Life-long learning in paediatrics

1. Key insights on autism spectrum disorder from global burden of disease 2021

Source: Global burden of disease study 2021 autism spectrum collaborators. The global epidemiology and health burden of the autism spectrum: Findings from the global burden of disease study 2021. Lancet Psychiatry. 2025 Feb;12(2):111-121. doi: 10.1016/S2215-0366(24)00363-8. Epub 2024 Dec 19. PMID: 39709974; PMCID: PMC11750762.

The latest estimates from the global burden of disease (GBD) 2021 study offer critical updates on the prevalence and health burden of autism spectrum disorder (ASD) worldwide. These findings, driven by significant methodological refinements, provide valuable context for the medical, academic and clinical research communities in India. Notably, the revised approach in GBD 2021 yields a substantially higher global prevalence estimate for ASD compared to previous iterations, primarily by moving away from potentially underestimating passive case finding methods. This underscores the need for robust, active case ascertainment in epidemiological studies, a crucial consideration for research in India. The study also highlights important variations in prevalence by sex and geography, the persistent burden across the lifespan and key limitations in current global data that necessitate focused research efforts, particularly in under-represented regions like India.

The GBD 2021 study estimates that in 2021, approximately one in 127 people globally were autistic. This represents a marked increase from the one in 271 estimated in GBD 2019. This significant shift is primarily attributed to a necessary revision in the GBD methodology, specifically the exclusion of studies relying on passive case finding (such as registry or administrative data), which are now understood to likely underestimate the true prevalence of ASD. This methodological improvement aligns global estimates more closely with those derived from high-quality epidemiological surveys employing active case ascertainment.

It is noteworthy that despite the overall increase in estimated prevalence, the GBD 2021 estimate for the USA remains more conservative than the one in 36 children aged 8 years reported by the US centres for disease control and prevention (CDC) in 2020. The CDC figure, based on a review of clinical and educational records, may potentially overestimate prevalence as it does not involve direct clinical evaluations characteristic of population diagnostic surveys. This highlights the inherent challenges and variations in prevalence estimates depending on the case ascertainment methodology employed.

The GBD 2021 data indicate a higher prevalence and associated health burden for ASD in males compared to females, with a global age-standardised sex ratio of 2.1–1. The exclusion of passive case finding data resulted in a considerable decrease in this estimated sex ratio, aligning with previous meta-analyses showing that registry and administrative data tend to produce higher sex ratios. This finding suggests a potential sex bias in the diagnosis of ASD and emphasises the critical need to evaluate and potentially alter screening procedures and services to ensure equitable identification and support for autistic individuals of all sexes. However, it is important to consider that the estimated sex ratio can be influenced by data availability, with data-rich regions potentially showing higher ratios than those with limited data.

Prevalence estimates varied substantially by geographical region in GBD 2021, ranging from one in 163 people in tropical Latin America to one in 65 people in high-income Asia Pacific. The high prevalence in the latter region is supported by robust, high-quality data from South Korea and Japan. This geographical variation is likely influenced by a complex interplay of factors, including differing exposures to risk factors, cultural variations in behavioural norms, the validity and choice of screening and diagnostic tools and factors related to survey participation and responses.

The analysis did not reveal substantial variation in ASD prevalence over time. Studies that have reported an increase in prevalence have often relied on registries or administrative records. Conversely, studies employing random sampling or consistent active case finding have not shown this trend. This aligns with the hypothesis that while registered diagnoses may have risen, the underlying prevalence of autistic characteristics in the population might have remained relatively stable. Nevertheless, the absence of strong temporal trends in this analysis should be interpreted with caution, given the 15-year time window used for modelling, which may limit the ability to detect more subtle long-term changes.

ASD ranks among the top ten causes of non-fatal health burden for young people (under 20 years), underscoring the critical importance of early detection and developmental support for autistic individuals. While much of the epidemiological research has focused on children and adolescents, the GBD 2021 data indicate that the prevalence and health burden of ASD persist across the lifespan, beginning to decline only from approximately age 60 years. The modelling of adult prevalence was influenced by excess mortality data due to limited direct prevalence data in older age groups. As this mortality data often originates from passive sources, it might potentially overestimate excess mortality and consequently underestimate prevalence in adulthood.

The changing burden of ASD across age highlights the need for tailored mental health services. Early intervention focusing on learning and behavioural support for young children, alongside programs enhancing parental understanding, is crucial. School-aged children and adolescents can benefit from interventions addressing social communication and skills. For autistic adults, services promoting independence, such as life skills and employment training, are important, though further research is needed to identify the full spectrum of effective adult services. A significant global challenge, particularly relevant to settings like India, is the limited timely and sustained access to necessary services for many autistic people and their caregivers, with access often being severely restricted or unavailable in low- and middle-income settings.

Several limitations in the GBD estimation process highlight crucial areas for future research, particularly relevant to the Indian context:

• Geographical data sparsity: The GBD analysis was informed by epidemiological data from a limited number of countries and regions (34 of 204 countries across 12 of 21 GBD regions). While the exclusion of passive case finding improved accuracy, it reduced geographical coverage compared to GBD 2019. There is a strong need for researchers and stakeholders in India to initiate population-representative diagnostic surveys using active case finding methods to accurately estimate prevalence within the country and its diverse regions. Such studies should also investigate the proportion of autistic individuals captured by passive methods to improve the utility of existing administrative data.

• Methodological heterogeneity between studies: Quantifying the precise contribution of true prevalence differences versus methodological variations (e.g., screening/diagnostic tools, thresholds and non-response handling) between studies remains challenging. Further research is needed to refine adjustments for such biases.

• Limitations of disability weights: GBD disability weights, based on lay descriptions, may not fully capture the lived experience and service needs of all autistic people, some of whom may not perceive their diagnosis as a disability. Future disability-weight surveys should involve consultation with autistic individuals to develop more appropriate lay descriptions and weights. The lack of location-specific disability weights is also a limitation.

