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Open research questions in Infant Nutrition and Health

445 gap statements mined from Infant Nutrition and Health papers in our 7.9M-paper local library, which holds 1,856 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The effects of HMO supplementation on immune function and gut microbiota in healthy mice are not well understood. The mechanisms by which HMOs modulate immune function and inflammation are not fully elucidated.

    Modulating effects of 2′-fucosyllactose and 6′-sialyllactose supplementation in a nutrient-rich skim milk base on immune function and gut microbiota in healthy mice · 2026 · DOI

  • The lack of a predictive model for sepsis in NEC patients. The need for early identification of high-risk groups for sepsis in NEC patients. The gap in understanding the factors associated with sepsis in NEC patients.

    Sepsis in neonates with necrotizing enterocolitis: outcomes and predictive model · 2026 · DOI

  • The small sample size of the study limits the precision of the findings. The complexity of necrotizing enterocolitis pathogenesis makes it challenging to identify reliable biomarkers. The need for larger multicenter validation studies to confirm the findings and establish the clinical utility of the identified biomarkers.

    Serum Olink proteomics-based exploration of novel predictive biomarkers for necrotizing enterocolitis · 2026 · DOI

  • The milk microbiota of women from southern Peru remains uncharacterized. There is a need to characterize the bacterial composition and diversity of human milk in this population.

    Breast Milk Microbiota at One Month Postpartum in Women from Arequipa, Peru, Assessed by Full-Length 16S rRNA Gene Nanopore Sequencing · 2026 · DOI

  • There is a need to identify risk factors and predictive parameters for NEC requiring surgery. The current literature lacks a comprehensive analysis of the association between gestational age, birth weight, and the risk of NEC. There is a gap in understanding the short-term outcomes of NEC in preterm infants.

    Risk Factors and Predictive Parameters of Necrotizing Enterocolitis in Preterm Infants—A Single-Center Retrospective Study · 2025 · DOI

  • The paper mentions that the data on the effects of G-CSF are confusing. The authors also highlight the importance of proper nutrition for infants and the potential defects in nervous system development due to lack of neurotrophic factors.

    Bioactive Components of Human Milk and Their Impact on Child’s Health and Development, Literature Review · 2024 · DOI

  • 2’-Fucosyllactose (2’-FL), the most abundant human milk oligosaccharide (HMO), exhibits potent anti-inflammatory properties, yet the underlying mechanisms remain incompletely understood.

    2′-Fucosyllactose and its metabolites propionate/butyrate suppress inflammation through a shared TLR4/p38 MAPK-dependent pathway in vitro and in vivo · 2026 · DOI

  • Significant methodological challenges persist across all approaches, including the lack of standardized sampling protocols that account for temporal variation in milk composition, and difficulties in adapting analytical technologies originally designed for other matrices.

    Measuring nutrient content in human milk: are we there yet? · 2026 · DOI

  • Achieving enteral feed volumes alone was insufficient to prevent EUGR, highlighting the importance of early protein and energy optimisation, timely advancement to full fortification, and routine growth monitoring in resource-limited settings.

    Postnatal growth trajectories and extrauterine growth restriction in very low birth weight infants managed without routine parenteral nutrition in a resource-limited south African neonatal unit · 2026 · DOI

  • Asymptomatic physiological hypercalcaemia in exclusively breastfed infants is recognised but has not been systematically characterised when breastfeeding is continued.

    Breast milk–associated physiological hypercalcaemia: an observational study of clinical, biochemical and radiological outcomes · 2026 · DOI

  • Probiotic use is decomposed into four clinical decision dimensions: timing of initiation, strain formulation, supplementary feeding type when own mother's milk is insufficient and management during antibiotic and antacid exposure.

    PROTECT-Preterm: emulating target trials of dynamic probiotic strategies for necrotising enterocolitis, late-onset sepsis and mortality in very preterm infants – a study protocol · 2026 · DOI

  • The mechanisms underlying defective epithelial regeneration remain poorly understood despite advances in single-cell omics.

    Molecular and Chromatin Accessibility Programs Underlying Epithelial Injury and Impaired Regeneration in Neonatal Necrotizing Enterocolitis · 2026 · DOI

  • The biological relationship between maternal diet and neonatal intestinal vulnerability remains unclear.

    Maternal High-Fat Diet Worsens Necrotizing Enterocolitis via Effects on Mitochondrial Function in Newborn Mice · 2026 · DOI

  • Background and objectives The relationship between early feeding patterns and growth and neurodevelopment in term high-risk infants remains unclear.

    Association of early feeding patterns with physical growth and neurodevelopment in term high-risk infants: a retrospective study · 2026 · DOI

  • Breast milk contains abundant glutamine and glutamate, yet their roles in neonatal gut health remain controversial.

    The Glutamine Metabolic Switch Influences the Response of Neonatal Intestinal Macrophages to Breast Milk · 2025 · DOI

  • Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants and the most common cause of neonatal death, whereas the molecular mechanism of intestinal injury remains unclear accompanied by deficiency of effective therapeutic approaches.

    Git2 deficiency promotes MDSCs recruitment in intestine via NF-κB-CXCL1/CXCL12 pathway and ameliorates necrotizing enterocolitis · 2024 · DOI

  • High protein intake supports initial growth in preterm infants, although the long-term benefits remain unclear.

    Formula protein versus human milk protein and the effects on growth in preterm born infants · 2024 · DOI

  • Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear.

    Necrotizing enterocolitis in monochorionic twins: Insights from an identical twin model · 2024 · DOI

  • The interactions between human milk and the regulation of innate immune homeostasis in newborns, and their impact on intestinal health, are not fully understood.

    The Human Milk-derived Peptide Drives Rapid Regulation of Macrophage Inflammation Responses in the Neonatal Intestine · 2024 · DOI

  • However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear.

    Scattered Crypt Intestinal Epithelial Cell Apoptosis Induces Necrotizing Enterocolitis Via Intricate Mechanisms · 2024 · DOI

  • While 24-hour (diurnal) variations in human milk composition for term-born infants have been reported, evidence concerning diurnal variation of preterm human milk composition remains inconclusive.

    Chrononutrition: 24-hour variation in macronutrients in very preterm human milk · 2026 · DOI

  • The genetic basis of impaired intestinal barrier function in preterm infants is poorly understood.

    Single Immunoglobulin Interleukin1-Related Receptor-TWIST1 Axis Regulates Barrier Function in Neonatal Intestine · 2026 · DOI

  • Investigate whether the observed enhanced proliferative response is due to additive effects or genuine synergistic interactions between 2′-FL and 6′-SL, - Determine the effects of SMP + 6′-SL supplementation on immune function and gut microbiota, - Examine the potential benefits of multi-component HMO supplementation on immunoregulatory…

    Modulating effects of 2′-fucosyllactose and 6′-sialyllactose supplementation in a nutrient-rich skim milk base on immune function and gut microbiota in healthy mice · 2026 · DOI

  • Larger multicenter validation, - Mechanistic investigation of FGF5, - Functional studies on the potential protective role of FGF5 in intestinal barrier…

    Serum Olink proteomics-based exploration of novel predictive biomarkers for necrotizing enterocolitis · 2026 · DOI

  • The study had a retrospective observational design, - The sample size available for neurodevelopmental assessment was limited, - Some baseline variables had missing…

    Association of early feeding patterns with physical growth and neurodevelopment in term high-risk infants: a retrospective study · 2026 · DOI

Most-cited papers in Infant Nutrition and Health

Most recent work

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Open questions raised by papers listed on this page include: (1) The effects of HMO supplementation on immune function and gut microbiota in healthy mice are not well understood (“Modulating effects of 2′-fucosyllactose and 6′-sialyllactose supplementation in…”, 2026); (2) There is a need to characterize the bacterial composition and diversity of human milk in this population (“Breast Milk Microbiota at One Month Postpartum in Women from Arequipa, Peru,…”, 2026); (3) Asymptomatic physiological hypercalcaemia in exclusively breastfed infants is recognised but has not been systematically characterised when breastfeeding is continued (“Breast milk–associated physiological hypercalcaemia: an observational study of…”, 2026); (4) The mechanisms underlying defective epithelial regeneration remain poorly understood despite advances in single-cell omics (“Molecular and Chromatin Accessibility Programs Underlying Epithelial Injury and…”, 2026); (5) The biological relationship between maternal diet and neonatal intestinal vulnerability remains unclear (“Maternal High-Fat Diet Worsens Necrotizing Enterocolitis via Effects on…”, 2026). 445 gap statements have been mined from Infant Nutrition and Health papers in our 7.9M-paper local library, which holds 1,856 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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