Search Results (141)

Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy. Full article

Hepatobiliary disorders during pregnancy represent a significant cause of maternal and fetal morbidity, requiring careful differentiation between physiological adaptations of pregnancy and true hepatic pathology. This narrative review provides a comprehensive overview of three major hepatobiliary conditions encountered during pregnancy: gallstone disease, intrahepatic cholestasis of pregnancy (ICP), and viral hepatitis (HAV, HBV, HCV, HDV, and HEV). Pregnancy-induced hormonal and immunological changes influence disease pathogenesis, clinical presentation, diagnostic interpretation, and therapeutic decision-making. Gallstone disease remains the most common non-obstetric surgical condition in pregnancy, with contemporary evidence supporting timely laparoscopic intervention when indicated. ICP is characterized by pruritus and elevated serum bile acids and is associated with increased risks of preterm birth, fetal distress, and stillbirth, necessitating close surveillance and individualized delivery planning. Viral hepatitis poses unique challenges because of the potential for vertical transmission, maternal complications, and adverse neonatal outcomes. Universal antenatal screening for hepatitis B and C is increasingly recognized as a cornerstone of care. For HBV, maternal antiviral prophylaxis combined with neonatal immunoprophylaxis has reduced mother-to-child transmission to below 1%, whereas the role of direct-acting antivirals for HCV during pregnancy continues to evolve. HEV remains the most severe viral hepatitis in pregnancy, carrying disproportionately high maternal mortality in endemic regions. Across all conditions, multidisciplinary management involving hepatologists, gastroenterologists, obstetricians, maternal–fetal medicine specialists, surgeons, and neonatologists is essential to optimize outcomes. This review synthesizes current evidence, highlights pregnancy-specific diagnostic and therapeutic considerations, and identifies emerging areas of research that may further improve maternal and neonatal outcomes. Full article

Pregnancy is associated with profound metabolic, hormonal, and immunological adaptations accompanied by dynamic alterations in maternal gut microbiota composition and function. Emerging evidence suggests that maternal diet is a major regulator of these microbiota-related changes and may influence maternal–fetal health through microbial metabolites and host signaling pathways. Fermented foods and functional dietary components, including prebiotics, probiotics, synbiotics, and polyphenols, have gained increasing attention because of their potential to modulate gut microbial diversity, intestinal barrier integrity, inflammatory responses, and metabolic homeostasis. Mechanistically, these effects are mediated through pathways involving short-chain fatty acids, G protein-coupled receptors, nuclear factor kappa B signaling, histone deacetylase inhibition, and immune cell regulation. Altered microbiota-associated signaling has been linked to gestational metabolic disorders such as obesity, gestational diabetes mellitus, and preeclampsia, as well as fetal immune and metabolic programming. Particular emphasis is placed on the maternal–infant microbiome axis, highlighting how maternal nutrition and microbiota-mediated signaling may influence microbial transmission, fetal programming, and early-life microbiome development. This review summarizes current evidence regarding pregnancy-associated gut microbiota alterations and discusses the molecular mechanisms through which fermented foods and functional nutrition may influence maternal and fetal health outcomes. Full article

Cytomegalovirus (CMV) remains one of the most relevant congenital and early-life infections in pediatrics because of its high global seroprevalence, lifelong latency, and potential for reactivation or reinfection. Biologically, the virus poses a particular threat during pregnancy, when maternal primary infection carries a substantially higher risk of transplacental transmission than non-primary infection, with fetal and neonatal consequences that vary according to gestational timing and host vulnerability. In children, CMV infection is common in the first years of life and may contribute to a broad spectrum of outcomes, ranging from asymptomatic infection to severe multisystem disease, neurodevelopmental impairment, and sensorineural hearing loss. Clinically, the document highlights the importance of timely maternal diagnosis, differentiation between primary and recurrent infection, and integration of prenatal, neonatal, radiological, and audiological assessment. Attention is given to symptomatic and asymptomatic newborns, preterm infants, and infants exposed through breast milk. The availability of antiviral strategies in pregnancy and infancy strengthens the rationale for early identification and risk stratification. Universal newborn screening emerges as a potentially valuable approach to improve case detection, enable prompt follow-up, and reduce long-term disability. Overall, a multidisciplinary and early-intervention framework is essential to optimize prevention, diagnosis, treatment, and long-term outcomes in pediatric CMV infections. Full article

