The methodology behind the analysis reflects the modern standards of evidence synthesis. The research team searched MEDLINE through PubMed, Embase, Scopus, and Web of Science from database inception to July 2026, casting a wide net for observational studies that evaluated laboratory-confirmed enteric infections against stunting outcomes in children. Nineteen studies passed the quality threshold for the qualitative synthesis, and fourteen contributed effect estimates to the quantitative meta-analysis. The authors followed the PRISMA 2020 reporting guidelines, pooled odds ratios using random-effects models, and assessed risk of bias with the Newcastle–Ottawa Scale. Certainty of evidence was judged using the GRADE framework, the same structured approach that underpins World Health Organization guideline development. This combination of transparent searching, formal bias assessment, and pre-specified subgroup analyses gives the review a methodological rigor that many entries in the stunting literature have lacked.

The headline number deserves unpacking. An odds ratio of 1.94 means that children with laboratory-confirmed enteric infections had roughly 94 percent higher odds of being stunted, defined as height-for-age more than two standard deviations below the reference median, compared with children without such infections. That is a substantial association in a field where effect estimates often hover close to unity. But the pooled figure came with an I-squared statistic of 85.6 percent, indicating that more than eight-tenths of the variability among studies reflected real differences between populations and methods rather than random noise. In practical terms, the pooled odds ratio describes an average of a highly heterogeneous body of evidence, and the authors were careful not to oversell it. Heterogeneity of this magnitude is common in observational meta-analyses of infection and nutrition, where study settings range from urban slums to rural highlands and diagnostic tools range from microscopy to multiplex PCR.

To probe that heterogeneity, the team conducted pre-specified subgroup analyses across pathogen domains: bacterial, viral, protozoal, helminthic, and non-specific parasitic infections. The most consequential finding of the review may be what did not emerge. Despite wide differences in the biology of these organisms, the associations with stunting were broadly comparable across domains, with no statistically significant differences between pathogen groups. Bacteria such as enteroaggregative Escherichia coli, viruses such as rotavirus, protozoa such as Giardia and Cryptosporidium, and soil-transmitted helminths all appeared to leave children at similar elevated risk of growth faltering. The authors interpret this convergent pattern as evidence that multiple enteric pathogens may impair child growth through shared biological pathways rather than through pathogen-specific mechanisms.

That interpretation aligns with two decades of research into environmental enteric dysfunction, a subclinical condition of the small intestine that has become a central hypothesis in child growth biology. Repeated exposure to fecal pathogens is thought to provoke chronic mucosal inflammation, villous atrophy, increased intestinal permeability, and malabsorption, collectively blunting the child’s ability to convert food into linear growth. Studies cited in the review, including the Environmental Enteric Dysfunction Biopsy Initiative and work linking the condition to carnitine deficiency and altered fatty acid oxidation, describe a gut that is chronically inflamed and metabolically compromised even in children who never present with overt diarrhea. Chronic inflammation also suppresses the growth hormone–insulin-like growth factor-1 axis, the endocrine engine of linear growth, providing a plausible mechanistic bridge from a fecal-contaminated environment to a stunted child.

Meta-regression added a second layer of insight by identifying participant age and adjustment status as significant sources of between-study heterogeneity. The association between enteric infection and stunting was strongest among children younger than two years, which the authors read as a signal about the first 1000 days of life, the window from conception through roughly the second birthday during which linear growth velocity is highest and the developing gut and immune system are most vulnerable to disruption. This timing matters for intervention design. A child whose gut is repeatedly infected during the period of most rapid growth may sustain deficits that nutritional supplementation later in childhood cannot fully reverse, echoing longitudinal findings from the MAL-ED birth cohort across eight low- and middle-income country sites, which documented that even asymptomatic enteropathogen infections measurably depressed linear growth.

The finding that statistical adjustment for confounders shaped the observed effect estimates is equally important for readers interpreting the evidence. Observational studies of infection and stunting must contend with a dense thicket of confounding: household wealth, maternal education, water and sanitation access, breastfeeding practices, and diet all influence both infection risk and growth. Studies that adjusted more comprehensively for these factors produced different effect estimates than those that did not, and the meta-regression captured this as a source of heterogeneity. The very low GRADE rating applied to the pooled evidence reflects these inherent limitations. Association is not causation, reverse causality remains possible, since malnourished children may be more susceptible to infection as well as more harmed by it, and the Review authors are explicit that their pooled estimate should guide hypothesis formation and intervention priority-setting rather than be read as a precise causal coefficient.

The geographical scope of the underlying studies, spanning Ethiopia, Bangladesh, Indonesia, Peru, Zambia, Madagascar, the Philippines, Zimbabwe, and other low- and middle-income settings, underscores that the stunting–infection relationship is concentrated where sanitation infrastructure is weakest. Several included studies examined the interaction between enteric infections and environmental enteric dysfunction directly, and others evaluated how water, sanitation, and hygiene interventions perform in children carrying different pathogen burdens. Collectively, this literature suggests that the classic nutrition-centric framing of stunting, in which food insecurity is treated as the dominant driver, captures only part of the story. A child can consume adequate calories and still fail to grow if a chronically inflamed gut cannot absorb them.

For policymakers, the practical implications of the review are captured in its stated impact summary: the findings support integrating infection prevention, sanitation, and nutritional interventions into child stunting reduction programs, rather than pursuing these strategies in silos. That means pairing supplementary feeding and dietary diversification with safe water, improved sanitation, deworming where helminth burden is high, and, where available, vaccination against enteric pathogens. The absence of differences between pathogen domains complicates any pathogen-by-pathogen targeting strategy and instead argues for broad environmental measures that reduce exposure to the fecal–oral pathway as a whole. The vulnerability of children under two further suggests that interventions should begin in pregnancy and infancy, when the marginal return on preventing gut disruption is highest.

The review, published on 26 September 2026 with the DOI 10.1038/s41390-026-05520-4, arrives at a moment when the global health community is assessing why stunting prevalence has declined more slowly than under-five mortality. By quantifying a roughly twofold elevation in stunting odds associated with enteric infections across bacterial, viral, protozoal, and helminthic domains, and by flagging the first 1000 days as the period of maximal vulnerability, it offers both a synthesis of a fragmented literature and a clear agenda for what must come next: longitudinal studies with molecular diagnostics, better confounder control, and intervention trials that test whether breaking the infection–inflammation cycle unlocks growth that nutrition alone cannot deliver. The evidence may be graded very low in certainty, but the direction of the signal, and the scale of the population at risk, give it a weight that few will ignore.

Subject of Research: The association between enteric infections across four pathogen domains and childhood stunting in low- and middle-income countries

Article Title: Enteric infections and childhood stunting: a systematic review and meta-analysis across four pathogen domains

Article References: Pauzi, R. Y., Iqhrammullah, M., Ihtiaringtyas, S., Ilmi, A. N., Kumaratih, L. W., Yuliana, P. T., Aqila, R. A., & Raizma, E. Z. N. (2026). Enteric infections and childhood stunting: a systematic review and meta-analysis across four pathogen domains. Pediatric Research. https://doi.org/10.1038/s41390-026-05520-4

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05520-4

Keywords: childhood stunting, enteric infections, meta-analysis, systematic review, environmental enteric dysfunction, gut microbiology, pediatric growth, first 1000 days, soil-transmitted helminths, water sanitation and hygiene, low- and middle-income countries, GRADE evidence

Neonatal hypoglycaemia is far from a rare curiosity. Up to 15% of otherwise healthy newborns experience blood glucose levels low enough to be flagged in the first hours of life, and among infants with risk factors such as prematurity, being small or large for gestational age, or maternal diabetes, the incidence can climb to roughly half. The transition from the constant glucose supply of the placenta to independent metabolic regulation is inherently precarious, and many healthy babies dip transiently while adapting to life outside the womb. The concern is what happens when the dip is prolonged or severe: prior research has linked severe neonatal hypoglycaemia to abnormal fine motor function, deficits in visual-motor integration and symptoms consistent with attention-deficit/hyperactivity disorder later in childhood. That long shadow is what drives clinicians to monitor, feed and, when necessary, treat aggressively.

Conventional management relies on early identification of at-risk infants, prompt feeding, frequent glucose checks and, for symptomatic or severe cases, intravenous dextrose. The problem is that IV dextrose is invasive, demands NICU admission, separates mother and baby, interrupts breastfeeding and generates anxiety and cost. Oral 40% dextrose gel promised a way around all of that. It is cheap, stable, easy to administer through the buccal mucosa and works within minutes without displacing a feed. The landmark Sugar Babies trial in New Zealand, published in 2013, appeared to prove the concept: at-risk late preterm and term infants treated with dextrose gel were less likely to fail treatment and less likely to be admitted to the NICU for hypoglycaemia. The much larger hPOD multicentre trial later confirmed a modest reduction in hypoglycaemia incidence but found no reduction in NICU admission, planting the first seeds of doubt.

Since then, the picture has grown murkier rather than clearer. Some recent trials reported no significant difference between dextrose gel and control in treatment success, while others suggested the gel helps maintain blood glucose in specific subgroups such as infants of diabetic mothers or late preterm babies. A previous meta-analysis had concluded that the gel significantly lowered NICU admissions, but it included fewer studies and roughly 1,000 fewer participants than the new synthesis. Motivated by that expanding but inconsistent evidence base, an international team of researchers registered a protocol with PROSPERO and set out to pool every available randomized trial of 40% dextrose gel for both prevention and treatment of neonatal hypoglycaemia, following the PRISMA 2020 reporting standards.

The search strategy was exhaustive. The team combed PubMed, Embase, Web of Science, Scopus and the Cochrane Library from inception to March 2026, retrieving 1,332 records. After deduplication, 1,285 studies were screened by title and abstract, 58 went to full-text review, and eight randomized controlled trials ultimately met the eligibility criteria. Together they enrolled 4,368 neonates, 2,256 assigned to 40% dextrose gel and 2,112 to control. The trials spanned New Zealand, Australia, India, Argentina, Italy, Ireland and the Czech Republic, and they varied enormously in design: some gave the gel prophylactically in the delivery room or at one hour of life, others used it to treat established asymptomatic hypoglycaemia; comparators ranged from placebo gel to breastfeeding alone to formula milk; and hypoglycaemia thresholds ranged from below 1.8 mmol/L to below 2.6 mmol/L or below 45 mg/dL.

The pooled results were uniformly null. Across five prevention trials involving 3,618 infants, dextrose gel did not significantly reduce the incidence of hypoglycaemia, with a pooled risk ratio of 0.92 and a 95% confidence interval of 0.76 to 1.11, accompanied by moderate heterogeneity. In three treatment trials covering 750 infants, treatment success, defined as avoiding IV dextrose, showed no significant difference, with a risk ratio of 1.10 and striking heterogeneity of 95%. Recurrent hypoglycaemia, NICU admission, breastfeeding at discharge and any formula feeding all likewise showed no statistically significant differences. The NICU result deserves particular attention: the pooled risk ratio was 0.87, but when the massive hPOD trial was excluded in sensitivity analysis, heterogeneity collapsed and the estimate became a statistically significant 24% reduction in admissions, hinting that protocol differences, such as a single prophylactic dose versus multiple doses, may determine whether the gel delivers on its promise.

The authors are careful to stress what these numbers do and do not mean. Non-significant findings, they emphasize, are not evidence of equivalence. The confidence intervals for several outcomes, particularly treatment success and NICU admission, are wide enough to encompass both clinically meaningful benefit and potential harm. For treatment success, the interval spans a possible 23% reduction to a 57% increase. Certainty of evidence, graded using the GRADE framework, ranged from moderate for breastfeeding at discharge down to very low for treatment success, reflecting serious risk of bias in one trial, substantial inconsistency and imprecision across outcomes. Publication bias assessments using Doi plots and trim-and-fill adjustments did not materially change the conclusions, but with fewer than ten studies per outcome, those methods have limited power.

Why might the gel underperform expectations? The review offers several technical explanations. Doses varied from a single 200 mg/kg dose to multi-dose regimens totalling up to 1,000 mg/kg, and timing ranged from the delivery room to two hours after birth, yet no clear dose-response or timing effect emerged. Comparators mattered too: in the Argentine trial, formula-fed controls actually achieved higher treatment success than gel-treated babies, since formula feeding is itself an effective hypoglycaemia remedy. Definitions of hypoglycaemia differed across trials, and measurement methods varied from laboratory glucose oxidase assays to bedside glucometers, introducing misclassification that biases estimates toward the null. Subgroup signals persisted, however: infants of diabetic mothers in one Indian trial showed a marked benefit, and late preterm infants in an Italian study had higher glucose levels with gel, while extremely preterm infants under 32 weeks in the GEHPPI trial showed none, with identical hypoglycaemia rates of 29% in both arms.

On the reassuring side, the gel appears harmless to breastfeeding. Despite concerns that any neonatal supplementation can delay breastfeeding initiation and shorten duration, the pooled analysis found no difference in breastfeeding at discharge or formula use, with zero heterogeneity across trials. No adverse events were reported in any of the included studies, though the authors caution that long-term neurodevelopmental safety remains untested. Clinically, the team suggests the gel’s low cost, safety profile and ease of administration still justify a role as an adjunctive therapy, particularly in resource-limited settings or while awaiting IV access, but not as a replacement for intravenous dextrose when clearly indicated, and always within standardized protocols covering dosing, monitoring and escalation.

The research agenda that follows is demanding. The authors call for dose-finding trials comparing multi-dose regimens with single-dose prophylaxis, population-specific trials stratified by the underlying mechanism of hypoglycaemia, continuous glucose monitoring to replace intermittent heel-prick checks, and long-term neurodevelopmental follow-up. Until such trials arrive, the humble sugar gel remains what it has arguably always been: a plausible, cheap and safe tool whose true value, for whom, at what dose and at what hour of life, medicine has not yet pinned down.

Subject of Research: The efficacy of 40% oral dextrose gel for preventing and treating neonatal hypoglycaemia, assessed in an updated systematic review and meta-analysis of randomized controlled trials.

Article Title: Efficacy of Oral Dextrose Gel for Neonatal Hypoglycaemia: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials With 4368 Patients

Article References: Al‐Enezi, R. T., Alshebeeb, F. A., Panikulam, J. R., AlKhaldi, D. B., Almutairi, R. B., Alenezi, R. T., Aljassar, A. M., Aldosari, R. B., Alkandari, F. A., Dashti, A. A., Aldhahi, K. A., Abdul‐Hafez, H. A., & Alharran, A. M. (2026). Efficacy of Oral Dextrose Gel for Neonatal Hypoglycaemia: An Updated Systematic Review and Meta‐Analysis of Randomized Controlled Trials With 4368 Patients. Endocrinology, Diabetes & Metabolism, 9(5), Article e70327. https://doi.org/10.1002/edm2.70327

Image Credits: AI Generated

DOI: 10.1002/edm2.70327

Keywords: neonatal hypoglycaemia, oral dextrose gel, systematic review, meta-analysis, randomized controlled trials, NICU admission, newborn health, breastfeeding, intravenous dextrose, GRADE evidence, neonatal intensive care, glucose monitoring

The review, led by Ali Msheik of Hamad Medical Corporation in Doha, Qatar, together with colleagues in trauma surgery, neurocritical care, and medical ethics, synthesized all available systematic reviews of viscoelastic hemostatic assays in neurocritical illness. These assays, which include thromboelastography known as TEG, TEG Platelet Mapping, and rotational thromboelastometry known as ROTEM, differ fundamentally from standard coagulation tests. Instead of isolating plasma and timing a single clotting reaction, they measure the actual physical behavior of clot formation in whole blood: how quickly the clot initiates, how strongly it propagates, how firm the final clot becomes, and how readily fibrinolysis breaks it down. In principle, this gives clinicians a real-time picture of hemostasis that standard tests cannot capture.

To assess the accumulated evidence, the researchers followed PRISMA 2020 reporting guidelines, the Joanna Briggs Institute manual for umbrella reviews, and MOOSE recommendations, searching PubMed, Embase, Scopus, the Cochrane Library, and Web of Science from database inception to January 2026. Two physician reviewers with experience in neurocritical care independently screened records, extracted data, and appraised methodological quality. The screening funnel was dramatic: of 272 records identified, 199 were screened after duplicate removal, and only four systematic reviews survived full-text assessment. The authors emphasized that this narrowing reflects the strict restriction to review-level evidence with reproducible methods and extractable neuro-specific data, not a post hoc reshaping of the question.

Those four reviews encompassed 73 study occurrences representing 63 unique primary studies, spanning traumatic brain injury, subarachnoid hemorrhage, and mixed populations with ischemic stroke and coronary artery disease. A corrected covered area analysis quantified how much the underlying evidence overlapped, finding only slight overall redundancy at 5.3 percent. Within traumatic brain injury, however, the two dedicated reviews shared 12 primary studies, a corrected covered area of 29.4 percent, while the subarachnoid hemorrhage and antiplatelet therapy reviews shared no studies with other clusters. This low overall overlap means the field is not merely recycling the same small trials, an encouraging sign for the maturity of the evidence base even as quality concerns remain.

The methodological appraisal revealed uneven rigor. Using AMSTAR-2, a validated tool for assessing systematic reviews, only one review, a 2021 meta-analysis of thromboelastography in traumatic brain injury by Cannon and colleagues, achieved moderate confidence, supported by a registered protocol, a comprehensive search, duplicate screening, and structured bias assessment. The remaining reviews earned low or critically low confidence ratings owing to absent protocols, incomplete reporting of excluded studies, and limited transparency. When the authors then applied GRADE criteria to rate certainty in individual outcomes, most estimates in traumatic brain injury and subarachnoid hemorrhage fell to low or very low certainty, a consequence of predominantly observational designs, inconsistent definitions, and imprecise effects.

Within those constraints, the prognostic signal was remarkably consistent. Across two reviews covering 32 unique studies in traumatic brain injury, viscoelastic assays repeatedly identified clinically relevant coagulation disturbances. Abnormal clot strength and disturbed fibrinolytic activity were associated with mortality across 18 observational studies, with radiographic hemorrhage progression in 14 studies, and with the need for neurosurgical intervention in nine, though confounding and heterogeneous outcome definitions limited those latter findings. In subarachnoid hemorrhage, a single review of 19 primary studies found that hypercoagulable profiles, particularly increased clot firmness, were consistently linked to delayed cerebral ischemia in six studies and to early brain injury severity in four. These associations make biological sense: dysregulated clot formation and breakdown plausibly contribute to secondary brain injury, hemorrhage expansion, and delayed ischemia after aneurysm rupture.

The therapeutic story was different. No review provided convincing evidence that viscoelastic-guided interventions improved outcomes in traumatic brain injury or subarachnoid hemorrhage, meaning the assays currently function as crystal balls rather than steering wheels in these conditions. The one bright spot came from mixed ischemic populations: moderate-certainty evidence from a meta-analysis of ten studies, including randomized trials, suggested that TEG-guided antiplatelet therapy in patients with ischemic stroke and coronary artery disease was associated with fewer composite ischemic and bleeding events than standard care. Mortality effects, however, remained uncertain because reporting was sparse and inconsistent, and because the population blended cardiac and cerebrovascular patients, the finding cannot be directly transferred to pure stroke care without further validation.

The authors are explicit about what this means for practice. Viscoelastic assays, they conclude, may be most appropriately used as adjunctive diagnostic and prognostic tools in neurocritical care rather than as standalone guides for transfusion or hemostatic treatment decisions in brain trauma and aneurysmal hemorrhage. The finding challenges a seductive assumption, one that has driven adoption in trauma and cardiac surgery, that simply identifying a coagulation disturbance and acting on it automatically improves outcomes. In the neurocritical setting, the leap from detection to benefit has not yet been demonstrated in rigorous trials, and current clinical guidelines accordingly do not recommend routine viscoelastic testing in these populations.

Several structural obstacles help explain the gap between prognostic promise and therapeutic proof. Included studies frequently came from single centers using institution-specific protocols, with inconsistent assay platforms, variable clinical cutoffs, and differing transfusion and antiplatelet practices. Without harmonized thresholds and standardized definitions of what counts as an actionable abnormality, clinicians cannot translate an abnormal tracing into a uniform treatment decision, and trialists cannot pool results meaningfully. These limitations reduce generalizability and complicate the interpretation of every association reported to date.

The research agenda that follows is clear. The authors call for large prospective neuro-specific cohorts using standardized viscoelastic thresholds, randomized trials testing VHA-guided transfusion or reversal strategies specifically in traumatic brain injury and subarachnoid hemorrhage, harmonization of assay parameters and clinical definitions, mechanistic studies linking viscoelastic abnormalities to neurovascular pathophysiology, and targeted evaluation of TEG-guided antiplatelet therapy in stroke populations alone. Until that work is done, the review suggests, clinicians and policymakers should read abnormal viscoelastic findings as important prognostic information, valuable for risk stratification and communication, while resisting the temptation to build treatment algorithms on evidence that has yet to bear their weight. For a technology that has already transformed hemostasis management in trauma and cardiac surgery, neurocritical care remains the unfinished frontier.

Subject of Research: Viscoelastic hemostatic assays for prognosis and treatment guidance in neurocritical illness

Article Title: The utility of viscoelastic hemostatic assays in neurocritical illness

Article References: Msheik, A., Peralta, R., Al-Rumaihi, G., Rizoli, S., Al Mokdad, Z., de Oliveira Manoel, A. L., & Al-Thani, H. (2026). The utility of viscoelastic hemostatic assays in neurocritical illness. Journal of Emergency and Disaster Medicine, 2(1), Article 10. https://doi.org/10.1007/s44467-026-00012-1

Image Credits: AI Generated

DOI: 10.1007/s44467-026-00012-1

Keywords: viscoelastic hemostatic assays, thromboelastography, ROTEM, traumatic brain injury, subarachnoid hemorrhage, ischemic stroke, coagulopathy, neurocritical care, umbrella review, antiplatelet therapy, delayed cerebral ischemia, GRADE evidence