Universal cervical length screening for preterm birth is not useful after 24 weeks of gestation.

INTRODUCTION: Cervical length measurement using transvaginal sonography at 18+0 -24+0 weeks of gestation is used to identify women at risk of preterm delivery, who may benefit from treatment with progesterone to prevent premature birth. Few and conflicting data exist regarding the predictive value of cervical length measurement performed at later gestational ages. The primary objective of this study was to evaluate the predictive accuracy for spontaneous preterm birth of a single cervical length measurement performed between 24 and 32 weeks of gestation in asymptomatic singleton pregnancies at low risk for spontaneous preterm birth. The secondary objective was to test the predictive accuracy of different cervical length thresholds in the same population. MATERIAL AND METHODS: This was a historical cohort study conducted in a tertiary referral hospital. A total of 2728 asymptomatic women with singleton pregnancy at low risk for spontaneous preterm birth were recruited. Of these women, 1548 had cervical length measured at 24+0 -27+6 weeks of gestation and 2191 women at 28+0 -32+0 weeks. In all, 1010 women were present in both gestational age windows. Maternal demographics, medical and obstetrical history, and pregnancy outcome were reviewed. The predictive value of cervical length for spontaneous preterm birth was evaluated through logistic regression analysis. Results were adjusted for confounding factors. RESULTS: Overall, spontaneous preterm birth occurred in 53/2728 women (1.9%). In both the 24+0 -27+6 and 28+0 -32+0 weeks groups, a shorter cervical length was significantly associated with spontaneous preterm birth (p < 0.01), but it had a low predictive value, as shown by the receiver operating characteristics curve analysis (areas under the curve 0.62, 95% CI 0.50-0.74 for the 24+0 -27+6 weeks group, and 0.61, 95% CI 0.52-0.70 in the 28+0 -32+0 weeks group). When the predictive accuracy for preterm delivery of different cervical length cut-offs was evaluated, the sensitivity and positive predictive value were low in both gestational age windows, irrespective of the threshold used. CONCLUSIONS: In asymptomatic women with singleton pregnancy at low risk for spontaneous preterm birth, the predictive value of cervical length after 24+0 weeks of gestation is low. Therefore, cervical length screening in these women should be discouraged.

Tryptophan degradation enzymes and Angiotensin (1-7) expression in human placenta.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are key enzymes for tryptophan degradation, regulating immune tolerance during pregnancy. The intrauterine renin-angiotensin system is also involved in the progression of a healthy pregnancy. Angiotensin(1-7) maintains the integrity of fetal membranes via counteracting the pro-inflammatory actions of Angiotensin II. No data are available on placental Angiotensin(1-7) co-expression with TDO. We aimed to characterize TDO mRNA expression and its localization in different areas of the placenta of physiological pregnancies delivered at term; its co-expression with Angiotensin(1-7) and its correlation with the plasma kynurenine/tryptophan (Kyn/Trp) ratio was investigated. This prospective observational study included a nonconsecutive series of 20 singleton uncomplicated pregnancies delivered vaginally. TDO mRNA was expressed in both maternal and fetal sides of the placentas and TDO protein also in the villi and it was co-expressed with IDO1 in almost half of the placental cells at these sites. The percentage of TDO+ and IDO1+ cells appeared to be influenced by maternal pre-gestational smoking and newborn weight. A strong correlation was found between the percentage of TDO+ and IDO1+ cells in the villi. TDO+ cells also expressed Angiotensin(1-7), with a higher percentage on the fetal side and in the villi compared to the maternal one. Kyn/Trp plasma ratio was not correlated with IDO and TDO expression nor with the patient's characteristics. Collectively, our data indicate that TDO is detectable in placental tissue and is co-expressed with IDO and with Angiotensin(1-7)+ on the fetal side and in the villi.

Immunohistochemical Evaluation of FGD3 Expression: A New Strong Prognostic Factor in Invasive Breast Cancer.

Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p < 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

Tryptophan metabolism and immune regulation in the human placenta.

The placenta represents the maternal-fetal vascular interface. It is capable of supplying the bioenergetic needs of the developing conceptus. It is composed of different cell types that engage in highly varied functions, ranging from attachment, invasion and vascular remodeling to cell fusion, hormone production, and nutrient transport. A deep knowledge of the immunological mechanisms responsible for maintaining an active tolerance towards an allogeneic fetus and the anti-inflammatory properties of the placenta can be useful to clarify the pathogenesis of adverse events in pregnancy. While the systemic mechanisms of this immunological regulation in pregnancy have been well studied, the metabolic processes involved in the placental immune response are still poorly understood. The aim of this review is to summarize the most important information concerning the immune regulation in pregnancy, focusing on the role of tryptophan (Trp) catabolism performed by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in the placenta.