Cow's Milk Formula Research Articles

Effects of regular soy formula intake between 1 and 2months of age on food sensitization in infancy.

The effects of regular soy formula (SF) intake on the development of food sensitization in infancy remain unclear. This study aimed to assess the effects of regular SF intake between 1 and 2months of age on food sensitization development by 6months of age. Using data from a randomized controlled trial of a birth cohort from four Japanese hospitals that assessed cow's milk allergy development, we performed a retrospective cohort study of 235 infants who avoided cow's milk formula and supplemented breastfeeding with SF as required between 1 and 2months of age. Regular SF intake was defined as SF consumption of ≥14 days per month and ≥1350 ml per month. Food sensitization was defined as positive skin prick test reactions to hen's egg, cow's milk, wheat, and/or soy. Using multivariable logistic regression models that adjusted for parental, perinatal, and environmental factors, we calculated the adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization by 6months of age. From the 235 participants, 114 (48.5%) had regular SF intake. The adjusted odds ratios of regular SF intake for food, hen's egg, and cow's milk sensitization were 0.32 (95% confidence interval: 0.16-0.62, p= .0007), 0.42 (0.20-0.88, p= .02), and 0.33 (0.14-0.81, p= .02), respectively. Regular SF intake between 1 and 2months of age in infants avoiding cow's milk formula was significantly associated with a reduced risk of food sensitization in infancy.

Effect of Fortified Formula on Growth and Nutritional Status in Young Children: A Systematic Review and Meta-Analysis.

Previous reviews of the effect of young child formulas on health outcomes in infants and toddlers have been inconclusive. In this study, we undertook a contemporary synthesis of studies investigating the effects of consuming fortified milk beverages (compared to cow’s milk or unfortified comparator formula) on growth and/or nutritional status in children 1−3 years of age. Five electronic databases were searched (PubMed, Web of Science, Scopus, ProQuest, and Cochrane Library) for randomised controlled trials comparing fortified milk against control milk in young children (9−48 months), published between January 1990 and June 2022. Outcomes were growth, body composition, biochemical markers, and/or nutritional status. Mean differences (MD) were pooled using random-effects meta-analysis where there were ≥3 studies. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Nineteen articles (12 studies; n = 4795) met the inclusion criteria. Heterogeneity was substantial, likely attributable to considerable variation in study characteristics. Fortified milk was associated with increased weight gain (MD = 0.14 kg [95% CI 0.06, 021], p = 0.0003) compared with control milk. Subgroup analyses demonstrated increases in weight in lower-income countries, and in studies with intervention periods > 6 months. There were no effects of fortified milks on other anthropometric measures. Haemoglobin (MD = 3.76 g/L [95% CI 0.17, 7.34], p = 0.04) and ferritin (MD = 0.01 nmol/L [95% CI 0.00, 0.02], p = 0.02) concentrations were increased in infants consuming fortified milks. Fortified milk beverages appear to offer a safe and acceptable source of complementary nutrition as a short-term strategy for addressing nutritional deficits and may modestly promote weight gain in vulnerable populations when provided for periods > 6 months. This study was prospectively registered with PROSPERO (CRD42022339920) and funded by the Infant Nutrition Council.

DESENSITIZATION TO EXTENSIVELY HYDROLYZED FORMULA IN INFANT WITH COW'S MILK PROTEIN ALLERGY

<h3>Introduction</h3> Cow's Milk Protein Allergy (CMPA) is typically managed by avoidance. Limited evidence of oral desensitization for delayed-type hypersensitivity (DTH) reactions exist in the drug literature. We present a case of desensitization with hydrolyzed formula in an infant with CMPA. <h3>Case Description</h3> Allergy was consulted by NICU for a 5-month-old male infant with formula intolerance. Infant was born at term with gastroschisis and short bowel syndrome, with need for small bowel resection and gastrostomy tube placement. Maternal breast milk was insufficient to meet the infant's needs. Transition to formula was complicated by the development of bloody stools with cow's milk and hydrolyzed cow's milk formula consistent with CMPA. Introduction of elemental formulas was limited by the development of delayed onset vomiting and diarrhea felt to be consistent with Food Protein Induced Enterocolitis Syndrome (FPIES) to cornstarch. Donor breast milk was not available for outpatient use. Oral desensitization to Alimentum RTF, a cornstarch free hydrolyzed formula was successful, and the patient was discharged on this formula. <h3>Discussion</h3> Both FPIES and CMPA are predominantly delayed type hypersensitivity reactions. While desensitization approaches initially developed for management of IgE mediated drug allergy, similar approaches have been successful in management of both IgE mediated food allergy and delayed type hypersensitivity reactions to drugs. We report a potential option for oral desensitization in a patient with CMPA for whom typical therapy was contraindicated.

