Triploidy identified through second-trimester serum screening

OBJECTIVES: To describe the maternal serum marker patterns of triploid pregnancies and estimate the second-trimester prevalence of triploidy. METHODS: Forty-two cases of triploidy were identified in six serum screening programmes, five in the United Kingdom, one in Canada. This study describes the serum marker patterns, serum screening results for Down syndrome, trisomy 18 and open neural tube defects, and maternal age of these triploidy cases. The risk cut-off levels were > or = 1 in 250 for Down syndrome, > or =2.5 MoMs alpha-fetoprotein for open neural tube defects and > or =1:100 for trisomy 18 screening. The estimated second-trimester prevalence of triploidy was based on 22 triploidy cases ascertained in 599 934 pregnancies from three routine screening programmes, which attempted complete ascertainment of aneuploidy cases. RESULTS: The observed second-trimester rate of triploidy was 0.37 per 10 000 fetuses. Two different serum marker patterns were seen in triploid pregnancies, distinguished from each other by typically very high or very low levels of total hCG or free beta-hCG. The median maternal ages were respectively 33 years for triploidy with human chorionic gonadotrophin levels < 1.0 MoM, and 26 years for those with hCG levels > or =1.0 MoM. Fifty-seven percent of the pregnancies with a triploid fetus had a risk estimate > or =1:100 for trisomy 18 alone, 10% had an alpha-fetoprotein > or =2.5 MoM, 5% were screen positive for Down syndrome alone, and 19% had an increased risk or positive results for more than one anomaly. CONCLUSION: The simultaneous use of maternal serum tests designed to screen prenatally for Down syndrome, neural tube defects, and an increased risk of trisomy 18 resulted in a screen-positive result for 90% of pregnancies with triploidy.     

Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustment for cross-identification and double-positive results

Second trimester screening for fetal Down syndrome and trisomy 18 is available through separate protocols that combine the maternal age-specific risk and the analysis of maternal serum markers. We have determined the extent to which additional Down syndrome affected pregnancies may be identified through trisomy 18 screening, and the extent to which additional cases of trisomy 18 may be screen-positive for Down syndrome. The combined false-positive rate, taking into consideration those pregnancies that are screen-positive by both protocols, has also been determined. Sensitivity and false-positive rates were determined by computer simulation of results that incorporated previously published statistical variables into the model. Using second trimester risk cut-offs of 1:270 for Down syndrome and 1:100 for trisomy 18, it was found that few additional cases of Down syndrome are identified through trisomy 18 screening. However, approximately 6-10% of trisomy 18 affected pregnancies will be screen-positive for Down syndrome but screen-negative for trisomy 18. For women aged 40 or more, the false-positive rate for trisomy 18 exceeds 1% and approximately half of these cases will also be screen-positive for Down syndrome. For a population with maternal ages equivalent to that in the United States in 1998, after adjusting for the cross-identification, the sensitivity for three-analyte trisomy 18 screening is 78%. If this testing is performed in conjunction with Down syndrome "triple" screening, the Down syndrome sensitivity is 75% and the combined false-positive rate is 8.5%. If the three-analyte trisomy 18 screening is performed with the Down syndrome "quad" screen, the trisomy 18 sensitivity remains at 78%, the Down syndrome sensitivity is 79%, and combined false-positive rate is 7.5%. Sensitivity and false-positive rates are also provided for other widely used Down syndrome and trisomy 18 risk cut-offs. Sensitivity and false-positive rates that take into consideration cross-identification and double-positives should be helpful for pre-test counseling and the evaluation of serum screening programs.     

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.     

Age-specific risk of fetal loss observed in a second trimester serum screening population

OBJECTIVE: The purpose of this study was to investigate age-specific spontaneous fetal loss rates of pregnancies without known chromosomal or structural abnormalities from mid-second trimester onward. STUDY DESIGN: The study consisted of 264,653 women screened between October 1995 and September 2000 with available pregnancy outcomes. Pregnancies associated with fetal chromosomal or structural abnormalities, insulin dependent diabetes mellitus, and multiple pregnancies were excluded. Spontaneous fetal losses at or after 15 weeks of gestation were identified. Women were grouped according to maternal age at expected date of delivery. Spontaneous fetal loss rates in each group were evaluated after adjusting fetal losses associated with amniocentesis and identifiable ethnic groups. RESULTS: Fetal loss rates increased in both younger and older women. The lowest rate was seen in women at mid-20s. Compared with Caucasian and Asian women, black women had higher fetal loss rate at nearly every age group. CONCLUSION: The results of the study provided a baseline age-specific spontaneous fetal loss rate of pregnancies at a specified gestational window.     

Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening

Of the 65 328 pregnancies of South Australian mothers screened by the South Australian Maternal Serum Antenatal Screening (SAMSAS) Programme between 1 January 1991 and 31 December 1997, 3431 (5.25%) were declared at increased risk of fetal Down syndrome. Fetal or neonatal karyotype was determined in 2737/3431 (79.8%) of these pregnancies, including 16 with early fetal loss. Interrogation of the database of the South Australian Neonatal Screening Service showed 643 live-born infants whose phenotype was not subsequently questioned among the 694 pregnancies whose karyotype was not determined. Of the remaining 51/3431 pregnancies, 19 ended in early fetal loss without karyotyping and no newborn screening or other records could be found for 32 cases. The 129 instances of abnormal karyotype found were Down syndrome (84), trisomy 18 (four), trisomy 13 (three), triploidy (two), female sex chromosome aneuploidy (six) and male sex chromosome aneuploidy (five), inherited balanced rearrangements (19), mosaic or de novo balanced abnormalities (four) and unbalanced karyotypes (two). In the pregnancies declared at increased risk of fetal Down syndrome, only the karyotype for Down syndrome occurred with a frequency greater than that expected for the general, pregnant population.     

Double-positive maternal serum screening results for down syndrome and open neural tube defects: An indicator for fetal structural or chromosomal abnormalities and adverse obstetric outcomes

OBJECTIVE: The study was designed to evaluate whether double positive maternal serum screening results for Down syndrome and open neural tube defects indicate an increased risk of adverse perinatal outcome. STUDY DESIGN: A retrospective case-control study was conducted. In a cohort of 170,394 women who underwent maternal serum triple screening in Ontario, Canada, between October 1995 and September 1998, 189 women received positive screening results for both Down syndrome and neural tube defects. Each case was matched to 5 control subjects who had negative screening results for test center, maternal age, and specimen date. The risks for adverse perinatal outcomes were compared. RESULTS: Women with double-positive screening results had significantly higher risks of having fetuses with structural abnormalities (odds ratio, 14.5) and chromosomal anomalies (odds ratio, 36.3). They also had higher risks of having preeclampsia (odds ratio, 6.7), small-for-gestational age (odds ratio, 9.7), preterm delivery (odds ratio, 5.9), miscarriage, and intrauterine fetal death (odds ratio, 11.8). CONCLUSION: Double-positive maternal serum screening results are associated with fetal structural and chromosomal abnormalities and/or adverse pregnancy outcomes. Close fetal and maternal surveillance are indicated when such pregnancies are identified.     

Maternal serum screening for fetal trisomy 18: benefits of patient-specific risk protocol

OBJECTIVE: Our goal was to evaluate the effectiveness of two approaches to screen pregnancies for trisomy 18. STUDY DESIGN: We analyzed the outcome of all pregnancies that were screen positive for trisomy 18 by multiple marker screening (alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin) from May 1993 to June 1998. We compared the results of a fixed cutoff protocol to a protocol that incorporates maternal age to generate a patient-specific risk figure. RESULTS: A total of 45,145 patients were screened. By using the fixed cutoff protocol, 113 patients (0.25%) were screen positive. The risk-based approach was associated with a 0.55% screen-positive rate (250 patients). Eight of 12 cases (67% detection rate) of trisomy 18 were identified by using the risk method, and only 5 cases (42% detection rate) were detected by using the fixed cutoff method. By using the risk-based protocol, 21 pregnancies with chromosomal abnormalities (8, trisomy 18; 7, triploidy; 5, trisomy 21; and 1, mosaic 45X/46XX) were detected. Subsequent fetal death occurred for 42 patients whose fetuses were chromosomally normal and without structural malformations. CONCLUSION: The patient-specific risk protocol to screen for trisomy 18 is a beneficial adjunct to screening programs already in place for Down syndrome and neural tube defects. Patients found to be screen positive for trisomy 18 are at significant risk for adverse pregnancy outcome.     

