Second-trimester Maternal Serum Markers Research Articles

The effect of a vanishing twin on first- and second-trimester maternal serum markers and ultrasound screening for aneuploidy.

A vanishing twin (VT) is the early demise of a twin fetus. It is estimated to occur in 20-30% of pregnancies associated with assisted reproductive technology. VT becomes increasingly prominent when assisted fertilization is used, because one or more embryos are transferred to the uterus. Maternal serum screening tests during pregnancy can screen for trisomy chromosomes 21, 18, and 13 and are divided into first- and second-trimester tests. In singleton pregnancies, the first trimester screening test is performed at 11-13 weeks and 6 days of gestation. It consists of two serum markers, pregnancy-associated plasma protein A and β-human chorionic gonadotropin (β-hCG), and measures nuchal translucency thickness. The second-trimester screening test was performed at 15-20 weeks and 6 days of gestation. It consists of four serum markers: alpha-fetoprotein, β-hCG, unconjugated estriol, and inhibin A. More effective screening for trisomy 21 in singleton pregnancies is achieved by analyzing cell-free DNA in the maternal blood. A VT includes a demise of the fetus. Although it affects maternal serum markers, it has not been corrected. Five studies examined the effect of VT on maternal serum markers, but the results were controversial. This study aimed to review the patterns of changes in maternal serum markers in VTs, interpret prenatal tests for pregnant women with VTs in clinical practice, and consider what information should be provided.

Relations between second-trimester aneuploidy screening results and prediction of labour induction success in term pregnancies

We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group (p < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term. IMPACT STATEMENT What is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%. What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.

Second-trimester maternal serum markers in the prediction of preeclampsia.

To determine whether late second-trimester maternal serum biomarkers are useful for the prediction of preeclampsia during the third trimester, a case-control study including 33 preeclamptic and 71 healthy pregnancies was conducted. Maternal serum concentrations of placental protein 13 (PP13), pregnancy-associated plasma protein (PAPP-A), pentraxin3 (PTX3), soluble FMS-like tyrosine kinase-1 (sFlt-1), myostatin and follistatin-like-3 (FSLT-3) were measured at 24-28 weeks' gestation. All the concentrations of these markers were compared between the preeclamptic and control groups. Receiver operating characteristic (ROC) curve analysis was applied to assess sensitivity and specificity of serum markers with significant difference. The levels of PP13 and sFlt-1 were significantly increased and FSLT3 was significantly decreased in patients with preeclampsia. However, the concentration of PAPPA, PTX3 and myostatin did not differ significantly. In screening for preeclampsia during the third trimester by PP13, sFlt-1 and FSLT3, the detection rate was 61.3%, 48.1% and 39.1%, respectively, at 80% specificity, and the detection rate increased to 69.8% by combination of these three markers. Maternal serum levels of PP13, sFlt-1 and FSLT3 play an important role in predicting late-onset preeclampsia, and the combination of these three markers significantly increases the detection rate for prediction.

First- and second-trimester maternal serum markers of pre-eclampsia in twin pregnancy.

To evaluate the distribution of first- and second-trimester maternal serum markers in twin pregnancy with and without pre-eclampsia. One-hundred and forty-four twin and 109 unaffected singleton pregnancies were recruited from the same institution. First- and second-trimester maternal blood samples were stored and measured retrospectively for serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (β-hCG) and α-fetoprotein (AFP). All had measurement of first-trimester serum markers, and 167 (66%) had second-trimester tests. Values were expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight, as appropriate. Pre-eclampsia was diagnosed in 12 (9.0%) twin pregnancies of 133 continuing beyond 22 weeks. In unaffected twin pregnancies, all serum markers were statistically significantly increased (P < 0.0001), consistent with a doubling of concentration. Among twin pregnancies, those with pre-eclampsia had a significantly reduced median PlGF compared with surviving unaffected twin pregnancies (0.96 MoM vs 1.46 MoM; P < 0.0002, two-tailed), whilst median PAPP-A, which is known to be reduced in affected singleton pregnancies, was increased (3.91 MoM vs 2.43 MoM; P < 0.0005, two-tailed). The levels of free β-hCG (P < 0.02) and AFP (P < 0.05) were also significantly raised, but to a lesser extent than was the level of PAPP-A. Using a logistic regression algorithm based on first- and second-trimester PlGF and PAPP-A, together with previously published uterine artery Doppler and mean arterial pressure measurements in the same series, the predicted pre-eclampsia detection rate was 65% for a 10% false-positive rate. In twin pregnancy, the predicted detection rate of pre-eclampsia using first- and second-trimester maternal serum and biophysical markers is good. In contrast to singleton pregnancy, PAPP-A levels are raised in the first trimester of twin pregnancies destined to develop pre-eclampsia and therefore a different prediction algorithm is needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Screening for Down syndrome in the second trimester of pregnancy

