Passive immunization plays a pivotal role in prenatal care. This study aimed to assess maternal awareness, knowledge, and adherence to vaccinations during pregnancy, specifically for pertussis, influenza, and respiratory syncytial virus (RSV), while also evaluating how the approval of the RSV vaccine during pregnancy has been received by women and healthcare professionals. A cross-sectional survey was conducted at Mangiagalli Hospital in Milan between August and November 2024. Pregnant women were asked to complete a self-administered questionnaire regarding socioeconomic characteristics, knowledge of vaccine-preventable diseases, and vaccination acceptance. Multivariate logistic regression examined associations between socioeconomic factors and vaccination behavior. A total of 390 participants were considered for final analysis. 89.7% of women had received or would receive the pertussis vaccine, 72.3% the influenza vaccine (P < .001), and 74.9% the RSV vaccine (P < .001). Education, employment status, and number of children were significantly associated with higher vaccination rates. The gynecologist was the primary source of information for most women (60.5%). Barriers to vaccination included a lack of prior discussion with healthcare providers and concerns about vaccine safety. Nevertheless, 83.8% of women would be favorable to receiving all vaccines together and 86.4% would prefer receiving the vaccine themselves rather than having monoclonal antibodies administered to their neonates. Maternal education and effective communication with healthcare providers are crucial in improving vaccination acceptance during pregnancy. Personalizing vaccination counseling for women with lower educational levels and those expecting their first child is essential.

This longitudinal, prospective, multicentre observational cohort study investigates the associations between maternal nutritional status - assessed using the first trimester SIMPLE score and pregestational BMI - and fetal growth trajectories and velocity, as proxies for intrauterine development. Healthy women with singleton pregnancies undergoing first trimester screening were enrolled. Adherence to a healthy lifestyle was evaluated using the SIMPLE score, categorising participants into low (< 6) and high (≥ 6) adherence groups. Fetal growth parameters - including biparietal diameter, head circumference, abdominal circumference (AC), femur length and estimated fetal weight (EFW) - were assessed during second and third trimester ultrasounds, and birth outcomes were recorded. Multi-adjusted linear mixed models examined associations between SIMPLE score groups, individual score items, pregestational BMI and fetal growth, with analyses stratified by fetal sex. Out of 938 enrolled women, 109 (11·6 %) were classified as the low-adherence group. Multi-adjusted linear mixed models showed that low adherence was associated with decreased EFW acceleration from the second to the third trimester. Stratification by fetal sex confirmed the association only among male fetuses. Analysis of pregestational BMI and individual SIMPLE score items revealed significant positive associations between pregestational BMI, AC and EFW growth velocity and a negative association between first trimester Hb (> 110 g/l) and EFW growth velocity. Overall, these findings confirm the clinical utility of the SIMPLE score, demonstrating significant associations with intrauterine growth trajectories and velocity, independent of other markers of nutritional status (e.g. pregestational BMI).

Cesarean delivery has evolved from an operation of last resort to the most frequently performed major surgical procedure worldwide, with nearly 29 million births each year. Advances in anesthesia, surgical technique, and perioperative care have greatly improved safety, yet the expansion of cesarean delivery raises complex clinical, psychological, and societal questions. This article introduces the American Journal of Obstetrics and Gynecology (AJOG) supplement "Cesarean Delivery", which assembles expert reviews, clinical opinions, original research, clinical trials, and perspectives addressing key aspects of this transformation. Topics include preoperative ultrasound to guide incision planning, evolving methods of uterine closure, Enhanced Recovery After Surgery (ERAS) guidelines, management of complex cases such as placenta accreta, and the prevention of infection, hemorrhage, and thromboembolism. This issue introduces a new quality index that evaluates outcomes for the maternal-newborn dyad, integrating cesarean rate with both maternal and neonatal outcomes to provide a more meaningful measure of obstetric performance. Psychological sequelae such as post-traumatic stress disorder and postpartum depression, and neonatal consequences of elective and preterm cesarean deliveries are also discussed. Collectively, these contributions redefine cesarean delivery as part of an integrated continuum of care-one that values surgical technique, maternal and infant outcomes, and the ethical balance between safety and autonomy.

