Screening for trisomy 21 in twin pregnancies by maternal age and fetal nuchal translucency thickness at 10–14 weeks of gestation

Objective To determine the prevalence of increased fetal nuchal translucency thickness in twin pregnancies and to evaluate screening for trisomy 21 by a combination of translucency thickness and maternal age.
Design Prospective screening study at 10 to 14 weeks of gestation.
Setting Fetal Medicine Centre.
Population 22,518 self-selected pregnant women at 10 to 14 weeks of gestation, including 21,477 singleton and 448 twin pregnancies with live fetuses.
Methods Fetal nuchal translucency thickness was measured by ultrasound examination at 10–14 weeks. Sensitivity and false positive rates of screening for trisomy 21 by a combination of fetal nuchal translucency thickness and maternal age were calculated.
Main outcome measures Prevalence of increased nuchal translucency thickness and detection of trisomy 21.
Results In the 448 twin pregnancies the nuchal translucency thickness was above the 95th centile of the normal range (for crown-rump length in singletons) in 65/896 fetuses (7.3%), including 7/8 (88%) with trisomy 21. Increased translucency was also present in four fetuses with other chromosomal abnormalities. In the chromosomally normal twin prebmancies the prevalence of increased nuchal translucency was higher in fetuses from monochorionic (8.4%; 16/190) than in those with dichori-onic pregnancies (5.4%; 37/688). The minimum estimated risk for trisomy 21, based on maternal age and fetal nuchal translucency thickness, was 1 in 300 in 19.5% (175/896) of the twins including all eight of those with trisomy 21.
Conclusions In twin pregnancies the sensitivity of fetal nuchal translucency thickness in screening for trisomy 21 is similar to that in singleton pregnancies, but the specificity is lower because translucency is also increased in chromosomally normal monochorionic twin pregnancies.     

The influence of smoking on the pregnancy-associated plasma protein A,free beta human chorionic gonadotrophin and nuchal translucency

Objective To analyse the effects of smoking on first trimester parameters used in prenatal screening for Down's Syndrome.
Design A chart study.
Setting Primary care centres and maternity clinics of the participating universities' and central hospitals.
Population Three thousand and one hundred fifteen women screened by nuchal translucency measurement and 4436 women screened by maternal serum samples. Only normal singleton pregnancies were included.
Methods The mean multiples of median of pregnancy associated plasma protein A (PAPP-A), free beta human chorionic gonadotrophin (β-hCG) and nuchal translucency were compared by independent samples t test after logarithmic transformation of the data between smokers and non-smokers.
Main outcome measures PAPP-A and free β-hCG concentrations and nuchal translucency measurements.
Results PAPP-A was significantly reduced and nuchal translucency increased if the mother smoked. The smokers were more frequently considered as being at high risk for Down's Syndrome.
Conclusions Correcting PAPP-A median for smokers down by 20% might improve the accuracy of the risk evaluations given to individual women. If the association between increased nuchal translucency and smoking can be confirmed, it poses interesting questions as to the reasons for increased nuchal translucency among normal pregnancies.     

Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes

OBJECTIVE: The purpose of this study was to determine the association between first-trimester trisomy 21 screening markers (free human chorionic gonadotropin-beta [hCG], pregnancy-associated plasma protein A [PAPP-A], and nuchal translucency) and adverse pregnancy outcome. STUDY DESIGN: This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development-sponsored study of first-trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were evaluated. RESULTS: PAPP-A <1st percentile (OR 5.4, 95% CI 2.8-10.3) and PAPP-A <5th percentile (OR 2.7, 95% CI 1.9-3.9) and free beta-hCG <1st percentile (OR 2.7, 95% CI 1.3-5.9) were associated with increased risk of intrauterine growth restriction (IUGR) with positive predictive values of 24.1%, 14.1%, and 14.3%, respectively. PAPP-A <5th percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency >99th percentile (OR 3.5, 95% CI 1.1-11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the 29 other chromosomal abnormalities (55%). Low free beta-hCG, low PAPP-A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality. CONCLUSION: Extreme values of first-trimester free beta-hCG, PAPP-A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP-A levels below the 1st percentile suggests that patients within this group may benefit from increased surveillance for this condition.     

Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience

Objective To evaluate the performance of a one-stop multidisciplinary clinic of screening for fetal chromosomal anomalies in the first trimester of pregnancy by a combination of maternal serum biochemistry and ultrasonography.
Design Retrospective review of screening performance.
Setting District General Hospital maternity unit.
Population All women booked for routine antenatal care at Harold Wood Hospital between 1 June 1998 and 31 May 2001. The population included 12,339 women with singleton pregnancies presenting at 10–14 weeks of gestation.
Methods Women were offered screening using a combination of maternal serum free β-hCG and pregnancy associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. Those with an estimated risk of  ≥1 in 300  of carrying a fetus with trisomy 21 or trisomy 18 or trisomy 13 were offered the option of an invasive diagnostic test. Follow up of the outcome of all pregnancies was carried out.
Main outcome measures Uptake of screening and invasive testing, detection rate for fetal chromosomal abnormalities and false positive rate.
Results The uptake of first trimester screening was 97.5% and the uptake of invasive testing in the increased risk group was 77%. The rate of detection of trisomy 21 was 92% (23 of 25), of trisomy 13 or 18 was 100% (all 15) and of all aneuploidies was 96% (49 of 51). The false positive rate was 5.2%.
Conclusion First trimester screening for trisomy 21 and other aneuploidies can be delivered in an efficient manner in a one-stop multidisciplinary clinic. The detection rates are far better than can be achieved by second trimester serum screening.     

Prospective first-trimester screening for trisomy 21 in 30,564 pregnancies

OBJECTIVE: This study was undertaken to evaluate the performance of a 1-stop clinic for first-trimester assessment of risk (OSCAR) for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness, and maternal serum-free ss- human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein-A (PAPP-A). STUDY DESIGN: OSCAR was carried out in 30,564 pregnancies at 11 to 13 + 6 weeks. Patient-specific risks for trisomy 21 and detection and false-positive rates were calculated. RESULTS: The median maternal age was 34 (range 15-49) years. Chromosomal abnormalities were identified in 330 pregnancies, including 196 cases of trisomy 21. The estimated risk for trisomy 21 was 1 in 300 or greater in 7.5% of the normal pregnancies, in 93.4% of those with trisomy 21 and in 88.8% of those with other chromosomal defects. CONCLUSION: The most effective method of screening for chromosomal defects is by first-trimester fetal NT and maternal serum biochemistry.     

First-trimester nuchal translucency measurement and echocardiography at 16 to 18 weeks of gestation in prenatal detection for trisomy 18

BACKGROUND: Trisomy 18, the second most common autosomal trisomy, has the highest incidence of congenital heart disease of all chromosomal abnormalities. This study assessed the use of nuchal translucency (NT) measurement and fetal echocardiography at 16 to 18 weeks of gestation in prenatal detection for trisomy 18. METHODS: Screening for chromosomal aneuploidy using fetal NT measurement was performed at 10 to 14 weeks of gestation. Detailed fetal echocardiography was performed at 16 to 18 weeks of gestation immediately before genetic amniocentesis for fetal karyotyping in singleton pregnancies with increased fetal NT thickness. RESULTS: Of the 3151 singleton pregnancies included in our study, 171 cases (5.4%) of increased (> or =3.0 mm) NT were noted. Fetal chromosomal abnormalities were identified in 22 (12.9%) of these pregnancies, including 9 with trisomy 21, 5 with trisomy 18, 4 with 45,X and 4 with unbalanced structural abnormalities. Major defects of the heart and the great arteries were identified in 13 (7.6%) of these pregnancies with increased NT. These included eight pregnancies that also had the diagnosis of chromosomal aneuploidy. Among the 22 fetuses with confirmed aneuploidy, all 5 fetuses with trisomy 18, 1 of the 4 fetuses with 45,X and 2 of the 9 fetuses with trisomy 21 had increased fetal NT thickness associated with abnormal fetal echocardiography findings. CONCLUSIONS: Screening for Down syndrome and cardiac defects using first-trimester fetal NT measurement in combination with fetal echocardiography at 16 to 18 weeks of gestation is a feasible and sensitive procedure for the prenatal detection of trisomy 18.     

