Formula Intake Research Articles

Regulation mechanisms of allergenic epitope sites in casein by microbial and plant-derived proteases

Casein (CN) is the primary factor leading to allergic reactions in infants to bovine milk, severely limiting the intake of bovine milk formula by allergic infants. This study investigates the conformational changes and regulation of linear epitopes during the hydrolysis of CN by five proteases derived from microbial and plant sources using multiple spectroscopic techniques combined with LC/MS-MS. The results showed that the IgE inhibition rates for SD (subtilisin hydrolysate), PD (papain hydrolysate), BD (bromelain hydrolysate), KD (proteinase K hydrolysate), and FD (ficin hydrolysate) were 43.19%, 41.99%, 35.45%, 48.15%, and 14.80%, respectively. The differences in antigenic residues remaining after hydrolysis by different proteases mainly result from the varying degrees of structural alteration of CN and the hydrolysis allergic epitope regions. This study provides theoretical basis for understanding the mechanism by which proteases reduce the allergenicity of CN. It also offers new insights into the development of multienzyme combinatorial hydrolysis strategies.

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.

High Concentrations of Immunoglobulin G Against Cow Milk Proteins and Frequency of Cow Milk Consumption Are Associated With the Development of Islet Autoimmunity and Type 1 Diabetes—The Trial to Reduce Insulin-dependent Diabetes Mellitus (IDDM) in the Genetically at Risk (TRIGR) Study

BackgroundThe Trial to Reduce IDDM in the Genetically at Risk (TRIGR) (NCT00179777) found no difference type 1 diabetes risk between hydrolyzed and regular infant formula. However, cow's milk consumption during childhood is consistently linked to type 1 diabetes risk in prospective cohort studies. ObjectiveOur primary aim was to study whether humoral immune responses to cow’s milk and cow’s milk consumption are associated with type 1 diabetes in TRIGR children. MethodsTRIGR comprised 2159 children with genetic susceptibility to type 1 diabetes born between 2002-2007 in 15 countries. Children were randomized into groups receiving extensively hydrolyzed casein or a regular cow’s milk formula and followed until age 10. Type 1 diabetes related autoantibodies and antibodies to cow’s milk proteins were analyzed. Infant formula intake was measured by structured dietary interviews and milk consumption with a food frequency questionnaire. Associations of milk antibodies and milk consumption with the risk to develop type 1 diabetes were analysed by Cox survival model. ResultsCow’s milk antibody levels both in cord blood [HR for islet autoimmunity 1.30 (95% CI 1.05-1.61); type 1 diabetes 1.32 (1.02-1.71)] and longitudinally from birth to 3 years [islet autoimmunity 1.39 (1.07-1.81); type 1 diabetes 1.43 (1.04-1.96)] were associated with increased risk of developing type 1 diabetes. The amount of regular infant formula was associated with a reduced islet autoimmunity risk in the regular infant formula group [0.92 (0.85-0.99)]. Furthermore, frequent liquid milk consumption after infancy was associated with an increased risk of islet autoimmunity or type 1 diabetes. ConclusionsElevated cow's milk antibody levels and high consumption of liquid milk after infancy are related to type 1 diabetes development in children with an increased genetic susceptibility to type 1 diabetes. Enhanced antibody levels to cow’s milk may provide a biomarker of immune system prone to develop islet autoimmunity. Trial registry numberNCT00179777

Tolerance of Infants Fed a Hydrolyzed Rice Infant Formula with 2'-Fucosyllactose (2'-FL) Human Milk Oligosaccharide (HMO).

