Search Results (3,439)

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

Background and Clinical Significance: Budd–Chiari syndrome (BCS) is a rare disorder characterized by hepatic venous outflow obstruction, often associated with underlying hypercoagulable states. Pregnancy represents a physiologic prothrombotic condition that may precipitate disease onset. Case Presentation: We report a case of de novo BCS diagnosed in the second trimester in a previously healthy 36-year-old multiparous patient. Evaluation revealed cirrhotic liver morphology, portal hypertension, and bleeding esophageal varices requiring emergent treatment. The patient’s course included a transjugular intrahepatic portosystemic shunt (TIPS) procedure with complications, anticoagulation, multidisciplinary care, and a work-up revealing a JAK2 mutation consistent with an underlying myeloproliferative disorder. Despite apparent maternal stabilization and reassuring fetal growth, the pregnancy resulted in intrauterine fetal demise at 34 weeks’ due to placental abruption, followed by postpartum hemorrhage. Conclusions: This case highlights the diagnostic and therapeutic challenges of BCS in pregnancy, and demonstrates that favorable maternal stabilization does not preclude severe obstetric complications. Full article

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5–29.9 kg/m²) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate–uncoupler–inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies. Full article

Maternal obesity has been associated with offspring fetal programming, increasing the risk of developing chronic diseases in adulthood, including type 2 diabetes, hypertension, and behavioral disorders such as anxiety and depression. Milk whey (MW) peptides, administered as a supplement, reduce food intake and body weight in overweight rodents. The aim of this work was to study the possible metabolic and behavioral restorative effects of a bovine MW supplement against the negative fetal programming of juvenile offspring. Dam Wistar rats were fed during gestation and lactation with a standard (SD) or a hypercaloric diet (HD); after weaning, the male offspring were fed SD or SD and MW. HD dams showed increases in blood cholesterol, body weight, and calorie intake, while administering MW in offspring from HD mothers reduced these alterations. Serum corticosterone, LDL cholesterol, fasting blood glucose, and glucose intolerance were significantly higher in offspring from HD dams; however, MW did not affect these changes. Offspring from HD dams showed signs of anxiety that were not reversed by MW, as well as a reduction in hippocampal BDNF that was partially restored with MW. Maternal HD consumption during pregnancy and lactation elicited negative developmental programming of adult offspring metabolism, which was partially restored by bovine MW supplementation. Full article

Background: Hydroxychloroquine (HCQ) is commonly recommended during pregnancy in women with systemic lupus erythematosus (SLE), but real-world patterns of early-pregnancy HCQ continuation, reduction, or interruption remain clinically relevant. This study aimed to evaluate the association between HCQ exposure intensity during early pregnancy and composite fetal adverse pregnancy outcomes in pregnancies complicated by SLE. Methods: This retrospective cohort study included 513 pregnancies complicated by SLE. HCQ exposure intensity during early pregnancy, defined as conception to 13 weeks and 6 days of gestation, was classified into three groups: no HCQ exposure, reduced/interrupted HCQ exposure, and full HCQ exposure. The primary outcome was composite fetal adverse pregnancy outcome, defined as fetal loss, preterm birth, or fetal growth restriction. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with full HCQ exposure as the reference group. Results: Among 513 pregnancies, 96 (18.7%) had no HCQ exposure, 68 (13.3%) had reduced/interrupted HCQ exposure, and 349 (68.0%) had full HCQ exposure during early pregnancy. Composite fetal adverse pregnancy outcomes occurred in 47/96 (49.0%), 48/68 (70.6%), and 136/349 (39.0%) pregnancies, respectively (p < 0.001). After adjustment for maternal age, primiparity, lupus nephritis history, antiphospholipid antibody positivity, chronic hypertension, prednisone dose > 15 mg/day, and baseline immunosuppressant use, reduced/interrupted HCQ exposure was associated with higher odds of composite fetal adverse pregnancy outcome compared with full HCQ exposure (adjusted OR 4.17, 95% CI 2.25–7.75, p < 0.001). No independent association was observed for no HCQ exposure after adjustment (adjusted OR 1.30, 95% CI 0.78–2.16, p = 0.309). Conclusions: In pregnancies complicated by SLE, reduced or interrupted HCQ exposure during early pregnancy was independently associated with an increased risk of composite fetal adverse pregnancy outcomes, while no independent association was observed for no HCQ exposure after adjustment for baseline risk factors. These findings highlight the potential clinical importance of maintaining HCQ treatment continuity during early pregnancy. Full article

