Soy-based infant formula is associated with an increased prevalence of comorbidities in fragile X syndrome

Cara J. Westmark; Chad Kniss; Emmanuel Sampene; Angel Wang; Amie Milunovich; Kelly Elver; David Hessl; Amy Talboy; Jonathon Picker; Barbara Haas-Givler; Amy Esler; Andrea L. Gropman; Ryan Uy; Craig Erickson; Milen Velinov; Nicole Tartaglia; Elizabeth M. Berry-Kravis

doi:10.3390/nu12103136

Soy-based infant formula is associated with an increased prevalence of comorbidities in fragile X syndrome

Cara J. Westmark, Chad Kniss, Emmanuel Sampene, Angel Wang, Amie Milunovich, Kelly Elver, David Hessl, Amy Talboy, Jonathon Picker, Barbara Haas-Givler, Amy Esler, Andrea L. Gropman, Ryan Uy, Craig Erickson, Milen Velinov, Nicole Tartaglia, Elizabeth M. Berry-Kravis

Pediatrics - Neuropsychology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Article number	3136
Pages (from-to)	1-15
Number of pages	15
Journal	Nutrients
Volume	12
Issue number	10
DOIs	https://doi.org/10.3390/nu12103136
State	Published - Oct 2020

Bibliographical note

Funding Information:
Study Population & Participant Recruitment. The FXCRC was established in 2006 with support from the National Fragile X Foundation (NFXF) and subsequently expanded in 2009 with support by a grant from the Centers for Disease Control and Prevention (CDC) and consists of 22 FXS clinics and research facilities across the United States. The FXCRC developed FORWARD in 2011 to facilitate multisite data collection on individuals with FXS and to assist researchers in identifying participants who may be interested in and meet the eligibility criteria for specific research projects [18]. More than 1350 of the registrants are full-mutation FXS, and 1102 have a completed Clinical Report Form with seizure history. The study population included full-mutation FXS individuals enrolled in FORWARD and whose parents/caregivers had previously agreed to be contacted for research studies. Per FORWARD internal review board (IRB) guidelines, participants must be contacted directly by clinic directors for participation in research studies. Thus, for recruitment, participants in FORWARD with a history of seizures were identified as well as 4-fold more control participants. Controls were FXS participants without a reported history of seizures. Cases and controls were reasonably balanced on age and sex. The Principal Investigator, at the UW-Madison, contacted the clinical directors at all FORWARD sites and invited them to participate in the study. Individual clinics that agreed to participate in the study were provided a list of eligible participants associated with their site by the staff at FORWARD. The clinics sent parents/guardians a letter that informed them of the proposed study, invited them to participate, and emphasized the voluntary and confidential nature of the research. The letter requested that the primary caregiver of the participant with FXS return an enclosed card with their contact information to the UWSC for participation in the project.

Funding Information:
Funding: This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), grant number HD097067. FORWARD was supported by cooperative agreements U01DD000231, U19DD000753 and U01DD001189, funded by the CDC. This article’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services.

Funding Information:
This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), grant number HD097067. FORWARD was supported by cooperative agreements U01DD000231, U19DD000753 and U01DD001189, funded by the CDC. This article?s contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Autism
Fragile X syndrome (FXS)
Infant formula
Seizures
Soy

Access

10.3390/nu12103136

OpenUrl availability

Full text

Cite this

Westmark, C. J., Kniss, C., Sampene, E., Wang, A., Milunovich, A., Elver, K., Hessl, D., Talboy, A., Picker, J., Haas-Givler, B., Esler, A., Gropman, A. L., Uy, R., Erickson, C., Velinov, M., Tartaglia, N., & Berry-Kravis, E. M. (2020). Soy-based infant formula is associated with an increased prevalence of comorbidities in fragile X syndrome. Nutrients, 12(10), 1-15. Article 3136. https://doi.org/10.3390/nu12103136

Westmark, CJ, Kniss, C, Sampene, E, Wang, A, Milunovich, A, Elver, K, Hessl, D, Talboy, A, Picker, J, Haas-Givler, B, Esler, A, Gropman, AL, Uy, R, Erickson, C, Velinov, M, Tartaglia, N & Berry-Kravis, EM 2020, 'Soy-based infant formula is associated with an increased prevalence of comorbidities in fragile X syndrome', Nutrients, vol. 12, no. 10, 3136, pp. 1-15. https://doi.org/10.3390/nu12103136

