Risk of ADHD in children born through assisted reproductive techniques: a systematic review and meta-analysis

To evaluate the association between assisted reproductive techniques (ART) and the risk of attention-deficit hyperactivity disorder (ADHD) in children. A systematic search was done in PubMed, Embase, Web of Science, and Scopus. Cohort and case-control studies were included. Effect sizes were pooled using hazard ratios (HRs) with 95% confidence intervals (CIs), and subgroup analyses were performed by sex, multiplicity of pregnancy, and gestational age. Heterogeneity and publication bias were assessed, and the certainty of evidence was evaluated using GRADE criteria. Children conceived through in vitro fertilization (IVF)/intracytoplasmic sperm injection had a slightly increased risk of ADHD compared to those conceived spontaneously (HR 1.07, 95% CI: 1.04, 1.10), with a moderate certainty of evidence. Three studies on ovulation induction /intrauterine insemination led to a pooled effect size of HR 1.13 (95% CI: 1.04, 1.23) with a moderate certainty of evidence. Subgroup analyses indicated an increased risk in both boys and girls. Singleton pregnancies exhibited a higher risk, while no significant association was observed in multiple pregnancies. Term births showed an elevated risk, with a higher but non-significant effect size in preterm births. Moderate certainty of evidence suggests that the magnitude of observed risk of ADHD is small in ART-conceived children, which is reassuring for parents and clinicians. Long-term monitoring, developmental screening, and tailored counselling for parents of ART-conceived children might be useful.