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

Abstract

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.

Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

“…Besides, the pathways associated with memory, cognition, eating behavior and extracellular matrix organization were also enriched. The alterations of these pathways were previously implicated in FXS (Lumaban and Nelson, 2015;O'Leary and Nolan, 2015;Reinhard et al, 2015;Bostrom et al, 2016;Westmark, 2021). Collectively, these results suggested that RA alleviated defective social novelty behavior in Fmr1 KO mice possibly through restoring anomalous expressed genes and biological processes to normal.…”

“…The impairment of cognitive abilities and infant diet, was previously implicated in the individuals with FXS (Bostrom et al, 2016;Westmark, 2021). The corresponding GO terms of them, cognition and eating behaviors, were also enriched after RA administration (Figure 4F).…”

Effects of Soy-Based Infant Formula on Weight Gain and Neurodevelopment in an Autism Mouse Model

“…Our prior work indicated increased autistic behaviors in autism and FXS with consumption of soy-based infant formula [19][20][21]. The overall prevalence of autism or developmental delay in the IFSII/Y6FU dataset was 2.86% (0.85% for females and 5.0% for males) compared to 1.85% autism (0.069% for females and 2.97% for males) reported by the Autism and Developmental Disabilities Monitoring (ADDM) Network [33].…”

“…We searched the evidence-based literature regarding possible adverse health effects associated with consumption of soy-based infant formulas but found a dearth of published reports and no studies specific to developmental disorders such as FXS. To address this gap in the literature, we conducted retrospective medical record and survey analyses and found associations between postnatal consumption of soy-based infant formula and an increased incidence of seizures and/or autistic behavior in autism and FXS [18][19][20][21]. Here, we hypothesize that the high consumption of soy protein during postnatal development is a dietary exposure that increases the risk of developing obesity, particularly in vulnerable populations such as FXS.…”

Improving Reproducibility to Enhance Scientific Rigor through Consideration of Mouse Diet

“…These data served as the premise to conduct a case–control survey study evaluating the impact of early childhood feeding on the severity of common fragile X syndrome (FXS) phenotypes using the Fragile X Online Registry With Accessible Research Database (FORWARD), a national registry of FXS families. The project included collaboration with 10 FXS clinics across the U.S. and the data indicate that children with FXS who were fed soy-based infant formula had higher comorbidity of autism, allergies, and gastrointestinal problems [ 10 , 11 ]. The findings have significant implications for babies who are fed soy-based infant formula and could justify newborn screening for FXS if an early dietary intervention reduced disease comorbidities.…”