Search Results (5,571)

Background: Ankyloglossia is a congenital anomaly characterized by restricted tongue mobility due to a short, thick, or tight lingual frenulum. Methods: This narrative review synthesizes current concepts on etiology, clinical presentation, diagnostic approaches, functional implications, and management for ankyloglossia in newborns. Results: Ankyloglossia can compromise breastfeeding dynamics, manifesting as suboptimal latch, maternal nipple pain, and inefficient milk transfer, and may influence orofacial function if unrecognized. Because anatomical appearance alone does not reliably predict function, evaluation should prioritize structured functional assessments over purely morphological descriptors. Management should be individualized and stepwise, beginning with lactation support and positioning strategies, and progressing to frenotomy when clear functional limitation persists. In appropriately selected cases, timely intervention can improve feeding efficiency and caregiver comfort while minimizing disruptions to early bonding and nutrition. Post-procedure follow-up is important to confirm functional gains and address residual feeding mechanics. Conclusions: A coordinated, multidisciplinary approach aligns diagnosis and treatment with the infant’s functional needs and family goals, promoting safe, effective, and patient-centered care. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that presents particular therapeutic challenges in children. It is characterized by pulmonary vasoconstriction and vascular remodeling, leading to right ventricular strain and eventually right heart failure. Although advances in pharmacotherapy have improved outcomes, treatment options remain limited. This review aims to evaluate the potential role of sotatercept, a novel fusion protein recently approved for adult PAH, and to assess the translatability of adult data to the pediatric population. Methods: A narrative synthesis of preclinical studies and randomized controlled trials was conducted to summarize the current evidence on sotatercept. In addition, pathophysiological, developmental, and therapeutic differences between adult and pediatric PAH were critically examined to assess relevance and applicability to younger patients. Results: Clinical trials in adults (PULSAR, STELLAR, ZENITH, HYPERION) confirm sotatercept’s efficacy on background therapy, with significant reductions in pulmonary vascular resistance, improvements in 6 min walk distance, enhanced right ventricular function, and risk reductions in clinical worsening events. However, extrapolation to pediatric PAH faces challenges including etiological differences (e.g., PAH-CHD predominance, PPHN in infants), age-inappropriate endpoints (e.g., 6MWD infeasible in young children), variable growth-related pharmacokinetics, and compensatory RV physiology delaying overt failure. Safety concerns are manageable in adults but raise pediatric-specific alarms: activin inhibition’s theoretical tumorigenic potential (dual tumor suppressor/promoter role), pubertal/fertility disruption (FSH suppression, gonadal maturation delay), and skeletal growth interference—unproven clinically yet demanding long-term monitoring. The ongoing MOONBEAM trial will provide initial pharmacokinetic/safety data in children. Conclusions: Sotatercept represents a promising, first-in-class therapeutic option for PAH with the potential to transform disease management. Nevertheless, dedicated pediatric studies are crucial to confirm safety, efficacy, and appropriate dosing and to define its role in the long-term treatment of children with PAH. Full article

Background: Severe Alpha-1-Antitrypsin deficiency (AATD), phenotype PiZZ, is a leading cause of liver disease in neonates, children, and adults. Nevertheless, the prevalence of liver disease and mortality within PiZZ adults remains unclear. Between 1972 and 1974, a cohort of 129 individuals with severe AATD (PiZZ) was identified through the Swedish national screening of 200,000 newborns. The cohort has been followed up regularly since birth. This prospective cohort follow-up study, with a cross-sectional comparison at 50 years of age, aims to characterize the natural history of liver disease and mortality in this cohort in their early fifties, compared with an age-matched control group (PiMM) randomly selected from the population registry. Methods: Study participants completed questionnaires regarding occupation, medical history, medication, and alcohol consumption. They underwent physical examination and measurement of liver stiffness using transient elastography (TE, FibroScan^®). Blood samples were obtained for evaluation of liver function, alcohol consumption, calculation of liver fibrosis scores, and detection of viral hepatitis and autoimmune liver disease. Results: Ninety-five PiZZ and 124 PiMM individuals participated in the study, of whom 47 PiZZ and 96 PiMM underwent TE measurement. PiZZ individuals had significantly higher median liver stiffness compared with PiMM individuals (5.9 kPa vs. 4.5 kPa, p < 0.01). No significant differences were found in Fib-4 score or the Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) between the groups. Since identification of the cohort at birth, 13 (10%) of the 129 PiZZ individuals have died. Of these, liver disease was the main or underlying cause of death in 8 individuals (6%). Conclusions: In their early fifties, PiZZ individuals show a small but significant increase in liver stiffness measured by TE, indicating early liver fibrosis. In contrast, conventional fibrosis scores, such as Fib-4 and NFS, do not differ between PiZZ individuals and PiMM, suggesting that serum-based fibrosis scores may underestimate fibrosis in AATD. In this cohort, liver disease and its complications represented the main cause of death in PiZZ individuals by the age of 50, an observation that is uncommon in the general population at this age. 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