Antenatal screening for fetal anomalies has provided women and their partners with information to make reproductive choices based on the risk of serious chromosomal or structural defects since the 1990s. Alternative tests include first-trimester screening (combined ultrasound and maternal serum markers), second-trimester maternal serum markers and noninvasive cell-free DNA testing. The recent recommendations by the Royal Australian and New Zealand College of Obstetrics and Gynaecology and the Human Genetics Society of Australasia against second-trimester triple testing are based on unsound performance criteria, raise several contestable issues around access and equity and challenge the principles of governments providing affordable options.

Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy

Objective: To evaluate first and second-trimester maternal serum markers in pregnancies complicated with inherited thrombophilias. Methods: A case-control study was conducted in 50 pregnancies complicated with hereditary thrombophilia and 100 control pregnancies. Results: Each woman with inherited thrombophilia received low molecular weight heparin (LMWH) throughout her pregnancy. Gravidity, parity, number of first-trimester and second-trimester abortions, and rate of adverse pregnancy outcomes (APO) were significantly higher in the thrombophilia group compared to the control group (P < 0.001 for all). Among the thrombophilia group median values of pregnancy associated placental protein-A (PAPP-A) (0.6 vs. 0.9; P < 0.001) and free β-human chorionic gonadotropin (β-hCG) (0.9 vs. 1.1; P = 0.001) in the first trimester; median values of α-fetoprotein (AFP) (0.7 vs. 1.1; P = 0.027), unconjugated estriol 3 (uE3) (0.9 vs. 1.1; P < 0.001), and hCG (0.7 vs. 1.2; P < 0.001) in the second trimester were significantly lower with respect to control pregnancies. Multivariate analysis revealed that low uE3 and hCG levels were independently associated with APO. Conclusion: Pregnant women with hereditary thrombophilias, all of whom were treated with LMWH, had decreased levels of all first and second trimester serum markers. In addition, levels of hCG and uE3 in the second trimester could independently predict placenta-related disorders and adverse outcomes in these patients.

Early Detection of Preeclampsia Using Inhibin A and Other Second-Trimester Serum Markers

Objective: The purpose of this study was to determine whether second-trimester maternal serum markers including inhibin A are useful for the detection of preeclampsia. Methods: Between January 2005 and March 2009, we analyzed the data of 4,764 subjects who underwent second-trimester multiple-marker screening for Down syndrome. Serum samples were assayed at 15+0 to 20+6 weeks for maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE₃) and inhibin A. We reviewed all medical records retrospectively, and assessed the relationships of several markers with preeclampsia using logistic regression analysis. Results: The study sample included 41 patients who developed preeclampsia and a control group consisting of the other 4,723 healthy subjects treated between January 2005 and March 2009. There were no significant differences in gestational ages at blood sampling, maternal weights, gravidity and parity between the two groups. However, the mean ages, Apgar scores, gestational age at delivery and neonatal weights were significantly different between the study group and the control group. The levels of markers in the study group were significantly increased compared to the control group, 1.76 ± 2.68 for inhibin A, 1.18 ± 0.69 for MSAFP, and 1.62 ± 1.18 for hCG, but uE₃ did not differ significantly between the two groups. The AUC of inhibin A was 0.715, but the AUC of a three-marker combination model (0.800) was even better. A mid-trimester inhibin A concentration of 1.5 MoM or greater had a sensitivity of 60% and a false-positive rate of 16% for the prediction of preeclampsia. Inhibin A was the best predictor of preeclampsia. Three other markers were reliable predictive markers of preeclampsia. Conclusions: Inhibin A and other second-trimester serum markers may be useful for early detection of preeclampsia. Inhibin A was in fact the most important predictable marker among the markers we surveyed. The results of this study support those of previous studies, and provide quantified data elucidating the occurrence of preeclampsia.

First- and Second-Trimester Maternal Serum Markers for Aneuploidy and Adverse Obstetric Outcomes

Maternal serum levels of the first- and second-trimester markers for aneuploidy have been shown to be associated with adverse obstetric outcomes in the absence of aneuploidy or neural-tube defects. The likelihood of an adverse obstetric outcome increases as the values of the marker become more extreme, and as the number of abnormal markers increases. Although many of the associations between maternal serum markers for aneuploidy and adverse obstetric outcomes are statistically significant, the sensitivity and positive predictive values for the individual outcomes are too low for them to be clinically useful as screening tests. Currently in the United States there is not a uniformly accepted practice for the care of women with abnormal maternal serum markers regarding risk of future obstetric complications. There are no randomized trials assessing any type of intervention or treatment for patients with abnormal serum markers. Various strategies to manage patients with unexplained abnormal serum markers have been proposed. This article reviews the relationships between these markers and adverse obstetric outcomes. In addition, potential management strategies and future areas of research are discussed.

