Search Results (7,932)

Background/Objectives: Maternal diet during pregnancy may influence neonatal outcomes, but dietary behaviours are socially patterned and were measured differently across cohorts. We therefore evaluated whether cohort-specific, partially harmonized maternal dietary patterns were associated with adverse birth outcomes after accounting for maternal and socioeconomic characteristics in two Italian birth cohorts. Methods: We analyzed 3234 mother–infant dyads from Piccolipiù (2011–2015) and 1564 from MAMI-MED (2020–ongoing). Maternal diet was captured by cohort-specific food questionnaires and grouped into food categories. Principal component analysis identified dietary patterns; pattern scores were categorized into tertiles and combined into five joint-adherence profiles. Logistic regression estimated odds ratios (OR) for preterm birth (PTB, <37 weeks), low birth weight (LBW, ≤2500 g), macrosomia (≥4000 g), and small/large for gestational age (SGA/LGA), with progressive adjustment for maternal age, pre-pregnancy body mass index (BMI), education, employment, and (Piccolipiù) income. Results: Two comparable patterns emerged in both cohorts: Western (processed foods, fried items, snacks/sweets, sugar-sweetened beverages) and Prudent (fruit, vegetables, fish, whole grains/yogurt). Western adherence was more common among younger women and those with disadvantage, whereas Prudent adherence tracked higher education, employment and income. After full adjustment, dietary profiles were not consistently associated with PTB, SGA or LGA in either cohort. In Piccolipiù, preferential Prudent adherence was associated with lower odds of LBW (OR 0.49; 95% CI 0.24–0.92) and higher odds of macrosomia (OR 1.56; 95% CI 1.06–2.30). Across cohorts, higher pre-pregnancy BMI predicted macrosomia/LGA, while lower education increased the probability of PTB and LBW. Conclusions: Across two Italian birth cohorts, maternal dietary patterns were socially stratified, whereas pre-pregnancy BMI and maternal education were more consistently associated with birth outcomes than dietary-pattern adherence per se. Full article

Interest in the genomic sequencing of healthy newborns has raised a discussion on whether this technology should be introduced into existing newborn screening (NBS) programs. This qualitative study explores a multi-stakeholder perspective on the future of genomic sequencing in NBS. Semi-structured interviews were conducted with 26 professionals involved in NBS or in clinical genome sequencing in the Netherlands. Participants highlighted opportunities such as the possibility to use one test for a wide range of genetic conditions, reducing diagnostic odyssey, expanding the scope of NBS, and increasing program efficiency. Challenges were raised regarding genetic variant interpretation, expected increased parental anxiety, data privacy issues, difficulties with information provision, and high costs. Three areas of tension between participants’ perspectives were identified: screening strategy, screening performance, and roles and responsibilities. It was emphasized that implementing genomic sequencing should not risk reducing the current high NBS participation, and that enhancing knowledge, communication, and collaboration between all stakeholders is needed. Although most participants did not believe genomic sequencing as a first-tier test is currently desirable and feasible, they acknowledged it has a role to play in the future of NBS. Future decision-making should consider the potential impact on the participation rate, program quality, and balancing benefits and harms. Full article

Hyperekplexia is a neurologic disorder of marked perinatal significance. Affected neonates display generalized hypertonia and exaggerated startle reflex in response to innocuous stimuli, potentially leading to life-threatening apneic episodes. Although symptom severity typically diminishes during the first year of life, affected individuals often continue to exhibit disabling motor dysfunction and frequent unprotected falls throughout adulthood. Currently, no targeted therapeutic interventions are available. The pathophysiology involves partial or complete disruption of inhibitory glycinergic neurotransmission. Mutations in the gene encoding the neuronal glycine transporter GlyT2 (SLC6A5) represent the second-most frequent genetic etiology of human hyperekplexia. To investigate the mechanistic basis for the heightened severity of symptoms during the perinatal period, we examined the role of GlyT2 in neuronal differentiation using the PC12 cell model. Pharmacological induction of differentiation demonstrated that clones stably expressing GFP-GlyT2 exhibit increased expression of neuronal differentiation markers and enhanced neurite outgrowth—both in number and length—relative to parental PC12 cells. These clones also displayed elevated cytosolic calcium levels, which were attenuated by calmodulin overexpression, subsequently downregulating differentiation marker expression. We hereby proved that GlyT2 is clearly implicated in growth cone progression and differentiation of PC12 cells into neurons by increasing internal calcium and binding to growth cone proteins. Finally, our results were validated in primary neurons. Full article