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assesement of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Polish multi-centre research

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assessment of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Poland's multi-centers research. OBJECTIVES: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. Enlarged nuchal translucency (NT) is observed in about 80% of fetuses affected with chromosomal abnormalities and congenital heart defects (CHD). MATERIAL AND METHODS: The aim of this study were to determine value and the medians of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) and nuchal translucency thickness in the first trimester in a prospective study of a non-selected Polish population. RESULTS: All examinations have been performed according to the Fetal Medicine Foundation (FMF) rules. We have included 800 women between 11 weeks 0 days and 13 weeks 6 days gestation into a biochemical examination. Women booked into the clinic were offered screening, using a combination of maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. The maternal serum were measured using the Kryptor analyzer (Brahms Diagnostica). All pregnant women have been divided into 2 groups younger than (first group) and older than (second group) 35 years of age. CONCLUSIONS: Nomogrames for free beta-hCG and PAPP-A levels in physiological pregnancy between 11(+0) and 13(6) weeks were determined in the examined population. A positive correlation between PAPP-A and CRL levels, as well as a weak negative correlation between free beta-hCG and CRL, were demonstrated.     

The effect of cigarette or sheesha smoking on first-trimester markers of Down syndrome

Objective  To investigate the influence of cigarette or sheesha smoking on first-trimester markers of Down syndrome.
Design  A prospective observational study.
Setting  Primary care centres and antenatal clinics of Maternity and Children Hospital, King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah, Saudi Arabia.
Population  Women with a singleton pregnancy who were either nonsmokers ( n = 1736) or cigarette smokers ( n = 420) or sheesha smokers ( n = 181).
Methods  Fetal nuchal translucency thickness (fetal NT), maternal serum free beta-human chorionic gonadotrophin (free β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were measured at 11 weeks 0 days to 13 weeks 6 days of gestation in all women. Women were grouped according to smoking status, confirmed by maternal serum cotinine measurements, and analyte levels between groups were compared.
Main outcome measures  Fetal NT, maternal serum free β-hCG, PAPP-A and cotinine measurements.
Results  Compared with nonsmoking women, fetal NT was significantly increased and free β-hCG and PAPP-A levels were significantly decreased in both cigarette and sheesha smokers. There were significant relationships between all three markers and the number of sheeshas consumed per day.
Conclusions  Cigarette and sheesha smoking significantly affect first-trimester markers of Down syndrome (fetal NT, free β-hCG and PAPP-A). Correction for this effect in women who smoke might improve the effectiveness of first-trimester screening for Down syndrome in these women. The underlying mechanism(s) relating smoking to the changes in first-trimester markers require further studies.     

Combined measurement of fetal nuchal translucency, maternal serum free beta-hCG, and pregnancy-associated plasma protein A for first-trimester Down's syndrome screening.

PURPOSE: It has been proposed that first-trimester Down's syndrome screening has a higher detection rate compared to second-trimester biochemical screening. This study investigated the accuracy of Down's syndrome screening during gestational weeks 10 to 13 using the combination of fetal nuchal translucency (NT) measurement with maternal serum concentrations of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). METHODS: A total of 1,514 women with singleton pregnancies were enrolled in this study. Fetal NT was measured using the criteria published by the Fetal Medicine Foundation. Maternal serum concentrations of free beta-hCG and PAPP-A were determined by microtiter-plate ELISA. Down's syndrome risk was calculated using multivariate Gaussian distribution and Alpha software. RESULTS: Seventeen (1.12%) of the 1514 screened pregnancies had a fetal NT of at least 3 mm, and 41.2% of these had a poor pregnancy outcome, including four fetal aneuploidies. The odds of a fetal aneuploidy when the NT was greater than 2.0 multiples of median (MoM) was 90, when serum PAPP-A concentration was less than 0.45 MoM, it was 8.6, and when serum free beta-hCG concentration was greater than 2.2 MoM, it was 4.7. Using a risk cut-off level of 1 in 400, nine of 10 fetal aneuploidies were identified with a 4.7% false-positive rate, including two with trisomy 21, one with trisomy 18, and three with Turner's syndrome. CONCLUSIONS: This study demonstrated that Down's syndrome screening using the combined test in the first trimester had a higher detection rate than that of serum screening in the second trimester. Implementation of NT measurement in the first trimester provides substantial advantages for Down's syndrome detection and early diagnosis of fetal structural abnormalities.     

