Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome,using a sialic acid-specific lectin immunoassay

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11-13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free beta-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free beta-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free beta-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester.     

First trimester screening for aneuploidy: Serum biochemical markers

The article reviews screening for Down syndrome in the first trimester (8-13 gestational weeks) with maternal serum analytes. In the first trimester, 2 serum markers stand out: pregnancy-associated plasma protein-A, a large glycoprotein tetramer, and free beta-human chorionic gonadotropin (beta-hCG), 1 of the 2 subunits of the glycoprotein hormone hCG. Some data indicate that hCG itself may be as effective as free beta-hCG in the first trimester. Maternal serum levels of pregnancy-associated plasma protein-A are low and free beta-hCG are high (consensus multiple of the medians, 0.4 and 1.8, respectively) in Down syndrome pregnancy. The consensus estimate of screening performance by using pregnancy-associated plasma protein-A and free beta-hCG in combination with maternal age is 60% detection rate at a 5% false positive rate. This is similar to the screening performance of second trimester double markers, but not as good as the screening performance of second trimester triple or quad markers. For this reason, first trimester screening with serum markers alone cannot be recommended except in cases in which second trimester screening cannot be done.     

ADAM12 as a marker of trisomy 18 in the first and second trimester of pregnancy.

BACKGROUND: ADAM12 (a disintegrin and metalloprotease 12) is a placentally derived glycoprotein that appears to be involved in growth and differentiation. The maternal serum concentration of ADAM12 appears to be a very good marker of trisomy 21 in the early first trimester when levels are reduced, and in the second trimester around 16-18 weeks levels are elevated. One small preliminary study of first trimester pregnancies with trisomy 18 found reduced levels in the maternal serum, and we examine herein the potential of ADAM12 as a marker of trisomy 18 in both the first and second trimester of pregnancy. MATERIALS AND METHODS: The concentration of ADAM12 was determined by a time-resolved immunofluorometric assay in 132 first and 12 second trimester cases of trisomy 18, and 389 first and 341 second trimester gestational age-matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and used to determine the population distribution parameters for the trisomy 18 and control groups. Correlation with previously established pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (beta-hCG) multiples of the median (MoMs) and nuchal translucency thickness (NT) MoM were determined and used to model the performance of first trimester screening with ADAM12 in combination with other first trimester markers. RESULTS: The maternal serum concentration of ADAM12 in the first trimester was significantly reduced with a median MoM of 0.829 (p < 0.001) and a mean log10 MoM SD of 0.2663 compared to 0.3353 in the controls. In the second trimester small series ADAM12 was significantly increased with a median MoM of 2.09 (p = 0.001) and a mean log10 MoM SD of 0.2607 compared to 0.4318 in controls. There was a significant correlation of ADAM12 MoM with gestational age (r = 0.510) in trisomy 18 cases, and the median MoM increased from 0.51 at 10 weeks to 1.28 at 13 weeks and 2.09 across the 14-18 week window. ADAM12 was correlated with PAPP-A (r = 0.1918) in the first trimester of cases with trisomy 18 but less so with NT (r = 0.1594) and free beta-hCG (r = 0.0938). Modeled detection rates incorporating ADAM12, free beta-hCG, and NT were 92% at 1% false positive rate (88% at 0.5%) A combination of all four markers had a detection rate of 96.5% at a false positive rate of 1% (95% at 0.5%). CONCLUSION: ADAM12 may be a useful addition to early screening for trisomy 18 alongside other chromosomal anomalies, particularly if biochemical screening can occur before 10 weeks.     

Effect of fetal gender on first trimester markers and on Down syndrome screening.

OBJECTIVES: The purpose of the present study was to evaluate whether a gender-related difference exists in first trimester markers used for Down syndrome screening, namely nuchal translucency (NT), maternal serum pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (beta-hCG), and whether this has an influence on screening performance. METHODS: A total of 1325 patients with a singleton pregnancy underwent combined first trimester screening at 10-13 weeks' gestation. Maternal serum PAPP-A and free beta-hCG were analyzed by fluoroimmunoassay, nuchal translucency (NT) was measured by transvaginal sonography. Only patients with normal outcomes and known fetal gender were included in the study. Data were categorized by gestational age and by fetal gender. RESULTS: There were no significant gender-related differences in NT and PAPP-A levels. However, free beta-hCG was significantly higher (p=0.00004) in the presence of a female fetus than in the presence of a male fetus. Women with female fetuses had a higher median calculated Down syndrome risk (1:5490) compared to those having males (1:6451). This difference was not, however, statistically significant. CONCLUSION: First trimester free beta-hCG is significantly higher in pregnancies with a female fetus.     