• Severity estimation: The estimation of severity levels based on intellectual disability proportions lacked granularity by location, age or sex. Future GBD cycles aim to incorporate variations in healthcare access into severity estimations, which would be beneficial for understanding the nuanced burden in settings like India.

• Absence of gender-specific estimates: GBD does not currently estimate prevalence by gender. Given the emerging evidence of greater gender diversity among autistic people, future research is needed to understand the implications for service needs.

Uncaptured comorbidity and mortality burden: GBD’s comorbidity adjustments may underestimate the burden of co-occurring mental and physical health conditions common in autistic individuals. Furthermore, while GBD 2021 did not directly estimate years of life lost for ASD, there is strong evidence of elevated premature mortality risk, particularly from suicide. A separate analysis estimated a significant number of excess suicide deaths among autistic people globally in 2021. Future research and, critically, enhanced clinical efforts in India must focus on preventing and managing comorbidities and reducing the risk of premature mortality in autistic individuals.

The GBD 2021 findings serve as a crucial call to action for the Indian medical, academic and clinical research communities. The updated global prevalence estimate highlights the substantial number of individuals affected by ASD. The significant non-fatal health burden in young people underscores the urgency of early identification and intervention strategies tailored to the Indian context. Furthermore, recognising the persistent burden in adulthood necessitates increased attention to the needs of autistic adults, a population often under-represented in both research and service provision in India.

2. The alarming trajectory of childhood obesity: Averting a future crisis in India and globally

Source: Global burden of disease 2021 adolescent body mass index collaborators. Global, regional and national prevalence of child and adolescent overweight and obesity, 1990–2021, with forecasts to 2050: A forecasting study for the global burden of disease study 2021 . Lancet. 2025 Mar 8 ;405(10481):785-812. doi: 10.1016/S0140-6736(25)00397-6. Epub 2025 Mar 3. PMID: 40049185; PMCID: PMC11920006.

The global burden of childhood and adolescent obesity is rising at an unprecedented rate, posing serious implications for public health systems, economic productivity and intergenerational wellbeing. A recently published global analysis reveals a substantial increase in prevalence over the past three decades, with concerning projections for the future. These data call for urgent, multisectoral and context-specific action, particularly in countries like India facing a dual burden of undernutrition and overnutrition.

Between 1990 and 2021, the global prevalence of obesity among children and adolescents increased by 244%. Projections indicate a further 120.7% increase between 2021 and 2050. If current trends continue, approximately 746 million children and adolescents – nearly one-third of the global population under 20 – will be affected by overweight or obesity by 2050, with 360 million of them classified as having obesity.

Younger populations (ages 5–14 years), particularly boys, are predicted to experience the most rapid increases. The most significant growth is expected in North Africa, the Middle East and Latin America and the Caribbean, where one-third of all children with obesity will reside by mid-century. In some Oceanic countries, childhood obesity prevalence may reach 70% by 2050.

The apparent plateauing of overweight prevalence in certain regions is not indicative of improvement but reflects a shift from overweight to obesity. No region is projected to experience stabilisation or reversal of obesity trends before 2050.

The projected rise in childhood and adolescent obesity carries substantial implications across clinical, societal, economic and environmental domains. Obesity in early life is associated with increased risks of non-communicable diseases, reduced quality of life and premature mortality. It also contributes to the persistence of obesity into adulthood, thus exacerbating long-term health system burdens and economic losses.

Countries with high or rapidly growing obesity prevalence are already witnessing increasing demand for clinical management in adolescents. However, the more urgent priority remains primary prevention, particularly in countries where the transition from overweight to obesity is still underway. The years 2025–2030 represent a critical window for intervention. Failure to act during this period could result in avoidable health emergencies, especially in low- and middle-income countries (LMICs) such as India.

While biological factors such as age and sex account for some variation, the observed rapid rise and regional disparities point to predominantly modifiable drivers. These include systemic changes in transport, food environments, advertising practices, urbanisation and socio-economic inequality. Globalisation and environmental degradation, along with aggressive commercial determinants (e.g., food marketing and pricing strategies), have created obesogenic environments that exceed the capacity of individual behaviour change alone to counteract.

As such, individual-level interventions – though valuable – must be supported by upstream policy actions that target environmental and systemic drivers. Interventions must be adapted to local realities; policy transferability is limited, and country-specific approaches are essential.

The report recommends tailored interventions based on whether a population is currently overweight- or obesity-predominant. The overall public health goal should be to achieve normal weight prevalence, but preventing the transition from overweight to obesity is a feasible and critical intermediate target.

In overweight-predominant populations (e.g., many areas of Asia and sub-Saharan Africa), prevention-focused policies are essential. These may include ‘double-duty’ maternal and child health programs, fiscal tools such as taxation of unhealthy foods and subsidisation of healthy alternatives.

Protecting local food systems, promoting universal nutritious school meals and engaging schools and families in behaviour change programs are key strategies. India, Pakistan and China, due to their large populations, must be prioritised in global prevention efforts.

In obesity-predominant settings (e.g., Oceania, Latin America, parts of North Africa and the Middle East), urgent scale-up of clinical services is required, including intensive lifestyle therapy, pharmacological interventions and, where indicated, bariatric surgery in post-pubertal adolescents. Equity in access to such treatments is a pressing concern in LMICs. In addition, structural policies – urban planning, advertising restrictions food labelling regulations – should be implemented to address root causes. Integrated approaches that address multiple forms of malnutrition and promote food security and environmental sustainability are increasingly necessary.

A particularly critical focus must be on preconception and perinatal interventions aimed at interrupting the intergenerational transmission of adiposity and metabolic disorders. Investment in adolescent nutrition and early-life care has long-term implications for population health trajectories.

The study incorporates data from 180 countries and territories, providing disaggregated estimates by age and sex, allowing for targeted policymaking. However, limitations include reliance on body mass index cutpoints, modelling in data-sparse areas and under-representation of children aged 5–14 years. The projections assume the continuation of current trends and do not account for potential future policy interventions.

