Neurodevelopmental Outcomes in Infants Fed with Soy Formula: A Retrospective, National Population-Based Observational Cohort Study

Abstract

Background Soy-based infant formulas are increasingly popular, but data regarding their effects on neurodevelopmental outcomes during early childhood is scanty. Objective This study investigated the effect of consuming soy-based infant formula at 9–12 mo after birth on the subsequent development of epilepsy, neurodevelopmental disorders, and developmental status. Methods This nationwide retrospective administrative study used health screening examinations and linked insurance claims data of children born in Korea during 2008 and 2009. Infants who received soy formula were compared with those who received cow's milk formula using propensity score matching that considered birth history, economic status, clinical conditions, and drug prescription records. Exposure was defined as soy formula feeding determined from questionnaires completed by the parents when children were 9–12 mo old. Outcomes were epilepsy, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental status. Children were followed until 31 December, 2017. Results A total of 153,841 eligible participants were enrolled; 11,535 (7.5%) children received soy formula, while 142,864 (92.5%) received cow's milk formula. The incidence rate of epilepsy during the follow-up period was 29.8 per 100,000 person-years (95% CI: 19.48, 41.65) in the soy formula group and 22.6 per 100,000 person-years (95% CI: 31.97, 59.07) in the cow's milk formula group, with no significant difference (aHR: 1.318; 95% CI: 0.825, 2.106). The 2 groups also had no difference based on prespecified analysis using different definitions of epilepsy. Likewise, no significant associations of soy formula with ADHD (aHR: 1.26; 95% CI: 1.00, 1.60) or ASD (aHR: 0.99; 95% CI: 0.54, 1.83), or delays of developmental stages were observed. Conclusions Feeding with soy formula rather than cow's milk formula had no apparent association with increased risks of epilepsy, ADHD, ASD, and developmental status, according to this cohort composed of a general pediatric population.

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

“…These mouse studies corroborate recent retrospective medical record and survey analyses of human subjects indicating associations between consumption of soy-based infant formula and increased seizures, autism, gastrointestinal problems, and allergies in autism and FXS, while long-term consumption of breastmilk is protective against autism in FXS [ [18][19][20][21]39]. The mouse work also corroborates a national population level study based on health screening examinations linked with insurance claims data, indicating associations between consumption of soy-based infant formula, and an increased incidence of epilepsy in children and ADHD in boys [40,41].…”

Associations between Delayed Introduction of Complementary Foods and Childhood Health Consequences in Exclusively Breastfed Children

“…Data were obtained from the National Health Screening Program for Infants and Children (NHSPIC) and the Linked NHIS Claims Database. Information on CF introduction time and feeding practices was collected through questionnaires answered by parents [12,13]. Length/height and weight were measured in the screening program when the children were 4 -< 7 months and 9 -< 13 months old and annually until the age of seven.…”

“…These secondary outcomes were used to estimate the realworld effects of the delayed introduction of CF. These clinical conditions were assessed after 24 months, except for the diagnosis of attention-deficit/hyperactivity disorder (ADHD), which was assessed after 48 months, based on previous validation studies [13]. All analysis codes were based on the diagnostic categories from the International Classification of Diseases, 10th Revision (ICD-10), utilizing previously validated definitions (Supplementary Table S1).…”