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Abstract Background In Italy, exclusive breastfeeding (EBF) rates at hospital discharge range unsatisfactorily between 20–97%. Methods In 2023, the Project for Hospital Policy on Breastfeeding (HPB) has been launched to promote breastfeeding in Italian Maternity Hospitals (MHs) as a joint initiative of the Italian Scientific Societies involved in perinatal care together with the National Midwife (FNOPO) and Nurse (FNOPI) Boards and with Vivere Onlus, a family association. The HBP Project has been designed as an uncontrolled before-after study to increase EBF rate at hospital discharge in the population of healthy, term infant with a normal weight at birth following an intervention bundle comprising: 1) Establishment of a local hospital Working Group; 2) Adoption of a hospital policy; 3) Implementation of breastfeeding monitoring; 4) Training for perinatal care professionals; 5) Enhanced implementation of the practices of skin-to-skin contact (SSC) and mother-baby rooming-in; 6) Development/Improvement of perinatal care protocols. Results We report the pre-intervention assessment of 89 out of the 111 enrolled MHs (80.2%) at the beginning of the Project (Time 1 or T1). Almost all MHs (96.6%) have a multi-professional Breastfeeding Working Group, while a hospital policy on breastfeeding is available only in 48.2%. Moreover, only 56.2% of the 9,777 perinatal health workers have been trained in breastfeeding. Over a 1-month period, SSC has been practiced in the delivery room by 76.9% of 6,304 term healthy newborn infants and rooming-in by 83.4% of 6,735 healthy term newborns of normal weight at birth. Over a 4-month period, 69.1% of 33,367 healthy term newborns of normal birth weight were exclusively breastfed at hospital discharge. Noticeably, EBF rate of MHs ranges from 4% up to 100%, the second quartile being 73%. Conclusion At T1 of the HPB Project, breastfeeding rates at hospital discharge for healthy, term infants with a normal weight at birth appear to be suboptimal among Italians MHs. Particularly, the range of EBF rates among participating centers is wide, with 50% of the MHs having EBF rate lower than 73%. Therefore, the ongoing HPB Project might represent not only an opportunity to increase the initiation of breastfeeding and to improve quality of health care in the whole study group of MHs, but possibly also to level differences between centers.

Soft tissue sarcomas accounts for 1–2% of adult malignancies. Undifferentiated pleomorphic sarcoma (UPS) is a rare subtype that lack immunohistochemical markers for a specific definition. About 18% of sarcomas are at a locally advanced stage, often requiring several cycles of chemotherapy and radiotherapy, in addition to surgery. For a young woman, this can mean delaying pregnancies with a high risk of therapy-induced ovarian damage. For this reason, proper counseling on fertility preservation plays a key role. In addition, all women of childbearing age with cancer, should be informed about the importance of planning a pregnancy to improve maternal and neonatal outcomes. We report a rare case of a 40-year-old woman with a UPS who, during CT scan after chemotherapy to decide on surgery, find out she was pregnant. After counseling, the patient decides to go ahead with the pregnancy.

Abstract Background Ophthalmia neonatorum is an acute conjunctivitis that occurs in newborns within the first month of life. The most serious infections are due to Chlamydia trachomatis and Neisseria gonorrhoeae, that may cause permanent damages. The use of ophthalmic prophylaxis varies widely around the world, according to the different health and socio-economic contexts. To date in Italy there is no a clear legislation regarding ophthalmia neonatorum prophylaxis at birth. Methods We invited all birth centers in Italy to carry out a retrospective survey relating the last three years. We collected data regarding demographics of neonates, drugs used for ophthalmic prophylaxis and results of the screening of pregnant women for Chlamydia trachomatis and Neisseria gonorrhoeae vaginal infections. Results Among 419 birth centers, 302 (72,1%) responded to the survey. Overall 1041384 neonates, 82,3% of those born in the three years considered, received ophthalmic prophylaxis. Only 4,585 (0,4%) of them received one of the drugs recommended by the WHO. The Centers that participated to the survey reported 12 episodes of Chlamydial conjunctivitis and no Gonococcal infection in the three years. Only 38% of the Centers performed vaginal swabs to pregnant women: 2,6% screened only for Neisseria, 9,6% only for Chlamydia and 25,8% for both germs. Conclusions The data obtained from the survey showed a low incidence of neonatal conjunctivitis due to either Neisseria gonorrhoeae or Chlamydia trachomatis in Italy. Due to the lack of legislation regulating the prophylaxis of ophthalmia neonatorum in newborns, the Italian Society of Neonatology, the Italian Society of Obstetrics and Gynecology and the Italian Society of Perinatal Medicine have recently issued new recommendations on this topic.

Objectives: To compare the utilization of prenatal services between immigrant and Italian women during the COVID-19 pandemic.Methods: A cross-sectional survey was conducted at 3 maternity care centers in Italy.Results: We included 1,312 women, 1,198 (91.3%) were Italian and 114 (8.7%) were immigrants. A significantly higher proportion of Italians underwent 8 or more prenatal care visits (64.4% vs. 54.4%, p = 0.03) and more immigrants than Italians attended their appointments at hospital settings (45% vs. 18%, p < 0.001). Regarding prenatal course, Italians were more likely than immigrants to attend a non-hospital setting or an online class (49.6% and 30.2% vs. 34.9% and 11.6%, p = 0.008). A higher influenza vaccine uptake among immigrants compared with Italians was observed (39.5% vs. 19.8%, p < 0.001). Among women not receiving certain prenatal services, immigrants were more likely to state COVID-19 pandemic was the main reason for non-compliance.Conclusion: Immigrant pregnant women were more likely to receive prenatal services at a hospital setting than their Italian counterparts. Among women who did not comply with prenatal services, immigrants were more likely to cite the pandemic as their main reason.

