Search Results (919)

The metabolic mechanisms linking prenatal particulate matter (PM) to fetal growth remain unclear. A prospective cohort of 616 mother–fetus pairs in Guangzhou had ultrasound-based fetal growth parameters repeatedly measured from mid to late pregnancy. Fetal head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD) were standardized as z-scores. Estimated fetal weight (EFW) trajectories were classified as average, slow, and rapid growth. Residential PM₁, PM_2.5, and PM₁₀ were assessed with 1 km spatiotemporal models. Multinomial logistic regression analyzed PM-EFW trajectory associations. Generalized estimating equations evaluated PM–fetal growth z-score relationships. Maternal plasma glucose and insulin levels at mid-pregnancy were examined as intermediate factors. Each 5 μg/m³ increase in PM was associated with higher odds of rapid EFW growth versus average growth (OR _PM1 = 1.56, 95% CI: 1.03, 2.37; OR _PM2.5 = 1.44, 95% CI: 1.10, 1.88; OR _PM10 = 1.28, 95% CI: 1.05, 1.56). Positive associations were also observed for BPD, HC, and AC z-scores, with PM₁ showing the numerically larger effect estimates. Maternal fasting plasma glucose and insulin resistance may partly explain the observed associations of PM exposure with rapid EFW growth and fetal growth parameters, with estimated proportions of 5.0–29.4%. This study highlights the potential risk of accelerated fetal growth associated with maternal PM exposures, and maternal glucose metabolism may represent a plausible pathway. 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/Objectives: Large-for-gestational-age (LGA) birth is associated with adverse perinatal outcomes and increased risk of metabolic disease later in life. Despite these risks, epigenetic studies of LGA remain limited, particularly those using umbilical cord blood DNA methylation (DNAm) as the tissue of interest. Methods: We conducted an epigenome-wide association study of cord blood DNAm in a nested case–control sample from the Gestational Regulators of Weight (GROW) cohort. The analysis included 28 term LGA infants and 63 term appropriate-for-gestational-age (AGA) controls. DNAm was measured using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analyses were performed with adjustment for residual principal components and estimated cord blood cell-type proportions. Results: No CpG sites reached statistical significance after false discovery rate correction. Twenty-four CpGs showed nominal associations with LGA status at p-value < 1.00 × 10⁻⁴, including five CpGs with absolute methylation differences greater than 0.05. Among annotated loci, the strongest interpretable signals included cg06750897 in PBX1 (Δβ = 0.110, p-value = 1.70 × 10⁻⁵) and two nearby CpGs in SMAD3, cg23731272 (Δβ = 0.111, p-value = 4.31 × 10⁻⁵) and cg02486855 (Δβ = 0.109, p-value = 9.45 × 10⁻⁵). These two SMAD3 CpGs showed concordant hypermethylation in LGA infants and formed a candidate regional methylation signal in exploratory targeted regional analysis. Conclusions: In this pilot study, LGA was associated with modest cord blood DNAm differences, although no CpG sites reached genome-wide significance. The strongest interpretable signals involved PBX1 and SMAD3, suggesting candidate loci for further evaluation in larger studies of fetal overgrowth. 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

Our first objective was to quantify the associations between health-related events (HRE) before insemination, the relative increase in estrus intensity (REI) at insemination, and the probability of cow-level pregnancy per artificial insemination (P/AI) in organic Holstein dairy cows. Quantifying these associations may aid on-farm decision-making, such as setting the voluntary waiting period, choice of type of semen, do-not-breed and culling decisions. A second objective was to develop predictive models to estimate P/AI based on readily available data, and present common goodness-of-fit results also used in the machine learning community. All data were collected from a certified organic dairy farm in the western USA from 2019 to 2021. Health-related and reproduction data were obtained through Dairy Records Management Systems (DRMS; Raleigh, NC, USA). Activity data were collected using pedometers (IceRobotics, Stirling, UK) mounted on the rear legs. The REI, defined as walking steps per hour before insemination divided by the cow’s baseline steps per hour, was available for 17,238 inseminations from 4759 cows. The REI was categorized as ≤200%, >200–400%, >400–600%, or >600%. The HRE were available for 65,684 inseminations from 13,365 cows. The HRE were categorized as mastitis, metabolic