Detection of dysplastic lesions by fluorescence in a model of colitis in rats after previous photosensitization with 5-aminolaevulinic acid

Fetal nuchal translucency can be measured in most pregnant women in the first and early second trimester. The size of translucency varies slightly with gestational age and crown rump length and is independent of maternal age. Most authors have used a nuchal thickness of > or = 2.5 mm or > or = 3 mm to define abnormal, although some have suggested that the normal variation with gestation requires that different thresholds be used at different gestational ages. The accuracy of nuchal translucency measurement varies between examiners and between patients, likely in relation to examiner skill and image resolution. The small size of a nuchal translucency, less than 3 mm in most cases, probably approximates the threshold of normal interexaminer and intraexaminer variability. The presence of a thickened nuchal translucency is associated with chromosomal abnormality and perhaps with structural abnormality even when the karyotype is normal. Because of the reported variations in the populations studied, the methods used, and the results of screening, it is inappropriate at this time to assign a numeric risk to any individual patient with this finding. However, in both high-risk and low-risk groups, the positive predictive value appears to be high enough that patients with increased nuchal translucency should be counseled by their obstetrician and prenatal diagnostic testing should be offered. Because early genetic diagnosis by CVS has a substantially higher procedure-associated loss rate than amniocentesis in the second trimester, many patients may elect to wait for chromosomal testing. If so, disappearance of nuchal thickening should not be taken as reassurance. As a screening test to be widely applied to a general or low-risk population, the utility of fetal nuchal translucency measurement is uncertain. The reported sensitivity for identification of trisomy 21 has ranged from about 40% to 80%, and the sensitivity for identification of other aneuploidies may be lower than for Down's syndrome. From a cost-risk-benefit standpoint, universal first-trimester ultrasound screening has not been appropriately compared with standard risk assessment using maternal age and multiple-marker serum screening, with amniocentesis as the predominant diagnostic method. Also, the issues of availability and reimbursement have not been addressed. Currently, measurement of nuchal translucency is not a substitute for the standard of obstetrical care, which is to offer multiple-marker serum screening to every pregnant woman at 15 to 20 weeks. Similarly, it is inappropriate to substitute nuchal translucency measurement for genetic counseling and CVS or amniocentesis in women above 35 years of age or those with a significant positive history. Finally, the data are not clear as to whether a normal nuchal translucency decreases the likelihood of chromosomal abnormality in a high-risk population, and such women should not be discouraged from invasive testing because of a normal first-trimester ultrasound study. The data supporting the association between thickened nuchal transluency and chromosomal abnormality are compelling, but further study is needed before adopting routine nuchal translucency screening. Combining first-trimester ultrasonography with early serum screening is currently being investigated and may ultimately prove to be the most efficient means of screening for chromosomal anomaly.     

First-trimester nuchal translucency: a risk analysis on fetal chromosome abnormality

PURPOSE: To investigate the importance of nuchal translucencies in the first trimester of pregnancy as an ultrasonographic marker for fetal chromosome abnormalities. MATERIALS AND METHODS: One hundred two first-trimester fetuses with a nuchal translucency of 3 mm or more were karyotyped. Multiple logistic regression analysis was performed to estimate the risk of fetal chromosomal abnormalities related to nuchal translucencies. RESULTS: Fifty-five (54%) of the fetuses had a normal karyotype. Forty-seven (46%) had an abnormal karyotype. The risk of chromosome abnormality was strongly increased in fetuses with a septated nuchal translucency compared with fetuses with a nonseptated nuchal translucency. CONCLUSION: First-trimester nuchal translucency is an important ultrasonographic marker for chromosomal abnormalities in the fetus. The presence of a normal karyotype in a fetus is a strong indication that detailed ultrasonographic examination for associated anomalies should be undertaken.     

Ultrasound imaging of fetal neck anomalies: implications for the risk of aneuploidy and structural anomalies

This study summarizes 24,000 transvaginal ultrasound examinations which were performed in a predominantly low-risk population at 14-16 weeks' gestation. 1254 (5.2 per cent) fetuses had a nuchal fold or a non-septated cystic hygroma. Of these fetuses, 140 (11.1 per cent) had additional structural anomalies. Cardiovascular anomalies were the most commonly detected structural malformations. Forty-three (3.4 per cent) fetuses were aneuploid. Trisomy 21 was the most common chromosomal anomaly (n = 27). Aneuploidy was significantly more common in fetuses who had a nuchal finding and an associated structural anomaly. The prevalence of nuchal fold and non-septated cystic hygroma, as well as the incidence of their associated structural anomalies, was similar. Based on these data, it is concluded that a complete ultrasonic survey of the fetus and karyotyping are advocated in fetuses with a nuchal abnormality, irrespective of maternal age or triple serum screening results.     