Unilateral non-hemorrhagic adrenal infarction (NHAI) is a very uncommon cause of acute abdomen in pregnancy. Diagnosis is highly challenging due to its rarity, heterogeneity of clinical presentation, and inconclusiveness of the initial workup. Timely recognition is pivotal to ensuring optimal outcomes. Here we describe a case of spontaneous unilateral NHAI diagnosed in a singleton pregnant woman at 32 weeks’ gestation at our centre and provide the findings of an extensive literature review on the topic. We identified 22 articles describing 31 NHAI cases in 30 obstetric patients: NHAI occurs more frequently on the right side and in the third trimester, and diagnosis is formulated more than 24 h after clinical presentation in 50% of cases; second-level imaging is always necessary to reach a definitive diagnosis and start appropriate treatment. A high degree of clinical suspicion is needed to promptly recognize NHAI in pregnancy, thus allowing appropriate multidisciplinary management and timely treatment initiation. Promotion of knowledge and awareness of NHAI as a potential cause of acute abdomen in pregnancy is mandatory to improve clinical practice and, ultimately, perinatal outcomes.

During intrauterine life, external stimuli including maternal nutrition, lifestyle, socioeconomic conditions, anxiety, stress, and air pollution can significantly impact fetal development. The human brain structures begin to form in the early weeks of gestation and continue to grow and mature throughout pregnancy. This review aims to assess, based on the latest research, the impact of environmental factors on fetal and neonatal brain development, showing that oxidative stress and inflammation are implied as a common factor for most of the stressors. Environmental insults can induce a maternal inflammatory state and modify nutrient supply to the fetus, possibly through epigenetic mechanisms, leading to significant consequences for brain morphogenesis and neurological outcomes. These risk factors are often synergic and mutually reinforcing. Fetal growth restriction and preterm birth represent paradigms of intrauterine reduced nutrient supply and inflammation, respectively. These mechanisms can lead to an increase in free radicals and, consequently, oxidative stress, with well-known adverse effects on the offspring’s neurodevelopment. Therefore, a healthy intrauterine environment is a critical factor in supporting normal fetal brain development. Hence, healthcare professionals and clinicians should implement effective interventions to prevent and reduce modifiable risk factors associated with an increased inflammatory state and decreased nutrient supply during pregnancy.

Pregnancies complicated by severe polyhydramnios are associated with a high rate of underlying fetal anomaly. Amnioreduction may be offered to alleviate maternal symptoms. This is a retrospective study of amnioreductions performed on singleton and twin gestations complicated by symptomatic polyhydramnios between 2010 and 2023 at our tertiary referral center. The indications, procedural techniques and pregnancy and neonatal outcomes were retrieved from an archive database and reviewed with the use of the maternal and child medical record chart, the hospital electronic clinical discharge report and telephone recalls. Our study comprised 86 pregnancies, 65 singletons and 21 twin pregnancies. Fetal anomalies were identified in 79% of cases, mainly gastrointestinal obstructive anomalies; 9.3% of cases were idiopathic. The median gestational age at first amnioreduction was 32.5 weeks, and peri-procedural complications were rare (1 case of placental abruption and 2 cases of preterm delivery). The median gestational age at delivery was 36.5 weeks, with a median prolongation of the pregnancy from the time of first drain until birth of 30 days. Preterm labor < 37 weeks occurred in 48.8% of procedures, with 26.7% of patients delivering before 34 weeks and pPROM < 36 weeks recorded in 23.2% of cases. In conclusion, amnioreduction offered to alleviate maternal symptoms is a reasonably safe procedure with a low complication rate. These pregnancies necessitate management in a tertiary referral center because of their need for a multidisciplinary approach both prenatally and postnatally.

Objectives: To assay the presence of the SARS-CoV-2 genome in vaginal, rectal, and placental swabs among pregnant women and in newborn nasopharyngeal swabs and to investigate the immunological response and maternal antibody transfer through the umbilical cord blood and milk of unvaccinated mothers. Methods: Vaginal, rectal, and placental specimens, maternal and neonatal serum, and milk were collected from a wide cohort of pregnant Italian women with confirmed SARS-CoV-2 infection admitted to the hospital between February 25, 2020 and June 30, 2021. Samples were tested in selected reference laboratories according to a shared interlaboratory protocol. Results: Among 1086 enrolled women, the SARS-CoV-2 positive rate detected in all specimens ranged from 0.7% to 8.4%. Respectively, 45.2% of maternal sera collected during pregnancy and 39.7% of those collected at birth tested positive for immunoglobulin G, whereas 50.5% tested positive among neonates. Nasopharyngeal swabs were positive in 0.8% of the newborns, and immunoglobulin G was detected in 3.0% of the milk samples. The highest immunological response was recorded within 30 days during pregnancy and within 60 days of birth and in the neonatal population. Conclusion: Vertical transmission should be considered a rare event; although, a good maternal immunological response and antibodies transfer throughout the umbilical cord blood was detected.

