Exploring Plasma-Level Gut Microbiota Mediators and Pro-Inflammatory Markers in Pregnant Women with Short Cervix and Gestational Diabetes Mellitus.

The composition of the gut microbiota (GM) undergoes significant changes during pregnancy, influenced by metabolic status, energy homeostasis, fat storage, and hormonal and immunological modifications. Moreover, dysbiosis during pregnancy has been associated with preterm birth, which is influenced by factors such as cervical shortening, infection, inflammation, and oxidative stress. However, dysbiosis also affects the levels of lipopolysaccharide-binding protein (LBP), short-chain fatty acids (SCFAs), and free fatty acids (FFA) in other tissues and the bloodstream. In this study, we investigated the plasmatic levels of some pro-inflammatory cytokines, such as matrix metalloproteinases-8 (MMP-8), interleukin-8 (IL-8), heat shock protein 70 (Hsp70), and microbial markers in pregnant women with a short cervix (≤25 mm) compared to those with normal cervical length (>25 mm). We examined the differences in the concentration of these markers between the two groups, also assessing the impact of gestational diabetes mellitus. Understanding the relationship between GM dysbiosis, inflammatory mediators, and cervical changes during pregnancy may contribute to the identification of potential biomarkers and therapeutic targets for the prevention and management of adverse pregnancy outcomes, including preterm birth.

A 10-Year Observational Study on Twin Pregnancy: Role of Fetal Sex Pairing on Obstetric Outcome.

Fetal sex contributes to the determination of obstetric outcome, as pregnancies carrying male babies seem to have an increased risk of maternal-fetal complications. Most studies have been conducted on singleton pregnancies, whereas less evidence is available for twins. A 10-year retrospective observational study was conducted on a cohort of 1180 women with twin pregnancy delivered at a single tertiary hospital. Clinical data on maternal characteristics, and obstetric and neonatal outcomes were collected, and the analysis was performed on monochorionic (MC) and dichorionic (DC) diamniotic twins separately. The group of DC twins included 837 cases, and those conceived by assisted reproductive technologies (ART) were more likely to have one or both female fetuses rather than males. The incidence of hypertensive disorders of pregnancy (HDP) was higher in same-sex pairs than in opposite-sex pairs. No differences were found regarding other obstetric and neonatal outcomes among the three sex-pairing groups. The MC twins group included 228 cases, and in female-carrying pregnancies a higher incidence of gestational diabetes (GDM) was observed compared to the male group. Furthermore, male pairs had significantly lower Apgar scores than females. Fetal sex seems to have a mild effect in twins compared to singleton pregnancies, suggesting a more complex set of factors contributing to pregnancy outcome in multiple pregnancies. However, we observed a higher incidence of HDP among same-sex DC pairs, a higher rate of GDM among MC female-female pairs, and a worse adaptation to extrauterine life among male-male pairs in MC twins.

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.

The role of family history of preterm delivery in the individual risk of spontaneous preterm delivery: a case-control study.

PURPOSE: To investigate the role of family history of preterm delivery (PTD) in the individual risk of spontaneous preterm delivery. METHODS: A retrospective case-control study was conducted on 354 patients who delivered between 2018 and 2020. 177 women who delivered preterm were matched with 177 controls who had full-term delivery. A questionnaire was administered to investigate the family history of PTD of both the patient and her partner. Cases and controls were matched for the anamnestic risk factors for PTD. RESULTS: Seventeen of 173 women (9.8%) in the PTD group reported being born preterm, compared to five of 169 women (2.9%) in the control group (p = 0.01), with an odds ratio (OR) of 3.57 (95% confidence interval, CI 1.29-9.92). Women who delivered preterm also reported more frequently having a sibling who was born preterm (12.4% vs. 4.2%, p = 0.01), with an OR of 3.18 (95% CI 1.31-7.7). No association was found between the partner's family history of premature delivery and the patient's risk of preterm delivery in the present pregnancy. CONCLUSIONS: Pregnant patients who were born prematurely or who have siblings born preterm have an increased risk of preterm delivery in their own pregnancies. Assessment of female personal and family history of PTD should be used to identify women at risk of having a PTD in the present pregnancy.

Tryptophan degradation enzymes expression in the placenta and the Kynurenine/Tryptophan ratio in maternal plasma after elective cesarean section.

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) metabolize tryptophan in the kynurenine pathway. We evaluated these enzymes' mRNA expression in maternal and fetal sides of the placenta of uncomplicated, unlabored full-term pregnancies after elective cesarean section and compared it with that of placentas obtained from vaginal delivery. Tryptophan and kynurenine plasmatic levels after cesarean section were measured, to investigate their possible correlation with IDO1 and TDO mRNA (TDO2) expression. The results suggested that IDO1 and TDO2 expression was higher in the maternal side of the placenta and that labor significantly affects TDO2 expression and the plasma Kynurenine/Tryptophan ratio.

