India, a country with the second largest population in the world, does not have a national newborn screening programme as part of its health policy. With funding support from the Grand Challenges Canada, a pilot newborn screening programme was implemented for the Udupi district of South India to study the need and viability of a national programme in India. Six disorders were selected for the study based on the availability of funding and recommendation from pediatricians in the district. Here, we report the observed incidence during the study. A cost-effectiveness analysis of implementing newborn screening in India was performed. It is evident from our analysis that the financial loss for the nation due to these preventable diseases is much higher than the overall expenditure for screening, diagnosis, and treatment. This cost-effectiveness analysis justifies the need for a national newborn screening programme in India.

The sustainable developmental goals emphasize good health, reduction in preventable neonatal and under-five mortalities, and attaining zero hunger. However, South Asian countries report a higher incidence of neonatal and under-five mortalities when compared to the Western world, many of which are attributed to maternal and perinatal micronutrient deficiencies. Isolated nutrient deficiency in the absence of calorie deficit poses a diagnostic challenge since such deficiencies present with acute multisystemic and enigmatic manifestations. Thiamine (vitamin B1) is a micronutrient of prime importance which exerts indispensable roles in energy metabolism. Deficiency of thiamine can lead to catastrophic consequences. This review provides insight into the biochemical actions of thiamine in energy metabolism, the compromised aerobic metabolism resulting from thiamine deficiency, and the crucial role of thiamine in the proper functioning of the nervous, cardiovascular, and immune systems. The review also explores the acute life-threatening consequences of thiamine deficiencies in neonates and infants and the speculative role of thiamine in other pathologies like encephalopathy, sepsis, and autism spectrum disorders. However, routine assessment of thiamine in pregnant women and neonates is yet to be implemented, due to the lack of affordable and automated diagnostic techniques, and the cost-intensive nature of mass spectrometry-based quantification. Conclusion: Physicians are recommended to have a low threshold for suspecting thiamine deficiency especially in vulnerable populations. Laboratory diagnosis of thiamine deficiency needs to be implemented as a standard of care, especially in endemic regions. Further, public health policies on food fortification, mandatory supplementation, and surveillance are imperative to eliminate thiamine deficiency-induced health hazards. What is Known:• South Asian countries report a higher incidence of neonatal and under-five mortalities, many of which are attributed to maternal and perinatal micronutrient deficiencies.• Preventable causes of neonatal/ infantile deaths include birth factors (low birth weight, birth asphyxia), infectious diseases (pneumonia, diarrhoea, tetanus, tuberculosis, measles, diphtheria, malaria, acute infections), deficiency diseases and genetic diseases (vitamin & mineral deficiencies, IEMs, congenital heart disease, unexplained PPHN, SIDS etc). What is New:• Acute thiamine deficiency presenting as multisystemic syndromes, has unfortunately been a long standing unresolved public health concern. However, accessible surveillance and diagnostic strategies remain elusive in most clinical settings.• Despite decades of reports and emerging guidelines, diagnosis of thiamine deficiency is often missed and policy mandates at national level are yet to be implemented even in endemic countries.• This review provides a comprehensive summary of the biochemical role of thiamine, its key functions and effects on major organ systems, the diagnostic gap, the enigmatic presentation of acute thiamine deficiency, the plausible role of thiamine in other pathologies and the preventive measures at individual and community level.