ABSTRACT: Objectives: It is now well established that in utero vertical SARS-CoV-2 transmission can occur during the late third trimester. However, little is known about other gestational ages. Recently, an increased risk of early miscarriage was reported in pregnant women who were SARS-CoV-2-positive. The objective of the current study was to evaluate the putative SARS-CoV-2 vertical transmission during the first trimester of pregnancy. Design: This is an observational study on pregnant women who were SARS-CoV-2-positive during the first trimester. Fetal and syncytiotrophoblastic specimens were collected by hysterosuction from 17 pregnant women who were SARS-CoV-2-positive and voluntarily terminated the pregnancy between week 8 and 12. We investigated the viral vertical transmission using SARS-CoV-2 RNA detection in the fetus and syncytiotrophoblast by two different techniques. Results: The results suggest that SARS-CoV-2 vertical transmission is indeed possible during the first trimester in asymptomatic women. Although maternal viremia was never detected, roughly 30% of the fetuses and 17% of the syncytiotrophoblasts were found to be SARS-CoV-2-positive. Conclusion: Indeed, SARS-CoV-2 can spread to the fetus through the syncytiotrophoblast. Concerningly, this happens in asymptomatic pregnant women as well. Possible long-term detrimental consequences on fetal development still need to be assessed. This should be taken into consideration in the management of pregnant women by implementing preventive strategies.

There is currently no worldwide agreement on the real need to administer conjunctival antibiotics to neonates at birth to prevent neonatal conjunctivitis (usually defined as ophthalmia neonatorum) by Chlamydia trachomatis and Neisseria gonorrhoeae. Therefore, there is wide variability in antibiotic administration, conditioned mainly by the social and health context. In Italy, a law enacted in 1940 required doctors and midwives to administer ophthalmic prophylaxis with 2% silver nitrate to all newborns at birth. This law was repealed in 1975 and since then there has been no clear guidance on the use of ophthalmia neonatorum prophylaxis at birth. Since neonatal conjunctivitis caused by C. trachomatis and N. gonorrhoeae is not reported, we carried out a nationwide survey of 1,041,384 neonates across all Italian birth centers to evaluate the incidence of ophthalmia neonatorum and the current practice of prophylaxis. After analyzing the results, we formulated an intersociety position statement on the prevention of ophthalmia neonatorum to update and standardize this prevention strategy in Italy.

Abstract Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Introduction Currently, the adherence to nutritional guidelines is low, with alarming rates of obesity worldwide and micronutrient deficiencies documented even in industrialised countries. As a consequence, nutritional screening and counselling represent a critical subject in early pregnancy, aiming to improve pregnancy outcomes and population health.Methods and analysis In this setting, the development of a simple and reproducible nutritional checklist is of utmost importance. The Simple Study is a longitudinal prospective multicentre study aiming to identify the associations between maternal nutritional habits in the first trimester, early markers of placental function and pregnancy outcomes on a large population of singleton pregnancies in Italy.Ongoing healthy singleton pregnancies will be enrolled at the ultrasound scan of the first trimester combined screening test (11+0–13+6 gestational weeks). A nutritional score measuring the adherence to a healthy diet and nutritional deficiencies will be collected at recruitment. Fetal (crown-rump length, nuchal translucency (NT), biparietal diameter, femur length) and utero placental (placental volume, uterine arteries Doppler velocimetry) ultrasound data and biochemical placental markers (pregnancy-associated plasma protein A, free ß-human chorionic gonadotropin) will be collected. Second and third trimester ultrasound records and birth outcomes will be recorded from medical registers. This study will set the stage for introducing a reproducible, time-saving and low-cost nutritional screening in pregnancy. The nutritional score will allow the implementation of specific corrective measures with potential large impact on placentation and pregnancy outcomes.Ethical and dissemination Ethical approval for this study was obtained from the Milano Area 1 Ethics Committee (No 46091, 7 November 2018) prior to the commencement of the research.The dissemination plan includes the presentation of abstracts and findings at national and international scientific meetings.

Background: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD. Methods: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements. Results: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% (p = 0.003) and 23.1% in Group 2 (p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant. Conclusions: Our findings showed the potential of TENS in the treatment of VBD.

Abstract The availability of a COVID-19 vaccine has raised the issue of its compatibility with breastfeeding. Consequently, the Italian Society of Neonatology (SIN), the Italian Society of Pediatrics (SIP), the Italian Society of Perinatal Medicine (SIMP), the Italian Society of Obstetrics and Gynecology (SIGO), the Italian Association of Hospital Obstetricians-Gynecologists (AOGOI) and the Italian Society of Infectious and Tropical Diseases (SIMIT) have made an ad hoc consensus statement. Currently, knowledge regarding the administration of COVID-19 vaccine to the breastfeeding mother is limited. Nevertheless, as health benefits of breastfeeding are well demonstrated and since biological plausibility suggests that the health risk for the nursed infant is unlikely, Italian scientific societies conclude that COVID-19 vaccination is compatible with breastfeeding.

Introduction Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysis Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is

The impact of SARS-CoV-2 infection in pregnancy remains underexplored. Here, the authors provide a comprehensive characterization of virus and immunological parameters in 31 SARS-CoV-2-infected pregnant women, finding evidence of vertical transmission in two of the mother-child pairs.

