Children's neurodevelopment at school age after hysterosalpingography with iodinated contrast: a cohort study

PURPOSE: Hysterosalpingography (HSG) with iodinated contrast used during fertility work-up can transiently disrupt thyroid function during early neurodevelopment due to the Wolff-Chaikoff effect. We examined neurodevelopmental outcomes in school-aged children conceived after HSG.

METHODS: 69 children conceived within <6 months after HSG with oil-based (iodine content: 480mg/ml) or water-based contrast (iodine content: 250 mg/ml) within the H2Oil randomised clinical trial (NCT05168228) were compared with children of similar age, sex, and parental education conceived without fertility treatments (n=44) (NTR9574). Primary outcomes were intelligence quotient (IQ), behaviour, and academic performance. Secondary outcomes were neurocognitive domain scores. We used linear regression adjusted for age, sex, and parental education, applying false discovery rate correction. We examined timing subgroups (<4, 4-12, >12 weeks post-HSG) versus the control group using polynomial contrasts.

RESULTS: Children conceived within 6 months after HSG had lower mean IQ (104.3 versus 113.1; adjusted estimate: -6.81; 95%CI -10.97 to -2.65; p=0.02) and lower information processing and attention control scores (-0.52 SD; 95%CI -0.84 to -0.19; p=0.02). IQ scores were lowest when conception occurred shortly after HSG, while children conceived >12 weeks after HSG did not differ from the control group. No differences were observed for behaviour or academic performance. Sensitivity analyses did not support confounding by prematurity, low birth weight, maternal smoking during pregnancy, or conception using assisted reproductive technologies.

CONCLUSION: Replication in larger, adequately powered cohorts is needed to assess the potential long-term implications of HSG with iodinated contrast for neurodevelopmental outcomes of the offspring.