Major fetal abnormalities associated with positive screening tests for Smith-Lemli-Opitz syndrome (SLOS)

OBJECTIVE: Determine the relationship between positive screening interpretations for Smith-Lemli-Opitz syndrome (SLOS) and other fetal abnormalities, to aid counseling and diagnostic activities. METHODS: An SLOS screening algorithm was incorporated into California's second-trimester screening program for Down syndrome and open neural tube defects (ONTDs). Between 2002 and 2004, 777 088 pregnant women were given an SLOS risk interpretation, using alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotrophin (hCG) measurements. Outcomes were obtained in 98.8% of screen-positive pregnancies. RESULTS: SLOS screen positives, alone or in combination with screen positives for other fetal disorders (Down syndrome, trisomy 18, ONTD), were associated with a high risk for fetal pathology. Type and frequency of chromosomal or anatomic abnormalities (or fetal death) varied according to screen-positive combination. Among 2018 screen-positive pregnancies, 644 fetal deaths were identified. Among the 1374 viable pregnancies, 519 were screen positive for SLOS alone; two SLOS cases and 51 other serious abnormalities were identified (14 aneuploidies; 37 anatomic). The remaining 855 were also screen positive for at least one other disorder; two SLOS cases and 327 other abnormalities were identified (180 aneuploidies; 157 anatomic). CONCLUSION: For screening programs implementing the SLOS algorithm, the present data may be useful for counseling and to guide diagnostic studies.     

Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome.

OBJECTIVES: Prenatal screening during the first-trimester using fetal nuchal translucency (NT) measurement and maternal serum levels of free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) has become an established method for the detection of fetal Down syndrome. Increasing evidence has shown that some of the fetal structural abnormalities could be identified during NT scanning. Second trimester maternal serum alpha-fetoprotein (MSAFP) measurements and ultrasound scans have been widely used in clinical practice to identify fetal neural tube defects (NTDs). In this study, we evaluated the effectiveness of early diagnosis of fetal acrania during NT scanning. METHODS: We reviewed the medical records of 5890 pregnancies that were delivered in our hospital between January 1, 1999 and January 31, 2001. Among them, 3600 pregnant women received NT-based Down syndrome screening at 10-13 weeks' gestation. Pregnancies with fetal NTDs were evaluated and their maternal serum levels of free beta-hCG and PAPP-A were compared with those of the normal control pregnancies. RESULTS: Seven of the 3600 pregnancies were identified with fetal acrania and all of them were detected during first-trimester NT scanning. Among the seven cases, five had measurements of maternal serum concentration free beta-hCG and PAPP-A concentration, yet there were not significant difference between the pregnancies with fetal acrania and those of the control pregnancies (PAPP-A, 1.13 vs. 0.96; free beta-hCG, 1.10 vs. 1.06; P>0.05). Two of the seven affected patients did not have maternal serum biochemical measurements due to the immediate termination of pregnancies. CONCLUSIONS: We demonstrated that pregnancies with fetal acrania could be easily identified at the time of NT scanning. Careful ultrasound inspection of fetal structure during NT measurements at 10-13 weeks of gestation provides an encouraging advantage for early diagnosis of fetal acrania.     

First trimester combined test for Down syndrome screening in unselected pregnancies — A report of a 13-year experience

ObjectiveTo analyze the performance of the first trimester Down syndrome screening in a single medical center in Northern Taiwan.Materials and methodsFrom April 1999 to June 2012, a total of 25,104 pregnant women at gestational age of 10 weeks to 13 weeks 6 days received first trimester “combined test” for Down syndrome screening. The test combines the ultrasound scan of nuchal translucency thickness and maternal biochemical serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG). A positive screen was defined as an estimated Down syndrome risk ≥1/270, and either chorionic villous sampling or amniocentesis was performed for fetal chromosomal analyses.ResultsSeventy-eight of the 25,104 pregnancies were proven to have fetal chromosome anomalies. The detection rates for trisomy 21, trisomy 18, Turner syndrome, and other chromosome anomalies were 87.5% (21/24), 69.2% (9/13), 81.8% (9/11), and 60% (18/30), respectively, with a false positive rate (FPR) of 5.4% (1353/25,026). Further evaluation of the detection rates for trisomy 21, by gestational age at 11, 12, and 13 weeks, were 92.3%, 87.5%, and 66.7%, respectively.ConclusionThe first trimester combined test is an effective screening tool for Down syndrome detection with an acceptable low false positive rate. The best timing of screening will be between 11 and 12 weeks' gestation.     