Early, continuing exposure to cow's milk formula and cow's milk allergy: The COMEET study, a single center, prospective interventional study

BackgroundCow's milk allergy (CMA) is a common food allergy among infants. Information regarding the best timing for first exposure to cow's milk formula (CMF) is controversial and more evidence is required. Few randomized control trials have tried to accurately assess the timing and preventive effect of exposure to CMF on small cohorts. ObjectiveThis study assessed the association between early, continuing exposure to CMF on the basis of the parents’ preferences and the development of immunoglobulin E (IgE)–mediated CMA in a large birth cohort. MethodsNewborns were prospectively recruited shortly before birth and divided into 2 groups according to parental feeding preference for the first 2 months of life: (1) exclusive breastfeeding (EBF); or (2) at least 1 meal of CMF (with or without breastfeeding) daily. Infants were followed up monthly until the age of 12 months. ResultsAmong 1992 infants participating in the study, 1073 (53.86%) were in the EBF group until 2 months of age. IgE-mediated CMA was confirmed in 0.85% (n = 17); all were in the EBF group. Within this group, the prevalence of IgE-mediated CMA was 1.58% compared with 0 in the other groups (relative risk, 29.98; P < .001). Post hoc analysis revealed IgE-mediated CMA prevalence of 0.7% in the per-protocol EBF group vs 3.27% among breastfed infants who were exposed to a small amount of CMF during the first 2 months of life. A family atopic background did not affect the results. ConclusionEarly, continuing exposure to CMF from birth has the potential to prevent the development of IgE-mediated CMA and should be encouraged. However, the exposure needs to be consistent because occasional exposure increases the risk of developing IgE-mediated CMA and should be avoided.

Protein and carbohydrate content of infant formula purchased in the United States.

The protein and carbohydrate composition of formula fed infants' diets in the United States (US) has not been described. The aims of this study were to characterize these dietary exposures in infant formula purchased in the US and to estimate the proportion of formula purchased which is hypoallergenic or lactose-reduced formula. Powdered infant formula purchase data from all major physical stores in the US prior to the COVID-19 pandemic, between 2017 and 2019, were obtained from Information Resources, Inc. Protein and carbohydrate composition and scoop sizes for each formula were obtained from manufacturers. Ready to feed liquid products, products for premature infants and products for over 1year old were not included. Total volumes of term formula purchased were 216million kg of formula powder (equivalent to 1.65 billion litres) over 3 years. Intact protein formula was 67.9% of formula purchased, 26.6% was partially hydrolysed and 5.5% was hypoallergenic (5.2% extensively hydrolysed protein; 0.3% amino acid based). Soy protein formula represented 5.1% of formula purchased. Carbohydrate content overall was 52.7% lactose, 42.3% glucose polymers and 5.0% sucrose. 23.7% of formula purchased included sucrose as a carbohydrate. Of all formula purchased, 59.0% was lactose reduced, containing a non-lactose carbohydrate. Of 'standard' formula, defined as intact protein, non-thickened, cow's milk formula, 32.3% was lactose reduced. The proportion of hypoallergenic formula purchased significantly exceeded the prevalence of cow's milk protein allergy and increased over the 3-year study period from 4.9% to 7.6% of all formula sold. US infants are exposed to unnecessarily high levels of non-lactose carbohydrates and hypoallergenic formula, and this may represent a significant nutritional health risk.