The current and projected trajectories of childhood and adolescent obesity necessitate a global, multisectoral response. In countries like India, addressing overweight and obesity must become a priority alongside ongoing efforts to combat undernutrition. Integrated, ‘double-duty’ policies that are cost-effective, scalable and context-sensitive are urgently required. Governments must prioritise investment in surveillance, prevention and – where necessary – clinical care, while also regulating the systemic drivers of the epidemic.

This is a narrow but critical window for intervention. Proactive, evidence-based public health action over the next 5 years can significantly alter the trajectory of childhood obesity and mitigate its long-term health and socioeconomic consequences.

3. Navigating plant-based diets and child growth

Source: Meyer R, Protudjer JL. Plant-based diets and child growth. Curr Opin Clin Nutr Metab Care. 2025 May 1;28(3):274-283. doi: 10.1097/MCO.0000000000001119. Epub 2025 Mar 19. PMID: 40130635.

The global dialogue surrounding sustainable and healthy diets has brought plant-based eating into sharp focus. As medical practitioners, academicians and clinical researchers in India, where vegetarianism has deep cultural roots and varying forms, understanding the implications of these dietary patterns on child growth and nutritional adequacy is paramount. This review, drawing on recent observational studies, offers valuable insights and highlights critical considerations for our unique context. While the data suggest generally comparable growth outcomes, they also underscore potential risks and the indispensable role of informed professional guidance.

This review synthesises findings from 12 observational studies published between 2017 and 2024 examining the impact of vegan and vegetarian diets on child growth compared to omnivorous diets.

• Growth outcomes: The majority of studies (ten out of 12) found no statistically significant difference in most growth parameters between children following plant-based diets (vegetarian and vegan) and those on omnivorous diets. However, a trend towards lower growth parameters, including a higher risk of undernutrition, was observed in children on plant-based diets. Conversely, these diets were also associated with lower rates of overweight. One study specifically noted shorter stature in children on a vegan diet, and another reported significantly lower birth weight and weight at 6 and 12 months in infants born to vegan mothers. It is crucial to note that none of the reviewed studies assessed children who received professional dietary advice.

• Nutrient adequacy concerns: While generally comparable in overall energy intake, plant-based diets may have a lower energy contribution from protein, although often still meeting requirements. Concerns exist regarding protein quality and the bioavailability of certain micronutrients vital for growth and development, such as zinc, iron, Vitamin A, calcium, Vitamin D and Vitamin B12, particularly in poorly planned diets.

  • Micronutrient highlights: Plant-based sources of zinc have lower bioavailability due to phytate content. While iron intake can be comparable or higher in plant-based diets, the non-heme iron found in plants has lower bioavailability than heme iron from animal products. Dietary and supplemental iron intake generally met estimated average requirements across diet groups, but iron supplementation should be considered, especially for children on vegan diets. Vitamin A intake is often comparable or higher in vegetarian and vegan children globally. However, a study among preschool children in India found a higher prevalence of Vitamin A deficiency in vegetarians compared to omnivorous children. This highlights the importance of considering geographical location and local dietary practices when assessing micronutrient status. Calcium intake is equivocal across dietary patterns, and bioavailability from plant sources varies. Vitamin D intake is generally suboptimal across all dietary patterns, necessitating supplementation regardless of diet. Vitamin B12 is a significant concern in predominantly plant-based diets, while intake from food alone is lower, supplementation often leads to higher overall intake in vegans. Deficiency is more prevalent in vegan children compared to omnivores and vegetarians.

• Body composition: Studies indicate that children on vegetarian diets may have a lower percentage of fat mass and a lower ratio of fat to lean mass. Vegan children may have lower fat mass index and certain skinfold measurements compared to omnivores. Plant-based diets have also been associated with a healthier cardiovascular risk profile.

• Clinical implications and guidance: The review emphasises that while most children on well-planned plant-based diets grow adequately, the highlighted risks of undernutrition and micronutrient deficiencies necessitate professional guidance. The lack of studies assessing children who received professional dietary advice underscores a critical gap. Healthcare professionals with expertise in plant-based nutrition are crucial for providing advice on achieving macro and micronutrient adequacy, including supplementation, particularly for Vitamin B12. Regular growth monitoring, especially during vulnerable periods like the first 2 years of life and puberty, is recommended. Dietary assessments, including food diaries and potentially nutritional blood markers, are advisable at key developmental stages.

• Societal recommendations: Most healthcare societies suggest that well-planned plant-based diets can be safe and healthy for children across all age groups, provided they are followed under the supervision of a qualified healthcare professional with expertise in this area. However, universal guidelines on the specific support needed are currently lacking.

• Limitations and future research: A significant limitation is the observational nature of the studies due to ethical considerations around randomisation. Heterogeneity in the types of plant-based diets studied and the ages of the children included also pose challenges. There is a paucity of data on growth and nutrient adequacy in children who have received professional dietary advice. Future research should focus on these areas, particularly in young children (under 2 years) who have high growth velocity.

For Indian medical practitioners and researchers, these findings affirm that while plant-based diets can support healthy growth in children, meticulous planning and monitoring are essential. Given the diversity of plant-based dietary practices across India, understanding regional variations in nutrient intake and potential deficiencies (such as the noted Vitamin A deficiency in some Indian vegetarian children) is vital. We must equip ourselves with the knowledge and tools to provide evidence-based guidance to families choosing plant-based diets for their children. Collaborative research efforts focusing on the growth and nutritional status of children on various forms of plant-based diets in India, especially those receiving professional dietary counselling, are urgently needed to inform local guidelines and optimise child health outcomes.

4. Empowering caregivers – A novel approach to mental health support for families of autistic children

Source: Leadbitter K, Langhorne S, Smallman R, Chu P, Ellis C, Harrison L, Hutton T, Butter C, et al. REACH-ASD Team. Clinical effectiveness of an online psychoeducational and psychotherapeutic programme for caregivers of children newly diagnosed as autistic: A parallel, assessor-masked, randomised controlled trial in the UK (REACH-ASD). Lancet Psychiatry. 2025 Apr;12(4):289-302. doi: 10.1016/S2215-0366(25)00036-7. Epub 2025 Mar 11. PMID: 40086467.

