Search Results (175)

Biofilms are a spontaneously formed slimy matrix of extracellular polymeric substances (EPS) enveloping miniature bacterial colonies, which aid in pathogen colonization, shielding the bacteria from antibiotics, as well as imparting them resistance towards the same. Biofilms employ a robust communication mechanism called quorum sensing that serves to keep their population density constant. What is most significant about biofilms is that they contribute to the development of bacterial virulence by providing protection to pathogenic species, allowing them to colonize the host, and also inhibiting the activities of antimicrobials on them. They grow on animate surfaces (such as on teeth and intestinal mucosa, etc.) and inanimate objects (like catheters, contact lenses, pacemakers, endotracheal devices, intrauterine devices, and stents, etc.) alike. It has been reported that as much as 80% of human infections involve biofilms. Serious implications of biofilms include the necessity of greater concentrations of antibiotics to treat common human infections, even contributing to antimicrobial resistance (AMR), since bacteria embedded within biofilms are protected from the action of potential antibiotics. This review explores various contemporary strategies for controlling biofilms, focusing on their modes of action, mechanisms of drug resistance, and innovative approaches to find a solution in this regard. This review interestingly targets the extracellular polymeric matrix as a highly effective strategy to counteract the potential harm of biofilms since it plays a critical role in biofilm formation and significantly contributes to antimicrobial resistance. Full article

Background: Since the COVID-19 pandemic, managing acute infections in symptomatic individuals, regardless of vaccination status, has been widely debated and extensively studied. Even more concerning, however, is the impact of COVID-19 on pregnant women—especially its effects on fetuses and newborns. Several studies have documented complications in both expectant mothers and their infants following infection. Methods: In our previous works, we provided scientific evidence of the bacteriophage behavior of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). This demonstrated that a well-defined combination of two antibiotics, amoxicillin and rifaximin, is associated with the same statistics for subjects affected by severe cases of SARS-CoV-2, regardless of vaccination status. We considered the few cases in the literature regarding the management of pregnancies infected with SARS-CoV-2, as well as previous data published in our works. In this brief case series, we present two pregnancies from the same unvaccinated mother—one prior to the COVID-19 pandemic and the other during the spread of the Omicron variant—as well as one pregnancy from a mother vaccinated against COVID-19. We describe the management of acute maternal infection using a previously published protocol that addresses the bacteriophage and toxicological mechanisms associated with SARS-CoV-2. Results: The three pregnancies are compared based on fetal growth and ultrasound findings. This report highlights that, even in unvaccinated mothers, timely and well-guided management of symptomatic COVID-19 can result in positive outcomes. In all cases, intrauterine growth remained within excellent percentiles, and the births resulted in optimal APGAR scores. Conclusions: This demonstrates that a careful and strategic approach, guided by ultrasound controls, can support healthy pregnancies during SARS-CoV-2 infection, regardless of vaccination status. Full article

Background/Objective: Early-onset neonatal sepsis (EOS), defined as infection occurring within the first 72 h after birth, remains a major contributor to neonatal morbidity and mortality worldwide. Although advances in perinatal care have improved overall outcomes, the diagnosis of EOS continues to be challenging. Clinical presentations are often nonspecific, laboratory confirmation is often delayed, and immune responses vary considerably among neonates. Expanding our understanding of the molecular mechanisms underlying EOS is essential in enhancing early detection, refining risk stratification, and guiding therapeutic strategies. This systematic review aims to synthesize the available information on the molecular pathways involved in EOS, focusing on pathogen-induced inflammation, systemic immune responses, sterile inflammatory processes, interactions between infectious and non-infectious pathways, as well as emerging molecular diagnostic approaches. Methods: A comprehensive review of original research articles and reviews published between January 2015 and January 2025 was conducted; studies were included based on their focus on human neonates and their analysis of molecular or immunological mechanisms relevant to EOS pathogenesis, immune dysregulation, or novel diagnostic strategies. Results: Pathogen-driven inflammation typically involves the activation of Toll-like receptors (TLRs), the recruitment of neutrophils, and the release of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, particularly in response to vertical transmission of organisms like Escherichia coli and Streptococcus agalactiae. Systemic inflammatory responses are marked by cytokine dysregulation, contributing to multi-organ dysfunction. Sterile inflammation, often initiated by hypoxia–reperfusion injury or intrauterine stress, amplifies susceptibility to sepsis. Interactions between immune, metabolic, and endothelial pathways further exacerbate tissue injury. Recent advances, including transcriptomic profiling, microRNA-based biomarkers, and immune checkpoint studies, offer promising strategies for earlier diagnosis and individualized therapeutic options. Conclusions: EOS arises from a complex interplay of infectious and sterile inflammatory mechanisms. A deeper molecular understanding holds promise for advancing correct diagnostics and targeted therapies, aiming to improve neonatal outcomes. Full article