Background: Despite well-established racial/ethnic disparities in cancer outcomes, little is known about the extent to which race/ethnicity influences adverse pregnancy outcomes (APOs) among women with early onset cancer. We evaluated racial/ethnic disparity in the occurrence of cancer during pregnancy and APOs among women with cancer in the United States. Methods: Data consisted of 17.6 million singleton deliveries among females aged 18–49 years from the National Inpatient Sample. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Results: From 2000 to 2022, the prevalence of births among women with cancer increased more than 225%, from 120.4 to 391.8 per 100,000. After accounting for sociodemographic and behavioral/lifestyle factors and comorbidity index among women with cancer (n = 49,824, mean age = 33.4 years), non-Hispanic Black women had the highest odds for hypertensive disorders of pregnancy (OR = 1.67, CI: 1.54–1.82), preterm birth (OR = 1.44, CI: 1.26–1.64) and fetal death (OR = 3.04, CI: 1.99–4.63). Asian or Pacific Islander and Native American women had the highest odds for gestational diabetes (OR = 2.48, CI: 2.17–2.85) and fetal growth restriction (OR = 1.92, CI: 1.00–3.69), respectively. Among racial/ethnic minority women, the odds for maternal mortality and several APOs were significantly higher among those with cancer than those without cancer, with the odds for APOs being highest for breast cancer (OR = 1.39, CI: 1.23–1.56). Conclusions: This large population-based study showed significant racial and ethnic disparities in APOs among women with a concurrent cancer diagnosis at delivery. Targeted management of APO risk factors during pregnancy among racial/ethnic minority populations with cancer may help reduce adverse maternal and neonatal outcomes. Full article

Background and Objectives. Mother-to-child transmission (MTCT) or vertical transmission of human immunodeficiency virus (HIV) is largely preventable in settings where prevention of MTCT (PVT) strategies are consistently implemented. Romania represents a particular epidemiological context, as individuals from the historical pediatric HIV cohort have now reached reproductive age. This study assessed current PVT outcomes in northeastern Romania and explored the remaining circumstances in which transmission still occurs. Materials and Methods. We performed a retrospective observational analysis at the Regional HIV/AIDS Center of Iași (“Sfânta Parascheva” Clinical Hospital of Infectious Diseases), including all pregnant women living with HIV and their HIV-exposed infants followed between 2023 and 2025. Maternal data comprised age, place of residence, origin from the Romanian pediatric cohort, antiretroviral therapy (ART) adherence, and HIV RNA viral load in the third trimester. Obstetric characteristics, delivery mode, neonatal antiretroviral prophylaxis, and infant HIV RNA PCR results during follow-up up to 18–24 months were also evaluated. Results. A total of 61 HIV-positive pregnant women and 53 HIV-exposed infants were included. Viral suppression during pregnancy was documented in 59 women (96.7%), while two cases of detectable viremia in late pregnancy were linked to poor ART adherence. All women delivered by elective cesarean section, and all infants received neonatal antiretroviral prophylaxis, with Raltegravir added in selected higher-risk situations. Overall, MTCT was 3.8% (2/53). No transmission events were recorded in 2023 or 2024; both cases occurred in 2025 (15.4% of infants born that year) and exclusively in the context of maternal viremia. Women originating from the historical pediatric HIV cohort accounted for 31.1% (19/61) of pregnancies, and no transmission was observed among their infants. Conclusions. In northeastern Romania, PVT programs remain highly effective when maternal viral suppression is achieved. Residual transmission was confined to situations of maternal viremia driven by ART non-adherence, highlighting the continued importance of adherence support during pregnancy. Full article

Objective: To evaluate the diagnostic performance of an in-house-developed IgG Western blot (WB) for congenital toxoplasmosis and its complementary role with other serological markers. Methodology: For this purpose, the study utilized 42 mother–child pairs, evaluating the WB in comparison with a Composite Reference Standard (CRS). Cohen’s Kappa coefficient measured agreement, while McNemar’s test compared WB with Combined Serology (neonatal IgG titers higher than the mother’s (IgG↑), IgM, IgA). Results: The WB demonstrated a sensitivity of 75.0% and a specificity of 100.0%. Kappa indicated substantial agreement with the CRS (κ = 0.67; 95% CI: 0.44–0.89). McNemar’s test found no statistically significant difference between WB and Combined Serology (p = 0.7516). Crucially, WB detected 4 unique cases missed by Combined Serology, and Combined Serology detected 6 cases missed by WB. This complementarity increased the overall diagnostic rate from 82.14% to 96.43%. Conclusions: IgG-WB is a crucial complementary diagnostic tool, especially for asymptomatic newborns. Its integration significantly improves diagnostic certainty, allowing for more timely treatment for congenital toxoplasmosis. Full article

