Search Results (206)

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder unique to pregnancy, closely associated with severe adverse maternal and fetal outcomes such as preterm birth and intrauterine fetal death. Its pathogenesis involves a complex interplay of genetic, hormonal, metabolic, and environmental factors, with a higher risk observed in southern China and among individuals co-infected with hepatitis B virus. Substantial evidence demonstrates a significant dose–response relationship between serum total bile acid (TBA) levels and perinatal outcomes, with TBA ≥ 40 μmol/L commonly used as a criterion for severe ICP. However, most existing prediction models are based on single-center, retrospective studies with small sample sizes and insufficient external validation, limiting their clinical generalizability. In recent years, nomograms and machine learning methods have demonstrated advantages in the early prediction and risk stratification of ICP. Deep learning models and multi-omics integration strategies have further enhanced predictive accuracy. Nevertheless, challenges remain regarding model interpretability, data standardization, and cross-population applicability. Future research should leverage large-scale, multi-center prospective cohorts, integrating multi-omics technologies, including genomics, metabolomics, gut microbiome profiling with artificial intelligence to develop clinically actionable and interpretable risk prediction tools. Integrating these tools into electronic health record systems and mobile platforms may facilitate the early identification and individualized management of ICP, ultimately improving maternal and neonatal outcomes. Full article

Background: Perinatal deaths remain a major public health concern and present unique medico-legal challenges. Forensic autopsy plays a crucial role in determining the cause of death, distinguishing live birth from stillbirth, assessing fetal viability, and identifying traumatic or non-natural causes of death. Methods: This retrospective study included all perinatal cases referred to the Gaziantep Forensic Medicine Group Presidency between 2021 and 2024. Demographic characteristics, gestational age, autopsy findings, histopathological and toxicological examinations, hydrostatic lung test results, and final forensic diagnoses were evaluated. Results: Seventeen of 339 infant forensic cases met the inclusion criteria. Fourteen underwent complete forensic autopsy, whereas three were evaluated by external postmortem examination and medical records. Despite a multidisciplinary forensic investigation that included external examination, complete forensic autopsy, systematic macroscopic organ evaluation, routine histopathological examination, hydrostatic lung flotation testing, toxicological analysis when indicated, review of maternal medical and obstetric records, judicial investigation records, and placental and umbilical cord histopathology whenever available, no definitive cause of death could be established in six cases. Advanced decomposition prevented determination in two cases. One case was classified as an undiagnosed natural death, whereas no specific cause of death could be assigned in the remaining three cases. Placental examination was available in only a minority of cases, whereas umbilical cord histopathology was performed in nearly all autopsied cases. Causes of death included traumatic injury, pulmonary immaturity, intrauterine infection, congenital anomalies, maternal drug exposure, placental abruption, maternal disease, and umbilical cord pathology. Conclusions: Perinatal death investigations require a multidisciplinary forensic approach integrating autopsy, histopathology, toxicology, placental examination, and clinical information. Beyond determining the cause of death, forensic evaluation is essential for assessing live birth, fetal viability, suspected abuse, maternal violence, medical malpractice, and criminal investigations. Full article

