for maternal age, maternal weight, smoking status, and gestational age. Maternal serum markers (free beta-human chorionic gonadotropin [hCG], total hCG, alpha-fetoprotein) expressed in multiple of median and maternal renal function markers (creatinine, beta2-microglobulin, alpha1-microglobulin) were assayed. The percentage of patients in the Down syndrome at-risk group (>1:250) using free beta-hCG was significantly higher (P < .02) in the renal disease group (48%) than in the control group (12%). No significant difference was observed for total hCG (25% vs 15%). Down syndrome screening using free beta-hCG is not applicable in patients with renal disease whatever the maternal serum creatinine and can be used with caution when total hCG is used.

Correlation between First-Trimester Maternal Serum Markers, Second-Trimester Uterine Artery Doppler Indices and Pregnancy Outcome

Aims: The aim of this study was to assess the correlation between first trimester maternal serum free beta-human chorionic gonadotropin (fBHCG), pregnancy-associated plasma protein A (PAPPA), second-trimester uterine artery (UA) Doppler measurements and adverse pregnancy outcomes. Methods: Serum levels of PAPPA and fBHCG were determined at the first trimester, and patients underwent bilateral UA Doppler assessments at 20–25 weeks of gestation. A serum PAPPA level <0.4 MoM was termed as low and the abnormal Doppler findings were the presence of bilateral notches and RI >0.52 (mean) or unilateral notch and RI >0.66 (90th percentile). Results: Mean PAPPA level was significantly lower in cases with unilateral or bilateral notches (1.09; 0.79 and 0.80 MoM for 0, 1 and 2 notches, p < 0.001). Fifty-two cases (12.8%) had a low PAPPA level; in this group the incidence of abnormal Doppler was significantly higher (34.6 vs. 18.4%, p = 0.011). In the presence of abnormal Doppler in a case with a low serum PAPPA the risk of pregnancy-induced hypertension (OR = 4.56, p = 0.0067), low birth weight (OR = 6.8, p = 0.0002) and the risk of at least one complication (OR = 7.6, p = 0.00001) were significantly high. Conclusion: Combination of first- and second-trimester findings might improve the efficiency of screening for pregnancy complications.

Maternal serum human placental growth hormone at 11 to 13 weeks in trisomy 21 and trisomy 18 pregnancies

To investigate the maternal serum concentration of human placental growth hormone (hPGH) in trisomy 21 and trisomy 18 pregnancies at 11 to 13 weeks of gestation and to examine the possible association between fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). The maternal serum concentration of hPGH at 11 to 13 weeks was measured in a case-control study from 28 pregnancies with fetal trisomy 21, 28 with trisomy 18 and 112 pregnancies with euploid fetuses. The median hPGH multiple of the median (MoM) in trisomy 21 and trisomy 18 pregnancies were compared with euploid pregnancies. Serum hPGH was significantly lower in trisomy 21 (0.93 MoM) and trisomy 18 (0.62 MoM) compared to euploid pregnancies (1.02 MoM). There was a significant association between serum hPGH and PAPP-A in both the euploid (r = 0.258, p = 0.006) and trisomy 21 pregnancies (r = 0.410, p = 0.030) but not in trisomy 18 pregnancies (p = 0.445). In the first trimester, serum hPGH in trisomy 21 and trisomy 18 pregnancies is reduced. This is the opposite of findings in previous studies reporting that in the second trimester, trisomy 21 and 18 pregnancies have increased hPGH.

Association offirst‐trimester low PAPP‐A levels with preterm birth

To determine the association of, and predictive ability of, pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin (beta-hCG), and nuchal translucency (NT) with preterm birth (PTB). A 5-year retrospective cohort study of women who underwent first-trimester combined screening was performed. Maternal medical, antepartum, and pregnancy outcome data were obtained. PAPP-A and beta-hCG were converted to multiples of the median (MoM), and primary exposure was defined as < or =10th percentile MoM for PAPP-A. Secondary exposures were defined as > or = 90th percentile MoM for beta-hCG and NT values of > or = 20 and 25 mm. The primary outcome was PTB before 35 weeks and the secondary outcome was PTB before 32 weeks. Univariate, bivariate, multivariate, and receiver-operator analyses were used. Of the 2231 patients meeting inclusion criteria with complete outcome data available, 222 had a PAPP-A level < or =10th percentile MoM. Abnormally low PAPP-A was associated with an increased risk for PTB < 35 weeks [adjusted odds ratio (aOR) 2.0, 1.0-3.8] and < 32 weeks (aOR 2.7, 1.1-6.4), even after adjusting for prior PTB, tobacco exposure, chronic hypertension, and body mass index. PAPP-A < or =10th percentile was not sufficiently predictive of PTB < 35 weeks (area under curve = 0.63, 95% CI 0.53-0.72). Neither abnormally high beta-hCG nor increased NT was associated with an increased risk for PTB. PAPP-A < or =10th percentile is associated with an increased risk for PTB, but is not sufficiently predictive to be used clinically.

