Soy Formula Research Articles

Current Guidelines and Future Strategies for the Management of Cow's Milk Allergy.

Exclusive breast feeding is recommended in all guidelines as the first choice feeding. Cow milk allergy (CMA) can be diagnosed by a diagnostic elimination diet for 2 to 4 weeks with a hypo-allergenic formula, followed by a challenge test with intact cow milk protein. The most often used hypo-allergenic formula for the diagnostic elimination diet and the therapeutic diet is a CM based extensive hydrolysate. CM-based partial hydrolysates cannot be recommended in the management of CMA because of insufficient efficacy and possible reactions, but about half of the infants with CMA may tolerate a partial hydrolysate. The pros and cons of other dietary options are discussed in this paper. The use of an amino acid-based formula and/or rice based hydrolysate formula during the diagnostic elimination and therapeutic diet is debated. When available, there is sufficient evidence to consider rice hydrolysates as an adequate alternative to CM-based hydrolysates, since some infants will still react to the CM hydrolysate. The pros and cons of dietary options such as soy formula, buckwheat, almond, pea or other plant based dietary products are discussed. Although the majority of the plant-based beverages are nutritionally inadequate, some are nutritionally adapted for toddlers. However, accessibility and content vary by country and, thus far there is insufficient evidence on the efficacy and tolerance of these plant-based drinks (except for soy formula and rice hydrolysates) to provide an opinion on them.ConclusionA diagnostic elimination diet, followed by a challenge remains the diagnostic standard. The use of an awareness tool may result in a decrease of delayed diagnosis. Breastmilk remains the ideal source of nutrition and when not available a CM extensively hydrolyzed formula, rice hydrolysate or amino acid formula should be recommended. More evidence is needed regarding plant-based drinks.

Newborn with Failure to Thrive and Diarrhea.

Newborn with Failure to Thrive and Diarrhea.

Parental Reports on Early Autism Behaviors in Their Children with Fragile X Syndrome as a Function of Infant Feeding.

This study evaluates the prevalence of autistic behaviors in fragile X syndrome as a function of infant diet. Retrospective survey data from the Fragile X Syndrome Nutrition Study, which included data on infant feeding and caregiver-reported developmental milestones for 190 children with fragile X syndrome enrolled in the Fragile X Online Registry with Accessible Database (FORWARD), were analyzed. Exploratory, sex-specific associations were found linking the use of soy-based infant formula with worse autistic behaviors related to language in females and self-injurious behavior in males. These findings prompt prospective evaluation of the effects of soy-based infant formula on disease comorbidities in fragile X syndrome, a rare disorder for which newborn screening could be implemented if there was an intervention. Gastrointestinal problems were the most common reason cited for switching to soy-based infant formula. Thus, these findings also support the study of early gastrointestinal problems in fragile X syndrome, which may underly the development and severity of disease comorbidities. In conjunction with comorbidity data from the previous analyses of the Fragile X Syndrome Nutrition Study, the findings indicate that premutation fragile X mothers should be encouraged to breastfeed.

Cost-effectiveness Analysis of Hypoallergenic Milk Formulas for the Management of Cow's Milk Protein Allergy in the United Kingdom.