It is well established that pregnancy induces deep changes in the immune system. This is part of the physiological adaptation of the female organism to the pregnancy and the immunological tolerance toward the fetus. Indeed, over the three trimesters, the suppressive T regulatory lymphocytes are progressively more represented, while the expression of co-stimulatory molecules decreases overtime. Such adaptations relate to an increased risk of infections and progression to severe disease in pregnant women, potentially resulting in an altered generation of long-lived specific immunological memory of infection contracted during pregnancy. How potent is the immune response against SARS-CoV-2 in infected pregnant women and how long the specific SARS-CoV-2 immunity might last need to be urgently addressed, especially considering the current vaccinal campaign. To address these questions, we analyzed the long-term immunological response upon SARS-CoV-2 infection in pregnant women from delivery to a six-months follow-up. In particular, we investigated the specific antibody production, T cell memory subsets, and inflammation profile. Results show that 80% developed an anti-SARS-CoV-2-specific IgG response, comparable with the general population. While IgG were present only in 50% of the asymptomatic subjects, the antibody production was elicited by infection in all the mild-to-critical patients. The specific T-cell memory subsets rebalanced over-time, and the pro-inflammatory profile triggered by specific SARS-CoV-2 stimulation faded away. These results shed light on SARS-CoV-2-specific immunity in pregnant women; understanding the immunological dynamics of the immune system in response to SARS-CoV-2 is essential for defining proper obstetric management of pregnant women and fine tune gender-specific vaccinal plans.

Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations contributing to the pathogenesis of metabolic diseases. In this pilot study, plasma microRNAs (miRNAs) of obese pregnant women with/without GDM were profiled at delivery. Nineteen women with spontaneous singleton pregnancies delivering by elective Caesarean section were enrolled: seven normal-weight (NW), six obese without comorbidities (OB/GDM(−)), and six obese with GDM (OB/GDM(+)). miRNA profiling with miRCURY LNA PCR Panel allowed the analysis of the 179 most expressed circulating miRNAs in humans. Data acquisition and statistics (GeneGlobe and SPSS software) and Pathway Enrichment Analysis (PEA) were performed. Data analysis highlighted patterns of significantly differentially expressed miRNAs between groups: OB/GDM(−) vs. NW: n = 4 miRNAs, OB/GDM(+) vs. NW: n = 1, and OB/GDM(+) vs. OB/GDM(−): n = 14. For each comparison, PEA revealed pathways associated with oxidative stress and inflammation, as well as with nutrients and hormones metabolism. Indeed, miRNAs analysis may help to shed light on the complex epigenetic network regulating metabolic pathways in both the mother and the foeto-placental unit. Future investigations are needed to deepen the pregnancy epigenetic landscape in MO and GDM.

Maternal sepsis represents a leading cause of mortality and severe morbidity worldwide. In Italy, it is the second cause of direct maternal mortality. Delay in recognition and treatment initiation are the drivers of sepsis-associated adverse outcomes. Between November 2017 and October 2019, the Italian Obstetric Surveillance System coordinated a prospective population-based study on maternal sepsis occurring before or after childbirth from 22 weeks’ gestation onward and up to 42 days following the end of pregnancy. A nested 1:2 matched case-control study on postpartum sepsis was also performed. Maternal sepsis was diagnosed for the presence of suspected or confirmed infection alongside signs or symptoms of organ failure. The aim of this study was to assess maternal sepsis incidence and its associated risk factors, management, and perinatal outcomes. Six Italian regions, covering 48.2% of the national births, participated in the project. We identified an incidence rate of 5.5 per 10,000 maternities (95% CI 4.80–6.28). Seventy percent of patients had a low education level and one third were foreigners with a language barrier. Genital, respiratory, and urinary tract infections were the predominant sources of infection; the majority of cases was caused by E. coli and polymicrobial infections. The presence of vascular and indwelling bladder catheters was associated with a nine-fold increased risk of postpartum sepsis. There were no maternal deaths, but one fourth of women experienced a serious adverse event and 28.3% required intensive care; 1.8% of newborns died. Targeted interventions to increase awareness of maternal sepsis and its risk factors and management should be promoted.

Abstract Discordant placental echogenicity is observed in MC pregnancies complicated with twin anemia‐polycythemia sequence, but could also belong to complicated singleton gestation.

Italy has been one of the hardest hit countries in the European Union since the beginning of the SARS-CoV-2 pandemic, and Regione Lombardia (RL) has reported the largest number of cases in the country. This population-based retrospective study analyzed RL records of 122,942 pregnant women to describe SARS-CoV-2 vaccination uptake in the pregnant population, to compare pregnant women vaccine uptake vs. women of childbearing age and to evaluate the impact of vaccination status in pregnant women on admissions to intensive care units during 2021. Vaccination uptake according to citizenship and educational level and the comparison between pregnant and non-pregnant women was performed by Z test. A logistic regression was performed to compare age groups. Out of 122,942 pregnant women, 79.9% were vaccinated at the end of 2021. The vaccine uptake rate was significantly lower in pregnant versus non-pregnant women but increased after the issuing of official recommendations. Vaccine administration was significantly higher among pregnant women with Italian citizenship and with a high level of education in all trimesters. In conclusion, the role of official recommendations with explicit communication about the importance and safety of vaccination in pregnancy is critical to obtain trust and acceptance among pregnant women.

