Functional autoantibodies against Endothelin-1 receptor type A and Angiotensin II receptor type 1 in patients with preeclampsia.

OBJECTIVES: Functional autoantibodies against Angiotensin II Receptor type 1 (AT1-AA) and Endothelin-1 Receptor type A (ETA-AA), which belong to the class of functional autoantibodies, have been discovered in patients with preeclampsia and in rodent models of pregnancy-induced hypertension. The aim of the study was to investigate the expression of these autoantibodies in relation to disease progression. STUDY DESIGN: We included 10 controls and 41 cases defined as patients with gestational-induced hypertension, preeclampsia or HELLP syndrome. MAIN OUTCOME: Serum obtained in the first trimester as well as at the time of disease development were analyzed by means of a biological assay of beating cardiomyocytes. We also measured the protein expression of IL-17A in these samples. RESULTS: 100% of samples from patients with gestational induced hypertension, preeclampsia or HELLP syndrome expressed AT1-AA when they presented with clinical symptoms but not in samples from the first trimester. 44% of samples from patients with severe preeclampsia or HELLP syndrome expressed ETA-AA but only when they presented with clinical symptoms. The controls expressed neither AT1-AA nor ETA-AA. Approximately 40% of patients with severe preeclampsia or HELLP syndrome expressed IL-17A, both at the time of the onset of symptoms and in the first trimester. CONCLUSION: Autoantibodies against the Angiotensin II receptor 1 and Endothelin receptor are developed in relation to pregnancy-induced hypertension and not present at the start of the pregnancy in these patients. IL-17A is increased in some patients with severe preeclampsia, but the expression is not related to the development of clinical symptoms.

The Impact of the Biological Variability or Assay Performance on AMH Measurements: A Prospective Cohort Study With AMH Tested on Three Analytical Assay-Platforms.

This study examined longitudinal, age-related and intra-individual variation in Anti-Müllerian Hormone (AMH) in regular menstruating women and correlated the hormonal levels to the antral follicle count (AFC). The impact of variations on an algorithm for calculation of follitropin-dose for ovarian stimulation were also tested. The study was carried out at a fertility clinic of a tertiary university hospital and had a prospective trial design. Twenty-six healthy women not receiving infertility treatment aged 22 to 50 years participated. Blood sampling for hormonal analysis was done every fifth day throughout three consecutive menstrual cycles, AFC was determined with 3-dimentional ultrasound and AMH measured by different assays from Beckman Coulter, Roche and Ansh Labs. Outcome measures were maximum and minimum difference in absolute and relative terms for each study subject during the test-period, coefficient of variation (Cv) for AMH for each cycle and cycle-day and correlation between AMH and AFC. The impact from variable AMH levels on an algorithm calculating follitrophin-delta dose in ovarian stimulation was explored. A significant longitudinal age-independent variation in AMH-levels and coefficient of variation in cycles and cycle days was found. A strong correlation between AMH-levels and AFC was confirmed and a case of significant divergence between assays was seen. Variations in AMH had a significant impact on an algorithm calculated dosage of gonadotrophins in ovarian stimulation. The finding of a substantial longitudinal variation in AMH question one recording being sufficient in quantifying gonadotrophins for ovarian stimulation, decision making and prognostication related to infertility treatment and counseling. Occasionally, commercial assays may fail to recognize specific AMH cleavage-products.

Prevalence of xenobiotic substances in first-trimester blood samples from Danish pregnant women: a cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the prevalence of xenobiotic substances, such as caffeine, nicotine and illicit drugs (eg, cannabis and cocaine), in blood samples from first-trimester Danish pregnant women unaware of the screening. DESIGN: A cross-sectional study examined 436 anonymised residual blood samples obtained during 2014 as part of the nationwide prenatal first-trimester screening programme. The samples were analysed by ultra performance liquid chromatography with high-resolution time-of-flight mass spectrometry. SETTING: An antenatal clinic in a Danish city with 62 000 inhabitants, where >95% of pregnant women joined the screening programme. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence and patterns of caffeine, nicotine, medication and illicit drug intake during the first trimester of pregnancy. RESULTS: The prevalence of prescription and over-the-counter drug detection was 17.9%, including acetaminophen (8.9%) and antidepressants (3.0%), of which citalopram (0.9%) was the most frequent. The prevalence of illegal drugs, indicators of smoking (nicotine/cotinine) and caffeine was 0.9%, 9.9%, and 76.4%, respectively. Only 17.4% of women had no substance identified in their sample. CONCLUSIONS: This study emphasises the need for further translational studies investigating lifestyle habits during pregnancy, as well as the underlying molecular mechanisms through which xenobiotic substances may affect placental function and fetal development.