Background: Cow’s milk protein allergy (CMPA) is the most common food allergy in early childhood. In most children CMPA resolves by age 5 or 6; however, if not treated correctly can provoke nutritional deficiency resulting in poor growth. Management consists of excluding cow’s milk from the diet, with hypoallergenic formulas (or non-dairy alternatives) being introduced to meet nutritional requirements.Objectives: To compare the cost-effectiveness of hypoallergenic formulas in reducing allergic manifestations and promoting immune tolerance in infants with immunoglobulin E (IgE)-mediated symptoms of CMPA.Methods: A trial-based decision analytic cohort model was developed to simulate the occurrence of urticaria, eczema, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA in the United Kingdom. Amino acid-based formula (AAF), extensively hydrolysed casein formula containing Lactobacillus rhamnosus Gorbach Goldin (EHCF+LGG), extensively hydrolysed whey formula (EHWF), and soy formula (SF) were compared using the National Health Service (NHS) perspective, 3-year time horizon and 3.5% discount rate for cost and health consequences. Hypoallergenic formulas comparative efficacy was sourced from a prospective cohort study. Resources required to manage allergic symptoms were sourced from published literature, validated by a UK clinician, and applied to UK cost resources. Results were reported as cost per additional child free from allergic manifestations at 3 years and cost per additional immune tolerant child at 3 years.Results: In the base case, infants receiving EHCF+LGG were associated with lower NHS resource use and improved CMPA tolerance. Over the 3-year treatment period, savings of £119, £476, and £2645 were achieved with EHCF+LGG compared to SF, EHWF and AAF, respectively. Infant formula accounted for the largest proportion of resource consumption averaging 47% for all comparators, with a minimum of 31% for SF and a maximum of 69% for AAF over 3 years. General practitioners’ visits constituted the second highest cost component, approximately 16% of total costs across comparators. The results were robust to deterministic and probabilistic sensitivity analyses.Conclusions: Compared to AAF, SF, and EHWF hypoallergenic formulas, EHCF+LGG was the most cost-effective, associated with lower total costs and contributing to a higher proportion of children being symptom-free and developing immune tolerance 3-years after diagnosis.

Manganese Intake in Babies: Drinking Water plus Formula Can Cause High Exposures.

Manganese Intake in Babies: Drinking Water plus Formula Can Cause High Exposures.

Effect of formula milk on the roughness and hardness of tooth enamel

Background: Demineralisation and remineralisation is a natural process in tooth enamel. It is influenced by the content of calcium and phosphorus in saliva, which concentrations are affected by the consumption of food, including formula milk. Demineralisation and remineralisation determine the roughness and hardness of the enamel surface. Purpose: This study compared the effect of formula milk on the roughness and hardness of tooth enamel. Methods: Maxillary premolar extracted teeth were demineralised with 37% phosphoric acid for 90 seconds and then divided into four treatment groups. For four days, the teeth were immersed twice a day in cow formula for five and ten minutes (Group I and II) and soy formula for five and ten minutes (Group III and IV). Before and after the immersion in milk, the teeth were submerged in artificial saliva. The enamel surface roughness and hardness were measured three times using a surface roughness tester and a Vickers microhardness tester, before and after demineralisation and after immersion in milk. Data were analysed using Kruskal–Wallis and post hoc Mann–Whitney tests. Results: There was no significant difference (p=0.88) observed in the roughness reduction among the treatment groups. The highest increase in hardness was noted for the ten-minute cow formula milk group (93.27 ± 16.00). The increase of hardness was higher after immersion for ten minutes. A substantial difference (p=0.03) was seen in the increase of hardness between the treatment groups. Conclusion: Immersion in cow and soy formula milk for five and ten minutes does not reduce the enamel roughness, but it increases the enamel hardness.

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

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

A formula-fed infant with profound dehydration, cerebral venous sinus thrombosis, and intracranial hemorrhage.

Chronic food protein-induced enterocolitis syndrome (FPIES) is a cell-mediated gastrointestinal food hypersensitivity described almost exclusively in infants fed cow's milk or soy formula. A timely diagnosis is challenging due to a number of factors, including broad differential diagnoses, absence of specific biomarkers, and delayed symptom onset. This report aimed to highlight how the severity of presentation can further impede a timely diagnosis in chronic FPIES. Methods: A case of presumed chronic FPIES to soy with previously unreported complications of intracranial hemorrhage and cerebral venous sinus thrombosis was described. We reported a case of a female infant fed a soy formula who presented during the third week of life with intermittent and progressive emesis, diarrhea, and lethargy, which culminated in severe dehydration, with early hospital course complications of seizures, intracranial hemorrhage, and cerebral venous sinus thrombosis. Although not recognized until weeks into the hospital course, many of the presenting symptoms and laboratory abnormalities were characteristic of chronic FPIES. An ultimate consideration of FPIES led to transition to amino acid-based formula and gradual resolution of gastrointestinal symptoms. Close outpatient follow-up was essential in facilitating subsequent age-appropriate solid food introduction. The severity of presentation in FPIES can represent an additional barrier to a timely diagnosis. Early consideration of this entity in the differential diagnosis of patients with typical FPIES features, regardless of the additional presence of atypical and severe complications, may help with more timely recognition and intervention. In addition, there is an increased need for close follow-up as an outpatient in severe FPIES cases.