disease (i.e., hypocalcemia, ketosis, displaced abomasum, digestive problems), reproductive disease (i.e, metritis, endometritis, pyometra, retained fetal membranes), lameness, 2 different diseases, ≥3 different diseases, or as healthy (none of these diseases prior to insemination). Combinations (COMBO) between REI categories and 0, 1, or ≥2 HRE were also created. Data were split into training and test sets. The training data were used to fit three logistic regression models that included either HRE, or REI, or COMBO. Each of the three models also included the covariates of 3-mo herd-average P/AI prior to insemination, days in milk, and the fixed effects of parity, insemination season, days after the previous insemination or days to 1st insemination. A random effect accounted for repeated inseminations within cow. Parameter estimates, odds ratios, and the estimated marginal means of the estimated P/AI of the fixed effects were obtained from the logistic regression models. The models’ estimates were applied to the test datasets, and discrimination and calibration statistics were calculated to judge goodness-of-fit. Unadjusted mean P/AI were 0.31, 0.28 and 0.28 for the HRE, REI and COMBO training datasets. For the HRE model, estimated P/AI ranged from 0.20 (≥3 different HRE) to 0.30 (healthy). The estimated P/AI associated with four REI categories were not different from 0.27 in the REI model. The estimated P/AI associated with the combinations of HRE and REI in the COMBO model varied from 0.18 after ≥2 HRE and >200–400% REI, to 0.30 when inseminations were in healthy cows with REI >600%. Inseminations in older cows, in the spring, and outside 18–24 d after the previous insemination were also associated with lower estimated P/AI. The area underneath the Receiver Operating Characteristic curve ranged from 0.57 (COMBO) to 0.60 (HRE) for the test data, indicating fair discrimination ability of the models. Calibration plots showed that the prediction models produced unbiased predicted P/AI. In conclusion, the results showed no conclusive evidence of greater estimated P/AI related to greater REI as a measure of estrus activity. More HRE were associated with lower estimated P/AI. Combinations of low REI and more HRE were associated with notably decreased estimated P/AI. The logistic regression models produced unbiased predicted P/AI. We found no evidence that the strength of the relationship between REI and P/AI depended on the HRE category. The applications of the results are as follows. First, these predictive models may help inform insemination decisions in organic dairy cows, although further external validation is recommended, and the discriminatory performance is weak. Second, a variety of goodness-of-fit statistics were calculated to allow comparisons of the current logistic regression analyses with future analyses made by other machine learning techniques. Full article

Background: Increased placental thickness has been associated with adverse perinatal outcomes and fetal functional and structural abnormalities. However, whether marked third-trimester placental thickening is associated with a distinct maternal clinical profile compared with pregnancies with normal placental thickness remains insufficiently characterized. This study aimed to compare maternal characteristics, comorbidities, medication exposure, infection history, and fetal findings between pregnancies with marked placental thickening, defined as placental thickness ≥70 mm, and gestational-age-matched control pregnancies with a placental thickness <70 mm and no documented maternal or fetal abnormalities. Methods: This retrospective matched case–control study included singleton pregnancies referred for fetal echocardiography to a tertiary referral center in Łódź, Poland, between 1 January 2022 and 14 March 2025. Placental thickness was measured sonographically in a perpendicular plane from the chorionic plate to the basal plate, excluding the umbilical cord insertion site. Only anterior and/or fundal placentas assessed at ≥28 weeks of gestation were included. Among pregnancies with recorded third-trimester placental thickness measurements, 99 cases with placental thickness ≥70 mm were identified as the thick-placenta group. A control group of 99 pregnancies with placental thickness <70 mm was selected and matched for gestational age. Control pregnancies had no documented maternal disease, no fetal structural or functional abnormalities, and no exposure to the medications analyzed in this study. Maternal demographic characteristics, body mass index, comorbidities, infection history, obstetric history, and medication use were compared