The purpose of this research was to assess the growth, tolerance, and compliance outcomes associated with the consumption of a hydrolyzed rice infant formula (HRF) enriched with 2'-Fucosyllactose (2'-FL) a Human Milk Oligosaccharide (HMO), and nucleotides in an intended population of infants. This was a non-randomized single-group, multicenter study. The study formula was a hypoallergenic HRF with 2'-FL, Docosahexaenoic acid (DHA), Arachidonic acid (ARA), and nucleotides. Infants 0-90 days of age who were formula fed and experiencing persistent feeding intolerance symptoms, symptoms of suspected food protein (milk and/or soy) allergy, or other conditions where an extensively hydrolyzed infant formula was deemed an appropriate feeding option were recruited by pediatricians from their local populations. The primary outcome was maintenance of weight-for-age z-score. Weight, length, head circumference, formula intake, tolerance measures, clinical symptoms and questionnaires were collected. Thirty-three infants were enrolled, and 27 completed the study, on study product. Weight-for-age z-scores of infants showed a statistically significant improvement from Visit 1 to Visit 4 (p = 0.0331). There was an adequate daily volume intake of 762 ± 28 mL/day, average daily number of stools of 2.1 ± 0.3, and mean rank stool consistency of 2.38 ± 0.18. After 28 days of switching to a HRF, 86.8 ± 5.9% of the symptoms resolved or got better by Visit 4 as reported by parents. HRF with 2'-FL HMO was safe, well tolerated, and supported weight gain in infants with suspected cow's milk allergy or persistent feeding intolerance.

Growth and gut comfort of healthy term infants exclusively fed with a partially hydrolysed protein-based infant formula: a randomized controlled double-blind trial.

This study aimed to investigate growth and gut comfort of healthy infants fed with a partially hydrolysed cow's milk protein-based infant formula (pHF) compared to a standard intact cow's milk protein-based formula (IPF). A double-blind, multi-center, randomized, controlled trial was performed. Healthy full-term, exclusively formula-fed infants (n = 345), aged ≤28 days were allocated to consume either a pHF (n = 173) or an IPF (n = 172) until the age of 17 weeks. The primary outcome was equivalence of weight gain (g/d) until the age of 17 weeks. The secondary outcomes were equivalence of other growth parameters, i.e., infants' weight, length, head circumference, body mass index (BMI) and anthropometric Z-scores, while tertiary outcomes were gut comfort, formula intake, and adverse events (AEs). Overall, 288 infants completed the study (pHF group: 138, IPF group: 150). No differences were observed between the two groups in weight gain (g/d) during the three-months intervention [p = 0.915 for the Per Protocol (PP) population]. The 90% CI was [-1.252 to 1.100] being within the pre-defined equivalence margin of ±3.0 g/d. Similar findings were observed in the Full Analysis Set (FAS) and the sensitivity analysis. Regarding the secondary outcomes, no differences over the intervention period were shown between the two groups in both the PP and FAS analysis sets. Average Z-scores were in the normal range based on World Health Organization (WHO) growth standards for both groups at all time points in both analysis sets. Stool consistency, amount, and colour were different in the two groups. No differences were observed in gut comfort, stool frequency, and formula intake, between the two groups. In total 14 AEs and 22 serious adverse events (SAEs) were reported of which 15 (12%) and 1 (5%) were considered as (possibly) related to the study product, respectively. The study demonstrates that the consumption of pHF results in adequate infant growth, equivalent to that of infants consuming IPF. Furthermore, the overall gut comfort was comparable between the two groups. Therefore, it can be concluded that the pHF is safe for and well tolerated by healthy infants. https://clinicaltrials.gov/study/NCT05757323?id=NCT05757323&rank=1, identifier (NCT05757323).

Baby Food Pouches, Baby-Led Weaning, and Iron Status in New Zealand Infants: An Observational Study.

Iron deficiency in infants can impact development, and there are concerns that the use of baby food pouches and baby-led weaning may impair iron status. First Foods New Zealand (FFNZ) was an observational study of 625 New Zealand infants aged 6.9 to 10.1 months. Feeding methods were defined based on parental reports of infant feeding at "around 6 months of age": "frequent" baby food pouch use (five+ times per week) and "full baby-led weaning" (the infant primarily self-feeds). Iron status was assessed using a venepuncture blood sample. The estimated prevalence of suboptimal iron status was 23%, but neither feeding method significantly predicted body iron concentrations nor the odds of iron sufficiency after controlling for potential confounding factors including infant formula intake. Adjusted ORs for iron sufficiency were 1.50 (95% CI: 0.67-3.39) for frequent pouch users compared to non-pouch users and 0.91 (95% CI: 0.45-1.87) for baby-led weaning compared to traditional spoon-feeding. Contrary to concerns, there was no evidence that baby food pouch use or baby-led weaning, as currently practiced in New Zealand, were associated with poorer iron status in this age group. However, notable levels of suboptimal iron status, regardless of the feeding method, emphasise the ongoing need for paying attention to infant iron nutrition.