The impact of crown–rump length measurement error on combined Down syndrome screening: a simulation study

To evaluate the impact of a 5-mm error in the measurement of crown-rump length (CRL) in a woman undergoing ultrasound and biochemistry sequential combined screening for Down syndrome. Based on existing risk calculation algorithms, we simulated the case of a 35-year-old-woman undergoing combined screening based on nuchal translucency (NT) measurement and early second-trimester maternal serum markers (human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) expressed as multiples of the median (MoM)). Two measurement errors were considered (+ or - 5 mm), for four different CRLs (50, 60, 70 and 80 mm), with five different NT measurements (1, 1.5, 2, 2.5 and 3 mm) in a patient undergoing biochemistry testing at 14 + 4, 15, 16, 17 or 18 weeks' gestation. Four different values for each maternal serum marker were tested (1, 1.5, 2 and 2.5 MoM for hCG, and 0.5, 0.8, 1 and 1.5 MoM for AFP), leading to a total of 3200 simulations of the impact of measurement error. In all cases the ratio between the risk as assessed with or without the measurement error was calculated (measurement error-related risk ratio (MERR)). Over 3200 simulated cases, MERR ranged from 0.53 to 2.14. In 586 simulations (18.3%), it was < 0.66 or > 1.33. Based on a risk cut-off of 1/300, women would have been misclassified in 112 simulations (3.5%). This would go up to 33 (27.5%) out of the 120 simulations in women with 'borderline' risk, with 1.5 MoM for hCG and 0.5 MoM for AFP, and NT measurement of 1 or 2mm. Down syndrome screening may be highly sensitive to measurement errors in CRL. Quality control of CRL measurement should be performed together with quality control of NT measurement in order to provide the highest standard of care.

Second‐trimester Down syndrome maternal serum marker screening: a prospective study of 11 040 twin pregnancies

To analyze the value of Down syndrome (DS) second-trimester maternal serum screening in large series of twin pregnancies. Prospective study of second-trimester maternal serum markers [alpha fetoprotein (AFP) and free beta-human chorionic gonadotrophin (beta-hCG)] in 11,040 twin pregnancies, 27 of which were trisomy 21-affected. Comparison with 64,815 singleton pregnancies, of which 86 were trisomy 21-affected. Markers were expressed in multiple of median (MoM) corrected by a previously defined coefficient (2.1 for AFP and 2.07 or 2.16 for free beta-hCG, dichorionic or monochorionic, respectively). Trisomy 21 frequency was 1/649 for twins and 1/754 in singletons (NS). Mean detection rate was 63% (71% when both twins were affected and 60% when one was affected), versus 74.4% in singletons. False-positive rates were 10.8% in twins versus 10.3% in singletons (NS). No significant differences in MoM AFP and free beta-hCG values were noted between twins and singletons (0.92 and 0.78 for AFP and 1.54 and 2.68 for free beta-hCG, respectively). Our study demonstrates that second-trimester DS maternal serum marker screening can be performed in twin pregnancies.

Maternal serum screening in cases of mosaic and translocation Down syndrome

To determine if the second-trimester maternal serum markers (MSM) screening for Down syndrome (DS) is efficient in DS mosaicism or structural rearrangement cases. DS mosaic or translocation cases were reviewed from databases of routine MSM DS screening. The control group consisted of 977 trisomy 21 cases included in a series of 854 902 patients (routine screening). DS risk was calculated by combination of maternal age and MSM [alpha-fetoprotein (AFP) and human choriogonadotrophin (hCG) or free beta-hCG and/or uE3] expressed in multiples of median (MoM). Mosaic DS cases were divided into three groups, < 10%, 10-49%, and >or= 50% trisomy 21 cells. Translocation DS cases were divided into three groups, isochromosome, Robertsonian, or reciprocal translocation. Detection rate (DR) and MoMs were evaluated in each group. As many as 76 cases of nonstandard trisomy 21 were collected. For mosaic DS cases (n = 43) DR was 69.8% (not significantly different from the 70.8% of control group). When mosaicism was less than 10%, the DR dropped to 25%. For translocation DS cases (n = 33) DR was 75.7% (not significantly different from control group) whatever the types of translocation. In the nonstandard DS cases, second-trimester MSMs gave the same detection rate as for standard trisomy 21, except the cases with low-level mosaicism (<10%).