between groups. Continuous variables were compared using Welch’s t-test and the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Results: The study included 99 pregnancies with marked placental thickening and 99 control pregnancies with normal placental thickness. Gestational age at examination was comparable between groups, with a mean of 35.5 weeks in controls and 35.0 weeks in the thick-placenta group (p = 0.662, Welch’s t-test). Median gestational age was also not significantly different between groups (35.4 vs. 36.43 weeks; p = 0.340, Mann–Whitney U test). Mean placental thickness was significantly greater in the thick-placenta group than in controls (81.4 mm vs. 46.9 mm; p < 0.0001). Maternal age and anthropometric characteristics were comparable between groups, whereas BMI > 25 kg/m² was more common in the thick-placenta group. In contrast to the clinically healthy control group, maternal infection was documented in 100.0% of thick-placenta cases, hormonal treatment in 97.0%, history of COVID-19 in 52.5%, hypothyroidism in 44.4%, prior miscarriage in 37.4%, aspirin or anticoagulant use in 32.3%, gestational diabetes mellitus in 25.3%, and pregnancy-induced hypertension in 7.1%. All evaluated maternal clinical factors were significantly more common in the thick-placenta group than in controls. Fetal cardiac or extracardiac dysfunction was present in 68.7% of thick-placenta pregnancies. Conclusions: In this gestational-age-matched case–control study, pregnancies with marked third-trimester placental thickening showed a distinct maternal profile compared with healthy controls with normal placental thickness. Despite comparable gestational age, maternal age, and maternal anthropometric characteristics, the thick-placenta group demonstrated a significantly higher infectious, hormonal, metabolic, and endocrine burden. These findings indicate that, in this selected tertiary referral cohort, placental thickness ≥70 mm was associated with a higher burden of maternal clinical abnormalities and fetal functional findings. Rather than representing an independent marker of placental maladaptation or maternal-fetal risk, marked placental thickening should be interpreted as a clinically relevant ultrasound finding that may prompt careful review of maternal history and targeted fetal assessment. Prospective studies are needed to determine which maternal factors are independently associated with placental thickening and to clarify their relationship with fetal function and perinatal outcomes. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with placental structural and functional alterations that may impair trophoblast integrity and maternal–fetal exchange. Ezrin, radixin, and moesin (ERM) proteins are membrane–cytoskeleton linker proteins involved in microvillous organization, cell polarity, and signal transduction. This study aimed to investigate placental ERM protein expression in GDM and to explore ERM-associated molecular pathways through bioinformatic analysis. Methods: This prospective observational study included placental tissues obtained from 40 women with GDM and 40 healthy pregnant women. Immunohistochemical staining for ezrin, radixin, and moesin was performed on paraffin-embedded placental sections, and quantitative image analysis was conducted using QuPath software (version 0.7.0) to calculate H-scores. Correlation and receiver operating characteristic (ROC) analyses were performed to evaluate associations between ERM expression and clinical parameters. In addition, bioinformatic analyses were conducted using the publicly available GSE154414 placental transcriptomic dataset to investigate ERM-associated signaling pathways and interaction networks. Results: Ezrin immunoreactivity was significantly increased in the GDM group compared with controls (118.63 ± 20.56 vs. 107.95 ± 17.41, p = 0.026), whereas Radixin and Moesin expression levels did not differ significantly between groups (p > 0.05). Ezrin expression demonstrated significant positive correlations with maternal body mass index, birth weight, fasting glucose, and HbA1c levels. ROC analysis demonstrated modest discriminatory performance of the Ezrin H-score for distinguishing GDM from control pregnancies (AUC = 0.645, p = 0.018). Bioinformatic analyses identified enrichment of ERM-associated pathways involved in cytoskeletal remodeling, inflammatory signaling, and protein phosphorylation-related cellular processes. Conclusions: Placental Ezrin expression was significantly increased in women with GDM and was positively associated with maternal glycemic parameters. These findings suggest that altered Ezrin expression may reflect adaptive cytoskeletal remodeling in diabetic placentas. ERM-associated signaling pathways may contribute to placental responses to metabolic stress in GDM. Full article