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

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

Type 1 diabetes (T1D) is an autoimmune disease with a strong genetic component (~70% heritability). Early identification of individuals at risk is crucial for early intervention or risk assessment. Although polygenic risk scores (PRS) have shown promise in risk assessment, most current approaches remain constrained by linear assumptions and limited generalizability. We aimed to develop a neural network-driven classifier using T1D-associated single nucleotide polymorphisms (SNPs). In addition, we explored the inclusion of an entropy-derived feature as a complementary variable, representing the degree of genetic variability within an individual’s genotype profile across the 67 T1D-associated SNPs, to evaluate its potential additive contribution to the model performance. We analyzed genotype data from 11,909 individuals in the UK BioBank (546 T1D cases and 11,363 controls). Sixty-seven well-known SNPs associated with T1D were utilized as inputs to the model, using two distinct allele-encoding strategies. A feed-forward neural network was evaluated under varying case–control ratios through five-fold cross-validation. Performance was assessed using the area under the receiver operating characteristic curve (AUC) on a held-out test set and on an external European cohort as a validation cohort. Across five-fold cross-validation, the best configuration achieved a median AUC of 0.903. On the held-out UK Biobank test set, the model generalized well, with an AUC of 0.8889 (95% CI: 0.8516–0.9262). A probability-based risk framework, constructed using five risk groups (“very low”, “low”, “intermediate”, “high”, and “very high” risk), yielded a negative predictive value (NPV) of 98.9% for the “very low” risk group and a Positive Predicted Value (PPV) of 61.9% with a specificity of 97.3% for the “very high” risk group, assuming a 10% T1D prevalence. External validation in the German Diabetes Study reproduced clear case–control separation; for individuals with recent onset diabetes and glutamic acid decarboxylase antibodies (GADA+) vs. controls, specificity reached 91.9% in the “high” risk group (PPV of 94.3%) and 97.6% in the “very high” risk group (PPV of 95.7%). The proposed neural network reliably predicts T1D genetic risk using a compact SNP panel of 67 SNPs and maintains accuracy in both internal and external European cohorts. Its probabilistic output enables clinically interpretable risk thresholds, while entropy features contributed modestly to performance. These results demonstrate that a neural network-based approach achieves discriminative performance that is comparable to established T1D genetic risk models, while offering flexible probability-based risk stratification and architectural extensibility for future integration of additional features. 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

Respiratory Syncytial Virus infection is a significant cause of morbidity and mortality in infants. Maternal vaccination with the bivalent vaccine Abrysvo^® in the third trimester (24–36 weeks) is an effective strategy to prevent severe respiratory illnesses in newborns. However, the introduction of this new technology faces structural obstacles that amplify inequalities. This rapid literature review sought to map and synthesize evidence on inequalities and inequities in adherence and accessibility to maternal vaccination among Black pregnant women. A rapid literature review was conducted using a mixed-methods approach (narrative synthesis and thematic analysis), following guidelines adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Handbook. The research question was structured using the acronym Population/Problem, Exposure, Comparison, and Outcome, focusing on Black pregnant women, maternal vaccination, comparison with other groups, and barriers/determinants. The search was conducted in databases such as PubMed (via Medical Literature Analysis and Retrieval System Online), Scopus and Literatura Latino-Americana e do Caribe em Ciências da Saúde, covering studies published between 2022 and 2025 that presented disaggregated analysis by race. The analysis and interpretation of the findings were guided by Critical Race Theory. The analysis of the twelve included studies (mainly from the United States, the United Kingdom, and Brazil) revealed systematic and robust disparities. Black pregnant women had lower vaccination coverage and were less likely to receive timely recommendations compared to White pregnant women. The barriers identified include: institutional distrust (resulting from structural racism), poor access to prenatal care, inadequate communication, and socioeconomic factors. Inequities are structural and multifactorial phenomena. To ensure that the benefits of the vaccine are distributed equitably, strategies such as anti-racist training for healthcare teams, active vaccination outreach, and continuous monitoring of data disaggregated by race are essential. Full article

Pyridoxine-dependent epilepsy due to ALDH7A1 deficiency (PDE-ALDH7A1) is a rare but treatable epileptic encephalopathy caused by disruption of lysine catabolism and secondary depletion of pyridoxal-5′-phosphate (PLP). Although seizures are often controlled with pyridoxine supplementation, many patients continue to experience neurodevelopmental impairment, underscoring the importance of early diagnosis and improved therapeutic strategies. Central to both diagnosis and pathophysiology is the accumulation of lysine-derived metabolites, most notably α-aminoadipate semialdehyde (α-AASA), its cyclic Schiff base Δ¹-piperideine-6-carboxylate (P6C), and pipecolic acid. These metabolites have become the biochemical hallmarks of PDE-ALDH7A1, linking ALDH7A1 pathogenic variants to PLP inactivation and neuronal dysfunction. However, their chemical instability and analytical requirements pose challenges for universal diagnostics and newborn screening. This review summarizes current understanding of lysine catabolism in health and disease, critically evaluates the diagnostic utility and limitations of classical biomarkers, and discusses emerging insights into their pathophysiological roles. We further highlight recent discoveries of novel, chemically stable biomarkers, including 6-oxopiperidine-2-carboxylic acid (6-oxo-PIP), 2-oxopropylpiperidine-2-carboxylic acid (2-OPP), and 6-hydroxy-2-aminocaproic acid (HACA), identified through advanced metabolomics approaches. These metabolites show promise for newborn screening and provide new mechanistic links between metabolic stress, seizure susceptibility, and ongoing neurological morbidity despite pyridoxine treatment. Collectively, advances in biomarker discovery are reshaping diagnostic strategies for PDE-ALDH7A1 and offering new perspectives on disease mechanisms, paving the way for earlier detection and the development of more effective, mechanism-based therapies. Full article

