Soy Formula Research Articles

Early Postnatal Diet Differentially Affects the Fecal Microbiome and Metabolome (FS04-02-19)

ObjectivesInfants who receive breastmilk have better immune response compared to formula fed children in part due to differences in their gut microbiome and metabolome. The aim of the study is to describe microbiota and metabolome differences and associations between these factors’ in 3 and 12 month old infants who exclusively received breast milk (BM) or either soy (SF) or dairy (DF) formula until 4 months of age. MethodsSamples from 3 month old infants (BM = 10, DF = 8, SF = 9) and 12 month old infants (BM = 22, DF = 12, SF = 10) were obtained from infants fed formula or BM exclusively for 4 months. Fecal metabolomics and microbiota were assessed by LC-MS and 16s rRNA sequencing, respectively. Data analyses were conducted using standardized pipelines (QIIME 1.9, R, and Metabo-Analyst). ResultsAt 3 months of age, both the fecal microbiome and metabolites were affected by diet. The BM group had the lowest microbial diversity (Shannon index) and the SF had the highest diversity (P < 0.01) at genera taxonomic level while DF fell in the middle. There were 41 metabolites affected by diet at 3 months of age (P < 0.05, FDR < 0.05). Hippuric, succinic, lactic and uric acids were higher in the BM group and butyric and propionic acids were higher in the formula groups (P < 0.01). Correlation analyses revealed extensive associations within each diet type. For instance, we observed positive associations between succinic acid and Lactobacillus in BM group and lactic acid with Salmonella and Clostridium in SF group. Streptococcus and butyric acid in the DF, and Bifidobacterium and indole-2-carboxylic acid in the SF were negatively associated. At 12 months of age, there were no differences in microbial diversity and only fecal inosine remained significantly (P < 0.05) different among the diet groups. This metabolite was found to be negatively associated with Bifidobacterium in the breastfed group (P < 0.01). ConclusionsThere is a strong effect of diet on the fecal metabolome and microbiota at 3 months of age. Additionally, multiple associations between the two across various diets are apparent, suggesting that differences in specific gut bacteria influence the metabolite milieu. Future mechanistic studies will examine the roles of microbiota and metabolites in immune function. Funding SourcesUSDA-ARS Project 6251-51000-010-05S and NIH P20GM121293.

Soy Intake Since the Prepubertal Age May Contribute to the Pathogenesis of Endometriosis in Adulthood.

High prevalence of endometriosis was reported in Asian women as a result of their traditionally high intake of soy foods during infancy. Soy is widely used in infant feeding after weaning from breast milk or cow milk. This study thus aimed to determine to what extent soy intake before puberty may contribute to the development of endometriosis. For this purpose, immature (6-week old) female rats were fed with various soy formulas (0%, 10%, 20%, 30%, 40%, 50%, and 60%). Normal control animals were fed with a soy-free diet. At 13 weeks of age, animals (except the normal control) underwent a transplantation surgery to establish endometriosis. Estradiol valerate and oxytocin were used to induce pelvic pain. Endometrial implant levels of glutathione (GSH) and malondialdehyde (MDA) allowed estimating tissue oxidative status. Physiological ovarian function was assessed by histological analysis of ovaries. Results showed that soy-fed animals grew faster than animals receiving a soy-free diet (P < .001). In animals supplemented with more than 10% of soy, the intensity of pelvic pain increased (P < .001) as well as the volume of ectopic foci. In addition, tissue levels of MDA and GSH increased (P < .001). The ovarian function was altered and the number of luteinized unruptured follicles increased. In conclusion, although animals supplemented with soy at the prepubertal stage displayed a good growth performance, regular soy consumption may promote the development and progress of endometriosis in adulthood, especially when soy content in food is more than 10%.