The impact of pneumatic tube transport on whole blood coagulation and platelet function assays.

Pneumatic tube is an attractive way to transport blood samples from the emergency department to the central laboratory facility. We aimed to investigate the impact of pneumatic tube transportation on blood samples for analysis of whole blood coagulation and platelet function. We included 21 healthy adult individuals and measured global coagulation assays by rotational thromboelastometry (ROTEM) and platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) using impedance aggregometry (ROTEM Platelet), on samples transported manually or by pneumatic tube transport. Statistical testing was performed with paired tests with post-hoc Bonferroni correction for multiple testing. Our data revealed no difference in the far majority of ROTEM parameters (P > 0.003), while significantly decreased values were observed for INTEM clotting time (CT) (P = 0.002) and maximum clot firmness (MCF) including the amplitude after 10 min (A10) (P < 0.0001). No statistically significant difference was observed on impedance aggregometry results when manual transport was compared to pneumatic tube transport (P > 0.003). This study indicates that only minor and unsystematic differences between manual transport and pneumatic tube transport may be observed in ROTEM analyses, and that there is no influence from pneumatic tube transport on impedance aggregometry analyses using AA and ADP.

First trimester serum levels of the soluble transcobalamin receptor, holo-transcobalamin, and total transcobalamin in relation to preeclampsia risk.

BACKGROUND: Human placenta expresses CD320, a receptor that ensures the uptake of holo-transcobalamin (holoTC). Soluble CD320 (sCD320) is present in the circulation and its concentration increases during pregnancy. AIMS: To investigate a possible association of sCD320, holoTC and total transcobalamin (TC) with the risk of subsequent preeclampsia using serum samples from asymptomatic first trimester pregnant women. Moreover, we aimed to establish reference intervals of the aforementioned biomarkers for first trimester pregnant women who remained healthy throughout pregnancy. STUDY DESIGN: This study was a retrospective case-control study that we performed on biobank serum samples. Cases (n = 50) and controls (n = 198) (matched for gestational age and date of sample collection) were asymptomatic women in early pregnancy [median (range) gestational age = 10 (8-12) weeks]. Cases developed preeclampsia while the controls remained normotensive throughout pregnancy. We measured the serum concentration of sCD320, holoTC, and total TC by using in-house ELISA methods. RESULTS: First trimester median concentrations of sCD320, holoTC and total TC were not significantly different between cases and controls. The odd ratio for developing preeclampsia based on exposure to low or high levels of sCD320, holoTC or total TC at first trimester was not significant. The reference intervals (2.5-97.5% percentiles (median)) derived from the controls were 50-170 (90) pmol\L for sCD320, 20-140 (70) pmol\L for holoTC and 560-1300 (810) pmol\L for total TC. CONCLUSIONS: The risk of preeclampsia is not predicted by first trimester serum concentrations of sCD320, holoTC or total TC. The first trimester reference intervals for the three parameters is reported.

First trimester combined screening - focus on early biochemistry.

First trimester combined screening (cFTS) for foetal trisomy 21 has become an established method in many countries. The screening is based on a combination of maternal-age-related risk, ultrasound (nuchal translucency) and two maternal serum biochemical markers, free beta human chorionic gonadotropin (FbhCG) and pregnancy associated plasma protein A (PAPP-A). The concentrations of these biochemical markers are affected by several maternal and pregnancy factors, which are discussed herein. Improvements in the algorithm have extended the screening to include trisomy 21 in mono- and dichorionic twin pregnancies, trisomy 18, trisomy 13 and triploidy. The results from large databases have shown that the screening algorithms are efficient for a range of rare autosomal trisomies and marker chromosomes and for a broad range of other chromosomal aberrations. Recent data show that the strength of the individual markers is highly dependent on the gestational age of sampling and indicate a general increase in the performance of the screening for trisomy 21 when using blood samples from early in the first trimester at gestational age 8-10 weeks.