Introduction: A multifactorial etiology has been implicated in the development and maintenance of vestibulodynia (VBD), and atrophic changes of the vestibular mucosa have been observed in many patients. Aim: To assess the vestibular mucosa thickness in patients with VBD by comparing this sample with a control group of healthy fertile women and postmenopausal patients with symptoms of genitourinary syndrome of menopause (GSM). Methods: Vestibular mucosa thickness was measured with a 20 MHz ultrasound probe (DermaScan C, Cortex Technology, Denmark), including both the epidermis and dermis. Main outcome measures: All women were evaluated by anamnesis, physical examination, and self-report symptoms. Thickness of the vestibular mucosa (expressed in micrometers) was determined by the B-mode, excluding the hyperechogenic entrance echo and hypoechogenic subcutis. Clinical data related to VBD and GSM were recorded using a 0- to 10-point visual analog scale related to dyspareunia and vulvar pain/burning (0 = no pain; 10 = worst possible pain). Results: A total of 85 patients were recruited: 24 with VBD, 20 with GSM-related symptoms, and 20 matched controls. Vestibular mucosa thickness measurements were not significantly different between the VBD (mean ± DS: 1,092.5 ± 226.1 μm) and GSM groups (1,059.7 ± 221.5 μm), while the parameter was significantly lower (P

Introduction Gestational diabetes mellitus (GDM) is the most frequent metabolic complication during pregnancy and is associated with development of short-term and long-term complications for newborns, with large-for-gestational-age (LGA) being particularly common. Interestingly, the mechanism behind altered fetal growth in GDM is only partially understood.Research design and methods A proteomic approach was used to analyze placental samples obtained from healthy pregnant women (n=5), patients with GDM (n=12) and with GDM and LGA (n=5). Effects of altered proteins on fetal development were tested in vitro in human embryonic stem cells (hESCs).Results Here, we demonstrate that the placental proteome is altered in pregnant women affected by GDM with LGA, with at least 37 proteins differentially expressed to a higher degree (p

Objective To evaluate changes in awareness of maternal sepsis among healthcare providers resulting from the WHO Global Maternal Sepsis Study (GLOSS) awareness campaign.Design Independent sample precampaign/postcampaign through online and paper-based surveys available for over 30 days before campaign roll-out (pre) and after study data collection (post). Descriptive statistics were used for campaign recognition and exposure, and odds ratio (OR) and percentage change were calculated for differences in awareness, adjusting for confounders using multivariate logistic regression.Setting and participants Healthcare providers from 398 participating facilities in 46 low, middle and high-income countries.Intervention An awareness campaign to accompany GLOSS launched 3 weeks prior to data collection and lasting the entire study period (28 November 2017 to 15 January 2018) and beyond.Main outcome measures Campaign recognition and exposure, and changes in awareness.Results A total of 2188 surveys were analysed: 1155 at baseline and 1033 at postcampaign. Most survey respondents found the campaign materials helpful (94%), that they helped increase awareness (90%) and that they helped motivate to act differently (88%). There were significant changes with regard to: not having heard of maternal sepsis (−63.4% change, pre-OR/post-OR 0.35, 95% CI 0.18 to 0.68) and perception of confidence in making the right decisions with regard to maternal sepsis identification and management (7.3% change, pre-OR/post-OR 1.44, 95% CI 1.01 to 2.06).Conclusions Awareness raising campaigns can contribute to an increase in having heard of maternal sepsis and an increase in provider perception of confidence in making correct decisions. Offering the information to make accurate and timely decisions while promoting environments that enable self-confidence and support could improve maternal sepsis identification and management.

Summary: Background: Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management. Methods: We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups. Findings: Between Nov 28, 2017, and Dec 4, 2017, of 2965 women assessed for eligibility, 2850 pregnant or recently pregnant women with suspected or confirmed infection were included. 70·4 (95% CI 67·7–73·1) hospitalised women per 1000 livebirths had a maternal infection, and 10·9 (9·8–12·0) women per 1000 livebirths presented with infection-related (underlying or contributing cause) severe maternal outcomes. Highest ratios were observed in LMICs and the lowest in HICs. The proportion of intrahospital fatalities was 6·8% among women with severe maternal outcomes, with the highest proportion in low-income countries. Infection-related maternal deaths represented more than half of the intrahospital deaths. Around two-thirds (63·9%, n=1821) of the women had a complete set of vital signs recorded, or received antimicrobials the day of suspicion or diagnosis of the infection (70·2%, n=1875), without marked differences across severity groups. Interpretation: The frequency of maternal infections requiring management in health facilities is high. Our results suggest that contribution of direct (obstetric) and indirect (non-obstetric) infections to overall maternal deaths is greater than previously thought. Improvement of early identification is urgently needed, as well as prompt management of women with infections in health facilities by implementing effective evidence-based practices. Funding: UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction, WHO, Merck for Mothers, and United States Agency for International Development.

Objectives1. To assess the performance of an extended questionnaire in identifying cases of SARS-CoV-2 infection among obstetric patients. 2. To evaluate the rate of infection among healthcare workers involved in women's care.Study designA prospective cohort study of obstetric patients admitted to MBBM Foundation and Buzzi Hospital (Lombardy, Northern Italy) from March 16th to May 22nd, 2020. Women were screened on admission by a questionnaire investigating major and minor symptoms of infection and high-risk contacts in the last 14 days. SARS-CoV-2 assessment was performed by RT-PCR on nasopharyngeal swabs. Till April 7th, a targeted SARS-CoV-2 testing triggered by a positive questionnaire was used; from April 8th, a universal testing approach was implemented.ResultsThere were 1,177 women screened by the questionnaire, which yielded a positive result in 130 (11.0%) cases. SARS-CoV-2 RT-PCR was performed in 865 (73.5%) patients, identifying 51 (5.9%) infections. During the first period, there were 29 infected mothers, 4 (13.8%) of whom had a negative questionnaire. After universal testing implementation, there were 22 (3%, 95% CI 1.94% - 4.04%) infected mothers, 13 (59.1%) of whom had a negative questionnaire; rate of infection among asymptomatic women was 1.9%. Six of the 17 SARS-CoV-2-positive women with a negative questionnaire reported symptoms more than 14 but within 30 days before admission. Isolated olfactory or taste disorders were identified in 15.7% of infected patients. Rate of infection among healthcare workers was 5.8%.ConclusionsAn exhaustive triage questionnaire can effectively discriminate women at low risk of SARS-CoV-2 infection in the context of a targeted and a universal viral testing approach. In 15.7% of infected women, correct classification as a suspected case of infection was due to investigation of olfactory and taste disorders. Extension of the assessed time-frame to 30 days may be worth considering to increase the questionnaire's performance.