Potential for Manganese-Induced Neurologic Harm to Formula-Fed Infants: A Risk Assessment of Total Oral Exposure.

Background:High oral exposure and biological vulnerabilities may put formula-fed infants at risk for manganese-induced neurotoxicity.Objectives:We sought to characterize manganese concentrations in public drinking water and prepared infant formulas commonly purchased in the United States, integrate information from these sources into a health risk assessment specific to formula-fed infants, and examine whether households that receive water with elevated manganese concentrations avoid or treat the water, which has implications for formula preparation.Methods:Manganese was measured in 27 infant formulas and nearly all Minnesota community public water systems (CPWS). The risk assessment produced central tendency and upper-end exposure estimates that were compared to a neonatal animal-based health reference dose (RfD) and considered possible differences in bioavailability. A survey study assessed esthetic concerns, treatment, and use of water in a Twin Cities community with various levels of manganese in drinking water.Results:Ten percent of CPWSs were estimated to exceed the EPA health advisory level of . Manganese concentrations in formula ranged from 69.8 to , with amino formula concentrations. Central tendency estimates of soy and amino acid formula reconstituted with water at the CPWS 95th percentile manganese concentration exceeded the neonatal-based RfD. Upper-end estimates of manganese intake from formula alone, independent of any water contribution, equaled or exceeded the neonatal-based RfD. In the survey study, we observed increased awareness of esthetic issues and water avoidance at higher manganese concentrations, but these concentrations were not a reliable consumption deterrent, as the majority of households with inside tap drinking water results above reported drinking the water.Discussion:Excessive exposure to manganese early in life can have long-lasting neurological impacts. This assessment underscores the potential for manganese overexposure in formula-fed infants. U.S. agencies that regulate formula and drinking water must work collaboratively to assess and mitigate potential risks. https://doi.org/10.1289/EHP7901

Early-life Exposures and Age at Breast Development in the Sister Study Cohort

Abstract Purpose: Early age at breast development (thelarche) has been associated with increased breast cancer risk. Average age at thelarche has declined over time, but there are few established risk factors for early thelarche. We examined associations between pre- and postnatal exposures and age at thelarche in a U.S. cohort of women born between 1928 and 1974. Methods: Breast cancer-free women ages 35–74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003–2009 (N = 50,884). At enrollment, participants reported their age at thelarche, which we categorized as early (≤10 years), average (11–13 years), and late (≥14 years), as well as information on early-life exposures. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche relative to average age at thelarche using polytomous logistic regression for each early-life exposure, adjusted for birth cohort, race/ethnicity and family income level in childhood. We examined modification by birth cohort, race/ethnicity, family income, relative weight at age 10, and extent of breast cancer family history through stratification. Results: Early thelarche was more common in recent birth cohorts and among non-Hispanic Black and Hispanic women. Early thelarche (≤10 years) was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI, 1.09–1.43), maternal diethylstilbestrol (DES) use (OR = 1.23, 95% CI, 1.04–1.45), maternal smoking during pregnancy (OR = 1.20, 95% CI, 1.13–1.27), and young maternal age (OR 1.30, 95% CI, 1.16–1.47 for <20 vs 25–29 years). Being firstborn was also associated with early thelarche (OR = 1.25, 95% CI, 1.17–1.33). Low birthweight (<2500 vs 2500–3999g) was suggestively associated with both early (OR = 1.06, 95% CI, 0.96–1.17) and late (OR = 1.15, 95% CI, 1.05–1.25) thelarche, as was use of soy formula in infancy (Early: OR = 1.10, 95% CI, 0.93–1.30; Late: OR = 1.07, 95% CI, 0.92–1.25). Patterns were generally similar across strata of modifiers of interest. Conclusion: Associations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment may influence breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.