Comparison of two different methods for measuring anti-mullerian hormone in a clinical series.

BACKGROUND: Anti Mullerian hormone (AMH) has previously been measured using a manual method, but a fully automated assay from Roche Diagnostics was recently introduced. The aim of this study was to compare the results from the AMH gen II ELISA and Elecsys Cobas AMH methods in a clinical setting to evaluate whether the assays achieve the goals of analytical performance. A prospective observational study with 23 women seeking laparoscopic sterilization was conducted. Blood samples were collected preoperatively as well as 1 week and 1, 3 and 6 months postoperatively; they were evaluated with the AMH gen II ELISA and Elecsys Cobas AMH methods. The assays were validated according to the optimal performance of biochemical assays: CV Analytical < 0.25* CV Within Biological Variation. FINDINGS: We found a good correlation between the two methods; there was a bias of approximately 32 %. The total within-person biological variability ranged from approximately 21 to 32 %. The analytical variability of the AMH gen II ELISA and Elecsys Cobas methods ranged from 5.5 to 10.3 % and 2.8 to 3.3 %, respectively. Applying the goals for optimal assay performance, the Elecsys Cobas method achieved optimal performance throughout the measuring range, whereas the AMH Gen II only achieved optimal performance in the high end of the measuring range. Furthermore, the Elecsys Cobas assay had a low limit of quantitation of 0.5 pmol/l compared to 3.0 pmol/l for the AMH gen II ELISA. CONCLUSIONS: In the clinical setting, the Elecsys Cobas AMH assay performs well according to the optimal standard for biochemical assays.

Impact of metformin on anti-Müllerian hormone in women with polycystic ovary syndrome: a secondary analysis of a randomized controlled trial.

Conclusions on the effect of metformin on circulating anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) are ambiguous. We performed a secondary analysis of a randomized, double-blind, placebo-controlled cross-over trial. Fifty-six women with hyperandrogenemic PCOS were included. Each woman served as her own control receiving a daily dose of either 1700 mg metformin or placebo for 6 months. After a 3-month wash-out period they received the opposite treatment. The decrease in AMH from a median of 49.5 to 46.9 pmol/L after 6 months on metformin was overall not significant (p = 0.81), nor were changes in obese women (from 49.5 to 38.2 pmol/L; p = 0.53). Comparing individual metformin/placebo AMH values, a small absolute decrease of 9.3 pmol/L (p = 0.03) was observed in obese women after 6 months relative to baseline, suggesting a trend towards decreasing values after metformin treatment, mainly in obese women.

[Anti-Müllerian hormone is a clinical useful measure of the ovarian reserve]. / Antimüllersk hormon er et klinisk anvendeligt mål for ovariereserve

Anti-Müllerian hormone (AMH) is produced by the growing follicles in the ovaries. The number of follicles in this pool is proportional to the number of primordial follicles in the resting pool (the "ovarian reserve"), thus AMH is believed to be a surrogate marker of the ovarian reserve. AMH is a useful adjunct in the evaluation of a woman's "reproductive age", being an important parameter in counselling for reproduction. AMH is also used in pretreatment evaluation of infertile patients guiding proper hormone stimulation. Furthermore, AMH can be used as a tumour marker for granulose cell tumours.

First trimester screening for other trisomies than trisomy 21, 18, and 13.

OBJECTIVE: The objective of the study was to evaluate the performance of first trimester combined screening in cases of placental/fetal, mosaic or non-mosaic, autosomal trisomy other than trisomy 21, 18, or 13, and in cases of aneuploidy for a marker chromosome with focus on biochemical markers. METHOD: We identified 66 cases in three large databases including 357 675 pregnancies from October 2003 to January 2014. RESULTS: Seventy-seven percent of the 66 cases were screened positive at the combined first trimester screening (cFTS) for trisomy 21 or trisomy 18 or 13. The multiple of median (MoM) of Pregnancy Associated plasma protein A (PAPP-A) of the different aneuploidy groups ranged from 0.2 to 0.5 MoM, whereas the MoM of maternal serum free - ß - human chorionic gonadotropin (FßhCG) was approximately 1.0 MoM. The exceptions being 0.2 MoM for cases involving chromosome 8 (n = 7) and 0.5 MoM for cases involving chromosome 9 (n = 3). The nuchal translucency MoM was approximately 1.0 MoM in all aneuploidy groups. CONCLUSION: The cFTS program for trisomy 21, 18, and 13 is also sensitive to a broad range of rare chromosomal trisomies and chromosomal mosaicisms, primarily because of a strong detection capacity of PAPP-A MoM.