Toxoplasmosis remains one of the most common parasitic infections affecting humans, with significant implications for pregnancy and fetal health. Maternal primary infection during gestation can result in transplacental transmission of Toxoplasma gondii, leading to a wide spectrum of congenital disease. The risk of vertical transmission increases with gestational age, whereas disease severity is inversely related—early infections causing severe neurological and ocular damage, and late infections often resulting in subclinical forms. Advances in serological testing, including IgG avidity assays and molecular diagnostics such as PCR on amniotic fluid, have improved early detection and management. Prenatal treatment with spiramycin or pyrimethamine–sulfadiazine–folinic acid combinations has been associated with reduced transmission and less severe fetal disease in several studies, although the magnitude of benefit remains debated. Long-term follow-up is essential, as late-onset manifestations, particularly chorioretinitis and neurodevelopmental impairment, are common. This narrative review was based on a comprehensive literature search of major medical databases and summarizes current knowledge on the epidemiology, pathophysiology, diagnosis, treatment, and outcomes of toxoplasmosis in pregnancy. Particular emphasis is placed on high-prevalence countries, where greater parasite genetic diversity, distinct epidemiological patterns, and a higher burden of congenital disease pose unique clinical and public health challenges. Despite progress in understanding parasite biology, pathogenesis, and treatment efficacy, congenital toxoplasmosis continues to be underdiagnosed and underreported, especially in low-resource settings. Ongoing challenges include optimizing screening strategies, ensuring access to standardized therapies, and strengthening surveillance systems. Full article

Early life stress (ELS) and adverse childhood experiences are critical determinants of neurodevelopmental trajectories and long-term somatic and psychiatric health outcomes. This narrative review synthesizes current evidence, identified through searches in PubMed, Scopus, and Web of Science, on the neurobiological and epigenetic mechanisms through which early environmental exposures shape developmental programming and stress responsivity across the lifespan. A central framework is the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which mediates adaptive and maladaptive stress responses. During sensitive developmental periods, including prenatal, perinatal, and early postnatal stages, increased neuroplasticity confers heightened vulnerability to environmental influences, resulting in persistent alterations in stress regulation systems, brain circuitry, and endocrine function. The review further examines the role of maternal stress during gestation, with emphasis on placental regulatory mechanisms and fetal programming processes that establish long-term physiological set points. In parallel, emerging evidence on paternal stress is considered, highlighting potential contributions of germline epigenetic modifications and postnatal environmental transmission pathways. At the molecular level, epigenetic mechanisms—including DNA methylation, histone modifications, and non-coding RNA regulation—are discussed as key mediators linking early environmental exposures to stable changes in gene expression without alterations in DNA sequence. Collectively, the evidence supports ELS as a fundamental biological embedding process with enduring consequences for health across the lifespan. A deeper understanding of these mechanisms, alongside the identification of reliable biomarkers, is essential for early detection and the development of targeted preventive and intervention strategies in pediatric populations. Full article

Pregnancy represents a critical eco-biological window during which maternal physiology integrates environmental exposures, lifestyle factors, and interconnected microbial ecosystems to shape fetal development and long-term health. From a One Health perspective, defined here as the interconnection between maternal health, environmental determinants, and microbial ecosystems across generations, the maternal microbiome functions as a dynamic interface linking the external environment to the intrauterine milieu, translating ecological signals into immunological, metabolic, and neuroendocrine pathways that influence placental function and developmental programming. Across gut, vaginal, oral, and mammary niches, maternal microbial communities operate as an integrated network regulating systemic inflammation, metabolic homeostasis, and the production of bioactive metabolites, including short-chain fatty acids, bile acids, and tryptophan derivatives. This review proposes an integrated systems framework in which pregnancy is viewed as a transient ecological system shaped by ten interconnected maternal determinants, encompassing microbial niches, nutrition, lifestyle factors, medical interventions, mode of delivery, and postnatal microbial transmission, that converge on shared microbiome-mediated signaling pathways affecting fetal and neonatal immune, metabolic, and neurodevelopmental trajectories. Broader macro-environmental drivers, including biodiversity loss, urbanization, pollution, and industrialized lifestyles, are considered as upstream modulators of maternal microbial ecology within a One Health context. A systems model is presented to illustrate how environmental inputs are biologically transduced through maternal microbial networks to influence placental function, fetal development, and early-life health trajectories. Framing pregnancy as an integrated eco-biological continuum highlights the maternal microbiome as a central hub of intergenerational health and may support microbiome-informed preventive strategies and public health approaches aimed at reducing the burden of non-communicable diseases (NCDs) of early-life origin. Full article