Caregivers of children with autism often experience significant emotional and psychological burdens that can adversely affect their mental health and overall wellbeing. The diagnosis of autism not only transforms the life of the affected child but also profoundly impacts the entire family structure, reshaping daily routines, aspirations and relationships. Despite this, the mental health needs of caregivers have been largely under-addressed in mainstream interventions, particularly in resource-limited settings such as India, where both mental health services and trained personnel remain in short supply. The findings from the Empower-Autism trial offer promising insights into how targeted interventions can mitigate this burden, highlighting the importance of caregiver support in the context of autism.

The trial’s design was rooted in a rigorous evidence review process. Researchers began by systematically reviewing existing literature to evaluate the effectiveness of previous interventions for caregivers of children with autism. The review revealed a gap in evidence, particularly with respect to interventions like Acceptance and Commitment Therapy (ACT), which, while conceptually promising, lacked robust empirical support in this context. Likewise, psychoeducational programs for caregivers, although commonly used, demonstrated preliminary benefits, but the studies often suffered from methodological weaknesses and high risk of bias.

This identified gap in the literature formed the basis for the Empower-Autism intervention. The program combines psychoeducational strategies with the therapeutic framework of ACT, aiming to provide caregivers of newly diagnosed children with autism not only with relevant information but also with emotional and psychological tools to enhance coping, adjustment and overall wellbeing. Notably, the program was delivered entirely online, a strategic decision that addresses the logistical and geographical barriers that many caregivers, particularly in rural or underserved areas, face when seeking in-person support.

The trial yielded promising results, particularly at the 12-month follow-up. Caregivers who participated in the Empower-Autism program reported significant improvements in mental health and overall well-being compared to those who received treatment as usual. These positive outcomes were sustained over the course of 12 weeks, 6 months and 12 months, suggesting that the intervention’s effects were long-lasting. In addition, caregivers who received the intervention reported increased confidence in their understanding of autism, improved adjustment to the diagnosis and enhanced family wellbeing.

However, not all outcomes showed improvement. Parenting stress, self-efficacy, the emotional climate of the home and child-specific outcomes (such as adaptive behaviour or emotional difficulties) did not show significant changes compared to the control group. These results underscore that while caregiver support is crucial, it is not a panacea for all the challenges within the child-caregiver dynamic. The complex nature of caregiving, particularly in the context of autism, means that various factors influence outcomes, and different intervention approaches may be necessary to address different aspects of the caregiving experience.

From a safety perspective, the intervention was well-tolerated, with no significant adverse events reported. The rate of adverse events was similar across both the intervention and control groups, and none of the adverse events were attributed to the intervention itself. Furthermore, the program’s effects appeared consistent across different socioeconomic statuses, baseline mental health conditions of caregivers and the age of the child, suggesting its broad applicability across diverse caregiver demographics.

Nevertheless, the trial was not without limitations. Due to the nature of the intervention, caregivers were not blinded to their group assignment, which may have introduced bias. In addition, the primary outcome measure – mental health – was self-reported, which, while appropriate given the lack of objective tools for non-clinical populations, could have introduced some degree of subjective bias. Secondary outcome measures, which were rated through blinded assessments, either showed no difference or had substantial missing data, largely due to disruptions caused by the COVID-19 pandemic. Furthermore, the trial did not include certain high-need groups, such as caregivers with complex mental health issues, significant sensory impairments or those involved in safeguarding concerns. Therefore, while the results are promising, they do not fully capture the needs of all caregiver populations.

For India, the findings from this trial are particularly relevant. This study represents the first well-powered randomised controlled trial to demonstrate that a psychoeducational and psychotherapeutic intervention can significantly improve the mental health of caregivers in a sustained and clinically meaningful way. The remote delivery format of the program is especially pertinent in the Indian context, where geographical, logistical and social barriers often limit access to in-person mental health services. India’s growing digital infrastructure offers a unique opportunity to implement such programs at scale, making it feasible to reach caregivers across diverse regions, particularly in rural and underserved areas.

However, the generalizability of these findings to the Indian context necessitates further research. Future studies should aim to replicate this trial across various Indian settings, including both urban and rural areas, to assess the effectiveness and feasibility of the intervention in different sociocultural contexts. It is also critical to investigate the mechanisms through which the intervention works – identifying which components of the program are most effective in driving positive outcomes. In addition, further research is needed to adapt the program for high-need populations, including caregivers of children with more complex disabilities or those facing additional challenges such as mental illness or severe socioeconomic hardship.

In conclusion, the Empower-Autism trial offers an important model for addressing the mental health needs of caregivers of children with autism. It demonstrates that psychoeducational and psychotherapeutic interventions can lead to significant and sustained improvements in caregiver wellbeing. For India, where the burden on caregivers is often compounded by a lack of resources and access to support, this intervention presents an opportunity to enhance the support system for these families. Moving forward, it is essential to continue research to refine and adapt such interventions, ensuring they reach all caregivers in need and contribute to the holistic development of children with autism.

5. Cortical folding scaling in at-risk neonates: Distinguishing the effects of preterm birth and congenital heart disease

Source: Bonthrone AF, Cromb D, Chew A, Gal-Er B, Kelly C, Falconer S, Arichi T, Pushparajah K, Simpson J, Rutherford MA, Hajnal JV, Nosarti C, Edwards AD, O’Muircheartaigh J, Counsell SJ. Cortical scaling of the neonatal brain in typical and altered development. Proc Natl Acad Sci U S A. 2025 Apr 15;122(15):e2416423122. doi: 10.1073/pnas.2416423122. Epub 2025 Apr 8. PMID: 40198710.

The mammalian, adult human and child cortices demonstrate a universal scaling law relating exposed surface area to total surface area and cortical thickness. This study assessed the applicability of this law to typically developing neonates and infants with congenital heart disease (CHD) or preterm birth, utilising brain magnetic resonance imaging data from 345 typically developing infants, 73 preterm infants and 107 infants with CHD. The study also evaluated multivariate morphological terms capturing brain size, shape and folding processes.