Bisphenols, phthalates, and other plastic-associated compounds are endocrine-disrupting chemicals (EDCs), common environmental contaminants that can disrupt hormonal homeostasis. Human exposure to such chemicals occurs mainly through food packaging, consumer goods, medical devices, and the environment, starting right from early development stages up to adulthood. These chemicals might cause damage to male reproductive systems as a result of being anti-androgens and estrogenic chemicals. However, the proper development of the male reproductive system requires well-regulated hormonal signaling pathways; hence, exposure to such compounds during the developmental stages poses a great risk. Environmental exposure to plastics during fetal development may influence the development of the testes, reduce the function of the Leydig cells, disrupt steroidogenesis, and produce epigenetic modifications, as documented through studies. This has been shown to increase the risk of developing reproductive disorders and reduce the production of testosterone. Therefore, one of the pathophysiological links between endocrine disruptor exposure and ED might be testosterone deficiency. Apart from disrupting testosterone production, the plastic-sourced EDCs could influence various physiological processes associated with erectile performance, such as those related to vasculature, inflammation, metabolism, and endocrinology. In this review, a comprehensive overview of the scientific data on the effect of plastic-based EDCs on testosterone regulation and male reproductive health has been provided. The role of developmental programming, endocrine disruption, oxidative stress, epigenetics, and vascular dysfunction has been explored in detail. Moreover, the possible involvement of micro- and nanoplastics has also been reviewed. From the data that is currently available, there seems to be a physiologically plausible association between plastic-based contaminants, testosterone dysregulation, and adverse reproductive outcomes. Full article

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

Intrauterine fetal death, also termed stillbirth, remains a major clinical challenge, with a substantial proportion of cases unresolved despite standard postmortem evaluation, limiting effective risk stratification and prevention. This structured narrative review synthesizes evidence from genetic, immune-mediated, and pharmacogenetic studies to summarize possible contributors to stillbirth with potential application in precision-oriented diagnostics and prevention of unexplained stillbirth. Integration of cytogenetic and sequencing approaches enhances detection of clinically relevant abnormalities in previously unexplained cases, while exome sequencing reveals additional molecular diagnoses beyond conventional chromosomal analyses. Genetic contributors include chromosomal abnormalities and a wide spectrum of heterogeneous monogenic disorders affecting cardiac electrophysiology, neuromuscular function, metabolic homeostasis, and early developmental processes. Immune-mediated placental dysfunction, particularly obstetric antiphospholipid syndrome, emerges as a clinically actionable mechanism characterized by vascular and inflammatory injury and associated angiogenic imbalance. Emerging pharmacogenetic evidence indicates that genetic variability in drug metabolism and receptor signaling may influence therapeutic response in placenta-mediated complications. Collectively, these findings support an integrated, mechanism-based framework combining genomic, immune, and pharmacogenetic data with phenotypic characterization to advance etiologic resolution, improve recurrence risk assessment, and enable precision-based diagnostic and preventive strategies in stillbirth. Full article

The heart is a highly energy-demanding organ that depends on metabolic flexibility to adjust substrate utilization in response to changes in nutrient availability, endocrine signals, and energetic demands. Accumulating evidence demonstrates that dietary patterns are key determinants of myocardial metabolic homeostasis, affecting substrate selection, mitochondrial function, nutrient-sensing pathways, and long-term transcriptional and epigenetic regulation. This review analyzes the molecular mechanisms through which diet regulates cardiac metabolism and explores how chronic nutritional exposures influence the myocardial energetic phenotype. The physiological regulation of cardiac substrate utilization is described, with