Drug exposure during pregnancy and early life is typically considered a short-term clinical intervention rather than a determinant of long-term pharmacological outcomes. Consequently, the developmental context is largely absent from drug discovery and drug development paradigms, where efficacy, safety and target engagement are evaluated predominantly in adult, steady-state systems. This disconnect may contribute to unexplained variability in drug response and toxicity later in life. Pregnancy is accompanied by dynamic remodeling of the maternal gut microbiota and its metabolic output, generating bioactive microbial metabolites that regulate immune tone, metabolic homeostasis and the expression of drug-metabolizing enzymes and transporters. These microbial signals intersect with pharmacological interventions across gestation, shaping maternal pharmacokinetics, placental regulation and fetal drug exposure during developmentally sensitive windows. Importantly, microbiota–drug interactions initiated during pregnancy do not terminate at birth. Instead, they extend into infancy through vertical microbial transmission, breast milk-mediated metabolic signaling, and the immaturity of neonatal drug-handling systems, collectively contributing to developmental programming of drug responsiveness beyond early life. In this review, we propose a microbiota-informed framework that reframes perinatal drug exposure as a developmentally embedded signal operating across a maternal–placental–infant continuum. This perspective introduces a missing developmental dimension into drug discovery and highlights new opportunities to improve translational predictability and precision pharmacotherapy across the life course. Full article

Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management. Full article

Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) remains the main strategy to prevent malaria in pregnancy. However, continued drug pressure may also contribute to the emergence of resistant parasites and impact the gametocyte carriage and subsequent infectiousness. Pregnant women are thought to be a potential reservoir for malaria transmission due to the increased carriage of gametocytes following long-lasting infections. We used molecular methods to examine 100 Plasmodium falciparum (P. falciparum) isolates collected from Mozambican women at delivery in 2014-15 to determine sulfadoxine-pyrimethamine (SP) resistance polymorphisms in P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes, as well as the presence of gametocytes by RT-qPCR. Overall, 54% and 7% of parasites harbored quintuple and sextuple pfdhfr/pfdhps mutant haplotypes, respectively. Gametocytes were detected in 34% of isolates. Gametocyte carriage was significantly associated with quintuple mutant infections (AOR = 7.5, p = 0.001), which accounted for 80% of infections with detectable gametocytes. Results indicate the relevance of ongoing surveillance of SP resistance in Mozambique to guide future evaluation of alternative intermittent preventive treatment in pregnancy (IPTp) approaches as resistance levels evolve and anticipate potential implications for parasite transmission and maternal–fetal health. Full article

Since the elimination of smallpox, mpox (monkeypox) is the most medically significant orthopoxvirus infection. As a result of numerous regional, national and global outbreaks of MPXV (mpox virus), there is an abundance of new data available on the effects of the different viral clades on clinical obstetrical and perinatal outcomes when infection occurs in pregnancy. In addition, there have been additional placentas from cases of congenital MPXV infection available for study. These recent data indicate that there are prominent differences between viral strains and their effects on the fetus, with MPXV Clade I strains (Ia, Ib) having the greatest risk for an adverse outcome in pregnancy, and Clade II strains (IIa, IIb) having far less risk. In particular, the ongoing outbreak of MPXV Clade Ib in the DRC indicates that there is a significant risk for adverse perinatal outcomes associated with infection in pregnancy, especially during the first trimester. These outcomes include spontaneous abortion, stillbirth, neonatal death and congenital mpox. The placenta in cases of congenital infection demonstrates abundant virus in the chorionic villi, with prominent involvement of Hofbauer cells. Similar to smallpox, transplacental transmission and adverse pregnancy outcomes are an important feature of certain strains of this orthopoxvirus infection when occurring in pregnant women. Full article

Pregnancy represents a distinct immunological and physiological state that modifies maternal susceptibility to SARS-CoV-2 and influences the clinical and biological course of COVID-19. Accumulating evidence indicates that the interaction between viral entry determinants, gestation-specific immune modulation, placental endocrine–angiogenic pathways, and systemic inflammatory responses underlies the characteristic manifestations of SARS-CoV-2 infection during pregnancy. This review consolidates current understanding of SARS-CoV-2 viral structure, receptor biology, and the gestational regulation of key entry cofactors, including ACE2, TMPRSS2, NRP1, CTSL and FURIN, within reproductive and placental tissues. The review further integrates documented mechanisms of cytokine-mediated immune dysregulation, endothelial injury, thrombo-inflammation, and steroidogenic alteration observed in affected pregnancies, and examines their contribution to placental malperfusion, preeclampsia-like presentations, fetal growth abnormalities and preterm birth. Published molecular and computational studies characterising trophoblast antiviral defenses, receptor expression patterns, and structural determinants of Spike–ACE2 affinity are synthesised to contextualise the biological basis of placental susceptibility and the rarity of confirmed transplacental transmission. Current evidence on maternal clinical outcomes, fetal and neonatal consequences, vaccination efficacy, therapeutic considerations and contemporary management guidelines is also critically reviewed. By integrating molecular, immunological, pathological and clinical insights, this article provides a comprehensive framework for understanding the interaction between SARS-CoV-2 infection and pregnancy-specific physiology, with implications for risk assessment, preventive strategies and maternal–fetal care. Full article