Predictive models for the growth of Cronobacter sakazakii in reconstituted powdered infant formula

Cronobacter sakazakii has been implicated in foodborne illnesses in neonates and infants resulting from the consumption of contaminated infant formula. The objective of this research was to develop predictive models for the growth of C. sakazakii in infant milk formula (IMF) and infant soy formula (ISF). Growth kinetics for a five strain cocktail of C. sakazakii were obtained at several isothermal conditions at 8.5, 10, 15, 20, 25, 28, 32, 35, 37, 40, 42, 45, and 47 °C in reconstituted IMF and ISF. Initial protocol resulted in clumping of colonies leading to difficultly in enumerating C. sakazakii. Protocol was then modified by addition of Tween-80 and stomaching the samples, which resulted in breaking up of colonies effectively.The growth data were fitted to three primary models (Baranyi, Gompertz, and Logistic) to describe the growth of C. sakazakii at each isothermal condition. For IMF, the psuedo-R2 and the root mean square error (RMSE) ranged from 0.96-0.99 and 0.07-0.34 log CFU/mL, respectively. For ISF, the psuedo-R2 and the RMSE ranged from 0.98-0.99 and 0.08-0.27 log CFU/mL, respectively.Two different secondary models were used to describe the effect of temperature on growth rate of C. sakazakii for each product. For the modified Ratkowsky’s equation, psuedo-R2 and the RMSE values were 0.99 and 0.004- 0.0169 (log CFU/mL)/h, respectively. For the Gamma model, psuedo-R2 and the RMSE values were 0.99 and 0.004-0.006 (logCFU/mL)/h, respectively. C. sakazakii grew faster in IMF, when compared to ISF.Primary and secondary models were integrated and solved numerically to determine the growth of C. sakazakii at varying temperature profiles. Six dynamic models were validated with one sinusoidal and three ‘real-life’ temperature profiles. The dynamic models from Baranyi (RMSE ranging from 0.12-0.39 log CFU/mL) and logistic models (RMSE ranging from 0.25-0.79 log CFU/mL) predicted C. sakazakii growth better, compared to the Gompertz dynamic models (RMSE ranging from 0.46-0.67 log CFU/mL). These predictive models can help improve microbial risk assessment and develop appropriate risk management strategies.

Randomized controlled trial on the influence of dietary intervention on epigenetic mechanisms in children with cow\u2019s milk allergy: the EPICMA study

Epigenetic mechanisms could drive the disease course of cow’s milk allergy (CMA) and formula choice could modulate these pathways. We compared the effect of two different dietary approaches on epigenetic mechanisms in CMA children. Randomized controlled trial on IgE-mediated CMA children receiving a 12-month treatment with extensively hydrolyzed casein formula containing the probiotic L.rhamnosus GG (EHCF + LGG) or with soy formula (SF). At the baseline, after 6 and 12 months of treatment FoxP3 methylation rate and its expression in CD4+ T cells were assessed. At same study points IL-4, IL-5, IL-10, and IFN-γ methylation rate, expression and serum concentration, miRNAs expression were also investigated. 20 children (10/group) were evaluated. Baseline demographic, clinical and epigenetic features were similar in the two study groups. At 6 and 12 months, EHCF + LGG group showed a significant increase in FoxP3 demethylation rate compared to SF group. At the same study points, EHCF + LGG group presented a higher increase in IL-4 and IL-5 and a higher reduction in IL-10 and IFN-γ DNA methylation rate compared to SF group. A different modulation of miR-155, -146a, -128 and -193a expression was observed in EHCF + LGG vs. SF. Dietary intervention could exert a different epigenetic modulation on the immune system in CMA children.

Correlation Between Soy Milk Formula Consumption with Plasma Estradiol Level and Growth of Children in Denpasar