Abstract Vitamin D plays a pivotal role in the regulation of calcium-phosphorus metabolism, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur. Besides its historical skeletal functions, in the last years it has been demonstrated that vitamin D directly or indirectly regulates up to 1250 genes, playing so-called extraskeletal actions. Indeed, recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious, allergic and autoimmune diseases. Thus, vitamin D deficiency may affect not only musculoskeletal health but also a potentially wide range of acute and chronic conditions. At present, the prevalence of vitamin D deficiency is high in Italian children and adolescents, and national recommendations on vitamin D supplementation during pediatric age are lacking. An expert panel of the Italian Society of Preventive and Social Pediatrics reviewed available literature focusing on randomized controlled trials of vitamin D supplementation to provide a practical approach to vitamin D supplementation for infants, children and adolescents.

SARS-CoV-2 infection has been related to adverse pregnancy outcomes. A placental role in protecting the fetus from SARS-CoV-2 infection has been documented. Nevertheless, it is still unclear how the placenta is affected in SARS-CoV-2 infection. Here we assessed placental mitochondrial (mt) and oxidative features in COVID-19 and healthy mothers. mtDNA levels, DNA oxidative damage, expression levels of genes involved in antioxidant defenses, mitochondrial dynamics and respiratory chain subunits were investigated in placentas from singleton pregnancies of 30 women with SARS-CoV-2 infection during the third trimester (12 asymptomatic, 18 symptomatic) and 16 controls. mtDNA levels decreased in COVID-19 placentas vs. controls and inversely correlated with DNA oxidative damage, which increased in the symptomatic group. Antioxidant gene expressions decreased in SARS-CoV-2 mothers (CAT, GSS). Symptomatic cases also showed a lower expression of respiratory chain (NDUFA9, SDHA, COX4I1) and mt dynamics (DNM1L, FIS1) genes. Alterations in placental mitochondrial features and oxidative balance in COVID-19-affected mothers might be due to the impaired intrauterine environment, generated by systemic viral effects, leading to a negative vicious circle that worsens placental oxidative stress and mitochondrial efficiency. This likely causes cell homeostasis dysregulations, raising the potential of possible long-term effects.

MicroRNAs are gene expression regulators associated with several human pathologies, including those generated by viral infections. Their role in SARS-CoV-2 infection and COVID-19 has been investigated and reviewed in many informative studies; however, a thorough miRNA outline in SARS-CoV-2-infected pregnant women (SIPW), at both systemic and placental levels, is missing. To fill this gap, blood and placenta biopsies collected at delivery from 15 asymptomatic SIPW were immediately analysed for: miRNA expression (n = 84) (QPCR array), antiviral/immune mRNA target expression (n = 74) (QGene) and cytokine/chemokines production (n = 27) (Multiplex ELISA). By comparing these results with those obtained from six uninfected pregnant women (UPW), we observed that, following SARS-CoV-2 infection, the transcriptomic profile of pregnant women is significantly altered in different anatomical districts, even in the absence of clinical symptoms and vertical transmission. This characteristic combination of miRNA and antiviral/immune factors seems to control both the infection and the dysfunctional immune reaction, thus representing a positive correlate of protection and a potential therapeutic target against SARS-CoV-2.

Hypertensive disorders affect about one third of all people aged 20 and above, and are treated with anti-hypertensive drugs. Preeclampsia (PE) is one form of such disorders that only develops during pregnancy. It affects ten million pregnant women globally and additionally causes fetal loss and major newborn disabilities. The syndrome's origin is multifactorial, and anti-hypertensive drugs are ineffective in treating it. Biomarkers are helpful for predict its development. Generic drugs, such as low dose aspirin, were proven effective in preventing preterm PE. However, it does not cure the majority of cases and many studies are underway for fighting PE with extended use of additional generic drugs, or through new drug development programs.This review focuses on placental protein 13 (PP13). This protein is only expressed in the placenta. Impaired PP13 DNA structure and/or its reduced mRNA expression leads to lower blood PP13 level that predict a higher risk of developing PE. Two polymorphic PP13 variants have been identified: (1) The promoter PP13 variant with an “A/A” genotype in the -98 position (versus “A/C” or “C/C”). Having the “A/A” genotype is coupled to lower PP13 expression, mainly during placental syncytiotrophoblast differentiation and, if associated with obesity and history of previous preeclampsia, it accurately predicts higher risk for developing the disorder. (2) A thymidine deletion at position 221 causes a frame shift in the open reading frame, and the formation of an early stop codon resulting in the formation of DelT221, a truncated variant of PP13. In pregnant rodents, both short- and long- term replenishment of PP13 causes reversible hypotension and vasodilation of uterine vessels. Long-term exposure is also accompanied by the development of larger placentas and newborns. Also, only w/t PP13 is capable of inducing leukocyte apoptosis, providing maternal immune tolerance to pregnancy.Based on published data, we propose a targeted PP13 therapy to fight PE, and consider the design and conduct of animal studies to explore this hypothesis. Accordingly, a new targeted therapy can be implemented in humans combining prediction and prevention. Keywords: Preeclampsia, Galectins, LGALS13, Polymorphism, Placenta, Gene expression, Promoter regulation, Immune tolerance, Endothelial layer, Signaling pathways

