Pre-eclampsia predictive ability of maternal miR-125b: a clinical and experimental study.

Pre-eclampsia (PE) is a systemic maternal syndrome affecting 2-8% of pregnancies worldwide and involving poor placental perfusion and impaired blood supply to the foetus. It manifests after the 20 week of pregnancy as new-onset hypertension and substantial proteinuria and is responsible for severe maternal and newborn morbidity and mortality. Identifying biomarkers that predict PE onset prior to its establishment would critically help treatment and attenuate outcome severity.

First trimester HtrA1 maternal plasma level and spontaneous preterm birth.

Objectives: High temperature requirement A1 (HtrA1) is a serine protease detected in maternal plasma and in placental tissues during normal gestation and in various pathological conditions. The purpose of this study was to determine whether the maternal plasma concentration of HtrA1 in first trimester, alone or combined with other maternal factors, can be used to identify women at risk for spontaneous preterm birth (SPTB).

Study Design: This is a cohort study on pregnant women at 12 weeks of gestation recruited between 2014 and 2016 and prospectively followed until delivery.

Association between first trimester plasma htra1 level and subsequent preeclampsia: A possible early marker?

Introduction: Preeclampsia (PE) is associated with risk of maternal and fetal mortality and morbidity. Several promising predictors of PE have been identified, but early pregnancy screening for PE remains insufficient, and randomized controlled trials that used biomarkers to identify high-risk women have been disappointed. Our aim is to identify a possible early marker of PE.

Induction of the apoptotic pathway by oxidative stress in spontaneous preterm birth: Single nucleotide polymorphisms, maternal lifestyle factors and health status.

The purpose of the present study was to search for associations between spontaneous preterm birth (sPTB), single nucleotide polymorphisms (SNPs) associated with the apoptotic pathway as triggered by oxidative stress, maternal lifestyle and health status. SNP genotyping [rs7560 for c-Jun N-terminal kinase (JNK), rs9517320 for mammalian STE20-like protein kinase 3 (MST3), rs1049216 for caspase 3 (CASP3)] in the placenta and maternal blood of 300 controls with at-term birth and 43 cases of sPTB was performed. No association was identified in genotype frequencies or combinations of foetal/maternal genotypes between single SNPs and sPTB.

Intrapartum test for detection of Group B Streptococcus colonization during labor.

Purpose: The purpose of this study was to evaluate the potential improvement of introducing an intrapartum test for the detection of Group B Streptococcus (GBS) during labor and to estimate its cost-effectiveness versus antepartum GBS screening culture.

Materials And Methods: Three hundred and thirteen women at beginning of labor, with unknown GBS status or with antepartum GBS screening culture were enrolled. A vaginal-rectal specimen was collected from each woman for GBS detection by real-time PCR.

Impact of Probiotic SYNBIO(®) Administered by Vaginal Suppositories in Promoting Vaginal Health of Apparently Healthy Women.

The purpose of this study was to investigate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether it promotes normalization and maintenance of pH and Nugent score. A single-arm, open-label controlled towards the baseline (pre-post) study including 35 apparently healthy women was conducted. Each woman was examined three times during the study.

Evaluation of quantitative fFn test in predicting the risk of preterm birth.

Objective: To evaluate diagnostic accuracy of quantitative fetal fibronectin (qfFN) test in predicting preterm birth (PTB) risk <34 weeks' gestation or within 14 days from testing. We explored the predictive potential of the test in five-predefined PTB risk categories based on predefined qfFN thresholds (<10, 10-49, 50-199, 200-499 and ≥500 ng/mL).

Methods: Measurement of cervicovaginal qfFN with Rapid fFN 10Q System (Hologic) in 126 women with singleton pregnancy (23-33 weeks' gestation) reporting signs and symptoms indicative of preterm labour (PTL).

Non-Invasive Prenatal RHD Genotyping Using Cell-Free Fetal DNA from Maternal Plasma: An Italian Experience.

Background: This study assessed the diagnostic accuracy of a non-invasive approach to fetal RHD genotyping using cell-free fetal DNA in maternal plasma and a combination of methodological strategies.

Methods: Real-time PCR (qPCR) was performed on 216 RhD-negative women between weeks 10+0 and 14+6 of gestation (1st qPCR). qPCR was repeated (2nd qPCR) to increase the amount of each sample for analysis, on 95 plasma aliquots that were available from first trimester blood collection (group 1) and on 13 samples that were collected between weeks 18+0 and 25+6 of gestation (group 2).