Screening for fetal anomalies in the 12th week of pregnancy by transvaginal sonography in an unselected population

The advantages and limitations of transvaginal (TV) sonography in detecting fetal anomalies in the 12th week of pregnancy were examined in a prospective screening study of an unselected population. During a 3-year period, 3991 examinations were performed and 35 fetuses were identified as having 43 anomalies (0.9 per cent). Most of these malformations were either severe structural disorders or isolated nuchal changes when karyotyping revealed chromosomal aberration in six cases. Twenty-one pregnancies were terminated and three fetuses died. Routine transabdominal (TA) ultrasonographic examinations were performed at 18 and 30 weeks in all those pregnancies where the TV scan had not found fetal anomalies. TA sonography identified 19 abnormal fetuses and ten cases remained undetected. TV sonography detected 51 per cent of malformed fetuses which were diagnosed prenatally (not including cases with nuchal oedema) and 41 per cent of the total were found in this study. Besides offering the possibility of early termination, first trimester screening has the advantage of identifying a transient sonographic sign, nuchal oedema, which can be used as a marker in screening for fetal chromosomal abnormalities. However, standard mid-second-trimester TA scanning is still recommended, since a significant number of malformations cannot be detected so early in pregnancy.     

Depressive symptoms among international exchange students, and their predictors

Screening for fetal cardiac defects is traditionally based on the ultrasonographic examination of the four-chamber view of the fetal heart at mid-gestation, which has been shown to identify 26% of major cardiac defects. Pathological studies in fetuses with increased nuchal translucency at 10-14 weeks of gestation, a sonographic marker for chromosomal abnormalities, have shown an association between increased nuchal translucency and congenital abnormalities of the heart. This study reports the prevalence of cardiac defects in 1427 chromosomally normal fetuses with increased nuchal translucency thickness, and examines the potential value of this sonographic marker in screening for major cardiac defects. The diagnosis of cardiac defects was made either by postmortem examination in terminations of pregnancy and intrauterine or neonatal deaths or by clinical examination and appropriate investigations in live births. The prevalence of major cardiac defects was 17 per 1000 (24 of 1427 fetuses) and increased with translucency thickness from 5.4 per 1000 for translucency of 2.5-3.4 mm to 233 per 1000 for translucency of > or = 5.5 mm. These findings suggest that measurement of nuchal translucency thickness at 10-14 weeks may prove to be a useful method of screening for abnormalities of the heart and great arteries in addition to its role in screening for chromosomal defects.     

Increased nuchal translucency as a marker for fetal chromosomal defects

BACKGROUND: Screening for trisomy 21 (Down's syndrome) by measuring maternal serum alpha-fetoprotein, chorionic gonadotropin, and estriol concentrations and then performing chorionic-villus sampling or amniocentesis identifies approximately 60 percent of fetuses with this disorder. We used ultrasonography to detect increased nuchal translucency and cystic hygroma, which are characteristic features of fetuses with chromosomal defects. METHODS: We performed transvaginal ultrasonography in 10,010 unselected adolescents and women less than 40 years of age with live singleton fetuses at 10 to 15.9 weeks of gestation. Increased fetal nuchal translucency was defined as an area of translucency at least 3 mm in width, and cystic hygromas were defined as septated, fluid-filled sacs in the nuchal region. Subjects whose fetuses had these findings were offered fetal karyotyping. Information on pregnancies, deliveries, and neonates was subsequently obtained from hospital records and national birth and malformation registries. RESULTS: Nuchal translucency or cystic hygroma was seen in 76 fetuses (0.8 percent), of which 18 (24 percent) had an abnormal karyotype. The sensitivity for trisomies 21, 18, and 13 combined was 62 percent (13 of 21 fetuses), and the sensitivity for trisomy 21 alone was 54 percent (7 of 13 fetuses). CONCLUSIONS: The use of transvaginal ultrasonography to detect increased nuchal translucency and cystic hygroma is a sensitive test for fetal aneuploidy. It can be done earlier in pregnancy than serum screening, and it decreases the subsequent need for chorionic-villus sampling or amniocentesis.     