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.

Electronic Package Leaflets for Vaccines: What Are People's Perceptions in Italy?

In Italy, the paper package leaflet (PPL) is the official document that is approved by the Italian Medicines Agency (AIFA) for each medicine. PPLs of all medicines, including vaccines, are freely available online by accessing the AIFA website. To investigate people's attitudes toward possible access to the PPLs of vaccines and the acceptability of switching to an electronic package leaflet (e-leaflet) in the future, we surveyed three target groups (pregnant women, young parents, and older people) in Italy, via an online survey. We collected 321 questionnaires from the cohorts, which comprised 104 pregnant women, 105 young parents, and 112 older people. The results indicate in all target groups that health care professionals (HCPs) do not usually offer the vaccine PPL during the vaccination session: only about 10.7% of respondents receive the PPL without asking for it, with pregnant women receiving it the most frequently. The acceptance rate for switching from a PPL to an e-leaflet is fairly high in all target groups (76.9% in pregnant women, 81.9% in young parents, and 66.1% in the elderly), especially if the option exists to request a paper print, to make sure that people with a low level of digital skills can access the PPL information as well. HCPs have an important role in ensuring access to the PPLs of vaccines. HCPs should be trained to inform their patients about the different options for accessing the PPLs (as well as online access) to increase their patients' knowledge and satisfaction.

Hospital Admission in the Latent versus the Active Phase of Labor: Comparison of Perinatal Outcomes.

Background: Admission in the latent phase of labor has been associated with increased risk of obstetric interventions compared to admission in the active phase. We aimed to investigate the relationship between labor phase at admission and obstetric and neonatal outcomes. Methods: A retrospective cohort study was conducted on 1005 women with uncomplicated singleton pregnancy admitted for spontaneous labor. Cesarean section rate and other perinatal outcomes were compared between women admitted in the latent phase and those admitted in the active phase. Results: Admission occurred in the active phase of labor for 331 women (32.9%) and in the latent phase for 674 (67.1%). Admission in the latent phase was more frequent in nulliparous than in multiparous (p < 0.01) and for Italian patients compared to foreigners. The incidence of caesarean section was similar between groups. Admission in the latent phase increased the likelihood of epidural analgesia (OR 3.47, 95% CI 1.96−6.14, in nulliparous, and OR 2.58, 95% CI 1.37−4.84, in multiparous) and increased the rate of augmentation of labor with oxytocin in multiparous (OR 2.87, 95% CI 1.05−7.85), without difference in neonatal outcomes. Conclusions: Admission in the latent phase is associated with more frequent use of epidural analgesia, without an increase in cesarean section or adverse neonatal outcomes.

Patient's experience with the Arabin cervical pessary during pregnancy: A questionnaire survey.

INTRODUCTION: The cervical pessary is used in women with precocious cervical ripening to prevent preterm birth. Up to now however, there have been no systematic studies on compliance and tolerance, which vary among different study cohorts. MATERIAL AND METHODS: A questionnaire was administered to 166 women treated with the Arabin cervical pessary in one center. Data were analysed about the patient's experience before insertion (adequacy of information received), during treatment (follow-up, impact on daily life, perceived discomfort, side effects) and at the time of removal (pain, if the patient's expectations had been met regarding the treatment). RESULTS: Information received before the insertion of the Arabin cervical pessary was considered adequate in 163/166 (98.2%) women. An increase in vaginal discharge was experienced by 70/166 (42.2%) women. Discomfort or other side effects were reported in 13.8% and 16.3% of cases, respectively. Overall, 77% of women reported an improved quality of life and 94% considered the follow-up during pregnancy adequate. Removal was moderately painful for 58/166 (35%) of women. Patient's expectations regarding the treatment were exceeded in the majority of cases (75.3%). In a final step, we compared our results to previous studies regarding the use of the pessary in singleton and twin pregnancies. CONCLUSION: Although some trials report high rates of non-compliant patients, this could not be confirmed by our study. In contrast, most women reported having a positive experience and that they were motivated to continue the treatment when they were continuously followed by experienced clinicians.

Effectiveness of cervical pessary in women with arrested preterm labor compared to those with asymptomatic cervical shortening.