To comprehend the current state and future of newborn screening (NBS), it is essential to understand its history. Over the past six decades, this well-established and exemplary population-based screening program has been guided by screening principles dating back more than half a century. Advances in laboratory and point-of-care testing, diagnostic methods, and a surge of available treatments and even cures have made it challenging to balance screening criteria that have not kept pace with the current landscape. The availability to screen as well as the demand from parents and stakeholders to screen for more and increasingly complex conditions while limiting the retention of NBS specimens and genetic material has been both exciting and challenging. This paper shares the history of NBS in the United States, followed by the development and integration of genomic sequencing as a complement to current practice. It explores evidence supporting the concomitant use of biomarker- and DNA-sequencing-based approaches for NBS, how disorders are selected for inclusion, and available treatments, and offers recommendations regarding what to consider and how to proceed in this ever-changing NBS landscape. Full article

Background: Glutaric aciduria type-1 (GA-1) is a genetic disorder caused by glutaryl-coenzyme A dehydrogenase deficiency, leading to the accumulation of glutaryl-CoA and its derivatives. Clinical manifestations include neurological abnormalities; however, the underlying pathological mechanisms remain unclear. Early diagnosis and intervention are crucial for minimizing adverse outcomes. To date, diagnostic methods have certain limitations, and there is a critical need for a sensitive biomarker for diagnosis. We aimed to characterize metabolic dysregulation and identify candidate biomarkers associated with GA-1 in biochemically confirmed patients compared to age- and sex-matched control subjects. Methodology: Untargeted metabolomics profiling of GA-1 patients (n = 29) was compared to matched control subjects by age and sex. Multivariate and univariate statistical analyses were performed to identify dysregulated metabolites. Results: Our findings revealed 220 endogenous human metabolites. Notably, there was a strong enrichment in carboxylic acids and derivatives, including amino acids and derivatives, hydroxy and keto acids, fatty acyls, sphingolipids, phosphatidylcholines, and nucleotides and nucleosides. Pathway analysis indicates alterations in the biosynthesis of cardiolipin and phosphatidylcholine, as well as in pyrimidine metabolism, the urea cycle, and amino sugar metabolism. We demonstrated a robust performance model for 6-Methylnonanoyl-CoA, displaying strong discriminative power. Conclusions: We identified broad dysregulation across various biochemical classes, reflecting an imbalance in energy metabolism that involves carbohydrate and lipid pathways. The results also highlight dysregulation in sphingolipids, phospholipids, and nucleotide metabolism. These findings are preliminary and the clinical relevance of these findings in patients with GA-1 requires further investigation. We identified candidate biomarkers capable of distinguishing GA-1 patients from controls; however, these findings require validation in independent cohorts. Full article

Background: Adverse newborn outcomes in patients with severe maternal morbidity (SMM) are understudied, and this study examines their association with insurance type (Medicaid vs. commercial) in patients who experienced SMM. The aim of this study is to examine disparities in preterm birth, low birthweight, and neonatal intensive care (NICU) admission among Medicaid vs. commercially insured patients with severe maternal morbidity in Maryland. Methods: This cross-sectional study analyzed data from 588 SMM patients enrolled in Maryland’s Severe Maternal Morbidity (SMM) Surveillance Program (August 2020–December 2023). We utilized unadjusted and multivariable logistic regression models to evaluate the relationship between primary insurance type and the outcomes of interest: preterm birth (<37 weeks), low birthweight (<2500 g), and neonatal intensive care unit (NICU) admissions. Results: Of 588 patients with SMM, 45.1% had Medicaid. These patients were younger, more often non-Hispanic Black or Hispanic, had higher parity and comorbidity scores, and initiated prenatal care later compared with commercially insured patients. Medicaid patients had 2.2 to 2.6 times higher odds of adverse newborn outcomes after adjusting for other socio-demographic and medical factors. Patients’ comorbidities significantly increased the odds of adverse newborn outcomes, as did all other primary SMM causes other than obstetric hemorrhage. Conclusions: Adverse newborn outcomes were more prevalent among Medicaid than commercially insured patients who experienced SMM. Differences in maternal health status and primary SMM cause partly explain the observed differences in newborn outcomes. Our findings emphasize the need for comprehensive prenatal care and improved healthcare access for women with high-risk pregnancies. Full article