Determination of lactose in low-lactose and lactose-free dairy products using LC-MS

An LC–MS method was developed for routine determination of lactose in low-lactose and lactose-free dairy products. The lactose was separated on an amide column under an isocratic elution condition. Baseline separation of lactose from common interferents, including epilactose, lactulose, and allolactose were achieved under this LC conditions. The lactose chloride-35 adduct ions were detected by a single quadrupole MS in ESI- mode. 13C labeled lactose was used as an internal standard. The LOQ was estimated at 2.6 mg/100 g in a soy based infant formula. The recovery was found within the range of 90%–109% in the spiking study on commercial dairy products at spiking levels between 3.4 and 461 mg/100 g. The analysis of lactose concentration in the NIST SRM 1849a showed an accuracy of 109%. The RSD in the analysis of those commercial products were less than 4.3%. This method is sensitive and selective enough and fit for the routine determination of lactose in low-lactose and lactose-free dairy products.

Ready-to-use therapeutic foods for the treatment of malnourished children and infants.

Ready-to-use therapeutic foods (RUTF) allow effective community-based management of severe acute malnutrition (SAM). Current interest focuses on their optimal composition and use. Studies of alternative RUTF have yielded differing results. Partial soybean, sorghum flour, and whey protein replacement RUTF were inferior to standard RUTF. In contrast, soy-based RUTF was as effective as milk-based RUTF and an alternative RUTF with added oats lead to superior recovery in comparison to standard RUTF.Reducing the dose of RUTF in the later phases of SAM recovery resulted in small reductions in the growth of uncertain clinical significance.Although iron and vitamin A status improve during treatment with standard RUTF, a significant proportion of children remained deficient. Alternative soya, maize, and sorghum-based formulas with no milk protein may improve recovery of iron status compared to standard RUTF.Finally, in children with SAM, plasma essential fatty acids and conversion to long-chain polyunsaturated fatty acids are reduced. Despite the improvement, these parameters remain lower than in normal children after 3 months. New RUTF formulations may provide a cost-effective alternative to standard RUTF. Future research should focus on addressing micronutrient deficiency, lipid metabolism, and long-term recovery.

Exposure assessment of glyphosate residues in soy-based infant formulas from the Brazilian market

Exposure assessment of glyphosate residues in soy-based infant formulas from the Brazilian market

The Impact of Formula Choice for the Management of Pediatric Cow’s Milk Allergy on the Occurrence of Other Allergic Manifestations: The Atopic March Cohort Study

To compare the impact of different formulas on the occurrence of other atopic manifestations and the time of immune tolerance acquisition. In a 36-month prospective cohort study, the occurrence of other atopic manifestations (eczema, urticaria, asthma, and rhinoconjunctivitis) and the time of immune tolerance acquisition were comparatively evaluated in immunoglobulin E-mediated children with cow's milk allergy (CMA) treated with extensively hydrolyzed casein formula containing the probiotic L. rhamnosus GG (EHCF+LGG), rice hydrolyzed formula, soy formula, extensively hydrolyzed whey formula (EHWF), or amino acid-based formula. In total, 365 subjects were enrolled into the study, 73 per formula cohort. The incidence of atopic manifestations was 0.22 (Bonferroni-corrected 95% CI 0.09-0.34) in the EHCF+LGG cohort; 0.52 (0.37-0.67) in the rice hydrolyzed formula cohort; 0.58 (0.43-0.72) in the soy formula cohort; 0.51 (0.36-0.66) in the EHWF cohort; and 0.77 (0.64-0.89) in the amino acid-based formula cohort. The incidence of atopic manifestations in the rice hydrolyzed formula, soy formula, EHWF, and amino acid-based formula cohorts vs the EHCF+LGG cohort was always greater than the prespecified absolute difference of 0.25 at an alpha-level of 0.0125, with corresponding risk ratios of 2.37 (1.46-3.86, P<.001) for rice hydrolyzed formula vs EHCF+LGG; 2.62 (1.63-4.22, P<.001) for soy formula vs EHCF+LGG; 2.31 (1.42-3.77, P<.001) for EHWF vs EHCF+LGG; and 3.50 (2.23-5.49, P<.001) for amino acid-based formula vs EHCF+LGG. The 36-month immune tolerance acquisition rate was greater in the EHCF+LGG cohort. The use of EHCF+LGG for CMA treatment is associated with lower incidence of atopic manifestations and greater rate of immune tolerance acquisition.