Background: Congenital infections included in the TORCH complex remain an important cause of fetal and neonatal morbidity and mortality, being associated with miscarriage, intrauterine growth restriction, congenital malformations, neurological impairment, and long-term developmental sequelae. Prenatal serological screening may contribute to the early identification of maternal infections and facilitate preventive and therapeutic interventions. However, data regarding the utilization of TORCH screening and associated socio-demographic determinants in Romania remain limited. Objective: This study aimed to evaluate the self-reported uptake of prenatal serological testing for one or more infections included in the TORCH complex, particularly Toxoplasma gondii, rubella virus, cytomegalovirus (CMV), herpes simplex virus (HSV), and syphilis, and to identify socio-demographic, obstetrical, and prenatal care-related factors associated with TORCH testing among pregnant women in Romania. Materials and Methods: A cross-sectional observational study was conducted using an online self-administered questionnaire completed by 1301 pregnant women from Romania. Data collection was performed between August 2022 and March 2023 through digital platforms, including social media and pregnancy-related forums. The primary outcome was self-reported performance of serological testing for at least one TORCH-related infection during pregnancy. Associations between explanatory variables and TORCH testing were evaluated using chi-square tests and multivariable binary logistic regression models. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: Overall, 75.6% of participants reported undergoing serological testing for at least one infection included in the TORCH complex during pregnancy, while 49.3% reported a complete TORCH panel. The most frequently reported investigations were for Toxoplasma gondii (92.8%) and rubella virus (89.9%), whereas HSV testing was less commonly reported (42.5%). Lower educational level was the strongest independent factor associated with reduced likelihood of TORCH testing (adjusted OR = 0.08; 95% CI: 0.03–0.19; p < 0.001) (adjusted OR—aOR). Unemployment status (aOR = 0.70; 95% CI: 0.50–0.99; p = 0.045) and multiparity (aOR = 0.62; 95% CI: 0.49–0.77; p < 0.001) were also associated with lower testing uptake. In contrast, participation in prenatal education programs was associated with increased likelihood of TORCH testing (aOR = 1.37; 95% CI: 1.04–1.80; p = 0.024). The number of prenatal consultations was not independently associated with testing uptake. Conclusions: The uptake of prenatal serological screening for congenital infections (assessed using an expanded Romanian panel that includes hepatitis B and HIV in addition to the classical TORCH agents) in Romania appears to be influenced predominantly by socio-educational and behavioral factors rather than by the quantitative utilization of prenatal care services alone. Given the online recruitment strategy and the predominantly urban and highly educated sample, the reported uptake rates may overestimate population-level coverage. Significant inequalities in access to preventive prenatal investigations were observed, particularly among women with lower educational and socio-economic status. Strengthening prenatal education programs and improving equitable access to standardized prenatal screening may contribute to optimizing congenital infection prevention and maternal–fetal health outcomes. Full article

During pregnancy, hormonal, metabolic, and immunological changes influence the composition and function of maternal microbial communities. Increasing evidence suggests that the maternal microbiota—particularly in the vaginal, gut, and oral environments—plays a significant role in maintaining pregnancy homeostasis and supporting fetal development. In healthy pregnancies, the vaginal microbiota is typically dominated by Lactobacillus species, which help maintain a low vaginal pH and protect against ascending infections. However, disruption of this balance (vaginal dysbiosis) has been associated with obstetrical complications such as intrauterine infection and preterm birth. Similarly, the maternal gut microbiota undergoes trimester-specific changes that contribute to metabolic adaptations required for fetal growth, while alterations in microbial composition have been linked to metabolic disorders including gestational diabetes mellitus and preeclampsia. Changes in oral microbiota and periodontal disease have also been associated with adverse pregnancy outcomes through systemic inflammatory pathways and potential microbial translocation to the placenta. Recent advances in sequencing technologies have improved the understanding of host–microbiome interactions in pregnancy, although the existence of a placental microbiome remains controversial. Overall, maternal microbiota plays an important role in pregnancy physiology, and its dysregulation may contribute to obstetrical complications. Understanding these mechanisms may facilitate the development of microbiome-based diagnostic and therapeutic strategies in maternal–fetal medicine. Full article

Preterm birth is a major cause of neonatal morbidity and mortality, and many spontaneous cases remain idiopathic. Increasing evidence suggests that intrauterine inflammation may occur in the absence of detectable infection, leading to the recognition of sterile intrauterine inflammation as an important mechanism contributing to threatened preterm labor and spontaneous preterm birth. This review summarizes current knowledge regarding the role of damage-associated molecular patterns (DAMPs), alarmins, pattern recognition receptors, inflammasome activation, cellular senescence, and pyroptosis in the initiation of sterile inflammatory pathways associated with labor. Key mediators including HMGB1, IL-1α, fetal cell-free DNA, platelet-activating factor, and S100 proteins appear to promote inflammatory activation within fetal membranes and the amniotic cavity. The review also discusses the emerging contribution of fetal immune activation, maternal–fetal immune dysregulation, maternal microchimerism, and epigenetic mechanisms to idiopathic preterm birth. Current diagnostic and therapeutic options remain limited, and no targeted treatment for sterile intrauterine inflammation has yet been established. Future approaches may include precision biomarkers, multiomics-based risk stratification, targeted immunomodulatory therapies, and modulation of maternal–fetal immune interactions. Improved understanding of sterile inflammatory mechanisms may ultimately support development of personalized strategies to prevent preterm birth and improve perinatal outcomes. Full article