Fear of Pregnancy Loss and Fetal Karyotyping: A Place for Third-Trimester Amniocentesis?

Objective: To assess the complications of third-trimester amniocentesis for fetal karyotyping in women unwilling to accept the fetal loss risks of second-trimester amniocentesis. Methods: Retrospective study of singleton pregnancies that underwent a third-trimester amniocentesis for karyotyping. 150 complete charts between 1998 and 2005 were reviewed. Results: The indications were: isolated abnormal second-trimester biochemical markers (n = 57), isolated maternal age >38 years (n = 46), integrated risk (maternal age, first-trimester nuchal translucency, second-trimester maternal serum markers) >1/250 (n = 22), history of chromosomal abnormality (n = 17) or maternal choice (n = 8). The median maternal age and gestational age at sampling were: 40 years (23–48), 32.4 weeks (29.7–37.1). Median interval between amniocentesis, definitive result of amniocentesis, and delivery were 14 days (7–42), and 49 days (10–67) respectively. There were no abnormal karyotypes and no termination of pregnancy. Six women out of 150 (4%) had spontaneous labor before 36 weeks (2% after 36 weeks). Conclusion: The risk of spontaneous labor before 37 weeks after late amniocentesis is 4% (2% before 36 weeks). This technique provides a late but safe reassurance to women who are unwilling to accept the risks of earlier fetal karyotyping. This is of interest to countries such as France where legislation permits late termination of pregnancy.

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.

Medians for second-trimester maternal serum markers: geographical differences and variation caused by median multiples-of-median equations

Objectives: To establish gestational age-specific mid-trimester normal medians for the prenatal serum markers α fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3) for a Belgian population by using...

Second-Trimester Maternal Serum Markers in Twin Pregnancy with Complete Mole: Report of 2 Cases

We present second-trimester serum marker levels in cases of twin pregnancy with complete hydatidiform mole and a coexistent fetus (CHMCF). Second-trimester inhibin A (InhA) levels have not been previously reported in such cases. Second-trimester maternal serum screening, alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and InhA measurements combined with maternal age to estimate a patient's risk of Down syndrome during pregnancy was performed as a routine prenatal test in 2 cases of CHMCF. Hospital records containing serum marker data, patient history, pathology reports, and pregnancy outcome were reviewed. In cases of CHMCF, maternal serum AFP and uE3 levels were similar to those of a normal singleton pregnancy, whereas hCG and InhA levels were markedly increased. Second-trimester maternal serum marker profiles in cases of CHMCF are a composite of normal singleton and molar tissue secretions. We have found, for the first time, that second-trimester InhA levels are markedly increased in these cases. Serum marker levels may be useful in diagnosis of CHMCF, prenatal counseling, and evaluation of risk for persistent trophoblastic disease.

Stability of first- and second-trimester serum markers after storage and shipment

The purpose of this study was to examine the levels of first- and second-trimester maternal serum markers used in Down syndrome screening in relation to the time between sample collection and arrival at the laboratory. The FASTER trial, designed to compare first- and second-trimester screening tests for aneuploidy, has recently been completed, having recruited more than 38,000 patients. According to the trial protocol, all blood samples were drawn in serum separator tubes, centrifuged within 30 min and stored at 4 degrees C until shipment by air express. To examine the effect of delayed shipment, serum marker levels (expressed as multiple of the median--MoM) were evaluated in the first- and second-trimester samples and stratified by the number of days between serum collection and laboratory receipt. Under specified collection and shipment conditions, first and second-trimester screening marker mean levels and degrees of variance were stable for up to 9 days, with the exception of unconjugated estriol, which was stable for up to 6 days. The levels of first- and second-trimester Down syndrome screening markers can be measured reliably when the sample is centrifuged, refrigerated until shipment and received in the laboratory within a week of being drawn. A conservative approach would be to restrict testing to within 6 days of draw, with the intent to keep shipping delays to a minimum.

Maternal serum invasive trophoblast antigen (hyperglycosylated hCG) as a screening marker for Down syndrome during the second trimester.

