First Trimester Placental Biomarkers for Pregnancy Outcomes.

The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.

Before Is Better: Innovative Multidisciplinary Preconception Care in Different Clinical Contexts.

CONTEXT: Implementation of pre-conception care units is still very limited in Italy. Nowadays, the population's awareness of the reproductive risks that can be reduced or prevented is very low. Purpose and main findings: We presented a new personalized multidisciplinary model of preconception care aimed at identifying and possibly reducing adverse reproductive events. We analyzed three cohorts of population: couples from the general population, infertile or subfertile couples, and couples with a previous history of adverse reproductive events. The proposal involves a deep investigation regarding family history, the personal histories of both partners, and reproductive history. PRINCIPAL CONCLUSIONS: Preconception care is still neglected in Italy and under-evaluated by clinicians involved in natural or in vitro reproduction. Adequate preconception counseling will improve maternal and fetal obstetrical outcomes.

Endometrial Microbiota and Immune Tolerance in Pregnancy.

Recent studies have demonstrated that the uterus has its own microbiota. However, there is no consensus on endometrial microbiota composition, thus its role in the healthy uterine environment is still a frontier topic. Endometrial receptivity is key to embryo implantation, and in this specific context immunological tolerance against fetal antigens and the tightly regulated expression of inflammatory mediators are fundamental. According to recent evidence, endometrial microbiota may interact in a very dynamic way with the immune system during the peri-conceptional stage and later during pregnancy. For this reason, a condition of dysbiosis might lead to adverse pregnancy outcomes. The aim of this review is to summarize the evidence on the molecular mechanisms by which the endometrial microbiota may interact with the immune system. For this purpose, the link between dysbiosis and reproductive disorders, such as infertility, recurrent pregnancy loss (RPL), and preterm birth, will be discussed. In conclusion, the most recent findings from molecular analyses will be reported to illustrate and possibly overcome the intrinsic limitations of uterine microbiota detection (low endometrial biomass, high risk of contamination during sampling, and lack of standardization).

Labour induction at term: clinical, biophysical and molecular predictive factors.

PURPOSE: The aim of this multicentric study is to compare clinical, biophysical and molecular parameters in the prediction of the success of labour induction with prostaglandins. METHODS: We included 115 women, who underwent to labour induction at term with vaginal prostaglandin gel. We evaluated the diagnostic efficiency of endocervical phosphorylated insulin-like growth factor-binding protein (phIGFBP-1), cervicovaginal interleukins 6 (IL-6) and 8 (IL-8). We analyzed the transvaginal sonographic measurement of cervical length. A receiver-operating characteristics (ROC) curve was used to determine the most useful cut-off point. A multivariate logistic regression model was used to analyze the combination of significant predictive variables following univariate analysis. We analyzed all the data searching for the parameters that best predict the beginning of the active phase of labour within 12 h. RESULTS: 36.5 % of the patients delivered within 12 h. The Bishop score was >4 in the 43 % of patients with an active phase. The best cut-off values at ROC curves for cervical length, IL-6 and IL-8 were respectively 22 mm, 5 mg/dl and 20,237 mg/dl. At univariate analysis, all predictors of success, with the exception of IL-6, were significantly associated with the beginning of the active phase. Multivariate analysis of the Bishop score (OR 2.3), phIGFBP-1 test (OR 11.2) and IL-8 (OR 6.6) showed that the variables were independent and therefore useful in combination to predict the success of labour induction. CONCLUSION: The phIGFBP-1 test is a fast and easy test that can be used with Bishop score and IL-8 to reach an high positive predictive value in the prediction of the success of labour induction with prostaglandins.

Combination of biochemical markers in predicting pre-term delivery.