Soy milk formula is a formula which contains soybean as a substitute for cow's milk protein. Consumption of soy formula has caused widespread concern especially related to the effect of isoflavones. We aimed to determine the correlation of plasma estradiol level and to compare physical growth in children who consumed soy milk formula with children who consumed cow's milk formula. This was a case-control study of children aged six months to two years old who were treated at pediatric outpatient clinic in Sanglah Hospital and private pediatric outpatient clinic in Denpasar from April to July 2015. Subjects were divided into children who consumed soy milk formula and children who consumed cow’s milk formula. Data regarding physical examination, anthropometric measurements, diet types and estradiol level were obtained. Total 28 subjects enrolled. We found significant difference in estradiol level between the two groups (OR: 0.33; p = 0.001; 95% CI = 0.17 - 0.64). We found no significant difference in sexual development between those two groups (OR: 1.25; p = 0.12; 95% CI = 0.92 - 1.71). Furthermore we found no significantly different in physical growth of subjects who consumed soy milk formula compared to cow's milk formula (p>0.05). Soy milk formula consumption did not associated with significant difference of sexual development and growth in children consuming soy milk compared to cow’s milk. However, it related to increament of estradiol level.

Concentrations of Purine Metabolites Are Elevated in Fluids from Adults and Infants and in Livers from Mice Fed Diets Depleted of Bovine Milk Exosomes and their RNA Cargos

Humans and mice absorb bovine milk exosomes and their RNA cargos. The objectives of this study were to determine whether milk exosome- and RNA-depleted (ERD) and exosome- and RNA-sufficient (ERS) diets alter the concentrations of purine metabolites in mouse livers, and to determine whether diets depleted of bovine milk alter the plasma concentration and urine excretion of purine metabolites in adults and infants, respectively. C57BL/6 mice were fed ERD (providing 2% of the microRNA cargos compared with ERS) and ERS diets starting at age 3 wk; livers were collected at age 7 wk. Plasma and 24-h urine samples were collected from healthy adults who consumed (DCs) or avoided (DAs) dairy products. Spot urine samples were collected from healthy infants fed human milk (HM), milk formula (MF), or soy formula (SF) at age 3 mo. Purine metabolites were analyzed in liver, plasma, and urine; mRNAs and microRNAs were analyzed in the livers of female mice. We found that 9 hepatic purine metabolites in ERD-fed mice were 1.76±0.43 times the concentrations in ERS-fed mice (P<0.05). Plasma concentrations and urine excretion of purine metabolites in DAs was ≤1.62±0.45 times the concentrations in DCs (P<0.05). The excretion of 13 purine metabolites in urine from SF infants was ≤175±39 times the excretion in HM and MF infants (P<0.05). mRNA expression of 5'-nucleotidase, cytosolic IIIB, and adenosine deaminase in mice fed ERD was 0.64±0.52 and 0.60±0.28 times the expression in mice fed ERS, respectively. Diets depleted of bovine-milk exosomes and RNA cargos caused increases in hepatic purine metabolites in mice, and in plasma and urine from human adults and infants, compared with exosome-sufficient controls. These findings are important, because purines play a role in intermediary metabolism and cell signaling.

Products of Early and Advanced Glycation in the Soy Milk Proteome.

Thermal processing of soy milk kills pathogens and denatures anti-nutrition factors warranting microbiological safety, better digestibility, and longer storage. Additionally, Maillard reactions are triggered, yielding glycated proteins (Amadori/Heyns products) and a heterogeneous group of advanced glycation end-products (AGEs). These modifications alter the nutritional value, antigenicity, and digestibility of proteins. They also raise concerns about potentially toxic effects. This study aims at characterizing these modifications in proteins from different soy milk products. Here, glycation and AGE-modification sites in the proteome of ultrahigh-temperature-treated natural soy milk, soy milk sweetened with hexose (fructose)-containing sweeteners (SSM), and sucrose as well as soy-based infant formulas (SIFs) from different manufacturers are reported for the first time. A bottom-up proteomic approach based on nano reversed-phase high-perfomance liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoRP-HPLC-ESI-MS/MS) (collision-induced dissociation (CID) and electron transfer dissociation modes) identified 229 glycated peptides and 128 AGE-modified peptides resembling 53 proteins. The glycation sites are mainly derived from hexoses, whereas Nδ -carboxyethylarginine and methylglyoxal-derived hydroimidazolone are the main AGEs in soy milk. The qualitative and quantitative data obtained here indicate that early glycation increases with harsher processing conditions (SIFs) and the addition of hexose-containing sweeteners (SSMs), whereas the latter sweeteners (but not the harsher processing) triggered more AGE modifications.