Does vaginal bleeding influence first-trimester markers for Down syndrome?

OBJECTIVES: To examine the effect of early vaginal bleeding on first-trimester screening markers for Down syndrome. METHODS: A retrospective study was conducted on 1755 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome on the basis of ultrasound and maternal serum markers. Fetal delta-nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG were compared between pregnancies with (n = 252) and without (n = 1503) an episode of vaginal bleeding. Subgroup analysis for the intensity of bleeding (spotting n = 191; light n = 32; heavy n = 29) was performed. RESULTS: The median +/- SD (log(10)) for delta-NT, multiple of medians (MoM) PAPP-A and MoM free beta-hCG (corrected for maternal weight, smoking and ethnicity) was - 0.17 +/- 0.62, 1.10 +/- 0.28, 1.1 +/- 0.28 and - 0.15 +/- 0.51, 0.98 +/- 0.26, 0.94 +/- 0.3 in pregnancies with and without a history of early vaginal bleeding, which were not significantly different. Exclusion of patients with spotting from the vaginal bleeding group revealed significantly higher maternal serum free beta-hCG MoM values (median +/- SD (log(10))) compared to patients without bleeding, 1.29 +/- 0.27 vs 0.96 +/- 0.3(p = 0.011). Screen-positive (cut off of 1:350) rate after combined first-trimester screening was 28.1% in patients with light vaginal bleeding and 8.4% in patients without bleeding (p = 0.001). CONCLUSIONS: Light vaginal bleeding before first-trimester combined screening for Down syndrome leads to a higher screen-positive rate after combined first trimester screening, without a significant difference in serum levels of the screening markers.     

Comparison of serum markers in first-trimester down syndrome screening

OBJECTIVE: To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. METHODS: Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. RESULTS: Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. CONCLUSION: Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. LEVEL OF EVIDENCE: II-2.     

Maternal serum screening for Down syndrome in the first trimester: experience from Belarus.

We have carried out a large retrospective study of alpha-fetoprotein (AFP), free-beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein (PAPP-A) in the first trimester of pregnancy. Unlike other studies all women had routine ultrasound dating, carried out during a nuchal translucency measurement project. A total of 13,477 serum samples were tested for AFP and 11,659 for free beta-hCG. A subset of 1564 samples from unaffected pregnancies were also tested for PAPP-A on a case-control basis. All three markers were also determined in 31 samples from pregnancies with Down syndrome. Equations were derived to express results in multiples of the median using both gestational age and crown rump length and to adjust for maternal weight. Statistical modelling with Gaussian distribution parameters obtained in the study were used to predict the detection rate for a 5 per cent false-positive rate. The predicted rates were: 73.7 per cent for all three markers; 69.1 per cent for PAPP-A and free beta-hCG; 47.4 per cent for PAPP-A and AFP; 57.6 per cent for free beta-hCG and AFP. As these rates are similar to those in the second trimester, health planners may now want to consider a change in policy from second-trimester to first-trimester screening with biochemical markers.     

Second-trimester levels of pregnancy-associated plasma protein-A and free beta-hCG in pregnancies with trisomy 13