Estimating the effect of gestational age on test performance of combined first-trimester screening for Down syndrome: a preliminary study

To establish how different methods of estimating gestational age (GA) affect reliability of first-trimester screening for Down syndrome. Retrospective single-center study of 100 women with a viable singleton pregnancy, who had first-trimester screening. We calculated multiples of the median (MoM) for maternal-serum free beta human chorionic gonadotropin (free beta-hCG) and pregnancy associated plasma protein-A (PAPP-A), derived from either last menstrual period (LMP) or ultrasound-dating scans. In women with a regular cycle, LMP-derived estimates of GA were two days longer (range -11 to 18), than crown-rump length (CRL)-derived estimates of GA whereas this discrepancy was more pronounced in women who reported to have an irregular cycle, i.e., six days (range -7 to 32). Except for PAPP-A in the regular-cycle group, all differences were significant. Consequently, risk estimates are affected by the mode of estimating GA. In fact, LMP-based estimates revealed ten "screen-positive" cases compared to five "screen-positive" cases where GA was derived from dating-scans. Provided fixed values for nuchal translucency are applied, dating-scans reduce the number of screen-positive findings on the basis of biochemical screening. We recommend implementation of guidelines for Down syndrome screening based on CRL-dependent rather than LMP-dependent parameters of GA.

Contingent triple‐screening for Down syndrome in the second trimester: a feasibility study in Mainland Chinese population

To explore the efficacy of contingent triple-screening for Down syndrome (DS), that is, performing triple-screening in pregnant women with DS risks between 1/270 and 1/1000 at routine double-screening, in a Mainland Chinese population. Maternal serum concentrations of alpha fetoprotein (AFP), free-beta human chorionic gonadotropin (free beta-hCG), and unconjugated estriol (uE3) were measured by time-resolved fluoroimmunoassay in 24 double-screening false-negative (DSFN) and 322 double-screening true-negative (DSTN) pregnancies with DS risks between 1/270 and 1/1000 at routine double-screening performed at 15-20 weeks' gestation. DS risk of each pregnancy was calculated by computer software. The detection rate (DR), false-positive rate (FPR), and costs of contingent triple-screening were calculated and compared with routine double-screening methods. Six of 24 DSFN and 3 of 322 DSTN were contingent triple-screening positive. Compared with routine double-screening, DR of contingent triple-screening increased by 10% (from 50% to 60%) without a significant increase of FPR (p > 0.05). When compared with routine triple-screening, uE3 costs in contingent triple-screening were reduced by more than 84.3%. Second-trimester maternal serum contingent triple-screening could be effective and suitable for prenatal care in Mainland China. Governments and Health Agencies of other developing countries may also find this strategy cost-effective.

Correlation of free fetal DNA with beta-human chorionin gonadotropin in circulation in pregnant women with high risk of Down's syndrome

To investigate significance and correlation of free fetal DNA (fDNA) and beta-human chorionic gonadotropin (beta-hCG) in circulation in pregnant women with high-risk of Down's syndrome (DS). Pregnant women with a male fetus at second trimester screening for Down's syndrome were chosen, including 5 women with a trisomy 21 fetus (DS group), 21 women with DS high-risk pregnant women (DS high-risk group) matched with 22 normal pregnant women as control group. Free fDNA in maternal plasma were extracted. Male DYS14 gene was labled as fDNA, real-time PCR was used to detect fDNA expression. The concentration of beta-hCG in maternal serum was detected by chemiluminescence immune assay. The relationship between level of free fDNA and beta-hCG concentration was analyzed by Pearson correlation analysis. (1) The mean level of free fDNA was (127 +/- 58) GE/ml in DS group, which was significantly higher than (78 +/- 28) GE/ml in DS high-risk group and (48 +/- 21) GE/ml in control group,respectively (P < 0.01). When compared the level of free fDNA between DS high-risk group and control group, it reached statistical difference (P < 0.01). (2) The mean concentration of beta-hCG was (97 +/- 43) kU/L in DS group, which was significantly higher than (58 +/- 25) kU/L in DS high-risk group and (38 +/- 19) kU/L in control group, respectively (P < 0.01). The level of beta-hCG in DS high-risk group was also significantly higher than control group (P < 0.01). (3) The positive relationship between the level of free fDNA in maternal plasma and beta-hCG concentration in maternal serum was observed among three groups (r = 0.83, P < 0.05; r = 0.76,P < 0.01; r = 0.86,P < 0.01). Free fDNA in maternal plasma might be a candidate marker used for prenatal DS screening. However, its clinical value need to be evaluated because of positive correlation between free fDNA and beta-HCG in maternal circulation.

