Vaccination coverage during pregnancy and factors associated with refusal of recommended vaccinations: An Italian cross sectional study.

Background: The vaccines recommended during pregnancy are the Tdap, the influenza vaccine, and, during the SARS-CoV-2 pandemic, the vaccine against COVID-19. This survey aimed at determining vaccination coverage among pregnant women and adverse events, reasons for vaccine refusal, and factors associated with vaccine uptake. Methods: A single-center cross-sectional study was conducted on women who delivered between March and April 2022 at Careggi University Hospital in Florence, Italy. Information on the vaccinations (Tdap, influenza and COVID-19) received during pregnancy were collected through in-person interviews. Results: Among 307 enrolled women (response rate 99 % on a study population of 310 eligible women), 74 % of patients were vaccinated with Tdap, 82 % against COVID-19, and only 33 % against influenza. Vaccination coverage for Tdap and COVID-19 was significantly higher among Italian than foreign patients (80 % vs 51 %, p < 0.001 and 86 % vs 69 %, p = 0.002, respectively), and for Tdap was higher among patients followed in the private vs public care setting. The main reasons behind refusal of vaccinations were low risk perception of influenza (41 %), insufficient information received from the prenatal care provider regarding the Tdap (35 %), and, for the COVID-19, fear of vaccine side effects (64 %), and concerns about effects on the fetus (70 %). Conclusions: Adherence to the influenza vaccine was low because of reduced perception of the disease risks. The difference in vaccination coverage between Italians and foreigners is an example of healthcare disparity. Better information provided to patients about vaccines' efficacy and safety is advisable to increase acceptance of recommended vaccines.

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.

Antepartum unscarred uterine rupture caused by placenta percreta: a case report and literature review.

The main risk for uterine rupture is the presence of a uterine scar due to prior cesarean delivery or other uterine surgery. However, rupture in an unscarred uterus is extremely rare, and risk factors include multiple gestations, trauma, congenital anomalies, use of uterotonics and placenta accreta spectrum.Placenta accreta spectrum, also known as morbidly adherent placenta, is becoming increasingly common and is associated with significant maternal and neonatal morbidity and mortality.We report a case of unscarred uterine rupture due to placenta percreta in a multiparous woman that required emergency peripartum hysterectomy.

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.

Maternal Oxygen Administration during Labor: A Controversial Practice.

Oxygen administration to the mother is commonly performed during labor, especially in the case of a non-reassuring fetal heart rate, aiming to increase oxygen diffusion through the placenta to fetal tissues. The benefits and potential risks are controversial, especially when the mother is not hypoxemic. Its impact on placental gas exchange and the fetal acid-base equilibrium is not fully understood and it probably affects the sensible placental oxygen equilibrium causing a time-dependent vasoconstriction of umbilical and placental vessels. Hyperoxia might also cause the generation of radical oxygen species, raising concerns for the developing fetal cells. Moreover, this practice affects the maternal cardiovascular system, causing alterations of the cardiac index, heart rate and vascular resistance, and unclear effects on uterine blood flow. In conclusion, there is no evidence that maternal oxygen administration can provide any benefit in the case of a non-reassuring fetal heart rate pattern, while possible collateral effects warn of its utilization. Oxygen administration during labor should be reserved for cases of maternal hypoxia.

Vaginal Microbiome in Pregnant Women with and without Short Cervix.

Cervical shortening is a recognised risk factor for pre-term birth. The vaginal microbiome plays an essential role in pregnancy and in maternal and foetal outcomes. We studied the vaginal microbiome in 68 women with singleton gestation and a cervical length ≤25 mm and in 29 pregnant women with a cervix >25 mm in the second or early third trimester. Illumina protocol 16S Metagenomic Sequencing Library Preparation was used to detail amplified 16SrRNA gene. Statistical analyses were performed in R environment. Firmicutes was the phylum most represented in all pregnant women. The mean relative abundance of Proteobacteria and Actinobacteriota was higher in women with a short cervix. Bacterial abundance was higher in women with a normal length cervix compared to the group of women with a short cervix. Nonetheless, a significant enrichment in bacterial taxa poorly represented in vaginal microbiome was observed in the group of women with a short cervix. Staphylococcus and Pseudomonas, taxa usually found in aerobic vaginitis, were more common in women with a short cervix compared with the control group, while Lactobacillus iners and Bifidobacterium were associated with a normal cervical length. Lactobacillus jensenii and Gardenerella vaginalis were associated with a short cervix.

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.

Neonatal Outcomes of Term Infants Born with Meconium-Stained Amniotic Fluid.