Human T-cell lymphotropic virus (HTLV), a retrovirus associated with severe conditions such as leukemia/lymphoma and myelopathy, exhibits variable global prevalence, with higher rates observed in regions such as northeastern Brazil and sub-Saharan Africa. While intrauterine transmission can occur via viral expression in placental tissue and contact with umbilical cord blood, the predominant route is vertical transmission through breastfeeding. Diagnostic testing, particularly serological screening with ELISA and confirmatory methods such as Western blot and PCR, is essential for early detection during pregnancy. The implementation of prenatal screening programs, as seen in Japan and Brazil, has proven effective in reducing vertical transmission by guiding interventions such as breastfeeding cessation in infected mothers. Beyond clinical implications, the psychosocial impact on affected pregnant women highlights the need for an interdisciplinary approach. Although the association between HTLV infection and adverse obstetric outcomes remains controversial, studies suggest increased risks of preterm birth, low birth weight, and other neonatal complications. Given the importance of early diagnosis and prevention, universal prenatal screening protocols represent a critical strategy to reduce viral transmission and its long-term consequences. Full article

Background: Histologic chorioamnionitis (HCA) is a placental inflammatory condition characterized by neutrophilic infiltration of the fetal membranes, often occurring without overt clinical signs or symptoms. Risk factors include prolonged labor, premature rupture of membranes (PROM) exceeding 12 h, nulliparity, labor dystocia, and lower socioeconomic status. Although HCA frequently presents as a subclinical condition, its early diagnosis remains challenging. Nevertheless, HCA is associated with an increased risk of maternal and neonatal morbidity, including early-onset neonatal sepsis, cerebral palsy, and long-term neurodevelopmental impairment. We report the case of a 29-year-old primigravida at 40 + 0 weeks of gestation, admitted for decreased fetal movements. Discussion: Cardiotocographic (CTG) monitoring revealed a “zigzag pattern” in the absence of maternal fever, leukocytosis, or tachycardia. Due to the CTG findings suggestive of possible fetal compromise, in addition to reduced fetal movements, an emergency cesarean section was performed. Intraoperative findings included heavily meconium-stained amniotic fluid, then the examination of the placenta confirmed acute HCA with a maternal inflammatory response, without evidence of fetal inflammatory response. Conclusion: This case highlights the crucial role of CTG abnormalities, particularly the “zigzag pattern,” as an early marker of subclinical intrauterine inflammation. Early recognition of such patterns may facilitate timely intervention and improve perinatal outcomes in cases of histologic chorioamnionitis. Full article

The intrauterine environment is increasingly recognised as a critical period for the emergence of mental health vulnerabilities. This review explores how adverse maternal exposures, such as psychological stress, infection, malnutrition, and environmental toxins, can disrupt foetal neurodevelopment via epigenetic mechanisms, contributing to the risk of psychiatric and neurodevelopmental disorders. Focusing primarily on human studies, we synthesise evidence on DNA methylation, histone modifications, and non-coding RNAs as key pathways through which the intrauterine environment influences gene regulation in the developing brain. We examine how timing of exposure, foetal sex, and gene–environment interactions modulate these effects, with particular attention to disorders such as schizophrenia, autism spectrum disorder, depression, and anxiety. The placenta emerges as a central mediator, both reflecting and shaping epigenetic changes in response to maternal signals. We also discuss the reversibility of epigenetic marks and highlight emerging interventions, including nutritional supplementation and maternal mental health support, that may buffer or reverse prenatal epigenetic programming. Methodological challenges are addressed, including tissue specificity and causal inference, and future directions are proposed toward integrating epigenetic biomarkers into early risk assessment and precision mental health and psychiatry. This review emphasises the importance of the prenatal period as a window of vulnerability and opportunity for shaping lifelong mental health. Full article