Soy-Based Infant Formula: Are Phyto-Oestrogens Still in Doubt?

Although Scientific Societies have stated that there are very few indications for the use of soy-based formula (SF) in infant nutrition, their utilization rates have been repeatedly found to be higher than expected. It is likely that a significant role in this regard is played by the belief that the use of SF during infancy can reduce the risk of the development of several diseases later in life. Although no definitive data that can substantiate these claims have been collected, many people perceive soy consumption to confer significant health benefits and might also use soy for infant nutrition. However, not all the problems regarding safety of SF in infants have been definitively solved. Among risks, the potentially toxic role of the phyto-oestrogens contained in SF is not definitively established. In vitro and animal studies have raised suspicions that SF could have potentially negative effects on sexual development and reproductive function, neurobehavioral development, immune function, and thyroid function. Several studies in humans have aimed to assess whether the results of animal studies can be applied to humans and whether SF can be used in infants following the official recommendations. The results are somewhat conflicting. The aim of this narrative review is to discuss what is presently known regarding the impact of phyto-oestrogens in SF on early and late child development. PubMed was used to search for the studies published from January 1980 to June 2017 using the keywords: “soy,” “soy formula,” “child,” “phytoestrogens.” Analysis of the literature showed that a global evaluation of the impact of modern SFs on human development seems to suggest that their use is not associated with relevant abnormalities. Only children with congenital hypothyroidism need adequate monitoring of thyroid function.

Resting gamma power during the postnatal critical period for GABAergic system development is modulated by infant diet and sex.

Gamma band activity (30-50 Hz) plays an essential role in brain development and function, but neither the early postnatal development nor subject and environmental factors influencing this development have been reported. We documented the development of resting gamma power using high density EEG recordings obtained each month from postnatal month 2 to 6 in 518 healthy infants who were breast-fed (170; 85 boys), fed milk formula (186; 97 boys), or fed soy formula (162; 90 boys). Gamma power was determined for 44 sites distributed over major brain regions and analyses were adjusted for background variables relevant to neurodevelopment. The results show gamma power follows a gradually increasing function across this time period that varies in topographic magnitude and is differentially influenced by subject and environmental variables-among which gestation, head circumference, and infant diet-sex interactions figure most prominently. Relationships between gamma power and standardized measures of infant behavioral development appear to be emerging but are in flux during this time. Since this postnatal period is considered critical in the development of the GABAergic system underlying the generation of gamma activity, the observed findings may reflect organizational changes that will influence the future development of gamma-related behavioral and neurocognitive functions.

Soy-based infant formula feeding and menstrual pain in a cohort of women aged 23-35 years.

Is soy formula feeding during infancy associated with menstrual pain in reproductive-age women? Our data suggest that soy formula feeding during infancy is associated with several indicators of severe menstrual pain in reproductive-age women. A prior study observed greater severity of menstrual pain in young women who as infants participated in feeding studies and were assigned to soy-based formula feeding. We used data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1696 African-American women ages 23-35 years at enrollment. Data on infant soy formula feeding was ascertained by self-administered questionnaire for 1553 participants, with 89% of participants receiving assistance from their mothers. Information on menstrual pain indicators was collected by web- and telephone-interview. We estimated the relative risk (RR) and 95% confidence interval (CI) using log-binomial regression, or log-multinomial regression, adjusting for participant age and maternal education. Women ever fed soy formula as infants were more likely than unexposed women to report ever use of hormonal contraception for menstrual pain (RR 1.4, CI: 1.1-1.9) and moderate/severe menstrual discomfort/pain with 'most periods', but not 'every period', during early adulthood (ages 18-22 when not using hormonal contraception) (RR 1.5, CI: 1.1-2.0). We relied on retrospective recall to ascertain infant exposure to soy formula feeding and data on menstrual pain indicators. Our observations add to the growing body of literature from animal and human studies on the reproductive health consequences of early-life exposure to soy formula. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and, in part, by funds allocated for health research by the American Recovery and Reinvestment Act. This research was also supported by grant K99NR017191 (KU). None of the authors has a conflict of interest. Not applicable.