First trimester screening for Down's syndrome using maternal serum PAPP-A and free β=hCG in combination with fetal nuchal translucency thickness

The aim of this study was to evaluate the potential effectiveness of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free β-hCG in combination with nuchal translucency thickness in first trimester screening for Down's syndrome. Maternal serum levels of PAPP-A and free β-hCG were assayed in stored sera from 32 Down's syndrome and 200 unaffected pregnancies. Fetal nuchal translucency was measured by ultrasound at the time of blood sampling. Screening of Down's syndrome using a combination of maternal age, PAPP-A, free β-hCG and nuchal translucency would achieve a detection rate of 75.8% for a false positive rate of 5%.     

Fetal karyotyping in twin pregnancies: selection of technique by measurement of fetal nuchal translucency

Objective To examine the usefulness of selecting the appropriate techque for fetal karyotyping in twin pregnancies by using maternal age and fetal nuchal translucency thickness to determine risk for chromosomal defects in each fetus.
Setting Fetal Medicine Centre, London, United Kingdom.
Subjects Sixty-seven twin pregnancies identified at the time of an ultrasound scan for determination of fetal nuchal translucency thickness, where the parents requested karyotyping.
Intervention The risk for chromosomal defects in each fetus was calculated from the maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation. If the estimated risk for either fetus was 1 in 50 or greater, chorion villus sampling was the method of choice, whereas if the risk was less than 1 in 50 second trimester amniocentesis was performed.
Results The estimated risk for trisomies was more than 1 in 50 in 34 pregnancies and 23.5% of these fetuses were found to be chromosomally abnormal. In contrast, in the 33 low risk pregnancies chromosomal abnormalities were found in only 1.5% of the fetuses.
Conclusions In twin pregnancies the technique for fetal karyotyping may be selected by calculating the risk for chromosomal abnormality based on maternal age and fetal nuchal translucency thickness.     

First trimester fetal ultrasound parameters associated with PAPP-A and fβ-hCG

Objective: To study the association of fβ-hCG and PAPP-A measured at 11–14 weeks of gestation with delta crown-rump-length (dCRL), delta fetal heart rate (dFHR) and delta nuchal translucency (dNT). To calculate adjusted MoM taking into consideration these associations. Methods: Retrospective cross-sectional study on 5,536 singleton euploid pregnancies participating in a first trimester screening program for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry. Adjusted MoM were calculated for fβ-hCG and PAPP-A and compared to the observed MoM (calculated by the Fetal Medicine Foundation screening algorithm). Results: fβ-hCG correlates positively with dCRL and negatively with dNT, whereas PAPP-A shows a positive correlation with dNT and a negative one with dCRL and dFHR. After adjustment for the ultrasound parameters, the median MoM values for fβ-hCG and PAPP-A changed from 1.02 and 0.92 observed MoM to 0.98 and 0.99 adjusted MoM respectively. The difference between the observed and adjusted MoM was statistically significant (p?<?0.001). Delta CRL increases with gestation and this effect manifests mainly after CRL of 62?mm. Conclusions: Adjustment for dCRL, dFHR and dNT improves the calculation of MoM for fβ-hCG and PAPP-A. CRL measurement overestimates fetal size at the end of the screening period 11–14 weeks.     

Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities

There is extensive evidence that effective screening for major chromosomal abnormalities can be provided in the first trimester of pregnancy. Prospective studies in a total of 200,868 pregnancies, including 871 fetuses with trisomy 21, have demonstrated that increased nuchal translucency can identify 76.8% of fetuses with trisomy 21, which represents a false-positive rate of 4.2%. When fetal nuchal translucency was combined with maternal serum free-beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in prospective studies in a total of 44,613 pregnancies, including 215 fetuses with trisomy 21, the detection rate was 87.0% for a false-positive rate of 5.0%. Studies from specialist centers with 15,822 pregnancies, which included 397 fetuses with trisomy 21, have demonstrated that the absence of the nasal bone can identify 69.0% of trisomy 21 fetuses, which represents a false-positive rate of 1.4%. It has been estimated that first-trimester screening by a combination of sonography and maternal serum testing can identify 97% of trisomy 21 fetuses, which represents a false-positive rate of 5%, or that the detection rate can be 91%, which represents a false-positive rate of 0.5%. In addition to increased nuchal translucency, important sonographic markers for chromosomal abnormalities, include fetal growth restriction, tachycardia, abnormal flow in the ductus venosus, megacystis, exomphalos and single umbilical artery. Most pregnant women prefer screening in the first, rather than in the second, trimester. As with all aspects of good clinical practice, those care givers who perform first-trimester screening should be trained appropriately, and their results should be subjected to external quality assurance.     

Screening for fetal aneuploidies and fetal cardiac abnormalities by nuchal translucency thickness measurement at 10–14 weeks of gestation as part of routine antenatal care in an unselected population

Objectives To evaluate first trimester pregnancy screening for fetal aneuploidy and congenital heart defects by maternal age and nuchal translucency measurement and screening for fetal aneuploidies and congenital heart defects by ultrasound in an unselected population.
Design A prospective study.
Setting Fetal medicine unit, St George's Hospital, London.
Sample 4523 consecutive viable fetuses at 10–14 weeks with a crown–rump length between 38 and 80 mm were scanned transabdominally (93%) or transvaginally (7%).
Methods Screening was performed by calculating the background risk from maternal age, gestational age and obstetric history, which was then adjusted with the nuchal translucency measurement in relation to crown–rump length (adjusted risk).
Main outcome measures Measurements of crown–rump length and nuchal translucency thickness. An adjusted risk of > 1:270 was considered as a positive screening test. Pregnancy outcome was obtained through karyotyping, outcome questionnaires and examination of the newborn infants.
Results Mean maternal age was 29.4 years and mean gestational age 12.2 weeks. Screening was positive in 230/4523 fetuses (5.1%), when the adjusted risk (mean 1:2649) was > 1:270. Fetal karyotype was abnormal in 23 (0.51%) cases, including twelve with trisomy 21, five trisomy 18, one trisomy 13, one trisomy 10, one monosomy X and two triploidies. For a false positive rate of 4.7%, the sensitivity of this test was 78% in detecting any fetal aneuploidy. Only one out of nine major congenital heart defects in this population was found within the 110 euploid fetuses with increased nuchal translucency thickness (> 2.5 mm).
Conclusion Screening for fetal aneuploidy by maternal age and nuchal translucency measurement can be effective in an unselected population. However, our results do not support its effectiveness in the detection of cardiac abnormalities.     

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period.     

First trimester maternal serum placenta growth factor (PIGF)concentrations in pregnancies with fetal trisomy 21 or trisomy 18

Placenta growth factor (PIGF), an angiogenic factor belonging to the vascular endothelial growth factor family, pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotrophin (beta-hCG) were measured in maternal serum from 45 pregnancies with trisomy 21, 45 with trisomy 18 and 493 normal controls at 10-13 completed weeks of gestation. In the normal pregnancies maternal serum PIGF levels increased exponentially with gestation. The median multiple of the median (MoM) PIGF concentration in the trisomy 21 group (1.26 MoM) was significantly higher (p<0.0001) than in the control group (1.00 MoM). In the trisomy 18 group the median PIGF was lower (0.889 MoM) but this did not quite reach significance (p=0.064). The corresponding median MoM values for PAPP-A were 1.00 MoM for the controls, 0.49 MoM for trisomy 21 and 0.16 MoM for trisomy 18. The median MoM values for free beta-hCG were 1.00 MoM for the controls, 2.05 MoM for trisomy 21 and 0.38 MoM for trisomy 18. In the control group there was a small but significant correlation of PIGF with free beta-hCG (r=+0.1024) and PAPP-A (r=+0.2288). In the trisomy 18 group there was a significant association between PIGF and free beta-hCG (r=+0.2629) but not with PAPP-A (r=+0.0038). In the trisomy 21 group there was a small but significant association with PAPP-A (r=+0.1028) but not with free beta-hCG (r=+0.0339). The separation of affected and unaffected pregnancies in maternal serum PIGF is small, and therefore it is unlikely that measurement of PIGF would improve screening for these abnormalities provided by the combination of fetal nuchal translucency and maternal serum PAPP-A and free beta-hCG.     