Growth Patterns of Indonesian Infants with Cow's Milk Allergy and Fed with Soy-Based Infant Formula.

PurposeThe use of soy-based infant formula has increased widely in infants with cow's milk allergy (CMA). This study aimed to provide evidence on the growth pattern of CMA infants fed with soy-based infant formula in an Indonesian setting.MethodsA multi-site, intervention study was conducted among full-term and normal birth weight CMA infants. Within six months, the subjects were provided with a soy-based infant formula. Weight, height, and head circumference were measured at baseline, weeks 4, 8, 12, 16, 20, and 24. Adverse events were recorded by scoring atopic dermatitis and symptom-based clinical scores.ResultsBased on the World Health Organization growth chart, we found that most of subjects had normal nutritional status for weight-for-age, length-for-age, weight-for-length, and head-circumference-for-age. There were statistically significant differences between baseline and end-line for weight-for-age, length-for-age, weight-for-length, and head circumference-for-age nutritional status. No allergic symptoms or intolerance toward soy formula were observed at the end of the intervention period.ConclusionThese results show that infants fed with soy-based infant formula have a normal pattern of growth.

Systemic reaction to an extensively hydrolyzed formula in an infant with cow's milk anaphylaxis.

Cow's milk allergy is the most common cause of food allergy in young children. Ingestion of milk products in children with a milk protein allergy can lead to anaphylaxis and must be avoided. Some guidelines suggest the use of an extensively hydrolyzed formula (EHF) in these cases; however, rare allergic reactions can still occur. Here, we presented a 3-month-old boy who developed anaphylaxis to a cow's milk formula. Subsequently, he developed a rare systemic reaction to soy and to an EHF. The patient had an unremarkable medical history and presented with signs and symptoms consistent with anaphylaxis after being fed cow's milk formula for the first time. Symptoms included immediate vomiting, wheezing, stridor, angioedema of eyelids and lips. Although intramuscular epinephrine was given, the patient continued to clinically deteriorate, becoming more lethargic and necessitating admission to the pediatric intensive care unit. Subsequently, a trial of soy formula ingestion reproduced the symptoms and an EHF was given. However, immediately after taking an EHF, he developed facial angioedema and diffuse urticarial lesions. In most patients with a cow's milk allergy, an extensively based formula can be tolerated safely due to a hydrolyzed protein chain. However, medical providers must be vigilant when switching formula because a rare systemic allergic reaction to EHF can still occur.

PNS37 Economic Analysis for Early Introduction of Amino Acid Formula for Cow's Milk Protein Allergy in the GCC Countries

Cow’s milk protein allergy (CMPA) is the most common food allergy in infants, affecting ∼5% of infants globally. Appropriate substitution for cow milk products is imperative in the critical growing period for infants and to avoid malnutrition and/or nutrient deficiencies. Almost 100% of infants with CMPA will respond to an amino acid formula (AAF), this may allow to use AAF as a therapeutic trail with high negative predictive value. The lack of response to an AAF formula excludes CMPA in clinical practice. The objectives were to estimate the budget impact (BI) of early introduction of AAF (Neocate®) on healthcare payers’ budget in Gulf Co-operation Council (GCC) countries for CMPA management. BI estimation was conducted for three GCC countries: Kingdom of Saudi Arabia (KSA), Kuwait and United Arab Emirates (UAE) in children <24 months suspected with CMPA. A global decision tree model was adapted to compare the estimated costs in current practice where AAF is used as first-line therapeutic trial of suspected CMPA versus current practice of testing, medications, and referral or using alternative formulae. Model inputs included population data, total costs associated with drug acquisition and disease management. The proposed early introduction of AAF (Neocate®) in the management of CMPA exhibited considerable cost savings; 10% (SAR 15,102,542) in KSA, 10% (KWD 306,565) in Kuwait, 17% (AED 1,842,018) in UAE government sector, and 13% (AED 4,232,932) in UAE private sector. The cost impact was driven primarily by minimal use of soy formula in both KSA (58%; SAR 4,204,540), reduced medication cost in Kuwait (37%; KWD 5,630) and decreased examination cost in UAE-government sector (58%; AED 351,919) and private sector (50%; AED 1,508,918). The early introduction of AAF (Neocate®) in children <24 months suspected with CMPA will be cost-saving from a healthcare payer’s perspective of GCC countries for the management of CMPA.