OBJECTIVE: To examine the levels of free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in second-trimester maternal serum from pregnancies affected by trisomy 13 and compare these with the known reduced levels of these markers in first-trimester cases in an attempt to better understand the pathophysiology of changes in marker levels in chromosomally abnormal pregnancies between the first and second trimester. METHODS: Using the Kryptor immunoassay system, we measured free beta-hCG and PAPP-A in 32 singleton pregnancies affected by trisomy 13 between 14 and 20 weeks of gestation. Using medians established in a previous study, these results were compared against 450 normal singleton pregnancies over the same gestational range. The data were combined with data from 82 cases of trisomy 13 previously examined in the first trimester (11-13 weeks) and an analysis of analyte trend was performed. RESULTS: The median free beta-hCG in multiples of the appropriate gestational median (MoM) in the second-trimester samples was not significantly different from the controls (1.15 (95% CI 0.827-1.651) vs 1.00). The median PAPP-A MoM in the second-trimester samples was significantly lower (p<0.001) than in controls (0.25 (95% CI 0.164-0.373) vs 1.00). Seventy-eight percent of cases were below the 5th centile of normal for PAPP-A. The combined cases in the first trimester had a median free beta-hCG MoM of 0.58 (95% CI 0.454-0.668) and a median PAPP-A MoM of 0.26 (95% CI 0.218-0.320). For PAPP-A, there was no significant change in median across the gestational period of 11 to 20 weeks, whilst for free beta-hCG, there was a significant increase with gestation (r=0.458, p<0.001). CONCLUSIONS: Although PAPP-A levels are reduced in trisomy 13 pregnancies in the second trimester, this isolated lower marker value is unlikely to be of value in screening for trisomy 13 in the second trimester. The aetiology of reduced levels of PAPP-A in cases with trisomy 13 may be similar to that in cases with trisomy 18, but different from that in cases with trisomy 21 since the temporal pattern in trisomies 13 and 18 are different from that in trisomy 21.     

Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction.

OBJECTIVE: To verify whether adrenomedullin (AM) and nitric oxide (NO) concentrations are changed in the maternal and fetal circulation in pregnancies complicated by intrauterine growth restriction (IUGR) compared to normal pregnancies, and to determine any relationship between them. METHODS: Forty-six small for gestational age (SGA) and 34 appropriate for gestational age (AGA) infants were included in the study. Umbilical and maternal venous AM and NO concentrations were determined. RESULTS: Umbilical NO concentrations in SGA infants (mean +/- SD; 176.2 +/- 75.8 micromol/L) were significantly greater than in AGA infants (143.4 +/- 39.2 micromol/L) (p = 0.015). However, umbilical AM concentrations were similar in SGA and AGA infants with 14.2 +/- 4.4 pmol/mL and 14.5 +/- 6.2 pmol/mL, respectively (p > 0.05). There was no relationship between NO and AM levels in umbilical blood (r = 0.09, p = 0.40). No difference was found between either AM or NO levels in the maternal plasma of the two groups. CONCLUSIONS: We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.     

Appropriate biochemical parameters in first-trimester screening for Down syndrome.

Meta-analysis was used to calculate maternal serum marker distribution parameters for Down syndrome risk estimation in the first trimester. Data from 44 series were combined: relating to pregnancy associated plasma protein (PAPP)-A in 18, free beta human chorionic gonadotrophin (hCG) in 17, alpha-fetoprotein (AFP) in 26 and unconjugated oestriol (uE3) in 9. All levels were expressed in multiples of the normal median (MOM) for gestational age. Individual PAPP-A levels were available for 439 first and second-trimester Down syndrome pregnancies. The median MOM value increased with gestation: 0.35 at 6-8 weeks (31 cases), 0.40 at 9-11 weeks (197), 0.62 at 12-14 weeks (113) and 0.94 thereafter (98). A cubic regression equation was fitted so it could be estimated for each week of gestation. For the other markers the median value in Down syndrome was estimated from the weighted mean across all first-trimester series: 1.98 MOM for free beta-hCG in 579 cases; 0.79 MOM for AFP in 243 and 0.74 MOM for uE3 in 226. Variance-covariance matrices were calculated directly in unaffected pregnancies and from the difference between affected and unaffected pregnancies in Down syndrome. Based on these parameters we estimate that screening at 9-11 weeks with PAPP-A and free beta-hCG will yield a 64.6 per cent detection rate for a 5 per cent false-positive rate. Adding a third marker will increase detection to 66.6 per cent for AFP and 68.6 per cent for uE3; using all four markers it increases to 70.1 per cent. Routine ultrasound nuchal translucency measurement in addition to serum testing will increase the rates to 86.4 per cent, 87.2 per cent, 87.9 per cent and 88.3 per cent, respectively.     