Clinical case of early debut of food allergy in a child up to 6 months

Introduction: It is believed that if the child ate only a cow’s milk formula (CMF), and сow's milk allergy is the only possible at the age of &lt;6 months. This approach leads to erroneous treatment tactics.&#x0D; Presentation of the clinical case: a child aged 3 months with the debut of atopic dermatitis (AtD) of light degree (on the scale of the assessment of the researcher IGA 2). The patient was fed on artificial with a CMF from 1,5 months. Infant was examined at the place of residence. The CMF was changed to full hydrolysis CMF and without examination. Additionally, cosmetics were applied to the skin as needed. The child was examined by an allergologist after 3-4 weeks of diet. Negative dynamics were observed. Atopic dermatitis has become moderately severe with secondary infection complications (IGA 3, 50% affected skin). Prick-tests with allergens of milk, eggs, wheat, fish were carried out. High sensitization to egg and controversial to cow’s milk was found. The results were clarified during enzyme immunoassay: IgE ovomucoid – 0.78 IU/ml (norm &lt;0.3 IU/ml); cow's milk 0.01 kUA/ l; casein – 0.01 kUA / l (norm &lt;0.1 kUA/l). &#x0D; Considering the infected AtD, "hydrocortisone + natamycin + neomycin" 2 times a day was used in the therapy. Cosmetics on infected foci was canceled, while maintaining the treatment of dry unaffected skin. It is recommended to limit household contacts with eggs. After 2 weeks, the rash is residual (IGA 0-1). The cow’s milk formula was returned to the diet without exacerbations of the skin process. &#x0D; Conclusion: The case illustrates that sensitization in children can begin and be maintained without oral ingestion of the allergen. Sensitization at the age of up to 6 months is likely with a moderate – severe recurrent course of dermatitis. A specific allergological examination can be conduct with a developed disease at an early age. Skin tests and enzyme immunoassay are applicable in infants. The appointment of a diet without examination is unreasonable and should not be used.

Goat Milk Based Infant Formula in Newborns: A Double-Blind Randomized Controlled Trial on Growth and Safety.

Objectives:We aimed to determine the growth and safety parameters in newborns fed a goat milk based infant formula (GMF) using a randomized double-blind trial, in which a cow milk formula (CMF) served as a control and a breast fed (BF) group as a reference.Methods:Healthy term infants (n = 218) aged up to 14 days were recruited from 25 European study centers and randomized to GMF or CMF. Weight, length, head circumference were measured at baseline, and at 14, 28, 56, 84, and 112 days at the study clinics. Adverse events were recorded and stool characteristics, reflux, fussiness, colic, and flatulence were self-reported by parents in 3-day diaries. Anthropometric measurements were transformed to WHO standardized age- and sex-adjusted z-scores. Analyses of covariance and linear mixed modeling were used to statistically analyze growth, while adjusting for potential confounders when studying the breast-fed group (n = 86).Results:Comparing the GMF to the CMF group, weight gain [mean difference 227.8 g (95% CI −16.6 to −439.0)] and z-scores for anthropometric measurements were similar after 112 days intervention. Infant formula groups showed greater mean (SD) weight z-scores than the BF group from 84 days onwards (GMF: 0.28 (0.84), CMF: 0.12 (0.88), BF −0.19 (1.02), P < 0.05), whereas length and head circumference z-scores were similar. Incidences of serious adverse events and reflux, fussiness, colic, and flatulence were similar among the three groups.Conclusion:Our data demonstrate that GMF provides adequate growth, has a good tolerability, and is safe to use in infants.

The Foetal Origins of Allergy and Potential Nutritional Interventions to Prevent Disease.

The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the “first 1000 days” from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the “soup” of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal and infant nutrition and the microbiome are easier to employ than changing other aspects of the environment but require large controlled trials before recommending changes to current practice.

The Macronutrient Composition of Infant Formula Produces Differences in Gut Microbiota Maturation That Associate with Weight Gain Velocity and Weight Status.

This proof-of-principle study analyzed fecal samples from 30 infants who participated in a randomized controlled trial on the effects of the macronutrient composition of infant formula on growth and energy balance. In that study, infants randomized to be fed cow milk formula (CMF) had faster weight-gain velocity during the first 4 months and higher weight-for-length Z scores up to 11.5 months than those randomized to an isocaloric extensive protein hydrolysate formula (EHF). Here we examined associations among infant formula composition, gut microbial composition and maturation, and children’s weight status. Fecal samples collected before and monthly up to 4.5 months after randomization were analyzed by shotgun metagenomic sequencing and targeted metabolomics. The EHF group had faster maturation of gut microbiota than the CMF group, and increased alpha diversity driven by Clostridia taxa. Abundance of Ruminococcus gnavus distinguished the two groups after exclusive feeding of the assigned formula for 3 months. Abundance of Clostridia at 3–4 months negatively correlated with prior weight-gain velocity and body weight phenotypes when they became toddlers. Macronutrient differences between the formulas likely led to the observed divergence in gut microbiota composition that was associated with differences in transient rapid weight gain, a well-established predictor of childhood obesity and other comorbidities.