P11.02: First-trimester combined screening for aneuploidy in a Brazilian population from a private center in Rio de Janeiro: a preliminary study

The aim of this study was to assess the effectiveness of first-trimester screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels for aneuploidy in a Brazilian population in Rio de Janeiro. This was a retrospective study of 546 women who underwent combined screening for aneuploidy between 11 + 0 and 13 + 6 weeks of gestation in a fetal medicine unit in Rio de Janeiro (Perinatal Group—Laranjeiras). NT was measured according to the criteria set by the Fetal Medicine Foundation (FMF). Maternal serum free β-hCG and PAPP-A levels were measured, and the risk of aneuploidy was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1: 100 or above. All subjects were followed up for pregnancy and fetal outcome. Among the 546 women who underwent the screening program, 37% were 35 years old or above. 15 fetuses (2,7%) were screen positive; this included 2 cases of trisomy 21 and 1 case of trisomy 18. The sensibility was 75% and the specificity was 98%; the positive predictive value was 21%, and the negative predictive value was 99.5%. Among the 545 screen negative fetuses, there was only one case in which aneuploidy was missed and the infant was live born. First-trimester combined screening for aneuploidy was highly effective in the Brazilian population analyzed in this preliminary study.

P11.18: Impact of ductus venosus assessment in screening Down syndrome protocols

Screening by combination of nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta hCG) and pregnancy-associated plasma protein-A (PAPP-A) is an effective strategy to detect Down syndrome. Our objective is to estimate the improvement in screening efficiency when ductus venosus (DV) Doppler studies are added to existing Down syndrome (DS) screening protocols. First-trimester combined screening for DS was prospectively carried out, from February 2007 to January 2009, in 4408 singleton pregnancies at 11 + 0 to 13 + 6 gestational weeks, including maternal age, biochemistry (beta hCG and PAPP-A) and nuchal translucency. Ductus venosus pulsatility index for veins was calculated at the same time. The maternal serum biochemistry was measured using the Kryptor analyzer (Brahms Diagnostica) in a two-step strategy. The detection rate (DR) and false-positive rates (FPR) for standard screening strategy (maternal age, NT and biochemistry) and the same strategy but including DV assessment were calculated. The mean maternal age was 33 (range 18–46) years. The mean gestation age at blood test was 71 (+/− 10) days. The mean gestation age at scan was 12,6 (range 10,5–13.6) weeks. The population included 35,8% over 35 years. Down syndrome was identified in 16 pregnancies. At a fixed 1% FPR, the DR for trisomy 21 at screening time was 68,8% for standard screening strategy and 81,3% when including DV assessment, respectively. Compared to the standard DS screening strategies, DV assessment can improve screening efficiency by significantly reducing the false-positive rate. Early evaluation of DV can be introduced to standard DS screening strategies in experienced centers as a first level screening test to reduce invasive test rate derived from the extended existing DS screening protocols.

OP02.08: Tricuspid regurgitation in screening pregnancies at 11 + 0 to 13 + 6 weeks of gestation

To investigate the performance of first-trimester screening for aneuploidies, but also for the pregnancy outcome, by including assessment of tricuspid blood flow in the combined test of maternal age, fetal nuchal translucency (NT) thickness and serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A). Screening by the combined test was performed in singleton pregnancies, between 11 + 0 to 13 + 6 weeks of gestation. In all cases tricuspid flow was assessed to determine if there was tricuspid regurgitation. It was noted as final parameters: chromosomal defects, fetal intrauterine demise, major cardiac anomalies, perinatal death. Were included 727 pregnancies, 720 with chromosomally normal fetuses or the delivery of a phenotypically normal baby—euploid group, 5 with trisomy 21, 1with trisomy 18, 1 with trisomy 13. Tricuspid regurgitation was observed in 1,4% (10 cases) of the 720 euploid fetuses and 40% (2 cases) of the fetuses with trisomy 21 and in both cases of fetuses with trisomies 18 and 13. The prevalence increases for chromosomal defects, fetal death, and major cardiac anomalies if there is tricuspid regurgitation. It may be assumed that in a screening policy based on maternal age, fetal NT, serum free beta-hCG and PAPP-A, the assessment of tricuspid flow in all pregnancies would increase the detection rate of trisomies, and also could change the management of pregnancies with normal euploid babies. Assessment of tricuspid flow could improve the performance of first-trimester screening for trisomies. Could also become a tool in assessment the risk in pregnancy. There is need to confirm this, by further studies, of a larger sample of cases.