Preterm premature rupture of membranes (pPROM) is a leading cause of preterm birth (PTB) and is increasingly recognized for its association with neurodevelopmental disorders (NDDs). The disruption of fetal membrane integrity introduces potential infection and inflammation into the intrauterine environment, triggering immune responses that may affect fetal development. Placental inflammation plays a pivotal role in mediating these effects, exposing the fetus to cytokines, oxidative stress, and potential microbial insults that contribute to adverse neurodevelopmental outcomes. This review examines the current evidence of the mechanistic pathways linking pPROM-induced placental inflammation to NDDs, emphasizing the roles of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in the inflammatory responses. We discuss how these immune activations lead to immune cell recruitment and excessive (or uncontrolled) production of inflammatory mediators, leading to an overall inflammatory imbalance that has been linked to disrupted fetal brain development in animal models. Animal models provide critical insights into how both sterile and pathogenic placental inflammation alter fetal neurodevelopment, while human studies, though limited, highlight promising biomarkers and potential therapeutic targets. This review identifies critical knowledge gaps and outlines future directions to mitigate the impact of placental inflammation on long-term infant health. Full article

Infective endocarditis (IE) during pregnancy, while uncommon, is associated with substantial maternal and fetal morbidity and mortality due to the complex physiological adaptations of pregnancy. Hemodynamic alterations, including increased cardiac output and changes in vascular resistance, combined with immunological modulation, predispose pregnant individuals to increased risk of infection and associated complications. Predominant pathogens implicated in pregnancy-associated IE are Staphylococcus aureus, Streptococcus viridans, and Enterococcus faecalis, with S. aureus infections frequently leading to poorer clinical outcomes. Diagnosis remains challenging due to commonly atypical presentation and relies on microbiological identification via blood cultures in conjunction with imaging modalities such as transthoracic echocardiography. IE in pregnancy is associated with increased maternal mortality rates (5–17%) and adverse fetal outcomes, including preterm birth, intrauterine growth restriction (IUGR), and fetal loss. Management necessitates careful selection of antimicrobial therapy to ensure efficacy while minimizing fetal toxicity, especially in settings of increased antimicrobial resistance. Anticoagulation and surgical interventions must be judiciously considered, with surgical timing individualized based on the severity of heart failure and coordinated multidisciplinary care. In conclusion, IE during pregnancy constitutes a significant clinical challenge, underscoring the need for enhanced diagnostic strategies, optimized therapeutic protocols, and the development of pregnancy-specific management guidelines to improve maternal and fetal outcomes. Full article

Antenatal inflammation/infection is a major cause of neonatal apnoea and hypoventilation. Prostaglandin E2 (PGE₂) is a key inflammatory mediator associated with depression of fetal and neonatal breathing. We aimed to determine whether antenatal ibuprofen, a cyclooxygenase inhibitor that reduces synthesis of PGE₂, restores fetal breathing movements (FBM) in late-gestation fetal sheep exposed to systemic lipopolysaccharide (LPS). Fetal sheep (125 days gestation, d; term ~148 d) were instrumentally monitored for continuous measurement of FBM and physiological parameters. At 130 d fetuses were randomly allocated between groups receiving i.v. saline (CTL_SAL, n = 9), escalating doses of LPS (i.v.) over 3 days (LPS_SAL, n = 8), or ibuprofen one hour after each LPS dose (LPS_IBU, n = 8). Regular plasma samples were collected for PGE₂ assessment. At 135 d, cerebrospinal fluid and brainstem tissue were collected at autopsy for assessments of PGE₂ expression, and immunohistochemical quantification of astrocytes and microglia within key brainstem respiratory centres was performed to assess inflammation. LPS exposure increased PGE₂ levels in plasma, cerebrospinal fluid and the RTN/pFRG (p < 0.05) and decreased the incidence, amplitude and amount of the accentuated (>5 mmHg) FBMs. Ibuprofen reduced plasma and RTN/pFRG PGE₂ expression (p < 0.01 and p = 0.031, respectively) but did not restore FBMs. Astrocyte and microglial density increased in the RTN/pFRG, NTS and raphe nucleus in LPS_IBU fetuses, compared to LPS_SAL (p < 0.05). Antenatal ibuprofen treatment did not restore depressed FBM, despite reducing the circulating and brainstem PGE₂ levels in LPS-exposed fetal sheep. Other inflammatory pathways or more specific targeting of PGE₂ may be more effective in preventing apnoea caused by exposure to intrauterine infection/inflammation. Full article

