Formula-fed Infants Research Articles

Breast milk oligosaccharides are the most essential ingredient in breast milk, affecting the health of infants: A review

Breastfeeding remains the “gold standard” of nutrition for children in the first years of life. However, factors such as hypogalactia, maternal stress, health problems and simply an unwillingness to breastfeed deprive the baby of breast milk (BM) and challenge pediatricians to choose an alternative food for the baby. The BM composition is complex, dynamic, and of scientific interest, and the attention of most scientists is directed to BM oligosaccharides (BMOs). Many benefits of BMOs have been proven in relation to the child's health, including the formation of the intestinal microbiota, maturation of the immune response, contribution to the barrier function of the intestine, and protection against pathogens. In the absence of breastfeeding, modern formulas containing BMOs can be used. The addition of a combination of 5 BMOs is a promising and effective approach to maintaining the overall health of formula-fed infants.

Metal availability shapes early life microbial ecology and community succession.

The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.

56 Iron deficiency is common in extreme preterm infants despite prophylactic iron supplementation

Abstract Background Iron deficiency (ID) in childhood is linked to adverse neurodevelopmental outcomes in the long-term. Extremely premature infants (EPI; born < 28 weeks gestation) are more susceptible to ID due to a multitude of factors including lower iron reserves at birth, rapid growth, immature erythropoiesis, and multiple phlebotomy tests during hospital stay. Therefore, professional societies advise prophylactic iron therapy for these infants from 2-6 weeks age until 6-12 months. However, there is paucity of data on the iron status in EPI receiving this prophylactic iron supplementation. Objectives To investigate the prevalence and risk factors associated with ID in EPI. Design/Methods A retrospective cohort study analyzed a Provincial database of EPIs born between 2005-2018. Infants with congenital malformations, chromosomal anomalies and blood disorders were excluded. All included infants received prophylactic iron supplementation from 2-4 weeks of chronological age that was recommended to continue at discharge until 9-12 months corrected age (CA). At 4-6 months CA, these infants underwent blood testing. ID was defined as serum ferritin < 20mcg/L at 4 months CA or SF < 12mcg/L at 6 months CA. Through a univariate analysis using single-variable logistic regression, factors linked to ID were identified. Those with a p-value < 0.20 progressed to a multivariable model, retaining variables with a p-value < 0.05. Results Of 146 infants, 45.9% had ID. ID group had lower mean ferritin (16.4 µg/L vs 50.0 µg/L, p < .001) and reticulocyte hemoglobin equivalent (28.4pg vs 31.6pg, p < .001) compared to the non-ID group. ID prevalence reduced from 59.7% in 2005-2011 to 40.3% in 2012-2018 cohort. Exclusive or partial breastfeeding at 4-6 months CA was protective against ID (Odds: 0.2, p = 0.003). Iron therapy at 4-6 months CA was not protective in the final model. Notably, 27.4% stopped iron therapy before 4-6 months CA, and exclusive formula-fed infants had notably lower iron intake than breastfed infants (66.1% vs 99.1%, p = 0.006). Conclusion Nearly half of the EPI exhibited ID at 4-6 months CA despite prophylactic iron supplementation. About a quarter discontinued therapy before reaching this age. Breastfeeding at this age was protective against ID. This high prevalence of ID in EPI underscores the need of future studies to discern strategies to mitigate ID in this vulnerable population.

Macronutrient Intake during Complementary Feeding in Very Low Birth Weight Infants Comparing Early and Late Introduction of Solid Foods: A Secondary Outcome Analysis.

Background/Objectives: Very low birth weight (VLBW) infants may require enhanced nutrition, even during complementary feeding. However, there are limited data on macronutrient intake during this period, particularly concerning the individual timing of the introduction of solid foods in a representative VLBW infant population. Methods: This prospective observational study analyzed macronutrient intake in VLBW infants with a gestational age < 32 weeks based on whether solid foods were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks corrected age) Nutritional intake was analyzed using a 24 h recall at 6 weeks CA and 3-day dietary records at 12 weeks, 6, 9, and 12 months CA. Results: In total, 115 infants were assigned to the early and 82 to the late group. The timing of solid food introduction did not affect macronutrient intake, except for a lower fat and higher carbohydrate intake (% of energy) in the early group at 12 weeks and 6 months CA: early vs. late, fat-12 weeks: 47.0% vs. 49.0%, 6 months: 39.2% vs. 43.3%; carbohydrates-12 weeks: 44.9% vs. 43.2%, 6 months: 51.3% vs. 48.0%. Apart from docosahexaenoic acid (DHA) and arachidonic acid (AA), dietary intake recommendations were met in both groups. While nutrient intakes varied significantly between breastfed and formula-fed infants, those with comorbidities exhibited similar nutrient intake levels compared to those without. Conclusions: Our findings suggest adequate macronutrient intakes in VLBW infants irrespective of the timing of solid introduction. However, there is a notable need to enhance dietary intakes of DHA and AA. Future research is crucial to assess whether current nutrient intakes are sufficient for VLBW infants with comorbidities.

6805 Impact of Feeding Types on Catch-Up Growth in Early Infancy Among Small-for-Gestational-Age Infants: A Nationwide Korean Study

Abstract Disclosure: J. Choi: None. Y. Choe: None. S. Yang: None. Purpose: The study aimed to compare growth patterns and catch-up growth (CUG) in small-for-gestational-age (SGA) infants up to age four, based on feeding type during the first 4-6 months, using nationwide data. Methods: A total of 42,295 children born SGA (21,917 boys, 52.%) who underwent the first (4-6 month), 2nd (9-12 month), 3rd (18-24 month) and 5th (42-48 month) National Health Screening Program for Infants and Children (NHSPIC) under the National Health Insurance Service from 2007 to 2014 were included. The study population was categorized into two groups based on the primary milk feeding type recorded in the self-reported questionnaire during the first round of NHSPIC: the ”Breastfed”group, and the "Formula-fed" group. Catch-up growth (CUG) was defined as a Height Standard Deviation Score (Ht SDS) of 3rd percentile or above at the 5th NHSPIC visits. We used propensity scores to 1:1 match breastfed and formula-fed group based on sex, birth weight, cesarean section, socioeconomic status, residance. Multivariate logistic regression analysis was performed to evaluate the effect of milk feeding type on CUG at 4 years of age. Results: 49.1% of infants (n = 20,774) were breastfed and 50.9% (n = 21,521) were formula-fed. The median birth weight was 2.7 kg (interquartile range: 2.5-2.9 kg), and 98.7% of the children (n = 41,752) achieved CUG by the 5th NHSPIC round. Following propensity score matching, both groups included 19,308 infants. At four years of age, the breastfed group showed a lower likelihood of achieving CUG compared to the formula-fed group (aOR 0.794, 95% CI 0.665-0.948). During the 1st NHSPIC round, the breastfed group had a significantly lower weight Z-score (mean: -0.05, range: -0.64 to 0.41) than the formula-fed group (mean: 0.14, range: -0.42 to 0.78, p &amp;lt; 0.001). This trend was more pronounced from the 1st to 2nd round, with greater decreases in both weight and height Z-scores for the breastfed group (weight difference: -0.36, range: -0.74 to 0.02; height difference: -0.21, range: -0.62 to 0.20) compared to the formula-fed group (weight difference: -0.17, range: -0.53 to 0.20; height difference: -0.13, range: -0.53 to 0.28, p &amp;lt; 0.001). However, from the 2nd round, the breastfed group demonstrated faster gains in both weight and height (p &amp;lt; 0.001). Conclusion : In a study of Korean SGA infants, those breastfed during the first 4-6 months post-birth had lower CUG rates at four years compared to formula-fed infants. The breastfed group exhibited less weight and height gain, especially between the 1st and 2nd NHSPIC rounds, aligning with the initial phase of solid food introduction. These findings may suggest the need for enhanced nutritional supplementation for breastfed SGA infants. Further research is necessary to explore other factors that may impact growth during this critical developmental period. Presentation: 6/3/2024

Preliminary risk assessment of exposure to 3-monochloropropanediol and glycidyl fatty acid esters from infant formula and baby food products on the Saudi market

3-Monochloropropanediol fatty acid esters (3-MCPDE) and glycidyl esters (GE) are well-identified processing-induced chemical toxicants detected in infant formula and baby foods worldwide. We analysed the levels of 3-MCPDE and GE in infant formula and baby food products available in Saudi Arabia, followed by a dietary risk assessment for exposure to these contaminants in infants and young children from birth to 3 years. Eighty-five commercial infant formulas (n = 35) and baby foods (n = 50) available for consumption by infants and babies purchased from the Saudi market during 2022 were analysed for these contaminants using gas chromatography-tandem mass spectrometry. 3-MCPDE and GE were detected in 100 and 80% of the samples, with a mean concentration of 57 µg/kg (range: 2–285 µg/kg) and 30 µg/kg (range: not detected–217 µg/kg), respectively. The highest concentration was found in milk-based formula for infants 0–6 months (285 µg/kg) and the lowest was found in fruit purees (2 µg/kg). Preliminary exposure and risk assessment showed increased exposure to 3-MCPDE for infants exclusively fed infant formula with exposure declining with age due to the introduction of solid foods. GE exposure levels reached 0.8 µg/kg body weight per day, which declined over time with margin of exposure values below 25,000. These results indicate that the levels of 3-MCPDE and GE in infant formula may pose potential risks to infants exclusively fed formula; therefore, adopting EU regulations should reduce the presence of these processing contaminants in essential infant foods.

Comparative Study of Prebiotics for Infants Using a Fecal Culture System: Insights into Responders and Non-Responders

Background: The gut microbiota of breast-fed infants is dominated by infant-type human-residential bifidobacteria (HRB) that contribute to infant health; thus, it is crucial to develop infant formulas that promote the establishment of a gut microbiota enriched with infant-type HRB, closely resembling that of breastfed infants. Methods: We compared various non-digestible prebiotic oligosaccharides and their combinations using a fecal culture system to explore which candidates could promote the growth of all infant-type HRB and rarely yield non-responders. The analysis included lactulose (LAC), raffinose (RAF), galactooligosaccharides (GOS), and short- and long-chain fructooligosaccharides. Fecal samples were collected from seven infants aged 1.5–10.2 months and cultured with each oligosaccharide individually or their combinations. Results: No single oligosaccharide effectively promoted the growth of all infant-type HRB, although GOS promoted the growth of HRB other than Bifidobacterium longum subsp. longum. Only the LAC/RAF/GOS group evenly and effectively promoted the growth of all infant-type HRB. Accordingly, acetate production was higher in fecal cultures supplemented with GOS or LAC/RAF/GOS than in the other cultures, suggesting that it is a superior combination for all infant-type HRB and rarely yields non-responders. Conclusions: This study can aid in developing infant formulas that help align the gut microbiota of formula-fed infants with that of breastfed infants.

Update of the risk assessment of brominated phenols and their derivatives in food.

The European Commission asked EFSA to update its 2012 risk assessment on brominated phenols and their derivatives in food, focusing on five bromophenols and one derivative: 2,4,6-tribromophenol (2,4,6-TBP), 2,4-dibromophenol (2,4-DBP), 4-bromophenol (4-BP), 2,6-dibromophenol (2,6-DBP), tetrabrominated bisphenol S (TBBPS), tetrabromobisphenol S bismethyl ether (TBBPS-BME). Based on the overall evidence, the CONTAM Panel considered invivo genotoxicity of 2,4,6-TBP to be unlikely. Effects in liver and kidney were considered as the critical effects of 2,4,6-tribromophenol (2,4,6-TBP) in studies in rats. A BMDL10 of 353 mg/kg body weight (bw) per day for kidney papillary necrosis in male rats was identified and was selected as the reference point for the risk characterisation. The derivation of a health-based guidance value was not considered appropriate due to major limitations in the toxicological database. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Around 78,200 analytical results for 2,4,6-TBP in food were used to estimate dietary exposure for the European population. Considering the resulting MOE values, all far above an MOE of 6000 that does not raise a health concern, and accounting for the uncertainties affecting the exposure and hazard assessments, the CONTAM Panel concluded with at least 95% probability that the current dietary exposure to 2,4,6-TBP does not raise a health concern. Due to lack of occurrence data, no risk assessment could be performed for breastfed or formula-fed infants. No risk characterisation could be performed for any of the other brominated phenols and derivatives included in the assessment, due to lack of data both on the toxicity and occurrence.

Tsg101 knockout in the mammary gland leads to a decrease in small extracellular vesicles in milk from C57BL/6J dams and contributes to leakiness of the gut mucosa and reduced postnatal weight gain in suckling pups

Human milk contains 2.2 ± 1.5×1011 small extracellular vesicles (sEVs) per milliliter and human infants consume 1.7×1014 milk sEVs (sMEVs) daily in 800 mL milk. Infant formula contains trace amounts of sMEVs. To date, eight adverse effects of milk depletion and five beneficial effects of sMEV supplementation have been reported including studies in infants and neonate mice. Formula-fed infants do not realize the benefits of sMEVs. Most of the phenotyping studies reported to date have the limitation that sMEV depletion and supplementation were initiated after mice were weaned. Here, we used a genetics approach for assessing effects of sMEV depletion on the development of suckling mice. Newborn C57BL/6J pups were fostered to Tumor Susceptibility Gene 101 (Tsg101) mammary-specific knockout (KO) dams or C57BL/6J dams (controls) in synchronized pregnancies. Tsg101 KO was associated with an 80% decrease of sMEVs. Postnatal weight gain and gut health (histology, morphology, and barrier function) were assessed until weaning at age three weeks. We observed a significant decrease in weight gain, length of small intestine, villi height, crypt depth, and intestinal barrier function in male and female pups fostered to Tsg101 dams compared to pups fostered to control dams. The effect size varied between 11 and 32 percent. Maternal Tsg101 KO did not affect the dams’ health, content of macronutrients and dry mass of milk and had no effect on the amount of milk consumed by pups. We conclude that sMEVs are important for growth and gut health in neonate mice.

Feeding Method, Nicotine Exposure, and Growth during Infancy

ObjectiveTo answer three questions: 1) Are infants breastfed by smokers at risk of rapid weight and length gain? 2) Is rapid growth during infancy partially attributable to ingestion of smokers’ breastmilk? 3) If so, what are the implications for breastfeeding by smokers? Study DesignUsing data from the Norwegian Mother, Father and Child Cohort Study and Medical Birth Registry of Norway (N=54,522) we examined changes in weight, length, weight-for-length z-score (WFLZ) during infancy in the context of maternal smoking (0, 1-10, >10 cigarettes/day) and feeding method during the first 6 months (breastfed, formula-fed, mixed-fed). We fit generalized linear models, adding a smoking by feeding method interaction term to evaluate the effect of ingesting smokers’ breastmilk. ResultsBreastfed infants of both light and heavy smokers experienced WFLZ gains of 0.05 (95% CI: 0.01, 0.09), and 0.13(95% CI: 0.07, 0.18) respectively. Among mixed-fed infants, only heavy maternal smoking predicted WFLZ gain (0.10; 95% CI: 0.05, 0.16). Among exclusively formula-fed infants maternal smoking did not predict rapid growth. Interaction models suggest that infants ever-breastfed (i.e., breastfed and mixed-fed groups combined) by heavy smokers gained weight (100 grams; 95%CI: 30, 231) and length (2.8 mm; 95%CI:0.1, 5.6) attributable to ingesting smoker’s breastmilk. ConclusionsInfants breastfed by smokers experience rapid growth, some of these gains are attributable to ingesting smokers’ breastmilk. Among infants breasted by light smokers, these gains are within the range of normative growth patterns for healthy, breastfed infants.

Micronutrient Intake during Complementary Feeding in Very Low Birth Weight Infants Comparing Early and Late Introduction of Solid Foods: A Secondary Outcome Analysis.

Background/Objectives: The complementary feeding period is crucial for addressing micronutrient imbalances, particularly in very low birth weight (VLBW) infants. However, the impact of the timing of solid food introduction on micronutrient intake in a representative VLBW population remains unclear. Methods: This prospective, observational study investigated micronutrient intake during complementary feeding in VLBW infants categorized based on whether solids were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks CA). Nutritional intake was assessed using a 24 h recall at 6 weeks CA and with 3-day dietary records at 12 weeks and at 6, 9, and 12 months CA. Results: Among 218 infants, 115 were assigned to the early group and 82 to the late group. In total, 114-170 dietary records were valid for the final analysis at each timepoint. The timepoint of solid introduction did not affect micronutrient intake, except for a higher iron and phosphorus intake at 6 months CA in the early group (early vs. late: iron 0.71 vs. 0.58 mg/kg/d, adjusted p-value (p-adj.) = 0.04; phosphorus 341 vs. 286 mg/d, p-adj. = 0.04). Total vitamin D, calcium, zinc, and phosphorus greatly met intake recommendations; however, dietary iron intake was insufficient to equalize the iron quantity from supplements during the second half year CA. While nutrient intakes were similar between infants with and without comorbidities, breastfed infants had lower micronutrient intakes compared with formula-fed infants. Conclusions: This study suggests that micronutrient intakes were sufficient during complementary feeding in VLBW infants. However, prolonged iron supplementation may be necessary beyond the introduction of iron-rich solids. Further research is essential to determine micronutrient requirements for infants with comorbidities.

Infant formula feeding and associated factors in Debre Berhan City: A community based cross-sectional study

IntroductionGlobally, there is rising concern over the growing reliance on breast milk substitutes (BMSs). However, limited studies have been conducted to explore this issue in Ethiopia. ObjectiveTo assess infant formula feeding and associated factors among mothers of infants aged 0–6 months in Debre Berhan City, 2023. Methods and materialsThis cross-sectional study used a multistage sampling technique to select 656 mothers residing in Debre Berhan city. The data was collected through face-to-face interviews using a semi-structured questionnaire. Bivariable and multivariable logistic regression models were employed to identify the factors associated with infant formula feeding. The findings are then presented as frequencies, percentages, and odds ratios. ResultsThe prevalence of infant formula feeding in Debre Berhan city was 39.7 %. In addition, having a female child [AOR = 1.75, 95 % CI: 1.08–2.86], receiving a college education or higher [AOR = 5.79, 95 % CI: 2.38–14.08], being in the age category of 25–34 [AOR = 2.38, 95 % CI: 1.10–5.15] or 35–45 [AOR = 3.43, 95 % CI: 1.35–8.69], being a prime mother [AOR = 1.81, 95 % CI: 1.12–2.94], receiving breastfeeding advice [AOR = 4.64, 95 % CI: 2.78–7.75], delivering via a C-section [AOR = 5.39, 95 % CI: 2.54–11.42], initiating breastfeeding late [AOR = 2.26, (95 % CI: 1.41–3.64)], or being unaware of the risks associated with infant formula feeding [AOR = 5.48, 95 % CI: 3.20–9.39] were the factors that drove mothers towards infant formula feeding. ConclusionIn Debre Berhan city, the prevalence of infant formula feeding was high. Fortunately, with appropriate interventions, most of the factors that led to infant formula feeding could be effectively addressed.

Tailored recommendations for infant milk formula intake results in more accurate feeding.

Based on theoretical calculations and actual formula intake data, we conclude that larger infants require a significantly higher daily formula milk intake than smaller infants, and we postulate that infants could benefit from more tailored formula milk intake recommendations. • Adequate energy intake during the infancy period is crucial to support optimal growth and organ development, with the potential for long-lasting health effects. • Current available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve. • Based on using both theoretical calculations and actual formula intake data, larger infants require a significantly higher daily formula milk intake than smaller infants. • Exclusive formula-fed infants could benefit from more tailored formula milk intake recommendations, in early infancy.

Reliability and validity of the German version of the Iowa infant feeding attitude scale (IIFAS-G) and relations to breastfeeding duration and feeding method

BackgroundPublic health initiatives (e.g., the Baby Friendly Hospital Initiative) have led to an increase in breastfeeding rates worldwide. However, as (exclusive) breastfeeding duration is still below WHO recommendations, it is crucial to understand the factors that influence decisions on breastfeeding practice. Modifiable psychological factors such as intention to breastfeed have therefore become targets of recent interventions. As the intention to breastfeed is among the strongest predictors of breastfeeding duration, reliable tools for measuring the intention to breastfeed are needed. The Iowa Infant Feeding Attitude Scale (IIFAS) measures attitudes towards infant feeding and is used in various languages and across different cultural contexts. However, there has been no German version of the IIFAS (IIFAS-G) so far. The aim of this study was to investigate reliability, validity, and associations of the IIFAS-G with feeding method and breastfeeding duration.MethodsBetween August and November 2022, a total of 353 mothers (Mage = 35 years, SDage = 4.2 years) of singleton infants (47.3% female (1 undetermined), Mage = 10.8 months, SDage = 4.7 months, age range: 3-547 days; 90.4% living in Switzerland) participated in an online survey. The IIFAS-G was administered as a part of a larger study on early child development and infant feeding method.ResultsThe translated IIFAS-G showed unsatisfactory model fit for the two factor 17-item solution. Four items showed low factor loadings. After item reduction, a 13-item two factor solution showed satisfactory model fit (CFI = 0.92, TLI = 0.90, RMSEA = 0.07) and high internal consistency (Cronbach’s α = 0.85). The IIFAS-G score was higher for mothers who exclusively breastfed their infants compared to mothers who additionally or exclusively fed infant formula. Moreover, mothers with higher IIFAS-G scores were less likely to stop breastfeeding their child over the course of 1.5years (HR = 0.87).ConclusionA shorter two-factor IIFAS-G is proposed to investigate attitudes towards breastfeeding and formula feeding in German-speaking mothers.

Importance of Human Breast Milk in the Early Colonization of Streptococcus mutans.

Background and objectives: The development of the oral microbiome begins in the prenatal stage. Breast milk contains antimicrobial proteins, microorganisms, metabolites, enzymes, and immunoglobulins, among others; therefore, differences have been noted in the type of microorganisms that colonize the oral cavity of children who are breastfed compared to those who are formula-fed. Our objective was to establish the relationship between breastfeeding, formula feeding, or mixed feeding (breastfeeding and formula) with the presence of S. mutans in a population of children under 6 months of age. Materials and Methods: The patients were recruited from the Child Care Center of Ciudad Juárez, Chihuahua, and from the pediatric dentistry postgraduate clinics of the Autonomous University of Ciudad Juárez; children exclusively fed maternally, with formula, and/or mixed were included. Those who had been fed within the previous hour were excluded. The sample was taken with a smear of the jugal groove using a sterile micro-brush. For the identification of Streptococcus mutans, a culture of Mitis Salivarius Agar (Millipore) was used. Results: 53.3% corresponded to females and 46.7% to males, 36.7% corresponded to maternal feeding, 23.3% corresponded to formula feeding, and 40% corresponded to mixed feeding. In 90% of the infants, the parents indicated that they did not perform oral hygiene. The CFU count showed that infants who were exclusively breastfed had an average of 9 × 10 CF/mL, formula-fed infants had an average of 78 × 10 CFU/mL, and those who had mixed feeding 21 × 10 CFU/mL. Conclusions: According to the results obtained, it was possible to corroborate that exclusive breastfeeding limits the colonization of Streptococcus mutans compared to those infants who receive formula or mixed feeding; these results could have a clinical impact on the dental health of infants by having a lower presence of one of the main etiological factors involved in dental caries and the type of microbiome established in the oral cavity.

Unravelling the evolutionary dynamics of antibiotic resistance genes in the infant gut microbiota during the first four months of life

BackgroundAlongside microbiota development, the evolution of the resistome is crucial in understanding the early-life acquisition and persistence of Antibiotic Resistance Genes (ARGs). Therefore, the aim of this study is to provide a comprehensive view of the evolution and dynamics of the neonatal resistome from 7 days to 4 months of age using a high-throughput qPCR platform.MethodsIn the initial phase, a massive screening of 384 ARGs using a high-throughput qPCR in pooled healthy mother-infant pairs feces from the MAMI cohort was carried out to identify the most abundant and prevalent ARGs in infants and in mothers. This pre-analysis allowed for later targeted profiling in a large number of infants in a longitudinal manner during the first 4 months of life. 16S rRNA V3-V4 amplicon sequencing was performed to asses microbial composition longitudinally. Potential factors influencing the microbiota and ARGs in this period were also considered, such as mode of birth and breastfeeding type.ResultsFollowing the massive screening, the top 45 abundant ARGs and mobile genetic elements were identified and studied in 72 infants during their first months of life (7 days, 1, 2, and 4 months). These genes were associated with resistance to aminoglycosides, beta-lactams and tetracyclines, among others, as well as integrons, and other mobile genetic elements. Changes in both ARG composition and quantity were observed during the first 4 months of life: most ARGs abundance increased over time, but mobile genetic elements decreased significantly. Further exploration of modulating factors highlighted the effect on ARG composition of specific microbial genus, and the impact of mode of birth at 7 days and 4 months. The influence of infant formula feeding was observed at 4-month-old infants, who exhibited a distinctive resistome composition.ConclusionsThis study illustrates the ARG evolution and dynamics in the infant gut by use of a targeted, high-throughput, quantitative PCR-based method. An increase in antibiotic resistance over the first months of life were observed with a fundamental role of delivery mode in shaping resistance profiles. Further, we highlighted the influence of feeding methods on the resistome development. These findings offer pivotal insights into dynamics of and factors influencing early-life resistome, with potential avenues for intervention strategies.

Statistical approaches for component-wise censored composite endpoints.

Composite endpoints defined as the time to the earliest of two or more events are often used as primary endpoints in clinical trials. Component-wise censoring arises when different components of the composite endpoint are censored differently. We focus on a composite of death and a non-fatal event where death time is right censored and the non-fatal event time is interval censored because the event can only be detected during study visits. Such data are most often analysed using methods for right censored data, treating the time the non-fatal event was first detected as the time it occurred. This can lead to bias, particularly when the time between assessments is long. We describe several approaches for estimating the event-free survival curve and the effect of treatment on event-free survival via the hazard ratio that are specifically designed to handle component-wise censoring. We apply the methods to a randomized study of breastfeeding versus formula feeding for infants of mothers infected with human immunodeficiency virus.

Effects of feeding patterns during the first 6 months on weight development of infants ages 0–12 months: a longitudinal study

The purpose of this study was to investigate the effect of feeding patterns during the first 6 months on weight development of infants ages 0–12 months. Using monitoring data from the Maternal and Child Health Project conducted by the National Center for Women and Children’s Health of the Chinese Center for Disease Control and Prevention from September 2015 to June 2019, we categorized feeding patterns during the first 6 months as exclusive breastfeeding, formula feeding, or mixed feeding. We calculated weight-for-age Z scores (WAZ) according to the World Health Organization’s (WHO) 2006 Child Growth Standard using WHO Anthro version 3.2.2. A multilevel model was used to analyze the effect of feeding patterns during the first 6 months on the WAZ of infants ages 0–12 months in monitoring regions. Length of follow-up (age of infants) was assigned to level 1, and infants was assigned to level 2. Characteristics of infants, mothers, and families and region of the country were adjusted for in the model. The average weight of infants ages 0–12 months in our study (except the birth weights of boys who were formula fed or mixed fed) was greater than the WHO growth standard. After we adjusted for confounding factors, the multilevel model showed that the WAZ of exclusively breastfed and mixed-fed infants were statistically significantly higher than those of formula-fed infants (coefficients = 0.329 and 0.159, respectively; P < 0.05), and there was a negative interaction between feeding patterns and age (both coefficients = − 0.020; P < 0.05). Infants who were exclusively breastfed were heavier than formula-fed infants from birth until 12 months of age. Mixed-fed infants were heavier than formula-fed infants before 8 months, after which the latter overtook the former. Infants’ weight development may be influenced by feeding patterns during the first 6 months. Exclusive breastfeeding during the first 6 months may be beneficial for weight development of infants in infancy.

Measurement of iron absorption and iron gains from birth to 6 months in breastfed and formula-fed infants using iron isotope dilution.

Little is known about iron kinetics in early infancy. We administered stable iron isotopes to pregnant women and used maternal-fetal iron transfer to enrich newborn body iron. Dilution of enriched body iron by dietary iron with natural isotopic composition was used to assess iron kinetics from birth to 6 months. In breastfed (BF, n = 8), formula-fed (FF, n = 7), or mixed feeding (MF, n = 8) infants, median (interquartile range) iron intake was 0.27, 11.19 (10.46-15.55), and 4.13 (2.33-6.95) mg/day; iron absorbed was 0.128 (0.095-0.180), 0.457 (0.374-0.617), and 0.391 (0.283-0.473) mg/day (BF versus FF, P < 0.01); and total iron gains were 0.027 (-0.002-0.055), 0.349 (0.260-0.498), and 0.276 (0.175-0.368) mg/day (BF versus FF, P < 0.001; BF versus MF, P < 0.05). Isotope dilution can quantify long-term iron absorption and describe the trajectory of iron depletion during early infancy.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM. Colonic GM (profiled by 16S ribosomal RNA gene amplicon sequencing) was compared in preterm pigs fed colostrum for 4 days, either before, after, or together with formula feeding for 4 days. Correlations between GM and gut parameters were assessed on day 5 or 9. Both exclusive and partial colostrum feeding induced higher GM diversity, lower Enterococcus abundance, and improved intestinal maturation parameters (villus structure, digestive enzymeactivities, permeability), relative to exclusive formula feeding (all p < 0.05). Across feeding regimens, Enterococcus abundance was inversely correlated with intestinal maturation parameters. Conversely, there was no correlation between GM changes and early NEC lesions. Bovine colostrum inhibits formula-induced Enterococcus overgrowth and gut dysfunctions just after preterm birth but these effects are not causally linked. Optimising diet-related host responses, not GM, may be critical to prevent NEC in preterm newborn pigs and infants. Supplement of bovine colostrum to formula feeding modified the gut microbiota by increasing species diversity and reducing Enterococcus abundance, while concurrently improving intestinal functions in preterm pigs. Diet-related changes to the gut microbiota were not clearly associated with development of necrotizing enterocolitis (NEC) in preterm pigs, suggesting that diet-related gut microbiota effects are not critical for diet-related NEC protection. The study highlights the potential to use bovine colostrum as a supplement to formula feeding for preterm infants lacking human milk.