Ten years of experience with first-trimester screening for fetal aneuploidy employing biochemistry from gestational weeks 6+0 to 13+6.

OBJECTIVES: To validate the performance of first-trimester screening for fetal aneuploidy employing blood samples drawn in gestational weeks 6-13. METHODS: Prospective combined first-trimester screening for fetal aneuploidy in Denmark was validated in two large datasets: (1) a dataset from the Central Denmark Region including 147,768 pregnancies from October 2003 to October 2013, and (2) a national dataset including 220,739 pregnancies from January 2008 to August 2011. RESULTS: For trisomy 21, the weekly median multiple of the median (MoM) increased from 0.37 in week 6 to 0.70 in week 13 (pregnancy-associated plasma protein-A), and from 0.99 in week 6 to 2.68 in week 13 (free ßhCG). The overall detection rate (DR) for fetal trisomy 21 was 91.2%. Employing blood samples from gestational week 9, the DR was 97% (p = 0.05). For fetal trisomy 18, trisomy 13 and triploidy, the overall DRs after first-trimester screening were 79.5, 86 and 85%. In the national dataset, the overall DR for trisomy 21 was 86.3% ranging from 89 (weeks 9 and 10) to 80% (weeks 12 and 13). CONCLUSION: The results from both datasets show that blood sampling in gestational weeks 9-10 is a robust and high-performance strategy, which can be applied for routine first-trimester screening in clinical practice. © 2014 S. Karger AG, Basel.

Autocorrelation and cross-correlation between hCGß and PAPP-A in repeated sampling during first trimester of pregnancy.

BACKGROUND: Theoretically, repeated sampling of free ß-human chorionic gonadotropin (hCGß) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester of pregnancy might improve performance of risk assessment of trisomy 21 (T21). To assess the performance of a screening test involving repeated measures of biochemical markers, correlations between markers must be estimated. The aims of this study were to calculate the autocorrelation and cross-correlation between hCGß and PAPP-A in the first trimester of pregnancy and to investigate the possible impact of gestational age at the first sample and time between sampling on the correlation. METHODS: A prospective study was conducted including 3891 unaffected singleton pregnancies. Two measurements of hCGß and PAPP-A were obtained during the first trimester in each pregnancy. Correlations between the four parameters, hCGß first, hCGß second, PAPP-A first and PAPP-A second, were estimated and presented in terms of Pearson's r coefficients. Furthermore, the correlation between paired samples as a function of time between samples was investigated. RESULTS: The study demonstrated high correlation between first and second samples of hCGß and PAPP-A with a correlation coefficient of 0.80 and 0.79, respectively. By contrast, the correlations between hCGß and PAPP-A were low. In addition, the study demonstrated that the correlation between paired samples of hCGß and PAPP-A decreases with earlier gestational age at the first sample and with increasing time between samples. CONCLUSIONS: We have developed a parameter set in terms of correlations between biochemical markers, which can be incorporated into a T21 screening algorithm based on repeated measures within the first trimester.

Downregulation of zinc finger protein 132 in prostate cancer is associated with aberrant promoter hypermethylation and poor prognosis.

