Background. The purpose of this study was to assess outcomes in pregnancies with a positive screen of first-trimester combined test (nuchal translucency, pregnancy-associated plasma protein-A and ...free beta-human chorionic gonadotropin). Methods. Using a cut-off level of 1 in 270, 216 (7.1%) women had a positive screen. Among them, 187 delivered their babies in our hospital and the adverse outcomes, such as spontaneous abortion, intrauterine fetal demize, preterm prelabor rupture of the membranes, preterm labor, intrauterine growth restriction, gestational hypertensive disorders, placenta previa, chromosomal abnormalities and fetal structural anomalies, were identified and compared with the 2097 women who screened negative for Down's syndrome. Results. Pregnancies with a positive screen had a significantly higher risk of adverse outcomes than those with negative screens (30.5% versus 15.3%; odds ratio 2.4; p < 0.001), especially for those complicated by spontaneous abortion (odds ratio 11.4; p < 0.05) and placenta previa (odds ratio 4.3; p < 0.05). Conclusions. Besides fetal chromosomal abnormalities and structural abnormalities, pregnancies with a positive screen for Down's syndrome in the first-trimester had a significantly higher incidence of subsequent adverse obstetric outcomes.
博士
國立臺灣大學
生化科學研究所
104
Human chorionic gonadotropin (hCG) is a hormone secreted mainly by syncytiotrophoblasts governing many crucial functions of placental development, such as progesterone ...production from corpus lutein of ovaries in the first trimester of pregnancy, angiogenesis of uterine vasculature, immune modulation and adaptation, and cytotrophoblast differentiation. hCG contains two components, alpha and beta subunits, and the latter is placenta-specific. A low maternal serum level of hCG in early pregnancy could indicate miscarriage, fetal growth retardation, and subsequent pre-eclampsia. Maternal serum hCG levels increase dramatically from the implantation of the embryo, and reach a peak at approximately 10 weeks of gestation. Mechanisms contributing to this phenomenon are not yet known. Mammalian glial cells missing 1 (GCM1) is a placenta-specific transcription factor involved in placental cell invasion, cell-cell fusion, and angiogenesis. A knockout of mouse GCM1 induces malformation of placenta and early embryonic lethality approximately 10 dpc. It is reported that hCGb is regulated by two transcriptional factors, Sp1 and TFAP2. Whether GCM1 regulates hCGb remains elusive.
In this study, we have identified that hCGb is among the GCM1 target genes through ChIP-chip analysis. We further discovered that TFAP2C, GCM1, and hCGb are co-localized at the syncytiotrophoblasts through immunohistochemical study of the placental tissue. The protein expression and secretion levels of hCGb are up- and down-regulated by GCM1 overexpression and knockdown in choriocarcinoma cell lines, respectively. hCG treatment reciprocally enhances GCM1 transcription, post-translational modification (Serine269/275 phosphorylation and acetylation), and contributes to GCM1 stability through the LH/CG receptor (LH/CGR), cAMP signaling pathway and CBP transactivation, and further enhances the target genes of GCM1, including syncytin-1 and hCGb. These data indicate that GCM1 plays an important and positive role in hCGb production and auto-regulation; either knockdown of LH/CGR or hCGb suppress GCM1 and its target gene expressions. We have identified the precise binding region of GCM1 on the hCGb promoter using a luciferase reporter assay, ChIP, and electrophoretic mobility shift assay, which was previously found to be the same binding region of TFAP2, suggesting that GCM1 and TFAP2C simultaneously regulate hCGb. Indeed, the regulation of hCGb by TFAP2C is through GCM1. The LH/CGR-cAMP-GCM1-hCGb pathway is inhibited by the PKA inhibitor, H89, indicating that the cAMP-PKA pathway is the dominant pathway in the GCM1-hCGb positive loop. Finally, by use of a functional assay, the fusion of BeWo cells was enhanced by hCG treatment, which is GCM1-dependent. Our study reveals a novel mechanism for regulating hCGb and placental cell differentiation.
To assess the relationship between the first-trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels and pregnancies complicated by preterm delivery.
The correlation between ...PAPP-A levels and gestational age at delivery was analyzed by linear regression. The probabilities of low PAPP-A multiples of the median (MoM) levels between preterm delivery and control population were analyzed by logit model.
A positive correlation was noted between the first-trimester PAPP-A MoM levels and gestational age at delivery between 34-38 weeks (p < 0.001). Lower PAPP-A MoM level had a significantly higher likelihood of preterm delivery (p < 0.05). When preterm premature rupture of membranes (PPROM) and preterm labor (PTL) were analyzed separately, there was an increasing likelihood of PPROM with decreasing PAPP-A MoM levels (p < 0.05), but not for PTL with intact membranes.
Low maternal serum PAPP-A levels during the first trimester may reflect a trophoblast invasion defect in the maternal-fetal interface, resulting in subsequent preterm delivery, particularly in those of PPROM.