Abnormal first-trimester fetal nuchal translucency and Cornelia De Lange syndrome

BACKGROUND:Cornelia de Lange syndrome is a genetic disorder associated with delayed growth and characteristic facial features. There is no definitive biochemical or chromosomal marker for the prenatal diagnosis of this syndrome. We describe a case of Cornelia de Lange syndrome associated with an increased nuchal translucency in the first trimester.CASE:A large nuchal translucency was identified in a fetus during a first trimester ultrasound. Subsequent second- and third-trimester sonograms demonstrated severe fetal growth restriction, limb shortening, and abnormal facial features, despite normal fetal karyotype per chorionic villus sampling. Neonatal evaluation confirmed the diagnosis of Cornelia de Lange syndrome.CONCLUSION:Sonographic finding of an increased nuchal translucency in early pregnancy is associated with fetal aneuploidy and various structural and genetic abnormalities. Increased nuchal translucency may identify fetuses that require vigilant assessment, especially when found in association with other abnormalities.     

Down syndrome screening marker levels in women with a previous aneuploidy pregnancy

BACKGROUND: In Down syndrome screening programmes, women with a previous affected pregnancy are assumed to have the same marker distribution as those without a family history. This assumption needs to be tested. METHODS: Information on previous aneuploidy pregnancies was routinely sought on the test request forms in three centres, Leeds, Romford and the Fetal Medicine Centre, London. For each woman with a previous aneuploidy (case), five unaffected pregnancies to women without a history were selected as controls. The markers tested included maternal serum free beta-human chorionic gonadotrophin (hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein, unconjugated estriol and ultrasound nuchal translucency thickness. RESULTS: There were 375 cases: 303 with previous Down syndrome, 63 with Edwards syndrome and 9 with Patau's syndrome. There was a statistically significant difference between cases and controls, in the distribution of free beta-hCG and PAPP-A levels, adjusted for gestation. On average, free beta-hCG was increased by 10% in a subsequent pregnancy after aneuploidy (p < 0.005, Wilcoxon rank sum test) and for PAPP-A the increase was 15% (p < 0.0001). No other marker was significantly different. CONCLUSION: Risk calculation algorithms need to be modified to take account of the increased marker levels. Until data from sufficient affected pregnancies are available for study, it would be prudent to assume that the same increase as in unaffected pregnancies applies.     

Pregnancy-associated plasma protein A, free beta-hCG, nuchal translucency, and risk of pregnancy loss

OBJECTIVE: To estimate the likelihood of clinical early and late pregnancy loss as a function of first-trimester maternal serum analytes and fetal nuchal translucency measurements. METHODS: Study subjects were recruited for a National Institute of Child Health and Human Development-sponsored multicenter cohort study initially designed to study the detection of Down syndrome during the first trimester of pregnancy. The cohort consisted of women who had a live fetus between 10 and 14 weeks of gestation and had no significant vaginal bleeding. Women with prior fetal trisomy (T21/18) and those with structural or chromosomal abnormalities in the index pregnancy were excluded. First-trimester screening consisted of pregnancy-associated plasma protein A (PAPP-A), free beta-hCG, and nuchal translucency. Pregnancy loss rates in women with various levels of PAPP-A, free beta-hCG, or nuchal translucency (less than 1st, less than 5th, more than 95th, and more than 99th percentile) were compared with losses in women with normal values (5th to 95th percentile). RESULTS: The mean gestational age at screening of 7,932 women meeting study criteria was 12.1 weeks. Loss rates were only 0.36% at less than 20 weeks after normal free beta-hCG, PAPP-A, and nuchal translucency. Conversely, low levels of PAPP-A and free beta-hCG as well as increased nuchal translucency were individually associated with increased early loss. These associations persisted after controlling for maternal age and race using logistic regression analysis. CONCLUSION: Normal values of PAPP-A, free beta-hCG, and nuchal translucency are associated with a very low risk of pregnancy loss at less than 20 weeks.