Total Human Chorionic Gonadotrophin Research Articles

Screening for Down syndrome at 14 weeks of pregnancy

To investigate whether statistical parameters used in Down syndrome screening between 15 and 22 weeks of pregnancy can be used at 14 weeks, we assayed alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and inhibin-A in 16 pregnancies with Down syndrome in the 14th week of pregnancy and expressed values in multiples of the normal median. The median and standard deviation values for these 16 pregnancies were not materially different from those published for 15-22 weeks. It is reasonable, therefore, to offer Down syndrome screening using these markers starting at 14 completed weeks of pregnancy instead of 15 weeks. It needs to be recognized, however, that serum AFP measurement for neural tube defect screening is less effective at this time than between 16 and 18 weeks of pregnancy.

Second-trimester maternal serum screening for Down's syndrome: free beta-human chorionic gonadotrophin (HCG) and alpha-fetoprotein, with or without unconjugated oestriol, compared with total HCG, alpha- fetoprotein and unconjugated oestriol

The aim of our study was to compare three protocols for second-trimester maternal serum screening for Down's syndrome in the same serum samples, using two triple tests [total human chorionic gonadotrophin (HCG), alpha-fetoprotein, unconjugated oestriol; and free beta-HCG, alpha-fetoprotein, unconjugated oestriol] and a double test (free beta-HCG and alpha-fetoprotein). The three protocols were compared in a series of 23 serum samples from Down's syndrome pregnancies and in a cohort of 2516 pregnant women receiving routine antenatal care between June 1992 and June 1993. Among the 23 affected cases, at a cut-off risk of 1:380, the detection rate of Down's syndrome was comparable with the double test (74%; 17/23) and the triple tests (65%; 15/23) (not significantly different). At the same cut-off risk, in the cohort of 2516 pregnant women screened between 15 and 18 weeks gestation, both protocols using free beta-HCG achieved a significant reduction of the number of false positive cases (P = 0.013 and 0.004 for double and triple tests respectively). We conclude that, compared to total HCG, alpha-fetoprotein and unconjugated oestriol, use of free beta-HCG and alpha-fetoprotein represents a better second-trimester screening test for Down's syndrome, because it significantly decreases the false positive rate at a lower running cost. The addition of unconjugated oestriol to the double test adds no further advantage.

PRENATAL DIAGNOSIS OF A DELETION OF 18q IN A FETUS ASSOCIATED WITH MULTIPLE-MARKER SCREEN POSITIVE RESULTS

We report here the observations of positive maternal serum screening tests for Down syndrome, cytogenetic and molecular analysis, and dysmorphic fetal features in a pregnancy with 18q-syndrome. A 33-year-old primigravida was referred for genetic counselling because of multiple-marker screen positive results. At 14 weeks' gestation, the woman had a Down syndrome risk of 1:107 calculated from a maternal serum alpha-fetoprotein (MSAFP) level of 1.49 multiples of the median (MOM), a total human chorionic gonadotrophin (hCG) level of 2.42 MOM, and a serum unconjugated oestriol (uE3) level of 0.55 MOM. At 17 weeks' gestation, a repeat test showed a Down syndrome risk of 1:10 calculated from an MSAFP level of 1.09 MOM and a free beta-hCG level of 12.3 MOM. Genetic amniocentesis revealed a de novo deletion of 18q22.2-qter. Intrauterine fetal death occurred at 21 weeks' gestation. At birth, the fetus manifested clinical findings of the 18q-syndrome. The phenotype was correlated with the extent of the deletion. Linkage analysis of the family confirmed the extent and paternal origin of the deletion.

Effect of allowing for ethnic group in prenatal screening for Down's syndrome.

We conducted a study to investigate ethnic group differences in levels of serum markers used in screening for Down's syndrome [serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha- and free beta-hCG, and dimeric inhibin-A], to estimate the extent to which maternal weight differences between ethnic groups explain these differences, and to estimate the effect of adjusting for ethnic group and maternal weight on screening performance. Serum measurements were taken from women who were screened prenatally for Down's syndrome. AFP, uE3, and hCG concentrations were available from 9462 white, 4215 black, and 4392 South Asian women with singleton pregnancies without Down's syndrome or neural tube defects between 15 and 22 weeks' gestational age. Frozen serum samples were available from a subset of 922 white, 449 black, and 135 South Asian women and were used for measurement of free alpha-hCG, free beta-hCG, and inhibin. Values were expressed as multiples of the median (MOM) for women of the same gestational age. There were statistically significant differences in the serum marker levels between ethnic groups that were not explained by differences in maternal weight. The main differences were found in black women compared with white women; black women had serum AFP levels 22 per cent higher (95 per cent confidence interval 20-24 per cent), total hCG levels 19 per cent higher (16-22 per cent), and free beta-hCG levels 12 per cent (3-21 per cent) higher. The other differences were less than 10 per cent. Adjusting for ethnic group only had a small estimated effect on screening performance: a maximum of about 0.5 per cent extra detection at a 5 per cent false-positive rate. At a fixed risk cut-off level, the false-positive rate will not be materially different between different ethnic groups. Adjusting serum markers for ethnic groups improves Down's syndrome screening performance to a very small extent. It is worthwhile because of its established value in AFP screening for open neural tube defects.

Serum markers for Down's syndrome in relation to number of previous births and maternal age.

We conducted a study to investigate the effect of parity on the following six serum markers used in screening for Down's syndrome, after adjusting them for ethnic group and maternal weight: alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and dimeric inhibin A. We aimed to estimate the effect of adjusting for any differences found on the screening performance. AFP, uE3, and hCG concentrations were available from 16,666 women with singleton pregnancies without Down's syndrome or neural tube defects and without insulin-dependent diabetes mellitus, who were screened between 15 and 22 weeks' gestational age. Stored serum samples were available on a subset of 1347 women and these were used to measure free alpha-hCG, free beta-hCG, and inhibin A. Serum concentrations were expressed as multiples of the median (MOM) for women of the same gestational age, weight, and ethnic group. Of the six markers, only hCG levels were affected by parity; hCG levels decreased by 3.1 per cent per previous birth (95 per cent confidence interval 2.2-4.0 per cent); there was no significant relationship between the number of previous abortions and hCG level after adjustment for the number of previous births. The effect of previous births on hCG was not due to maternal age. Only AFP was affected by maternal age, but the effect was small; levels increased by 4.4 per cent per 10 years of age (3.2-5.7 per cent). It is not worthwhile adjusting serum markers for parity or for maternal age in prenatal screening for Down's syndrome because their effect on the performance of screening is negligible.

Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy. International Prenatal Screening Research Group.

To determine the value of serum screening for Down's syndrome at 8-14 weeks of pregnancy using seven potential serum markers (alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, pregnancy associated plasma protein A (PAPP-A), and dimeric inhibin A). Stored blood samples collected from women at about 10 weeks of pregnancy, prior to having chorionic villus sampling procedure on account of advanced maternal age, were retrieved from pregnancies associated with Down's syndrome and from matched unaffected pregnancies. Twenty-one obstetric centres in nine countries. Seventy-seven pregnancies associated with Down's syndrome each matched with five controls (except in two cases that were matched with four controls) for maternal age (same five year age groups), duration of storage of the serum sample (same calendar year), and gestational age (usually same week of pregnancy). The levels of two potential markers differed between affected and unaffected pregnancies sufficiently to be of value in screening--free beta-hCG and PAPP-A. The median free beta-hCG level in affected pregnancies was 1.79 times the median level for unaffected pregnancies, and the median PAPP-A level was 0.43 times the normal median. These two markers were combined with maternal age to estimate a woman's risk of having a fetus with Down's syndrome. A screening programme that used a risk cutoff level of 1:300 would detect 63% of affected pregnancies and also classify 5.5% of unaffected pregnancies as screen positive. None of the other five markers added more than 2% detection for the same false-positive rate. The performance of screening using maternal age and serum-free beta-hCG and PAPP-A at 10 weeks of pregnancy was better than the double test (alpha-fetoprotein and hCG with maternal age) and similar to the triple test (alpha-fetoprotein, unconjugated oestriol and hCG with maternal age) at 15-22 weeks.

Age-independent indices in second-trimester serum screening for Down's syndrome are useless.

Serum screening for fetal Down's syndrome in the second trimester is far more efficient in older mothers than in younger ones because the risk calculation is based on maternal age. In recent publications, several authors have tried to better the 'classical' test for Down's syndrome screening by creating an age-independent index. This procedure, however, requires the assumption that at least for one parameter the mean MOM or the variance is not constant in relation to maternal age, leading to a smaller overlap in younger women. This study, based on almost 3000 normal cases and 161 cases with Down's syndrome, could not demonstrate any relationship between maternal age and MOM distribution for alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotropin (hCG), and free beta hCG. We conclude that for a constant false-positive rate, the detection rate of the 'classical' test for Down's syndrome screening in younger women cannot be bettered by creating an age-independent index.

More in-vitro bioactive, shorter-lived human chorionic gonadotrophin charge isoforms increase at the end of the first and during the third trimesters of gestation.

In the present study we analysed the dynamics of serum human chorionic gonadotrophin (HCG) charge isoform distribution throughout normal gestation and characterized some of the biological features of the several HCG glycoforms present in the circulation of pregnant women. Blood samples were obtained from normal pregnant women at 10-11, 12-15, 23-26 and 35-38 weeks of gestation. The sera were fractionated by preparative chromatofocusing and the separated HCG isoforms were identified and quantified by radioimmunoassay. The in-vitro biological activity and the plasma half-life of the several circulating HCG isoforms were determined by conventional methods. HCG isoforms became less acidic as pregnancy advanced. In samples taken at 10-11 weeks of gestation, the most acidic HCG molecules (pH < 3.7) comprised > 80% of total HCG recovered after chromatofocusing; this proportion decreased to 58, 60 and 47% in samples taken from weeks 12.1 to 38.4 of gestation. Meanwhile, the relative proportion of less acidic isoforms recovered within pH values 6.49-4.50 increased at the end of the first trimester (12-15 weeks), remained constant until weeks 23-26 and then increased further by the end of the third trimester. Less acidic isoforms had higher in-vitro biological potency per immunological unit than the more acidic analogues. Regardless of the trimester of pregnancy, the plasma half-life of the highly acidic (elution pH < 3.7) isoforms varied from 84.4 to 150 min (116.3 +/- 23.0; mean +/- SD), whereas the corresponding half-life of mid-acidic (pH 4.25-5.31) and low-acidic (pH 5.74-6.50) HCG isoforms ranged from 31.0 to 115.3 (75.5 +/- 20.6) and 15.3 to 58.3 (41.2 +/- 14.3) min respectively (P < 0.01, highly acidic versus mid- and low-acidic analogues and mid-acidic versus least acidic isoforms). The overall data indicate that the human trophoblast is able to regulate the exact intensity, biochemical composition and duration of the gonadotrophic stimulus secreted during the course of normal gestation. They also suggest that the decrease and maintenance of low serum HCG concentrations during the second and third trimesters of gestation may be partially caused by changes in the carbohydrate structure of the HCG molecule.

Detection of pregnancies with trisomy 18 in screening programmes for Down's syndrome.

It is possible to identify pregnancies with trisomy 18 as part of screening programmes for Down's syndrome that use maternal age, IX fetoprotein (AFP), unconjugated oestriol (uE3), and either total human chorionic gonadotrophin (total hCG) or its subunit, free ~-hCG. While the detection rates and false positive rates using risk as the test variable have been published for maternal age with (a) AFP, uE3, and hCG 2 and with (b) AFP and free ~-hCG3 this has not been done for maternal age with AFP, uE3,and free ~-hCG. Here we summarise the parameters of the distributions of the markers in affected and unaffected pregnancies, and in affected pregnancies we calculate the' standard deviation for the free ~-hCG and the correlation between free i3-hCG and AFP and between free ~-hCG and uE3.We then estimate the detection rates and false positive rates. The parameters of the distribution of all four markers in unaffected pregnancies have been published. In trisomy 18 pregnancies: (a) the parameters for AFP, uE3, and total hCG were taken from reference 2; (b) the median free ~-hCG was taken from reference 3; (c) the standard deviation for free ~-hCG was calculated by taking the difference in variance between trisomy 18 and unaffected pregnancies from reference 3 and adding this to the unaffected variance from reference 4; (d) the correlation between AFP and free ~-hCG was calculated by taking the difference in covariance between trisomy 18 and unaffected pregnancies obtained from reference 3, adding this to the unaffected covariance from reference 4 and then dividing by the standard deviations in (a) and (c); (e) there is no available correlation between uE3 and free ~-hCG and so it is assumed to be the same as in unaffected pregnancies. The truncation limits (that is, the range over which the distributions are Gaussian) for AFP, uE3, and total hCG were taken from reference 2. The limits for free i3-hCG are not yet known and are therefore assumed to be the same as for total hCG because of the high correlation between these two markers. Table 1 shows the parameters for the serum markers in the detection of trisomy 18. As in Down's syndrome pregnancies, trisomy 18 pregnancies tend to have low values for AFP and uE3, but unlike Down's pregnancies they have low levels of total hCG and free ~-hCG. Table 2 shows the detection rates, false positive rates, and odds of being affected given a positive result (OAPR) when using maternal age (England and Wales, 1984-88), AFP, uE3, and either total hCG or free ~-hCG. The birth prevalence of trisomy 18 is taken as one tenth that of Down's syndrome' with a spontaneous fetal loss rate of 70% between 16 weeks and term. A mid-trimester risk cut off of 1 in 100 with AFP, uE3, and total hCG in combination with maternal age yields a detection rate of 59% and a false positive rate of 0·19%. The OAPR at term is 1:23. With a 1% fetal loss rate due to amniocentesis there would be 0·23 unaffected fetal losses for every term pregnancy

Screening for Down's syndrome: the first two years experience in Bristol.

To evaluate the effectiveness of a programme for antenatal screening for Down's syndrome using alpha fetoprotein and total human chorionic gonadotrophin as maternal serum markers. A district general hospital providing a screening service to a local purchasing authority and (under contract) to another purchasing authority in the same region. Patients were counselled and screened between 15 and 20 weeks gestation and Down's risk estimates calculated using the maternal serum marker results as modifiers of the age related risk. Outcome was determined in collaboration with the Regional Cytogenetics Unit. Detection rate for Down's syndrome, false positive rate, uptake of screening, and uptake of amniocentesis. In two years 22816 women were screened (approximately 84% of population); 32 Down's pregnancies were identified, 19 (59.4%) had a reported risk of > or = 1:250 and 20 (62.5%) a reported risk of > or = 1:300. Of those screened before 17 weeks, 16/20 (80%) had a reported risk of > or = 1: 300 compared with 4/12 (33%) of those screened later (P = 0.008); 4.64% of patients screened had reported risks > or = 1: 250 and 5.87% reported risks of > or = 1:300. Amniocentesis uptake was 70% in patients with reported risks of > or = 1:300. Overall the screening programme was effective but screening before 17 weeks was very much more effective than screening later.

Screening for Down syndrome during the first and second trimesters: Impact of risk estimation parameters

Objectives: To evaluate impact of risk estimation parameters for screening for Down Syndrome during the first and second trimesters. Methods: We prospectively examined for their performance in the prenatal prediction of trisomy 21, alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic gonadotropin (hCG), and its free subunits (free α-hCG, free β-hCG) at both the first and second trimesters, and the impact of three sets of published risk estimation parameters. A total of 14,612 pregnancies were studied. All Down syndrome specimens (12 and 11 cases for first and second trimesters, respectively) and a sample of the unaffected pregnancies were analyzed. Results: The median multiple of median (MoM) for total hCG was lower in the first trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative power was observed if the lower variability of the results in the first trimester is taken into account (interquartile range of 0.251 vs. 0.338). The choice of distribution parameters did not alter significantly the detection rates for the various combinations of markers ( p > 0.05). False positive rates were affected significantly however and for the combination AFP-uE3-free β-hCG they varied from 14.6% to 22.6% ( p < 0.001). Conclusions: Our results suggest that specific distribution parameters would be necessary to account for the lower variability of the markers in the first trimester and the peculiarity of the total hCG assay we used.

Doubts using family history, age, alpha‐fetoprotein and total human chorionic gonadotrophin in screening for Down's syndrome

Doubts using family history, age, alpha‐fetoprotein and total human chorionic gonadotrophin in screening for Down's syndrome

Rapid, automated quantification of total human chorionic gonadotropin in serum by a chemiluminescent enzyme immunometric assay

Total human chorionic gonadotropin (hCG-hCG beta) in serum was assayed with the immulite system, a fully automated random-access immunoassay analyzer that has a unique centrifugal procedure for solid-phase washing and a chemiluminescent detection system. The broad range of the hCG calibration curve (up to 5000 IU/L) is achieved by using a small serum sample size (5 microL), which provides sufficient volume for low-end sensitivity and prevents the possible high-dose hook effect in the working range of the assay. Within-run imprecision (CV) ranged from 3.9% to 5.9% for hCG between 10.5 and 2908 IU/L. Between-run imprecision ranged from 8.8% to 12.7% for hCG mean concentrations from 11.4 to 88.4 IU/L. The antibodies used in the immulite hCG assay system gave little or no interferences when high amounts of follitropin, lutropin, and thyrotropin were added. A complete recognition of the free beta-subunit of hCG was obtained (+/- 180%). In sera from women with molar pregnancies, we observed no high-dose hook effect at hCG concentrations up to 3000 kIU/L. The broad range of hCG concentrations encountered throughout normal pregnancy (up to 200 kIU/L) requires an extended working range to avoid high dilutions. In early pregnancy, accuracy in the range of 1000-5000 IU/L is enhanced by avoiding dilutions.

The influence of gravidity on Down's syndrome screening with free beta hCG.

Total human chorionic gonadotropin (hCG) levels have been shown in one previous small study to vary with gravidity. In order to establish if maternal serum free beta hCG was similarly affected, approximately 4500 pregnancies of varying gravidity were analysed. The results indicated that there was a 6 per cent higher median MOM in primigravid compared with multigravid women. The impact of such elevation in Down's syndrome screening programmes will be minimal.

Changes in the localization of human placental glucose transporter 1 (GLUT1) throughout pregnancy

Objective: Our purpose was to investigate the biochemical composition of the coelomic fluid in first-trimester anembryonic pregnancies.Study Design: Coelomic and maternal serum were obtained from 17 anembryonic pregnancies and 17 apparently normal pregnancies between 7 and 12 weeks of gestation that were matched for gestational age. Electrolytes, total proteins, urea, creatinine, lactate, and human chorionic gonadotropin concentrations and pH were measured.Results: Significantly higher pH (p < 0.005) and bicarbonate levels (p < 0.001) and significantly lower total protein (p < 0.05), phosphate (p < 0.005), and human chorionic gonadotropin (p < 0.001) levels were found in coelomic fluid from anembryonic pregnancies compared with normal pregnancies. No difference was found for chloride, sodium, potassium, urea, creatinine, and lactate between the study and control groups.Conclusions: The fluid collected in anembryonic pregnancies is of exocoelomic origin and its biochemical characteristics reflect a failure of most placental biological mechanisms such as metabolic function, transport function, and endocrine activity.

Biochemical composition of the coelomic fluid in anembryonic pregnancy

Our purpose was to investigate the biochemical composition of the coelomic fluid in first-trimester anembryonic pregnancies. Coelomic and maternal serum were obtained from 17 anembryonic pregnancies and 17 apparently normal pregnancies between 7 and 12 weeks of gestation that were matched for gestational age. Electrolytes, total proteins, urea, creatinine, lactate, and human chorionic gonadotropin concentrations and pH were measured. Significantly higher pH (p < 0.005) and bicarbonate levels (p < 0.001) and significantly lower total protein (p < 0.05), phosphate (p < 0.005), and human chorionic gonadotropin (p < 0.001) levels were found in coelomic fluid from anembryonic pregnancies compared with normal pregnancies. No difference was found for chloride, sodium, potassium, urea, creatinine, and lactate between the study and control groups. The fluid collected in anembryonic pregnancies is of exocoelomic origin and its biochemical characteristics reflect a failure of most placental biological mechanisms such as metabolic function, transport function, and endocrine activity.

Doubts using family history, age, alpha-fetoprotein and total human chorionic gonadotrophin in screening for Down's syndrome.

BJOG: An International Journal of Obstetrics & GynaecologyVolume 101, Issue 8 p. 710-711 Doubts using family history, age, alpha-fetoprotein and total human chorionic gonadotrophin in screening for Down's syndrome F. A. Sanusi, Corresponding Author F. A. Sanusi Registrar Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexDr F. A. Sanusi, Department of Obstetrics and Gynaecology, Edgware General Hospital, Wellhouse NHS Trust, Edgware, Middlesex HA8 OAD, UK.Search for more papers by this authorJ. McCauley, J. McCauley Senior House Officer Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this authorS. Oganwu, S. Oganwu Registrar Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this authorL. W. Bernhardt, L. W. Bernhardt Consultant Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this authorM. D. Simanowitz, M. D. Simanowitz Clinical Director Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this author F. A. Sanusi, Corresponding Author F. A. Sanusi Registrar Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexDr F. A. Sanusi, Department of Obstetrics and Gynaecology, Edgware General Hospital, Wellhouse NHS Trust, Edgware, Middlesex HA8 OAD, UK.Search for more papers by this authorJ. McCauley, J. McCauley Senior House Officer Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this authorS. Oganwu, S. Oganwu Registrar Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this authorL. W. Bernhardt, L. W. Bernhardt Consultant Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this authorM. D. Simanowitz, M. D. Simanowitz Clinical Director Department of Obstetrics and Gynaecology, Edgware General Hospital, Edgware, MiddlesexSearch for more papers by this author First published: August 1994 https://doi.org/10.1111/j.1471-0528.1994.tb13191.xCitations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume101, Issue8August 1994Pages 710-711 RelatedInformation

Initial findings of the ontario provincial maternal serum screening program for neural tube defects and fetal trisomies

Objectives: To evaluate impact of risk estimation parameters for screening for Down Syndrome during the first and second trimesters. Methods: We prospectively examined for their performance in the prenatal prediction of trisomy 21, alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic gonadotropin (hCG), and its free subunits (free α-hCG, free β-hCG) at both the first and second trimesters, and the impact of three sets of published risk estimation parameters. A total of 14,612 pregnancies were studied. All Down syndrome specimens (12 and 11 cases for first and second trimesters, respectively) and a sample of the unaffected pregnancies were analyzed. Results: The median multiple of median (MoM) for total hCG was lower in the first trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative power was observed if the lower variability of the results in the first trimester is taken into account (interquartile range of 0.251 vs. 0.338). The choice of distribution parameters did not alter significantly the detection rates for the various combinations of markers (p > 0.05). False positive rates were affected significantly however and for the combination AFP-uE3-free β-hCG they varied from 14.6% to 22.6% (p < 0.001). Conclusions: Our results suggest that specific distribution parameters would be necessary to account for the lower variability of the markers in the first trimester and the peculiarity of the total hCG assay we used.

Antenatal screening of down syndrome: Performance of five bio-chemical markers

Objectives: To evaluate impact of risk estimation parameters for screening for Down Syndrome during the first and second trimesters. Methods: We prospectively examined for their performance in the prenatal prediction of trisomy 21, alphafetoprotein (AFP), unconjugated estriol (uE3), total human chorionic gonadotropin (hCG), and its free subunits (free α-hCG, free β-hCG) at both the first and second trimesters, and the impact of three sets of published risk estimation parameters. A total of 14,612 pregnancies were studied. All Down syndrome specimens (12 and 11 cases for first and second trimesters, respectively) and a sample of the unaffected pregnancies were analyzed. Results: The median multiple of median (MoM) for total hCG was lower in the first trimester (1.83 vs. 2.01 in the second trimester) but no loss in discriminative power was observed if the lower variability of the results in the first trimester is taken into account (interquartile range of 0.251 vs. 0.338). The choice of distribution parameters did not alter significantly the detection rates for the various combinations of markers (p > 0.05). False positive rates were affected significantly however and for the combination AFP-uE3-free β-hCG they varied from 14.6% to 22.6% (p < 0.001). Conclusions: Our results suggest that specific distribution parameters would be necessary to account for the lower variability of the markers in the first trimester and the peculiarity of the total hCG assay we used.

Elevated serum human chorionic gonadotropin as evidence of secretory response in severe preeclampsia

OBJECTIVE: Because preeclampsia is a trophoblastic disorder and human chorionic gonadotropin is secreted from trophoblast, we sought to determine whether measurement of serum human chorionic gonadotropin might reflect a different trophoblastic secretory response of preeclampsia. STUDY DESIGN: Twenty patients with mild preeclampsia and 12 with severe preeclampsia were matched with 32 healthy, normotensive women in the third trimester with singleton pregnancies. Serum total human chorionic gonadotropin and total human chorionic gonadotropin-β were measured by a two-site immunoenzymometric assay, and total hCG-α was determined by a double-antibody radioimmunoassay. Wilcoxon signed-rank and Mann-Whitney rank-sum tests were used for statistical analysis. RESULTS: Serum total human chorionic gonadotropin, total human chorionic gonadotropin-α, and total human chorionic gonadotropin-β levels were significantly higher in severely preeclamptic women (p < 0.05), but not in those with mild preeclampsia, compared with those in their matched controls. CONCLUSION: Elevated serum human chorionic gonadotropin levels in severely preeclamptic women might reflect a significantly pathologic change and secretory reaction of the placenta. (AM J OBSTET GYNECOL 1994;170:1135-8.)