OBJECTIVES: To systematically evaluate the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical development in preterm infants. METHODS: A computerized search was performed in the databases including China National Knowledge Infrastructure, Wanfang Data, Weipu, PubMed, Embase, and the Cochrane Library to identify randomized controlled trials of the effect of prophylactic use of hydrolyzed protein formula on gastrointestinal diseases and physical growth in preterm infants. RevMan 5.3 software was used to perform a Meta analysis for the included studies. RESULTS: A total of 7 randomized controlled studies were included. The results of Meta analysis showed that compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula could reduce the risk of neonatal necrotizing enterocolitis (RR=0.40, P=0.04) and feeding intolerance (RR=0.40, P=0.005), and had no significant effect on the growth of weight, length and head circumference (P>0.05). CONCLUSIONS Compared with the whole protein formula, the prophylactic use of hydrolyzed protein formula in preterm infants may reduce the occurrence of necrotizing enterocolitis and feeding intolerance, and can meet the nutrient requirement of physical development. However, the evidence is limited, and the results of this study cannot support the routine prophylactic use of hydrolyzed protein formula in preterm infants.
Enterocolitis, Necrotizing/prevention & control* ; Gastrointestinal Diseases/prevention & control* ; Humans ; Infant ; Infant Formula/chemistry* ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Randomized Controlled Trials as Topic

Folic acid belongs to the group of water-soluble B vitamins and naturally exists in multiple forms in a wide variety of foods such as legumes, vegetables, liver, and milk (Iyer and Tomar, 2009; Lyon et al., 2020). It is involved in many biochemical reactions critical for cell division, such as purine and pyrimidine biosynthesis, DNA/RNA biosynthesis, and amino acid metabolism (Iyer and Tomar, 2009). Mammals cannot synthesize folic acid and thus they must acquire it from food. Although folic acid is ubiquitous in foods, folic acid deficiency still often occurs due to various causes such as unhealthy diet (Hildebrand et al., 2021; Iimura et al., 2022), disease-related malabsorption (Arcot and Shrestha, 2005), medication-related depletion (Arcot and Shrestha, 2005), or vitamin B12 deficiency (Fishman et al., 2000). Folic acid deficiency has been associated with several health problems, such as anemia (Carmel, 2005; Bailey and Caudill, 2012), cancer (Duthie, 1999), cardiovascular diseases (Wald et al., 2002), neural tube defects in newborns (van der Put et al., 2001), neuropsychiatric dysfunction (Shea et al., 2002), depression (Falade et al., 2021), inflammatory diseases (Suzuki and Kunisawa, 2015; Jones et al., 2019), and eye diseases (Sijilmassi, 2019). To prevent folic acid deficiency, its daily intake (400 μg/d) has been recommended for adults in the European Union, and its increased intake (600 μg/d) is advised for women before and during pregnancy (FAO/WHO, 2002; IOM, 2004). The New Zealand government mandated the fortification of non-organic wheat flour with folic acid in July 2021, and the UK government mandated the fortification of non-wholemeal wheat flour with folic acid in September 2021 (Haggarty, 2021).
Adult ; Animals ; Female ; Flour ; Folic Acid/metabolism* ; Folic Acid Deficiency/prevention & control* ; Food, Fortified ; Humans ; Infant, Newborn ; Mammals/metabolism* ; Pregnancy ; Triticum/metabolism*