Background: SSRIs (Selective Serotonin Reuptake Inhibitors) are the most useful drugs to treat depression during pregnancy. Intrauterine exposure to SSRIs may increase the risk of growth restriction, preterm birth and neonatal complications. However, advantages in treating depression seem to exceed potential drug side effects in respect un-treated depression. SSRIs undergo extensive hepatic first-pass metabolism with the involvement of several cytochrome P450 (CYPs) enzymes. Genetic polymorphisms may influence the expression and activity of CYPs genes. The first aim of this study was to evaluate neonatal outcomes in depressed mothers exposed to SSRIs during pregnancy. SSRIs pharmacogenetics was also evaluated in a subset of mothers and fetuses.Methods: In this case-control study, cases (n = 42) were Caucasian women with a diagnosis of depression and/or anxiety, treated with SSRIs for the whole pregnancy. Controls (n = 85) were Caucasian women without a psychiatric diagnosis and not exposed to SSRIs during pregnancy. Exclusion criteria for both groups were other psychotropic drugs, anti-epileptics, drug of abuse, alcohol addiction, maternal or fetal infectious diseases, fetal/neonatal chromosomal genetic abnormalities. Maternal and fetal blood samples were obtained at delivery to analyze genotype in 33 cases.Results: The population was homogenous for demographic, anthropometric, socio-economic and obstetric variables except for smoking and mean hemoglobin values before delivery. Obstetric features were comparable. Newborns exposed to SSRIs during fetal life were significantly more likely to be Low Birth Weight (LBW) (birth weight

Introduction: Sex steroids are regulating factors for intrauterine growth. 17-β Estradiol (E2) is particularly critical to a physiological pregnancy, as increased maternal E2 was correlated to lower fetal weight at delivery. The placenta itself is a primary source of estrogens, synthetized from cholesterol precursors. Cytochrome P450 aromatase (encoded by CYP19A1 gene) is a rate-limiting enzyme for E2 biosynthesis. CYP19A1 transcription is supported by Estrogen Related-Receptor Gamma (ERRγ- ESRRG gene), which thus has an indirect role in placental steroidogenesis. Here we investigated maternal E2 levels and placental CYP19A1 and ESRRG expressions in pregnancies with IntraUterine Growth Restriction (IUGR).Methods: Singleton pregnancies were studied. E2 was measured in maternal plasma by electrochemiluminescence in 16 term controls and 11 IUGR (classified by umbilical artery doppler pulsatility index) at elective cesarean section, and also in 13 controls during pregnancy at a gestational age comparable to IUGR. CYP19A1 and ESRRG expressions were analyzed in placental tissue. Maternal/fetal characteristics, placental and molecular data were compared among study groups and tested for correlations.Results: Maternal E2 plasma concentrations were significantly decreased in IUGR compared to controls at delivery. When analyzing normal pregnancies at a gestational age similar to IUGR, E2 levels were not different to pathological cases. However, E2 levels at delivery positively correlated with placental efficiency. Placental CYP19A1 levels were significantly higher in IUGR placental tissue vs. controls, and specifically increased in female IUGR placentas. ESRRG expression was not different among groups.Discussion: We report a positive correlation between 17-β Estradiol levels and placental efficiency, that might indicate a disrupted steroidogenesis in IUGR pregnancies. Moreover, we show alterations of CYP19A1 expression in IUGR placentas, possibly indicating a compensatory effect to the adverse IUGR intrauterine environment, also depending on fetal sex. Further studies are needed to deeper investigate IUGR alterations in the complex interaction among molecules involved in placental steroidogenesis.

OBJECTIVES:To construct monochorionic (MC) twin-specific longitudinal Doppler references for umbilical artery pulsatility index (UA-PI), middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and ductus venosus (DV) PI derived from a strictly selected cohort of uncomplicated MC twins. The secondary aim of the study was to compare our findings with singleton reference charts. METHODS:A retrospective evaluation was made of all consecutive uncomplicated MC twin pregnancies referred to our Unit from 2010 to 2018. Fortnightly serial examinations were performed of UA-PI, MCA-PI, MCA-PSV and DV-PI, according with the clinical protocol, from 20 to 37 weeks of gestation. We included cases with at least four ultrasound examinations, delivery at our hospital and complete neonatal follow up. A two-step method was used to trace the estimated centile curves: estimation of the median was performed with appropriate fractional polynomials by a multilevel model and estimation of the external centiles through the residuals (quantile regression). The comparison with singletons was made by plotting the references derived from the present study on the referred charts commonly used for singletons. RESULTS:The study group comprised 150 uncomplicated MC twin pairs. Estimated centiles (3rd, 5th, 10th, 50th, 90th, 95th, 97th) of UA-PI, MCA-PI, MCA-PSV and DV-PI in function of the gestational age are presented. The comparison with singletons showed substantial differences, with higher UA-PI and lower MCA-PI and PSV median values in MC twins. Median DV PI values were similar to the values for singletons, while the upper centiles were higher in MC twins. CONCLUSIONS:This study sets out MC twin-specific longitudinal references for UA-PI, MCA-PI, MCA-PSV and DV-PI derived from the largest series of uncomplicated MC twin pregnancies presently available. The comparison with singleton reference values underscores the deviation from physiology that is intrinsic to these unique pregnancies and supports the need for MC twin-specific charts.