Sudden parotid swelling due to spontaneous haemorrhage

BACKGROUND: To evaluate the implementation of nuchal translucency measurement as an additional examination within the first trimester routine ultrasound in an unselected population of women. METHODS: A prospective study in which all pregnant women during 1994, referred for the first trimester routine ultrasound scan, were asked to participate. Of a total of 1852 women with a viable pregnancy, results from 1444 women were evaluated. When a nuchal translucency of 4 mm or more was found, the woman was offered both a genetic amniocentesis in gestational week 13-15 and an additional ultrasound examination in gestational week 18-19. RESULTS: Six fetuses had a nuchal translucency of 4 mm or more and none of these had any chromosomal abnormality. Neither had any of the fetuses in the study, karyotyped for other reasons, any chromosomal defect and nor was there any child born with aneuploidy in the study population. No strong relation between major malformations e.g. abnormalities of the heart and increased nuchal translucency was found. The fetus with the largest nuchal translucency (=6 mm) was born healthy. CONCLUSION: The efficacy of nuchal translucency measurement needs further evaluation before it can be introduced as a screening method in an unselected pregnant population.     

Efficacy of a novel hydrogel formulation in human volunteers

This study investigates whether first-trimester screening for trisomy 21 by fetal nuchal translucency thickness preferentially identifies those fetuses destined to die in utero and examines the potential impact of such a method of screening on the live birth incidence of trisomy 21. In 70 pregnancies, trisomy 21 was diagnosed at 12 (range 11-14) weeks of gestation and the parents opted for elective termination which was carried out at 14 (12-20) weeks. In all cases, viability was established by ultrasound scan at the time of chorion villus sampling (CVS) and just before termination of pregnancy. Eight (11.4%) fetuses died in the interval between CVS and termination of pregnancy and this rate of lethality was higher than the 6.9% estimated rate for an unselected population of trisomy 21 fetuses. This 4.5% increase may, in part, be attributed to the effects of CVS and may also be due to patient selection on the basis of increased nuchal translucency. The rate of lethality increased with translucency thickness from 5.3% for those with translucency of 1-3 mm to 23.5% for translucency of > 7 mm. In trisomy 21, the rate of intrauterine lethality is associated with nuchal translucency thickness. Nevertheless, a policy of screening by maternal age and fetal nuchal translucency followed by selective termination of affected fetuses would still result in a more than 70% reduction in the live birth incidence of trisomy 21.     

Early prognostic ultrasonographic indices in pregnancy with fetal cystic hygroma

OBJECTIVE: Aim of this study was the correlation of same early ultrasonographic signs with fetal karyotype, prognosis of pregnancy and neonatal outcome. EXPERIMENTAL DESIGN: Volume of cystic hygroma and presence of septations are correlated with fetal karyotype and an ultrasonographic follow-up was carried out during pregnancy. Details concerning neonatal outcome were recorded at delivery. PATIENTS: Diagnosis was performed in 13 patients between 8.3 to 16.5 weeks' gestation referred to our center for prenatal diagnosis or for obstetric reasons. METHOD: Ultrasonographic examinations were performed using 5.0 and 6.0 MHz endovaginal convex probes. SURVEYS: Hygroma was diagnosed as a cystic dilatation in the nuchal region larger than 3 mm in diameter in the anterolateral aspects. The volume was calculated considering the lesion as spherical and using the standard formula for an ellipsoid volume; the presence of septations was considered. RESULTS: A volume greater than 70 cc3 and the presence of septations demonstrated a strictly correlation with fetal karyotype, evolution of the features, pregnancy and neonatal outcome. CONCLUSIONS: Prognosis varies depending on fetal karyotype, volume, presence of septations and other associated malformations. The volume of the hygroma and the presence of septa are associated with higher incidence of chromosomal diseases and a poorer fetal prognosis.     