Corticotropin-releasing hormone in amniotic fluid during gestation and labor and in relation to fetal lung maturation

Corticotropin-releasing hormone was discovered in the placenta, and its concentration in the maternal plasma was found to increase greatly during the latter half of pregnancy. We studied the concentration of immunoreactive corticotropin-releasing hormone in amniotic fluid in 59 uncomplicated and in 73 complicated pregnancies. The mean (+/- SE) value of corticotropin-releasing hormone in amniotic fluid in uncomplicated pregnancies was significantly higher in the third (24.1 +/- 3.3 pmol/L) than in the second (9.1 +/- 0.7 pmol/L) trimester, but no change was found during labor. In groups matched by gestational age, larger mean values of corticotropin-releasing hormone and cortisol were observed in the group in which the lecithin/sphingomyelin ratio was greater than 2 or the phosphatidylglycerol test was positive than in the group with a lecithin/sphingomyelin ratio less than 2 or a negative phosphatidylglycerol test result. In samples taken at an interval of 1 to 3 weeks, concomitant increases in corticotropin-releasing hormone and cortisol levels were found with the appearance of phosphatidylglycerol. Concentrations of corticotropin-releasing hormone in amniotic fluid were elevated in patients with diabetes and in women with preeclampsia and intrauterine growth retardation. We conclude that the intrauterine release of corticotropin-releasing hormone increases during the last trimester. This may stimulate the fetal pituitary-adrenal axis and promote fetal maturation.     

Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome.

OBJECTIVES: To compare early second-trimester maternal serum placenta growth factor concentrations in Down syndrome pregnancies and those in normal pregnancies. METHODS: A case-control study was performed to evaluate the maternal serum placenta growth factor concentrations in 36 Down syndrome and 320 normal pregnancies with matched gestational age during the second trimester. For the detection of serum concentrations of placenta growth factor, a quantitative sandwich enzyme immunoassay technique (R & D Systems Inc., Minneapolis, Minnesota, USA) was performed. RESULTS: Using a multiple linear regression model, maternal serum placenta growth factor level was associated with gestational age (p<0.001) and the existence of Down syndrome pregnancy (p<0.001). After converting maternal serum placenta growth factor concentrations of each analyte to multiples of the appropriate gestational median (MoM), placenta growth factor MoM (p<0.001) was revealed to be an independent variable for Down syndrome pregnancies after adjusting for the effects of maternal age (p<0.001), free beta-hCG (p<0.001) and AFP (p=0.014) by multivariate logistic regression analysis. CONCLUSIONS: Maternal serum placenta growth factor concentration was elevated in Down syndrome pregnancies during the early second trimester. Placenta growth factor might be a novel marker for maternal serum Down syndrome screening.     

Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay

AIM: To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome. METHODS: In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free beta-hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population. RESULTS: Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free beta-hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free beta-hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237). When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free beta-hCG was used and some 7% lower than when total hCG was used. CONCLUSION: Maternal serum GlyhCG, as measured by the sialic acid-binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester.     

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.     

Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy

OBJECTIVES: To investigate whether hypertensive disorders of pregnancy alter the maternal and fetal leptin levels. METHODS: Fifty primigravidas between 28 and 34 weeks of gestation were divided into three groups: group A consisted of 17 normal pregnant women with a mean gestational age of 31 weeks, group B consisted of 15 women with gestational hypertension without proteinuria with a mean gestational age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean gestational age of 31 weeks. RESULTS: The pre-eclamptics had significantly higher serum leptin levels than those in normal pregnancies (p<0.001) but no difference was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic women had significantly higher umbilical vein leptin levels (4.68+/-1.66ng/ml) compared to normal pregnancies (1.92+/-0.71ng/ml) and those with gestational hypertension (2.47+/-0.81ng/ml). CONCLUSIONS: Pre-eclampsia is associated with an increase in maternal plasma leptin levels and fetal of leptin production increases in gestational hypertension and even more in pre-eclampsia.     