Typically developing neonates were found to adhere to the cortical folding scaling law observed in mammalian brains, children and adults. This scaling was not significantly influenced by gestational age at birth, postmenstrual age at scan, sex or multiple birth in the typical population. This suggests that typical neonatal cortical development conforms to an intrinsic principle governing folding, potentially reflecting conserved molecular, cellular and mechanical shaping mechanisms. The allometric scaling coefficient linking surface area and supratentorial volume in typically developing neonates was higher than the theoretical geometric scaling coefficient, aligning with findings in typical adults and indicating increased gyrification with increased volume. The scaling coefficient between cortical thickness and volume in typical infants was higher than in typical adults, potentially reflecting the rapid increase and unique developmental trajectory of cortical thickness in early childhood.

In infants with CHD, cortical scaling was preserved, similar to typical neonates. However, CHD was characterised by a reduction in the multivariate morphological term representing size, indicating an effect on overall cortical growth. This suggests that reduced oxygen and nutrient delivery in utero in CHD affects brain size but not the fundamental processes of cortical folding. Lower isometric terms (size) in CHD infants were associated with reduced cerebral oxygen delivery. Reductions in cortical folding in CHD appeared proportionate to smaller brain volumes, rather than representing specifically disrupted folding mechanisms.

In contrast, preterm birth was associated with altered cortical folding scaling and altered cortical shape, indicated by significant differences in the folding scaling coefficient and reduced multivariate morphological terms capturing offset and shape compared to typical controls. This suggests that early exposure to the extrauterine environment disrupts the developmentally programmed processes of cortical folding. Preterm infants exhibited lower supratentorial brain volume, total surface area and gyrification index, but increased cortical thickness compared to controls. The neurobiological mechanisms underlying altered cortical folding in preterm infants are unclear but may involve changes in underlying white matter connections and altered neuronal maturation rather than large-scale neuronal loss. Altered cortical folding scaling coefficients and multivariate morphological offset terms have also been reported in adults born preterm, suggesting long-lasting effects.

The degree of altered shape in preterm infants was associated with cognitive abilities in early childhood. Lower shape terms, associated with lower surface area and higher cortical thickness, were linked to higher cognitive abilities in preterm infants, potentially suggesting adaptive changes in cortical thickness and surface area dynamics support cognitive development in this population.

The study highlights that evaluating scaling coefficients and multivariate morphology, which capture relationships between cortical metrics, provides a more nuanced understanding of developmental changes compared to assessing individual metrics in isolation. This approach distinguishes between proportionate size reductions (as seen in CHD) and disproportionate changes in surface area, gyrification index and cortical thickness that alter cortical shape (as seen in preterm birth). Distinct patterns of cortical microstructural changes previously reported in these groups further support the notion of distinct developmental alterations.

Limitations of the study include the use of whole-brain measures, potentially overlooking important regional scaling differences. The analysis focused on infants scanned at term-equivalent age, and cortical scaling dynamics may differ across earlier foetal and preterm periods. The observed differences were smaller than those reported in adult clinical populations, suggesting a need for longitudinal studies to track changes into later life.

In summary, typical neonatal cortical development follows the universal scaling law governing cortical folding. The study identifies distinct cortical developmental alterations in different at-risk populations: Reduced brain size with preserved scaling in infants with CHD, and altered cortical folding scaling and shape in preterm infants. Altered shape characteristics in preterm infants were associated with early childhood cognition.

6. The role of rare mutations in congenital heart disease: A large-scale study of genetic variants and their clinical implications

Source: Sierant MC, Jin SC, Bilguvar K, Morton SU, Dong W, Jiang W et al. Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes. Proc Natl Acad Sci U S A. 2025 Apr;122(13):e2420343122. doi: 10.1073/pnas.2420343122. Epub 2025 Mar 24. PMID: 40127276.

This study analysed de novo mutations (DNMs) and rare transmitted damaging variants in 248 genes in 11,555 individuals with CHD. It identified 60 genes significantly associated with CHD, which together accounted for 10.1% of the CHD cases in the study. The contributions from de novo and transmitted variants were similar in this gene set. Notably, DNMs in these 60 genes made up 58% of the total DNM signal across all 248 genes.

The mutations in these genes displayed varying phenotypic patterns. Thirty-three genes were linked to one CHD subtype, while 12 genes were associated with two to four subtypes. Seven genes were specifically associated with isolated CHD, while 37 genes were linked to extracardiac (EC) abnormalities. Genes that were mainly expressed in cardiomyocytes were linked to isolated CHD, while those expressed in broader tissues, like the brain, were also associated with neurodevelopmental delay (NDD).

Mutation frequency varied across these genes and was not entirely explained by the mutability of the genes themselves. A few genes (such as KMT2D, CHD7, PTPN11 and NOTCH1) accounted for a large portion of the DNMs, likely due to positive selection in the paternal germline or increased survival of embryos with mutations in these genes.

Certain variants were strongly associated with specific CHD types. For example, missense variants in NOTCH1, which change cysteine residues in the EGF-like domains, were linked to tetralogy of Fallot and conotruncal defects. Transmitted missense variants in MYH6 were associated with various CHD types and accounted for about 1% of the cases in the study.

Some individuals with mutations that cause syndromic CHD were not clinically diagnosed before genetic testing, often because the typical symptoms were absent. For genes where transmitted variants were more common, isolated CHD was more frequent, and there was a lower occurrence of EC features, including NDD. The risk of NDD varied by gene, with MYH6 variants linked to a 4% risk and CHD7 variants associated with a 95% risk.

The study also identified new genes related to CHD, including CUL3, LHX2, AHNAK, SVEP1, NR6A1 and CLUH, which are involved in biological pathways important for heart development. Analysis showed that the 60 key genes were more interconnected than expected, and these new genes fit into this network.

Loss-of-function mutations in certain genes exhibited variable expressivity, meaning the severity of CHD and EC/NDD features varied widely. Factors such as common genetic variants, environmental influences or subclinical CHD may contribute to this variability. In young children, the true incidence of NDD may be underestimated, although systematic reviews of certain genes provided similar estimates.