The efficiency of first-trimester serum analytes and maternal characteristics in predicting fetal growth disorders

To evaluate the association between first-trimester serum analytes, pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin, and fetal growth disorders, and to determine whether a prediction model for these growth disorders can be developed. Retrospective cohort study of patients seen for first-trimester aneuploidy screening. Pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin multiples of the median were evaluated for association with small- and large-for-gestational-age infants in combination with maternal characteristics. Univariate and backward stepwise logistic regression analyses were performed and the area under the receiver-operator curves used to determine the best prediction models. Neither pregnancy-associated plasma protein A nor free beta-human chorionic gonadotropin levels were associated with an increased risk of large-for-gestational-age infants. For small-for-gestational-age infants, the final model included black race, free beta-human chorionic gonadotropin multiples of the median >90th percentile, and pregnancy-associated plasma protein A multiples of the median <5th percentile as significant predictors (area under the curve = 0.58). Low pregnancy-associated plasma protein A and high free beta-human chorionic gonadotropin levels are associated with a small-for-gestational-age growth pattern; however, additional factors to improve the prediction model are needed.

Is placental size a good predictor of obstetric complications?

Is placental size a good predictor of obstetric complications?

Which ultrasound or biochemical markers are independent predictors of small‐for‐gestational age?

To investigate which ultrasound or biochemical markers in both the first and the second trimesters are the best predictors for fetal growth and small-for-gestational age (SGA). This was a prospective study of 619 Chinese women with a singleton pregnancy. At 11 to 13 + 6 weeks, fetal crown-rump length (CRL), placental volume (PlaV), uterine artery pulsatility index (UtA-PI), and the maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) were measured. Fetal biparietal diameter, femur length, abdominal and head circumference, PlaV and UtA-PI were then measured at 18-22 weeks. All markers were transformed to gestational age-specific Z-scores or multiples of the median (MoM). Birth weights were also transformed to Z-scores using the individualized gestational age-related optimal weight based on a locally derived nomogram. The relationship between all markers and the customized birth weight were examined, and their predictive powers for SGA were examined by regression analysis. Univariate analysis revealed that all markers except free beta-hCG correlated with birth weight Z-score. After multiple linear regression analysis, only PlaV, UtA-PI and CRL in the first trimester, and PlaV and UtA-PI in the second trimester, stood out as independent markers. Logistic regression analysis showed that PlaV was the only independent first-trimester predictor of SGA, and in the second trimester both PlaV and UtA-PI were independent predictors. The sensitivity of these first- and second-trimester markers in predicting SGA were 41% and 45%, respectively, at a false-positive rate of 20%. Combining them did not significantly improve prediction of SGA. Among the various known ultrasound and biochemical markers, only the first-trimester PlaV and the second-trimester PlaV plus UtA-PI are independent predictors for SGA.

Prospective validation of first‐trimester combined screening for trisomy 21

To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). This was a prospective screening study for trisomy 21 in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation using an algorithm combining maternal age, fetal NT thickness based on the mixture model for the assessment of NT, and maternal serum free beta-hCG and PAPP-A based on a multiple regression model for the assessment of serum biochemistry. The NT measurements were performed by 60 operators who had obtained The Fetal Medicine Foundation certificate of competence in the 11-13-week scan. The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. In the euploid fetuses the NT was above the previously defined 50(th), 95(th) and 99(th) centiles in 10 033 (51.2%), 618 (3.2%) and 123 (0.6%) cases and the respective values for trisomy 21 were 117 (95.9%), 94 (77.0%) and 57 (46.7%). The median fetal NT was within 0.1 mm of the expected in 47 (78.3%) of the 60 sonographers and within 0.2 mm in all. In the euploid fetuses the median free beta-hCG was 1.0 (range, 0.1-29.4) multiples of the median (MoM) and the median PAPP-A was 1.0 (range, 0.2-3.3) MoM. The median MoM values were 1.0 or close to 1.0 MoM for each subgroup of pregnancy characteristics, including gestations of 11, 12 and 13 weeks, maternal weight of < 60 kg, 60-80 kg and > 80 kg, different ethnic origins, cigarette smokers and non-smokers, natural conception and in vitro fertilization. For a false-positive rate of 3%, the detection rate of trisomy 21 in screening by maternal age and fetal NT was 81% (95% CI, 73-89%), by maternal age and maternal serum biochemistry it was 63% (95% CI, 56-72%) and by combined screening based on maternal age, fetal NT and maternal serum biochemistry it was 90% (95% CI, 84-96%). This study has validated the new risk algorithm and demonstrated that in combined screening for trisomy 21 based on maternal age, fetal NT and free beta-hCG and PAPP-A the detection rate is about 90% for a 3% false-positive rate.

