The discovery of circulating fetal nucleic acid in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. Thus far, a gender-and polymorphism-independent fetalspecific target that can be used for prenatal screening and monitoring in all pregnant women has not been reported. In addition, the origin of such circulating nucleic acid has remained unclear. Here we provide direct evidence that the placenta is an important source of fetal nucleic acid release into maternal plasma by demonstrating that mRNA transcripts from placenta-expressed genes are readily detectable in maternal plasma. The surprising stability of such placental mRNA species in maternal plasma and their rapid clearance after delivery demonstrate that such circulating mRNA molecules are practical markers for clinical use. The measurement of such plasma mRNA markers has provided a gender-independent approach for noninvasive prenatal gene expression profiling and has opened up numerous research and diagnostic possibilities.N oninvasive prenatal diagnosis is a long-sought goal in human genetics. Recent interest in cell-free DNA in plasma and serum (1, 2) has led to the discovery of fetal DNA in maternal plasma (3)(4)(5). This noninvasive source of fetal nucleic acid has already been shown to be clinically valuable in the prenatal investigation of many conditions, including fetal rhesus D status (6, 7), sex-linked diseases (8), and ␤ thalassemia (9). In addition, quantitative aberrations of fetal DNA have been described in many pathological conditions, including preeclampsia (10, 11), fetal chromosomal aneuploidies (12, 13), and hyperemesis gravidarum (14).Despite the promising clinical use of fetal DNA in maternal plasma for noninvasive prenatal diagnosis, a number of challenges remain and several fundamental biological issues about this phenomenon are unresolved. First, in studies reporting the quantitative abnormalities involving fetal DNA in maternal plasma, the Y chromosome is commonly used as a fetal-specific marker in women carrying male fetuses (10-14). The use of such Y-specific markers has limited the application of this technology to the 50% of pregnant women who are carrying male fetuses. The eventual routine clinical application of this technology, e.g., as a screening tool for fetal chromosomal aneuploidies (12, 13), will be catalyzed by the development of a gender-and polymorphism-independent fetal nucleic acid marker, which can be used in all pregnancies. Second, the source of fetal DNA in maternal plasma remains unclear. Although it has been suggested that such fetal DNA could have originated from the placenta (4), no empirical proof of this hypothesis has been put forward to date.Recently, a number of investigators have shown that in addition to DNA, RNA is also present in the plasma of human subjects, particularly those with cancer (15-18). The inherent lability of RNA has made these observations rather surprising. It has been suggested that circulating RNA may be stabilized by being protected in apoptotic ...

SUMMARY.Objective: To establish gestation-related reference intervals for thyroid hormones in a Chinese population. Materials and methods: A prospective study with 343 healthy pregnant women (5±41 weeks) and 63 non-pregnant controls. Thyroid stimulating hormone (TSH), free thyroxine (T 4 ) and tri-iodothyronine (T 3 ) (and human chorionic gonadotrophin) were measured by immunoassays. The median, 2´5th and 97´5th percentiles at 4-week intervals were calculated. Data were also analysed for signi®cant trends using ANOVA. Results: Free T 3 decreased during pregnancy, whereas free T 4 initially increased, peaking between 9±13 weeks and then decreased, the decline becoming signi®cant by week 21. TSH mirrored changes in free T 4 . Conclusion:The gestation-related reference intervals for thyroid hormones should alleviate the misinterpretation of thyroid function in pregnancy.

Background: Increased fetal DNA in maternal plasma/ serum has been reported in pregnancies complicated by preeclampsia. We hypothesize that fetal RNA may also be increased in maternal plasma in preeclampsia. Methods: We developed a real-time quantitative reverse transcription-PCR assay to measure the concentration of the mRNA of the corticotropin-releasing hormone (CRH) locus. Peripheral blood samples were obtained from healthy pregnant women both before and 2 h after delivery. Peripheral blood samples were also obtained from women suffering from preeclampsia and controls matched for gestational age. Plasma was harvested from these samples, and RNA was extracted. Plasma RNA was subjected to analysis by the reverse transcription-PCR assay. Results: CRH mRNA was detected in the plasma of 10 healthy pregnant women in the third trimester. CRH mRNA was found to be cleared very rapidly after cesarean section, with no detectable signal by 2 h postpartum. Plasma CRH mRNA concentrations were 1070 and 102 copies/mL, respectively, in 12 preeclamptic women and 10 healthy pregnant women matched for gestational age (Mann-Whitney test, P <0.001). Conclusion: Plasma CRH mRNA represents a new molecular marker for preeclampsia. Maternal plasma RNA is gender-and polymorphism-independent and may allow noninvasive gene-expression profiling of an unborn fetus.

Severe Acute Respiratory Syndrome (SARS) outbreak in 2002-03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. Lymphopenia along with neutrophilia was a feature of SARS, as it is in respiratory syncytial virus (RSV) and Ebola infections, to name a few. Direct infestation of lymphocytes, neutrophils and macrophages by SARS coronavirus (CoV) has been debated as a cause of lymphopenia, but there is no convincing data. Lymphopenia can be caused by glucocorticoids, and thus any debilitating condition has the potential to induce lymphopenia via stress mechanism involving the hypothalamic-pituitary-adrenal axis. Cortisol levels are elevated in patients with RSV and Ebola, and cortisol was higher in SARS patients with lymphopenia before any steroid therapy. Glucocorticoids also down-regulate the production of proinflammatory lymphokines. Because of the insidious presentation, SARS was treated with antibacterial, antiviral and supra-physiological doses of glucocorticoids. Treatment with glucocorticoids complicated the issue regarding lymphopenia, and certainly calls into question the status of lymphokines and their prognostic implications in SARS.