emphasis on fatty acids, glucose, ketone bodies, and branched-chain amino acids, underscoring the importance of metabolic flexibility in sustaining cardiac efficiency. The regulation of substrate transport and oxidation is examined, including the roles of the carnitine shuttle, insulin signaling, AMPK, mTOR, PPARα–PGC-1α, SIRT3, and other nutrient-sensing networks that coordinate mitochondrial ATP production. The effects of dietary composition and meal timing, such as caloric restriction and intermittent fasting, are discussed as modulators of myocardial metabolism. The adverse effects of chronic nutrient excess are reviewed, including lipotoxicity, glucotoxicity, insulin resistance, mitochondrial dysfunction, oxidative stress, pseudo-hypoxia, fetal metabolic reprogramming, and maladaptive cardiac remodeling. Recent findings on the gut–heart axis, microbiota-derived metabolites, circadian regulation, and metabolic–epigenetic interactions are also considered. Overall, current evidence supports the view that diet is an important and potentially modifiable regulator of the cardiac metabolic phenotype. Advancing the understanding of diet–metabolism interactions may enable the development of targeted nutritional strategies to maintain metabolic flexibility, enhance cardiac bioenergetics, and prevent the progression of heart failure and other cardiometabolic diseases. Full article

The reproductive and developmental toxicity of diquat (DQ), a widely used herbicide, during pregnancy remains insufficiently characterized. This study investigated the effects of repeated DQ exposure on fetal development and maternal metabolism in pregnant Sprague–Dawley rats. The rats were administered sublethal doses of DQ (28.88 and 57.57 mg/kg), and maternal serum sex hormones, fetal skeletal development, and serum metabolomic profiles were evaluated. Compared with controls, serum estradiol levels were significantly decreased in the high-dose exposure group, whereas luteinizing hormone and follicle-stimulating hormone levels remained unchanged. Significant alterations in malondialdehyde, superoxide dismutase, and glutathione levels indicated oxidative stress in exposed rats. Severe fetal skeletal ossification deficits and developmental delays were observed, with incomplete or failed ossification of the occipital bone, sternum, caudal vertebrae, and pelvis, with litter-level incidences reaching 100%. Metabolomic analysis identified distinct serum metabolic profiles between DQ-exposed and control groups, suggesting ovarian steroidogenesis, phenylalanine metabolism, and aldosterone synthesis and secretion as key pathways affected by DQ toxicity. These findings suggest that repeated maternal exposure to DQ induces oxidative stress, disrupts metabolic and hormonal homeostasis, and causes delayed fetal skeletal development. This study provides novel evidence for understanding the reproductive and developmental toxicity of DQ and its potential metabolic mechanisms. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy associated with adverse maternal and neonatal outcomes. Data on GDM in Central Asian populations remain limited. This study aimed to identify factors associated with GDM and evaluate selected obstetric outcomes among pregnant women in Kazakhstan. Methods: A retrospective case–control study based on medical record data was conducted among 256 pregnant women, including 106 women with GDM and 150 women with normal glucose tolerance. GDM was diagnosed using a 75 g oral glucose tolerance test according to the International Association of Diabetes and Pregnancy Study Groups criteria. Demographic, clinical, anthropometric, laboratory, and obstetric data were obtained from medical records. Multivariable logistic regression was used to identify factors statistically associated with GDM. Obstetric outcomes were compared using unadjusted analyses. Results: Women with GDM were older than controls (31.6 ± 5.8 vs. 28.6 ± 5.3 years, p < 0.001) and had a higher pre-pregnancy body mass index (BMI) (29 [25–33] vs. 26 [23–29] kg/m², p < 0.001). Thyroid-stimulating hormone levels were also higher in the GDM group (p = 0.026). In multivariable analysis, pre-pregnancy obesity (adjusted OR 4.54, 95% CI 2.08–9.91; p < 0.001) and educational level (overall p = 0.001) remained associated with GDM, whereas maternal age was not independently associated after adjustment. Hypertension (24.5% vs. 2.0%; p < 0.001), eclampsia (3.8% vs. 0%; p = 0.028), cesarean delivery (52.8% vs. 28.0%; p < 0.001), and fetal macrosomia (21.7% vs. 12.0%; p = 0.037) were more frequent among women with GDM. No significant difference was observed in neonatal birth weight. Conclusions: Pre-pregnancy obesity and educational level were independently associated with GDM. Women with GDM more frequently experienced hypertensive complications, cesarean delivery, and fetal macrosomia; however, these findings were based on unadjusted analyses and should be interpreted cautiously. Further multicenter prospective studies are needed to confirm these findings in Central Asian populations. Full article