Background Meconium-stained amniotic fluid (MSAF) is considered an alarming sign of possible fetal compromise and it has recently been reported that neonatal outcome correlates with the degree of meconium thickness. Methods We retrospectively studied 400 term infants allocated in clear amniotic fluid and grade 1, 2, and 3 MSAF groups on the basis of color and thickness of AF. Multivariable logistic regression analysis was performed to evaluate the potential independent effect of delivery with MSAF of different severity on the risk of a composite adverse neonatal outcome. Results We found that delivery with grade 2 (OR 16.82, 95% Cl 2.12-33.52; p = 0.008) and 3 (OR 33.79, 95% Cl 4.24-69.33; p < 0.001) MSAF is independently correlated with the risk of adverse neonatal outcome, such as the occurrence of at least one of the following: need of resuscitation in the delivery room, blood cord pH < 7.100, occurrence of meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPH), transient tachypnea of the newborn (TTN), acute respiratory distress syndrome (ARDS), hypoxic-ischemic encephalopathy (HIE), and sepsis. Conclusions There is a positive correlation between the severity of amniotic fluid meconium staining and thickness and the outcomes of term infants. Therefore, the evaluation and grading of MSAF during labor is useful in order to plan for the presence of a neonatologist at delivery for immediate and proper neonatal care.

The Interplay of Perceived Risks and Benefits in Deciding to Become Vaccinated against COVID-19 While Pregnant or Breastfeeding: A Cross-Sectional Study in Italy.

The present study examined the role of the perception of risks and benefits for the mother and her babies in deciding about the COVID-19 vaccination. In this cross-sectional study, five hypotheses were tested using data from a convenience sample of Italian pregnant and/or breastfeeding women (N = 1104, July-September 2021). A logistic regression model estimated the influence of the predictors on the reported behavior, and a beta regression model was used to evaluate which factors influenced the willingness to become vaccinated among unvaccinated women. The COVID-19 vaccination overall risks/benefits tradeoff was highly predictive of both behavior and intention. Ceteris paribus, an increase in the perception of risks for the baby weighed more against vaccination than a similar increase in the perception of risks for the mother. Additionally, pregnant women resulted in being less likely (or willing) to be vaccinated in their status than breastfeeding women, but they were equally accepting of vaccination if they were not pregnant. COVID-19 risk perception predicted intention to become vaccinated, but not behavior. In conclusion, the overall risks/benefits tradeoff is key in predicting vaccination behavior and intention, but the concerns for the baby weigh more than those for the mother in the decision, shedding light on this previously neglected aspect.

Amniotic Fluid Disorders: From Prenatal Management to Neonatal Outcomes.

Amniotic fluid volume assessment has become standard in the surveillance of fetal well-being, especially in high-risk pregnancies. Amniotic fluid disorders are a frequent and important topic in fetal and perinatal medicine. However, although important advances have been achieved, many important and challenging questions remain unanswered to date. An abnormally low amniotic fluid volume, referred to as oligohydramnios, has been traditionally considered a possible indicator of placental insufficiency or fetal compromise and is associated with an increased rate of obstetric interventions. An excess of amniotic fluid, referred to as polyhydramnios, may be secondary to fetal or maternal conditions and has been associated with a variety of adverse pregnancy outcomes, especially when it is severe. The ultrasonographic detection of an amniotic fluid disorder should prompt a proper workup to identify the underlying etiology. Data on the association of isolated oligohydramnios or idiopathic polyhydramnios with adverse obstetric and perinatal outcomes are conflicting. While the management of secondary oligohydramnios is usually guided by the underlying condition, the management of isolated oligohydramnios is poorly defined. Similarly, the management of idiopathic and secondary polyhydramnios is not yet standardized. There is an urgent need for randomized clinical trials to provide stronger recommendations on the management of these two common conditions.

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.

A Questionnaire Integrated with the Digital Medical Record Improved the Coverage of a Control Program for Congenital Chagas Disease in Tuscany, Italy.

The leading route of Chagas disease transmission in nonendemic countries is congenital. However, policies concerning screening, prevention, and management of congenital Chagas disease are rare in these settings. Since 2012, serological screening for Chagas disease should be provided for pregnant women at risk in Tuscany, Italy according to a Regional resolution. Due to difficulties in the implementation, in November 2019, a checklist aimed at identifying pregnant women at risk for Chagas disease was introduced in digital clinical records at Careggi University Hospital, Florence, Italy. In order to evaluate the effectiveness of the "Chagas checklist", data about the number of deliveries by women at risk and their screening coverage between 2012 and June 2022 were collected. Out of 1348 deliveries by women at risk, 626 (47%) Trypanosoma cruzi serology tests were performed during the study period. The annual screening coverage increased from an average of 40.3% between 2012 and 2019 to 75.7% between 2020 and June 2022, underlining the big impact of the checklist. Four Chagas disease serological tests out of 626 (0.6%) resulted positive, corresponding to 2 affected women. No cases of congenital transmission occurred. The study showed that a simple digital tool led to a tangible improvement in the coverage of the screening program; its application in a setting where digital charts are available will contribute to the control and elimination of congenital Chagas disease.