Effect of pulsatile oxytocin administration to the pregnant ewe in the last third of gestation on fetal ACTH and cortisol response to acute hypoxemia

OBJECTIVE: The aim of this study was to examine the effect of increased myometrial contractility throughout the last third of pregnancy on the ovine fetal response to short-term hypoxemia. METHODS: Oxytocin (600 microU/kg/minute, n = 5) or saline (n = 7) was infused for 5 minutes every 20 minutes into the maternal jugular vein starting at 95-99 days of gestation and continuing throughout the last third of gestation. Fetuses were subjected to a hypoxemic challenge (1 hour) at 131 days of gestation while fetal plasma ACTH and cortisol levels and nuchal muscle electromyogram activity were monitored. RESULTS: The fetal plasma ACTH concentration before and during the hypoxemic challenge was similar in the control and oxytocin groups. The fetal plasma cortisol concentration in the oxytocin group was significantly lower before and during the hypoxemia than in the controls. During hypoxemia, fetal nuchal muscle activity was significantly reduced only in the control group. CONCLUSION: Increased myometrial contracture frequency throughout the last third of pregnancy alters both the neuroendocrine and behavioral responses of fetal sheep to short-term hypoxemia.     

Screening for trisomy 21 by measuring nuchal translucency during the first trimester of pregnancy

The purpose of the present literature review is to assess the screening value of trisomy 21 by measurement of fetal nuchal translucency (NT) thickness in the first trimester. NT is a subcutaneous translucency between the skin and the soft tissues overlying the cervical spine, which disappears in the second trimester. Ultrasound examination was used to image a sagittal section of the fetus to measure the maximum thickness of the subcutaneous translucency. NT is physiological for a measurement < 3 mm but the incidence of chromosomal abnormalities (essentially trisomies 21, 18 and 13) increases when NT > or = 3 mm. Differential diagnoses include cystic hygroma and fetal hydrops. For screening purposes, a cut-off threshold value of > or = 3 mm, with a standardized technique, gave a sensitivity > or = 50%, a false positive rate < 5% and a positive predictive value > 1%. In the chromosomally normal group, prognosis was good, but incidence of structural defects and fetal loss increased, with a sharp rise in these complications for fetal translucency thickness > or = 5 mm.     

Using fetal nuchal translucency to screen for major congenital cardiac defects at 10-14 weeks of gestation: population based cohort study

OBJECTIVES: To examine the utility of measuring fetal nuchal translucency thickness in screening for major defects of the heart and great arteries at 10-14 weeks of gestation. DESIGN: Population based cohort study. SUBJECTS: 29 154 singleton pregnancies with chromosomally normal fetuses at 10-14 weeks of gestation. SETTING: Fetal medicine centre in London. MAIN OUTCOME MEASURE: Prevalence of major defects of the heart and great arteries. RESULTS: Of 50 cases with major defects of the heart and great arteries (prevalence 1.7 per 1000 pregnancies) 28 (56%, 95% confidence interval 42% to 70%) were in the subgroup of 1822 pregnancies with fetal nuchal translucency thicknesses above the 95th centile of the normal range. The positive and negative predictive values for this cut off point of nuchal translucency thickness were 1.5% and 99.9% respectively. CONCLUSIONS: Measurement of fetal nuchal translucency thickness-traditionally used to identify fetuses at high risk of aneuploidy-at 10-14 weeks of gestation can identify a large proportion of fetuses with major defects of the heart and great arteries.     

Biological control of nematode parasites of livestock in Fiji: screening of fresh dung of small ruminants for the presence of nematophagous fungi

OBJECTIVE: To assess risk factors and outcomes associated with nuchal cord at birth. STUDY DESIGN: A population-based, case-control study was conducted using linked birth and hospitalization records. Three thousand newborns were randomly selected from all singleton births with nuchal cord as noted on the birth record (n = 5,426) in King County, Washington, 1992-1993. For comparison, 3,000 controls were randomly selected from the 46,952 unaffected singleton births. RESULTS: An increased risk of nuchal cord was associated with induction of labor (odds ratio [OR] adjusted for maternal age and parity 2.0, 95% confidence interval [CI] 1.7-2.3), African American infant race (OR 1.3, 95% CI 1.0-1.6), primiparity (OR 1.2, 95% CI 1.0-1.5) and male sex (OR 1.2, 95% CI 1.0-1.3). After exclusion of selected obstetric complications, the risk of nuchal cord associated with induction of labor increased (OR 2.4, 95% CI 2.0-3.0). Nuchal cord was associated with increased risks of fetal distress (OR 2.7, 95% CI 2.1-3.4), meconium staining (OR 2.1, 95% CI 1.7-2.6), five-minute Apgar score < 7 (OR 1.6, 95% CI 1.1-2.4) and assisted ventilation < 30 minutes (OR 1.9, 95% CI 1.4-2.6). Although hospital charges for newborns with nuchal cord were slightly greater than for those without (P = .02), hospital lengths of stay did not differ significantly. CONCLUSION: Induction of labor was identified as an independent risk factor for nuchal cord. Certain adverse perinatal outcomes are increased in neonates with nuchal cord. However, neonates with nuchal cord do not have significantly longer neonatal hospital stays, and thus the adverse effects of nuchal cord may be transient.     