Yellow fever remains a major public health threat in endemic and re-emerging regions of Africa and South America, with recent outbreaks highlighting persistent gaps in prevention and surveillance. Pregnant women represent a particularly vulnerable population, yet the epidemiology, clinical impact, and preventive strategies for yellow fever in pregnancy are insufficiently characterized. Physiological and immunological changes during gestation may influence host responses to infection; however, current evidence does not demonstrate increased susceptibility to or severity of yellow fever during pregnancy. Adverse materno-fetal outcomes, including miscarriage, stillbirth, preterm birth, and, in rare cases, perinatal transmission, have been reported but remain poorly characterized. Diagnostic challenges, overlapping clinical presentations with other arboviral and hepatic diseases, and limited access to specialized care further complicate clinical management in many endemic settings. This perspective provides a comprehensive overview of yellow fever in pregnancy during the 2024–2026 outbreak in the Americas, including a risk-stratification framework for prevention. We summarize current evidence on epidemiology, pathophysiology, diagnosis, and supportive care, and examine prevention strategies with particular emphasis on vaccination. Accumulated observational evidence and substantial real-world experience have not demonstrated an increased risk of serious adverse events and generally support the effectiveness of yellow fever vaccination during pregnancy when administered with appropriate clinical judgment. In high-risk settings, the benefits of maternal immunization clearly outweigh theoretical concerns, supporting a flexible, risk-based approach, despite relatively limited evidence. We also discuss national and international policies, post-pregnancy booster recommendations, and the importance of integrating vaccination assessment into antenatal care. Finally, we highlight critical knowledge gaps and research priorities, including the need for prospective registries and strengthened pharmacovigilance. Coordinated clinical and public health strategies are essential to protect maternal and neonatal health and to reduce the burden of yellow fever in endemic and re-emerging settings. Full article

Background: Autophagy is a conserved intracellular degradation pathway essential for maintaining cellular homeostasis by recycling damaged organelles and proteins. Dysregulation of autophagy has been implicated in pregnancy-related complications such as preeclampsia and fetal growth restriction, underscoring its importance in maternal and fetal health. However, the autophagy status in the placental tissue of COVID-19-infected pregnant women remains unknown. Objective: To investigate autophagy activity in term placentas from pregnant women infected with COVID-19 compared to those from uninfected control pregnant women. Methods: In this prospective cross-sectional single-center study, 15 COVID-19-positive and 15 COVID-19-negative term pregnant women who delivered at Sultan Qaboos University Hospital between January 2020 and December 2022 were included. Immediately after delivery, the placental tissue samples were collected and assessed for autophagy activity using immunohistochemistry for LC3B and p62 markers, histopathological examination, and transmission electron microscopy. The proportion and intensity of LC3B and p62 staining were quantified. Statistical analysis was performed using the Mann–Whitney U test. Results: There was a significant reduction in p62 and LC3B expression in both the proportion and intensity in COVID-19 placentas compared to the control group. The proportion of p62 (p = 0.001) and LC3B (U = 46.000, p = 0.003) was significantly reduced in infected placentas. Similarly, intensity levels of both markers showed significant differences (p < 0.05), supporting the evidence of reduced LC3B/p62, suggesting autophagy modulation in COVID-19 patients’ placentas. Additionally, abnormal ultrastructural changes were observed in COVID-19–positive placentas, including mitochondrial injury, endoplasmic reticulum stress, microvillus loss, and basement membrane thickening. Conclusion: The study results from a limited sample size demonstrate a significantly altered autophagy flux in the placental tissues of term pregnant women with COVID-19 infection. These findings highlight the potential impact of COVID-19 infection on placental function and fetal development and underscore the need for further investigation into autophagy-modulating strategies to improve maternal–fetal health. 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