PURPOSE: The aim of this study was to evaluate the predictive performances of some biochemical markers in predicting pre-term delivery in asymptomatic women. METHODS: We included 491 asymptomatic women at 24 weeks' gestation, who underwent the endocervical phosphorylated insulin-like growth factor binding protein (phIGFBP-1) test, cervico-vaginal interleukins 6 (IL-6) and 8 (IL-8), and serum C-reactive protein (CRP). A receiver-operating characteristics (ROC) curve was used to determine the most useful cut off point. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for pre-term delivery following univariate analysis. RESULTS: ROC curves indicated that 33 µg/l was the optimal cut off value for phIGFBP-1 test, 21.3 ng/l for IL-6, 324 ng/l for IL-8, and 8.42 mg/l for CRP in predicting pre-term delivery. The univariate logistic regression analyses revealed an odds ratio of 3.04 for phIGFBP-1 test, 4.82 for IL-6, and 3.08 for CRP. The multivariate analysis of phIGFBP-1 test, IL-6, and CRP showed that they were independent variables and therefore useful in combination for predicting pre-term delivery. CONCLUSIONS: The phIGFBP-1 test, the cervico-vaginal IL-6, and the serum CRP are independent variables that can be used together to predict pre-term delivery in asymptomatic women.

Biochemical markers predicting pre-term delivery in symptomatic patients: phosphorylated insulin-like growth factor binding protein-1 and fetal fibronectin.

PURPOSE: The aim of this study was to evaluate the efficacy of the phosphorylated insulin-like growth factor-binding protein (phIGFBP-1) and of the fetal fibronectin test (fFN) in predicting pre-term delivery in symptomatic women. METHODS: We included 210 symptomatic women at 24-34 weeks' gestation, who underwent the phIGFBP-1 and fFN test. We analyzed the prevalence of pre-term delivery in these patients within 7 days upon admission, before the 34th and the 37th weeks' gestation. RESULTS: The 3.8% of women delivered within 7 days upon the admission, the 7.6% before 34 weeks and the 16.2% before 37 weeks' gestation. The phIGFBP-1 and fFN test had a high specificity and a high negative predictive value in predicting pre-term delivery within 7 days, before 34 and before 37 weeks' gestation. The logistic regression of phIGFBP-1 was statistically significant in predicting pre-term delivery with an odds ratio of 10.08 <34 weeks' gestation. The multivariate analysis showed that the phIGFBP test had a higher OR <34 weeks' gestation (p < 0.001) and that the two variables were independent and useful in combination to predict pre-term delivery (<37 weeks' gestation). CONCLUSION: The phIGFBP-1 test may be better that the fFN test in predicting pre-term delivery before 34 weeks' gestation.

Cervical phIGFBP-1 in the evaluation of the risk of preterm delivery.

BACKGROUND: To evaluate the accuracy of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions to predict premature delivery in symptomatic and asymptomatic pregnant women. METHODS: The study included 332 pregnant women: 109 symptomatic patients (study group) and 223 asymptomatic women (control group). For all women, qualitative and quantitative assessment of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions was carried out, but the quantitative assay was finally performed in 282 of 332. Student's test, the chi2 test, and Fisher's exact test were used as appropriate. RESULTS: The phosphorylated insulin-like growth factor binding protein-1 qualitative test was positive in 35 of 301 women (11.6%) and 11 (31.4%) of them delivered before 37 weeks; in the remaining 266 women with a negative test, there were 11 (4.7%) premature deliveries (relative risk = 5.8; 95% CI = 3.3-10.3). The mean values of quantitative phosphorylated isoform of insulin-like growth factor binding protein-1 were 56.9 microg/l (95% CI = 40.7-73.1) in cases of a positive qualitative test and 6.1 microg/l (95% CI = 4.0-8.3; p = 0.0001) in women with a negative result. The sensitivity, specificity, positive predictive value, and negative predictive value for phosphorylated isoform of insulin-like growth factor binding protein-1 test in symptomatic patients were 69.2%, 90.5%, 50%, and 95.6% respectively, while in the asymptomatic patients they were 22.2%, 91.8%, 11.8%, and 96% respectively. CONCLUSIONS: The phosphorylated isoform of insulin-like growth factor binding protein-1 in cervical secretions is a potential specific marker for preterm delivery occurring before 37 weeks. This test may have an important role in the management of women presenting with symptoms suggestive of preterm labour.