Comparison study of the new national standard infant formula and dietary reference intakes 2023

To compare the relationship between the nutrient limit in new national standard Infant Formula(GB 10765-2021)(New GB)and the corresponding nutrients in Dietary Reference Intakes for China 2023(DRIs 2023), to determine the scientific and reasonable base of each nutrient in New GB, and provide supports for future revision of it. Using a data conversion method, the adequate intake(AI) of each nutrient recommended by DRIs 2023 for infants aged 0-6 months and the nutrient limit in the New GB were input into the Excel table. Based on authoritative data on the representative weight of 0-6 month infants and the recommended energy values, the conversion was done, the ratio of the lower limit of each nutrient in New GB and the AI of corresponding nutrient, as well as the ratio of the upper limit of nutrients in New GB and their tolerable upper intake level(UL) were calculated. For most nutrients in New GB for infant formula, the ratio of the lower limit to their AI is close to 1. For those nutrients with a large ratio of the lower limit to AI, or with a ratio of the upper limit to UL were greater than 1, detail analysis was conducted. Based on DRIs 2023, the nutrient limit for each nutrient in New GB for infant formula was scientific and reasonable. For some nutrients with a large ratio, more studies should be done in the future to determine whether the limit in National Standard need to be adjusted.

Sex-Specific Differences in Nutrient Intake in Late Preterm Infants.

The study involved a retrospective analysis of preterm infants admitted to the NICU and evaluated between 34 0/7 and 36 6/7 weeks of corrected gestation. Late preterm infants appropriate for gestational age who were spontaneously fed formula milk ad-lib and free of any respiratory support for at least two days were included. The study excluded infants with short gut syndrome, severe chromosomal anomalies, or congenital heart conditions. We included 85 male and 85 female infants in this study. The data collected included sex, gestational age, birth weight, anthropometric data at birth, maternal data, nutritional intake, and neonatal morbidity. This study found that female infants consumed more volume, protein, and calories than male infants. The mean formula intake in female and male infants was 145.5 ± 20.8 mL/kg/d and 135.3 ± 19.3 mL/kg/d, respectively, with p = 0.002. However, ad-lib feeding duration was not different between the sexes. Growth velocity was also higher in female infants. This study is the first to demonstrate differences in formula milk intake among late preterm infants fed ad libitum. Additional research is needed to confirm our findings and understand sex-specific differences in neonatal nutrition in extremely early preterm infants.

Es Niño o Niña?: Gender Differences in Feeding Practices and Obesity Risk among Latino Infants

BackgroundObesity prevalence is significantly higher among Latino boys than girls. Weight status at 12 mo, a significant predictor of childhood obesity, is associated with feeding practices during infancy. ObjectivesThe objectives were to examine breastfeeding and formula-feeding practices overall and by infant gender and to examine relations among infant gender, milk-feeding practices, and obesity risk among Latino infants over the first year of life. MethodsLatino mother–infant dyads (n = 90) were recruited from a pediatric clinic. Mothers were interviewed at regular intervals (infants aged 2, 4, 6, and 9 mo), and 24-h feeding recalls were conducted when infants were aged 6 and 9 mo. Infants’ lengths and weights were retrieved from clinic records to calculate weight-for-length percentiles. A bivariate analysis was conducted to compare feeding practices by gender and mediation analysis to test whether feeding practices mediated the relation between gender and obesity risk. ResultsThe majority (80%) of mothers were born outside the United States. In early infancy, mixed feeding of formula and breastfeeding was common. At 6 and 9 mo of age, milk-feeding practices differed, with formula feeding more common for boys than girls. At 12 mo, 38% of infants experienced obesity risk (≥85th weight-for-length percentile). Infants’ obesity risk increased by 18% per 1 oz increase in powdered formula intake. Formula intake among boys was on average 1.42 oz (in dry weight) higher than that among girls, which, in turn, mediated their increased obesity risk (IERR = 1.27, 95% confidence interval: 1.02, 1.90). ConclusionsThe increased obesity risk among Latino boys compared with girls at 12 mo was explained by higher rates of formula feeding at 6 and 9 mo of age. Future investigations of cultural values and beliefs in gender-related feeding practices are warranted to understand the differences in obesity risk between Latino boys and girls.

Healthcare professionals and commercial milk formula recommendations in the urban Mexican context.