A FORMULA-FED INFANT WITH PROFOUND DEHYDRATION, SINUS VENOUS THROMBOSIS, AND INTRACRANIAL HEMORRHAGE

Introduction Chronic food protein-induced enterocolitis syndrome (FPIES) is a non-IgE gastrointestinal food allergy, typically manifesting in infancy with intermittent emesis and diarrhea, which may progress to dehydration and hypovolemic shock. Here we describe a case of chronic FPIES with previously unreported complications, including sinus venous thrombosis and intracranial hemorrhage. Case Description This female infant, the product a full term, healthy pregnancy, was initially thriving on soy formula until the 3 rd week of life when she developed progressively worsening diarrhea, emesis, and lethargy. By day of life 20, she was noted to have severe dehydration with 22% weight loss from birth. Laboratory abnormalities included anion gap metabolic acidosis, elevated lactate, hyperammonemia, hypoalbuminemia, neutrophilia with bandemia, hypereosinophilia, and thrombocytosis. Full sepsis work-up was negative as was testing for inborn errors of metabolism. Clinical course was complicated by seizures, respiratory failure, intracranial hemorrhage, and sinus venous thrombosis. Upon withdrawal of soy-based formula, laboratory abnormalities gradually improved. Resumption of feeds with extensively hydrolyzed cow's milk formula resulted in intermittent emesis. Concerned for chronic FPIES, the patient transitioned to amino acid-based formula with improvement in gastrointestinal symptoms. Discussion Here we present the first reported case of chronic FPIES complicated by sinus venous thrombosis and intracranial hemorrhage. Her diagnosis of chronic FPIES is presumptive without confirmatory food challenge; this has yet to be performed due to severity of initial presentation and patient's current young age of 2 months. This case highlights the potential severity of presentation, which may represent a barrier to timely diagnosis.

Infant diet and maternal gestational weight gain predict early metabolic maturation of gut microbiomes.

Commensal gut bacterial communities (microbiomes) are predicted to influence human health and disease1,2. Neonatal gut microbiomes are colonized with maternal and environmental flora and mature toward a stable composition over 2-3 years3,4. To study pre- and postnatal determinants of infant microbiome development, we analyzed 402 fecal metagenomes from 60 infants aged 0-8 months, using longitudinal generalized linear mixed models (GLMMs). Distinct microbiome signatures correlated with breastfeeding, formula ingredients, and maternal gestational weight gain (GWG). Amino acid synthesis pathway accretion in breastfed microbiomes complemented normative breastmilk composition. Prebiotic oligosaccharides, designed to promote breastfed-like microflora5, predicted functional pathways distinct from breastfed infant microbiomes. Soy formula in six infants was positively associated with Lachnospiraceae and pathways suggesting a short-chain fatty acid (SCFA)-rich environment, including glycerol to 1-butanol fermentation, which is potentially dysbiotic. GWG correlated with altered carbohydrate degradation and enriched vitamin synthesis pathways. Maternal and postnatal antibiotics predicted microbiome alterations, while delivery route had no persistent effects. Domestic water source correlates suggest water may be an underappreciated determinant of microbiome acquisition. Clinically important microbial pathways with statistically significant dietary correlates included dysbiotic markers6,7, core enterotype features8, and synthesis pathways for enteroprotective9 and immunomodulatory10,11 metabolites, epigenetic mediators1, and developmentally critical vitamins12, warranting further investigation.

Neonatal genistein exposure disrupts ovarian and uterine development in the mouse by inhibiting cellular proliferation.