Chromatin regulatory genes showed a high mutation burden, mainly from de novo loss-of-function variants, and were more likely to be associated with EC phenotypes, reflecting their broad roles in cell processes. A larger number of chromatin-related genes may contribute to CHD risk.

The study suggests that rare monoallelic variants (including de novo and transmitted mutations, large copy number variants and aneuploidy) account for at least 40% of structural CHD cases. Other genetic factors, such as recessive inheritance and common variants with small effects, as well as non-genetic factors like maternal health, also contribute.

Overall, the study supports the use of genomic analysis for early diagnosis of CHD, especially for individuals with mutations in syndromic genes linked to variable risks of NDD, hearing loss, arrhythmias and other issues. Early identification can guide clinical management and improve long-term outcomes. The findings underscore the need for expanded genomic analysis in CHD evaluation and suggest that many more CHD-related genes remain to be discovered.

7. Optimising paediatric partial-thickness burn dressings

Source: Van de Warenburg MS, Teeuwen B, Hummelink S, Ulrich DJ, Vehmeijer-Heeman ML. Does the dressing matter in paediatric partial-thickness burns: A systematic review and meta-analysis. Burns. 2025 May;51(4):107428. doi: 10.1016/j.burns.2025.107428. Epub 2025 Feb 18. PMID: 40088689.

Paediatric partial-thickness burns are frequent injuries, and despite their commonality, there is no consensus on the ideal dressing to use. This has led to variations in how they are treated worldwide, especially in low-resource settings like India. This systematic review and meta-analysis aimed at evaluating the best dressing options for second-degree burns in children sheds light on the issue and offers practical insights.

The review analysed a broad range of dressing options, focusing on outcomes such as healing time, pain management, scarring, infection rates and costs. One of the biggest takeaways from the analysis is the lack of consensus in burn care, with different burn centres adopting different approaches. Despite this, skin analogues and non-silver dressings showed promising results. These dressings were particularly effective in resource-limited settings such as low- and middle-income countries, where burn areas covering less than 10% of the body surface area showed quicker healing times compared to traditional treatments like Silver Sulfadiazine. In high-income countries, skin analogues also contributed to shorter hospital stays.

Pain management was another area where skin analogues excelled, reducing discomfort significantly during dressing changes. The analysis also highlighted that these non-silver dressings could reduce hypertrophic scarring in children compared to silver-based treatments. Another noteworthy finding was the potential cost benefits of skin analogues. These dressings are more cost-effective because they require fewer dressing changes and can shorten hospital stays.

When it comes to infection rates and the need for grafting, the review found no significant differences between the various dressing types. However, the authors pointed out some challenges with the study’s methodology, such as statistical variations and differences in study design, which makes it difficult to draw firm conclusions.

For India, the findings are particularly relevant. Non-silver dressings and skin analogues, due to their cost-effectiveness and reduced pain levels, could improve burn care in Indian hospitals, especially those in resource-limited areas. These options align well with India’s need for affordable, effective solutions to paediatric burns. Furthermore, reducing pain and improving the comfort of children with burns is critical in the Indian context, where parents and caregivers are often the first responders and have to deal with the emotional and physical burden of the injury.

However, the lack of consensus across studies highlights the need for standardised protocols in India’s burn care centres. Developing a nationwide guideline for burn treatment, based on evidence and local conditions, should be a priority. Given the variability in treatment outcomes across different demographic and resource settings, there is also an urgent need for context-specific research in India. Studies should compare different dressings available locally, assess healing times, infection rates and cost-effectiveness and explore the feasibility of implementing standardised protocols across all healthcare levels.

In conclusion, while no single dressing emerged as universally superior, the evidence points towards skin analogues and non-silver dressings as potentially more effective and cost-efficient options for treating paediatric partial-thickness burns in India. This systematic review calls for more localised research and the establishment of standardised burn care protocols to ensure better outcomes and reduce the burden of paediatric burns in India.

8. Navigating initial vasoactive therapy in paediatric septic shock – Epinephrine versus norepinephrine

Source: Eisenberg MA, Georgette N, Baker AH, Priebe GP, Monuteaux MC. Epinephrine versus norepinephrine as initial treatment in children with septic shock. JAMA Netw Open. 2025 Apr 1;8(4):e254720. doi: 10.1001/jamanetworkopen.2025.4720. PMID: 40214988; PMCID: PMC11992602.

Paediatric septic shock requires immediate hemodynamic support, and choosing the right initial vasoactive agent is critical. However, there is ongoing debate over whether epinephrine or norepinephrine should be the first-line treatment, particularly in children without known cardiac dysfunction. A recent retrospective cohort study used propensity matching to compare these two agents in 231 children with septic shock, offering valuable insights into this issue that are relevant for paediatric intensivists, emergency care providers and researchers, particularly in India.

The study found that while there was no significant difference in kidney outcomes (as measured by major adverse kidney events within 30 days), there was a notable difference in mortality rates. Children who received epinephrine as the initial vasoactive agent had significantly higher 30-day mortality compared to those who received norepinephrine.

For India, these findings are particularly important because they suggest that norepinephrine may be a better first-line choice in paediatric septic shock without known cardiac dysfunction. This could help reduce mortality, especially in settings where septic shock management practices are highly variable. The study highlights the need for more evidence to standardise protocols across India, as access to medications and clinical resources can differ significantly between regions.

The study also prompts further investigation into why norepinephrine might offer a mortality benefit without reducing kidney injury. This could be due to differences in how each drug affects systemic and regional perfusion, as well as the potential for myocardial stunning in paediatric sepsis. Although adult data suggest that epinephrine might cause more metabolic and cardiac complications, it is crucial to study these effects specifically in children.

However, the study has limitations that should be considered, such as its retrospective design and single-centre setting. While propensity matching helps control for some confounders, unmeasured factors such as illness severity or clinician preferences may still influence the outcomes. In addition, differences in where the drugs were administered (emergency department vs. intensive care unit) could affect the results.

