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, 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

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.

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

References

    1. Hagerman R.J., Berry-Kravis E., Hazlett H.C., Bailey D.B., Jr., Moine H., Kooy R.F., Tassone F., Gantois I., Sonenberg N., Mandel J.L., et al. Fragile X syndrome. Nat. Rev. Dis. Primers. 2017;3:17065. doi: 10.1038/nrdp.2017.65.
    1. Hagerman R.J., Hagerman P.J. Physical and Behavioral Phenotype. John Hopkins University Press; Baltimore, MD, USA: 2002. pp. 3–109.
    1. Riley C., Wheeler A. Assessing the fragile X syndrome newborn screening landscape. Pediatrics. 2017;139:S207–S215. doi: 10.1542/peds.2016-1159G.
    1. Westmark C.J., Westmark P.R., Malter J.S. Soy-based diet exacerbates seizures in mouse models of neurological disease. J. Alzheimers Dis. 2013;33:797–805. doi: 10.3233/JAD-2012-121426.
    1. Westmark C.J. Soy infant formula and seizures in children with autism: A retrospective study. PLoS ONE. 2014;9:e80488. doi: 10.1371/journal.pone.0080488.
    1. Westmark C.J. Soy infant formula may be associated with increased autistic behaviors. Autism-Open Access. 2013;3:20727.
    1. Jing H., Gilchrist J.M., Badger T.M., Pivik R.T. A longitudinal study of differences in electroencephalographic activity among breastfed, milk formula-fed, and soy formula-fed infants during the first year of life. Early Hum. Dev. 2010;86:119–125. doi: 10.1016/j.earlhumdev.2010.02.001.
    1. Li J., Dykman R.A., Jing H., Gilchrist J.M., Badger T.M., Pivik R.T. Cortical responses to speech sounds in 3- and 6-month-old infants fed breast milk, milk formula, or soy formula. Dev. Neuropsychol. 2010;35:762–784. doi: 10.1080/87565641.2010.508547.
    1. Adgent M.A., Daniels J.L., Edwards L.J., Siega-Riz A.M., Rogan W.J. Early-life soy exposure and gender-role play behavior in children. Environ. Health Perspect. 2011;119:1811–1816. doi: 10.1289/ehp.1103579.
    1. Pivik R.T., Andres A., Bai S., Cleves M.A., Tennal K.B., Gu Y., Badger T.M. Infant diet-related changes in syllable processing between 4 and 5 months: Implications for developing native language sensitivity. Dev. Neuropsychol. 2016;41:215–230. doi: 10.1080/87565641.2016.1236109.
    1. Harlid S., Adgent M., Jefferson W.N., Panduri V., Umbach D.M., Xu Z., Stallings V.A., Williams C.J., Rogan W.J., Taylor J.A. Soy formula and epigenetic modifications: Analysis of vaginal epithelial cells from infant girls in the IFED study. Environ. Health Perspect. 2017;125:447–452. doi: 10.1289/EHP428.
    1. Adgent M.A., Umbach D.M., Zemel B.S., Kelly A., Schall J.I., Ford E.G., James K., Darge K., Botelho J.C., Vesper H.W., et al. A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formula. J. Clin. Endocrinol. Metab. 2018;103:1899–1909. doi: 10.1210/jc.2017-02249.
    1. Li T., Badger T.M., Bellando B.J., Sorensen S.T., Lou X., Ou X. Brain cortical structure and executive function in children may be influenced by parental choices of infant diets. AJNR Am. J. Neuroradiol. 2020;41:1302–1308. doi: 10.3174/ajnr.A6601.
    1. Setchell K.D., Zimmer-Nechemias L., Cai J., Heubi J.E. Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet. 1997;350:23–27. doi: 10.1016/S0140-6736(96)09480-9.
    1. Bhatia J., Greer F., American Academy of Pediatrics Committee on Nutrition Use of soy protein-based formulas in infant feeding. Pediatrics. 2008;121:1062–1068. doi: 10.1542/peds.2008-0564.
    1. McCarver G., Bhatia J., Chambers C., Clarke R., Etzel R., Foster W., Hoyer P., Leeder J.S., Peters J.M., Rissman E., et al. NTP-CERHR expert panel report on the developmental toxicity of soy infant formula. Birth Defects Res. B Dev. Reprod. Toxicol. 2011;92:421–468. doi: 10.1002/bdrb.20314.
    1. Bailey D.B., Jr., Raspa M., Bishop E., Holiday D. No change in the age of diagnosis for fragile X syndrome: Findings from a national parent survey. Pediatrics. 2009;124:527–533. doi: 10.1542/peds.2008-2992.
    1. Sherman S.L., Kidd S.A., Riley C., Berry-Kravis E., Andrews H.F., Miller R.M., Lincoln S., Swanson M., Kaufmann W.E., Brown W.T. FORWARD: A registry and longitudinal clinical database to study fragile X syndrome. Pediatrics. 2017;139:S183–S193. doi: 10.1542/peds.2016-1159E.
    1. Centers for Disease Control and Prevention. [(accessed on 10 August 2020)]; Available online: .
    1. Clifford S., Dissanayake C., Bui Q.M., Huggins R., Taylor A.K., Loesch D.Z. Autism spectrum phenotype in males and females with fragile x full mutation and premutation. J. Autism Dev. Disord. 2007;37:738–747. doi: 10.1007/s10803-006-0205-z.
    1. Kaufmann W.E., Cortell R., Kau A.S., Bukelis I., Tierney E., Gray R.M., Cox C., Capone G.T., Stanard P. Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. Am. J. Med. Genet. A. 2004;129:225–234. doi: 10.1002/ajmg.a.30229.
    1. Dy A.B.C., Tassone F., Eldeeb M., Salcedo-Arellano M.J., Tartaglia N., Hagerman R. Metformin as targeted treatment in fragile X syndrome. Clin. Genet. 2018;93:216–222. doi: 10.1111/cge.13039.
    1. Kidd S.A., Lachiewicz A., Barbouth D., Blitz R.K., Delahunty C., McBrien D., Visootsak J., Berry-Kravis E. Fragile X syndrome: A review of associated medical problems. Pediatrics. 2014;134:995–1005. doi: 10.1542/peds.2013-4301.
    1. Utari A., Adams E., Berry-Kravis E., Chavez A., Scaggs F., Ngotran L., Boyd A., Hessl D., Gane L.W., Tassone F., et al. Aging in fragile X syndrome. J. Neurodev. Disord. 2010;2:70–76. doi: 10.1007/s11689-010-9047-2.
    1. Westmark C.J. Soy-based therapeutic baby formulas: Testable hypotheses regarding the pros and cons. Front. Nutr. 2017;3:59. doi: 10.3389/fnut.2016.00059.
    1. Asthma and Allergy Foundation of America. [(accessed on 10 August 2020)]; Available online:
    1. Gupta R.S., Springston E.E., Warrier M.R., Smith B., Kumar R., Pongracic J., Holl J.L. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128:9–17. doi: 10.1542/peds.2011-0204.
    1. Khan D.A., Solensky R. Drug allergy. J. Allergy Clin. Immunol. 2010;125:S126–S137. doi: 10.1016/j.jaci.2009.10.028.

Source: PubMed

3
Suscribir