Soy-based formula contains high concentrations of the isoflavone genistein. Genistein possesses estrogenic and tyrosine kinase inhibitory activity and interferes with cellular proliferation and development. To date, the acute and chronic effects of genistein on ovarian and uterine development have not been fully elucidated. In this study, mice at postnatal day 1 were subcutaneously injected with 100 mg/kg genistein for 10 consecutive days, and then their ovaries and uteri were collected on days 10, 21, and 90. Histological evaluation was performed after hematoxylin and eosin staining. The proliferating activity was indicated by the proliferating indicator protein Ki67. Results showed that the subcutaneous injection of genistein to neonatal mice induced the formation of multi-oocyte follicles and delayed the primordial follicle assembly in the ovaries. Genistein significantly enlarged the cross-sectional area of the uterine cavity and wall and disrupted the regularity between the uterine stroma and myometrium. Genistein exposure inhibited proliferative activity because fewer Ki67-positive nuclei were detected in ovarian and uterine cell populations than in the control. Furthermore, most ovaries from adult mice given neonatal genistein were without corpora lutea, and there appeared to be cystic follicles and hypertrophy of the theca, and cortical and medullary layers. Considering the high concentration of isoflavone in soy-based infant formulas and livestock feed, we suggest that the use of isoflavone-rich diets in humans and livestock receive closer examination.

Infant Formula Feeding Increases Hepatic Cholesterol 7α Hydroxylase (CYP7A1) Expression and Fecal Bile Acid Loss in Neonatal Piglets

During the postnatal feeding period, formula-fed infants have higher cholesterol synthesis rates and lower circulating cholesterol concentrations than their breastfed counterparts. Although this disparity has been attributed to the uniformly low dietary cholesterol content of typical infant formulas, little is known of the underlying mechanisms associated with this altered cholesterol metabolism phenotype. We aimed to determine the molecular etiology of diet-associated changes in early-life cholesterol metabolism with the use of a postnatal piglet feeding model. Two-day-old male and female White-Dutch Landrace piglets were fed either sow milk (Sow group) or dairy-based (Milk group; Similac Advance powder) or soy-based (Soy group; Emfamil Prosobee Lipil powder) infant formulas until day 21. In addition to measuring serum cholesterol concentrations, hepatic and intestinal genes involved in enterohepatic circulation of cholesterol and bile acids were analyzed by real-time reverse-transcriptase polymerase chain reaction and Western blot. Bile acid concentrations were measured by liquid chromatography-mass spectrometry in serum, liver, and feces. Compared with the Sow group, hepatic cholesterol 7α hydroxylase (CYP7A1) protein expression was 3-fold higher in the Milk group (P < 0.05) and expression was 10-fold higher in the Soy group compared with the Milk group (P < 0.05). Likewise, fecal bile acid concentrations were 3-fold higher in the Soy group compared with the Milk group (P<0.05). Intestinal mRNA expression of fibroblast factor 19 (Fgf19) was reduced in the Milk and Soy groups, corresponding to 54% and 67% decreases compared with the Sow group. In the Soy group, small heterodimer protein (SHP) protein expression was 30% lower compared with the Sow group (P<0.05). These results indicate that formula feeding leads to increased CYP7A1 protein expression and fecal bile acid loss in neonatal piglets, and this outcome is linked to reduced efficacy in inhibiting CYP7A1 expression through FGF19 and SHP transcriptional repression mechanisms.

EB 2017 Article: Soy protein isolate feeding does not result in reproductive toxicity in the pre-pubertal rat testis.

