First trimester maternal plasma proteomic changes predictive of spontaneous moderate/late preterm delivery.

OBJECTIVE: Identification of differentially expressed proteins (DEPs) in first trimester maternal plasma between pregnant women with a subsequent spontaneous moderate/late Preterm Delivery (sPTD) and women who delivered at term. The sPTD group consisted of women who delivered between 32°/7 and 366/7 weeks of gestation. METHODS: Isobaric tags for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS was used for the analysis of five first trimester maternal plasma samples obtained from women with a subsequent moderate/late preterm sPTD and five women with term deliveries. Enzyme-linked immunosorbent assay (ELISA) was further applied in an independent cohort of 29 sPTD cases and 29 controls to verify the expression levels of selected proteins. RESULTS: 236 DEPs, mainly linked to coagulation and complement cascade, were identified in first trimester maternal plasma obtained from the sPTD group. Decreased levels of selected proteins, namely, VCAM-1, SAA, and Talin-1, were further confirmed using ELISA, highlighting their potential as candidate predictive biomarkers for sPTD at32°/7 and 366/7 weeks of gestation. CONCLUSION: First trimester maternal plasma proteomic analysis revealed protein changes associated with subsequent moderate/late preterm sPTD.

First Trimester Maternal Plasma Aberrant miRNA Expression Associated with Spontaneous Preterm Birth.

Spontaneous Preterm Delivery (sPTD) is one of the leading causes of perinatal mortality and morbidity worldwide. The present case−control study aims to detect miRNAs differentially expressed in the first trimester maternal plasma with the view to identify predictive biomarkers for sPTD, between 320/7 and 366/7 weeks, that will allow for timely interventions for this serious pregnancy complication. Small RNA sequencing (small RNA-seq) of five samples from women with a subsequent sPTD and their matched controls revealed significant down-regulation of miR-23b-5p and miR-125a-3p in sPTD cases compared to controls, whereas miR-4732-5p was significantly overexpressed. Results were confirmed by qRT-PCR in an independent cohort of 29 sPTD cases and 29 controls. Statistical analysis demonstrated that miR-125a is a promising early predictor for sPTL (AUC: 0.895; 95% CI: 0.814-0.972; p < 0.001), independent of the confounding factors tested, providing a useful basis for the development of a novel non-invasive predictive test to assist clinicians in estimating patient-specific risk.

Evaluation of the efficacy of cervical pessary combined with vaginal progesterone in women with a short cervix and additional risk factors for preterm delivery.

OBJECTIVE: The aim of this study was to examine the efficacy of a combined management with cervical pessary and vaginal progesterone of women with a singleton pregnancy and a short cervix in both low and high risk-cases based on their previous obstetrical history and maternal factors. STUDY DESIGN: This was a prospective cohort study of women with a singleton pregnancy and a sonographically detected mid-trimester cervical length ≤ 25 mm. The high-risk group consisted of women with a history of a previous spontaneous preterm birth (PB), or a second-trimester miscarriage, or a loop electrosurgical excision procedure of the cervix (LEEP) while the low-risk group of women without such a history. All women were managed with cervical pessary and daily vaginal administration of 200 mg of progesterone. The primary outcome measure was spontaneous delivery before 34 weeks (238 days) of gestation. RESULTS: One hundred ninety-six cases with a CL ≤ 25 mm were detected during the study period. Fifty-two women declined to participate in the study. The remaining 144 women were divided into two groups based on the presence (n = 44) or absence (n = 100) of specific risk factors for PB. The rate of PTB < 34 weeks was similar in both low and high-risk pregnancies while a significantly higher rate of sPTB < 37 weeks was found in women with high-risk pregnancies (p = .005). CONCLUSION: The combined treatment of cervical pessary and vaginal progesterone has a similar influence on preterm delivery rate < 34 weeks, in both low and high-risk women, with a mid-trimester short cervix.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance with onset or first recognition during pregnancy, which is characterized by an increased insulin resistance. Gestational diabetes mellitus is associated with pregnancy-related maternal and fetal morbidity (both antenatal and perinatal). Myo-inositol has been suggested to improve insulin resistance in women with polycystic ovary syndrome. The aim of this study is to examine the impact of myo-inositol supplementation during pregnancy on the incidence of gestational diabetes mellitus. METHODS: We will conduct a single-center, open-label, randomized controlled trial. A total of 160 healthy pregnant women with singleton pregnancy at 11-13+6 weeks of gestation will be randomly allocated in two groups: intervention group (N = 80) and control group (N = 80). The intervention group will receive myo-inositol and folic acid (4000 mg myo-inositol and 400 mcg folic acid daily) from 11 to 13+6 weeks of gestation until 26-28 weeks of gestation, while the control group will receive folic acid alone (400 mcg folic acid daily) for the same period of time as intervention group. The primary outcome will be gestational diabetes incidence rate at 26-28 weeks of gestation, according to the results of a 75 g oral glucose tolerance test held at 26-28 weeks of gestation. The secondary outcomes will include fasting blood glucose levels, glycated hemoglobin levels, insulin resistance level (evaluated by homeostasis model assessment of insulin resistance and Matsuda Index), and incidence rate of diet-treated gestational diabetes and diabetes requiring insulin therapy at 26-28 weeks of gestation. DISCUSSION: This trial will provide evidence for the effectiveness of myo-inositol supplementation during pregnancy in reducing the incidence of gestational diabetes mellitus. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16142533 . Registered on 9 March 2017.