Maternal serum marker medians in Aboriginal Canadian women

OBJECTIVES: The study evaluates the differences between Aboriginal and Caucasian women in the levels of maternal serum markers used in second-trimester Down syndrome screening (alpha-fetoprotein, unconjugated estriol, and total human chorionic gonadotrophin). METHODS: A case-control study compared the levels of serum markers in 401 Aboriginal women and 1565 matched controls selected from 7717 Caucasian women. The cases and controls were screened in a single centre and matched for maternal age, parity, and sample date. Women with multiple pregnancies and pregnancies associated with Down syndrome, open neural tube defects, trisomy 18, and insulin-dependent diabetes mellitus as well as women without weight recorded were excluded from the study. RESULTS: No differences in the levels of maternal serum alpha-fetoprotein and total human chorionic gonadotrophin were observed between the two groups. Maternal serum unconjugated estriol was 12% higher in Aboriginal women. DISCUSSION: Since Aboriginal women make up only a small proportion of women screened, correcting the level of uE3 for this group will have little effect on the overall screening performance. However, if these results are confirmed by further study, individual centres may consider making this correction, so optimal screening performance can be achieved in Aboriginal women.     

Elevated second-trimester maternal serum inhibin A levels in Asian pregnancies with fetal down syndrome and other chromosomal abnormalities

SUBJECTS: To evaluate second-trimester maternal serum inhibin A levels in Asian pregnancies with fetal Down syndrome and other chromosomal abnormalities. METHODS: Inhibin A level was measured from the serum samples of 25 chromosomally abnormal pregnancies, including 15 cases of Down syndrome, 4 cases of trisomy 18, 1 case of trisomy 13, and 5 cases of sex chromosome aneuploidies (4 cases of 47,XXY and 1 case of 45,X) and in a cohort of 150 controls during the second trimester of pregnancy. RESULTS: The multiple of median levels of Down syndrome (1.74) and other chromosomally abnormal pregnancies (2.03) are significantly higher than that of normal pregnancies (p = 0.002 and p = 0.024, respectively). Only 3 of 15 (20%) Down syndrome cases had inhibin A levels at or above the 95th centile of the control values. CONCLUSIONS: Inhibin A levels are raised in Asian women affected with fetal Down syndrome and sex chromosome abnormality. In spite of the poor discrepancy of inhibin A, it might be a potential marker for Down syndrome screening in Asians.     

Trisomy 18 and maternal serum and amniotic fluid alpha-fetoprotein

Maternal serum and amniotic fluid alpha-fetoprotein levels were studied retrospectively in a total of 58 pregnancies with trisomy 18. In those pregnancies uncomplicated by either fetal exomphalos or neural tube defect the midtrimester maternal serum alpha-fetoprotein (MSAFP) levels were markedly reduced, the median value for 38 such pregnancies being 0.6 multiples of the median (MoM). Trisomy 18 with exomphalos was associated with a higher median MSAFP, but still within the normal range: 1.1 MoM, (nine pregnancies); trisomy 18 with exomphalos and neural tube defect (NTD) was associated with grossly raised levels: median MSAFP was 4.5 MoM (three pregnancies). Amniotic fluid alpha-fetoprotein (AFAFP) levels were normal in uncomplicated trisomy 18 pregnancies: median AFAFP, for 19 pregnancies, was 1.1 MoM. Exomphalos alone, or together with neural tube defect, was associated with greatly elevated levels of AFAFP; for exomphalos alone median AFAFP was 9.59 MoM (four pregnancies), and for exomphalos with neural tube defect the median AFAFP was 23.95 Mom (three pregnancies). Screening with low and high MSAFP, routine ultrasound, and amniocentesis on all women aged 35 years or over, together might identify over 50 per cent of pregnancies with trisomy 18.     