Approximately two million pregnancies in the United States are screened for Down syndrome annually by use of second-trimester maternal serum markers. At present, a combination of four markers can identify 75% of affected pregnancies when 5% of screened women are classified as candidates for amniocentesis. Although not currently included in screening panels, invasive trophoblast antigen (ITA) is a promising screening marker in serum or urine in both the second and first trimesters. This study aims at better defining the screening performance of serum ITA in the second trimester. In an earlier study, serum samples from an unbiased sampling of 45 Down syndrome (cases) and 238 unaffected (control) pregnancies between 14 and 20 weeks of gestation were collected from various centers in the United States. Samples were aliquoted and stored at -20 degrees C for 8 years. We measured ITA in these samples and determined the screening performance both univariately and in combination with other screening markers. The median ITA in Down syndrome pregnancies was >3.00 multiples of the median, higher than that found for human chorionic gonadotropin (hCG) or free beta-hCG. At a 5% false-positive rate, ITA univariately detected 38% and 40% of Down syndrome pregnancies, respectively, when assigned by date of last menstrual period or ultrasound date. Modeling yielded rates of 45% and 48%. ITA correlated strongly with hCG and free beta-hCG. When substituted for either of these in a multiple marker panel, ITA performed comparably. This study indicates that serum ITA is an effective marker for Down syndrome. It is highly correlated with both hCG and free beta-hCG and could replace either of them in a multiple marker panel.

Clinical application of inhibin a measurement: prenatal serum screening for Down syndrome.

Inhibin A is secreted in significant quantities by the corpus luteum and fetoplacental unit, suggesting a role in fertility and pregnancy. Negative feedback regulation of follicle-stimulating hormone during pregnancy is one expected function of inhibin A, but the complete repertoire of actions of this hormone in pregnancy, including paracrine and autocrine actions, is yet to be fully understood. Inhibin A levels have been carefully described throughout normal pregnancy and studied in association with maternal and fetal complication such as intrauterine growth restriction, preterm labor or delivery, and preeclampsia. The first clinical application of inhibin A measurement in pregnancy has been its use as a second-trimester maternal serum marker for Down syndrome. Our laboratory was among the first, in 1998, to implement Quad marker screening, inhibin A measurement in conjunction with alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin, to assess patients' risk of having a Down syndrome baby. The test performance of the Quad test has been validated by several large studies, detecting about 80% of Down syndrome pregnancies at a 5% false-positive rate. The present review describes Down syndrome and the use of inhibin A in second-trimester prenatal screening. We also address the method used for inhibin A measurement, the biology of inhibin A in Down syndrome pregnancy, and the effects of covariates and other fetal abnormalities on inhibin A levels.

Invasive trophoblast antigen (hyperglycosylated human chorionic gonadotropin) in second-trimester maternal urine as a marker for down syndrome: preliminary results of an observational study on fresh samples.

Down syndrome screening is commonly performed in the US using maternal age and three or four second-trimester maternal serum markers that can identify up to 75% of affected pregnancies by offering diagnostic studies to 5% of women. Invasive trophoblast antigen [ITA; hyperglycosylated human chorionic gonadotropin (hCG)] is a promising marker that can be measured in urine or serum in the first or second trimester. We report preliminary results for urinary ITA in an ongoing observational study. Women undergoing second-trimester amniocentesis for reasons not associated with biochemical testing provided consent and a urine (and possibly serum) sample that was tested within a few days. Demographic and pregnancy-related information was collected, along with karyotype. Screening performance was modeled for ITA alone and in combination with serum markers Twelve recruitment centers collected urine from 2055 women with singleton pregnancies between 15 and 20 weeks of gestation (2023 unaffected, 28 Down syndrome, and 4 pregnancies with other chromosome abnormalities). After correction for gestational age, urine concentration, and maternal race and weight, the ITA measurements were higher in women with a Down syndrome pregnancy (median ITA, 4.33 multiples of the median). At a 75% detection rate, the false-positive rate could be reduced by substituting ITA for hCG measurements (from 5.6% to 2.6% for the triple test) or by adding ITA measurements to existing combinations (from 3.3% to 2.0% for the quadruple test). Our data provide preliminary confirmation of the potential usefulness of urinary ITA measurements in detecting Down syndrome in a setting that simulates routine usage.

Medically assisted reproduction and second-trimester maternal serum marker screening for Down syndrome.

To evaluate the effect of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on total hCG, free ss-hCG, AFP and unconjugated estriol (uE3) used as markers for second-trimester Down syndrome maternal serum screening. Second-trimester maternal sera from 1515 singleton pregnancies (970 by IVF, 545 by ICSI) were compared with control sera (21 014 cases). Free ss-hCG, total hCG, AFP and uE3 were compared between the control group and the medically assisted reproduction groups. The percentages of at-risk patients (>/=1/250) were also compared. No differences in values of the maternal serum markers were observed between the medically assisted and control groups. When maternal age was taken into account, the screen-positive rate for Down syndrome screening did not differ between the two groups. Patients undergoing assisted reproduction techniques can be counseled for maternal serum Down syndrome screening with the same efficacy as patients with naturally conceived pregnancies.