Van Maldergem Syndrome (VMS) is a rare autosomal recessive disorder caused by pathogenic variants in the atypical cadherin genes DCHS1 or FAT4 and is marked by craniofacial, skeletal, and neurodevelopmental abnormalities. Although DCHS1–FAT4 binding is mediated by their respective extracellular domains, the in vivo function of the DCHS1 intracellular domain (ICD) is poorly defined. To test its function, we generated mice in which the DCHS1 ICD was deleted and replaced with a V5 epitope tag (Dchs1^ΔICD-V5). Homozygous Dchs1^{ΔICD-V5/ΔICD-V5} mice are viable but exhibit VMS-like craniofacial flattening with enlarged fontanelles and reduced palatine/maxillary structures, along with airway cartilage abnormalities including reduced mineralization and decreased tracheal circularity. In periventricular regions, wild-type DCHS1 expression shows polarized localization, whereas mice with the ICD deletion exhibit altered cell polarization within the subventricular zone, concomitant with changes in neural cellular distribution. Neonatal brains display reduced pYAP1: YAP1 ratios and increased Ki67+ proliferation with greater Ki67–neuronal co-localization within the periventricular zone. Together, these data identify the DCHS1 ICD as a critical effector for DCHS1 signaling and a regulator of polarity-dependent growth, with associated changes in Hippo pathway activity during craniofacial and neural morphogenesis. Additionally, our data establish Dchs1^{ΔICD-V5/ΔICD-V5} mice as a model that recapitulates core features of VMS, thereby allowing new mechanistic discoveries into its pathogenesis. Full article

The reciprocal relationship between genes and nutrients, known as nutrigenetics and nutrigenomics, has been established in many studies. However, current investigations of maternal and neonatal nutrition using a precision nutrition approach focused on genomics are limited, especially in the Middle East and North Africa (MENA) region. This review aims to summarize the impacts of the dietary micronutrients, folic acid, thiamine, and cobalamin on optimal health outcomes during pregnancy, fetal development, lactation, and infant growth. In this review, the roles of folic acid, thiamine, and cobalamin are discussed in the context of various aspects of pregnancy, such as preconception, fetal development, and lactation, highlighting how genetic events occurring during developmental periods can have consequential impacts on health outcomes later in life. Deficiency rates and related health consequences as well as the prevalence of genetic mutations related to these nutrients of interest in the MENA region are also elaborated on. How to advance knowledge and applications of precision nutrition, how genes interact with the neurochemical changes during pregnancy, and how this interaction impacts maternal eating behaviors, and consequently fetal development and infant and child growth and health, should be further explored in future studies. This includes taking advantage of cutting-edge technologies and the role of artificial intelligence in this endeavor. Full article

Objective: To evaluate the diagnostic and prognostic utility of the hemoglobin–albumin–lymphocyte–platelet (HALP) score and several systemic inflammatory indices derived from routine blood parameters—including the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), pan-immune inflammation value (PIV), and systemic inflammatory response index (SIRI)—for pathogen differentiation and clinical assessment in culture-proven late-onset neonatal sepsis (LOS). Methods: A retrospective analysis was conducted on a cohort of 150 neonates with culture-proven LOS. Systemic inflammatory indices were calculated at baseline (first week of life) and at the time of septic insult. The discriminative power of these indices was assessed via ROC curve analysis, with optimal cut-off points determined by the Youden Index. Risk stratification was performed using Odds Ratio (OR) modeling with 95% Confidence Intervals (CIs) to evaluate the predictive strength of each marker according to its respective threshold. Results: Diagnosis-phase assessments identified SII as the premier discriminator for microbiological etiology (AUC = 0.869; OR = 44.57), outperforming PLR and PIV. Although HALP demonstrated moderate efficacy in distinguishing pathogens, it lacked prognostic value regarding mortality. Conversely, SIRI displayed limited clinical utility, yielding the lowest predictive performance in our cohort. Conclusions: In neonatal sepsis, the HALP score provided additional clinical information when compared with several hematological inflammatory indices. Although HALP was not associated with mortality, prospective multicenter studies are needed to clarify the role of these cost-effective markers in pathogen differentiation and clinical assessment of LOS. Full article