Randomized Trial of Early Infant Formula Introduction to Prevent Cow’s Milk Allergy

To determine if the early introduction of cow’s milk formula (CMF) could prevent the development of cow’s milk allergy (CMA) in healthy infants.In the study, the researchers enrolled 491 newborns within 5 days of birth from 4 hospitals in Okinawa, Japan. Inclusion criteria were a gestational age of at least 35 weeks, a birth weight of at least 2000 g, and the absence of severe underlying disease.Participants were allowed to supplement with CMF before 1 month of age and underwent a screening oral food challenge (OFC) at that time. Those with a negative OFC result were randomly assigned to either the open-label CMF ingestion or avoidance. Those in the CMF ingestion group ingested at least 10 mL of CMF daily between 1 and 2 months of age, whereas those in the avoidance group were instructed to supplement with soy formula if needed during this time. At 3 months of age, an open OFC was performed on all participants. Those who were negative from both groups spontaneously ingested CMF to supplement breastfeeding until 6 months of age, at which time a second open OFC was performed on all participants.The modified intention-to-treat analysis revealed a significantly lower rate of CMA in the ingestion group versus the avoidance group at 6 months of age (0.8% vs 6.8%; respectively; P < .001). Approximately 70% were still breastfed, and no mothers had eliminated cow’s milk. There were no differences in the rate of eczema or sensitization to egg, wheat, or soy between groups.Daily ingestion of at least 10 mL of CMF between 1 and 2 months of life decreased the rate of OFC-confirmed CMA in infants. The early introduction of CMF did not impede breastfeeding.Data supporting the benefit of early introduction of allergenic foods in preventing allergy are accumulating. In this study, researchers examined the impact of introducing a specific daily minimum quantity of CMF in the general infant population, with favorable results. In further studies, researchers could provide interventions in a blinded manner and/or examine the impact of CMF introduction in infants at high-risk of allergy.

Corrigendum for Ha et al. Neurodevelopmental outcomes of infants fed soy formula versus cow milk formula: a retrospective, national population-based observational cohort study. J Nutr 2021;151(10):3045–52

Corrigendum for Ha et al. Neurodevelopmental outcomes of infants fed soy formula versus cow milk formula: a retrospective, national population-based observational cohort study. J Nutr 2021;151(10):3045–52

Lactose versus Lactose Free Regimen in Children with Acute Diarrhea

BACKGROUND: Acute diarrhea (AD) is the most frequent gastroenterological disorder, and the main cause of dehydration in childhood, and it is one of the most important causes of morbidity and mortality in children. AIM: Assessment of lactose-free formula effect in nutritional treatment in formula-fed children with acute diarrhea. PATIENTS AND METHODS: A cross-section interventional study carried out on 60 formula-fed children, under two years, referring with acute diarrhea, 30 children obtain lactose-free formulation and 30 children with no lactose-containing formula. According to the period of diarrheal stop and weight, changes compering two groups. RESULTS: Thirty-two males and 28 females children (7.25 ± 5.1 months) included. Children with lactose-free formula had a significantly slighter dated to diarrhea relief compared with control group children (p &lt; 0.01). No variance between two groups in weight change (6.9 ± 3.03 vs. 7.05 ± 3.07 kg, p = 0.2). (46.6%) of patients on Lactose free formula were discharged on the third post admission day, lactose-free formula has more effective recovery to those on cow milk formula (4.1 ± 1.2 vs. 6 ± 1.3 days, p &lt; 0.01 significant). CONCLUSION: Quick giving of lactose-free formulation to children on formula feeding show rapid relief of acute diarrhea.