Breastfeeding (BF) is considered an essential component of optimal care for child health and development. In the past two decades, global data have shown improvements in some, but not all, BF indicators. Despite these positive changes sales and per capita intake of commercial milk formula (CMF) have increased globally. The CMF industry invests millions of dollars in marketing, which targets families and healthcare professionals (HCP). In Mexico, more than half of the mothers (53%) who feed their infants with CMF chose their Brand on the recommendation of HCP. Understanding the reasons behind the current recommendations for the use of CMF by HCP is important for the design of BF interventions. The primary objective of this study was to explore Mexican HCP' beliefs, attitudes, perceptions, and practices about early infant feeding practices, and reasons for recommending CMF. The secondary objective was to explore pregnant women and mother's perceptions of the infant feeding recommendations they received from HCP, and of the factors that influenced their infant feeding decisions. The study was based on a secondary qualitative data analysis of a WHO/UNICEF multi-country study. We analyzed focus group discussions (FGDs) and in-depth interviews (IDIs) from Mexico. Data were collected through convenience sampling in Mexico City and Guadalajara. HCP (n = 34) analysis was based on IDIs, and pregnant women or mothers of children 0-18 months (n = 74) on FGDs and IDIs. Through a thematic analysis, we identified the socioecology of BF and triangulated HCP and women's accounts. HCP, pregnant women, and mothers recognized that several factors might have influenced their infant feeding decisions including healthcare facilities' policies and maternal work conditions. Although HCP believed that BF is the best way to feed newborns and young children, they routinely recommended CMF. On the other hand, pregnant women and mothers had a strong belief that BF is the best way to feed their babies. However, when women sought support from HCP, the latter often recommended switching to CMF. This study highlights the discordance between HCP perceptions and mothers' experiences of HCP recommendations about infant feeding. Our findings support a national call for policy actions.

Levels of organic pollutants and metals/metalloids in infant formula marketed in Brazil: Risks to early-life health

Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI – 3.57 and 0.36 μg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.

Impact of feeding volumes in the first 24 h of life on neonatal feeding intolerance.

This study investigates whether volumes of intake in the first 24 h of life (24 HOL), in relation to birth weight (BW) and gestational age (GA), impact neonatal feeding intolerance (FI). This study employed a retrospective chart review of 6,650 infants born at ≥35 weeks. The volumes of each formula feed per kg BW in the first 24 HOL were assessed. FI was defined as evidenced by chart documentation of emesis, abdominal distension, abdominal x-ray, and/or switching to a sensitive formula. Overall, the maximum volume of formula intake per feed was inversely correlated with GA and was higher in infants with FI (β = -1.39, p < 0.001) compared with infants without FI (β = -1.28, p < 0.001). The odds of emesis in late preterm infants with first feeding of >8 ml/kg [adjusted odds ratio (AOR) = 2.5, 95% confidence interval (CI): 1.4-4.6] and formula switching in the exclusively formula-fed group with volumes >10.5 ml/kg [AOR = 2.2, 95% CI (1.8-2.6)] were high. In the breastfeeding group, the odds of FI increased by 2.8-, 4.6-, and 5.2-fold with 5-10, 10-15, and >15 ml/kg of supplementations, respectively. A higher volume of intake in relation to BW often exceeds the physiological stomach capacity of newborns and is associated with early FI. Optimizing early feeding volumes based on infant BW and GA may decrease FI, which may be an issue of volume intolerance.

Risk assessment of 3-MCPD esters and glycidyl esters from the formulas for infants and young children up to 36 months of age

Esters of 2-monochloropropane-1,2-diol (2-MCPD), 3- monochloropropane-1,2-diol (3-MCPD), and glycidol are present in infant formulas, follow-on foods and similar compositions. They arise mainly from the vegetable oil content and may cause harmful effects in consumers. The contents of these substances in formulas were determined indirectly by converting the esters to the free form, followed by derivatization and analysis by gas chromatography-tandem mass spectrometry (GC-MS/MS). The validation results demonstrate that the method had sufficient specificity and adequate accuracy. The limits of detection (LOD) and limits of quantification (LOQ) for each of 2­MCPDE, 3­MCPDE, and GE were 1.5 and 5 µg/kg, respectively. Formula intake by children up to 36 months of age was surveyed, and the data was used to assess the risks due to 3-MCPD esters (3-MCPDE) and glycidyl esters (GE). The mean exposure dose of 3-MCPDE for different age groups ranged from 0.51 to 1.13 µg/kg bw per day. The corresponding mean GE exposure ranged from 0.031 to 0.069 µg/kg bw per day. Neither mean values nor the percentile 95% values of 3-MCPDE exposure doses exceed the recommended provisional maximum tolerable daily intake (PMTDI).