OBJECTIVES: To study the risk factors for food sensitization and the influence of food sensitization on quality of life and clinical signs in children with atopic dermatitis (AD). METHODS: A retrospective analysis was performed on the medical data of 241 children with AD, including demographic features, age of onset, severity of AD, quality of life, physical examination results, skin prick test (SPT) results, serum total IgE levels, and eosinophil count. According to the results of SPT, the children were divided into a food sensitization group (n=127) and a non-food sensitization group (n=114). The multivariate logistic regression analysis was used to identify the risk factors for food sensitization in children with AD. RESULTS: The prevalence rate of food sensitization was 52.7% (127/241) in the children with AD. The multivariate logistic regression analysis showed that birth in autumn or winter, age of onset of AD<12 months, severe AD, and total IgE>150 IU/mL were risk factors for food sensitization (P<0.05). Compared with the non-food sensitization group, the food sensitization group had a significantly poorer quality of life (P=0.008) and significantly higher prevalence rates of non-specific hand/foot dermatitis and palmar hyperlinearity (P<0.05). Compared with the single food sensitization group, the multiple food sensitization group had more severe AD and a significantly higher proportion of children with exclusive breastfeeding or total IgE>150 IU/mL (P<0.05). CONCLUSIONS The AD children born in autumn or winter, or those with early onset (<12 months), severe AD or total IgE>150 IU/mL have a higher risk of food sensitization. The AD children with food sensitization have a poorer quality of life and are more likely to develop non-specific hand/foot dermatitis and palmar hyperlinearity.
Allergens ; Child ; Cross-Sectional Studies ; Dermatitis, Atopic ; Food Hypersensitivity ; Humans ; Immunoglobulin E ; Infant ; Quality of Life ; Retrospective Studies ; Risk Factors

Objective: To assess the risk of foodborne diseases caused by Cronobacter sakazakii in infant formula powder from retail to feeding and provide formulate suggestions for safe feeding of infants at home. Methods: This study used the special monitoring and risk monitoring data of infant formula powder in Heilongjiang Province and combined data at home and abroad. The @RISK software was used to evaluate the disease risk caused by Cronobacter sakazakii in the process of infant formula powder from retail to feeding. Results: According to the results of this quantitative risk assessment, the risk of foodborne diseases caused by Cronobacter sakazakii at the current consumption pattern in Heilongjiang Province was 5.158×10^-5 persons/million (40.0 ℃ and 50.0 ℃), 1.072×10^-7 persons/million (60.0 ℃), 5.544×10^-14 persons/million (70.0 ℃). When the feeding time of infant formula powder was adjusted to 0-2 h and 2-3 h respectively, the above prediction results did not change. When it was adjusted to 3-4 h, the risk increased. If it was adjusted to 4-24 h, the number of Cronobacter sakazakii increased by 14-24 orders of magnitude at room temperature. If the initial pollution concentration (after flushing) was adjusted to 1 MPN/ml, the average disease risk per meal was 805.7 persons/million (40.0 ℃ and 50.0 ℃), 1.7 persons/million (60.0 ℃) and 9.1 × 10^-7 persons/million (70.0 ℃). The results of sensitivity analysis showed that the water temperature (70.0 ℃), initial pollution concentration, room storage time and temperature were important factors of risk. Conclusion: Controlling the contamination level of Cronobacter sakazakii in infant formula powder, controlling the feeding time within 3 h, storing in refrigerator and mixing with water with temperature not lower than 70.0 ℃ are effective measures to prevent infants from eating infant formula powder infected by Cronobacter sakazakii.
Infant ; Humans ; Cronobacter sakazakii ; Infant Formula ; Food Microbiology ; Powders ; Risk Assessment ; Foodborne Diseases

BACKGROUND: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. METHODS: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. RESULTS: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). CONCLUSIONS: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. TRIAL REGISTRATION UMIN000030786 .
Asthma ; epidemiology ; etiology ; Cohort Studies ; Dermatitis, Atopic ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; epidemiology ; etiology ; Humans ; Hypersensitivity ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Japan ; Male ; Vaccines, Inactivated ; adverse effects ; Viral Vaccines ; adverse effects