Background: Tryptophan (Trp) is critical to mothers and their conceptuses, and this amino acid is the precursor to serotonin (5-HT). 5-HT modulates placenta function and fetal neurodevelopment. It is not clear if the placenta directly synthesizes 5-HT or uses the serotonin transporter (SERT/Slc6a4) to accrue 5-HT from the dam. The hypothesis tested herein is that reduction in maternal Trp leads to reductions in maternal Trp, 5-HT, and 5-hydroxy-3-indoleacetic acid (5-HIAA, metabolite of serotonin) and reductions in these metabolites within the placenta and fetal brain of female and male conceptuses. Methods: Female mice were placed on a reduced tryptophan (Trp) diet (0.1%) or control diet (0.2%). Diets were provided for two weeks prior to breeding (periconception period) until conceptuses were collected at approximately 12.5 days post-coitus (dpc). Results: While no reductions in maternal Trp and 5-HT were observed, both metabolites were significantly reduced in the placenta and fetal brain of male and female conceptuses (p < 0.05). Female conceptuses were susceptible to reductions in maternal Trp with 549 and 29 transcripts altered in the female placenta and fetal brain, respectively, of reduced Trp dams compared to control dams. Transcriptomic changes, such as reduced expression in Slc6a4 and Slc6a19 (transporter for Trp), in placenta of female conceptuses correlated with reductions in Trp and 5-HT amounts. Conclusions: Findings might have clinical importance to pregnant women as they reveal even subtle reductions in one amino acid profoundly influence conceptus development and might lead to sexual disparity in risk for later diseases, including neurobehavioral disorders. Full article

Nanomaterials (NMs) offer substantial technological advantages, yet their potential adverse biological effects remain a critical concern. This study investigates the maternal–fetal toxicity of zinc oxide nanoparticles (ZnONPs) following a single intravenous (i.v.) administration in vivo, focusing on oxidative DNA damage, cytotoxicity, and transplacental transfer. The median lethal dose (LD₅₀) of ZnONPs was determined to be 154 mg/kg of body weight. Pregnant rats on gestational day 19 were exposed to two sub-lethal doses (3.09 and 7.71 mg/kg; corresponding to 1/50 and 1/20 of LD50). Subsequent analyses assessed Zn²⁺ accumulation, histopathological alterations in maternal organs, and induction of 8-hydroxydeoxyguanosine (8-OHdG) in maternal and fetal tissues. ZnONPs demonstrated systemic distribution, with pronounced accumulation in the liver, spleen, and placenta, and were shown to cross the placental barrier, leading to fetal exposure. Elevated Zn²⁺ concentrations were positively correlated with cytotoxicity and 8-OHdG induction across maternal and fetal compartments. These findings provide compelling evidence of ZnONPs-mediated cyto- and genotoxicity in both mothers and offspring, underscoring the need to define safety margins and regulatory thresholds for nanomaterial exposure in biomedical and environmental contexts. 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