Neurodevelopmental Outcomes in Infants Fed with Soy Formula: A Retrospective, National Population-Based Observational Cohort Study

BackgroundSoy-based infant formulas are increasingly popular, but data regarding their effects on neurodevelopmental outcomes during early childhood is scanty. ObjectiveThis study investigated the effect of consuming soy-based infant formula at 9–12 mo after birth on the subsequent development of epilepsy, neurodevelopmental disorders, and developmental status. MethodsThis nationwide retrospective administrative study used health screening examinations and linked insurance claims data of children born in Korea during 2008 and 2009. Infants who received soy formula were compared with those who received cow's milk formula using propensity score matching that considered birth history, economic status, clinical conditions, and drug prescription records. Exposure was defined as soy formula feeding determined from questionnaires completed by the parents when children were 9–12 mo old. Outcomes were epilepsy, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental status. Children were followed until 31 December, 2017. ResultsA total of 153,841 eligible participants were enrolled; 11,535 (7.5%) children received soy formula, while 142,864 (92.5%) received cow's milk formula. The incidence rate of epilepsy during the follow-up period was 29.8 per 100,000 person-years (95% CI: 19.90, 42.73) in the soy formula group and 22.6 per 100,000 person-years (95% CI: 16.40, 30.32) in the cow's milk formula group, with no significant difference (aHR: 1.318; 95% CI: 0.825, 2.106). The 2 groups also had no difference based on prespecified analysis using different definitions of epilepsy. Likewise, no significant associations of soy formula with ADHD (aHR: 1.26; 95% CI: 1.00, 1.60) or ASD (aHR: 0.99; 95% CI: 0.54, 1.83), or delays of developmental stages were observed. ConclusionsFeeding with soy formula rather than cow's milk formula had no apparent association with increased risks of epilepsy, ADHD, ASD, and developmental status, according to this cohort composed of a general pediatric population.

A partially hydrolyzed whey formula provides adequate nutrition in high-risk infants for allergy.

BACKGROUND/OBJECTIVESHydrolyzed formula is often fed to infants with gastrointestinal or immune issues, such as malabsorption or cow's milk allergy, because enzymatic treatment has rendered it more digestible and less allergenic than standard cow's milk formula (SF). Partially hydrolyzed formula (PHF) should be considered for those infants who are intolerant to extensively hydrolyzed formula. However, there are concerns about the nutritional insufficiencies of PHF. We aimed to evaluate the effects of PHF on the growth and health indicators in infants who were at high-risk of allergic disease and potential candidates for consuming PHF.SUBJECTS/METHODSA total of 83 infants aged 0–2 mon with a family history of allergies were assigned to consume either PHF or SF until 24 weeks of age. Anthropometric measures were obtained at baseline, 12 weeks, and 24 weeks; blood samples were drawn and evaluated at the end of the study.RESULTSNo significant differences were observed in weight, height, and weight-for-height at any time point in each sex between the PHF and SF groups. At 24 weeks of age, the weight-for-age and height-for-age z-scores of the SF group were higher than those of the PHF group, but there was no significant difference in the weight-for-height z-score. There were no significant differences in levels of white blood cells, hemoglobin, ferritin, protein, albumin, aspartate aminotransferase, alanine aminotransferase, eosinophil cationic protein, and immunoglobulin E.CONCLUSIONSIn this study, there were no differences in growth and blood panels between the infants consuming PHF or SF. Therefore, infants who are unable to tolerate SF can be fed PHF without nutritional concerns about growth.

Early Discontinuation of Cow's Milk Protein Ingestion Is Associated with the Development of Cow's Milk Allergy

Although early supplementation with cow's milk formula (CMF) reportedly increases the risk of cow's milk allergy (CMA) in breast-fed infants, little is known about the association between the timing of CMF discontinuation and subsequent CMA development. To elucidate the relationship between the timing of CMF discontinuation and CMA development in infants who received CMF in the early days of life. Using data from a randomized controlled trial of a birth cohort from 4 Japanese hospitals, we performed a subgroup analysis of participants who ingested CMF in the first 3 days of life. We compared the proportions of participants who developed CMA at age 6 months in those who discontinued CMF ingestion before age 1 month ("DISC <1-month group"), during age 1 to 2 months ("DISC 1-2-month group"), and during age 3 to 5 months ("DISC 3-5-month group") with those who continued CMF ingestion until age 6 months ("continuous group"). The risk ratios (RRs) and 95% CIs for CMA development were calculated. CMA incidence was significantly higher in the DISC <1-month group (n= 7 of 17, 41.2%; RR, 65.7; 95% CI, 14.7-292.5; P < .001), DISC 1-2-month group (n= 3 of 26, 11.5%; RR, 18.4; 95% CI, 3.2-105.3; P= .003), and DISC 3-5-month group (n= 7 of 69, 10.1%; RR, 16.2; 95% CI, 3.4-76.2; P < .001) than in the continuous group (n= 2 of 319, 0.6%). Early CMF discontinuation, particularly in the first month of life, was associated with CMA development in infants who received CMF in the first 3 days of life.

