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Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effect due to the trisomic chromosome a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to obtain more insights into the molecular etiopathology of aneuploidy. Using oligonucleotide microarrays, we analyzed whole genome expression profiles in cultured amniocytes (AC) and chorionic villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 13, 18 and 21. We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional levels of most of the genes on the supernumerary chromosome appeared similar to the respective chromosomal pair in normal karyotypes. A subset of chromosome 21 genes including the DSCR1 gene involved in fetal heart development was consistently up-regulated in different prenatal tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 18 vigorous downstream transcriptional changes were found. Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AIMS: To determine the TH-1/TH-2 cytokine pattern in peripheral blood leukocytes (PBL) in late second- and third trimester in normal pregnancies, in comparison to patients with spontaneous preterm delivery (PTD; < 37 completed weeks' gestation). METHODS: A cross-sectional retrospective study was performed in a tertiary care obstetric unit with healthy non-pregnant women (n=7); healthy pregnant women (n=25); patients (n=25) with preterm labor (defined as uterine contractions or changes in cervical length). The phenotypic analysis of TH-1/TH-2 immune deviation was examined in PBL. RESULTS: 26% PTD (n=13) were recorded. Patients delivering at term (n=37, 74%) were characterized by an upregulation of IL-2, IFN-gamma and IL-4 production during weeks 20-25, followed by a strong suppression in cytokine production, except for TGF-beta. Towards the end of pregnancy cytokine levels returned to normal as observed in non-pregnant women. In contrast, PTD showed an inverse pattern for IL-2 and IFN-gamma with marked suppression in IL-2 and IFN-gamma production between weeks 20-25, followed by a strong stimulation of these cytokines. No differences were observed in IL-4 and TGF-beta production. CONCLUSION: An inverse pattern in IL-2 and IFN-gamma production in PBLs between weeks 20-30 is seen in PTD as compared to patients delivering at term. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate clinical risk factors, cervical fetal fibronectin (fFN), cervical length, and mean gray value assessment in predicting of preterm delivery (PTD) in patients with signs and/or symptoms of preterm labor (PTL). STUDY DESIGN: One hundred and seventeen women with PTL between 24 and 34 weeks of gestation were included. Cervical swabs were tested for fFN using the rapid fFN assay. When 2-dimensional transvaginal ultrasound measurement of cervical length was completed, a region of interest (ROI) of constant size was defined in the midsection of the posterior wall, and the tissue-specific gray scale was determined. The end point were PTDs at <34 and <37 weeks of gestation. RESULTS: In univariate analysis, the three strongest predictors of spontaneous preterm birth <34 weeks were positive fFN (relative risk [RR] 8.9; 95% confidence interval [CI] 2.6-30.1), cervical length < or =2.5 cm (RR 6.9; 95% CI 1.6-29.7), and a low mean gray value of < or =5.97 (RR 7.9; 95% CI 2.3-27.2). Predictors significantly associated with spontaneous PTD at less than 37 weeks of gestation included previous PTD in multiparas (RR 3.9; 95% CI 1.6-9.5), positive fFN (RR 7.6; 95% CI 3.8-15.3), cervical length < or =2.5 cm (RR 2.6; 95% CI 1.4-5.1) and a low gray scale value of < or =6.54 (RR 4.5; 95% CI 2.3-8.9). In the final regression models used to predict spontaneous PTD <34 weeks and <37 weeks of gestation, both a positive fetal fibronectin (odds ratio [OR] 13.4; 95% CI, 2.5-72.1, P=0.003 vs. OR, 17.3; 95% CI 4.9-61.8, P<0.001) and a low gray scale value (OR 6.3 95% CI 1.3-29.4, P=0.02 vs. OR, 7.1; 95% CI 2-25.2, P=0.003) remained powerful predictors. The RRs of spontaneous PTD <37 weeks has been analyzed by a combination of these significant parameters. Low mean gray value < or =6.54 and negative fFN had a 10.3-fold (95% CI 2-74.5) increased risk of spontaneous preterm birth at <37 weeks. Combination of positive fFN and normal gray level (>6.54), had a higher increase risk of PTD (RR 18.1; 95% CI 4.4-76.7). When both factors were positive, the RR increases to 24.8 (95% CI 6.2-98.7). CONCLUSIONS: Combined use of rapid fFN and cervical gray value analysis improves the diagnostic efficiency and allows identification of women at risk for preterm delivery and in need for further prophylactic/therapeutic intervention. [ABSTRACT FROM AUTHOR]