Background/Objectives: This prospective cohort study assessed the impact of seasonal influenza during pregnancy on fetal and infant health outcomes. Methods: Pregnant women with laboratory-confirmed influenza were matched (1:4) by age and pregnancy loss history with women without influenza from annual cohorts in Suzhou, China, during 2015–2018. Participants underwent twice-weekly follow-up for influenza illness, and medical records were linked to ascertain outcomes. Multivariable regression models were used to estimate associations. Results: We included 441 pregnant women with influenza and 1764 without it. Four (0.9%) in the influenza group had late pregnancy loss, whereas one (0.1%) in the non-influenza group did. Influenza was associated with late pregnancy loss (adjusted hazard ratio [aHR] 31.1, 95% Confidence Interval [CI]: 1.3–756.8, p = 0.035). Four (0.9%) in the influenza group experienced early pregnancy loss, while five (0.3%) in the non-influenza group did. Influenza was not significantly associated with early pregnancy loss (aHR 2.1, 95% CI: 0.4–10.4, p = 0.374). By 8 months of age, infants born to 198 of the 441 mothers (44.9%) in the influenza group met the criteria for the program-defined child health monitoring indicator, compared with infants born to 650 of the 1764 mothers (36.8%) in the non-influenza group. Overweight/obesity was the largest contributor: 142 (32.2%) versus 470 (26.6%). Maternal influenza was associated with higher odds of meeting program-defined child health monitoring indicator in offspring (adjusted odds ratio [aOR] 1.4, 95% CI: 1.1–1.8, p = 0.006), with a significant contribution from overweight/obesity (aOR 1.3, 95% CI: 1.0–1.7, p = 0.045). Conclusions: In this cohort, influenza during pregnancy was associated with an increased risk of late pregnancy loss and program-defined child health monitoring indicator in offspring, particularly overweight/obesity. Because the observed association with pregnancy loss was based on a small number of events and had a wide confidence interval, it should be interpreted cautiously and confirmed in larger studies. These findings are consistent with current recommendations supporting influenza vaccination during pregnancy to protect maternal and infant health. Full article

Background/Objectives: Early-life undernutrition may exert lifelong and intergenerational effects on height and weight, but its impact on body shape remains unclear. Using the Great Chinese Famine (1959–1961) as a natural experiment, this study explored the associations between early-life undernutrition and body shape indices across two generations. Methods: We analyzed nine waves of longitudinal data from the China Health and Nutrition Survey (1991–2015), including 5156 participants (F1) born in 1955–1966 and their 2383 biological offspring (F2). F1 famine exposure was classified by birth year; F2 exposure was defined by parental status. Anthropometric indices including body adiposity index (BAI), body roundness index (BRI), waist-to-height ratio (WHtR), conicity index (COI), and a body shape index (ABSI) were derived from repeated measurements. Age-specific fitted curves of these indices were compared across exposure groups using mixed-effects models with fractional polynomials of age. Results: Fetal famine exposure was modestly associated with lower COI and ABSI in adulthood, particularly among men. Childhood famine exposure was significantly linked to lower BAI (−0.40), BRI (−0.26), WHtR (−0.0140), COI (−0.0188), and ABSI (−0.0008), with stronger associations in men (all P for sex interaction <0.05). Intergenerationally, maternal childhood exposure was associated with higher offspring BAI, whereas paternal childhood exposure was associated with lower BAI, BRI, WHtR, COI, and ABSI. Conclusions: Famine exposure showed more pronounced associations with body shape in men, and maternal and paternal exposures displayed different intergenerational patterns. These exploratory findings suggest the possibility that early-life undernutrition may relate to long-term phenotypes in a sex-specific manner, though this requires independent replication. Full article

