Soy-based Formula Research Articles

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.

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.

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.

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.

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.

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.

Types of Special Infant Formulas Marketed in Korea and Their Indications.

Infant formula is classified into standard cow's milk-based and special formulas. This review aimed at summarizing the types of special milk formulas currently sold in Korea, and the appropriate indications for the use of these formulas; lactose free formula, soy-based formula, protein hydrolysate formula, amino acid-based formula, preterm formula, medium chain triglyceride formula, low-phosphorus formula, protein-energy-enriched formula, and formulas for inborn errors of metabolism.

The contribution of minor folates to the total vitamin B9 content of Infant formula and clinical nutrition products

In the present study an optimization of trienzyme treatment combining α-amylase, protease and γ-carboxy peptidase allowing complete sample preparation within a working day for the analysis of vitamin B9 (folate) in infant formula and adult/pediatric nutritional products is presented. The optimized sample preparation was applied to a set of samples representing most of the products in the marketplace. Results on Standard Reference Material 1849a were well in agreement with certified values. The main contributor to total folate was folic acid, 5-methyl-tetrahydrofolate was the only minor contributor in milk-based products. Soy-based formulas contained polyglutamates of 5-formyl-tetrahydrofolate. The relative contribution of polyglutamates to the total folate content remained low in the types of product included in this study. The results suggest that a simple di-enzyme treatment could be enough for these products, nevertheless, this should be carefully evaluated prior to making a decision on the use of tri- or di-enzyme treatment.

Soy-Based Infant Formulas: A Review of Developmental and Nutritional Considerations

Soy-Based Infant Formulas: A Review of Developmental and Nutritional Considerations

EFFECT OF DIFFERENT TYPES OF MILK FORMULA AGAINST STREPTOCOCCUS MUTANS BIOFILM FORMATION IN VITRO

Objectives: The purpose of this study was to analyze the differences in the effect of milk-based, soy-based, and protein hydrolysate formulas against Streptococcus mutans (SM) biofilm formation.Methods: Infant formula used is intended for children aged 1-3 years, and each respective type of infant formula is represented by three distinct brands.Results: Our results showed a significant difference in the effect of milk-based, soy-based, and protein hydrolysate formulas against SM biofilm formation (p=0.002).Conclusion: Cow’s milk-based formula showed the lowest SM biofilm formation.

Management of Food Protein-Induced Enterocolitis Syndrome (FPIES): Current Approach and Future Needs

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE, cell-mediated food allergic gastrointestinal disorder triggered by ingestion of food proteins (cow milk, soy, rice, oat, egg, and others). The acute FPIES begins approximately 1–4 h after food ingestion with profuse, repetitive emesis that is accompanied by lethargy and pallor and may be followed later by diarrhea; 15% will require hospitalization because of hypotension and hemodynamic instability due to severe dehydration. A chronic FPIES is less frequent and develops from few days to 4 weeks after the offending food has been introduced and fed daily. Chronic FPIES presents with intermittent emesis, bloody diarrhea, dehydration, weight loss, and failure to thrive and has been only reported in young infants fed with cow’s milk and soy-based formulas. Acute FPIES to seafood has been reported in older children and in adults. The majority of patients react to a single food; however, FPIES can be triggered by more than one food, especially between cow milk/soy and rice/oats. Diagnosis of FPIES is based on the recognition of clinical manifestations, exclusion of alternative etiologies, and a physician-supervised oral food challenge (OFC). OFC is the gold standard; however, most patients do not need to undergo confirmatory OFC, especially if they have a history of severe reactions and become asymptomatic following elimination of the suspected food from diet until tolerance through OCF is proven. Management of FPIES is based on elimination of the trigger food in the diet, medical treatment of acute reactions due accidental exposure (intravenous hydration, methylprednisolone, ondansetron), nutritional counseling regarding avoidance of trigger foods, and introduction of the complementary foods and periodic oral food challenges to evaluate for resolution. The first international consensus guidelines on diagnosis and management of FPIES published in 2017 provide practical support for the providers caring for patients with FPIES.

Simultaneous Determination of Soyasaponins and Isoflavones in Soy (Glycine max L.) Products by HPTLC-densitometry-Multiple Detection.