INTRODUCTION:Assisted vaginal birth (AVB) refers to the obstetric procedure commonly performed during the second stage of labor, aimed to expedite delivery after evaluating alternatives options of cesarean birth or expectant management. OBJECTIVE:To evaluate the risk factors for AVB and to compare perinatal factors and outcomes of vacuum extraction when applied to the mid/low cavity versus the perineum. STUDY DESIGN:Retrospective observational monocentric study conducted on the cohort of women with singleton pregnancies who delivered vaginally in 2023 at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan. Multivariable logistic regression was used to identify factors independently associated with AVB. A secondary analysis compared maternal and neonatal outcomes between perineal and mid/low cavity vacuum applications. RESULTS:A total of 3455 vaginal births were included: 3090 spontaneous vaginal births and 365 AVB. After adjusting for all factors considered, maternal age (OR 1.04, 95% CI: 1.01-1.07), mode of conception (OR 1.58, 95% CI: 1.07-2.33), epidural analgesia (OR 6.25, 95% CI: 3.05-12.80), gestational age (OR 1.48, 95% CI: 1.31-1.67), and newborn male sex (OR 1.35, 95% CI: 1.06-1.73) were positively associated with AVB, whereas parity (OR 0.20, 95% CI: 0.14-0.29) was inversely associated. Compared to perineal applications, mid/low pelvic applications were associated with greater blood loss (p < 0.01), higher episiotomy rate (95.5% vs 88.2%, p = 0.03), and increased ultrasound use (62.4% vs 23.5%, p < 0.01). CONCLUSIONS:In this real-world cohort, AVB was mainly associated with well-established factors, confirming previous evidence. Mid/low cavity applications showed greater maternal morbidity than perineal applications, underscoring the importance of careful case selection and procedural planning.

Background:Maternal overweight (OW) and obesity are increasingly prevalent worldwide and have been linked to adverse pregnancy and delivery outcomes. This study aims to evaluate maternal and neonatal outcomes in pregnancies stratified according to pregestational body mass index (BMI) in a tertiary care setting in Italy. Methods:This retrospective study included all singleton live births between 2022 and 2024 at the IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Women were classified into four groups based on pregestational BMI: (1) underweight (UW, BMI < 18.5 kg/m2, n = 1796); (2) normal weight (NW, BMI 18.5-24.9 kg/m2, n = 11,710); (3) OW (BMI ≥ 25.0 kg/m2, n = 2313); and (4) obese (OB, BMI ≥ 30.0 kg/m2, n = 976). Delivery outcomes were compared among groups using binary logistic regression and generalized linear models adjusted for confounding factors. Results:Inclusion criteria were met by a population of 17,813 singleton pregnancies. Multivariate models confirmed that OB women were independently associated with virtually all adverse delivery outcomes, including higher odds of preterm birth (aOR 1.48), labor induction (aOR 1.69), emergency cesarean delivery (aOR 1.42), postpartum hemorrhage (aOR 1.40), APGAR score at 5 min lower than 6 (aOR 2.77), and admission to neonatal intensive care unit (aOR 2.05) compared to NW controls. OW women were at higher risk of emergency cesarean delivery and postpartum hemorrhage, while UW women showed largely comparable outcomes to NW women, with the sole exception of reduced birthweights and higher odds of episiotomy use. Conclusions:Maternal OW and OB are associated with increased maternal and neonatal morbidity, highlighting the complex obstetric challenges in this population. These findings underscore the need for a BMI-tailored obstetric care and preventive public health strategies targeting women of reproductive age.