Maternal nutrition during pregnancy plays a crucial role in fetal development and metabolic programming. Long-chain omega-3 polyunsaturated fatty acids (LC-PUFA n-3), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to influence mitochondrial function and cellular energy metabolism. The present preliminary study aimed to evaluate the effects of maternal omega-3 supplementation on mitochondrial bioenergetics in neonatal piglets. Pregnant sows were supplemented with either fish oil or algal oil rich in LC-PUFA n-3 (long-chain omega-3 polyunsaturated fatty acids) throughout gestation. Liver samples were collected from newborn piglets immediately after birth, and mitochondrial respiratory parameters, oxygen consumption rates, and selected oxidative stress markers were analyzed. The results indicated that maternal omega-3 supplementation was associated with improved mitochondrial respiratory parameters and enhanced oxidative phosphorylation efficiency in neonatal liver tissue. Both fish oil and algal oil supplementation showed similar trends in improving mitochondrial bioenergetic function. Although the study was exploratory and conducted on a limited number of animals, the findings suggest that maternal intake of LC-PUFA n-3 may influence mitochondrial metabolism in offspring. Further studies with larger experimental groups are required to confirm these observations and to better understand the mechanisms underlying these effects. Full article

Maternal Smoking During Pregnancy (MSDP) remains a major source of fetal toxicant exposure. We applied adductomics to profile reactive adducts at the human serum albumin cysteine-34 (HSA-Cys³⁴) locus, which integrates longer-term exposures. HSA-Cys³⁴ adducts formed by acrylonitrile and ethylene oxide, two tobacco-related toxicants previously linked to smoking in adults, were quantified and compared with cotinine and MSDP status. Their relationships with other reactive adducts were also examined. Neonatal dried blood spots (DBS) from 110 children were analyzed. Cotinine and 55 Cys³⁴ adducts were measured by Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS). Associations were evaluated using linear regression, chi-square tests, and principal component analysis. Eighteen adducts differed significantly by MSDP status after Bonferroni correction (p ≤ 9.1 × 10⁻⁴). S-acrylonitrile was markedly elevated in exposed newborns, including those whose mothers reported smoking cessation after early pregnancy (p < 0.001). S-acrylonitrile correlated with 31 adducts related to oxidative stress and thiol metabolism, whereas cotinine correlated with eight. S-ethylene oxide, though detectable in DBS, showed no consistent association with MSDP. Adductomics analysis of newborn DBS sensitively captures molecular signatures of prenatal tobacco exposure and related oxidative stress. Acrylonitrile adducts appear to better reflect cumulative MSDP exposure than cotinine, highlighting the utility of adductomics for improved exposure assessment and mechanistic insight. Full article

Objectives: Gestational diabetes is linked to increased inflammatory and metabolic stress during the neonatal period. Among the biomarkers elucidating the relationship between diabetes and inflammation, the interleukin-33 (IL-33)/ST2 signaling pathway is of particular interest. Research on the IL-33/sST2 axis in pregnancies complicated by diabetes indicates that these biomarkers are associated with maternal metabolic disorders and inflammation. Therefore, evaluating sST2 levels in infants of diabetic mothers is essential for identifying a biological marker of systemic inflammation resulting from intrauterine hyperglycemia and for clarifying the specific risks associated with this condition. The objective of this study was to examine sST2 levels in infants born to diabetic mothers and to assess their association with perinatal inflammation, metabolic stress, and clinical outcomes. Methods: This prospective observational study included term infants born at Pamukkale University Medical Faculty Hospital. The study group comprised term infants whose mothers had gestational diabetes, while the control group consisted of term infants born to healthy mothers without diabetes. sST2 levels were measured from serum samples obtained from cord blood at birth using the ELISA method. Factors influencing sST2 levels were analyzed using regression analyses. Results: sST2 levels were significantly higher in the diabetic group than in the control group (p < 0.001). The incidences of large for gestational age (LGA), small for gestational age (SGA), hypoglycemia, postnatal respiratory distress, and both the frequency and duration of neonatal intensive care unit admissions were also significantly elevated in the diabetic group. Multivariate analysis identified gestational diabetes as independent predictor. Conclusions: This study is among the first to demonstrate increased sST2 levels at birth in infants of diabetic mothers. The results indicate that intrauterine exposure to hyperglycemia due to gestational diabetes may be associated with heightened inflammation and metabolic stress in the neonatal period, and that sST2 may serve as a potential biomarker reflecting fetal exposure. Full article