A new high-throughput method was developed for the simultaneous analysis of isoflavones and soyasaponnins in Soy (Glycine max L.) products by high-performance thin-layer chromatography with densitometry and multiple detection. Silica gel was used as the stationary phase and ethyl acetate:methanol:water:acetic acid (100:20:16:1, v/v/v/v) as the mobile phase. After chromatographic development, multi-wavelength scanning was carried out by: (i) UV-absorbance measurement at 265 nm for genistin, daidzin and glycitin, (ii) Vis-absorbance measurement at 650 nm for Soyasaponins I and III, after post-chromatographic derivatization with anisaldehyde/sulfuric acid reagent. Validation of the developed method was found to meet the acceptance criteria delineated by ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. Calibrations were linear with correlation coefficients of >0.994. Intra-day precisions relative standard deviation (RSD)% of all substances in matrix were determined to be between 0.7 and 0.9%, while inter-day precisions (RSD%) ranged between 1.2 and 1.8%. The validated method was successfully applied for determination of the studied analytes in soy-based infant formula and soybean products. The new method compares favorably to other reported methods in being as accurate and precise and in the same time more feasible and cost-effective.

The Effect of Prenatal and Postnatal Administration of Manganese Chloride on the Developing Caudate Nucleus of the Corpus Striatum in Male Albino Rats and the Possible Beneficial Role of Vitamin E Supplementation: A Histological and Immunohistochemical study

Background: Although low levels of manganese (Mn) intake are necessary for human health but may also be toxic at high concentrations. Infants are subjected to risk of elevated Mn exposure from soy-based infant formulas and contaminated well-water which contain Mn at high levels. Young children are susceptible to be exposed to an elevated Mn levels because the developing brain is vulnerable to the chemical insult, as well as an increased absorption and retention of ingested Mn in comparison to the adults. Vitamin E is an antioxidant and is protectective to the biological membranes from oxidative stress.Aim of work: To investigate the effect of adminstration of manganese chloride (MnCL2) during pregnancy and lactation on the postnatal development of the caudate nucleus of the rat corpus striatum and to evaluate the role of vitamin E. Also, this work aimed to detect the effect of MnCL2 withdrawal..Material and Methods: Forty-pregnant female albino rats were divided into two equal groups (20 rats each): group I (control) and group II (MnCl2-treated). Litters of the control dams were sacrificed at the age of one day (group Ia), 10 days (group Ib), 20 days (group Ic) and 2 months (group Id). MnCl2-treated dams received MnCl2 at a dose of 50 mg /kg b.w. orally daily throughout conception till 20th day postnatally. Half of their male litters were sacrificed at the age of one day (group IIa), 10 days (group IIb) and 20 days (group IIc). The other half was sudivided at the age of 20 days into 3 equal groups: group IId received the same dose of MnCl2 till the age of 2 months, group IIe received vitamin E at a dose of 48 mg/kg b.w. orally daily till the age of 2 months concomitantly with MnCl2 and group IIf received distilled water orally daily till the age of 2 months. Animals in the previous three groups were sacrificed at the age of 2 months. Brains were processed to be studied using Einarson’s gallocyanin stain, H&E, transmission electron microscopy and immunohistochemical study for glial fibrillary acidic protein (GFAP).Results: As regard the postnatal development of the caudate nucleus, there was a gradual increase in the amount of Nissl's granules and the size of the neuronal nuclei with the presence of an apparent decrease in neuronal density. A gradual increase in the density of GFAP positive cells was noticed. Maternal MnCl2 administration affected the development of the caudate of the offsprings at the different ages studied. Many cells revealed degenerative changes in the form of darkly stained pyknotic or irregular rarified nuclei and vacuolated cytoplasm. There was progressive reduction in the amount of Nissl's granules. More abundant GFAP positive cells were noticed comparable to those in the control ages. On electron microscopic study, there were dark degenerated cells and deformed myelin sheath with splitting and fragmentation of their lamellae. Swollen mitochondria with disrupted cristae were noticed in the cytoplasm of many cells. These histological and immunohistochemical changes were found to be corrected with the administration of vitamin E and the cells had nearly normal appearance. These changes revealed no improvement on withdrawal of MnCl2 and it is nearly like that under usage.Conclusion: Gestational and lactational administration of MnCl2 had harmful effects on the structure of the caudate nucleus of the offsprings at different ages. Vitamin E can be used for prevention and treatment of these effects as an adjuvant therapy.