Endocrine-disrupting chemicals (EDCs) are a diverse group of environmental pollutants capable of interfering with hormonal and immune system regulation. In recent years, increasing concern has been raised about the effects of chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), insecticides, and parabens, on maternal and fetal health, primarily due to their widespread exposure in human populations. Pregnancy represents a critical window characterized by tightly regulated hormonal and immunological adaptations. Emerging evidence suggests that EDC exposure during this period may alter maternal microbiota, disrupt immune responses, and interfere with endocrine signaling. These changes may increase susceptibility to bacterial and viral infections, including bacterial vaginosis, urinary tract infections, and intrauterine infections, all of which are associated with adverse pregnancy outcomes. This review summarizes the current evidence on the sources and mechanisms of exposure to endocrine disruptors during pregnancy and examines the potential biological pathways linking endocrine disruption to the development of infections. Particular emphasis is placed on the interactions between immune regulation, hormonal signaling, and changes in the microbiome, which may contribute to increased susceptibility to infections. A deeper understanding of these complex mechanisms is critical to improve risk assessment, develop effective public health strategies, and ultimately protect maternal and fetal health in an environment of increasing chemical exposure. A literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including studies published up to January 2026. Full article

Background: Preterm birth, the leading cause of neonatal mortality, is associated with reduced nephron endowment and an increased risk of kidney disease in later life. In preterm infants, the interruption of nephrogenesis leads to a lower nephron number and structural abnormalities. Prenatal factors such as intrauterine growth restriction, and postnatal factors including nephrotoxic medications, patent ductus arteriosus, perinatal asphyxia, and infections contribute to this deficit. Ultrasound is a key tool for assessing renal volume at birth and can, when indexed to body weight, be used to estimate nephron endowment, which is known to vary widely among individuals. Methods: This study analyzed 52 preterm infants with birth weight < 1000 g, assessing combined renal volume (sum of right and left kidney volumes) indexed to body weight. Results: The mean combined kidney volume-to-body weight ratio was 12.12 (SD = 2.03). Values below the 10th percentile (9.46) or more than one standard deviation below the mean (10.11) may indicate nephron deficiency at birth. Conclusions: Standardized ultrasound-based parameters enable the early identification of neonates at risk for nephron deficit, supporting targeted preventive strategies. Long-term follow-up is essential to detect early renal functional impairment and reduce the risk of chronic kidney disease. Full article

Herpes simplex virus (HSV) infection is highly prevalent worldwide and poses important risks during pregnancy due to the potential for vertical transmission and severe neonatal disease. HSV-1 is traditionally associated with orofacial lesions and HSV-2 with genital infection; however, HSV-1 has emerged as a significant cause of genital and neonatal herpes. Physiological immunomodulation during pregnancy may facilitate viral reactivation and replication. Vertical transmission may occur intrauterinely, intrapartum, or postnatally, with approximately 85% of neonatal infections acquired during delivery through contact with infected genital secretions. The risk is highest when primary maternal infection occurs in the third trimester, before adequate transplacental transfer of protective antibodies. Neonatal infection may present as disease limited to the skin, eyes, and mouth; central nervous system involvement; or disseminated multiorgan disease, the latter associated with high morbidity and mortality. Maternal infection ranges from asymptomatic viral shedding to painful vesiculoulcerative lesions and, rarely, disseminated disease. Because asymptomatic shedding is common, diagnosis relies on laboratory confirmation using polymerase chain reaction (PCR) or viral culture, with type-specific serology aiding in distinguishing primary from recurrent infection. Management aims to reduce symptoms, viral shedding, recurrences near delivery, and vertical transmission. Acyclovir and valacyclovir are safe and effective in pregnancy. Suppressive therapy from 36 weeks’ gestation reduces recurrences and viral shedding at delivery and decreases the need for cesarean delivery, which is recommended when active lesions or prodromal symptoms are present at labor. Neonatal herpes requires prompt recognition and intravenous acyclovir therapy to reduce mortality and neurological sequelae. Preventive strategies include counseling, behavioral risk reduction, suppressive antiviral therapy, and avoidance of neonatal exposure to active lesions. Full article

