Open research questions in Infant Nutrition and Health

What the literature leaves open

• These findings provide a rigorously controlled characterisation of the immediate post-birth ruminant microbiota and suggest that, at the moment of sampling, community composition was more strongly associated with anatomical site than with maternal inoc- ulation route; whether this reflects longer-term colonisation dynamics remains to be determined by longitudinal investigation. Importantly, our inferences are restricted to the immediate post- natal period, and whether delivery method contributes to later divergence remains unknown.

  Microbial colonisation of the neonatal beef calf gastrointestinal tract: limited influence of birth delivery method across five anatomical regions · 2026 · DOI

• Abstract Gamma‐glutamyltransferase (γGT), a key enzyme in glutathione metabolism, is abundant in colostrum and may indicate neonatal gastrointestinal maturation, although normative serum values and associations with breast milk intake remain unclear, particularly in preterm infants.

  Gamma‐glutamyltransferase and immunoglobulin G in intestinal maturation: Pilot study in preterm and term infants and the influence of breast milk · 2026 · DOI

• Fish oil lipid emulsions (FO-ILE) have emerged as a potential therapeutic alternative; however, the optimal dose for balancing efficacy and safety remains uncertain.

  Fish oil emulsion for reversal of intestinal failure-associated liver disease in preterm infants: Three case reports and review of literature · 2026 · DOI

• HM composition during the complementary feeding period remains under-researched in New Zealand, with most studies classifying HM expressed beyond two weeks postpartum as “mature milk,” potentially overlooking changes in nutrient content, as HM composition is known to change over the course of lactation.

  Nutrient composition of human milk at 7–10 months postpartum and its contribution to infant energy intake · 2026 · DOI

• These findings suggest that oral SCFA exposure via human milk is insufficient to reduce infant allergy risk, and that gut SCFA production may be a more relevant target for future allergy prevention research.

  Human milk short-chain fatty acid concentrations are not associated with early childhood allergic disease · 2026 · DOI

• Despite 97% surgical repair success rate, 40% of affected infants require hospital readmission due to gastrointestinal complications, where underlying mechanisms remain poorly characterized.

  Untargeted cord blood metabolomics reveals altered lipid metabolism in neonates with gastroschisis · 2026 · DOI

• KEY MESSAGES: Broadly speaking, human milk has evolved to meet an infant's requirements but this might not always be the case as breastmilk composition can vary widely between mothers for some nutrients.

  Maternal Nutritional Status and Breastmilk Composition · 2026 · DOI

• Glycosaminoglycans (GAGs), including chondroitin sulphate (CS), are understudied due to existing protocols requiring sample volumes of at least 5 mL and lengthy extraction steps prior to instrumental analysis.

  Label-Free Determination of Chondroitin Sulphate from Microgram Quantities of Human Milk · 2026 · DOI

• Although Bacteroidetes and Bacteroides did not reach statistical significance, their effect sizes suggest a need for further investigation into their roles in NEC pathogenesis in full-term infants.

  Study of the gut microbiome profile in full-term infants with necrotizing enterocolits · 2026 · DOI

• The review has several limitations. First, we searched only English-language databases, potentially miss- ing studies published in other languages. Second, all studies included in the analysis were observational, and no RCTs were available; therefore, despite the observed association between pRBC transfusion and NEC deterioration, causality cannot be established. Third, owing to the limited number of included stud- ies, statistical tests for publication bias and sensitivity analyses may be unreliable. The reported OR is highly susceptible to bias and may be inflated because of the observational design and lack of adjust- ment for key confounders. Some sensitivity analyses were based on only 1–2 studies, yielding unstable estimates. Thus, these effect sizes should be interpreted with caution. Furthermore, because of the lim- ited available literature, we did not adopt a standardized definition of NEC deterioration. This heteroge- neity may affect the validity of our findings, and future studies should use standardized definitions to enable meaningful meta-analyses. Fourth, confounding by indication and time-varying confounding or reverse causation cannot be ruled out. Infants with more severe anemia or advanced NEC are sicker and more likely to receive pRBC transfusions, and these same factors may independently increase the risk of NEC deterioration, potentially explaining the observed association. In addition, transfusions may be given after clinical deterioration begins, making it unclear whether the transfusion preceded or followed dis- ease progression. This temporal ambiguity limits causal inference. Finally, because of the limited number of included studies, subgroup analyses could not be conducted according to the NEC severity, transfu- sion volume, number of transfusions, or timing of transfusion. These parameters may be associated with NEC progression and may provide valuable insights into the mechanisms underlying the observed 8 J. HUANG ET AL. association. However, due to insufficient available data, we were unable to incorporate these variables into the analysis. Future studies should systematically collect and report these variables to enable more comprehensive evaluations.

  Association between packed red blood cell transfusion and clinical deterioration in neonatal necrotizing enterocolitis: a systematic review and meta-analysis · 2026 · DOI

• Further studies on the study of the pathogenetic mechanisms of colic and the determination of the causal relationship between etiological factors and the brightness of clinical manifestations of colic, taking into account the eff ect of antibiotic therapy in the fi rst 5 months of life on the intestinal microbiome, will allow to develop eff ective strategies for prevention and treatment of colic in infants.

  FEATURES OF MICROBIAL COLONIZATION IN THE INTESTINES IN COLIC IN INFANTS WITH A HISTORY OF ANTIBIOTIC THERAPY · 2024 · DOI

• New research and further study of intestinal murmurs in premature newborns of different gestational ages with the development of clear criteria for data interpretation are needed to assess the maturity of the gastrointestinal tract, to create a diagnosis plan of food intolerance, and to develop an algorithm for early intervention.

  Food intolerance in premature babies: possibilities of additional diagnostics · 2023 · DOI

• Although probiotics have been routinely used for NEC prophylaxis in neonatal intensive care units around the world, clinical trials provide contradictory data, which fuels an ongoing debate about their efficacy and safety.

  Probiotic Use in Preterm Neonates: A Review and Bibliometric Analysis · 2022 · DOI

• Despitethe fact that lots of doctors argue their usual use of probioticsin premature newborns, other groups, including ESPGHANand АРР are more cautious admitting the main restrictions ofmany researches, methodological differences in the design ofa research and guidelines along with the conclusion that theeffectiveness of probiotics may vary widely.

  DO PROBIOTICS HAVE ANY FUTURE IN NEONATOLOGY? (ANALYSIS OF THE LATEST DATA. PART I) T. K. Znamenska, O. V. Vorobiova · 2021 · DOI

• Although the pathogenesisof these diseases remains incompletely defined andunderstood, one of the leading risk factors is the immaturityof the immune system, which determines the tendencyof premature infants to develop excessive inflammatoryresponse and disruption of the formation of "healthy" gutmicrobiota.

  OPPORTUNITIES AND PERSPECTIVES OF IMMUNE NUTRITION IN PRETERM INFANTS · 2021 · DOI

• However, there is great heterogeneity in the reviewed studies and scientific data on the use of gut microbiome characteristics and related biomarkers in GDM risk stratification and diagnosis are scarce.

  The role of gut microbiome in prevention, diagnosis and treatment of gestational diabetes mellitus · 2021 · DOI

• Many serological markers for the diagnosis of necrotizing enterocolitis are suggested, including: C-reactive protein, platelet activating factor, binding protein intestinal fatty acid, fecal calprotectin, matrix metalloproteinase inhibitors of matrix metalloproteinases, Claudin-3, endogenous antimicrobial peptide cathelicidin, citrulline, but there is no consensus as to their use in terms of clinical benefit.

  Modern possibilities of diagnostic and surgical treatment of neonatal necrotizing enterocolitis. (Review article) · 2015 · DOI

• There is insufficient evidence to support the claims that removing or reducing lactose, using hydrolyzed or soy protein or adding pre-/probiotics to formula benefits infants with fussiness, gas, or colic yet claims like "soy for fussiness and gas" encourage parents who perceive their infants to be fussy to purchase modified formula.

  A Critical Review of the Marketing Claims of Infant Formula Products in the United States · 2015 · DOI

• Background The mechanisms influencing successful outcomes of oral Immunotherapy (OIT) are poorly understood.

  Deep phenotyping of infants and toddlers undergoing food oral immunotherapy (DINOSAUR): design and baseline characteristics of a prospective multi-omics cohort · 2026 · DOI

• To date, the potential direct and synergistic effects of BI and HMO have not been fully explored.

  <i>Bifidobacteria infantis</i> and human milk oligosaccharides have independent and synergistic effects on immune response and amino acid metabolism in germ-free mouse models · 2026 · DOI

• While the biochemical composition of breast milk has been widely studied, the relationship between maternal metabolic status and the aqueous dynamics of foremilk remains underexplored, particularly in rapidly transitioning populations such as India.

  Establishing Reference Standards for Foremilk Composition in Relation to Maternal Metabolic Profiles: Evidence from Indian Populations · 2026 · DOI

• We further identified that T cell-derived soluble factors alone were insufficient to modulate intestinal stem cell fate, implying the need for physical interactions.

  Early-life mucosal T cells direct intestinal stem cell fate via a coordinated developmental program · 2026 · DOI

• IMPORTANCE Gastroenteritis continues to cause much morbidity among infants in high-income countries, and the relationship with the gut microbiome is not fully understood, especially for well-nourished and breastfeeding infants.

  Stool microbial composition is associated with recent and future diarrhea and fever events in breastfed Danish infants · 2026 · DOI

• On the contrary, the described possible consequences of the eff ects of colic on the behavior and quality of the disturbed digestion indicate that this is an understudied phenomenon.

  FEATURES OF MICROBIAL COLONIZATION IN THE INTESTINES IN COLIC IN INFANTS WITH A HISTORY OF ANTIBIOTIC THERAPY · 2024 · DOI

• However, in this context, only a few studies have explored the impact of the mode of delivery on the intestinal microbiome in children in Guangzhou, China.

  Influence of mode of delivery on infant gut microbiota composition: a pilot study · 2024 · DOI

Most-cited papers in Infant Nutrition and Health

• Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Timing of Introduction of Complementary Foods, and Hydrolyzed Formulas · PEDIATRICS · 2007 · 837 citations
• Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months · Canadian Medical Association Journal · 2013 · 777 citations
• Beneficial Effects of Breast Milk in the Neonatal Intensive Care Unit on the Developmental Outcome of Extremely Low Birth Weight Infants at 18 Months of Age · PEDIATRICS · 2006 · 453 citations
• Water, sanitation, and hygiene (WASH), environmental enteropathy, nutrition, and early child development: making the links · Annals of the New York Academy of Sciences · 2014 · 378 citations
• Antibiotic Exposure in Infancy and Risk of Being Overweight in the First 24 Months of Life · PEDIATRICS · 2015 · 322 citations
• Contemporary Outcomes for Infants with Necrotizing Enterocolitis—A Systematic Review · The Journal of Pediatrics · 2020 · 317 citations
• Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials · Canadian Medical Association Journal · 2006 · 129 citations
• Acquisition and establishment of the oral microbiota · Periodontology 2000 · 2021 · 122 citations
• Infant microbes and metabolites point to childhood neurodevelopmental disorders · Cell · 2024 · 118 citations
• Acute lower respiratory infections in childhood: opportunites for reducing the global burden through nutritional interventions · Bulletin of the World Health Organization · 2008 · 95 citations

Most recent work

• Risk Factors Associated with Extrauterine Growth Restriction (EUGR) Among Hospitalised Preterm Neonates <34 Weeks of Gestational Age: A Prospective Cohort Study · The Indian Journal of Pediatrics · 2026
• Neonatal Lactic Acidosis Associated With Antiretroviral Exposure: A Case Report · Cureus · 2026
• Standardised reporting framework for nutrition and growth in preterm nutrition studies: the NutriGrow Delphi study · Pediatric Research · 2026
• The protective effect of probiotics on intestinal mucosal injury and dysbiosis in infants with congenital heart disease undergoing cardiopulmonary bypass · Frontiers in Immunology · 2026
• Impact of breast milk composition on nutritional status of term neonates with congenital heart defects: A prospective study · World Journal of Clinical Pediatrics · 2026
• Study of the gut microbiome profile in full-term infants with necrotizing enterocolits · World Journal of Clinical Pediatrics · 2026
• Assessment of compliance to the guidelines on nutritional support in a neonatal intensive care unit: association with an electronic health Records implementation · BMC Medical Informatics and Decision Making · 2026
• Effect of infant formula with probiotics on intestinal microbiota · Archivos Latinoamericanos de Nutrición · 2026
• HUMAN MILK–BASED FORTIFIERS IN PRETERM INFANTS – CLINICAL BENEFITS AND LIMITATIONS IN THE LIGHT OF CURRENT EVIDENCE · International Journal of Innovative Technologies in Social Science · 2026
• Colostrum: Composition, Pharamacological Properties and Therapeutic Applications · Zenodo (CERN European Organization for Nuclear Research) · 2026

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