Intracoronary brachytherapy in the Cath Lab. Physics dosimetry, technology and safety considerations

The aim of this study was to examine the relationship between nuchal translucency measurements and outcome of pregnancy with special regard to fetuses with an enlarged nuchal translucency and a normal karyotype. Fetal nuchal translucency measurements were performed on consecutive mothers attending the prenatal diagnosis center of our hospital. A complete follow-up was obtained in 88.4% of the cases. Of the 74 fetuses (4.4%) with an enlarged nuchal translucency (> or = 3 mm), 25 (33.8%) had an abnormal karyotype. Two pregnancies ended in a spontaneous abortion before karyotyping was performed. In the remaining 47 eukaryotic fetuses with enlarged nuchal translucency, five (10.6%) had a structural anomaly, two were affected by genetic syndromes (4.2%) and an additional four fetuses (8.5%) were affected by a single-gene disorder. A spontaneous abortion or an intrauterine death occurred in 6.4% and in 2.1% of these fetuses, respectively. The total incidence of an unfavorable outcome in the group of chromosomally normal fetuses with enlarged nuchal translucency was 32%. In contrast, in the group with a normal nuchal translucency (< 3 mm), the incidence of an unfavorable outcome was 7.5%. There is a strong association between enlarged nuchal translucency measurements and congenital (structural and genetic) abnormalities, as assessed by receiver operator characteristic analysis. This may represent, in fetuses with a normal karyotype, a non-specific sign of a disturbance in the developmental process. In these cases, detailed ultrasound surveillance is recommended.     

Antimicrobial activity of ethanol, glycerol monolaurate or lactic acid against Listeria monocytogenes

Cytogenetic data about 145 chorionic villus samples obtained between the 13th and 35th week of gestation are reported. 'Late' chorionic villus sampling (CVS) was used to resolve different situations: failed amniotic fluid cell cultures (5 cases); confirmation of an abnormal karyotype, previously diagnosed as mosaic (14 cases); and ultrasound fetal malformation (23 cases). Most of the samples (103 cases) were analysed for the classical indications and in these cases, the principal aim was to obtain a rapid fetal karyotype. Excluding the cases used to check fetal karyotype, a chromosomal aberration was found in 11 out of 131 biopsies. In four cases of the group in which the fetal karyotype was checked (14 cases), the pathology observed at the first diagnosis was confirmed, while in the remaining ten cases the anomaly was not observed.     

First-trimester neck abnormalities: three-dimensional evaluation

In order to study the first trimester ultrasonographic differences between nuchal translucency and hygroma colli, we rescanned 25 fetuses (13 with nuchal translucency and 12 with hygroma colli) using transvaginal and three-dimensional ultrasonography, after obtaining a fetal karyotype report. Our objective was to test the premise that the different physiopathologic mechanisms of both processes would be reflected in detectable sonographic differences. Our retrospective analysis showed that the most striking ultrasonographic difference was the presence of bullae as well as greater irregularity, extent, and amplitude of the membrane in cases of hygroma colli. Fetuses with simple nuchal translucency had a more homogeneous linear membrane. Although detailed analysis was impossible in 30% of cases, we found three-dimensional ultrasonography to be a useful technique for establishing the differences between these two entities.     