Background: Early pregnancy loss, defined as the spontaneous loss of a pregnancy before 20 weeks of gestation or when the fetus weighs less than 500 g, remains a common obstetric complication, affecting up to 15% of clinically recognized pregnancies. Chromosomal abnormalities, particularly aneuploidies such as trisomies and monosomy X, account for 50–60% of first-trimester losses, with incidence increasing alongside maternal age. Additional risk factors include maternal medical conditions, uterine anomalies, infections, and modifiable lifestyle factors. Pregnancies conceived through assisted reproductive technologies also carry a slightly higher risk of miscarriage, often influenced by maternal age and embryo quality. Methods: Two pathologists, blinded to each other’s assessments, analyzed abortive material from patients who experienced spontaneous first-trimester abortion between January 2012 and January 2025 at Agostino Gemelli Hospital, Rome, Italy. Inclusion criteria were defined independently of patient demographics. No restrictions were applied regarding maternal age. With respect to gestational age, only first-trimester miscarriages (≤12 weeks of gestation) were considered. In cases of discordance, the case was reviewed and re-evaluated to reach a final diagnosis. Results: The findings of this study are presented as a proposed histopathological classification and diagnostic framework for first-trimester miscarriages. Specifically, a total of 1168 cases were categorized into eight distinct groups of miscarriage etiology based exclusively on the histomorphological features of chorionic villi and maternal decidua. Conclusions: Histopathological examination of products of conception is essential for confirming intrauterine pregnancy, identifying underlying maternal or fetal causes, and guiding future reproductive management, particularly in recurrent pregnancy loss. This study evaluates histopathological features of first-trimester losses, classifies findings by etiology, and proposes a practical diagnostic guide to support clinical decision-making and improve outcomes in subsequent pregnancies. Full article

Background: Chorioamnionitis (CA) is a major pathological cause of preterm labor and is associated with both short- and long-term adverse outcomes in neonates, including early-onset sepsis (EOS) and late-onset sepsis (LOS). Neonatal sepsis remains a significant contributor to morbidity and mortality in neonatal intensive care units (NICUs). Aim: This study aimed to evaluate the association between maternal chorioamnionitis and the incidence of early-onset and late-onset neonatal sepsis in preterm neonates born at <32 weeks’ gestation. Furthermore, the study investigated maternal and neonatal factors affecting the presentation of sepsis. Methods: A retrospective cohort study was conducted on the medical records of preterm neonates born between 2020 and 2022. Inclusion criteria were gestational age < 32 weeks, available microbiological or histological examination for chorioamnionitis, and complete maternal medical records. Infants were categorized into two groups based on the presence (CA group) or absence (non-CA group) of histological and/or microbial chorioamnionitis. Descriptive statistical analyses were performed, including calculation of frequencies and percentages for categorical variables and means with standard deviations and ranges for continuous variables. Results: A total of 189 neonates were included, with a mean birth weight of 1286 ± 405 g and a mean gestational age of 29.2 ± 2.1 weeks. The CA group consisted of 55 neonates (29.1%), while 134 (70.9%) were in the non-CA group. Early-onset sepsis (EOS) occurred in 23 neonates (12.2%), with a significantly higher incidence in the CA group compared to the non-CA group (21% vs. 8%, p = 0.014). Late-onset sepsis (LOS) developed in 66 neonates (34.9%), but no significant difference in incidence was observed between the two groups (p = 0.402). Parsimonious logistic regression analysis identified maternal chorioamnionitis as an independent predictor of EOS (Odds Ratio 2.07, 95% CI 1.85–5.08; p = 0.009). Conclusions: Intrauterine infection and inflammation caused by chorioamnionitis are linked to an increased risk of early-onset sepsis in neonates born before 32 weeks’ gestation. However, chorioamnionitis does not appear to significantly influence the incidence of late-onset sepsis, which appears to be more closely associated with postnatal factors. Full article