The isoflavone phytoestrogens found in the soy protein isolate used in soy infant formulas have been shown to have estrogenic actions in the developing male reproductive tract resulting in reproductive toxicity. However, few studies have examined potential estrogenicity of soy protein isolate as opposed to that of pure isoflavones. In this study, we fed weanling male Sprague-Dawley rats a semi-purified diet with casein or soy protein isolate as the sole protein source from postnatal day 21 to 33. Additional groups were fed casein or soy protein isolate and treated s.c. with 10 µg/kg/d estradiol via osmotic minipump. Estradiol treatment reduced testis, prostate weights, and serum androgen concentrations ( P < 0.05). Soy protein isolate had no effect. Estradiol up-regulated 489 and down-regulated 1237 testicular genes >1.5-fold ( P < 0.05). In contrast, soy protein isolate only significantly up-regulated expression of 162 genes and down-regulated 16 genes. The top 30 soy protein isolate-up-regulated genes shared 93% concordance with estradiol up-regulated genes. There was little overlap between soy protein isolate down-regulated genes and those down-regulated by estradiol treatment. Functional annotation analysis revealed significant differences in testicular biological processes affected by estradiol or soy protein isolate. Estradiol had major actions on genes involved in reproductive processes including down-regulation of testicular steroid synthesis and expression of steroid receptor activated receptor (Star) and cytochrome P450 17α-hydroxylase/(Cyp17a1). In contrast, soy protein isolate primarily affected pathways associated with macromolecule modifications including ubiquitination and histone methylation. Our results indicate that rather than acting as a weak estrogen in the developing testis, soy protein isolate appears to act as a selective estrogen receptor modulator with little effect on reproductive processes. Impact statement Soy protein isolate (SPI) is the sole protein used to make soy-based infant formulas. SPI contains phytoestrogens, which are structurally similar to estradiol. These phytoestrogens, daidzein, genistein, and equol, fit the definition of endocrine-disrupting compounds, and at high concentrations, have estrogenic actions resulting in reproductive toxicity in the developing male, when provided as isolated chemicals. However, few animal studies have examined the potential estrogenicity of SPI as opposed to pure isoflavones. In this study, SPI feeding did not elicit an estrogenic response in the testis nor any adverse outcomes including reduced testicular growth, or androgen production during early development in rats when compared to those receiving estradiol. These findings are consistent with emerging data showing no differences in reproductive development in males and female children that received breast milk, cow's milk formula, or soy infant formula during the postnatal feeding period.

Milk feeding and first complementary foods during the first year of life in the TEDDY study.

The aim was to describe milk feeding patterns and first weaning foods during the first year of life in a large prospective birth cohort of infants with increased genetic risk for Type 1 diabetes (T1D) recruited in 4 different countries: the United States, Finland, Germany, and Sweden. All enrolled children with dietary information (n=8,673) were included in the analyses; 1,307 (15%) children who dropped out before the first birthday were excluded from some analyses. Supplementary milk feeding in the first 3days of life was common in all the four countries, although the type of the supplementary milk differed by country and by maternal T1D. Donated human milk was commonly used only in Finland. In all the countries, the most common first supplementary food was cow's milk-based infant formula, especially among offspring of mothers with T1D. The use of specific types of infant formulas differed notably by country: Extensively hydrolysed formulas were most used in Finland, partially hydrolysed ones in the United States and in Germany, and soy formulas only in the United States. Infant formulas commonly included probiotics, prebiotics, and starches. During the first year of life, most of the infants received conventional cow's milk. Overall, milk feeding during the first 3days of life and thereafter until the first birthday differed markedly by maternal T1D status and across countries. These descriptive data may be useful in understanding early infant feeding practices and in planning potential interventions, which affect infant feeding.

Consumption of soy-based infant formula is not associated with early onset of puberty.

The use of soy products is common in young children with cow milk allergy (CMA). The aim was to examine prospectively the association between infantile consumption of soy-based formula, growth parameters and early pubertal signs, in comparison to cow milk-based formula. A nested case-control study was conducted, selected from a cohort of infants prospectively followed from birth until the age of 3years for eating habits and the development of IgE-mediated CMA. Infants who consumed only soy-based formula were included in the soy group. The control group was randomly selected from those without IgE-CMA and not receiving soy formula. Study participants were reevaluated between ages 7.8 and 10.5years by an interview, nutritional intake by 3days diaries, and height, weight, and pubertal signs by physical examination. The soy-fed group included 29 participants (17 males), median age 8.92years IQR (8.21, 9.42). The control group included 60 participants (27 males), median age 8.99years IQR (8.35, 9.42). The groups had comparable height and BMI z scores (- 0.17 ± 1.08 versus - 0.16 ± 1.01, p = 0.96, and 0.67 ± 1.01 versus 0.53 ± 1.02, p = 0.56, for soy and control groups, respectively). Four (three males and one female) from the soy-group (13.8%) and eight females from the control-group (13.3%) had early pubertal signs (p = 0.95). No association was detected between puberty and infantile nutrition, after controlling for BMI and family data. No association with puberty or differences between groups were found in current daily consumption of soy, micronutrients, energy, carbohydrates, fat, and protein. This is the first prospective, physical examination-based study, demonstrating no association between infantile soy-based formula consumption and growth and puberty parameters.