Early vaginal bleeding and first-trimester markers for Down syndrome

OBJECTIVES: To assess the effect of early vaginal bleeding on first-trimester markers for Down syndrome. METHODS: A retrospective study was conducted on 2330 normal singleton fetuses who underwent first-trimester combined screening for Down syndrome based on ultrasound and maternal serum markers. Fetal nuchal translucency (NT), maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-hCG and the false-positive rate of the test were compared between pregnancies with (n = 253) and without (n = 2077) a history of early vaginal bleeding. RESULTS: The mean +/- SD log(10) MoM for NT, PAPP-A and free beta-hCG was -0.024 +/- 0.101, 0.007 +/- 0.244, 0.047 +/- 0.273 and -0.011 +/- 0.108, -0.006 +/- 0.223, 0.008 +/- 0.264 in pregnancies with and without a history of early vaginal bleeding, with a p value of 0.07, 0.40 and 0.03 respectively. The false-positive rate was 2.4% and 3.6% (p = 0.33). CONCLUSIONS: An earlier episode of vaginal bleeding is associated with an increase in maternal serum free beta-hCG levels at first-trimester combined screening for Down syndrome. However, this phenomenon is unlikely to significantly affect the false-positive rate of the test.     

First-trimester nuchal translucency and maternal serum free beta-hCG and PAPP-A can detect triploidy and determine the parental origin

OBJECTIVE: To evaluate the levels of first-trimester screening markers in triploid pregnancies and to determine the parental origin of triploidy. STUDY DESIGN: During the five-year study period, 12322 patients with singleton pregnancies underwent combined first-trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) at 10 to 14 weeks' gestation. Maternal serum markers and NT were evaluated in cases of triploidy. Molecular analysis was performed using polymorphic markers to establish the parental source of triploidy. RESULTS: Eight cases of triploidy were detected at a rate of at least 1 in 1540. All cases were electively terminated early in gestation or resulted in spontaneous miscarriage. Two patterns of first-trimester markers emerged: type I, characterized by extremely high levels of free beta-hCG and elevated NT; and type II, characterized by very low levels of PAPP-A and free beta-hCG with normal NT. Molecular analysis demonstrated that type I triploidy is of paternal origin (diandric) and type II is of maternal origin (digynic). CONCLUSIONS: On the basis of these results, it may be possible to detect triploid pregnancies in the first trimester and determine their origin using combined first-trimester screening.     

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Between pregnancy biological variability of first trimester markers of Down syndrome: implications for screening in subsequent pregnancies.

In a group of 149 women who had undergone routine first trimester screening using fetal nuchal translucency thickness (NT) and maternal serum free beta-hCG and pregnancy associated plasma protein-A (PAPP-A) in two consecutive pregnancies the within person between pregnancy biological variability of these markers has been assessed. For fetal NT there was no correlation between NT MoM in the first and second pregnancy (r=0.0800). For maternal serum free beta-hCG MoM a significant correlation was observed (r=0.4174) as was also found for PAPP-A MoM (r=0.3270). The implications for such between pregnancy marker association is that women who have an increased risk of Down syndrome in their first pregnancy are 1.5-2 times more likely to repeat this event in their next pregnancy. This observation may be useful in counselling women in the first trimester screening of a subsequent pregnancy.     

Influence of maternal systemic lupus erythematosus on first-trimester combined screening for chromosomal abnormalities

OBJECTIVE: To explore the effect of maternal systemic lupus erythematosus (SLE) on first-trimester screening markers for Down syndrome. METHODS: A retrospective study was conducted on 1150 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome. Fetal delta nuchal translucency (NT), maternal serum PAPP-A and free beta-hCG were compared between pregnancies with SLE (n = 10) and without preexisting maternal disease (n = 1140). RESULTS: The medians +/- SD for delta NT, log(10) MoM of PAPP-A and free beta-hCG +/- SD in pregnancies with SLE and without maternal disease were - 0.18 +/- 0.29 versus - 0.18 +/- 0.33, 0.005 +/- 0.32 versus 0.02 +/- 0.26, and 0.22 +/- 0.19 versus - 0.014 +/- 0.28, with a p value of 0.7, 0.98 and 0.03, respectively. CONCLUSIONS: Patients with preexisting SLE have increased maternal serum-free beta-hCG levels in the first-trimester. But, because of the multimodal procedure of risk calculation there is no significant difference in the screen-positive rate after the combined first-trimester screening for trisomy 21.