Background: Congenital cytomegalovirus (cCMV) infection is one of the most common congenital infections worldwide and the leading cause of non-genetic sensorineural hearing loss. Although less frequent in preterm infants, cCMV may significantly worsen outcomes in an already vulnerable population. The risks and benefits of antiviral therapy in extremely preterm neonates remain unclear, as this group is largely excluded from clinical trials. Case presentation: We report a case of symptomatic cCMV infection in an extremely preterm infant born at 26 weeks and 2 days of gestation to a mother with primary CMV infection during the second trimester. High CMV viral loads were detected in urine and plasma shortly after birth. On day of life (DOL) 3, respiratory deterioration required intubation, with radiological findings consistent with CMV pneumonia and positive bronchoaspirate samples. Intravenous ganciclovir was initiated on DOL 16 and administered for six weeks, followed by oral valganciclovir for six months. Treatment was associated with a favourable clinical and virological response and no significant hematological toxicity. Ophthalmologic and audiological evaluations were normal. Neurodevelopmental assessment with Bayley III at one year of corrected age demonstrated age-appropriate performance across all domains. Discussion: A structured literature review identified 10 case reports, including 13 extremely preterm infants treated for cCMV infection. Antiviral dosing regimens were heterogeneous. The most frequent manifestations prompting treatment were laboratory abnormalities (92.3%), particularly thrombocytopenia and leukopenia or neutropenia. Neuroimaging abnormalities and intrauterine growth restriction or small for gestational age were each reported in 53.8% of cases. Long-term neurodevelopmental outcomes were normal in 38.5% of infants. Conclusions: Antiviral therapy for cCMV infection with ganciclovir and valgancyclovir in premature neonates is feasible and safe with careful monitoring, and appears to provide benefits. Nevertheless, well-designed studies that include pharmacokinetics and pharmacodynamics, virologic monitoring, and long term outcomes of development, vision and hearing are urgently needed. Full article

Background: Neonatal sepsis is a bloodstream infection and constitutes a major cause of morbidity and mortality among newborns. The diagnosis is primarily based on a positive blood culture result. An additional diagnostic and therapeutic challenge may be congenital infection, particularly in preterm infants. This is associated with the lack of routine screening of the maternal genital tract, except for testing for group B streptococci during earlier stages of an uncomplicated pregnancy. Case presentation: This paper presents a case of a neonate with early-onset sepsis (EONS) caused by Escherichia coli. Methods: We carried out analysis of documents combined with the case report method. Results: Preterm birth associated with PPROM constitutes a significant risk factor for early-onset neonatal sepsis (EONS). Conclusions: The case illustrates the dynamic course of congenital infection and the resulting need for immediate, life-saving interventions. It also demonstrates abnormalities identified in ancillary investigations involving both the visual system and the central nervous system (CNS), confirming the intrauterine onset of the infectious process. Full article