A longitudinal observational study of skeletal development between ages 3 mo and 6 y in children fed human milk, milk formula, or soy formula

BackgroundEarly infant feeding can affect skeletal development. Most children are fed with breast milk, dairy-based infant formula, or soy-based infant formula during the first year of life. The National Health and Nutrition Examination Survey 2003–2010 reports that 12% of the US infants consume soy-based infant formula. Despite potential effects of soy-associated isoflavones on skeletal development, studies investigating bone metabolism and structural and functional bone indices in children are lacking. ObjectiveThe aim of this observational study was to investigate early effects of soy-based infant formula (SF group) intake on bone metabolism and structure during the first 6 y of life comparing with those of infants fed with breast milk (BF group) and dairy-based infant formula (MF group). MethodsA total of 433 healthy infants were followed up from 3 mo to 6 y of age. Children’s skeletal development was assessed using dual-energy X-ray absorptiometry (DXA; N = 433) and peripheral quantitative computed tomography (pQCT; n = 78). The urinary biomarkers of bone metabolism (N-terminal telopeptide of type I collagen [NTx] and osteocalcin) were evaluated using immunoassays at 6, 24, 60, and 72 mo. ResultsNo statistically significant group differences were observed in bone mineral density (BMD) between the BF, MF, and SF groups, assessed using DXA or pQCT. At 6 y of age, children in the SF group showed significantly greater whole-body bone mineral content measured using DXA than those in the MF group. Six-month-old boys in the SF group demonstrated significantly greater levels of NTx than those in the MF group and significantly greater osteocalcin levels than those in the BF group. ConclusionsTogether, these data suggest that although infants at age 6 mo in the SF group showed some enhanced bone metabolism compared with those in the BF and MF groups, as indicated by the urinary biomarkers, no differences in bone metabolism or BMD were noted between ages 2 and 6 y.This trial was registered at clinicaltrials.gov as NCT00616395.

Pseudo-Bartter syndrome in an infant without obvious underlying conditions: A case report

Pseudo-Bartter syndrome (PBS) develops owing to renal or extrarenal chloride loss, leading to hypokalemic alkalosis. Whereas most adult cases result from diuretic/laxative abuse, many infantile cases occur secondary to cystic fibrosis. Rarely, infantile PBS is caused by renal salt loss with anomalies of the kidney/urinary tract or genetic disorders, such as Dent disease. Here, we report the case of a 10-mo-old girl with a one-month history of decreased formula intake and 5.6% body weight loss. She showed typical laboratory findings as PBS, including hypokalemia (2.7 mEq/L) and high levels of bicarbonate (32.7 mEq/L) with a plasma renin activity of 399 ng/mL/h. With minimum supplementation of potassium and sodium, an improvement in body mass index, from –1.13 SD to +0.52 SD, with complete resolution of laboratory data was obtained in approximately one month. No causative mutations were identified in candidate genes for Bartter–Gitelman syndrome. Due to profound hypochloruria (< 15 mEq/L), PBS of renal origin was unlikely. In addition, extrarenal chloride loss did not seem to be the case, because the patient never manifested gastrointestinal symptoms. Therefore, we speculate that a temporary decrease in chloride intake, coupled with the putative genetic/epigenetic disadvantage of chloride retention, such as a subtle renal leak, may be responsible for the PBS in our patient.

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.