Background: Migraine has been associated with vascular dysfunction and adverse pregnancy outcomes. However, the relationship between changes in migraine manifestations during pregnancy and fetal growth remains incompletely understood. This prospective study aimed to investigate whether migraine symptom progression during pregnancy is associated with abnormal fetal growth patterns and placental-mediated pregnancy complications among women with pre-existing migraine. Methods: This prospective cohort study included 400 pregnant women with a pre-pregnancy diagnosis of migraine who received antenatal care at the Department of Obstetrics and Gynecology, University Hospital “Dr Dragiša Mišović”, Belgrade, Serbia, between 2024 and 2026. Maternal migraine characteristics, pregnancy complications, and fetal growth assessments were evaluated. Fetal growth was categorized according to estimated fetal weight percentiles adjusted for gestational age. Univariable and multivariable logistic regression analyses were performed to identify factors associated with abnormal fetal growth. Because of the relatively small number of events, Firth’s penalized logistic regression was additionally performed as a sensitivity analysis. Results: Persistent or worsening migraine symptoms during pregnancy were more frequently observed among pregnancies complicated by impaired fetal growth, pregnancy-induced hypertension, gestational diabetes mellitus, abnormal gestational weight gain, and preterm birth. In univariable analyses, migraine worsening was associated with increased odds of abnormal fetal growth. However, after adjustment for maternal and obstetric factors, migraine worsening was no longer independently associated with abnormal fetal growth. Pregnancy-induced hypertension and inadequate gestational weight gain remained the strongest independent predictors. Findings were confirmed in sensitivity analyses using Firth’s penalized logistic regression. Conclusions: Among women with pre-existing migraine, persistent or worsening migraine manifestations during pregnancy were associated with a higher burden of placental-mediated complications and abnormal fetal growth patterns in unadjusted analyses. However, migraine worsening was not independently associated with abnormal fetal growth after adjustment for maternal and obstetric factors, suggesting that migraine symptom progression may represent a clinical marker of shared vascular, inflammatory, endothelial, and metabolic processes rather than an independent causal factor. Further prospective multicenter studies incorporating non-migraine control groups and detailed migraine phenotyping are warranted. Full article

The development of next-generation organotypic platforms and disease models has proven crucial for the progress toward personalized therapeutic solutions in cancer. Fetal bovine serum (FBS) is a nutrient-rich cell culture supplement that contains essential factors for cell growth. However, in addition to ethical and environmental concerns, the manufacturing of tumor models requires a more standardized and controlled environment. This has led to the commercialization of several alternatives for the substitution of FBS, in the form of both animal-based and synthetic products. We here test the use of two alternatives for the culture of glioblastoma cells in the fabrication of organotypic tumor models, in combination with an insightful review of the existing literature, which allows for the elucidation of the most relevant challenges and potential solutions. We assess metabolic activity and cell proliferation in both 2D and 3D culture systems to determine the influence of serum on cell attachment and growth. The 3D culture systems are fabricated by photopolymerization of gelatin methacrylamide to achieve hydrogels that closely mimic the native tissue’s extracellular environment. We aim to advance our understanding of the role of culture media in these models and provide practical guidance to optimize experimental design and enhance reproducibility, thereby facilitating their broader adoption by the research community. These studies are key for the biofabrication of next-generation organoids and other advanced in vitro tumor models. Full article