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

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.