The causal impact of maternal smoking around birth on offspring ADHD: A two-sample Mendelian randomization study

Background: The previous literature highlights a relationship between maternal smoking around birth (MSAB) and offspring attention-deficit/hyperactivity disorder (ADHD). These studies have focused on the causal effects of MSAB on offspring ADHD. Method: A Mendelian randomization analysis was conducted using summary statistics. Data on MSAB were obtained from a recent study including 391,992 participants. ADHD data were obtained from six sources for 246,888 participants. The present study used five methods to examine the causal impact from outcomes on exposures. The inverse variance weighted (IVW) was the main method of analysis, while the other four methods were supplementary methods. Result: The IVW revealed that MSAB was a risk factor for offspring ADHD (OR: 2.54; 95 % confidence interval [CI]: 1.61–4.00, p = 6.04 × 10⁻⁵). Concerning ADHD in both sexes, MSAB was associated with females (OR = 3.96, 95 % CI: 1.99–7.90, p = 8.98 × 10⁻⁵) and males (OR = 3.74, 95 % CI: 1.74–5.72, p = 1.48 × 10⁻⁴). In different diagnosis periods for ADHD, MSAB increased the risk of childhood (OR = 3.63, 95 % CI: 2.25–5.87, p = 1.31 × 10⁻⁷), late-diagnosed (OR = 2.99, 95 % CI: 1.74–5.14, p = 7.33 × 10⁻⁵), and persistent (OR = 4.77, 95 % CI: 1.88–12.14, p = 1.03 × 10⁻³) ADHD. The final analysis did not reveal heterogeneity. Conclusions: A causal impact of MSAB on offspring ADHD was observed. These findings highlight the need for careful consideration of prenatal exposure (MSAB) during the assessment of offspring ADHD. Additionally, it can provide targeted guidance for prenatal interventions. Future studies should analyze the effects of different doses of maternal smoking on ADHD.