Body mass index associated to rs2021966 ENPP1 polymorphism increases the risk for gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a condition of impaired glucose tolerance occurring in 1-14% of all pregnancies. This wide range reflects pathological involvement of single nucleotide polymorphisms (SNPs) and maternal weight as risk factors. This study evaluated the association of genetic component and maternal factors to identify women with higher risk of developing GDM.

Maternal smoking does not affect the amount of cell-free fetal DNA in maternal plasma during the 1st trimester of pregnancy.

CffDNA, from 344 non-smoking, 38 smoking and 33 ex-smoking pregnant women at 11 (+0)-13 (+6) gestational weeks, was extracted and quantified by the multicopy DYS14, as the fetal DNA marker and using the quantitative real-time PCR 7300 detection system. The smoking habit was based on maternal self-report, confirmed by cotinine levels and male fetuses were verified by phenotype at birth. The genders of newborns were compared with DYS14-cffDNA analysis, achieving a 100% diagnostic accuracy of the test.

Caspase 3 activation and PARP cleavage in lymphocytes from newborn babies of diabetic mothers with unbalanced glycaemic control.

Several epidemiological studies showed that gestational diabetes mellitus is the most frequent metabolic disorder of pregnancy, the pathogenesis of which has yet to be completely clarified. The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP-ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life. Our results showed a specific positive correlation between the levels of active Casp3 (17-19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response.

The potential usefulness of free fetal DNA in maternal blood for prenatal fetal gender determination in multiple pregnancies.

We applied a noninvasive prenatal test for the determination of fetal gender in multiple pregnancies by using free fetal DNA circulating in maternal blood in order to evaluate whether the quantification of male DNA could distinguish the fetal gender and the number of male and female fetuses in multiple pregnancies. We enrolled consecutively 44 women with twin pregnancies between 11-14 weeks of gestation. Peripheral maternal blood was collected, and genomic DNA was extracted from maternal plasma and analyzed for the multicopy DYS 14 sequence by using real-time PCR to quantify male DNA.

[Identification of preterm labor: the role of the fibronectin and ultrasound cervicometry and their association].

Objective: The aim of this study was to evaluate the effectiveness of the fetal fibronetcin (fFN) test and ultrasonographic cervical length measurement used alone or in combination with each other in order to further improve the identification of patients in preterm labor.

Methods: Prospective multicenter observational study on patients between 24 and 32 weeks of gestation with symptoms of preterm labor (total patients = 132). The endpoint was the delivery at 34 weeks or more.

Identification of universal mRNA markers for noninvasive prenatal screening of trisomies.

Objective: The discovery of placental transcripts in peripheral blood of pregnant women prompted us to investigate which was the most appropriate biological specimen, between plasma and serum, to easily detect them and to exploit hPL (human placental lactogen), betahCG (human chorionic gonadotrophin beta-subunit), LOC90625, and TFPI2 (tissue factor pathway inhibitor 2) levels in order to establish whether an abnormal variation degree of presence of these placental transcripts are likely to be associated to specific fetal trisomies.

Method: RNA was extracted from plasma and serum samples of 255 pregnant women bearing euploid fetuses, 17 bearing fetuses affected by trisomy 21 and 10 with fetuses affected by trisomy 18. Placental transcript analysis was performed by real time RT-PCR using relative quantification.

Persistence of male hematopoietic CD34+ cells in the circulation of women does not affect prenatal diagnostic techniques.

Objective: We aimed to verify whether fetal microchimerism, because of persisting fetal hematopoietic CD34(+) cells from previous pregnancies, could interfere with the development of genetic tests based on using these cells, isolated from maternal blood for the diagnosis of fetal aneuploidies.

Study Design: CD34(+) cells, isolated from blood of parous women with at least 1 son and nulliparous women, were analyzed by using qualitative polymerase chain reaction (PCR), quantitative PCR, and fluorescence in situ hybridization (FISH) to establish whether these molecular techniques are concurrently capable of detecting circulating male DNA.

Results: By qualitative PCR, male DNA was found both in parous and nulliparous women, whereas by quantitative PCR and FISH analyses, no male DNA or male nuclei were revealed except in 1 cultured CD34(+) sample from a nulliparous woman.