Inhibition of cow's milk allergy development in mice by oral delivery of β-lactoglobulin-derived peptides loaded PLGA nanoparticles is associated with systemic whey-specific immune silencing.

BackgroundTwo to four percentage of infants are affected by cow's milk allergy (CMA), which persists in 20% of cases. Intervention approaches using early oral exposure to cow's milk protein or hydrolysed cow's milk formula are being studied for CMA prevention. Yet, concerns regarding safety and/or efficacy remain to be tackled in particular for high‐risk non‐exclusively breastfed infants. Therefore, safe and effective strategies to improve early life oral tolerance induction may be considered.ObjectiveWe aim to investigate the efficacy of CMA prevention using oral pre‐exposure of two selected 18‐AA β‐lactoglobulin‐derived peptides loaded poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) in a whey‐protein induced CMA murine model.MethodsThe peptides were loaded in PLGA NPs via a double emulsion solvent evaporation technique. In vivo, 3‐week‐old female C3H/HeOuJ mice received 6 daily gavages with PBS, whey, Peptide‐mix, a high‐ or low‐dose Peptide‐NPs or empty‐NP plus Peptide‐mix, prior to 5 weekly oral sensitizations with cholera toxin plus whey or PBS (sham). One week after the last sensitization, the challenge induced acute allergic skin response, anaphylactic shock score, allergen‐specific serum immunoglobulins and ex vivo whey‐stimulated cytokine release by splenocytes was measured.ResultsMice pre‐treated with high‐dose Peptide‐NPs but not low‐dose or empty‐NP plus Peptide‐mix, were protected from anaphylaxis and showed a significantly lower acute allergic skin response upon intradermal whey challenge compared to whey‐sensitized mice. Compared with the Peptide‐mix or empty‐NP plus Peptide‐mix pre‐treatment, the high‐dose Peptide‐NPs‐pre‐treatment inhibited ex vivo whey‐stimulated pro‐inflammatory cytokine TNF‐α release by splenocytes.Conclusion & Clinical relevanceOral pre‐exposure of mice to two β‐lactoglobulin‐derived peptides loaded PLGA NPs induced a dose‐related partial prevention of CMA symptoms upon challenge to whole whey protein and silenced whey‐specific systemic immune response. These findings encourage further development of the concept of peptide‐loaded PLGA NPs for CMA prevention towards clinical application.

The Prevalence and Trends of the Early Introduction of Cow Milk to Newborns at Tertiary Care Center: A Risk of Atopy

Although all health organizations recommend exclusive breastfeeding (EBF), few neonates meet these recommended goals. The early intake of cow milk formulas (CMFs) has been linked to several childhood illnesses, including atopic diseases. Therefore, this study aimed to evaluate the prevalence of early exposure to CMFs in the nursery of a tertiary care hospital in Jeddah, Kingdom of Saudi Arabia. A retrospective review was conducted on the medical records of feeding practices of neonates born in King Abdulaziz University Hospital (KAUH) at Jeddah, Kingdom of Saudi Arabia. Two months from each year (May and December) were selected over the last five years. Approval from the ethical research committee at KAUH was obtained. Eight hundred and ninety-four different neonate files were reviewed. Four hundred and eighty-seven (54.5%) were males. Out of the total of 894, 838 (93.7%) newborns experienced an early introduction to CMFs, 797 (89.1%) received mixed CMF and breast milk, 41 (4.6%) received CMF only, and 56 (6.3%) received exclusive breastfeeding (EBF). Surprisingly, EBF has declined over time, from 39% in May 2016 to 1% in December 2020. The prevalence of early exposure to CMF was very high in newborns at KAUH nursery, and this prevalence was trending upwards. Extensive teaching programs on EBF and allergy prevention for mothers and related health care providers are highly recommended

Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow milk formula, or breast milk feeding during study follow-up. In the 147 infant boy participants, serum testosterone, luteinizing hormone, stretched penile length, anogenital distance, and testis volume were longitudinally assessed from birth to 28 weeks. We examined feeding-group differences in age trajectories for these outcomes using mixed-effects regression splines. Median serum testosterone was at pubertal levels at 2 weeks (176 ng/dL [quartiles: 124, 232]) and remained in this range until 12 weeks in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n = 55) and boys fed cow milk formula (n = 54). Compared with breastfed boys (n = 38), soy formula-fed boys had a more rapid increase in penile length (P = .004) and slower initial lengthening of anogenital distance (P = .03), but no differences in hormone trajectories. Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

The effect of feeding patterns on serum zonulin levels in infants at 3-4 months of age.