Measurement of fetal nasal width by ultrasonography

OBJECTIVE: This study was designed to determine the range of normal fetal nasal width by ultrasonography, which may be beneficial for detection of trisomy 21 and other chromosomal abnormalities. We hypothesize that a wide, saddle-shaped nose, which is one of the clinical neonatal anatomic features of trisomy 21, can be diagnosed prenatally. STUDY DESIGN: Fetal nasal width diameter was measured on 782 normal white fetuses by ultrasonography. Gestational ages ranged from 13.8 to 40.4 weeks. Mean and SD of fetal width diameter was calculated weekly by gestational age to establish normal values. RESULTS: The fetal nasal width increased as a function of gestational age, showing a polynomial curve during pregnancy (r = 0.912, p = 0.002). With use of mean +/- 1 SD as a cutoff value, the results showed a sensitivity of 80% with a specificity of 67% and a positive predictive value of 2.2% with a negative predictive value of 99.7% for the diagnosis of trisomy 21. CONCLUSION: The fetal nasal width diameter may be used as a biometric measurement and may be useful to identify trisomy 21 or other chromosomal abnormalities in conjunction with other already defined parameters used in a genetic ultrasonographic screen.     

An alternative for women initially declining genetic amniocentesis: individual Down syndrome odds on the basis of maternal age and multiple ultrasonographic markers

OBJECTIVE: Our purpose was to develop a method of calculating the individual odds of Down syndrome on the basis of a combination of maternal age and multiple ultrasonographic parameters that can be used to counsel women at high risk who initially decline amniocentesis. STUDY DESIGN: Maternal age and ultrasonographic biometry data were collected prospectively on 3254 normal and 30 Down syndrome singleton fetuses between 15 and 24 weeks' gestation. Humerus length data were expressed as multiples of the normal median. Log transformation of the humerus length data permitted their expression in gaussian frequency distributions and the calculation of likelihood ratios for Down syndrome on the basis of humerus length. We also developed likelihood ratios on the basis of the degree of nuchal skinfold thickening and the presence or absence of hyperechoic fetal bowel and hypoplastic fifth digit. RESULTS: The ultrasonographic parameters and maternal age did not significantly correlate with each other and were significant independent predictors of Down syndrome. We therefore calculated the individual odds of Down syndrome by using the product of the age-related risk and the likelihood ratios associated with nuchal thickening, humerus length shortening, and the presence or absence of hyperechoic fetal bowel or fifth digit hypoplasia, respectively. At a Down syndrome risk level of >1:50, a 60.0% detection rate with 4.5% false-positive rate was observed with a screen-positive rate of 5.5%, positive predictive value of 1:10, and odds ratio (95% confidence interval) of 28.4 (12.8 to 64.0). CONCLUSION: This is the first report of individual odds calculation based on multiple midtrimester biometry parameters and maternal age. The screening efficiency is similar to that reported with triple-analyte serum screening. These data are useful for counseling women who are at increased Down syndrome risk and initially decline amniocentesis.     

Prenatal diagnosis of fetal nuchal cystic hygroma in 22 cases

OBJECTIVE: To investigate the early diagnosis and prognosis of fetal nuchal cystic hygroma. METHODS: 72 cases of fetal nuchal cystic hygroma diagnosed in uterus were analyzed retrospectively. RESULTS: Most of the cases were diagnosed by B ultrasound between 15-26 gestational weeks. 55.9% the multipara had abnormal pregnant history, and 40% (4/10) of fetuses with karyotype performed had chrosome abnormality. Except for fetal deaths and induced abortions, 3 cases had term deliveries: one neonatal death, one was born with hygroma of 5.9 cm x 3.7 cm and transferred for surgery, and the other one with hygroma disappeared at the 37th week and baby was born at 40 week with normal appearance. CONCLUSIONS: This disease is one of common fetal morphological abnormalities. Few may recover spontaneously but most have poor outcomes.     

Screening of maternal serum for fetal Down's syndrome in the first trimester

BACKGROUND: Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of pregnancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester. METHODS: We measured serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated protein A in 4412 women (82 percent of whom were 35 years of age or older) who came to 16 prenatal diagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal nuchal translucency were also reported. Fetal chromosomal analysis was performed in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome. RESULTS: A total of 48 pregnancies affected by Down's syndrome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five serum markers were as follows: 17 percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measurements of serum hCG and its free beta subunit were highly correlated. When used in combination with the serum concentration of pregnancy-associated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal translucency varied considerably between centers and could not be reliably incorporated into our calculations. CONCLUSIONS: Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum.