Free Beta-human Chorionic Gonadotropin Research Articles

Maternal serum ADAM12s as a potential marker of trisomy 21 prior to 10 weeks of gestation

ADAM12s (a disintegrin and metalloprotease) is a placenta-derived glycoprotein that is involved in growth and differentiation and has been shown to be a potential first-trimester and second-trimester marker of trisomy 21 and other aneuploides. Maternal ADAM12s concentrations show a considerable temporal variation with gestational age and in the initial study levels were found to be significantly reduced in the early first trimester. Here we study the levels prior to 10 weeks of gestation to establish further the effectiveness or otherwise of ADAM12s as an early screening marker. Samples collected as part of routine first-trimester screening were retrieved from storage. In total, ten samples from singleton pregnancies with trisomy 21 were identified and were collected between the 8th and 9th weeks of gestation-of these 80% had been identified by combined first-trimester screening. A series of 62 gestational age-matched samples from singleton pregnancies collected during the same period formed the control group. ADAM12s was measured by a new DELFIA assay incorporating two monoclonals (6E6 and 8F8). Results were expressed as multiples of the median (MoM). The median MoM ADAM12s at a median gestation of 9.3 weeks was 0.61 which was significantly lower than in the controls (p = 0.011) when compared by the Mann-Whitney test. The corresponding median pregnancy associated plasma protein (PAPP-A) was 0.30 and free beta-human chorionic gonadotropin (beta-hCG) 2.02. Combining the data from this study and from the only other published study with data prior to 10 weeks suggests that ADAM12s may have the potential as an early screening marker for trisomy 21, but may not be as reduced as first thought.

Effect of maternal smoking on prenatal screening for Down syndrome and trisomy 18 in the first trimester of pregnancy

To assess the impact of maternal smoking on first-trimester prenatal screening results for Down syndrome and trisomy 18. Data on maternal smoking status, maternal age, gestational dating, levels of free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal blood and fetal nuchal translucency (NT) thickness were analyzed from a cohort of 53 114 women. Statistical analyses were carried out for crude and adjusted comparisons between smoking and nonsmoking groups. In women who smoked during the first trimester of pregnancy, PAPP-A and free beta-hCG levels from dried blood were significantly decreased (p < 0.001) and fetal NT thickness was significantly increased (p < 0.001). For an overall risk assessment combining maternal age and biochemical and ultrasound markers, no significant changes for Down syndrome were found with smoking, but significant increases in average risk as well as in positive rates were found for trisomy 18 (p < 0.001). A potential association between maternal smoking and trisomy 18 remains to be clarified. Adjustment for smoking is recommended in first-trimester prenatal screening for trisomy 18 and probably not warranted for Down syndrome because of the cancelling effects of decreased free beta-hCG and increased NT. Further research is required to demonstrate a biological association between maternal smoking and trisomy 18.

First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery

To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict preterm delivery. We examined 54 722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the median (MoM) of the expected normal median for a pregnancy of the same gestation and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length. The association between free beta-hCG, PAPP-A and delta NT and the incidence of preterm delivery before 37 weeks or early preterm delivery before 34 weeks was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratios (LR) for preterm delivery and early preterm delivery were also calculated after excluding other adverse pregnancy complications. The risk of preterm delivery increased with decreasing maternal serum PAPP-A. In the 3132 cases delivering before 37 weeks the PAPP-A MoM was 0.91 and in the 1060 cases delivering before 34 weeks the PAPP-A MoM was 0.90. At the 5th centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for delivery before 37 weeks and before 34 weeks were 1.92 and 2.35, respectively. The respective values for the 5th centile of free beta-hCG (0.41 MoM) were 1.18 and 1.08 and for the 95th centile of delta NT they were 0.91 and 0.77, respectively. Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk of preterm or early preterm delivery. The LR profiles provided at various levels of PAPP-A may be of some help in counseling women with such results and may raise awareness among healthcare professionals for increased surveillance in such cases.

Contingent screening for Down syndrome—results from the FaSTER trial

Comparison of contingent, step-wise and integrated screening policies. Mid-trimester Down syndrome risks were retrospectively calculated from FaSTER trial data. For contingent screening, initial risk was calculated from ultrasound measurement of nuchal translucency (NT), maternal serum pregnancy-associated plasma protein (PAPP)-A and free beta-human chorionic gonadotrophin (hCG) at 11-13 weeks, and classified positive (>1 in 30), borderline (1 in 30-1500) or negative. Borderline risks were recalculated using alpha-fetoprotein, hCG, unconjugated estriol (uE3) and inhibin at 15-18 weeks, and reclassified as positive (>1 in 270) or negative. For step-wise screening, initial negative risks were also recalculated. For integrated screening, a single risk was calculated from NT, PAPP-A and the second trimester markers. There were 86 Down syndrome and 32,269 unaffected pregancies. The detection rate for contingent screening was 91% and false-positive rate was 4.5%; initial detection rate was 60%, initial false-positive rate was 1.2% and borderline risk was 23%. Step-wise screening had 92% detection rate and 5.1% false-positive rate; integrated screening had 88% and 4.9% respectively. As predicted by modelling, the contingent screening detection rate for a fixed false-positive rate is comparable with step-wise and integrated screening, but substantially reduces the number needing to return for second trimester testing.

First trimester screening for Down's syndrome after assisted reproductive technology: non-male factor infertility is associated with elevated free beta-human chorionic gonadotropin levels at 10–14 weeks of gestation

We retrospectively compared the first trimester Down's syndrome serum screening markers free beta-hCG (fbetahCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation in 4,088 women with naturally conceived pregnancies and in women pregnant after ICSI (n = 163), IVF (n = 59) and frozen-thawed embryo transfer (n = 31), and we searched for a potential relationship between infertility cause and marker levels. We found lower serum PAPP-A levels in pregnancies after IVF and ICSI compared with spontaneously conceived pregnancies and non-male factor infertility was associated with elevated serum fbetahCG levels at 11-14 weeks of gestation.

Prediction of birth weight by fetal crown–rump length and maternal serum levels of pregnancy‐associated plasma protein‐A in the first trimester

To determine whether the first trimester crown-rump length (CRL), maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of birth weight. This was an observational study over 1.5 years in Chinese patients who underwent first-trimester combined screening for Down syndrome in a University fetal medicine unit. After excluding cases with multiple pregnancies, congenital malformations and in-utero deaths, the relationship between fetal CRL (expressed as standardized Z-score (Z-CRL)), maternal PAPP-A and fbeta-hCG levels (expressed as log(10) of multiples of the median) and birth weight (Z-BW) were analyzed by Pearson's correlation test followed by multiple regression to check for their independency. The predictive power of the independent predictors for small-for-gestational age (SGA, defined as birth weight < 10(th) centile) was then assessed using receiver-operating characteristics (ROC) curves, and the likelihood ratios were derived. A total of 2760 cases were included. Z-CRL, log(10) PAPP-A(MoM), and log(10) fbeta-hCG were positively correlated with Z-BW (P < 0.0001), but only Z-CRL and log(10) PAPP-A(MoM) were independent predictors (P < 0.0001). The areas under the ROC curves of PAPP-A(MoM) and Z-CRL were 0.608 and 0.593, respectively (P < 0.0001). Likelihood ratios increased with decreasing PAPP-A(MoM) and Z-CRL, but were around 1 when the markers were at or above the mean. First-trimester CRL and PAPP-A are independent factors that influence final birth weight. The lower the PAPP-A and the smaller the CRL, the higher the risk of a fetus becoming SGA. However, their predictive powers are not sufficiently good for them to be used alone for SGA screening.

Combining fetal nuchal fold thickness with second‐trimester biochemistry to screen for trisomy 21

To assess second-trimester screening for trisomy 21 by combining ultrasound nuchal fold (NF) measurement with maternal serum biochemistry. NF, maternal serum alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (beta-hCG) were determined concurrently at 14-19 weeks' gestation in a study population comprising 1813 women with singleton pregnancies, including 1257 unselected women undergoing serum screening for trisomy 21 (1999-2002), and 556 high-risk pregnancies prior to amniocentesis (2003-2005), 402 of whom had positive serum screening tests. The results were expressed in multiples of the gestation-specific normal median (MoMs). There were 1799 unaffected singleton pregnancies, and their NF values approximately fitted a log Gaussian distribution over a wide range. There was a weak but statistically significant correlation between log NF and log AFP (r = - 0.069, P < 0.005) and the correlation coefficient between log NF and log free beta-hCG was even smaller and not statistically significant (r = 0.038, P = 0.11). Among the seven trisomy 21 pregnancies, the median NF level was 1.53 MoM (geometric mean 1.75 MoM), a highly statistically significant increase compared with unaffected pregnancies (P < 0.0001, one-tail Wilcoxon Rank Sum Test). In pregnancies referred because of positive serum screening tests (391 unaffected, seven cases of trisomy 21, one of monosomy X and three other chromosomal anomalies) the use of NF to modify the serum screening risk would have reduced the invasive procedures in unaffected pregnancies by 46% without affecting the detection rate of trisomy 21 or other anomalies. Statistical modeling predicted that adding NF to AFP and free beta-hCG would increase detection more than would adding unconjugated estriol as well as inhibin-A, an analyte that is difficult to measure with precision. The addition of NF measurement to second-trimester biochemical markers improves screening performance, and could overcome drawbacks in the implementation of inhibin-A assay in clinical practice.

First‐trimester biochemical markers of aneuploidy and the prediction of small‐for‐gestational age fetuses

To examine the clinical utility of the first-trimester biochemical markers of aneuploidy in their ability to predict subsequent delivery of a small-for-gestational age (SGA) infant. We examined singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median (MoM) for a pregnancy of the same gestation. The association between free beta-hCG and PAPP-A and the incidence of SGA were assessed by comparing the relative incidence at MoM cut-offs and birth-weight centile cut-offs. At various marker levels the likelihood ratios (LR) for SGA were also calculated after excluding other adverse pregnancy complications. There were 46,262 pregnancies resulting in live births with birth weight at or above the 10(th) centile, and 3,539 below the 10(th) centile for gestation (SGA). There was a significant inverse association between the risk for SGA and maternal serum PAPP-A MoM but not free beta-hCG MoM. At the 5(th) centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for SGA below the 10(th), 5(th) and 3(rd) centiles of normal were 2.70, 3.21 and 3.66 and the respective detection rates for SGA were 12.0%, 14.0% and 16.0%. Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk for subsequent delivery of an SGA infant.

Serum screening of fetal chromosome abnormality during second pregnancy trimester: results of 26,803 pregnant women in Jiangsu Province

To evaluate the efficiency of the second trimester screening for fetal chromosomal anomaly using maternal serum marker. 27,313 pregnant women with the gestational age of 15 - 20 weeks were selected by stratified combined with cluster sampling from 13 counties over Jiangsu province and 5 townships, towns, or subdistricts from 6 randomly selected cities from southern, central, and northern Jiangsu, totally 95 communities, between July 2002 and November 2006. Questionnaire survey was conducted. Body weight was taken. Ultrasonography was used to confirm the gestational age. Peripheral blood samples were collected to detect the maternal serum alpha-fetoprotein (AFP) and free beta human chorionic gonadotrophin (f-betaHCG). The risk values of Down syndrome and Edwards syndrome were calculated. The women at high risk of Down syndrome and Edwards syndrome for their fetuses were recommended to receive genetic counseling and amniocentesis. All babies were followed up until six months to four years of age after birth. 26,803 of the 27,313 women (98%) were screened. The average was 25.1, and 1.7% of them were over 35. Serum screening showed that 1,244 (5%) were Down syndrome positive and 105 (0.4%) were Edwards syndrome positive. The final pregnant outcomes showed that 20 cases presented chromosomal abnormalities, of which 9 cases suffered from Down syndrome, 5 cases Edwards syndrome, and 6 cases other chromosomal abnormalities. The detection rate of Down syndrome and Edwards syndrome were 56% and 80% respectively. Under good quality control high prenatal detection rate of fetal chromosomal abnormalities can be reached by screening of maternal serum AFP and f-betaHCG during the second pregnancy trimester. Good cost-effectiveness depends on the incidence of targeted birth defects.

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

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

Genetic sonography after first‐trimester Down syndrome screening

Approximately 90% of Down syndrome cases are detected during first-trimester screening. We aimed to determine the potential effectiveness of second-trimester genetic sonography as a sequential screen for Down syndrome. In this simulation study, published statistical parameters for first-trimester free beta-human chorionic gonadotropin, pregnancy-associated plasma protein-A and nuchal translucency thickness, and second-trimester ultrasound markers (nuchal fold, hyperechoic bowel, short humerus, short femur, echogenic intracardiac focus, pyelectasis and major abnormality) were used to model the effectiveness of second-trimester genetic sonography combined with first-trimester screening. First-trimester combined screening alone resulted in a detection rate of 88.5% with a 4.2% false-positive rate. A follow-up genetic ultrasound examination in which only one sonographic marker was found and previous results were not taken into account would detect an additional 8% of Down syndrome cases for an additional false-positive rate of 13.2%. Using individual marker likelihood ratios to modify the first-trimester risk for screen-negative patients, genetic sonography detected an additional 6.1% of Down syndrome cases for an additional 1.2% false-positive rate, giving a total detection rate of 94.6% and a total false-positive rate of 5.4%. In a contingent protocol, in which genetic sonography would be performed only for patients with a first-trimester risk of between 1/300 and 1/2500, the detection rate was 4.8% and the false-positive rate was 0.7%, giving a total detection rate of 93.3% and a total false-positive rate of 4.9%. Second-trimester genetic sonography, if used properly, can be an effective sequential screen following first-trimester Down syndrome screening. Further studies on the role of the genetic sonogram as a follow-up to first-trimester combined screening are warranted.

Serum PAPP-A Levels at 10–14 Weeks of Gestation Are Altered in Women After Assisted Conception

The most sensitive and specific first-trimester Down syndrome screening test employs a combination of maternal age, nuchal translucency (NT) thickness, fβhCG, and PAPP-A. First trimester NT measurements do not differ significantly between pregnancies resulting from assisted reproductive technology (ART) and those resulting from spontaneous conception, but maternal blood levels of free beta human chorionic gonadotropin (fβhCG) are higher following in vitro fertilization-embryo transfer (IVF-ET), and levels of pregnancy-associated plasma protein-A (PAPP-A) are lower. Whether or not this results in a higher rate of false positive screening test results is controversial. The investigators compared the screen-positive rates of the first trimester Down syndrome screening test in women with singleton ART pregnancies to those of women whose pregnancies resulted from spontaneous conception. Participants included 130 women who were pregnant after IVF-ET (group 1); 54 who conceived after intracytoplasmic sperm injection (ISCI; group 2); and 914 control women who conceived spontaneously. Fetal NT thickness was estimated at 10–14 weeks’ gestation. Women who conceived via ICSI were 2.8 times as more likely to be screen positive than control women. Although ovarian stimulation in group 1 and group 2 women was associated with significantly lower PAPP-A levels than were present in the control group, women who conceived via IVF-ET were not more likely to be screen positive than control women. Levels of PAPP-A declined significantly as the number of retrieved oocytes or transferred embryos increased, but the levels of other markers were not affected. When a single embryo was transferred, or when ART conception occurred without ovarian stimulation, marker levels were similar to those following spontaneous conception. Although ICSI appears to be associated with a higher rate of false positive first trimester screening test results than that in spontaneously conceived pregnancies, women who conceive by other ART methods are not at increased risk.

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS. The concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log(10) MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (free beta-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers. The ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log(10) MoM (SD) of 0.268 (0.2678) compared to a mean log(10) MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free beta-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%--by adding ADAM 12 to the double test (AFP + free beta-hCG) was 4%, similar to that of adding uE3 to the double test. ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additional or alternative marker to those currently used in the second-trimester.

Are nuchal translucency, pregnancy associated plasma protein-A or free-β-human chorionic gonadotropin depending on maternal age? A multicenter study of 8,116 pregnancies

First-trimester screening according to Nicolaides uses maternal age to obtain a common background risk for trisomy 21. The likelihood ratios by nuchal translucency, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A are not with respect to maternal age. It was the aim of this study to investigate if likelihood ratios should better take care of it. Pearson's correlation and different models of regression analysis had been performed on the results of 8,116 first-trimester screenings. The total number of pregnancies was subdivided into three subgroups of healthy fetuses (n = 8,038); fetuses with Down's syndrome (n = 46) and fetuses with other genetic abnormalities (n = 32). Statistical testing was applied to each of the three groups. Strong independence from maternal age could be found for each of the first-trimester screening measurement parameter, as well for healthy and as for affected fetuses. Neither Pearson's test nor nonlinear regression models could detect a correlation. Accordingly significance of Pearson's test is not given. First-trimester screening would not be improved by considering the maternal age in the calculation of the likelihood ratios. Therefore the currently used algorithm is adequate. According, to the results, it seems to be proper as well to disregard the maternal age in newer test strategies advanced first-trimester screening (AFS) at all.

Comparing First Trimester Screening Performance: Routine Care Gynaecologists’ Practices vs. Prenatal Centre

To evaluate and compare the screening performance for fetal trisomy 21 in the first trimester of pregnancy in general gynaecologists' practices and specialised centres for prenatal care in Germany. This study included 15,026 serum samples analysed in our laboratory for free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation between 1.1.2000 and 31.12.2003. Fetal risk for trisomy 21 was calculated using nuchal translucency (NT) values and crown-rump-lengths (CRL), measured either in general gynaecologists' practices or in a tertiary level prenatal centre. The detection rate for a fixed risk cut-off (1:300) and a fixed false-positive rate (5 %) was calculated for NT, serum biochemistry, maternal age and the combination of these components. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A was 1 in 300 or greater in 5.1 % (362 of 6897) and 8 % (329 of 3840) of normal pregnancies, and in 78.9 % (15 of 19) and 88.5 % (23 of 26) of those with trisomy 21. For a fixed false-positive rate of 5 %, the respective detection rates of screening for fetal Down's syndrome by maternal age and serum free beta-hCG and PAAP-A, maternal age and fetal NT and by maternal age, fetal NT and maternal serum biochemistry were (general gynaecologists' practices/prenatal centre) 68.4/69.2 %, 42.1/65.4 % and 78.9/88.5 %, respectively. The screening results are satisfactory in both general gynaecologists' practices and a prenatal centre.

Maternal serum free‐β‐chorionic gonadotrophin, pregnancy‐associated plasma protein‐A and fetal nuchal translucency thickness at 10–13+6 weeks in relation to co‐variables in pregnant Saudi women

To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined.

Elevated maternal second‐trimester serum alpha‐fetoprotein as a risk factor for placental abruption

To analyze the association of second-trimester maternal serum alpha-fetoprotein (MSAFP) and free beta human chorionic gonadotrophin (MSbeta-hCG) levels to placental abruption. Fifty-seven women with placental abruption and 108 control women without placental abruption were tested for second-trimester MSAFP and MSbeta-hCG levels as a part of a trisomy 21 screening program. Discriminatory cutoff levels for MSAFP were sought to predict placental abruption. The median of the MSAFP multiples of median (MoM) (1.21) was significantly higher in the abruption group than in the control group (1.07) (p = 0.004). In multivariate analysis, elevated MSAFP remained an independent risk factor for placental abruption when adjusting for other risk factors (parity >/= 3, smoking, previous placental abruption, preeclampsia, bleeding in II or III trimester, and placenta previa). MSAFP >/= 1.5 MoM had a sensitivity of 29% and a false-positive rate of 10%. The levels of the MSbeta-hCG MoM did not differ between the cases and the controls. Although second-trimester MSAFP levels are higher in women with subsequent placental abruption, the clinical usefulness of this test is limited due to low sensitivity and high false-positive rate.

First‐trimester combined screening for trisomy 21 in a predominantly Chinese population

To examine the effectiveness of first-trimester fetal trisomy 21 screening using a combination of maternal age, nuchal translucency thickness (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels in a predominantly Chinese population in Hong Kong. This was a prospective study over a 1.5-year period of 2990 women who underwent combined screening for trisomy 21 between 11+0 and 13+6 weeks of gestation in a university fetal medicine unit. NT was measured according to the criteria set by The Fetal Medicine Foundation (FMF), maternal serum free beta-hCG and PAPP-A levels were measured, and the risk of trisomy 21 was calculated using The FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above. All subjects were followed up for pregnancy and fetal outcome. Of the 2990 women who underwent the screening program, 99% were Chinese. There were 57 twin pregnancies, giving a total of 3047 fetuses. Thirty-one percent of the women were 35 years old or above. One hundred and eighty-five (6.1%) fetuses were screen-positive; this included 14 cases of trisomy 21 and 17 cases of other chromosomal abnormalities. The positive predictive value was 16.7%. Among the 2862 screen-negative fetuses, only 18 (0.6%) cases had an unknown fetal outcome. There were no cases in which trisomy 21 was missed and the infant was liveborn. First-trimester combined screening for fetal trisomy 21 is highly effective among Chinese subjects.

Defining a DSM Infrastructure

Defining a DSM Infrastructure

First‐trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death

To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict future fetal loss. We examined 54,722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness, maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median for a pregnancy of the same gestation (MoM) and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length (CRL). The association between free beta-hCG, PAPP-A and delta NT and the incidence of fetal loss prior to 24 weeks, at or after 24 weeks or at any time, was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratio (LR) for fetal loss was also calculated. The rate of fetal loss increased with decreasing maternal serum free beta-hCG and PAPP-A and increasing delta NT. At the 5th centile of the normal outcome group for free beta-hCG (0.41 MoM) the odds ratio for fetal loss before 24 weeks, at or above 24 weeks and at any gestation was 3.1, 1.8 and 2.6, respectively. The respective values for the 5th centile of PAPP-A (0.415 MoM) were 3.3, 1.9 and 2.8 and for the 95th centile of delta NT they were 2.5, 1.9 and 2.2, respectively. There was almost no correlation between reduced levels (<or=0.50 MoM) of PAPP-A and reduced levels of free beta-hCG in either the normal pregnancy group (r = 0.041) or the group with fetal death (r = 0.072), indicating relatively independent prediction by either biochemical marker. Low levels of maternal serum PAPP-A and free beta-hCG and increased fetal NT are associated, in the absence of an abnormal karyotype, with an increased risk of impending fetal death. The likelihood ratio profiles provided at various levels of PAPP-A or free beta-hCG may be of some help in counseling women with such results and raise awareness among health-care professionals for increased surveillance in such cases.