BACKGROUND: Although the clinical importance of the immunological benefits of breastfeeding has been emphasized for decades, their direct relationship with acute pyelonephritis (APN) is still not clear. Our goal was to determine whether breastfeeding truly provides protection against APNs, while investigating the effects of other factors such as sex, age, mode of delivery, and birth weight on APN.METHODS: A total of 62 infants under 6 months of age who had both microbiologically and radiologically-confirmed APN were enrolled in the case group. Healthy infants (n = 178) who visited the hospital for scheduled vaccinations were enrolled in the control group. The following participant characteristics were compared between the case and control groups: age, sex, birth order among siblings, feeding methods, weight percentile by month, birth weight percentile by gestational age, gestational age at birth, and mode of delivery.RESULTS: Babies exclusively fed with manufactured infant formulae before 6 months of age had significantly higher risk for APN than breastfed or mixed-fed infants (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.687–7.031; P = 0.001). Firstborn babies had lower risk for APN than 2nd- or 3rd-born babies (OR, 0.43; 95% CI, 0.210–0.919). Other factors that increased the risk for APN were low birth weight percentiles (OR, 8.33; 95% CI, 2.300–30.166) and birth via caesarean section (OR, 2.32; 95% CI, 1.097–4.887). There were more preterm births in the case group (10.9% vs. 1.7%; P = 0.002), but this did not increase the risk for APN (OR, 4.47; P = 0.063).CONCLUSION: Feeding exclusively with formula before 6 months of age was related to higher risk for APN, which demonstrates that breastfeeding has a protective effect against APN. The other risk factors for APN were birth order (≥ 2nd-born), low birth weight, and birth via caesarean section.
Birth Order ; Birth Weight ; Breast Feeding ; Cesarean Section ; Feeding Methods ; Female ; Gestational Age ; Humans ; Infant Formula ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Parturition ; Pregnancy ; Premature Birth ; Pyelonephritis ; Reproductive History ; Risk Factors ; Siblings ; Urinary Tract Infections ; Vaccination

food elements and is applicable to extra-intestinal tissues. Prebiotics are recognized as a promising tool in the promotion of general health and in the prevention and treatment of numerous juvenile diseases. Prebiotics are considered an immunoactive agent, with the potential for long-lasting effects extending past active administration of the prebiotic. Because of its extremely low risk of serious adverse effects, ease of administration, and strong potential for influencing the composition and function of the microbiota in the gut and beyond, the beneficial clinical applications of prebiotics are expanding. Prebiotics are the third largest component of human breast milk. Preparations including galactooligosaccharides (GOS), fructooligosaccharides (FOS), 2′-fucosyllactose, lacto-N-neo-tetraose are examples of commonly used and studied products for supplementation in baby formula. In particular, the GOS/FOS combination is the most studied. Maintaining a healthy microbiome is essential to promote homeostasis of the gut and other organs. With more than 1,000 different microbial species in the gut, it is likely more feasible to modify the gut microbiota through the use of certain prebiotic mixtures rather than supplementing with a particular probiotic strain. In this review, we discuss the latest clinical evidence regarding prebiotics and its role in gut immunity, allergy, infections, inflammation, and functional gastrointestinal disorders.]]>
Gastrointestinal Diseases ; Gastrointestinal Microbiome ; Homeostasis ; Humans ; Hypersensitivity ; Infant Formula ; Infant ; Inflammation ; Microbiota ; Milk, Human ; Prebiotics ; Probiotics

PURPOSE: The Cow's Milk-related Symptom Score (CoMiSS™), which considers crying, regurgitation, stools, skin and respiratory symptoms, was developed as an awareness tool for evaluating cow's milk-related symptoms. The scoring ranges from 0 to 33. A score ≥12 was proposed as being likely cow's milk-related and suggestive of allergy to cow's milk. This study aimed to determine the age-related CoMiSS™ values in presumed healthy infants in Poland.METHODS: This was a cross-sectional study conducted in well-child clinics in two locations. Parents of the presumed healthy infants aged ≤6 months were approached during a routine checkup/vaccination visit. The exclusion criteria were as follows: presence of acute or chronic diseases, preterm delivery, treatment with therapeutic formula, and use of any food supplements (except vitamins) or medications.RESULTS: Data from 226 infants were obtained (median age [Q1–Q3], 4 months [3–4]). The overall median (Q1–Q3) and mean (standard deviation) CoMiSS™ values were 4 (2–7) and 4.7 (3.5), respectively. The 95th percentile was 11. Scores on some, albeit not all, components of the CoMiSS™ significantly differed between age groups (crying, stools) or feeding type groups (stools and skin symptoms). Eleven children (4.9%) scored ≥12.CONCLUSION: This study adds to earlier age-related CoMiSS™ data by providing CoMiSS™ values in presumed healthy infants in Poland.
Child ; Chronic Disease ; Cross-Sectional Studies ; Crying ; Dietary Supplements ; Food Hypersensitivity ; Humans ; Hypersensitivity ; Infant ; Milk ; Parents ; Poland ; Skin