BackgroundHIV-1 infected patients show impaired semen parameters. Currently, it is not clear whether HIV-1 infection itself or antiretroviral therapy have an effect on semen parameters. We aim evaluate semen quality in a large cohort of fertile HIV-1 infected men under stable highly active antiretroviral therapy (HAART) and to assess the effect of HAART type and duration on semen parameters.Materials and methodsBetween January 2010 and June 2014, we enrolled in a retrospective case-control study 770 HIV-1 patients under stable HAART asking a reproductive counselling with their HIV negative partner. Co-infections with HBV or HCV, genital tract infections and known causes of infertility represented exclusion criteria. Semen samples were analysed and compared with the WHO reference values. A multivariate analysis including HAART type and duration, age, viral load and CD4 count, was performed on 600 patients out of 770.ResultsThe median values of all semen parameters were significantly lower among HIV-1 infected patients compared to the WHO reference group, with a significant proportion of patients having values below the 5th percentile of the WHO reference value. In a multivariate analysis, only age and viral load negatively impacted progressive motility (β -0.3 (95% CI: -0.5; -0.0) %, pConclusionsHIV-1 infected patients showed a significant impairment of semen parameters compared to the reference values. HAART type and duration showed no associations with semen quality. Further research is needed to investigate implications for clinical care of HIV infected men desiring a child.

Background: Breastfeeding has effects on health throughout the lives of mothers and babies. In 2014 in Italy, 10,976 babies were born through ART (assisted reproductive technology), accounting for 2.2% of annual births. The study aims to assess how both social and biological variables and the mode of conception influence breastfeeding. Methods: This observational study involves 161 pregnancies from three different modes of conception: homologous in vitro fertilization, ovum donation, and spontaneous pregnancies. Neonatal and maternal characteristics were collected from the hospital database, while breastfeeding outcomes were obtained through telephone interviews. Results: The mode of conception did not influence any of the breastfeeding outcomes. Breastfeeding duration was negatively affected by smoking. Vaginal delivery, birth weight > 2500 g, delivery > 37 gestational weeks, breastfeeding intention, and rooming-in are positively associated with the initiation of breastfeeding, while skin-to-skin contact and receiving information concerning breastfeeding are the most significant variables associated with its exclusivity and duration. Conclusions: The duration and exclusivity of breastfeeding are mainly related with information thereon, promotion, and breastfeeding support, but not with the mode of conception. It is essential to adequately support women from the outset in breastfeeding, as recommended by the World Health Organization (WHO) guidelines.

Oocyte donations (OD) represent 4.5% of all in vitro fertilization (IVF) cycles. While OD pregnancies face increased risks of obstetrical complications, especially pregnancy-induced hypertension and pre-eclampsia (PE), little is known about the physiology and the physiopathology of placentation. We performed a prospective case-control study to analyze uterine artery Doppler pulsatility index (UtA-PI) and serum maternal 17β-estradiol (17β-E) at 11 + 0 to 13 + 6 weeks’ gestation in singleton pregnancies with different modes of conception. Study groups were: 55 OD, 48 IVF with autologous oocytes from fresh cycles (Autologous-Fresh IVF), 10 IVF with autologous oocytes from frozen cycles (Autologous-Frozen IVF) and 122 spontaneously conceived pregnancies (SC). The mean UtA-PI and serum maternal 17β-E at 11 to 13 + 6 weeks were significantly lower in OD as compared to SC and autologous IVF, either from fresh or frozen cycles. Oocyte donation presents lower UtA-PI and lower serum 17β-E in the first trimester of pregnancy. The etiology of these particularr differences is likely multifactorial and deserves further investigation.

HIV-1-affected couples’ desire to have children and free sexual intercourses with the use of pre-exposure prophylaxis for the negative partner has emerged as an alternative option to assisted reproduction in aviremic patients under highly active antiretroviral therapy (HAART). It is already known that sperm quality may be impaired in HIV-infected men. The underlying physiopathological mechanism is still debated. The aim of this study was to evaluate the effects of HAART on sperm DNA fragmentation, comparing HIV-1-infected patients taking HAART versus naïve HIV-1-infected patients. This is a prospective case-control study. Sperm nuclear DNA fragmentation rate was evaluated by the sperm chromatin dispersion test in 77 HIV-infected men: 53 HIV-1 patients receiving HAART (Group 1) versus 24 naïve HIV-1 patients not receiving HAART (Group 2). Complete semen analysis was performed according to WHO 2010 recommendations. Patients with HBV infection or HCV infection coinfections and genital tract infections wre excluded. All the patients did not present any clinical signs of their disease. Seminal parameters were examined in the two groups, showing no significant differences. Increased sperm DNA fragmentation > 30% was demonstrated in 67.9% of patients in Group 1 and 37.5% of patients in Group 2, respectively ( p = .02). A positive but nonsignificant trend toward increased fragmentation was reported with advancing patients’ age. In conclusion, sperm nuclear fragmentation rate is increased in HIV-1-infected patients taking HAART compared to HIV-1 patients not receiving HAART.