This study investigates the expression and biomarker potential of zinc finger protein 132 (ZNF132) in prostate cancer (PC) by transcriptional profiling and immunohistochemical analysis of tissue microarrays, including tumor specimens from 615 radical prostatectomy (RP) patients and 199 conservatively treated patients. Primary clinical endpoints were time to PSA recurrence and cancer-specific death, respectively. Compared to normal prostate epithelial cells from men without PC, ZNF132 transcript levels were significantly reduced in PC cells from patients with localized PC and further downregulated in metastatic PC. Likewise, ZNF132 protein expression was significantly lower in primary tumors from patients with metastatic compared to localized PC and further reduced in castrate-refractory PC, indicating that ZNF132 downregulation correlates with disease progression. Reduced ZNF132 immunoreactivity was significantly associated with high Gleason score and advanced T stage in both PC patient cohorts. By univariate analysis, no/weak ZNF132 staining was a significant adverse predictor of PSA recurrence after RP (p = 0.024) and cancer-specific death following conservative treatment (p = 0.009). In multivariate models, however, ZNF132 did not add significant independent value to established prognostic factors. Finally, bisulfite sequencing revealed frequent promoter hypermethylation of ZNF132 in both PC cell lines and PC tissue samples, indicating that ZNF132 is epigenetically silenced in PC. In summary, our results show that downregulation of ZNF132 is associated with aggressive PC and furthermore identify ZNF132 as a new candidate methylation marker for PC.

Impact of type 1 diabetes and glycemic control on fetal aneuploidy biochemical markers.

OBJECTIVE: To determine the influence of type 1 diabetes mellitus (T1DM) on the first trimester serum markers of fetal aneuploidy; pregnancy-associated plasma protein-A (PAPP-A) and free beta subunit of human chorionic gonadotropin (free ß-hCG) and to evaluate the influence of glycemic control on these parameters in the pregnant diabetic women. DESIGN: Retrospective study. SETTING: Data were extracted from electronic obstetric and laboratory databases at two Danish University Hospitals. POPULATION: Based on 36 415 pregnancies without T1DM (non-T1DM) and 331 pregnancies with T1DM; ß-hCG and PAPP-A were obtained at 8+0 to 14+2 gestational weeks. METHODS: Medians for PAPP-A and free ß-hCG were generated and multiple of the normal gestation-specific median (MoM) values were calculated for each separate pregnancy. After adjustment for maternal weight, ethnicity and smoking status, MoM values were compared across the T1DM and non-T1DM groups, respectively. Additionally, the relationship between PAPP-A MoM and HgbA1C was examined in 348 T1DM pregnancies by Spearman's rank correlation. MAIN OUTCOME MEASURES. Difference in biochemical marker levels between T1DM and non-T1DM. RESULTS: PAPP-A was 0.86 MoM in T1DM pregnancies and 1.01 MoM in non-T1DM pregnancies, p < 0.0001. Conversely, free ß-hCG was not altered in T1DM pregnancies (T1DM 0.99 MoM, non-T1DM 0.98 MoM; p=0.14). There was a significant inverse correlation between HgbA1C and PAPP-A (rho=-0.12, p=0.02). CONCLUSIONS: In T1DM pregnancies, PAPP-A MoM values were lower than in non-T1DM pregnancies. This suggests that correction should be considered in first trimester biochemical screening for fetal aneuploidy in T1DM women.

PAPP-A and free ß-hCG measured prior to 10 weeks is associated with preterm delivery and small-for-gestational-age infants.

OBJECTIVE: To evaluate whether measuring pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotrophin (ß-hCG) before 10 weeks of gestation affect the association between these biomarkers and adverse pregnancy outcomes. METHODS: Singleton pregnant women (9450) who attended the prenatal screening program, Aarhus University Hospital, Denmark, were included. Maternal serum levels of PAPP-A and free ß-hCG were measured between week 8 and 13 weeks and 6 days. The risk of preterm delivery (<37 weeks) and small for gestational age (SGA) (

First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker.

BACKGROUND: A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model. METHOD: In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model. RESULTS: The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP-A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free ß-hCG with or without nuchal translucency. CONCLUSION: The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.

PAPP-A, free ß-hCG, and early fetal growth identify two pathways leading to preterm delivery.

OBJECTIVE: To evaluate early fetal growth and the biomarkers, pregnancy-associated plasma protein A (PAPP-A) and free ß-human chorionic gonadotrophin (ß-hCG), in relation to preterm delivery. METHODS: A cohort study of 9450 singleton pregnant women who attended the prenatal screening program at Aarhus University Hospital between January 2005 and December 2007, was conducted. PAPP-A and free ß-hCG were measured in the first trimester. Early fetal growth was estimated by (GA(20)- GA(12))/Days(calendar), where GA(12) reflects the gestational age in days calculated from the crown-rump length at a 12-week scan, GA(20) reflects the gestational age in days calculated from the biparietal diameter at a 20-week scan, and Days(calendar) is the number of calendar days between the two scans. RESULTS: Low PAPP-A and low free ß-hCG were significantly associated with preterm delivery (<37 weeks). The association was even stronger when low PAPP-A and slow early fetal growth were combined, resulting in an adjusted odds ratio of 3.8 (95% CI, 1.6-8.7). Fast early fetal growth, but neither high PAPP-A nor high free ß-hCG, was significantly associated with preterm delivery. CONCLUSION: Two different biological pathways leading to spontaneous preterm delivery are suggested: fast early fetal growth and the combination of low PAPP-A and slow early fetal growth.

