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

Abstract

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.

Consumption of Breast Milk Is Associated with Decreased Prevalence of Autism in Fragile X Syndrome

“…A national registry of FXS families maintained by FORWARD was utilized to conduct a retrospective survey study evaluating associations between early childhood feeding practices and the severity of common FXS phenotypes. A detailed description of the study design, questionnaire, study population, recruitment success, and data collection have been previously described [ 19 ]. Briefly, the 55-point questionnaire, Fragile X Syndrome Nutrition Study, assessed demographics, infant feeding practices, frequency and severity of seizures, cognitive ability, autistic behaviors and comorbid diagnoses in an FXS population by parental survey.…”

“…Phase 2 occurred from 19 December 2019 through 7 February 2020 and consisted of mailing the questionnaire and reminders to participants who agreed to participate in the study. The participation response rate was 89% [ 19 ].…”

“…Variables of interest included caregiver reported data from survey questions (Q) ( Supplementary File S2 ) for incidence of autism, food allergies and diabetes (Q1); history of GI problems (Q2), age when GI problems started (Q3); history of seizures (Q4); age of first seizure (Q7); history of allergies (Q15); age of allergy onset (Q16); allergens (Q17); fed breast milk (Q18); age began feeding breast milk (Q19), reasons for feeding breast milk (Q20); age stopped being fed breast milk (Q21); reasons stopped feeding with breast milk (Q22); sex (Q48); and age (Q50 & Q55). Analysis of seizure type (Q5) was not assessed herein because caregiver reports of seizure type did not match clinical records [ 19 ]. Data were not corrected for infant length (Q51) or weight (Q52) measurements, which were identical between subjects classified as autistic by Q1a [20.2 (0.23) inches and 7.57 (0.13) pounds] and not autistic [19.8 (0.19) inches and 7.50 (0.14) pounds ( p = 0.18 and 0.70, respectively).…”

“…These data elicit the hypotheses that the consumption of soy-based infant formula could be associated with more severe FXS phenotypes [ 16 , 17 ] and that breastfeeding could be neuroprotective. To address the first hypothesis, a retrospective survey study, using the Fragile X Online Registry with Accessible Database (FORWARD [ 18 ]) as a sampling frame, indicates that soy-based infant formula is associated with statistically increased comorbidity of autism (1.5-fold), gastrointestinal (GI) problems (1.9-fold) and allergies (1.7-fold) [ 19 ]. The FORWARD nutrition survey also included data collection on the prevalence and duration of feeding with breast milk and reasons for commencement and cessation of breast milk.…”

Diet in the Treatment of Epilepsy

“…Westmark and colleagues contribute a survey-based study to this Special Issue regarding associations between caregiver-reported use of soy-based infant formula and disease comorbidities in their children with fragile X syndrome [ 7 ]. Fragile X is a rare developmental disability characterized by intellectual disability, autism and seizures.…”