Zonulin so far is the only known endogenous modulator of intercellular tight junctions which regulate the intestinal permeability. Breastfeeding is considered to enhance the integrity of the gastrointestinal tract; however, limited data are available about the effect of feeding patterns on intestinal permeability. We aimed to investigate the potential association between the mode of feeding (breast versus formula milk) and the serum zonulin levels as a marker of intestinal permeability. One hundred fifty-seven full-term, healthy infants, born after an uncomplicated pregnancy, were enrolled within 72-96 h of life. Blood samples from 105 infants were obtained at 3 to 4 months of life. Serum zonulin levels were measured by ELISA. Out of 105 infants, 52.4% (55) were female, and 58.1% (61) were delivered by caesarian section at a mean gestational age of 38.9 (SD ± 1.0) weeks. At the time of blood sampling, median age was 3.4 (IQR 3.20-3.50) months, and mean weight was 6332 (SD ± 692) gr. Infants were divided in three groups according to the feeding patterns: exclusive breastfeeding (n = 42), mixed feeding (n = 41), and cow's milk formula (n = 22). The feeding pattern had no impact on infants' serum zonulin levels. Moreover, zonulin levels were not affected by infant's clinical and epidemiological characteristics such as body weight or family history of autoimmune disease.Conclusion: In our study, different feeding patterns were not associated with serum zonulin levels in healthy infants at 3-4 months of age. What is Known: • Serum zonulin is upregulated in conditions with increased intestinal permeability • Breast milk favors the physiological decline of the intestinal permeability after birth in the neonates What is New: • Serum zonulin levels were not affected by the feeding pattern (breast milk versus formula) in infants at 3-4 months of age • Clinical and epidemiological characteristics of infants had no impact on zonulin levels.

Food protein-induced enterocolitis syndrome presenting after necrotizing enterocolitis in a preterm neonate: a case report

When bloody stools occur in a very-low-birth-weight infant in the neonatal intensive care unit (NICU), necrotizing enterocolitis (NEC) is a prime consideration, though food protein-induced enterocolitis syndrome (FPIES) can be causative and is difficult to distinguish from NEC. Food allergy is an adverse reaction following exposure to food due to an abnormal immunologic response to food, and cow’s milk allergy (CMA) is the most likely form of food allergy in infants. The clinical features and proper management of patients with FPIES are important to differentiate FPIES from NEC. However, there are very few study reports of preterm infants presenting with food allergy-induced enterocolitis after NEC. Here, we report a case of a very-low-birth-weight infant born at 28 weeks of gestational age who developed recurrent episodes of bloody stools when he was fed cow’s milk or given breast milk fortified with milk after NEC recovery on day of life (DOL) 29, 46, and 54. A male preterm infant born at 28 weeks of gestational age presented with bloody stools on DOL 7. He was diagnosed with early-onset NEC with abdominal tenderness, sluggish bowel sounds, increased C-reactive protein (CRP) level and pneumatosis intestinalis (PI). After recovery from NEC on DOL 20, the infant developed three recurrent episodes of bloody stools after being fed cow’s milk or breast milk fortified with dairy milk. He was suspected of having recurrent episodes of NEC, but the infant was fairly healthy and did not present abdominal tenderness or abnormal bowel sounds on physical examination. Consecutive blood tests revealed normal CRP levels and increasing eosinophil levels. Abdominal radiograph revealed mild thickening of the small bowel, with no evidence of PI. The infant was finally diagnosed with FPIES in addition to NEC. After the infant received hydrolyzed formula, the bloody stool symptoms were finally resolved. Our case suggests that infants with recurrent episodes of bloody stools with increasing systemic eosinophils count should be considered for the diagnosis of FPIES with cow’s milk formula. Rapid improvement and non-progression of systemic symptoms and signs after removing exposure to milk protein may differentiate FPIES from NEC.