Hypoxic-ischemic encephalopathy represents a major cause of neonatal mortality and long-term neurodevelopmental impairment. Therapeutic hypothermia has become the standard of care, significantly improving survival and outcomes. Nevertheless, its clinical implementation often lacks a standardized operational framework to ensure consistent efficacy and safety. The present work aimed to develop GRADE-based operational guidelines for therapeutic hypothermia, offering neonatologists a structured approach for identifying, treating, and monitoring newborns throughout the procedure. A panel of experts appointed by the Italian Society of Neonatology conducted a systematic review (PROSPERO registration CRD420250651303) of randomized controlled trials evaluating the effects of therapeutic hypothermia on neurodevelopmental outcomes. Literature searches were performed across Medline, Cochrane, Scopus, Embase, and Web of Knowledge databases, and studies were assessed using the Cochrane Risk-of-Bias 2 tool. Recommendations were formulated through consensus meetings following GRADE methodology and subsequently validated by an external multidisciplinary panel. Eight randomized controlled trials, encompassing a total of 1,843 newborns, met the inclusion criteria. Based on a comprehensive evaluation of study indications, characteristics, and outcomes, evidence-based recommendations were established. The risk-of-bias assessment revealed an even distribution between studies categorized as low and moderate risk. The resulting guidelines present a structured protocol covering all phases of therapeutic hypothermia - timing, clinical setting, management, and follow-up - and include proposals for expanding its application. To facilitate clinical implementation, the guidelines are accompanied by summary tables, graphical flowcharts, and algorithms designed for immediate use in neonatal intensive care settings. The GRADE-based recommendations presented here, now adopted as the Italian national clinical guidelines for therapeutic hypothermia in newborns, provide an evidence-driven and standardized framework to optimize neonatal care. These guidelines are intended to support daily clinical decision-making and will undergo periodic updates to incorporate emerging evidence and maintain their clinical relevance.

Background:We tested whether COVID-19 vaccination affects the risk of preeclampsia (PE) given the well-documented association between COVID-19 and PE, and their overlapping risk factors and pathophysiological pathways. Methods:We analysed individual level data from pregnant women prospectively enrolled from 18 countries in two consecutive cohorts between 2020 and 2022 during the COVID-19 pandemic using identical methodology. Pregnant women were recruited either with a COVID-19 diagnosis or as concomitant, consecutive, non-diagnosed controls from the same hospitals. Following vaccine availability, vaccination status was documented to define a vaccine-exposed subgroup. Multivariable logistic regression models assessed the odds of PE adjusting for confounders and cohort as a proxy for viral strain, stratifying by pre-existing morbidities and SARS-CoV-2 infection. Survival analyses estimated PE incidence according to vaccination status and pre-existing morbidities. Findings:Of 6527 pregnant women, 2166 (33.2%) were diagnosed with COVID-19 and 3753 (57.5%) were unvaccinated. Of the 2774 vaccinated women, 1795 (64.7%) received mRNA vaccines; 848 (30.6%) received the initial regimen plus a booster dose, of whom 66.6% received a booster with an mRNA vaccine. We confirmed an independent association between COVID-19 and PE (aOR: 1.45; 95% CI: 1.15-1.84), particularly in unvaccinated women (aOR: 1.78; 95% CI: 1.31-2.42). Overall, after adjusting for confounders, any vaccination gave a protective effect against PE during the index pregnancy (aOR: 0.85; 95% CI: 0.65-1.10), that was stronger with a booster dose (aOR: 0.67; 95% CI: 0.45-0.99). Among women with pre-existing morbidities who received a booster dose the odds were reduced by 58% (aOR: 0.42; 95% CI: 0.20-0.87) - an effect mainly observed in women diagnosed with COVID-19. Adjustment for study site and cohort year did not alter the magnitude of the effect. Vaccination amongst women who received a booster dose was also associated with decreased odds of maternal (aOR: 0.68; 95% CI: 0.55-0.83) and perinatal (aOR: 0.71; 95% CI: 0.54-0.95) morbidity and mortality, and preterm birth (aOR: 0.67; 95% CI: 0.53-0.85). Interpretation:COVID-19 vaccination with a booster reduces the odds of PE by 30% approaching 60% reduction among women with pre-existing morbidities. Funding:The original INTERCOVID study was supported in Oxford by the COVID-19 Research Response Fund from the University of Oxford (Ref 0009083).