Background/Objectives: Congenital rubella syndrome (CRS) is an infection caused by rubella virus transmitted to the fetus during pregnancy, which can cause congenital hearing loss. Cochlear implant can be an effective therapy in patients with severe to profound bilateral hearing loss. The aim of this study was to evaluate the benefits of cochlear implantation in patients with profound hearing loss caused by congenital rubella syndrome. Methods: In total, 38 patients with profound hearing loss caused by intrauterine rubella virus infection were considered for cochlear implantation. Patients ranged in age from 8 to 72 years on the day of surgery, with a mean age of 27 years and median of 25 years (SD = 13.2). Preoperatively, all patients underwent pure-tone audiometry, and free-field speech audiometry was conducted in a quiet environment with the patient wearing a fitted hearing aid. Postoperatively, patients underwent pure-tone audiometry to assess residual hearing, and free-field speech audiometry was conducted when the patients had an active implant. Results: The average preoperative hearing threshold (averaged across the seven frequencies from 0.125 to 8 kHz) was 99.2 dB HL (SD = 6.79), while the average postoperative hearing threshold was 103.4 dB HL (SD = 5.74). Twelve months after the operation, patients achieved a WRS in quiet scores ranging from 10% to 90%, with an average of 59.1% and median of 70% (SD = 25.8). Conclusions: Rubella during pregnancy can lead to severe congenital defects, with sensorineural hearing loss being the most common. Cochlear implants appear to be an effective treatment for profound hearing loss caused by congenital rubella syndrome. Full article

Congenital Rubella Syndrome (CRS) results from maternal infection with the rubella virus during pregnancy, particularly in the first trimester, when the risk of vertical transmission and severe fetal damage is highest. CRS is characterized by a broad spectrum of congenital anomalies, including sensorineural hearing loss, congenital heart defects, cataracts, neurodevelopmental delay, and behavioral disorders. Despite the absence of specific antiviral therapies, active immunization remains the only effective strategy to prevent rubella infection and its congenital consequences. Global immunization efforts, particularly in the Americas, have led to the elimination of rubella and CRS in several countries. However, challenges persist in the post-elimination era, including declining vaccine coverage, vaccine hesitancy, and setbacks caused by the COVID-19 pandemic. Diagnosis relies on maternal serology, fetal imaging, postnatal antibody testing, and molecular techniques. Management requires long-term, multidisciplinary follow-up due to the complex and lifelong sequelae affecting sensory, motor, and cognitive development. This review highlights the clinical, epidemiological, and pathophysiological aspects of CRS, while emphasizing the urgent need to maintain high vaccination coverage and strengthen surveillance systems. Sustained public health commitment is essential to prevent the reemergence of rubella and protect future generations from this preventable syndrome. Full article

In 2024, Europe experienced a significant upsurge in cases of Parvovirus B19 (B19V), the etiological agent of erythema infectiosum, also known as fifth disease. The prevalence of B19V in pregnant women, a particularly vulnerable population, holds critical clinical significance. Typically, B19V follows a well-documented seasonal pattern, with annual epidemics peaking in the spring and larger outbreaks occurring approximately every four years. B19V exhibits a tropism for erythroid precursor cells, potentially resulting in fetal anemia and, in the most severe scenarios, intrauterine demise. Severe in utero infections necessitate intrauterine erythrocyte transfusion (IUT), a highly specialized and technically demanding procedure that is exclusively performed in tertiary-level prenatal care units. This study delineates how the notable increase in B19V infections is also reflected in our prenatal diagnosis unit at Fondazione Policlinico Agostino Gemelli (FPG) IRCCS, Rome, Italy. According to our case series, since 2018, B19V has been identified as the second most common cause of fetal anemia during the study period (29%, 6 patients), yet it accounted for the majority of IUT procedures performed in 2024 (16 out of 19 cases, 84.2%). Given the rising incidence of severe intrauterine infections in recent epidemic cycles, healthcare professionals should maintain a high index of suspicion regarding the clinical manifestations of maternal B19V infection and its potential obstetric complications. Further research is imperative to evaluate the cost-effectiveness of routine screening for B19V immunity in pregnant women and to investigate the long-term neurodevelopmental and clinical outcomes of neonates affected by intrauterine B19V infection. Full article