@article{7ddea0eccce342e1a72492649811bb23,

title = "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.",

keywords = "Autism, Fragile X syndrome (FXS), Infant formula, Seizures, Soy",

author = "Westmark, {Cara J.} and Chad Kniss and Emmanuel Sampene and Angel Wang and Amie Milunovich and Kelly Elver and David Hessl and Amy Talboy and Jonathon Picker and Barbara Haas-Givler and Amy Esler and Gropman, {Andrea L.} and Ryan Uy and Craig Erickson and Milen Velinov and Nicole Tartaglia and Berry-Kravis, {Elizabeth M.}",

note = "Funding Information: Study Population & Participant Recruitment. The FXCRC was established in 2006 with support from the National Fragile X Foundation (NFXF) and subsequently expanded in 2009 with support by a grant from the Centers for Disease Control and Prevention (CDC) and consists of 22 FXS clinics and research facilities across the United States. The FXCRC developed FORWARD in 2011 to facilitate multisite data collection on individuals with FXS and to assist researchers in identifying participants who may be interested in and meet the eligibility criteria for specific research projects [18]. More than 1350 of the registrants are full-mutation FXS, and 1102 have a completed Clinical Report Form with seizure history. The study population included full-mutation FXS individuals enrolled in FORWARD and whose parents/caregivers had previously agreed to be contacted for research studies. Per FORWARD internal review board (IRB) guidelines, participants must be contacted directly by clinic directors for participation in research studies. Thus, for recruitment, participants in FORWARD with a history of seizures were identified as well as 4-fold more control participants. Controls were FXS participants without a reported history of seizures. Cases and controls were reasonably balanced on age and sex. The Principal Investigator, at the UW-Madison, contacted the clinical directors at all FORWARD sites and invited them to participate in the study. Individual clinics that agreed to participate in the study were provided a list of eligible participants associated with their site by the staff at FORWARD. The clinics sent parents/guardians a letter that informed them of the proposed study, invited them to participate, and emphasized the voluntary and confidential nature of the research. The letter requested that the primary caregiver of the participant with FXS return an enclosed card with their contact information to the UWSC for participation in the project. Funding Information: Funding: This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), grant number HD097067. FORWARD was supported by cooperative agreements U01DD000231, U19DD000753 and U01DD001189, funded by the CDC. This article{\textquoteright}s contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services. Funding Information: This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), grant number HD097067. FORWARD was supported by cooperative agreements U01DD000231, U19DD000753 and U01DD001189, funded by the CDC. This article?s contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = oct,

doi = "10.3390/nu12103136",

language = "English (US)",

volume = "12",

pages = "1--15",

journal = "Nutrients",

issn = "2072-6643",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "10",

}

TY - JOUR

T1 - Soy-based infant formula is associated with an increased prevalence of comorbidities in fragile X syndrome

AU - Westmark, Cara J.

AU - Kniss, Chad

AU - Sampene, Emmanuel

AU - Wang, Angel

AU - Milunovich, Amie

AU - Elver, Kelly

AU - Hessl, David

AU - Talboy, Amy

AU - Picker, Jonathon

AU - Haas-Givler, Barbara

AU - Esler, Amy

AU - Gropman, Andrea L.

AU - Uy, Ryan

AU - Erickson, Craig

AU - Velinov, Milen

AU - Tartaglia, Nicole

AU - Berry-Kravis, Elizabeth M.

N1 - Funding Information: Study Population & Participant Recruitment. The FXCRC was established in 2006 with support from the National Fragile X Foundation (NFXF) and subsequently expanded in 2009 with support by a grant from the Centers for Disease Control and Prevention (CDC) and consists of 22 FXS clinics and research facilities across the United States. The FXCRC developed FORWARD in 2011 to facilitate multisite data collection on individuals with FXS and to assist researchers in identifying participants who may be interested in and meet the eligibility criteria for specific research projects [18]. More than 1350 of the registrants are full-mutation FXS, and 1102 have a completed Clinical Report Form with seizure history. The study population included full-mutation FXS individuals enrolled in FORWARD and whose parents/caregivers had previously agreed to be contacted for research studies. Per FORWARD internal review board (IRB) guidelines, participants must be contacted directly by clinic directors for participation in research studies. Thus, for recruitment, participants in FORWARD with a history of seizures were identified as well as 4-fold more control participants. Controls were FXS participants without a reported history of seizures. Cases and controls were reasonably balanced on age and sex. The Principal Investigator, at the UW-Madison, contacted the clinical directors at all FORWARD sites and invited them to participate in the study. Individual clinics that agreed to participate in the study were provided a list of eligible participants associated with their site by the staff at FORWARD. The clinics sent parents/guardians a letter that informed them of the proposed study, invited them to participate, and emphasized the voluntary and confidential nature of the research. The letter requested that the primary caregiver of the participant with FXS return an enclosed card with their contact information to the UWSC for participation in the project. Funding Information: Funding: This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), grant number HD097067. FORWARD was supported by cooperative agreements U01DD000231, U19DD000753 and U01DD001189, funded by the CDC. This article’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services. Funding Information: This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), grant number HD097067. FORWARD was supported by cooperative agreements U01DD000231, U19DD000753 and U01DD001189, funded by the CDC. This article?s contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Department of Health and Human Services. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

KW - Autism

KW - Fragile X syndrome (FXS)

KW - Infant formula

KW - Seizures

KW - Soy

UR - http://www.scopus.com/inward/record.url?scp=85092904864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85092904864&partnerID=8YFLogxK

U2 - 10.3390/nu12103136

DO - 10.3390/nu12103136

M3 - Article

C2 - 33066511

AN - SCOPUS:85092904864

SN - 2072-6643

VL - 12

SP - 1

EP - 15

JO - Nutrients

JF - Nutrients

IS - 10

M1 - 3136

ER -

Soy-based infant formula is associated with an increased prevalence of comorbidities in fragile X syndrome

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this