3D vocal power Doppler sonography for the estimation of tumor volume and vascularization in stage IB1 cervical cancer.

PURPOSE: To evaluate the tumor's volume and intratumoral vascularization with 3D vocal power Doppler ultrasound in patients with stage 1B1 cervical cancer. METHODS: This was a prospective study on patients with cervical cancer and stage 1B1 disease, which took place between 2012 and 2015. All women had an initial 2D ultrasound examination for the estimation of the tumor volume. Following this, 3D volumes of the cervix were acquired and were further analyzed using the Virtual Organ Computer Aided Analysis (VOCAL) program. In the selected volume, the vascular pattern (linear or complex vascularization) was also examined. The ultrasonographic findings were compared to the histological ones following surgery. RESULTS: Twenty-seven patients were included. The average cervical tumor volume measured by the 2D ultrasound and 3D VOCAL-PD were 3.14 and 3.08 cm3, respectively. Both 2D and 3D VOCAL-PD overestimated the tumor staging. Further analysis showed a statistically significant superiority of 2D ultrasound over 3D VOCAL-PD for tumors equal or smaller than 2.5 cm3 with linear vascularity (p < 0.001), while for tumors of larger volume with complex vascularization, a statistically significant superiority of 3D VOCAL-PD was confirmed (p < 0.001). CONCLUSIONS: 3-D VOCAL-PD is extremely accurate and superior to 2D ultrasound for the estimation of tumor volume and vascularization when it is more than 2.5 cm3 and has a complex vascularization in patients with stage 1B1 cervical cancer.

Delayed interval delivery of the second twin in a woman with altered markers of inflammation.

BACKGROUND: Delayed interval intertwin delivery rates are expected to rise during the next years as potent and targeted tocolytic agents are employed and antenatal surveillance methods become more sophisticated and specific in predicting the critical delivery timepoint of optimal perinatal outcome. CASE PRESENTATION: We present a case of delayed intertwin delivery after delivery of the first twin due to premature prelabor rupture of the membranes. Maternal serum White Blood Cells and C-Reactive Protein levels remained high until delivery of the second twin (34 days after the first was delivered), although maternal temperature remained constant. The mother underwent close antenatal surveillance and she was hospitalized. She had an uncomplicated delivery of the second twin at 29+ 2 weeks by cesarean section due to an abnormal Non-Stress Test. CONCLUSION: We strongly suggest future evaluation of maternal serum inflammatory markers among these rare cases as these could predict intraamniotic infection.

Chorionic Villus Sampling in Assisted Versus Spontaneous Conception Twins.

Purpose To compare the outcome of chorionic villus sampling (CVS) in twin pregnancies following assisted reproduction technology (ART) versus twins that have been conceived spontaneously. Materials and Methods Retrospective analysis of dichorionic twin pregnancies that underwent CVS between 1986 and 2013 at our department which is a tertiary center for fetal medicine. 32 twin pregnancies after ART and 130 spontaneously conceived twin pregnancies, which underwent CVS, were analyzed. Results No difference was observed in the pregnancy loss rate between the two groups (0 % in the ART group vs. 3 % in the spontaneous twins group). The rate of preterm delivery before 28 weeks was higher in the ART group (18.8 %) compared to the control group (1.6 %). The perinatal mortality rate was similar in the two groups. Conclusion The pregnancy loss rate following CVS is similar in ART twins and in spontaneous twins. However, the risk of prematurity before 28 weeks is significantly higher in the ART group.

Emergency obstetric hysterectomy.

BACKGROUND: All cases of obstetric hysterectomies that were performed in our hospital during a seven-year study period were reviewed in order to evaluate the incidence, indications, risk factors, and complications associated with emergency obstetric hysterectomy. METHODS: Medical records of 45 patients who had undergone emergency hysterectomy were scrutinized and evaluated retrospectively. Maternal age, parity, gestational age, indication for hysterectomy, the type of operation performed, estimated blood loss, amount of blood transfused, complications, and hospitalization period were noted and evaluated. The main outcome measures were the factors associated with obstetric hysterectomy as well as the indications for the procedure. RESULTS: During the study period there were 32,338 deliveries and 9,601 of them (29.7%) were by cesarean section. In this period, 45 emergency hysterectomies were performed, with an incidence of 1 in 2,526 vaginal deliveries and 1 in 267 cesarean sections. All of them were due to massive postpartum hemorrhage. The most common underlying pathologies was placenta accreta (51.1%) and placenta previa (26.7%). There was no maternal mortality. CONCLUSIONS: Obstetric hysterectomy is a necessary life-saving procedure. Abnormal placentation is the leading cause of emergency hysterectomy when obstetric practice is characterized by a high cesarean section rate. Therefore, every attempt should be made to reduce the cesarean section rate by performing this procedure only for valid clinical indications.