Patient safety implications of wearing a face mask for prevention in the era of COVID-19 pandemic: a systematic review and consensus recommendations.

In the past, the use of face masks in western countries was essentially limited to occupational health. Now, because of the COVID-19 pandemic, mask-wearing has been recommended as a public health intervention. As potential side effects and some contraindications are emerging, we reviewed the literature to assess the impact of them in daily life on patient safety and to provide appropriate guidelines and recommendations. We performed a systematic review of studies investigating physiological impact, safety, and risk of masks in predefined categories of patients, which have been published in peer-reviewed journals with no time and language restrictions. Given the heterogeneity of studies, results were analyzed thematically. We used PRISMA guidelines to report our findings. Wearing a N95 respirator is more associated with worse side effects than wearing a surgical mask with the following complications: breathing difficulties (reduced FiO2, SpO2, PaO2 increased ETCO2, PaCO2), psychiatric symptoms (panic attacks, anxiety) and skin reactions. These complications are related to the duration of use and/or disease severity. Difficulties in communication is another issue to be considered especially with young children, older person and people with hearing impairments. Even if benefits of wearing face masks exceed the discomfort, it is recommended to take an "air break" after 1-2 h consecutively of mask-wearing. However, well-designed prospective studies are needed. The COVID-19 pandemic could represent a unique opportunity for collecting large amount of real-world data.

Obstetric and Neonatal Outcomes in Mild Idiopathic Polyhydramnios.

Background: Idiopathic polyhydramnios is a controversial clinical condition, as data on perinatal outcomes are conflicting and vary depending on the severity of the condition. The aim of the present study was to compare obstetric and neonatal outcomes between pregnant women with mild idiopathic polyhydramnios and a control population. Methods: A retrospective cohort study was performed at a single university hospital comparing the obstetrics and neonatal outcomes of pregnancies with mild idiopathic polyhydramnios (n = 109) and control pregnancies (n = 2550). Results: Cesarean section (CS) was significantly increased in the group with polyhydramnios compared to controls (46% vs. 32%, respectively, p = 0.047) due to a higher rate of emergency CS in the polyhydramnios group (p = 0.041) because of abnormal cardiotocography (7.3% vs. 2.9%; p = 0.018) or labor dystocia (8.2% vs. 2.9%; p = 0.006). No statistically significant difference was found in the Apgar score, in the rate of neonatal hypoxia, or in the incidence of macrosomia between groups. In four cases, additional diagnoses of anomalies were made after birth, with a rate of 3.2%, which is comparable to the general population. Conclusion: Besides an increased risk of CS, patients with mild idiopathic polyhydramnios should be reassured regarding maternal and feto-neonatal outcomes. The management of pregnancies with stable mild idiopathic polyhydramnios should not differ from uncomplicated pregnancies, except for the need for increased labor surveillance.

A study on the placenta in stillbirth: an evaluation of molecular alterations through next generation sequencing.

INTRODUCTION: Placental dysfunction is one of the most common causes of Intrauterine Fetal Demise (IUFD). Due to its characteristics, the placenta may be the target of molecular research aimed to investigate potential causes of IUFD. In the literature, there are no studies on human placentas that have investigated possible associations between somatic mutations and the occurrence of IUFD. The aim of this study was to identify the presence of gene mutations in placental tissues in a series of cases of IUFD and to evaluate potential correlations with placental microscopic findings. MATERIALS AND METHODS: Thirty-seven samples of formalin-fixed and paraffin-embedded placental tissues were retrospectively selected from pregnancies ending in IUFD between 23rd to 40th week. Six control placentas of physiological pregnancies were included as controls. After sampling, made according to standardized protocol and conventional histopathological examination, placental tissues were subjected to DNA extraction and sequencing by means of Next Generation Sequencing with a 56-gene panel. RESULTS: The most frequent mutation observed in 32/37 IUFD cases (86.5%) and absent in any of the 6 control placentas was in c-KIT gene, which is implicated in placental tissue differentiation. However, no significant correlation was found between the presence of individual gene mutations and placental histopatological findings. DISCUSSION: As the present study found an elevated frequency of c-KIT mutation in IUFD, it further supports the hypothesis that c-KIT is involved in abnormal tissue differentiation leading to altered placental vascularization and function.

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.