Background/Objectives: Fatty acids, the building blocks of lipids, contribute to numerous crucial life processes and are implicated in numerous disease pathologies. Circulating fatty acids can be extracted/trans-esterified to their respective methyl ester forms and quantified from a variety of biological samples. This study aims to identify quantifiable fatty acids (through alkali trans-esterification) in human circulation, assess the correlation of the detectable fatty acid methyl esters (FAMEs) compounds between whole blood, serum and plasma matrices and propose the most ideal matrix for quantification of FAMEs. Methods: This anonymised study was carried out in a tertiary hospital after obtaining ethical approval and involved analysis of residual fasting whole blood, serum and plasma samples obtained from 20 apparently healthy subjects attending the routine health check services at the study centre. Fatty acids were converted to its methyl ester form by methanolic KOH trans-esterification and subjected to GCMS analysis. Paired t test, Pearsons’s correlation, linear regression and Bland Altman test were employed to assess the agreeability between matrices. Results: 9 out of 37 FAME compounds were detected in all three matrices. Strong correlations and statistically significant regression equations were obtained for the 9 compounds between plasma and serum matrices. Undecanoate, pentadecanoate, linolenate, and palmitate levels were lowest in plasma, while stearate, heptadecanoate levels were highest in whole blood. Myristate was highest in serum, dodecanoate was highest in plasma while docosahexanoate was found to be comparable in all three matrices. Methyl ester forms of dodeconate, myristate, pentadecanoate, palmitate, heptadecanoate, stearate, and linolenate were observed in higher concentrations in plasma when compared to serum. Conclusions: The current study shows similar & correlating FAME concentrations between serum and plasma matrix; however, whole blood FAME concentrations appear significantly different. Plasma serves as the most ideal matrix for detection and quantification of circulating fatty acids.

Background: The disruption of metabolic pathways in patients with community-acquired pneumonia (CAP) may provide insights into disease progression. We aim to identify early disruption in the serum metabolome of CAP patients using untargeted metabolic approaches. Methods: We conducted a single-centre, prospective case-control study involving 105 participants (70 with CAP and 35 healthy controls), between January 2025 and November 2025. We also performed a subgroup exploratory metabolomic analysis among the 70 CAP patients, comparing 60 patients with severe CAP requiring ICU admission with the 10 non-severe CAP patients who did not require ICU admission. Untargeted serum metabolomics was performed using gas chromatography-mass spectrometry (GC-MS) to investigate metabolic dysregulation in patients with CAP. The analysis of the clinical data was performed using SPSS version 25.0. The data of metabolomics was analyzed using MetaboAnalyst version 6.0. After the preprocessing, log ₁₀ transformation, normalization and scaling, 93 GC-MS metabolites were retained from the initial 300 metabolites. Principal component analysis was done for unsupervised clustering, which was then followed by OPLS-DA for supervised group discrimination. Model performance was assessed using R²Y and cross-validation-derived Q² values, and model robustness and overfitting exclusion was further evaluated using permutation testing. Discriminatory metabolites were identified using VIP scores, fold change, log₂ fold change and univariate testing with false discovery rate correction where applicable. ROC analysis, heatmap-based clustering and pathway enrichment analysis were performed. Results: The variable importance in projection (VIP) scores showed that out of 93 untargeted metabolites studied using GC-MS, the greatest differences between the CAP patients and healthy controls were about malic acid (VIP:3.374, fold change 2.591), 4-hydroxybenzeneacetic acid (VIP:2.459, fold change 27.97), 2-hydroxybutyric acid (VIP:2.059, fold change 4.779), and 4-hydroxyphenyllactic acid (VIP:1.882, fold change 20.67). Key disrupted pathways in CAP patients included propanoate, glyoxylate, and dicarboxylate; tricarboxylic acid cycle; nitrogen; tyrosine, cysteine, and methionine; and amino acid pathways. Comparison between the severe CAP patients (ICU admission required) and non-severe CAP patients (no-ICU admission), VIP analysis identified boric acid, ethylene glycol, ethanimidic acid, linoleic acid, oleic acid, cholesterol, 3-hydroxybutyrate, and α-tocopherol as the principal discriminating metabolites, while pathway analysis revealed perturbations in glutathione metabolism, amino acid metabolism, the tricarboxylic acid cycle, pyruvate metabolism, and arachidonic acid metabolism. Conclusions: CAP patients demonstrated early disruptions of key metabolic pathways compared with healthy controls, spanning energy metabolism, amino acid pathways, redox balance, lipid inflammatory signalling, and gut–host metabolic axes. These findings highlight the potential utility of metabolomic profiling as an adjunctive clinical tool for early risk stratification and biochemical phenotyping in CAP. Trial registration: Clinical trials Registry of India (CTRI 2024/12/078631) registration was done 27.12.2024.