The management of meconium ileus (MI) has yet to reach a unified consensus among pediatric surgeons, particularly regarding diagnostics and variants, conservative treatment strategies, surgical approaches, and clinical outcomes. This topic was therefore selected for the 2024 Consensus Session of the Annual Congress European Paediatric Surgeons' Association (EUPSA). A structured literature review was conducted across Cochrane, Medline, and EMBASE databases up to April 2024. Nine pediatric surgeons appointed by the European Paediatric Surgeons' Association (EUPSA) Consensus Committee reviewed the evidence and developed topic-specific recommendations relating to (1) diagnostics and variants, (2) Gastrografin® (Bracco Diagnostics Inc, Monroe Township, NJ) application and outcomes, and (3) surgery-related outcomes. Findings were presented at the 2024 EUPSA Annual Congress, with consensus statements formulated through iterative discussion and refinement, incorporating feedback from congress participants. The consensus addresses antenatal and postnatal diagnosis, differentiation between simple and complex MI, conservative management using contrast enemas, surgical strategies, and short- and long-term outcomes, particularly in relation to cystic fibrosis (CF). Key recommendations include the use of contrast enema as the primary diagnostic modality and first-line treatment in uncomplicated cases, with surgical intervention indicated for complicated MI or failed conservative management. Enterostomy remains a widely used surgical approach, with technique guided by intraoperative findings and patient factors. Recommendations regarding stoma reversal emphasize the role of multidisciplinary assessment and preoperative evaluation including CF workup and confirmation of distal bowel patency. A peer-reviewed consensus statement on the diagnosis and management of MI has been developed, informed by current evidence and expert practice. This statement provides pragmatic guidance in the diagnosis and management of MI, including the role of contrast enema in uncomplicated cases and surgical intervention for complicated disease. It is recognized by the EUPSA as a valuable resource to support pediatric surgeons in clinical decision-making for this pathology.

Genotype-phenotype correlation of CFTR variants in cystic fibrosis patients.

BACKGROUND: This study aimed to evaluate the diagnostic and therapeutic utility of ultrathin colonoscopy for lower gastrointestinal disorders in neonates, including extremely preterm infants and to describe the associated clinical and etiological spectrum. We conducted a retrospective analysis of 15 neonates who underwent ultrathin colonoscopy at Tangdu Hospital (March 2018 to February 2026). Data on patient characteristics, clinical presentation, endoscopic findings, diagnostic yield (defined as the proportion of cases in which an etiologic diagnosis was established based on endoscopic and/or histopathologic findings.), and therapeutic outcomes were analyzed. The cohort included 15 neonates (53.3% preterm), with one extreme case of 26⁺³ weeks' gestation and 740 g birth weight. The most common symptom was abdominal distension (13/15, 86.7%). All procedures were completed safely without complications. Abnormal endoscopic findings were observed in 13 cases (86.7%), leading to definitive diagnoses: meconium ileus (n = 5), allergic proctocolitis (n = 4), necrotizing enterocolitis (n = 2), very early-onset inflammatory bowel disease (n = 1), and eosinophilic colitis (n = 1). Two examinations were normal. Ultrathin colonoscopy in neonates appears feasible, with a preliminary safety profile in this small, selected cohort from a single-center retrospective feasibility study, especially for non-emergent symptoms. It facilitates early etiological diagnosis and allows timely endoscopic intervention, however, larger prospective studies are warranted to confirm these preliminary observations. This study demonstrates the safety and feasibility of ultrathin colonoscopy for both diagnosis and therapeutic intervention in critically ill neonates, including an extremely preterm infant with a gestational age of only 26⁺³ weeks and a birth weight of 740 g. Ultrathin colonoscopy achieved a high diagnostic yield (86.7%) for neonatal lower gastrointestinal diseases and enabled immediate minimally invasive treatment, successfully avoiding surgery in meconium ileus. The application of this technique provides a new, less invasive diagnostic-therapeutic pathway. It can serve as a minimally invasive adjunct for non-surgical management of uncomplicated meconium ileus, reducing unnecessary surgical risks in neonates.

Microplastics (MPs) in the environment pose a significant threat to human health, particularly for vulnerable populations like infants. Over the past decades microplastics have infiltrated food systems, air, water, and consumer products, leading to widespread human exposure. Infant foods, including formula and complementary foods, may be contaminated with MPs during processing or packaging or through environmental pollutants. This scoping review was aimed to explore the extent of MP contamination in infant foods, its potential nutritional and health impacts, and the associated risks to the health of children. Following the search strategy, a comprehensive literature search was conducted across 5 electronic databases (PubMed, Google Scholar, Cochrane, Scopus, and EBSCO HOST). All records identified through the databases were exported into EndNote X9 reference manager for deduplication and selection in line with the inclusion criteria. In all, 1871 records were identified in which 28 studies met the inclusion criteria and were included in this review. All studies were published during 2020-2024. The studies were classified into 2 designs: systematic reviews (n = 16) and primary studies (n = 12). Studies detected MPs in infant formula, breast milk, food-contact materials, feeding bottles, indoor air, and selected human biological matrices, including placenta, meconium, and infant feces. Ingestion and inhalation emerged as the most consistently supported exposure pathways, while prenatal and breastfeeding-related exposures were supported by biomonitoring evidence and dermal exposure remained weakly evidenced. Reported polymer types varied widely, with limited and inconsistent reporting of particle size and nanoplastics across studies. No studies originated from Sub-Saharan Africa, highlighting a major geographic gap. This scoping review indicates that infants are exposed to MPs through multiple pathways-most consistently via ingestion and inhalation-yet infant-specific health effects remain poorly defined, underscoring the need for improved particle characterization, broader geographic evidence, and precautionary, nutrition-sensitive approaches to research and practice.

Advances in genomic technologies, particularly massively parallel sequencing of cell-free fetal DNA, have transformed prenatal screening and created opportunities for fetal therapies. First-tier screening for trisomy 21 (T21) now enables early identification of affected fetuses, raising the possibility of prenatal intervention. Down syndrome (DS) is increasingly recognized not only as a neurodevelopmental condition but also as an interferon-driven disorder of immune dysregulation. Preclinical studies using human cellular models and trisomic mice demonstrated abnormalities in oxidative stress and inflammatory pathways. Connectivity Map-guided identification of apigenin, a naturally occurring flavonoid, showed partial normalization of gene expression, reduced neuroinflammation, and improved hippocampal-dependent learning in a mouse model, supporting the concept that atypical fetal brain development in T21 may be modifiable. Parallel human studies have confirmed chronic hypercytokinemia and autoimmunity in DS, and postnatal treatment with JAK inhibitors has shown early clinical benefit. A similar therapeutic paradigm is emerging for cystic fibrosis, where noninvasive prenatal testing detects CFTR variants and highly effective CFTR modulators are increasingly used during pregnancy. Early reports suggest that in utero exposure may ameliorate fetal complications such as meconium ileus. Together, these advances support a framework in which selected genetic disorders may be treatable beginning in fetal life. IMPACT: Advances in engineering and computational science, coupled with new biological and genomic knowledge, have led to novel prenatal opportunities to improve child health and treat disease.

Total abdominal pneumatosis, gastric emphysema, and portal vein gas as an initial presentation of Hirschsprung disease: a case report

Human milk oligosaccharides (HMOs) are abundant and structurally diverse glycans that shape the development of infant gut microbiota. Yet, how individual HMOs and bacterial genes drive the community assembly remain elusive. Here, we reconstructed an eight-member infant Bacterial Community (iBaCo) from representing dominant taxa in human infant feces. When individual HMOs were the sole carbohydrate source, they showed deterministic effects on the iBaCo composition and metabolic output. Notably, the tetramer HMO lacto-N-tetraose (LNT), in spite of its identical monomer composition as lacto-N-neotetraose (LNnT), showed a strong effect on maintaining Bifidobacterium breve abundance in iBaCo, whereas LNnT did not. Monoculture growth profiling, proteomics, enzymatic kinetic assay, and molecular docking revealed that β-galactosidase D4BMY8 and the relevant downstream pathways are induced by LNT and that D4BMY8 has substrate preference on LNT over LNnT, enabling a faster growth of Bi. breve and accumulation of acetate and lactate in LNT compared to LNnT. Metabolic flux analysis indicated that the substrate-preference of β-galactosidase D4BMY8 drives the skewed energy cost toward lactate/acetate metabolic output. Finally, the D4BMY8-encoding gene lacZ5 is widely spread in all isolated Bi. breve genomes, but divergently distributed in infant metagenome-assembled Bi. breve genomes. Together, we demonstrated that a single enzyme-substrate interaction could orchestrate the composition and metabolic function of an infant bacterial community, which may contribute to the assembly of dynamic infant gut microbiota. Our integrative approach provides a mechanistic framework for understanding the interaction between diet, microbial community, and infant gut health.

We sought to determine whether a cystic fibrosis transmembrane conductance regulator (CFTR) mRNA could be administered to the fetus via the transamniotic route as a potential strategy for the perinatal management of cystic fibrosis-associated meconium ileus. Nine pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 109) of either a suspension of a human CFTR mRNA encapsulated by a semi-synthetic composite, lipopolyplex (mRNA group; n = 98), or of a suspension of the same composite free of mRNA (control group; n = 11), on gestational day 17 (E17; term = E21). At daily time points until term, fetal small bowel and lungs, along with maternal serum, were quantitatively screened for the human CFTR protein by ELISA. Statistical analysis was by the nonparametric Wilcoxon rank sum test with Bonferroni adjustment. Overall fetal survival was 85.3% (93/109), with no significant differences between the groups or time points. When controlled by mRNA-free injections, human CFTR was detected in the small bowel from the mRNA group at all time points (p < 0.001 for all), increasing initially over time. Human CFTR was detected comparably in the lungs from both groups, suggesting interspecies homology at that anatomical site. No human CFTR was detected in maternal serum. Encapsulated exogenous mRNA encoding for the cystic fibrosis transmembrane conductance regulator protein can be incorporated and translated by fetal small bowel cells after simple intra-amniotic injection in a healthy rodent model. Transamniotic mRNA delivery could become a novel strategy for the perinatal management of meconium ileus associated with cystic fibrosis.

Current evidence on the relationship between breast milk fatty acids and infant eczema is limited. The present study aimed to investigate the association between polyunsaturated fatty acids (PUFAs) in breast milk and the incidence of infant eczema and its relationship with infant gut microbiota. Twenty-five infants diagnosed with eczema and fifty healthy infants born during the same period were recruited at 1 month postpartum. A follow-up was conducted on healthy infants at 6 months postpartum to determine if any new-onset eczema occurred. Breast milk and infant feces were collected at each interview. In the case-control study, after adjusting for confounding factors, C20:3n-3, C20:5n-3, total n-3 PUFAs, and total n-3 PUFAs/total n-6 PUFAs in breast milk were significantly inversely associated with infant eczema risk. The abundance of Clostridium and Streptococcus in the gut of infants with eczema were significantly lower than those in control group (p <0.05). C20:3n-3 and total n-3 PUFAs in breast milk were positively correlated with Clostridium abundance. In the follow-up study, the decreases of C20:3n-3 and total n-3 PUFAs in the breast milk of new-onset eczema group were greater than those of healthy group at 6 months postpartum. Moreover, the abundance change of Clostridium in infants with new-onset eczema was significantly greater than that in healthy group. C20:3n-3 and total n-3 PUFAs in breast milk were associated with decreased risk of infant eczema, and this association may be related to the abundance of Clostridium in infant's gut.

Bifidobacterium species are widely used as probiotics; yet their strain-specific immunomodulatory mechanisms remain incompletely defined. In this study, we characterized the probiotic properties and immunomodulatory activities of two genetically distinct strains, B. lactis HOM2120, isolated from human milk, and B. longum HOM1190, isolated from infant feces. Genomic analyses revealed strain-specific features associated with environmental resilience and probiotic functionalities, including acid and bile tolerance, pathogen inhibition, and adhesion to intestinal epithelial cells, which were confirmed by in vitro assays. In RAW264.7 macrophages, HOM2120 preferentially enhanced phagocytosis and TNF-α production, whereas HOM1190 induced higher IL-6 secretion, reflecting distinct strain-specific immunomodulatory patterns. Transcriptomic profiling and qRT-PCR validation revealed distinct molecular signatures underlying these effects. HOM2120 preferentially activated NF-κB and STAT3 signaling pathways and induced higher Tnf expression, suggesting a bias toward cell-mediated immune responses. In contrast, HOM1190 more strongly modulated the PI3K–Akt signaling axis and upregulated Il6 and Cd80 expression, supporting enhanced antigen presentation and humoral immune–associated responses. These strain-specific immunological tendencies were further validated in mice. HOM2120 predominantly enhanced delayed-type hypersensitivity responses, indicative of cellular immunity, whereas HOM1190 more effectively increased hemolytic activity and antibody-producing cell numbers, reflecting preferential activation of humoral immunity. Collectively, these results suggest that HOM2120 and HOM1190 are functionally distinct yet synergistic probiotic candidates, supporting their potential application as functional food ingredients or therapeutic adjuncts to modulate host immunity.

Aim: In some settings, the diagnostic evaluation of cystic fibrosis (CF) may be delayed due to limited access to sweat chloride tests.This study aimed to describe the clinical and laboratory findings observed during the evaluation of children with positive newborn screening (NBS) results for CF.Materials and Methods: We retrospectively reviewed the data of children referred after positive NBS for CF who were evaluated at three pediatric pulmonology centers between 2015 and 2021.NBS was used as a referral tool, and the diagnosis of CF was established according to standard diagnostic criteria, including the sweat chloride test and/or genetic analysis.Demographic characteristics, clinical features, and laboratory findings were compared between those children diagnosed with CF after NBS and those not diagnosed with CF.Results: A total of 1,469 children were included, of whom 76 (5.2%) were diagnosed with CF.CF was more frequently observed in those children with parental consanguinity, a history of meconium ileus, steatorrhea, doll-like facial appearance, metabolic alkalosis, hyponatremia, hypokalemia, hypochloremia, and having a sibling with CF (all p<0.05). Conclusion:This large multicenter cohort study presents real-life data on the clinical and laboratory findings observed in those children with positive NBS for CF.This study does not propose an alternative diagnostic strategy to the sweat chloride test, but highlights supportive clinical features which may raise clinical suspicion and emphasizes the importance of timely referral and follow-up, particularly in settings where access to confirmatory testing may be delayed.

Probiotics are live microorganisms that confer health benefits to the host through adequate viability, safety, and functional interaction with host cells. In this study, Bifidobacterium longum subsp. infantis JNU311 (JNU311) was isolated from the feces of a 3-week-old newborn, and its probiotic potential was assessed. Among the tested Bifidobacterium strains, JNU311 achieved the highest viable cell count (1.5 × 109CFU/mL) after 36h in 10% skim milk, indicating suitability for fermented dairy applications. JNU311 did not inhibit growth of Lactobacillus acidophilus or Streptococcus thermophilus in mixed cultures. Functional characterization revealed that JNU311 was nonhemolytic and tolerant to acidic and bile conditions. Moreover, it exhibited bile salt hydrolase activity. The strain effectively adhered to HT-29 intestinal epithelial cells, showed no cytotoxicity in MTT assays, met antibiotic safety criteria, and reduced TNF-α production in LPS-stimulated RAW 264.7 cells. These findings support probiotic potential of JNU311 for use in health-promoting dairy products.

Predicting the risk of reoperative intervention for adhesive bowel obstruction in neonates: The neonatal adhesion risk score (NARS).

Small molecule therapies that restore function to the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein, referred to as CFTR modulators, have emerged as a key therapeutic approach for people with CF who carry responsive genetic variants. Their effects have been transformative to the lives of many of those living with CF. As the reach of CFTR modulators expands, new questions arise about their role beyond approved clinical indications for people with CF. One such area of growing interest is the use of CFTR modulator therapy during pregnancy to treat suspected meconium ileus, a particularly severe fetal and immediate postnatal manifestation of CF. In this review, we summarize the current data about use of CFTR modulator therapy during pregnancy, including reported effects in pregnant persons and their offspring. We describe the potential of this in utero therapy to prevent meconium ileus and to maintain exocrine pancreatic function in infants with CF. However, these potential benefits must be weighed carefully with the known and potential risks of CFTR modulator therapy. We address ethical implications and important knowledge gaps related to prenatal CFTR modulator use during pregnancy. Further evidence is needed to determine best practices for CFTR modulator use during pregnancy.

Although highly effective modulator therapy may reduce future gastrostomy tube (g-tube) placements, a better understanding of the benefits of g-tube placement is needed. To describe the characteristics of children with cystic fibrosis (CF) who underwent g-tube placement and determine if earlier placement is associated with improved clinical outcomes. Retrospective cohort analysis of children with CF born 2003-2019 and followed in the US CF Foundation Patient Registry. There were 2337 children with CF (22.9% of the study cohort) who underwent g-tube placement. Compared with children with CF who did not receive a g-tube, a higher proportion of g-tube recipients were diagnosed via meconium ileus or failure to thrive, born at <37 weeks' gestation or had only class I-III CF transmembrane conductance regulator mutations. G-tube recipients at age 0-1 years who were malnourished had improved body mass index (BMI) z-scores post-placement, though moderately to severely malnourished recipients did not achieve BMI z-scores >0. In contrast, only g-tube recipients at age ≥2 years who were severely malnourished achieved BMI z-scores >0. For g-tube recipients at age 0-1 years, per cent predicted of forced expiratory volume in 1 s (ppFEV1) at age 6-7 years was inversely correlated with malnutrition severity. In contrast, g-tube recipients at age ≥2 years had similar median ppFEV1 at age 6-7 years regardless of malnutrition severity, except those with severe malnutrition had slightly lower median ppFEV1. Timing of g-tube placement in children with CF, both in relation to age and severity of malnutrition, was associated with varying degrees of improvements in BMI z-scores and ppFEV1.

Background: Transumbilical laparoscopic-assisted (TULA) surgery is a minimally invasive technique that combines laparoscopic exploration with extracorporeal surgical management, offering potential advantages in neonatal abdominal surgery. However, comparative data with conventional open surgery in neonates remain limited. This study reports our single-center experience with TULA and compares its outcomes with those of a matched cohort of neonates undergoing open surgery. Methods: We performed a retrospective study on neonatal patients (<28 days of life) treated at our Pediatric Surgery Unit between 2015 and 2023. Twenty-five neonates underwent TULA for various intra-abdominal malformations. Each TULA patient was matched in a 1:2 ratio with neonates treated with open surgery based on gestational age, birth weight, and underlying diagnosis, resulting in a matched cohort of 50 patients. Primary outcomes included operative and anesthesia times, conversion rate, postoperative complications, length of hospital stay, and mortality. Results: The TULA cohort included 11 males and 14 females, with a mean gestational age of 37.5 ± 1.9 weeks and a mean birth weight of 2989 ± 675 g. Indications comprised intestinal malrotation, ileal atresia, duodenal stenosis, meconium ileus, and other abdominal pathologies. Mean operative time was comparable between groups (116 ± 37 min in the TULA group vs. 137 ± 65.9 min in the open surgery group; p = 0.52). Conversion from TULA to open surgery occurred in 16% of cases. No significant differences were observed in major postoperative complications or length of hospital stay between groups (p > 0.05). No mortality was reported. Conclusions: TULA represents a safe and effective surgical option for selected neonatal abdominal pathologies, with outcomes comparable to conventional open surgery. When performed in specialized centers with appropriate patient selection and multidisciplinary expertise, TULA offers favorable safety and cosmetic results.

Bifidobacteria are among the most dominant members of the human gut microbiota throughout life and are associated with host health. Multiple Bifidobacterium species have been isolated from human faeces, with species composition differing according to host age and between individuals. This species- and subspecies-level diversity reflects adaptation to host niches. Bifidobacterium catenulatum currently comprises two subspecies catenulatum and kashiwanohense, which appear to exhibit different ecological adaptations. Our previous study suggested undefined lineages closely related to B. catenulatum. In this study, we investigated these lineages through comparative genomic and phylogenetic analyses of 43 strains, including new isolates from human faeces.Phylogenetic reconstructions based on 16S rRNA gene sequences, multilocus sequence analysis, average nucleotide identity (ANI) and core-gene alignments consistently supported the delineation of two distinct taxa. The first group, consisting of 15 strains, exhibited ANI values of ≥96.41% among themselves but ≤94.79% compared with the known subspecies of B. catenulatum, confirming its classification as a novel species, which was recently validated as Bifidobacterium hominis. The second group, comprising four strains, showed ANI values ranging from 94.38 to 95.65% compared to the existing subspecies of B. catenulatum, indicating that they belong to the same species. However, phylogenetic analyses and distinct substrate utilization profiles supported their designation as a novel subspecies, B. catenulatum subsp. puerorum subsp. nov.Comparative genomic analyses revealed key differences in genes associated with gut adaptation. B. catenulatum subsp. puerorum harboured genes involved in human milk oligosaccharide (HMO) and urea metabolism, consistent with its isolation from infant faeces. In contrast, B. hominis exhibited strain-dependent variation in genes for HMO and xylooligosaccharide utilization. Phenotypic analyses supported these distinctions, including unique inulin utilization by B. catenulatum subsp. puerorum. Based on these findings, we characterized the two clades and propose the novel subspecies B. catenulatum subspecies puerorum, with type strain YIT 11099T (=JCM 37523T=DSM 118686T).

Over the past 50 years, therapeutic advances have significantly improved the management of cystic fibrosis (CF). Recently, cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been widely regarded as a therapeutic revolution, and their use is associated with a marked increase in pregnancies among affected women. However, pregnant women were excluded from clinical trials, limiting what is known about maternal and fetal safety. Maternal and fetal outcome tend to be poorer when the disease is severe, but there is limited data on such pregnancies exposed to CFTR modulators. While available data suggest a low risk of birth defects, information on neurological development is lacking and concerns remain regarding lung abnormalities in animal studies, as well as a few cases of congenital cataracts reported in humans. For fetuses affected by CF, the transplacental transfer of CFTR modulators could potentially prevent severe complications, such as meconium ileus, opening promising therapeutic avenues.

We reviewed the contemporary use of cystic fibrosis transmembrane conductance regulator modulator therapy (CFTRm) during pregnancy, including animal data and published human cases involving unaffected pregnant CF (heterozygote) carriers with a prenatal diagnosis of fetal cystic fibrosis (CF). In pregnant individuals with CF, continuation of CFTRm is associated with preserved maternal pulmonary function comparable to nonpregnant peers and favorable obstetrical outcomes. CFTRm crosses the placenta readily, appears at low levels in breastmilk, and concerns for cataracts from animal models have not been translated clinically. Among 20 reported fetal cases treated prenatally with CFTRm in unaffected carrier individuals, ultrasound findings of meconium ileus (MI) resolved in approximately two-thirds of cases. Several reports describe preserved or borderline exocrine pancreatic function and lower-than-expected sweat chloride levels. Nonresolution of MI was more common when therapy began later in gestation or in the presence of complications such as meconium peritonitis. MI was diagnosed at a mean gestational age of 24weeks, while treatment began at 31weeks, reflecting delays in both diagnosis and insurance coverage. The CF Foundation PROTECT Workshop identified key knowledge gaps, including optimal timing of prenatal diagnosis and therapy, fetal pharmacokinetics, neurodevelopmental safety, minimal effective dosing, and prevention of postnatal withdrawal.

This work constructed a recombinant lactic acid bacterium secreting β-galactosidase for GOS formation during milk fermentation. First, GalINF, a β-galactosidase derived from infant feces, was characterized to effectively produce GOS in milk, reaching a content of 10.03 g/L. To export GalINF in Lactococcus lactis, six signal peptide candidates were employed, resulting in extracellular activities as low as 52.83-85.65 U/L. Then, GalINF (114.6 kDa) was split into two complementary modules, M1-P723 and A724-I1023, which could be independently secreted and actively reconstituted with the help of the protein scaffold SpyCatcher/SpyTag. The resultant Lc. lactis B1RG exhibited an extracellular β-galactosidase activity of 544.22 U/L. Fermentation of pasteurized milk with Lc. lactis B1RG and the traditional yogurt starters reduced lactose to 19.67 g/L and yielded 7.17 g/L GOS. This work established an effective strategy to export large-sized proteins extracellularly and demonstrated the applicability of LAB secreting β-galactosidase for GOS-enriched fermented dairy products.