Background: Artificial intelligence (AI), which spans machine learning (ML), deep learning (DL), computer vision, and natural language processing (NLP), is now used across obstetric care, including ultrasound interpretation (biometry, anomaly detection), fetal monitoring (cardiotocography), maternal risk stratification (preeclampsia, preterm birth, hemorrhage), labor and delivery decision support, genomic screening, and telehealth. Methods: We conducted a narrative (non-systematic) review of the literature published between 2016 and 2026, distinguishing the level of evidence supporting each application. Results: Reported performance is frequently high for image-based tasks such as fetal biometry and anomaly detection (accuracy and AUC often exceeding 0.85), whereas intrapartum CTG analysis remains modest (AUROC ~0.60–0.70, overlapping the inter-observer variability of clinicians). Most published evidence is retrospective and internally validated; comparatively few tools have undergone external or prospective validation, and only a small number have received regulatory clearance. Limitations: The evidence base is heterogeneous, external validation and calibration are often absent, and we did not perform a formal risk-of-bias appraisal. Conclusions: AI has real potential to improve prenatal diagnosis and individualized care, but claims that it is ready for the clinic are often premature. Prospective and external validation, calibration and clinical-utility assessment, transparent reporting, attention to bias and equity, and sustained clinician oversight are prerequisites for safe adoption. Full article

Recurrent pregnancy loss (RPL) continues to be a significant challenge in reproductive medicine, particularly in women for whom standard examinations do not reveal a conclusive underlying reason. There is growing evidence that several instances may result from nuanced alterations in the endometrial milieu, particularly with decidualization and maternal–fetal immune tolerance. In recent years, vitamin D has gained recognition for its significance in early pregnancy, serving not only as a regulator of calcium metabolism but also as an active contributor to endometrial and immunological functions. The human endometrium exhibits the vitamin D receptor (VDR) and the enzyme CYP27B1, facilitating the local activation and signaling of vitamin D inside the uterine milieu. Experimental investigations have shown that vitamin D influences many processes critical for effective implantation and placentation, including stromal cell differentiation, cytokine equilibrium, trophoblast invasion, oxidative stress responses, and immune cell communication. Aberrant vitamin D signaling has been associated with heightened inflammatory activity, impaired decidual transformation, altered uterine natural killer cell functionality, and alteration of the Treg/Th17 equilibrium, all of which have been implicated in recurrent pregnancy loss. Concurrently, there is an increasing emphasis on the association between vitamin D and mitochondrial function as well as oxidative stress in decidual and endometrial cells. Interruption of these pathways may influence implantation and early embryonic development by impacting cellular metabolism and immunological control at the maternal–fetal interface. The clinical interest in vitamin D supplementation for women experiencing repeated reproductive failure is increasing; nevertheless, the existing results are conflicting, mostly due to the predominance of research focusing on circulating vitamin D levels rather than localized tissue-specific processes. Our review encapsulates new findings about the function of vitamin D in endometrial biology and reproductive immune regulation, emphasizing its involvement in decidualization, inflammatory signaling, oxidative stress, and maternal–fetal immunological tolerance in recurrent pregnancy loss. The potential ramifications for assisted reproduction and forthcoming tailored therapy techniques are also examined. Full article

Background/Objectives: Advanced maternal age (≥35 years) significantly increases the risk of fetal chromosomal abnormalities, particularly trisomies 21, 18, and 13. Non-invasive prenatal testing (NIPT) based on cell-free fetal DNA (cffDNA) in maternal plasma has substantially improved the accuracy and safety of prenatal screening. Methods: We previously developed and clinically validated a multiplex droplet digital PCR (ddPCR)-based NIPT assay for detecting fetal trisomies 21, 18, and 13 in Mongolia. The assay targeted specific loci on chromosomes 21, 18, and 13, using chromosome 1 as an internal reference. A Z-score threshold > 3 indicated high risk, and all positive results were confirmed by invasive karyotyping. Results: In this study, we collected 74 pregnant women of advanced maternal age and samples were successfully analyzed, with high technical performance (mean > 100,000 accepted droplets per reaction and clear signal separation). Ten high-risk pregnancy cases were identified (eight trisomy 21 and two trisomy 18), all of which showed complete concordance with confirmatory karyotyping. Complete concordance with available reference standard results were observed in this limited cohort. No trisomy 13 cases were detected. Conclusions: This ddPCR-based NIPT assay exhibited excellent diagnostic accuracy and reproducibility in a Mongolian cohort of advanced-maternal-age pregnancies. Its technical simplicity, relatively low cost, and minimal infrastructure requirements make it a promising tool for implementation in resource-limited settings. However, the small sample size limits generalizability, and larger multicenter studies are needed to confirm clinical utility across broader populations, including low-risk pregnancies. Full article