Background: Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide. Moreover, the prevalence of HPV infection is twice as high in pregnant women as in non-pregnant individuals. The aim of this review was to examine adverse pregnancy outcomes associated with cervicovaginal or placental HPV infection confirmed by a sensitive molecular method. Methods: We conducted searches on major medical databases including PubMed, EMBASE, Global Health, and the Cochrane Library to identify all studies examining HPV infection during pregnancy. Additionally, other online sources were consulted for relevant studies. Thirty-four records out of the initial 1868 identified were included in this review for thematic synthesis. The PRISMA-ScR guidelines were followed. Results: This scoping review included a total of 28 original observational studies, 1 systematic review, and 5 meta-analyses. Active HPV infection appears to significantly increase the risk of preterm premature rupture of membranes and preterm birth, as indicated by findings from published meta-analyses and systematic reviews. Determining the association of HPV infection with certain adverse pregnancy outcomes is challenging due to their frequency (such as miscarriage) or rarity (such as intrauterine fetal death). For conditions like preeclampsia and intrauterine fetal growth restriction, the limited number of heterogeneous studies precludes definitive conclusions. Moreover, the causes of these outcomes are typically multifactorial. The presence of HPV in trophoblasts and placental tissue is considered crucial for potential adverse pregnancy outcomes. There appears to be a strong correlation between cervicovaginal or urinary HPV infections and placental HPV infections in pregnant women. Conclusions: Persistent HPV infection seems to elevate the risk of preterm premature rupture of membranes and preterm birth. However, the currently available observational evidence does not allow for definitive conclusions regarding causality, and the reported findings should be interpreted as associations rather than proof of a causal relationship. The changes in frequency of certain perinatal complications in populations of women with high HPV vaccination rates may shed more light on this connection. Full article

Neosporosis, caused by Neospora caninum, is a major protozoal disease responsible for reproductive disorders and economic losses in livestock. Swine are susceptible to N. caninum infection, as evidenced by serological and experimental studies, but the impact of natural infection on reproduction failure remains poorly defined. The objective of this study was to investigate N. caninum transplacental transmission in naturally infected sows by detecting an active fetal immune response in their stillborn piglets. Paired maternal blood and umbilical cord blood (UCB) samples were collected from 247 sows and stillborn piglets across 39 farrow-to-finish farms in mainland Greece. Sera were tested for anti-N. caninum IgG and IgM antibodies using an indirect fluorescence antibody test. An IgG and IgM seropositivity for N. caninum of 8.91% and 3.64%, respectively, was reported in sows, while lower percentages of IgG and IgM antibodies (3.24% and 0.81%, respectively) were detected in UCB samples. Overall, antibodies were detected in 4.05% of UCB samples, indicative of in utero antibody production. Positive samples were more frequently encountered on smaller farms with up to 250 sows, possibly due to lower biosecurity standards. The detection of antibodies in UCB resulting from the fetal immune response to intrauterine N. caninum infection is indicative of the potential involvement of N. caninum parasitism in reproductive system disorders. Testing of UCB for the presence of anti-Neospora antibodies elucidates the dynamics of parasite transmission within the farm and provides evidence for the implementation of more efficient biosecurity and preventative measures. Full article

Background: The effect of intrauterine exposure to SARS-CoV-2 infection during pregnancy on neurodevelopment and growth trajectories during the first year of life remains under investigation. Methods: We retrospectively reviewed the electronic medical records of all pregnant women who received care at Mayo Health System and tested positive for SARS-CoV-2 (RT-PCR) from March 2020 through October 2021 and examined the effects of fetal sex and trimester of maternal SARS-CoV-2 infection on the risk of neurodevelopmental disorder diagnosis and growth trajectories of head circumference (HC) and body weight (BW) percentiles over the first year of life using linear mixed models. Results: We observed that a higher percentage of male infants (n = 357), compared to females (n = 344), have neurodevelopmental disorders (10.9% vs. 5.2%, p = 0.008), and infants exposed to maternal SARS-CoV-2 infection in the second (n = 183) or third trimester (n = 358) have a higher prevalence of neurological diagnoses compared to those exposed in the first trimester (n = 160) (1st vs. 2nd vs. 3rd trimester: 0% vs. 0.9% vs. 0.7%, respectively, p = 0.037). In addition, female infants, compared to males, had significantly lower BW (B = −0.04, p < 0.0001) and HC (B = −0.06, p < 0.0001) percentile growth trajectories over the first year of life. Moreover, infants exposed to maternal SARS-CoV-2 infection in the second trimester had a significantly lower BW percentile growth trajectory (B = −0.01, p = 0.006), while infants exposed to maternal SARS-CoV-2 infection in the third trimester had a significantly lower HC percentile growth trajectory (B = −0.02, p = 0.02). Conclusions: In utero exposure to maternal SARS-CoV-2 infection could have long-term effects on growth trajectories, depending on the infant’s sex and timing of exposure. Full article