Background/Objective: Actinomyces is a genus of anaerobic gram-positive bacteria. It forms part of human body microbiota commonly in the oral cavity and genital tract. During pregnancy, the organism may cause the rare chorioamnionitis, where the maternal genital tract or other sites such as the oral cavity will be the likely source of the pathogen. This condition may increase the risk of foetal morbidity and mortality, and preterm birth. Methods: The placenta of a 33-year-female, primigravida, who presented with preterm labour and eventual delivery of baby at 20 weeks gestation was sent for histopathological examination. Her antenatal and clinical history were reviewed, to identify possible aetiology for her preterm birth. Results: She is noted to have presented with sudden per-vaginal creamy coloured discharge with no associated odour and no irritation. The discharge became blood staining associated with labour pain, this followed by premature spontaneous rupture of membrane and pre-mature labour. Laboratory tests revealed leucocytosis, neutrophilia, monocytosis, high CRP and elevated derived fibrinogen. The patient was delivered of a live male baby weighing 0.35 kg, who died shortly after birth. Placenta microscopic examination revealed patchy severe acute chorioamnionitis and prominent clusters of Gram-positive filamentous bacteria with histopathologic features of Actinomyces spp. The mother before discharged was treated with oral antibiotic. Conclusions: The intrauterine Actinomyces spp. infection is associated with preterm birth and neonatal mortality, early diagnosis during ante-natal could perhaps prevent preterm birth and reduce the associated neonatal mortality. Full article

Zika virus (ZIKV) is a mosquito-borne flavivirus of the family Flaviviridae. The association between ZIKV and microcephaly was first described in Brazil in 2015. The risk of vertical transmission occurs in pregnant women with or without symptoms, and the risk of malformation appears to be worse when infection occurs in the first and second trimesters of pregnancy. The rate of vertical transmission varies from 26 to 65%, and not all fetuses develop malformations. The incidence of malformations resulting from transmission is uncertain, ranging from 6–8% in the US to 40% in Brazil. Congenital ZIKV syndrome is a set of clinical manifestations that can affect the fetus of a mother infected with ZIKV. The manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular changes, congenital contractures, early hypertension, and pyramidal and extrapyramidal signs. Other findings such as growth restriction and fetal miscarriage/death may also occur. Our aim in this article is to review the literature on mosquito transmission, clinical presentation, serologic diagnosis, intrauterine transmission, pre- and postnatal imaging diagnostic findings, and short- and long-term follow-up. Full article

Background: The neonatal period has a number of characteristics leading to an increased risk of severe and, in many cases, life-threatening complications. Renal venous thrombosis is one of them. It accounts for 16–20% of all thromboembolisms in the neonatal period. Due to the delicate balance in coagulation status in the first days after birth, conditions such as infections, hypoxia, hypotension, and dehydration can lead to the occurrence of this complication. The incidence of renal thrombosis is 2.2/100,000 live births, with cases of intrauterine renal thrombosis being even rarer (7% of cases). The diagnosis of the disease is usually performed using ultrasound examination and Doppler sonography, although contrast angiography is the gold standard for diagnosing these conditions. Case presentation: We present a clinical case of a male child with manifestations of diabetic fetopathy and prenatally occurring venous thrombosis of the right kidney, confirmed by ultrasound 2 h after birth. Results: The occurrence and evolution of venous thrombosis was monitored through a series of ultrasound examinations. Despite the restoration of renal blood flow after the initiation of therapy, long-term follow-up at 6 and 12 months revealed the onset of renal atrophy. Conclusions: Prenatal renal vein thrombosis is a rare but severe pathology for the newborns. Ultrasound examination is the method of first choice in cases of suspected renal vein thrombosis, as well as for renal blood flow restoration and for the monitoring of the fate of the affected kidney. Full article