Maternal satisfaction is a widely used indicator for evaluating the quality of maternity services and is linked to important psychological and relational outcomes. In Italy, limited data have been published on women’s childbirth experiences, generally showing high satisfaction, but highlighting areas needing improvement, such as communication and pain management, especially during emergency cesarean section or operative vaginal delivery. This study primarily aimed to assess women’s overall evaluation of their labor and delivery experiences. Additionally, we examined sociodemographic and obstetric factors that may influence maternal satisfaction and explored satisfaction across specific experiential domains. This is an observational, cross-sectional, non-pharmacological, non-profit, monocentric study conducted between June and October 2024 at the Unit of Obstetrics and Maternal Fetal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan. A total of 696 women were consecutively recruited during their postpartum hospital stay. Participants completed a pseudonymized questionnaire which consisted of three sections: sociodemographic data, obstetric history, and birth experience evaluation using a 5-point Likert scale. Maternal satisfaction was operationalized as a retrospective self-reported appraisal of care. We used logistic regression to estimate prevalence odds ratios (OR) and the corresponding 95

OBJECTIVE:Antiphospholipid antibodies (aPL) may directly affect placentation and trigger local complement-mediated inflammation/thrombosis. Obstetric complications in the antiphospholipid syndrome (APS) are still frequent despite therapy/close monitoring, and the identification of new risk biomarkers is an unmet need. We aimed to prospectively investigate the prognostic value of classification/nonclassification laboratory APS criteria and markers of complement activation for pregnancy complications, in particular preterm delivery (PTD). METHODS:We observed 60 women prospectively during pregnancy and postpartum: 33 aPL-positive (20 APS and 13 aPL-carriers) and 27 aPL-negative (5 systemic lupus erythematosus, 11 rheumatoid arthritis and 11 undifferentiated connective tissue diseases). aPL criteria tests, anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG/IgM and anti-β2glycoprotein I-Domain I IgG, complement products (C3, C4, C3a, C5a, sC5b-9, MBL) and complement pathway activity (classical pathway [CP], alternative pathway [AP], and lectin pathway [LP]) were measured in 231 available specimens. RESULTS:PTD was experienced in 21% of aPL-positive and 15% of aPL-negative women. Anti-PS/PT IgG/IgM titers were significantly higher in PTD versus non-PTD women (P < 0.05) at almost all time points. At variance with CP and AP, LP activity in aPL-positive PTD was lower than in non-PTD, reaching a statistically significant difference compared with aPL-negative PTD patients (P < 0.05). Moreover, LP activity significantly correlated with anti-PS/PT IgG/IgM titers, both measured in the first trimester (P < 0.05), and all of them significantly correlated with the week of gestation at delivery (P < 0.05). CONCLUSION:The reduced LP activity and the higher anti-PS/PT IgG/IgM titers in PTD aPL-positive women during the first trimester suggest their use as early prognostic tools for PTD in aPL-positive pregnant women.

BACKGROUND:Up to 25-35% of women receive antibiotics (ABX) during pregnancy, but little is known about the consequences on a key mucosal interface such as the mammary gland, and on the development of the neonatal gut's microbiota and IgA. We hypothesize that prenatal ABX negatively affect the immune functionality of mammary gland, the composition of breast milk microbiota, the development of neonatal fecal microbiota and the abundance of neonatal fecal IgA. METHODS:Case-control translational cohort study on women and neonates in the presence or absence (N = 41 + 41 pairs) of exposure to prenatal ABX for at least 7 consecutive days after 32 weeks of gestation. RESULTS:We will evaluate IgA concentration in breast milk and in neonatal feces up to one year after delivery. We will also evaluate clinical parameters, neurodevelopment and the composition of the IgA-coated and uncoated fractions of breast milk and fecal microbiota by means of magnetic-activated cell sorting (MACS) coupled with shotgun metagenomics. Finally, we will measure the concentration of the chemokine CCL28 on maternal serum and breast milk, as a marker of activity of the entero-mammary pathway. CONCLUSIONS:Our results might support a data-driven evaluation of breast milk immune function in women exposed to prenatal ABX. IMPACT:Breast milk IgA and microbiota are critical to determine the positive effects of breastfeeding in infants. This research protocol will investigate breast milk IgA, microbiota, and the IgA+ / IgA- fractions of neonatal fecal microbiota upon exposure to prenatal antibiotics. Fecal IgA and microbiota in infants exposed or not exposed to prenatal antibiotics will be analyzed up to 1 year after birth. This research will clarify the impact of prenatal antibiotics on the immune function of breast milk. This, in turn, might support the selective evaluation of breast milk IgA/microbiota in mothers exposed to prenatal antibiotics, or in donor human milk.