Folate and vitamin B12 concentrations in maternal and fetal blood, and amniotic fluid in second trimester pregnancies complicated by neural tube defects.

OBJECTIVE: To investigate maternal and fetal folate and vitamin B12 concentrations in pregnancies affected by neural tube defects (NTD). DESIGN: Measurement of folate and vitamin B12 concentrations in amniotic fluid, fetal blood and maternal blood samples in midgestation. SUBJECTS: 32 women undergoing termination of pregnancy at 14-21 weeks gestation for social reasons (n = 24) or for fetuses with neural tube defects (n = 8). INTERVENTIONS: Fetoscopy before intra-amniotic injection of prostaglandins. RESULTS: In normal pregnancies there was a positive correlation between maternal and fetal serum folate, and the fetal serum and red blood cell folate concentrations were higher than the maternal. There were no differences in amniotic fluid, maternal blood or fetal blood folate concentrations between pregnancies with NTD and normal pregnancies. Although amniotic fluid vitamin B12 was lower in pregnancies with NTD, maternal serum vitamin B12 concentration was not reduced. CONCLUSION: In this small group of pregnancies with NTD at mid-gestation there is no evidence to suggest folate or vitamin B12 deficiency.     

The level of ADAM12-S in maternal serum is an early first-trimester marker of fetal trisomy 18

BACKGROUND: ADAM12-S is a pregnancy-associated insulin-like growth factor binding protein-3 (IGFBP-3) and IGFBP-5 protease present in human gestational serum. Recently, maternal serum levels of ADAM12-S were found to be markedly reduced during the first trimester of pregnancies with a Down syndrome (DS) fetus. On the basis of this finding, it was suggested that ADAM12-S might be a useful maternal serum marker of fetal chromosomal disease. OBJECTIVE: Retrospective examination of the use of ADAM12-S as a marker for fetal trisomy 18. METHOD: Serum samples were obtained from ten women during the first semester of their pregnancies with fetuses that had trisomy 18. An ELISA was used to determine the levels of ADAM12 in maternal serum. Results were compared to ADAM12-S levels, previously measured in the serum of 170 women carrying normal pregnancies during the first trimester. RESULTS: In all cases, the ADAM12-S concentration in maternal serum samples was lower in trisomy 18 pregnancies than in normal pregnancies, with a median multiple of the median (MoM) of 0.28 (p < 0.001) CONCLUSION: A reduced concentration of ADAM12-S in maternal serum is a promising marker for foetal trisomy 18, as well as for DS.     

Second trimester prenatal screening for Down's syndrome using alpha-fetoprotein and free beta hCG: a seven year review

OBJECTIVE: To determine the value and impact over a seven year period of a second trimester screening programme for trisomy 21 and trisomy 18, using the two maternal serum markers alpha-fetoprotein and free beta human chorionic gonadotrophin. DESIGN: Retrospective review. SETTING: A biochemical screening laboratory serving three health districts with three antenatal clinics in both teaching and nonteaching hospitals. POPULATION: 67,904 pregnancies in women of all ages screened between 14 and 22 weeks of gestation between 1 April 1991 and 31 March 1998. METHODS: All women booked into three major antenatal clinics were offered biochemical screening. Women at increased risk of trisomy 21 or trisomy 18 (> or =1 in 250 at term) were offered an invasive diagnostic procedure. Follow up of the outcome of all pregnancies was performed. MAIN OUTCOME MEASURES: Detection rate for trisomy 21 and trisomy 18, false positive rates, uptake of screening, uptake of amniocentesis in women identified at increased risk, prevalence of trisomy 21 at birth, detection and false positive rates by maternal age, fetal loss rate after amniocentesis, report turn around time, and identification of other anomalies. RESULTS: Overall, 87% (67,904/78,501) of women underwent screening. The rate of detection of trisomy 21 was 75% (80/107; 95% CI 66 to 83) with a 5.1% false positive rate (3466/67,904; CI 4.9 to 5.3%). In women under 30 years of age the detection rate was 60% (18/30; CI 41 to 77) with a 2.6% false positive rate (956/36,371; CI 2.5 to 2.8). The rate of detection of trisomy 18 was 57% (8/14; CI 29 to 82) with a 0.7% false positive rate (475/67,904; CI 0.64 to 0.76). Uptake of amniocentesis was 83% (2912/3508). Women were 3.3 times more likely to refuse amniocentesis if the risk was close to the cutoff (1 in 250) than if the risk was > or =1 in 50. Fetal loss within 28 days of amniocentesis was 0.9% (25/2912). Prenatal screening identified 84 other anomalies in addition to 41 cases of impending fetal death. CONCLUSION: Second trimester prenatal screening for trisomy 21 and trisomy 18 using a simple two marker approach incorporating free beta hCG can achieve high detection rates over a long period of time. Health authorities who still have not introduced trisomy 21 screening should be encouraged by what can be achieved and should consider making such screening available to all women. Established second trimester detection rates of 75% for a 5% false positive rate will be the benchmark by which first trimester screening using nuchal translucency, PAPP-A and free beta hCG will be judged.     