Maternal nutritional status during pregnancy will affect the outcomes for the mother and the newborn. Maternal diet was assessed in 150 pregnant women during the first trimester of pregnancy by a 168-item food frequency questionnaire. Dietary patterns were explored by Factor analysis, and association of patterns with maternal and neonatal outcomes such as gestational diabetes mellitus (GDM), anemia and anthropometric indices were determined by analysis of variance and linear regression analysis. Three major dietary patterns were identified: 1) High Carbohydrate-Lower Fat (mean age, 27.67 ± 6.1; n = 34), 2) High Carbohydrate-Higher Fat (27.70 ± 4.1; n = 55), and 3) High Fiber (29.27 ± 5.8; n = 61). A significant difference was observed between maternal dietary patterns (p < 0.01) for GDM, while it was not significant for anemia. Also, the number of preterm and low birth weight (LBM) infants as well as mean weight, height and head circumference of the infants did not differ significantly between patterns, but there was a significant difference between the maternal dietary patterns about the number of macrosomic babies, which was higher in the second (n = 9) and third (n = 9) dietary patterns (p < 0.01). After adjusting for mothers' age, disease history, disease status, and energy intake, High Carbohydrate-Lower Fat dietary pattern was more associated with GDM than crude model (p = 0.01 vs. p = 0.02). The present study indicated a significant relationship between maternal dietary patterns before pregnancy and GDM and fetal macrosomia.
Anemia ; Birth Weight ; Diabetes, Gestational ; Diet ; Energy Intake ; Female ; Fetal Macrosomia ; Food Habits ; Head ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Linear Models ; Mothers ; Nutritional Status ; Pregnancy ; Pregnancy Outcome* ; Pregnancy Trimester, First ; Pregnancy* ; Pregnant Women

PURPOSE: The aim of this study was to identify the minimally meaningful dosage of inulin leading to a prebiotic effect in Indonesian infants. METHODS: In a randomized controlled double-blinded, parallel, 3-arm intervention study, 164 healthy formula-fed infants aged 3 to 5 months first obtained formula-A (without inulin) during a 4-week adaptation period. Subsequently, 142 subjects were subjected to a 4-week feeding period by administering either formula-A (no inulin), formula-B (0.2 g/100 mL inulin) or formula-C (0.4 g/100 mL inulin). The primary outcome parameter was %-bifidobacteria in faecal samples determined using quantitative polymerase chain reaction analyses. Secondary outcome parameters were faecal %-lactobacilli, pH and stool frequency, and consistency. Growth and tolerance/adverse effects were recorded as safety parameters. RESULTS: Typical %-bifidobacteria and %-lactobacilli at the end of the adaptation period in the study population were 14% and 2%, respectively. For faecal pH, significant differences between formula groups A vs. C and A vs. B were found at the end of the intervention period. Testing for differences in faecal %-bifidobacteria and %-lactobacilli between groups was hampered by non-normal data set distributions; no statistically significant differences were obtained. Comparisons within groups revealed that only in formula group C, all the three relevant parameters exhibited a significant effect with an increase in faecal %-bifidobacteria and %-lactobacilli and a decrease in pH. CONCLUSION: A consistent prebiotic effect along with a decrease in pH and increase in %-bifidobacteria and %-lactobacilli was found only in the group administered 0.4 g inulin/100 mL.
Dataset ; Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; Infant Formula ; Infant* ; Inulin* ; Polymerase Chain Reaction ; Prebiotics*