Efficacy of Soy-Based Formulas in Alleviating Gastrointestinal Symptoms in Infants With Milk-Based Formula Intolerance: A Randomized Clinical Trial.

A randomized, blinded pilot clinical study was conducted to assess gastrointestinal (GI) tolerance in healthy, full-term infants (2-9 weeks old), whose pediatricians recommended a formula change due to perceived cow's milk formula intolerance. Infants were randomized and exclusively fed either a commercial control soy formula (SF; n = 22), an experimental partially hydrolyzed SF (10% hydrolyzed, n = 23), or a 5% hydrolyzed SF (n = 26) for 2 weeks. Age-matched reference cohorts (n = 72) with no GI intolerance on milk-based formula were assessed in parallel. Results indicated that all SF-fed groups contributed to reduction (P < .05) in common GI tolerance symptoms to levels not different from the non-symptomatic reference cohort at study end. The control SF group had more reduced fussiness, gas, and crying and higher formed stools versus hydrolyzed SF groups. In conclusion, the study suggests that SFs reduced GI intolerance symptoms in otherwise healthy infants with poor tolerance on milk-based formulas.

Use of Soy-Based Formulas and Cow's Milk Allergy: Lights and Shadows.

Soybean (Glycine max) is a species of legume native to East Asia and used in childhood diet for over 2,000 years in the East. Soy protein formulas have been available for almost a century. Nowadays, the increase in cow's milk allergy and vegetarian dietary preferences are driving consumers toward cow's milk alternatives. In this paper, we reviewed the nutritional composition of soy-based infant formula and discussed their possible use in pediatric age, mainly focusing on prevention and treatment of cow's milk allergy. Protein quality is determined by digestibility and amino acid content. Purified or concentrated vegetable proteins (e.g., soy protein and gluten) have high digestibility (>95%), similar to those of animal ones. For some intact vegetable products (e.g., whole cereals and pulses), protein digestibility is lower (80–90%). Food processing and heat treatment also influence protein digestibility. Considering these data, we tried to evaluate the possible use of soybean and derivatives in pediatric age, including the nutritional composition of soy formulas and the clinical indications for their use. Moreover, since plant-based beverages are being perceived as healthy by consumers and their use is growing on the market, we recommend that soy drink should not be used as a substitute for infant formulas or cow's milk in children younger than 24 months.

Soy-Based Infant Formula is Associated with an Increased Prevalence of Comorbidities in Fragile X Syndrome.

A large number of adults and children consume soy in various forms, but little information is available regarding potential neurological side effects. Prior work indicates an association between the consumption of soy-based diets and seizure prevalence in mouse models of neurological disease and in children with autism. Herein, we sought to evaluate potential associations between the consumption of soy-based formula during infancy and disease comorbidities in persons with fragile X syndrome (FXS), while controlling for potentially confounding issues, through a retrospective case-control survey study of participants with FXS enrolled in the Fragile X Online Registry with Accessible Research Database (FORWARD). There was a 25% usage rate of soy-based infant formula in the study population. We found significant associations between the consumption of soy-based infant formula and the comorbidity of autism, gastrointestinal problems (GI) and allergies. Specifically, there was a 1.5-fold higher prevalence of autism, 1.9-fold GI problems and 1.7-fold allergies in participants reporting the use of soy-based infant formula. The major reason for starting soy-based infant formula was GI problems. The average age of seizure and allergy onset occurred long after the use of soy-based infant formula. We conclude that early-life feeding with soy-based infant formula is associated with the development of several disease comorbidities in FXS.