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.     

Maternal serum leptin concentration during the second trimester of pregnancy: association with fetal chromosomal abnormalities

Recent studies suggest that leptin, the product of the obese gene, is produced by the placenta during pregnancy. The present study addressed the question whether second trimester maternal serum leptin could be altered by fetal Down syndrome or Edwards syndrome. Maternal serum leptin concentrations were measured in 18 pregnancies complicated with Down syndrome, six pregnancies complicated with Edwards syndrome and 183 uncomplicated pregnancies during the second trimester of pregnancy. The present results demonstrate that leptin concentrations in uncomplicated pregnancies slightly decrease from the 16th week of pregnancy, reaching a minimum of 18.8 ng/ml around the 20th week, and then rapidly increase to 28.2 ng/ml by the 24th week. Leptin correlation with maternal body weight decreases from r=0.695 at 16-17 week of gestation to r=0.544 at >22 weeks of gestation. There was no significant difference between the mean MoMs of Down syndrome- (0.926) or Edwards syndrome- (0.960) affected pregnancies and normal pregnancies (1.002). A weak correlation (r=0.18, p<0.02) was observed between corrected leptin MoMs and human chorionic gonadotrophin (hCG) MoMs in normal pregnancies. It is assumed that around the 20th week of pregnancy placental leptin production is activated or at least is accelerated and it is added to the amount of leptin produced by maternal adipose tissue. Fetal Down syndrome or Edwards syndrome does not seem to alter maternal leptin concentration and therefore leptin cannot be used as a marker for these chromosomal abnormalities in the early second trimester of pregnancy.     

Re-evaluation of risk for Down syndrome by means of the combined test in pregnant women of 35 years or more

OBJECTIVE: Evaluation of combined test in pregnant women 35 years of age and over to detect fetal Down syndrome. MATERIALS AND METHODS: The study population included 408 pregnant women of 35 years and over, who requested the combined test (nuchal translucency, PAPP-A, free beta hCG, maternal age, cut-off 1:250) before deciding whether to undergo amniocentesis. RESULTS: The test was positive in 66 women who then requested amniocentesis for fetal karyotype determination; the other women had a negative test and declined amniocentesis. False-positives increased with maternal age from 6.6% at 35 years to about 50% at 40 to 41 and 100% in women over 41. Six cases of Down syndrome and two cases of trisomy 18 were detected. Not a single case of Down syndrome or trisomy 18 was missed, and other chromosome abnormalities were detected as well. CONCLUSIONS: The application of the combined test reduced the need for invasive testing to only 14% of the studied pregnant population, without missing any of the fetuses with trisomy 21 or 18.     

Accuracy of Down syndrome risks produced in a first-trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry

Over the past three years approximately 12 000 women have been screened in the first trimester through our OSCAR programme, which utilizes fetal NT and maternal serum free beta-hCG and PAPP-A. During this time 30 cases of Down syndrome were identified either prenatally or postnatally. Using an established procedure the accuracy of predicted risk for Down syndrome was assessed in a population of 30 cases of Down syndrome and 11 758 unaffected pregnancies. The correlation between predicted risk and prevalence of Down syndrome was very high (r=0.9995). It is concluded that risks produced by the Fetal Medicine Foundation combined risk algorithm agree very closely with Down syndrome prevalence and can be used with confidence when counselling women of their risk.