Given these limitations, the study authors call for prospective, multicentre trials, especially in India. Such trials could validate these findings across different paediatric populations, taking into account varying aetiologies of sepsis and comorbidities. They should also examine a broader range of outcomes, including kidney function, shock duration, length of stay and other complications. This research could ultimately lead to evidence-based, context-specific guidelines for vasoactive therapy in paediatric septic shock management across India.

In conclusion, while this study suggests that norepinephrine may be associated with lower mortality compared to epinephrine in children with septic shock without known cardiac dysfunction, its retrospective nature means the findings need to be interpreted cautiously. More prospective, multicentre research is needed to confirm these results and help standardise paediatric septic shock care in India.

9. The gut-brain axis in autism spectrum disorder – New links through tryptophan metabolites

Source: Aziz-Zadeh L, Ringold SM, Jayashankar A, Kilroy E, Butera C, Jacobs JP, Tanartkit S, MahurkarJoshi S, Bhatt RR, Dapretto M, Labus JS, Mayer EA. Relationships between brain activity, tryptophan-related gut metabolites and autism symptomatology. Nat Commun. 2025 Apr 14;16(1):3465. doi: 10.1038/s41467-025-58459-1. PMID: 40229237.

The connection between the gut and brain, known as the ‘gut-brain axis’, is an emerging area of research with growing implications for neurodevelopmental disorders, including ASD. While prior studies have suggested a role for gut microbiota and their metabolites in the development of ASD, the specific mechanisms linking gut metabolites to brain function and ASD symptoms have not been well understood. A recent cross-sectional study sought to uncover the relationships between brain activity, tryptophan-related gut metabolites and autism symptoms in children, providing important new insights.

The study involved 43 children diagnosed with ASD and 41 neurotypical children, employing a multi-modal approach that included faecal metabolomics, functional magnetic resonance imaging and behavioural assessments. The aim was to investigate the associations between specific gut microbial metabolites and brain activity patterns known to be altered in ASD as well as to assess how these factors relate to core ASD symptoms.

One of the key findings was that children with ASD had significantly lower levels of certain tryptophan-related metabolites, particularly kynurenate, in their faecal samples compared to neurotypical children. These altered metabolite levels were associated with changes in brain activity, particularly in the insular and cingulate cortices – regions involved in interoception (the perception of internal bodily states), which are frequently implicated in ASD. The study found that brain activity in these regions mediated the relationship between specific microbial metabolites and the severity of ASD symptoms, including sensory sensitivities and disgust propensity.

This study sheds light on the complex mechanisms at play in the gut-brain axis in ASD, highlighting the potential significance of tryptophan metabolism in influencing brain function and behaviour. The findings are particularly relevant for medical practitioners and researchers in India, where ASD is highly prevalent and presents significant challenges for families and the healthcare system.

For the Indian context, the study’s insights suggest several important areas for further exploration. First, there is a need to consider the gut-brain axis in understanding ASD, broadening our perspective beyond traditional neurological models. The identified metabolites, such as kynurenate and indolelactate, may serve as potential biomarkers for diagnosing or stratifying ASD, as well as novel targets for therapeutic interventions aimed at modulating the gut microbiome or metabolite pathways.

The study’s focus on brain regions associated with interoception and sensory sensitivities is particularly pertinent for clinical practice in India, where sensory processing issues are often a prominent feature of ASD. Further investigation into the relationships between gut metabolites and sensory sensitivities could lead to more effective strategies for managing these symptoms.

However, the study has its limitations, including a small sample size, strict inclusion criteria and the cross-sectional nature of the design, which limits its ability to establish causality. To address these limitations in the Indian context, future research should focus on larger, more diverse cohorts that reflect the heterogeneity of the ASD population in India. Longitudinal studies could help explore how these gut-brain relationships evolve over time, particularly during key developmental stages. In addition, interventional studies, such as trials involving probiotics, prebiotics or dietary interventions, could provide insights into the causal role of gut metabolites in ASD.

Furthermore, research should consider how local dietary practices, environmental factors, and genetic variations in India influence the gut microbiome and ASD symptomatology. The study also highlighted a potential link between prenatal antibiotic exposure and ASD, an area that warrants further exploration in the Indian context.

Advancing research capabilities in India will be crucial for deepening our understanding of ASD. Multi-modal research approaches, combining metabolomics, neuroimaging and behavioural phenotyping, will be necessary for uncovering the complexities of the gut-brain axis in ASD. Overcoming technical and logistical challenges in implementing these techniques across different research centres in India will be a key step in advancing the field.

In conclusion, this study provides strong evidence linking gut microbial tryptophan metabolites, brain activity in interoception-related regions and key ASD symptoms in children. These findings suggest a model where brain activity mediates the link between gut metabolites and ASD symptoms, offering new avenues for understanding the pathophysiology of ASD. While causality remains to be confirmed, this research lays the foundation for future studies in India that could lead to improved diagnostic and therapeutic approaches for children with ASD in the country.

10. Faecal impaction in children with functional constipation: The case for a uniform definition

Source: Gordon M, Balda A, Arrizabalo S, Sinopoulou V, Batarseh S, Shargawi J, Di Lorenzo C, Benninga MA, Tabbers M, Saps M. Faecal impaction in children aged 0–-18 years: A systematic review and metanarrative analysis of definitions used. BMJ Paediatr Open. 2025 Apr 7;9(1):e003085. doi: 10.1136/bmjpo-2024-003085. PMID: 40194919; PMCID: PMC11977476.

Functional constipation is one of the most common paediatric gastrointestinal disorders, and faecal impaction represents a significant complication with diagnostic and therapeutic implications. Despite its clinical relevance, there remains no universally accepted definition for faecal impaction in children aged 0–18 years. A recent systematic review employing a metanarrative analysis of randomised controlled trials (RCTs) underscores this definitional heterogeneity and its impact on both research standardisation and clinical practice.