Background: Several scenarios of abnormal fetal growth develop during pregnancy in women with pregestational diabetes. A trend towards a higher incidence of large-for-gestational-age (LGA) births among women with type 1 diabetes (T1D) is observed worldwide despite novel approaches to maternal glycaemic control. Fetal growth restriction (FGR) is commonly recognised as a severe condition. However, the risk of adverse outcomes in LGA fetuses generally remains underestimated. Methods: We conducted a comparative analysis of pregnancy outcomes across different birthweight categories in pregnancies with T1D based on published data (2001–2026). Results: Interactions between disorders of early placentation, impaired nutrient transfer, fetal overnutrition, and genetic background result in alterations in birthweight and disproportionate fetal adipose tissue deposition. Both FGR and macrosomia are associated with increased risks of adverse perinatal outcomes. Although stillbirth occurs at both extremes of fetal growth, term LGA fetuses may remain particularly vulnerable because routine surveillance methods, including arterial Doppler assessment, fail to identify compromised fetuses with excessive growth. Accelerated fetal growth in T1D pregnancies, when placentation is initially impaired, may cause growth-restricted fetuses to appear appropriate for gestational age (AGA). Routine assessment may classify these vulnerable fetuses as being at low risk of perinatal complications. Disproportionate growth, even among infants classified as AGA, is associated with shoulder dystocia, birth trauma, and operative delivery. Neonatal hypoglycaemia and respiratory disorders remain frequent complications across the spectrum of abnormal fetal growth. Conclusions: Increased glucose variability may explain differences in placental and fetal growth trajectories and the high rate of pregnancy complications in patients with target glycated haemoglobin levels and routine capillary glucose monitoring results. Fetal overgrowth reflects impaired intrauterine development and should be considered a high-risk condition requiring careful consideration of the timing and mode of delivery. Full article

Warfarin is a coumarin-derived oral anticoagulant widely used for the prevention and treatment of thromboembolic disorders, particularly in patients with mechanical heart valves. The drug exerts its anticoagulant effect by inhibiting vitamin K epoxide reductase, thereby impairing γ-carboxylation of vitamin K-dependent coagulation factors. Despite its clinical efficacy, warfarin therapy is associated with a narrow therapeutic index, substantial interindividual variability in dose response, numerous drug interactions, and significant hemorrhagic risk. Maternal warfarin therapy during pregnancy is strongly associated with fetal warfarin syndrome (FWS), a characteristic pattern of embryopathy resulting from in utero exposure to the drug. This review summarizes current knowledge regarding the physicochemical properties, pharmacological mechanisms, dose variability, toxicity, and developmental effects associated with warfarin exposure. Evidence from human clinical studies and vertebrate animal models is discussed to elucidate conserved developmental and molecular mechanisms underlying warfarin teratogenicity. The review also examines the signaling pathways disrupted by warfarin exposure, highlighting that its teratogenic effects extend beyond anticoagulation to the disruption of vitamin K-dependent developmental signaling. Inhibition of γ-glutamyl carboxylation, together with alterations in Gas6/TAM, PXR, Ras, and Wnt/β-catenin signaling pathways, impairs skeletal, vascular, and neural development, contributing to the characteristic abnormalities of fetal warfarin syndrome. Collectively, this review integrates clinical, molecular, and experimental findings to provide a comprehensive understanding of warfarin-induced developmental toxicity. Current knowledge is insufficient to fully elucidate the complex mechanisms underlying warfarin-induced embryopathy and fetal toxicity. Further investigations are warranted to identify safer anticoagulant regimens during pregnancy and to inform the development of novel therapeutic strategies that minimize fetal risk while maintaining maternal anticoagulation. Full article