Infant Immune System Research Articles

Effect of protein modification in synbiotic infant formula on probiotic metabolic activity and bacterial composition in an infant gut-model.

Aim: Microbial colonization of the neonatal gut is pivotal in priming the infant's immune system. Human milk (HM) is the best nutrition for infants and supports the development of the microbiota due to prebiotic compounds and probiotic microorganisms. When exclusive breastfeeding is not possible, infant formula (IF) with probiotics is a strategy to support the infant's microbiome development. However, knowledge about the effects of the infant gut microbiota and different compounds in IF on individual probiotic strains is limited, as strain-level detection in a complex ecosystem is challenging. The aim of the present study was to show the effects of IF with different protein forms on the metabolic activity of two probiotic strains isolated from HM in a complex ecosystem. Methods: By using an ex-vivo infant gut model containing infant donor-microbiota, the effects of IF with either intact or extensively hydrolyzed protein on the metabolic activity of the donor microbiota, as well as two probiotic strains [Limosilactobacillus fermentum (L. fermentum) CECT 5716 (Lf) and Bifidobacterium breve (B. breve) DSM 32583 (Bb)], were analyzed. A new bioinformatic pipeline combined with a specific infant microbiome database was used to explore shotgun metagenome datasets (1200 Megabases) for taxonomic identification and strain-level tracking. Results: Both protein forms (i.e., intact or extensively hydrolyzed protein) in IF supported infant gut microbial metabolic activity equally, as evidenced by similar levels of short-chain fatty acids (SCFAs). Interestingly, gut microbial metabolic activity was found to be differently activated in a strain-dependent manner. Taxonomic profiling of the microbiome at the strain level enabled monitoring of the prevalence and abundance of both probiotic strains, even in a complex ecosystem. Conclusion: Food matrix and host microbiota interactions should be considered when evaluating strain-specific probiotic effects in the future.

Transfer of celiac disease-associated immunogenic gluten peptides in breast milk: variability in kinetics of secretion.

Exposure to antigens is crucial for child immune system development, aiding disease prevention and promoting infant health. Some common food antigen proteins are found in human breast milk. However, it is unclear whether gluten antigens linked to celiac disease (CD) are transmitted through breast milk, potentially impacting the development of the infant's immune system. This study aimed to analyze the passage of gluten immunogenic peptides (GIP) into human breast milk. We evaluated the dynamics of GIP secretion after lactating mothers adopted a controlled gluten-rich diet. We prospectively enrolled 96 non-CD and 23 CD lactating mothers, assessing total proteins and casein in breast milk, and GIP levels in breast milk and urine. Subsequently, a longitudinal study was conducted in a subgroup of 12 non-CD lactating mothers who adopted a controlled gluten-rich diet. GIP levels in breast milk and urine samples were assayed by multiple sample collections over 96 hours. Analysis of a single sample revealed that 24% of non-CD lactating mothers on a regular unrestricted diet tested positive for GIP in breast milk, and 90% tested positive in urine, with significantly lower concentrations in breast milk. Nevertheless, on a controlled gluten-rich diet and the collection of multiple samples, GIP were detected in 75% and 100% of non-CD participants in breast milk and urine, respectively. The transfer dynamics in breast milk samples were long-enduring and GIP secretion persisted from 0 to 72h. In contrast, GIP secretion in urine samples was limited to the first 24h, with inter-individual variations. In the cohort of CD mothers, 82.6% and 87% tested negative for GIP in breast milk and urine, respectively. This study definitively established the presence of GIP in breast milk, with substantial inter-individual variations in secretion dynamics. Our findings provide insights into distinct GIP kinetics observed in sequentially collected breast milk and urine samples, suggesting differential gluten metabolism patterns depending on the organ or system involved. Future research is essential to understand whether GIP functions as sensitizing or tolerogenic agents in the immune system of breastfed infants.

Literature Review: Infant formulas with human milk oligosaccharides on gut microbiome and intestinal immune system

Background: Infant formula has a similar composition to breast milk, especially on key components like proteins, fats, and functional oligosaccharides. However, significant differences exist between bovine milk-based formula and human breast milk, particularly in the abundance and diversity of human milk oligosaccharides (HMOs). HMOs are pivotal in shaping the infant gut microbiome and immune system, with potential implications for infant health and development.Objectives: The literature review aimed to explore the role of HMOs in shaping the gut microbiome and strengthening the intestinal immune system in infants.Methods: Descriptive research was carried out in May-August 2023 using the literature review method. The design and implementation of this study referred to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for Randomized Controlled Trials (RCTs). Literature sources were obtained from PubMed, Elsevier, Medline, Nature, PLOS, MPDI, JAMA, and Scopus publication databases with a limitation of the last ten years (2013-2023). One hundred twenty articles were obtained with these keywords and then selected in stages according to predetermined criteria. Six articles that met the criteria were retrieved from 2013-2023. The articles obtained were compiled, analyzed, and concluded by looking for similarities and dissimilarities, giving views, comparing, and summarizing.Results: The review revealed that HMOs significantly influenced the composition and function of the infant's intestinal microbiota, inhibiting harmful pathogens in the intestine. Therefore, HMOs as prebiotics were crucial in promoting intestinal immune system health in infants.Conclusion: Human Milk Oligosaccharides (HMOs) in infant formula substantially impacted the gut microbiome composition and the infant's intestinal immune system. Studies consistently showed that HMOs influenced the growth and diversity of gut bacteria, leading to outcomes similar to those seen in breastfed infants.

Feeding Premasticated Food to Breastfeeding and Weaned Infants among Sudanese Women, Khartoum North

Premasticated of solid food, when an individual partially breaks down food by chewing and feeding it to another person, usually children, from mouth to mouth, using the hand or by other tools e.g. spoon is common various societies in the world. We also did not know whether Sudanese women practice the premasticated feeding. So, we conducted this study to assess breastfeeding, complementary feeding behavior, presence or absence and rates of premasticated food transfer and infant age, and assessed the food species and part used. The study was conducted in Khartoum North locality, Khartoum State, Sudan. We used descriptive cross-sectional design to complete the study. The study targeted nursing mother with a child less than 24 months of age. The sample size was calculated to be 800. Two thirds of surveyed nursing mothers have had heard of premastication of food. Most heard of it from older generations. Yet, 94 (11.9%) premasticated food for the current young children. They claimed that they start premastication of food after the sixth month of the infant age, and stop the practice before the 24th month. Although many scientists around the world have recognized the possibility of transmitting infection by premasticated food from the mother to the infant, the practice is not without significant benefits. Some authors believe that premastication of food by senior person and deliver it to the infant can help stimulating the immune system in infants. The study was reviewed and approved by the Research Ethics Committee at Alzaiem Alazhari University. Written informed consent was obtained from each individual participant.

Clinical Indicator Analysis for Predicting Pathogenic Pneumonia Infection in Newborns with Distributed Sensor Networks Data Analytics

Neonatal infections are prevalent as newborn children are prone to a range of infections because of their absence of immunity. Being susceptible to various diseases, the immune system of infants is not adequately developed to fight against protozoa bacteria, viruses and parasites. Pathogenic pneumonia is one of the most common infections identified within the neonatal group. It is a lung infection occurring in the neonates, which can start after a few hours of delivery or even after a week. The infection can even occur due to the normal flora found in the genital tract of the mother, and the respiratory distress caused by pathogenic pneumonia can even lead to the infant's death. The study examined the clinical indicator for assessing the occurrence of pathogenic pneumonia in infants. With the help of sensor networking in data analytics, the prediction of such a disorder has been assessed in-depth in the article.

Why breast milk matters

Midwives understand the benefits of breastfeeding, both for the infant and mother. However, the biochemical and physiological reasons for the superiority of breast milk are less widely known. This is, in part, because of the extraordinary complexity of breast milk's composition. Its key components include nucleotides, which benefit gut and immune development, human milk oligosaccharides, which promote an optimal gut biome, lipids in the milk fat globule membrane, which promote gut health and brain development, immunoglobulins, which modulate the infant's immune system, and an optimum protein content, which is high in the first 2 weeks after birth but decreases thereafter. A greater awareness and understanding of the mechanisms behind the benefits of breastfeeding could help midwives to have informed discussions with parents and potentially contribute to improving the UK's breastfeeding rates. Growing understanding of breast milk's unique composition may also help infant formula manufacturers drive innovation and improve the formulation of their products.

Is glycogen an important constituent of human milk?

Human milk stands as the optimal natural source of nutrition for infants, harboring a plethora of complex nutrients including water, carbohydrates, lipids, minerals, proteins, and vitamins, as well as a diverse array of bioactive molecules such as oligosaccharides and growth factors, etc. These components facilitate and safeguard the growth and development of infants. Furthermore, the composition and concentration of human milk subtly evolve across different stages of breastfeeding, adapting to the specific requirements of infants. Therefore, attaining a more precise and comprehensive understanding of human milk composition holds significant value. In this study, a succinct overview of the primary constituents of human milk and their fluctuations during various lactation periods was provided. Then, existing research is critically examined concerning the existence of free glycogen in raw human milk because previous studies indicate the presence of glycogen in human milk but do not determine whether glycogen exists in free form. Glycogen within human milk may exert influence on the growth, development, and establishment of the immune system in infants, but precise mechanisms must be determined. Elucidation of the existing form of glycogen particles in human milk will not only update our understanding of human milk composition, but will also strengthen the roles of glycogen in infant development. Through our exploration, the presence of free glycogen in human milk appears plausible. However, further experiments are needed to confirm the claim via solid evidence.

Early breastfeeding initiation: Exploring rates and determinants among postpartum women in Eastern Morocco

IntroductionBreast milk is the only complete food source for infants under the age of six months, as it provides the bioactive nutrients needed to strengthen the infant's immune system, promote growth, and facilitate tissue repair. Despite the many benefits of colostrum, the National Demographic and Family Health Survey of 2018 revealed that only 42% of women in Morocco were breastfeeding within an hour of giving birth. Therefore, the aim of this study was to determine the factors influencing breastfeeding initiation after discharge within the maternity ward of the Provincial Hospital of Taza, in the Eastern Region of Morocco. Materials and methodsA cross-sectional study was conducted over a four-month period among 400 women who had given birth and were breastfeeding in the maternity ward of Ibn Baja Hospital, in the city of Taza. Questionnaires were filled out on site to collect socio-demographic, obstetric, and timely breastfeeding initiation data, as well as its determinants, before the mothers' discharge from the maternity ward. Statistical analysis was performed using SPSS software. ResultsThe participants in this study were all breastfeeding mothers who had given birth at full term. Their average age was 28.43±6.18 years, and 94.5% of them were housewives. Of these, 74% lived in rural areas, 49% lived in large families, and 48% had been married for over 5 years. The study found that only 37% of mothers initiated breastfeeding within the first hour, 78% had a vaginal delivery, and 71.5% of mothers had at least a primary education compared to 75% of fathers. Among the newborns, the majority (99.5%) had a birth weight exceeding 2.5 kgs, of which 52% were female. 66% of mothers reported having already experienced breastfeeding, and 48.5% had information about early breastfeeding. 64.5% of the respondents had made the decision to breastfeed their newborns during pregnancy. Binary logistic regression analysis revealed the involvement of six factors in the determination of early breastfeeding, namely mother's age, parents' education, sex of the newborn, prior knowledge about early breastfeeding, as well as whether or not the mother had already been breastfed by her mother. ConclusionThe study found that just 37% of mothers initiated breastfeeding within one hour of delivery. This highlights the strong association between early breastfeeding initiation and factors such as parental education, newborn sex, prior knowledge about early breastfeeding, and the mother's breastfeeding history. To promote early breastfeeding initiation, it is recommended that women of childbearing age receive education on the topic, particularly those who are less educated.

Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease

Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (βindirect = −2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.

Examining the impact of nanoplastics and PFAS exposure on immune functions through inhibition of secretory immunoglobin A in human breast milk

Emerging contaminants such as nanoplastics (NPs) and per- and polyfluoroalkyl substances (PFAS), have been detected in the environment and breast milk, thus exposing infants to potentially harmful chemicals during breastfeeding. Breast milk contains secretory immunoglobulin A (SIgA), an antibody that plays a vital role in disease protection and the development of the infant's immune system. This study employed molecular simulation and fractional factorial designs to assess the toxicity of NPs and PFAS on breast milk and their influence on infant immunity by inhibiting SIgA. The research found that NPs and PFAS have higher binding affinities to SIgA compared to the control compound. Polycarbonate (−10.7 kcal/mol) had the highest binding affinity among plastics, while Perfluorodecanoic acid (PFDA, - 8.0 kcal/mol) had the highest binding affinity among PFAS. The relative toxic index was higher for PFAS (2.4) than for plastics (1.9), suggesting that PFAS may pose a higher overall toxicity burden on the protein. The presence of specific combinations of NPs and PFAS in breast milk may potentially harm breastfeeding infants, although additional experimental studies are required to validate these findings. These results underscore the potential risks associated with these emerging contaminants in breast milk and their impact on infant immunity.

How Do Human Milk Oligosaccharides Modulate the Immune System in Infants with Cow’s Milk Protein Allergy? Emerging Evidence and Clinical Implications

How Do Human Milk Oligosaccharides Modulate the Immune System in Infants with Cow’s Milk Protein Allergy? Emerging Evidence and Clinical Implications

Influence of technical and maternal-infant factors on the measurement and expression of extracellular miRNA in human milk.

Breast milk contains thousands of bioactive compounds including extracellular vesicle microRNAs (EV-miRNAs), which may regulate pathways such as infant immune system development and metabolism. We examined the associations between the expression of EV-miRNAs and laboratory variables (i.e., batch effects, sample characteristics), sequencing quality indicators, and maternal-infant characteristics. The study included 109 Latino mother-infant dyads from the Southern California Mother's Milk Study. Mothers were age 28.0 ± 5.6 and 23-46 days postpartum. We used principal components analysis to evaluate whether EV-miRNA expression was associated with factors of interest. Then, we used linear models to estimate relationships between these factors and specific EV-miRNA counts and analyzed functional pathways associated with those EV-miRNAs. Finally, we explored which maternal-infant characteristics predicted sequencing quality indicators. Sequencing quality indicators, predominant breastfeeding, and breastfeedings/day were associated with EV-miRNA principal components. Maternal body mass index and breast milk collection timing predicted proportion of unmapped reads. Expression of 2 EV-miRNAs were associated with days postpartum, 23 EV-miRNAs were associated with breast milk collection time, 23 EV-miRNAs were associated with predominant breastfeeding, and 38 EV-miRNAs were associated with breastfeedings/day. These EV-miRNAs were associated with pathways including Hippo signaling pathway and ECM-receptor interaction, among others. This study identifies several important factors that may contribute to breast milk EV-miRNA expression. Future studies should consider these findings in the design and analysis of breast milk miRNA research.

Early-life respiratory infections and developmental immunity determine lifelong lung health.

Respiratory infections are common in infants and young children. However, the immune system develops and matures as the child grows, thus the effects of infection during this time of dynamic change may have long-term consequences. The infant immune system develops in conjunction with the seeding of the microbiome at the respiratory mucosal surface, at a time that the lungs themselves are maturing. We are now recognizing that any disturbance of this developmental trajectory can have implications for lifelong lung health. Here, we outline our current understanding of the molecular mechanisms underlying relationships between immune and structural cells in the lung with the local microorganisms. We highlight the importance of gaining greater clarity as to what constitutes a healthy respiratory ecosystem and how environmental exposures influencing this network will aid efforts to mitigate harmful effects and restore lung immune health.

Formation of the infant's intestinal microbiota depending on the delivery method: long-term consequences and correction options: A review

Many studies have been devoted to human microbiome. It has been shown that the microbiome has a significant effect on almost all the vital functions of the host organism. The article addresses the role of various factors in newborns' intestinal microbiota formation. The main emphasis was on the delivery method since the intestinal microbiota of children born via vaginal delivery differs from those born by cesarean section. The microbiota of the mother's intestine and vagina greatly influences the formation of the intestinal microbiome. The delivery method affects not only the formation of the intestinal microbiota but also, indirectly, the development of the newborn's immune system. Changes in the intestinal microbiota associated with surgical delivery probably affect the formation of a newborn infant's immune system. Lack of colonization by the mother's flora during delivery may contribute to a greater risk of infectious and non-communicable diseases. Correcting the microbiota of children born by cesarean section using probiotics (mono- or multistrain probiotics) is essential. When prescribing a probiotic, it is important to choose a well-studied strain shown to be safe, with a positive experience in newborns, and approved for use in children from birth.

The genomic landscape of infant CD4 T cells and monocytes after BCG vaccination

Abstract The live-attenuated Bacille Calmette-Guérin (BCG) vaccine has been introduced a century ago to prevent tuberculosis and is still administered to >80% of newborns worldwide. Independent of its effect on TB, BCG introduction markedly reduced childhood mortality. Although BCG vaccine is routinely administered to infants, there is a gap in understanding the influence of BCG on the neonatal immune system. In adults, BCG induces trained or heterologous immunity. Here, to better understand the molecular changes in the infant immune system after BCG immunization, we performed RNA sequencing and ATAC sequencing in circulating CD4 T cells and monocytes of 28 infants prior to and 6–12 weeks after administering BCG. Consistent with data from BCG-vaccinated adults, the expression profile of 168 differentially expressed genes (DEG) supports the activation of monocytes after BCG vaccination, and ATAC sequencing data identified epigenetic modification that impact accessibility of genes in Nod1 and Nod 2 signaling pathways. In CD4 T cells, we identified a total of 322 DEG, including 95 upregulated and 226 downregulated genes. The functional enrichment and transcription factor analysis showed the enrichment of ErbB signaling pathways which regulate cell proliferation and differentiation mediated through MAPK signaling pathways. These results combined with peaks identified by ATAC sequencing were indicative of the expansion of Th1 CD4 T cells in BCG vaccinated infants. This study provides an understanding of molecular changes in monocytes and CD4 T cells after BCG vaccination that may explain the improved capacity of the infant immune system to respond to intracellular pathogens.

The Effect of Hypnobreastfeeding and Lactation Massage on Breast Milk Production

Mother's milk's nutritional content shields the infant's immune system, allowing for healthy growth and development. Because breastfeeding has positive health effects for both mother and child, it is strongly advised during the early stages of pregnancy. The truth of the matter is that a lot of mothers still struggle to exclusively breastfeed their children for the whole six months. Hypnobreastfeeding and lactation massage are two strategies that can help people who want to exclusively breastfeed get past their obstacles. This study sought to ascertain the impact of lactation massage and hypnobreastfeeding on breastfeeding mothers' ability to produce milk in the independent Palembang midwife's practice. The design of this study was a quasy experimental design with a pre-test post-test control group design technique in which 60 postpartum mothers were divided into two groups. The intervention group (n = 30) underwent hypnobreastfeeding and lactation massage as a sort of therapy and continued with measurements of breast milk and the control group (n = 30) did not receive any treatment or intervention. Questionnaires, checklists, guides for using hypnobreastfeeding and lactation massage, as well as breast pumps to measure milk supply, were the devices employed. With asymptotic statistical values, the results demonstrated that the delivery of hypnobreastfeeding therapy and lactation massage in the intervention group compared to the control group had a significant impact on milk production. Sig. (2-tailed) = 0.001, and the average increase in milk production between the intervention group and the control group was 25.03 ml compared to 8.56 ml.

Impact of the COVID-19 pandemic on infant feeding practices in the United States: Food insecurity, supply shortagesand deleteriousformula-feeding practices.

The coronavirus disease 2019 (COVID-19) pandemic increased food insecurity among UShouseholds, however, little is known about how infants, who rely primarily on human milk and/or infant formula, were impacted. We conducted an online survey with UScaregivers of infants under 2 yearsof age (N = 319) to assess how the COVID-19 pandemic impacted breastfeeding, formula-feedingand household ability to obtain infant-feeding supplies and lactation support (68% mothers; 66% White; 8% living in poverty). We found that 31% of families who used infant formula indicated that they experienced various challenges in obtaining infant formula, citing the following top three reasons: the formula was sold out (20%), they had to travel to multiple stores (21%)or formula was too expensive (8%). In response, 33% of families who used formula reported resorting to deleterious formula-feeding practices such as diluting formula with extra water (11%) or cereal (10%), preparing smaller bottles (8%)or saving leftover mixed bottles for later (11%). Of the families who fed infants human milk, 53% reported feeding changes directly as a result of the pandemic, for example, 46% increased their provisioning of human milk due to perceived benefits for the infant's immune system (37%), ability to work remotely/stay home (31%), concerns about money (9%) or formula shortages (8%). Fifteen percentof families who fed human milk reported that they did not receive the lactation support they needed and 4.8% stopped breastfeeding. To protect infant food and nutrition security, our results underscore the need for policies to support breastfeeding and ensure equitable and reliable access to infant formula.

Role of human milk oligosaccharide metabolizing bacteria in the development of atopic dermatitis/eczema.

Despite affecting up to 20% of infants in the United States, there is no cure for atopic dermatitis (AD), also known as eczema. Atopy usually manifests during the first six months of an infant's life and is one predictor of later allergic health problems. A diet of human milk may offer protection against developing atopic dermatitis. One milk component, human milk oligosaccharides (HMOs), plays an important role as a prebiotic in establishing the infant gut microbiome and has immunomodulatory effects on the infant immune system. The purpose of this review is to summarize the available information about bacterial members of the intestinal microbiota capable of metabolizing HMOs, the bacterial genes or metabolic products present in the intestinal tract during early life, and the relationship of these genes and metabolic products to the development of AD/eczema in infants. We find that specific HMO metabolism gene sets and the metabolites produced by HMO metabolizing bacteria may enable the protective role of human milk against the development of atopy because of interactions with the immune system. We also identify areas for additional research to further elucidate the relationship between the human milk metabolizing bacteria and atopy. Detailed metagenomic studies of the infant gut microbiota and its associated metabolomes are essential for characterizing the potential impact of human milk-feeding on the development of atopic dermatitis.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Vaginal Delivery and Breastfeeding Benefit Infant Immune Response to Hepatitis B Vaccine: A Prospective Cohort Study.

Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants, and the immune response of infants to vaccines is closely related to their immune system. This large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant's immune response to hepatitis B vaccine (HepB). A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018-2019 by cluster sampling method. Twenty (1.59%) of the 1,254 infants were nonresponders to HepB. Among the other 1,234 infants, 10.05% (124/1,234), 81.69% (1,008/1,234) and 8.27% (102/1,234) of infants had low, medium, and high responses to HepB, respectively. Logistic regression analysis showed that cesarean section (OR: 8.58, 95% CI: 3.11-23.65, p<0.001) and birth weight <3.18 kg (OR: 5.58, 95% CI: 1.89-16.51, p=0.002) were independent risk factors for infant nonresponse to HepB, and cesarean section (OR: 7.63, 95% CI: 4.64-12.56, p<0.001), formula feeding (OR: 4.91, 95% CI: 1.47-16.45, p=0.001), maternal anti-HBs negativity (OR: 27.2, 95% CI: 10.67-69.35, p<0.001), paternal non-response history of HepB (OR: 7.86, 95% CI: 2.22-27.82, p=0.014) and birth weight <3.22 kg (OR: 4.00, 95% CI: 2.43-6.59, p<0.001) were independent risk factors for infant low response to HepB. In cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial, it makes sense to enhance infant response by changing delivery and feeding patterns. Natural vaginal delivery and breastfeeding are beneficial to the infant's immune response to HepB.