This review included 76 RCTs assessing treatment interventions for paediatric functional constipation. Only seven of these studies provided an explicit definition of faecal impaction. In the majority, definitions were either absent or inferred indirectly from screening or exclusion criteria. Most studies relied on clinical assessment to diagnose impaction, though the parameters varied. Some used abdominal palpation to identify masses, others incorporated digital rectal examination to evaluate rectal loading, and several used a combination of both. Abdominal radiographs were inconsistently utilised and lacked uniform diagnostic thresholds. The duration of symptoms preceding diagnosis was largely omitted, noted explicitly in only one study.

This variability in defining faecal impaction presents challenges for diagnosis, management and research comparability. Clinically, it leads to inconsistent identification of impaction, which can delay timely intervention, affect the choice of disimpaction strategies and disrupt transition to maintenance therapy. In research, the lack of a standardised definition impedes meta-analyses and evidence synthesis, limiting the development of practice guidelines.

Digital rectal examination was reported frequently in the reviewed trials as a diagnostic tool. However, this stands in contrast to emerging guidance advocating limited use of rectal examination, especially in older children, due to concerns around acceptability, trauma and limited additional diagnostic value. In contexts like India, where cultural and ethical considerations surrounding paediatric rectal examination are prominent, reliance on DRE without clear justification remains problematic.

Radiographic evaluation was applied inconsistently across studies, further emphasising the lack of consensus. Given that abdominal X-rays are no longer routinely recommended in the evaluation of functional constipation due to poor correlation with clinical symptoms and high inter-observer variability, their role in diagnosing impaction requires reevaluation.

The lack of symptom duration as a diagnostic component is particularly notable. Chronicity is a critical aspect of constipation pathophysiology, and its exclusion from most definitions highlights a conceptual gap in understanding faecal impaction as a dynamic rather than static condition.

The authors of the review attempt to propose a consensus definition but acknowledge the complexity involved in reconciling existing clinical practices, cultural considerations and resource variability. The findings suggest that faecal impaction may be more appropriately conceptualised as a severe manifestation within the functional constipation spectrum, potentially overlapping with refractory constipation.

In the Indian context, where the burden of paediatric constipation and its complications is substantial, the implications are clear. The absence of a uniform, context-sensitive definition hinders the standardisation of care, limits the utility of international guidelines and complicates the development of local protocols. Further research in India is necessary to evaluate diagnostic practices, test the applicability of proposed definitions and inform consensus-building efforts that reflect both clinical utility and cultural feasibility.

This review highlights an urgent need for a globally accepted, operationally sound definition of faecal impaction in children. Such a definition must be informed by clinical evidence, validated diagnostic tools and relevance to diverse healthcare settings. Standardising this definition is foundational to improving outcomes in paediatric constipation management and facilitating rigorous, comparable research across populations.

11. Managing patent ductus arteriosus in extremely low birth weight infants – Balancing efficacy and safety

Source: Sutton CC, Slaughter JC, Alrifai MW, Hale J, Reese J. Response of the ductus arteriosus to acetaminophen or indomethacin in extremely low birth weight infants. J Perinatol. 2025 Mar;45(3):319-325. doi: 10.1038/s41372-024-02199-5. Epub 2024 Dec 18. PMID: 39695341; PMCID: PMC11888984.

Managing a hemodynamically significant Patent Ductus Arteriosus (PDA) in extremely low birth weight (ELBW) infants continues to challenge neonatal teams, especially when balancing efficacy with safety. Acetaminophen and indomethacin remain the mainstays of medical treatment, but which one is truly better – especially in the smallest and sickest neonates – is still up for debate.

A recent retrospective study compared the outcomes of PDA treatment in ELBW babies receiving either acetaminophen or indomethacin. Interestingly, both drugs showed similar rates of ductal closure after a single course – 16% for acetaminophen, 18% for indomethacin – suggesting that neither was significantly more effective in this regard. However, when taking into account not just full closure but also significant ductal constriction (which often precludes the need for further treatment), indomethacin appeared to edge out acetaminophen, with fewer infants going on to need surgery.

One notable point was the earlier use of indomethacin compared to acetaminophen, although this did not seem to influence the overall success rates in a statistically significant way. As for acetaminophen levels in the blood – they did not correlate with outcomes, echoing previous findings that drug concentration is not a reliable predictor of closure.

In real-world practice, especially in Indian neonatal intensive care units, acetaminophen is often the preferred choice. That’s largely because indomethacin comes with well-known risks: Kidney problems, gut issues and other non-steroidal anti-inflammatory drug-related side effects. But this safety advantage might be more perceived than proven, especially since this study found similar short-term side effect profiles for both drugs. It’s worth noting, though, that sicker babies were more likely to be given acetaminophen, which could skew the apparent safety data.

Then comes the elephant in the room – long-term safety. While acetaminophen seems gentler in the short term, there is growing concern, drawn from both animal studies and emerging human data, about its potential neurodevelopmental effects. Links have been reported between early-life acetaminophen exposure and later cognitive or behavioural issues, including autism. And although the liver-related toxicity risk in neonates is thought to be low, some murine models suggest that acetaminophen might affect developing lungs in ways that mirror bronchopulmonary dysplasia.

All of this puts Indian clinicians in a tough spot. We need treatments that work, are safe in the short- and long-term, and make sense in our resource-constrained settings. However, this study shows how little we still know about what’s truly best for ELBW infants with PDA. The medical closure rates in this study were low for both drugs, raising a red flag about how effective our current strategies really are for this population.

What’s clearly needed now are high-quality, India-specific studies – prospective, multicentre trials that not only compare these drugs head-to-head with standardised dosing but also follow these babies into childhood to understand the long-term consequences. Pharmacokinetic data from Indian populations would be particularly valuable, as would cost-effectiveness analyses tailored to our healthcare infrastructure.

In short, while acetaminophen and indomethacin might seem interchangeable in terms of short-term ductal closure, they are not the same story when it comes to long-term impact – and that story is far from complete. Until we know more, clinicians must continue weighing the risks and benefits case by case, all the while pushing for the kind of research that will give us clearer answers.