A Longitudinal Study of Estrogen-Responsive Tissues and Hormone Concentrations in Infants Fed Soy Formula.

Chemicals with hormonelike activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Estrogen-responsive postnatal development was compared in infants exclusively fed soy formula, cow-milk formula, and breast milk. We enrolled 410 infants born in Philadelphia-area hospitals between 2010 and 2014; 283 were exclusively fed soy formula (n = 102), cow-milk formula (n = 111), or breast milk (n = 70) throughout the study (birth to 28 or 36 weeks for boys and girls, respectively). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, and serum estradiol and follicle-stimulating hormone levels. We estimated MI, organ-growth, and hormone trajectories by diet using mixed-effects regression splines. Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal-cell MI trended higher (P = 0.01) and uterine volume decreased more slowly (P = 0.01) in soy-fed girls compared with cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk vs soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal-cell MI, uterine volume, and girls' estradiol and boys' breast-bud diameter trajectories. Relative to girls fed cow-milk formula, those fed soy formula demonstrated tissue- and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Studies are needed to further evaluate the effects of soy on child development.

Occurrence of glyphosate and AMPA residues in soy-based infant formula sold in Brazil

ABSTRACTGlyphosate is an herbicide widely used in the world, being applied in several crops, among them soybeans. Recently, glyphosate and its metabolite aminomethylphosphonic acid (AMPA) have been identified as possible contributors to the emergence of various diseases such as autism, Parkinson’s and Alzheimer’s diseases, as well as cancer. The child population-consuming cereal-based foods is the most exposed to the effects of pesticides because of their developmental phase and they have a higher food intake per kilogram of body weight than adults. The presence of glyphosate and AMPA residues in soy-based infant formulas was evaluated during the years 2012–2017, totalising 105 analyses carried out on 10 commercial brands from different batches. Glyphosate and AMPA were determined by liquid chromatography with fluorescence detection after derivatisation reaction. The method was validated and showed accuracy and precision with a limit of quantification (LOQ) of 0.02 mg kg−1. Among those samples that contained levels above the LOQ, the variation of glyphosate residues was from 0.03 mg kg−1 to 1.08 mg kg−1 and for AMPA residues was from 0.02 mg kg−1 to 0.17 mg kg−1. This is the first scientific communication about glyphosate and AMPA contamination in soy-based infant formula in Brazil, The study was conducted under good laboratory practice (GLP) and supported by good scientific practice.

Latest Insights on Food Protein-Induced Enterocolitis Syndrome: An Emerging Medical Condition.

Food protein-induced enterocolitis syndrome (FPIES) is a type of non-IgE-mediated gastrointestinal food hypersensitivity characterized by profuse vomiting that is frequently associated with pallor or/and lethargy and appears within 1 to 3 hours after ingestion of the offending food. A less frequent chronic form of FPIES is characterized by protracted vomiting, diarrhea, or both accompanied by poor growth. Although FPIES is considered a rare allergic disorder, increasing reports in recent years point to a real increase in incidence, or at least an increased awareness of this condition by pediatricians. The foods most frequently implicated are cow's milk, soy formula, grains, and fish, depending on the geographic area. Diagnosis is based on clinical manifestations and requires a high index of suspicion, since we still lack a diagnostic laboratory tool. Early recognition of FPIES and removal of the offending food are mandatory. International consensus guidelines on diagnosis and management have been published. Prognosis is usually good, with most children tolerating foods before 6 years of age.