OBJECTIVE: To determine whether the effectiveness of cervical pessary is different in women who experienced cervical shortening after a threatened preterm labor episode compared to those with asymptomatic short cervix. METHODS: Retrospective study on singleton pregnancies at risk for preterm delivery (PTD) due to cervical length <25 mm before 28 weeks, who were treated with Arabin cervical pessary. Two groups of patients were compared: those who had contractions causing shortening of the cervix, prior to pessary placement, and those who had asymptomatic cervical shortening. Patients carrying a multiple pregnancy and those who underwent iatrogenic PTD were excluded. The primary outcome was the incidence of PTD at different gestational ages. Secondary outcome was the rate of preterm premature rupture of membrane (pPROM). The groups were compared using univariate and multivariate analyses. RESULTS: 115 patients that met the inclusion criteria were identified. Of these, 91 (79%) had asymptomatic cervical shortening, while 24 (21%) had an episode of threatened preterm labor that resolved, and the pessary was placed after the contractions had stopped. The two groups were similar for maternal characteristics, obstetric history, mean gestational age and length of the cervix at the time of pessary insertion. The median gestational age at delivery was significantly lower (36.4 vs 38.0 weeks, p = .02), and the incidence of PTD significantly higher (58.3% vs 30.8%, OR 4.69, 95% CI 1.68-13.1, p < .01) among women who had arrested preterm labor before the pessary was placed compared to the asymptomatic group, after controlling for confounders. The incidence of PTD before 34 and before 32 weeks was also significantly higher in the symptomatic group (p = .02 and p = .005, respectively). Women with asymptomatic cervical shortening had a longer interval between the placement of the pessary and delivery (median 15 weeks). pPROM occurred with a similar incidence in both groups. CONCLUSIONS: Arabin cervical pessary to prevent preterm delivery seems be less effective in women with a short cervix following an episode of threatened preterm labor than in those with asymptomatic cervical shortening in the second trimester. This finding may help physicians to select patients in which cervical pessary is more likely to be effective, and to improve patient's counseling about this intervention.

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.

Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes.

OBJECTIVE: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. STUDY DESIGN: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. RESULTS: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1-3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03-5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3-9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04-1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) CONCLUSION: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks', when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.

Emerging Infectious Diseases in Pregnant Women in a Non-Endemic Area: Almost One Out of Four Is at Risk.

We report the results of a targeted testing strategy for five emerging infectious diseases (Chagas disease, human T-lymphotropic virus 1 infection, malaria, schistosomiasis, and Zika virus infection) in pregnant women accessing an Italian referral centre for infectious diseases in pregnancy for unrelated reasons. The strategy is based on a quick five-question questionnaire which allows the identification of pregnant women at risk who should be tested for a specific disease. One hundred and three (24%) out of 429 pregnant women evaluated in a 20 month period were at risk for at least one emerging infectious disease. Three (2.9%, all from sub-Saharan Africa) out of 103 at-risk women resulted in being affected (one case of Plasmodium falciparum malaria, two cases of schistosomiasis) and were appropriately managed. Prevalence of emerging infectious disease was particularly high in pregnant women from Africa (three out of 25 pregnant women tested, 12%). The proposed strategy could be used by health care professionals managing pregnant women in non-endemic setting, to identify those at risk for one of the five infection which could benefit for a targeted test and treatment.

Non-Clinical Variables Influencing Cesarean Section Rate According to Robson Classification.

Background and Objectives: The incidence of cesarean section (CS) has progressively increased worldwide, without any proven benefit to either the mother or the newborn. The aim of this study was to evaluate the association between CS rates and both clinical and non-clinical variables, while applying the Robson classification system. Materials and Methods: This is a retrospective observational study of pregnant women delivering at a tertiary care hospital between 2012 and 2017, either under public or private healthcare. The overall CS rate, and the elective and non-elective CS rate, divided by classes of Robson, were determined. The rate of vaginal deliveries and CSs was compared between the public and private setting. The distribution of incidence of non-elective CSs and their main indications were analyzed between daytime and nighttime. Results: 18,079 patients delivered during the study period: 69.2% delivered vaginally and 30.8% by CS. Robson class 5 was the most frequent (23.4%), followed by class 2B (16.8%). Of the 289 private practice deliveries, 59.2% were CSs. The CS rate was significantly higher in private compared to public practice: 59.2% and 30.4%, respectively (OR 3.32, 95% CI 2.62 ± 4.21). When only considering elective CSs, a statistically significant difference was found in Robson class 5 between private and public practice, with the latter having more CSs (94.2% and 83.8%, respectively (p = 0.046)). The rate of non-elective CS was significantly lower during nighttime than during daytime (17.2% vs. 21.5%, p < 0.01). During daytime, the higher incidence of CS occurred between 4:00 and 4:59 pm, and during nighttime between 9:00 and 9:59 pm. Failed induction was significantly more common as an indication to CS during daytime when compared to nighttime (p = 0.01). Conclusions: This study identified two non-clinical variables that influenced the CS rate: the type of healthcare setting (private vs. public) and the time of the day. We believe that these indications might be related more to the practitioner attitude, rather than objective delivery complications.