BACKGROUND:Pregnancy is a vulnerable period for intimate partner violence, as violence may emerge or intensify. On this basis, several international guidelines recommend systematic and repetitive screening of domestic violence during pregnancy. However, the adherence to these recommendations is unclear. METHODS:This prospective observational study involved women who delivered in an urban referral obstetrical hospital located in Milan, Northern Italy. Participants were enrolled after delivery and completed an anonymous questionnaire structured into four sections: demographic characteristics, pregnancy-related information, assessment of whether domestic violence screening was performed during gestation, and evaluation of any recent history of abuse. This latter issue was investigated through four different validated questionnaires. RESULTS:Among the 196 participants, nine (4.6%, 95%CI: 2.4-8.5%) reported having been screened at least once during pregnancy about a history of domestic violence. Some differences emerged according to the setting of antenatal care. The frequency of a history of abuses in the studied cohort differed according to the questionnaire used but was not rare, prevalences varying between 1.0% to 5.6%. CONCLUSIONS:Screening for intimate partner violence in pregnancy is seldom performed. A call for action is warranted.

Introduction: Pregnancy-associated plasma protein A (PAPP-A) is a glycoprotein produced by the syncytiotrophoblast and decidua, as well as vascular smooth muscle cells. While type 2 diabetes is typically associated with chronically low PAPP-A levels – contributing to vascular dysfunction – the relationship between glycometabolic control and PAPP-A in pregestational diabetes (pre-GD) remains under-explored. This study investigated the correlation between PAPP-A levels and glycated hemoglobin (HbA1c) in pregnant women with type 1 and type 2 pre-GD. Methods: This retrospective study analyzed 96 pregnant women with pre-GD (type 1 and type 2) who underwent first-trimester combined screening. PAPP-A levels were correlated with both pregestational and first-trimester HbA1c values. In type 2 pre-GD, multivariate analysis was employed to assess the impact of HbA1c on PAPP-A levels while accounting for ethnic differences. Results: In women with type 1 pre-GD, a significant inverse correlation was observed between PAPP-A and both pregestational (R = −0.69; p < 0.01) and first-trimester HbA1c (R = −0.49; p < 0.01). In type 2 pre-GD, multivariate analysis showed divergent results based on ethnicity: for each unit increase in HbA1c, PAPP-A decreased by 0.03 units in Caucasian women but increased by 2.7 units in South American women. Conclusion: These findings suggest that glycometabolic compensation significantly influences PAPP-A levels. Clinical risk assessments for aneuploidy should consider HbA1c as a continuous parameter rather than treating pre-GD history as a binary variable. Incorporating specific glycometabolic data and ethnicity may improve the accuracy of first-trimester screening for women with pre-GD.

BACKGROUND:Cardiovascular disease (CVD) is the leading indirect cause of maternal morbidity and mortality in high-income countries. Managing pregnant women with cardiac conditions requires multidisciplinary coordination and individualized planning. Early risk stratification, commonly performed using the modified World Health Organization (mWHO) classification, is essential to guide the management of pregnant women with heart disease. The Delivery Plan (DP) is proposed as a standardized tool to guide peripartum care in this population. OBJECTIVE:To evaluate expert consensus on the structure and implementation of a standardized DP for pregnant women with heart disease, using a modified Delphi methodology. METHODS:A two-round Delphi survey was conducted among 30 cardio-obstetric experts from five tertiary Italian centers. The first phase assessed current practices regarding cardiac follow-up and investigations in pregnancy. The second phase evaluated agreement on 21 proposed DP items across different mWHO risk classes and explored the role of non-cardiac risk factors. RESULTS:In phase one, consensus (≥70% agreement) was achieved for 78.4% of cardiac follow-up practices and 87.9% of diagnostic investigations. In phase two, all 21 DP items were endorsed for general inclusion. Stratification by mWHO risk class showed no consensus for mWHO I, partial agreement for mWHO II, and full consensus for mWHO II/III to IV. Strong agreement (median ≥ 9, IQR ≤ 2) was observed for most items in higher-risk classes. Additionally, obesity, hypertension, and preeclampsia were identified as relevant non-cardiac risk factors warranting structured planning. CONCLUSIONS:The study supports the use of a structured, risk-adapted DP for pregnant women with cardiac disease. High consensus in moderate-to-severe risk groups confirms the DP's utility in enhancing multidisciplinary coordination and may contribute to improved maternal-fetal outcomes, pending prospective validation.