Screening for fetal trisomy 21 in gestational weeks 6 and 7.

The objective was to examine the applicability of the two biochemical markers PAPP-A and free beta-hCG for fetal trisomy 21 (T21) in very early pregnancy: gestational weeks (GA) 6 and 7. Medians for the two markers were generated on 36,745 fetal T21 unaffected pregnancies from gestational weeks 6-14. Concentrations were converted to Multiples of the Medians (MoMs). Median MoM from T21 affected pregnancies were compared over three intervals of gestational age; the very early weeks 6 and 7, weeks 8-10 and weeks 11-14. Median MoM from 9 affected pregnancies with a very early blood sample had a PAPP-A median MoM of 0.269, compared to 0.392 in weeks 8-10 and 0.531 in weeks 11-14. On the contrary, free beta-hCG diverged from the median with increasing gestational age. Our data suggest that PAPP-A is a useful marker for very early testing in first trimester screening for fetal T21.

Promoter hypomethylation and upregulation of trefoil factors in prostate cancer.

Trefoil factors, mucin-associated peptides, are overexpressed in prostate cancer (PC). We hypothesized that promoter methylation contributes to the regulation of trefoil factors (TFF1, TFF2 and TFF3) in human prostate cells. Here we show hypomethylation of promoter regions of TFF1 and TFF3 in PC cell lines with significant TFF expression as compared to benign immortalized prostate cell lines and PC cell lines not expressing trefoil factor. The most striking difference was observed for CpG sites located close to the AUG start codon overlapping several putative binding sites for cellular transcription factors. TFF2 was hypermethylated and had no or very low expression in all prostate cell lines investigated. Treatment of methylated cell lines with 5-aza-2'-deoxycytidine restored TFF expression in cell lines not expressing TFF and increased expression significantly in low-expressing cell lines. In clinical samples, methylation of the promoter/enhancer regions of TFF1 and TFF3 was significantly lower in PC compared to benign prostatic hyperplasia. The present study shows an inverse relation between promoter methylation and expression of trefoil factors. Preliminary analysis on clinical samples suggests that this regulatory mechanism is responsible for the increased levels of TFF1 and TFF3 observed in PC. The overexpression and promoter hypomethylation of trefoil factors may serve as biomarkers in PC.

Performance of first-trimester screening between gestational weeks 7 and 13.

BACKGROUND: Screening for fetal chromosome abnormalities in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free beta human choriogonadotropin (free beta hCG). The blood sample is traditionally taken around week 12 of gestation, but the performance of earlier blood sampling is not well documented. METHODS: We studied 44,537 singleton pregnancies. Complete first-trimester screening took place between November 2003 and March 2009, and blood samples were taken between 7 weeks + 5 days and 13 weeks + 6 days. RESULTS: Of 120 cases of trisomy 21, 108 were diagnosed in the first-trimester screening (detection rate 90%). When the blood sample was taken before gestational week 10, the detection rate of trisomy 21 was 97% (70 of 72), whereas 80% were detected (38 of 48) after week 10 (chi(2) = 0.0035). For trisomy 18, trisomy 13, and triploidy, 65% (13 of 20) were detected before gestational week 10, and 73% (11 of 15) after (not significant). All 6 cases of triploidy before and after gestational week 10 were detected. The screen positive rate and the maternal age were similar before and after week 10 of gestation. CONCLUSIONS: Screening for fetal aneuploidy can be performed with good results with the blood sample taken as early as week 7 of gestation. Blood samples taken before gestational week 10 showed a high detection rate of fetal trisomy 21, with no difference in the detection of fetal trisomy 18, trisomy 13, or triploidy.