Associations between prenatal antibiotics exposure and preschoolers’ attention-deficit hyperactivity disorder symptom trajectories: Unveiling the potential intervention strategies

BACKGROUND: Understanding the effects of prenatal antibiotic exposure on the developmental trajectories of attention-deficit hyperactivity disorder (ADHD) in offspring and exploring intervention strategies are key to managing early-life health. METHODS: This research included 2387 motherchild pairs. Antibiotics were detected in maternal urine samples. At the ages of 3, 5, and 6 years, children's ADHD symptoms were evaluated. Group-based trajectory modeling was employed to fit ADHD symptom trajectories. Generalized linear models and quantile-based g-computation approaches were used to investigate individual and mixed relationships between prenatal antibiotic exposure and ADHD symptom trajectories stratified by child sex, maternal folic acid (FA)/vitamin D (VD) levels, and exclusive breastfeeding. RESULTS: Preschoolers' ADHD symptom trajectories were classified into three profiles: low risk, moderate risk, and high risk. First-trimester doxycycline and ciprofloxacin, second-trimester doxycycline and PVAs were associated with an increased risk of moderate-risk and high-risk ADHD symptoms among preschoolers. Antibiotic mixture exposure during the first trimester was positively correlated with high-risk trajectories, whereas exposure during the second trimester was associated with both moderate- and high-risk trajectories. The individual and joint effects of prenatal antibiotic exposure on ADHD symptom trajectories were more pronounced in girls. Furthermore, insufficient first-trimester FA supplementation and second-trimester VD deficiency may potentiate the relationship between specific antibiotic exposure and moderate-to-high risk trajectories. CONCLUSIONS: Both individual and mixed prenatal antibiotic exposure were positively associated with moderate-risk and high-risk trajectories of preschoolers' ADHD symptoms, and insufficient maternal FA supplementation and VD deficiency during early pregnancy may act as potential effect modifiers.