Formula Feeding Significantly Increases Risk of Iron Deficiency in Very Preterm Infants during the First 4-6 Months of Life

Introduction: Iron deficiency (ID) early in life is associated with adverse neurodevelopmental and behavioural outcomes later in life. Preterm infants are considered at increased risk of developing ID due to their relative lack of iron stores, accelerated growth during the first few weeks of life and multiple phlebotomies received while in hospital. Breast fed (BF) preterm infants are considered at particularly increased risk of ID due to the lower iron content of breast milk. Therefore, iron supplementation is routinely recommended for these infants. However, the supplemental iron requirements of formula fed (FF) preterm infants are generally deemed to be lower due to the presence of iron in formulas. The Canadian Pediatric Society recommends no additional iron supplementation for preterm infants with a birth weight <2kg if they are primarily FF with iron-rich formula. The American Academy of Pediatrics makes no general recommendation for iron supplementation in infants fed primarily with iron-rich formula. The primary objective of this study was to investigate how feeding type influences the iron status of very preterm infants at 4-6-months corrected age (CA). A secondary objective was to further explore the risk factors associated with ID in the FF group. Methods: A retrospective population-based cohort study was conducted at IWK Health using the Perinatal Follow-Up Program database, a provincial database containing relevant clinical information for all very preterm infants (<31 weeks gestational age) born in the province of Nova Scotia, Canada. All very preterm infants born in Nova Scotia from 2005-2018 were included. Infants with severe congenital malformations, chromosomal anomalies and/or hemolytic anemias were excluded. Information about presence of ID, feeding type, iron intake from formula, and supplemental iron therapy at 4-6-month follow-up was extracted, as were neonatal variables. ID was defined as serum ferritin <20 and <12 mcg/L at 4-and 6-months CA, respectively. Variables were compared between the FF and BF groups using chi square and unpaired t-tests. The FF group was further divided into ID and non-ID groups, which were compared using similar analysis techniques. Results: A total of 392 infants were studied (gestational age: 23-30 weeks; 55.75% male). Of these, 285 were exclusively FF with iron-rich formula and 107 were exclusively or partially BF. Mean birth weight, gestational age and neonatal variables were comparable between the two groups. Mean iron intake from formula in the FF group was 1.66 mg/kg/day. An elemental iron intake of ≥ 2mg/kg/day was obtained from formula alone in only 20.4% of FF infants. FF infants were also less likely to receive additional iron supplements (Table 1). However, mean total daily iron intake (from formula and supplements) was higher in the FF group. Despite this, 36.8% of infants in FF group developed ID versus 20.6% in BF group (p=0.002). Table 2 shows key characteristics of ID and non-ID FF infants. Mean gestational age and birth weight were both lower in the ID group. The ID group also had a higher percentage of infants born <1100g (p=0.01). More babies in the ID group received at least one blood transfusion (Odds:1.1-3.0). Other neonatal variables were comparable between the two groups. ID infants had a higher daily formula intake, daily iron intake from formula and total daily iron intake combined from formula and supplements. Conclusion: Most very preterm infants fail to receive elemental iron of 2mg/kg/day from formula alone. ID is significantly more prevalent in FF infants than BF infants despite higher iron intake overall. A possible explanation for this finding could be that the bioavailability of iron from formula is lower than from breast milk. Breast milk contains lactoferrin, which aids iron absorption. Thus, iron from breast milk may be better absorbed than iron from formula. Our observations suggest the need to revisit the international recommendations for iron supplementation in FF very preterm infants. Lower gestational age, lower birth weight and need for blood transfusions were associated with ID in FF infants. Plausibly, blood transfusions may lead clinicians to withhold necessary iron supplementation for fear of iron overload in these infants, leading to unintentional ID. We suggest that optimal iron supplementation in this population should be guided by a risk adapted strategy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Seasonal variation in vitamin D status of Japanese infants starts to emerge at 2 months of age: a retrospective cohort study.

Vitamin D seasonality has been reported in adults and children, suggesting that sunlight exposure has effects on 25(OH)D production. While vitamin D deficiency among infants has received significant attention, little is known about the extent to which vitamin D status during early infancy is affected by sunlight exposure. Here, we retrospectively analysed serum 25(OH)D levels of 692 samples obtained from healthy infants aged 1-2 months born at Saitama City Hospital, Japan (latitude 35·9° North) between August 2017 and September 2021. Data regarding the frequency of outdoor activities, formula intake and BMI were also collected and analysed. Month-to-month comparisons of vitamin D levels revealed significant variation in 25(OH)D levels in breastfed infants starting at 2 months, with maximal and minimal levels in September and January, respectively. An outdoor activity score of 0 was most common at 1 month (83·9 %) and a score of 3 was most common at 2 months (81·2 %), suggesting an increased amount of sunlight exposure at 2 months. Multiple linear regression analysis revealed the amount of formula intake to be significantly associated with vitamin D status at both 1 (t = 17·96) and 2 months (t = 16·30). Our results comprise the first evidence that seasonal variation of vitamin D begins at 2 months among breastfed infants from East Asia, though dietary intake appears to be the major determinant of vitamin D status. These findings provide new insights into the influence of dietary and non-dietary factors on vitamin D status during early infancy.

Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: a randomised multicenter controlled trial

BackgroundMilk fat globule membrane (MFGM), natural to breast milk, is essential for neonatal development, but lacking from standard infant formulas.ObjectivesTo evaluate the safety and tolerability of MFGM supplementation in formula for infants 0 to 12 months.MethodsIn a prospective, multicentre, double-blind, randomized trial, healthy term infants were randomized to a standard formula (SF, n = 104) or an MFGM-enriched formula (MF, n = 108) for 6 months and a corresponding follow-on formula until 12 months. Exclusively breast-fed infants (n = 206) were recruited as the reference group (BFR). Tolerance and safety events were recorded continuously. Anthropometric measurements were assessed at enrolment, 42 days and 4, 6, 8 and 12 months.ResultsInfants (n = 375) completed the study with average dropout of < 20%. Stool frequency, color, and consistency between SF and MF were not significantly different throughout, except the incidence of loose stools in MF at 6 months being lower than for SF (odds ratio 0.216, P < 0.05) and the frequency of green-colored stools at 12 months being higher in MF (CI 95%, odds ratio 8.92, P < 0.05). The BFR had a higher frequency of golden stools and lower rate of green stools (4–6 months) than the two formula-fed groups (P < 0.05). SF displayed more diarrhoea (4.8%) than MF (1%) and BFR (1%) at the 8-month visit (P < 0.05). BFR (0–1%) had significantly less (P < 0.05) lower respiratory infections than MF (4.6–6.5%) and SF (2.9–5.8%) at 6- and 8-months, respectively. Formula intake, frequency of spit-up/vomiting or poor sleep were similar between SF and MF. Growth rate (g/day) was similar at 4, 6, 8 and 12 months between the 3 groups, but growth rate for BFR was significantly higher than for SF and MF at 42 days (95% CI, P = 0.001).ConclusionsMFGM-enriched formula was safe and well-tolerated in healthy term infants between 0 and 12 months, and total incidences of adverse events were similar to that for the SF group. A few differences in formula tolerance were observed, however these differences were not in any way related to poor growth.

Effects of a Novel High-Quality Protein Infant Formula on Energetic Efficiency and Tolerance: A Randomized Trial.

Objectives:Protein overfeeding in infants can have negative effects, such as diabetes and childhood obesity; key to reducing protein intake from formula is improving protein quality. The impact of a new infant formula [study formula (SF)] containing alpha-lactalbumin, lactoferrin, partially hydrolyzed whey, and whole milk on growth and tolerance compared to a commercial formula (CF) and a human milk reference arm was evaluated.Methods:This randomized, double-blind trial included healthy, singleton, term infants, enrollment age ≤14 days. Primary outcome was mean daily weight gain. Secondary outcomes were anthropometrics, formula intake, serum amino acids, adverse events, gastrointestinal characteristics, and general disposition.Results:Non-inferiority was demonstrated. There were no differences between the formula groups for z scores over time. Formula intake [−0.33 oz/kg/day, 95% confidence interval (CI): −0.66 to −0.01, P = 0.05] and mean protein intake (−0.13 g/kg/day, 95% CI: −0.26 to 0.00, P = 0.05) were lower in the SF infants, with higher serum essential amino acid concentrations (including tryptophan) compared to the CF infants. Energetic efficiency was 14.0% (95% CI: 8.3%, 19.7%), 13.0% (95% CI: 6.0%, 20.0%), and 18.1% (95% CI: 9.4%, 26.8%) higher for weight, length, and head circumference, respectively, in SF infants compared to the CF infants. SF infants had significantly fewer spit-ups and softer stool consistency than CF infants.Conclusions:The SF resulted in improved parent-reported gastrointestinal tolerance and more efficient growth with less daily formula and protein intake supporting that this novel formula may potentially reduce the metabolic burden of protein overfeeding associated with infant formula.