The best approach for early prediction of fetal gender by using free fetal DNA from maternal plasma.

Objectives: Detection of free fetal DNA (ffDNA) in maternal blood during pregnancy has given rise to the possibility of developing new noninvasive approaches for early prenatal diagnosis. On a large-scale study, two protocols of real-time polymerase chain reaction (PCR) were compared in order to establish which Y-specific locus, either multicopy DYS14 or single copy SRY sequence, was the most suitable for developing a test with high diagnostic efficiency for early fetal gender assessment. The second aim was to assess whether the combination of the two detection systems could increase the performance of the prenatal test.

Soluble adhesion molecules: marker of pre-eclampsia and intrauterine growth restriction.

Objective: This study monitored circulating plasma levels of soluble vascular cellular adhesion molecule-1 (sVCAM-1), intracellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) in women with healthy pregnancies, with pregnancy-induced hypertension (PIH), with pre-eclampsia and with pregnancies with isolated intrauterine growth restriction (IUGR) in order to determine whether elevated concentrations have a predictive value for the clinical signs of those pregnancy-induced disorders.

Methods: Plasma concentrations of sVCAM-1, sICAM-1 and sE-selectin were determined in healthy pregnant women at each trimester of pregnancy and in pregnant women with PIH, pre-eclampsia and IUGR using commercial kits.

Results: In the group of healthy pregnant women, plasma levels of sVCAM-1, sICAM-1 and sE-selectin did not change throughout pregnancy.

Prenatal diagnosis of genetic abnormalities using fetal CD34+ stem cells in maternal circulation and evidence they do not affect diagnosis in later pregnancies.

In the present study, we report a new method for enrichment and analysis of fetal CD34+ stem cells after culture in order to determine whether it is feasible for noninvasive prenatal diagnosis. We also determined whether fetal CD34+ stem cells persist in maternal blood after delivery and assessed whether they have an impact on noninvasive prenatal diagnosis of genetic abnormalities. Peripheral blood samples were obtained from 35 pregnant women, 13 non-pregnant women who had given birth to male offsprings, 12 women who had never been pregnant, and eight pregnant women with male fetuses.

A new methodology of fetal stem cell isolation, purification, and expansion: preliminary results for noninvasive prenatal diagnosis.

We developed a combined methodological approach to enrich and to proliferate in vitro fetal CD34+ stem progenitor cells. Using a magnetic cell-sorting technique, CD34+ cells from pregnant women at the early-second trimester were isolated and enriched and compared to those isolated from blood of nonpregnant women. The number and frequency of CD34+ cells were significantly higher (p < 0.

Nitric oxide-releasing NSAIDs inhibit interleukin-1beta converting enzyme-like cysteine proteases and protect endothelial cells from apoptosis induced by TNFalpha.

Background: Nitric oxide (NO)-releasing NSAIDs are a new class of NSAID derivatives with markedly reduced gastrointestinal toxicity. Although it has been demonstrated that NO-NSAIDs spare gastric mucosal blood flow, molecular determinants involved in this effect are unknown.

Aim: To investigate the effect of aspirin, naproxen and flurbiprofen, and their NO-derivatives, on gastric apoptosis and endothelial cell damage induced by tumour necrosis factor-alpha (TNFalpha).

Doppler velocimetry of different sections of the fetal middle cerebral artery in relation to perinatal outcome.

To assess the standard curves of pulsatility index (PI) in different segments of middle cerebral artery (MCA): initial segment (MI) and subcortical segment (M2); to determine the variation of the flow velocity waveforms (FVW) of the M1 and M2 segments of MCA in presence of fetal distress and to establish the possible correlation between the two segments of MCA. 50 normal pregnancies from 25 weeks of gestation to term and 20 pregnancy with alteration of fetal growth rate were investigated with serial records of the FVW of the M1 and M2 segments of the MCA and of the umbilical artery (UA) with a colour Doppler system. Severe fetal distress was associated to cerebral-placental ratio below 1 (C/P < 1).

Effect of low-dose oral triphasic contraceptives on blood viscosity, coagulation and lipid metabolism.

The purpose of the study was to determine the relationship between hemorheological profile, i.e. blood viscosity, and other risk factors for cardiovascular and thrombotic diseases in women taking oral contraceptives and if blood viscosity may be considered a marker of cardiovascular risk in OC users.