Reducing measurement uncertainty is crucial to enable the adoption of rapid point-of-use techniques for clinical and industrial applications. Diagnosis of neonatal respiratory distress syndrome and liposome formulation quality control are two applications for which measuring the ratio of the lecithin to sphingomyelin composition of liposomes is important, for which no rapid measurement currently exists. Raman and infrared spectroscopies are two complementary approaches to examine characteristic molecular vibrations that can spectroscopically measure liposomes and, when combined with machine learning, predict their composition. We show that employing a data-fusion approach the uncertainty in the predicted compositions compared to the individual modalities (IR R²: 0.902 and Raman R²: 0.951) can be reduced to obtain more accurate and precise measurements (low-level fused model R²: 0.973, mean squared error: 0.024, prediction interval width: 0.303, high-level weighted fusion model R²: 0.970, mean squared error: 0.027, prediction interval width: 0.268). Full article

Background/Objectives: The neonatal Fc receptor (FcRn) plays a crucial role in extending the systemic half-life of monoclonal antibodies (mAbs), but its influence on ocular distribution remains incompletely understood. This study investigated the impact of FcRn on the ocular disposition of mAbs following systemic administration in rabbits. Methods: New Zealand White rabbits received a single intravenous dose (1 mg/kg) of either wild-type trastuzumab (TS-WT) or its FcRn non-binding variant (IHH). Plasma and ocular tissues (retina, iris–ciliary body, vitreous humor, aqueous humor, cornea, conjunctiva, and tears) were collected at terminal time points up to 336 h for TS-WT and 168 h for IHH. Antibody concentrations were quantified using a validated sandwich ELISA. Pharmacokinetic parameters and antibody biodistribution coefficients (ABC) were calculated to assess the FcRn-mediated effects on ocular distribution. Results: TS-WT demonstrated 2-fold higher systemic exposure compared to IHH. The iris–ciliary body exhibited the highest absolute exposure for both antibodies, with TS-WT showing significantly higher accumulation (ABC_0–168h: 14.95% vs. 8.89%). Retinal distribution remained comparable between antibodies (5.96% vs. 5.51%). Both antibodies were detectable in tears, with ABC value of ~4% reported for TS-WT. TS-WT also demonstrated markedly increased distribution in vitreous humor and tear fluid (3.5- and 5.5-fold higher ABC values, respectively) compared to IHH. The cornea (5.76% vs. 5.57%) and conjunctiva (7.71% vs. 7.21%) showed comparable relative distribution between TS-WT and IHH, while aqueous humor showed minimal differences (0.44% vs. 0.52%). Conclusions: This investigation reveals distinct tissue-specific patterns of FcRn-mediated mAb distribution within the eye. FcRn binding significantly enhanced antibody distribution in ocular tissues, such as the iris–ciliary body, and tears, with less pronounced effects on the retina, cornea, conjunctiva and aqueous humor. These findings provide mechanistic insights for optimizing mAb-based therapeutics for ocular disease and understanding the ocular toxicity of mAb-based therapeutics, such as antibody–drug conjugates. Full article

Background: Maternal control and the sense of support significantly influence a woman’s experience of birth. This study aimed to adapt and validate the Support and Control in Birth (SCIB) scale in Spanish women to assess maternal perceptions of support and control during birth, and to develop and validate an abbreviated version of the instrument. Methods: A cross-sectional study was conducted with a sample of 302 Spanish women who had given birth within the previous 6 months and were at least 1 week postpartum. Content, construct, and criterion validity, as well as reliability, were analysed using an expert panel, Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), Cronbach’s Alpha Coefficient, and Intraclass Correlation Coefficient (ICC). Criterion validity was assessed using the Generalised Anxiety Disorder Screener (GAD-7) and the Birth Satisfaction Scale–Revised (BSS-R). Results: The KMO test yielded a value of 0.925, and Bartlett’s test of sphericity was significant (p < 0.001). EFA identified three factors (Support, External control, and Internal control) that explained 56.49% of the total variance. CFA showed good model fit for most of the evaluated indices. The SCIB scale correlated negatively with the GAD-7 and positively with the BSS-R (p < 0.001), as well as with several obstetric and neonatal variables (p < 0.05): planned pregnancy, high-risk pregnancy, onset and type of delivery, birth plan, use of epidural analgesia, maternal involvement, postpartum complications, and newborn characteristics. Cronbach’s alpha was 0.951, and the ICC indicated excellent consistency and agreement (0.995; 95% CI: 0.990–0.998). Based on expert panel consensus, a 24-item abbreviated version was developed that exhibited psychometric properties similar to those of the original version and a high correlation with it (r > 0.90). Conclusions: The Support and Control in Birth (SCIB) scale is a valid and reliable instrument for assessing perceptions of support and control during birth in Spanish women. The 24-item abbreviated version is recommended. Full article