Placenta previa is an absolute indication for cesarean delivery and is associated with serious risks for maternal and neonatal health. At delivery, its prevalence is 0.5% to 1%, after being observed in up to 10% at the mid-trimester scan. Risk is highest with prior cesarean delivery and recurrence after a prior placenta previa is 4% to 8%. Twin gestations have a higher absolute prevalence (3.9 vs 2.8 per 1000 live births), and assisted reproduction carries a 6-fold risk compared to spontaneous conception. Maternal morbidity is dominated by hemorrhage: antepartum bleeding occurs in 40% to 60% and postpartum hemorrhage in 20% to 35%. Preterm birth drives neonatal risk: more than 40% of patients with placenta previa deliver before 37 weeks, and placenta previa accounts for 6% to 7% of indications for delivery before 35 weeks. Transvaginal ultrasound is the diagnostic gold standard and should be used to confirm transabdominal findings, measure the internal os distance, and exclude associated conditions (placenta accreta spectrum and vasa previa). Antenatal management and timing of delivery are based on the delicate equilibrium between the risk of maternal hemorrhage and the consequences of iatrogenic prematurity. For asymptomatic placenta previa, planned cesarean is generally recommended at 360 to 376 weeks (often earlier within this window for anterior previa). For low-lying placenta, internal-os distance guides delivery planning and current evidence supports a trial of labor in women with a distance of 11 to 20 mm. Operative care should be standardized within a multidisciplinary “placenta team” (obstetrics, anesthesia, interventional radiology, and urology as needed), with preparedness for major hemorrhage. Given the psychological burden—especially in complicated cases—structured debriefing and postpartum support are recommended.

Women with previous gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). Although early postpartum screening is recommended, metabolic changes occurring during the first year remain poorly characterized, and Italian guidelines do not include assessment at this time point. To evaluate glycaemic and metabolic changes one year after delivery in women with previous GDM and identify clinical and lifestyle predictors of postpartum glucose impairment. A cohort of 134 women with prior GDM was assessed at 6–12 weeks (T0) and one year postpartum (T1). Anthropometric, biochemical, nutritional, lifestyle, and quality-of-life parameters were collected. Dietary habits were evaluated using a 3-day food diary and the PREDIMED questionnaire; physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). Logistic regression models were used to identify predictors of altered OGTT at T1. At baseline, 32.9

Background/Objectives: Nausea and vomiting of pregnancy (NVP) are common and potentially debilitating symptoms of early pregnancy. However, data on their prevalence and impact in Italy are limited. This survey aimed to assess the frequency of NVP among Italian pregnant women and to evaluate its impact on quality of life. Methods: The survey was conducted in three public university hospitals in Italy during two separate periods. Women with multiple pregnancies or who conceived by medically assisted reproduction were excluded. The Questionnaire for Pregnancy Period, including the Pregnancy-Unique Quantification of Emesis (PUQE), was administered during a face-to-face interview at 18-22 weeks of gestation, coinciding with the morphological ultrasound. A structured telephone follow-up interview was performed within 14 days after delivery. This report presents the final analysis of all valid, completed questionnaires. Results: A total of 532 pregnant women were included (mean age 32.7 ± 4.9 years); 277 (52.1%) were primiparous. Overall, NVP was reported by 66.4% of participants. Nausea alone occurred in 28.0% of women, while nausea overall (with or without vomiting) was reported by 64.3%. Vomiting alone was reported by 2.1% and vomiting overall by 38.4% of participants. Symptoms began at a mean gestational age of 7.0 ± 2.8 weeks, lasted 9.7 ± 5.1 weeks, and were still present at the first interview in 30.3% of cases. More than half of the affected women (51.0%) reported limitations in daily activities, particularly work-related activities. Conclusions: This final analysis confirms a high prevalence of NVP among Italian pregnant women and highlights its substantial negative impact on quality of life. Systematic screening and appropriate management strategies should be considered in routine prenatal care.