A Review of Association betweenEarly Exposure to Infant-feeding formulas and Type 1 Diabetes among Children

The increasing incidenceof type 1 diabetes among children calls for a thorough understanding of the disease to stem its growth. Early exposure to infant-feeding formulas has been linked with the disease and several mechanisms of action have been proposed. However, it is unclear the exact mechanism by which infant-formulas aid in the pathogenesis of type 1 diabetes. This paper reviewed and articulated several hypotheses proposed as the mechanisms of action of infant formulas in the onset of type 1 diabetes. The Google search engine was used to search for relevant information on the internet from reputable sources such as PubMed, Google Scholar, among others.The majority of the studies reviewed overwhelmingly agreed early exposure to infant-feeding formulas may contribute to the pathogenesis of type 1 diabetes among children. Cow milk, for example, contains bovine insulin, which differs from human insulin with 3 amino acids, and can cause immune reactions in children. Gluten-containing diets such as wheat may cause proportional changes in immune cell populations or modify the cytokine/chemokine pattern towards an inflammatory profile. Concentrated soy-based formulas contain active estrogenic endocrine disruptors. Fruits, berries and roots may be infected with toxic antibiotics, which can start off autoimmunity. Nursing moms are therefore advised to breastfeedtheir babies for a long time before introducing infant-feeding formulas, especially those with a family with a history of diabetes.

Pediatric intestinal failure-associated liver disease.

The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients. Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined. IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.

Male testicular development is affected by estrogens but not altered in neonatal piglets receiving soy infant formula

Soy infant formula contains many phytochemicals, including phytoestrogens, which are structurally similar to estradiol (E2). As a result of their potentially estrogenic properties, soy infant formulas have been the subject of concern with regards to reproductive toxicity. To address these concerns regarding male reproductive development, we fed male piglets a soy‐based infant formula, a dairy milk‐based infant formula, milk formula supplemented with E2, or milk formula supplemented with putative estrogenic soy phytonutrient genistein (GEN), in comparison with piglets receiving sow's breast milk from postnatal day 2–21. In the E2 supplemented group, serum testosterone and testicular weight were significantly reduced compared to the milk formula‐fed and sow's milk controls. Testis tubule area, Sertoli cell and germ cell numbers were also increased in the E2 supplemented group compared to milk formula controls, P&lt;0.05. When compared to the sow's milk control, RNAseq analysis in testes showed that E2 supplemented milk formula altered expression of 2012 testicular genes (±1.5 fold, P&lt;0.100). Functional annotation analysis indicated up‐regulation of several pathways in the E2 supplemented group, including canonical Wnt signaling, cell differentiation and migration, angiogenesis and spermatogenesis. E2 also down‐regulated cholesterol and androgen synthesis pathways. Real‐time RT‐PCR confirmed the decrease in steroidogenic acute regulatory protein (Star) mRNA in the E2 supplemented group, suggesting a potential mechanism for the observed decrease in serum testosterone in this diet group. In contrast, GEN supplementation of milk formula altered 104 genes, soy formula 49 genes, and the pathways impacted had no clear links to testes function or sex organ development. These data show that early infant diet exposure to phytoestrogens in soy‐based infant formula are not estrogenic in the male reproductive system.Support or Funding InformationThis work was funded by USDA‐ARS Project 6026‐5100‐010‐05S.

Intestinal absorption of iron and calcium from soy and cow's milk-based infant formulas in weanling rats pups

ABSTRACT Objective: This study aimed to compare the intestinal absorption of iron and calcium between soy-based and cow's milk-based infant formulas in weanling rats. Methods: Twenty male Wistar rats, twenty-one days old on the first day of weaning, were used in this experiment, divided in two Groups, one Group was fed soy protein-based infant formula the other, cow's milk protein-based infant formula. During the study period (ten consecutive days) the animals received food and water ad libitum. Hematocrit and hemoglobin were evaluated on the first, fifth, and tenth days by the Wintrobe and cyanomethemoglobin methods. Feces and urine were collected, beginning on the fifth day, for three consecutive days. On the tenth day, hepatic iron content was also analyzed. Hepatic iron as well as fecal and urinary iron and calcium analyses were performed using an atomic absorption spectrophotometer. At thirty-one days of age, the animals were anesthetized with ketamine and xylazine and sacrificed by exsanguination via the vena cava. Results: The final concentration of hemoglobin in the group soy-based infant formula and milk-based infant formula were: 10.3±1.3g/dL and 10.9±1.0g/dL (p=0.310). The apparent absorption of iron and calcium, in that order, were: 73.4±10.2% and 70.2±9.5%; 97.2±0.7% and 97.6±1.0% (p=0.501; p=0.290). The apparent calcium retention was: 88.4% ±2.2 and 88.6±2.6% (p=0.848). Hepatic iron content was: 522.0±121.1mg/g and 527.8±80.5mg/g (p=0.907) . Conclusion: Intestinal iron and calcium absorption from soy-based infant formula is similar to that from milk-based infant formula in weanling rats.