Screening for Down's syndrome in the first trimester: Combined risk calculation, methodology, and validation of a web‐based system

To provide the necessary mathematical formulae to construct a risk calculation package for Down's syndrome using maternal serum free beta human chorionic gonadotrophin, pregnancy associated plasma protein A, and ultrasound nuchal translucency(NT) measurements in the first trimester for use in a web-based system. Swedish antenatal screening program. Swedish women choosing to have first trimester screening for Down's syndrome. A standard Gaussian approach to calculation of likelihood ratios for each marker value was used following conversion of analyte concentrations and NT measurements to multiples of the normal gestational median (MoM). Validation of the algorithm was carried out on a study group of 3,900 pregnancies (including 29 cases of Down's syndrome). Predicted detection and screen positive rates were compared with an alternative calculation package. Sensitivity and specificity of screening delivered by risk calculation package. A cut-off risk of 1 in 200 produced a detection rate of 90% at a 4.7% false-positive rate. In addition, use of the calculation package in a web-based system proved efficient in routine practice, providing rapid access by individual centers to results and easy central monitoring and auditing of the program. The system described here fulfills the requirement for an appropriately validated risk calculation package, is fully user configurable with easy access through a web-based system allowing extension of the screening program to multiple centers.

First‐trimester fetal nasal bone length in an ethnic Chinese population

To determine reference ranges of fetal nasal bone length (NBL) in a Chinese population and to assess the value of NBL measurement in screening for chromosomal defects in the first trimester. In this prospective study the fetal profile was examined and the fetal NBL and crown-rump length (CRL) were measured in Chinese women presenting with singleton pregnancies for first-trimester screening for aneuploidy between January 2004 and June 2007. Screening was performed on the basis of nuchal translucency (NT) measurement and maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A levels. NBL was measured in 7543 fetuses, of which 7517 were euploid. The best fit equation for median NBL in euploid fetuses in relation to CRL was: NBL (mm) = 0.4593 + (0.0186 x CRL(mm)). The NBL for gestational age (GA, in days) was given by the equation NBL(mm) = 0.2392 + (0.0027 x GA). There was no correlation between log(10)(NBL multiples of the median (MoM)) and log(10)(NT MoM) in unaffected pregnancies (r = - 0.009; P = 0.43). Only two of the 11 cases with trisomy 21 had an NBL outside the 5(th) or 95(th) centiles of the reference range for euploid fetuses. Reference ranges for NBL in a Chinese population suitable for screening for aneuploidy between 11 and 13 + 6 weeks' gestation have been derived. The NBL in Chinese fetuses is similar to that of other ethnic groups. However, unlike the determination of presence vs. absence of the nasal bone, NBL measurement is unlikely to further improve screening for aneuploidy.

Effect of deviation of nuchal translucency measurements on the performance of screening for trisomy 21

To examine the effect of deviations in median nuchal translucency thickness (NT) and the spread in measurements on the performance of screening for trisomy 21 by maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry. We simulated the NT and multiples of the median values for pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) for 500 000 euploid and 500 000 trisomy 21 pregnancies at 12 weeks of gestation. Detection rates for trisomy 21 and false-positive rates were calculated without adjustments in NT and by adding or subtracting values ranging from 0.1 to 1.0 mm to each observed measurement. In addition, the effects of variation in the scatter of NT measurements were examined by applying a multiplicative factor ranging from 0.5 to 2 to the SD. The detection rate of trisomy 21 for a fixed false-positive rate of 3% in screening by maternal age and fetal NT was 72%, and in screening by maternal age, fetal NT and serum free beta-hCG and PAPP-A it was 86%. A consistent underestimate or overestimate in the measured NT reduced the detection rate of trisomy 21 for a fixed-false positive rate. At a fixed screen-positive cut-off an underestimate in fetal NT reduced the detection rate whereas an overestimate in NT increased the false-positive rate. A widening in the scatter of measurements had only a small impact on the detection rate but it caused a major increase in the false-positive rate. High performance of screening necessitates appropriate measurement of fetal NT. This paper demonstrates the effect of deviations in the median and SD of NT from the expected on the performance of screening and can form the basis of audit of results of individual sonographers.