Iodinated contrast is commonly used in hysterosalpingography (HSG), a diagnostic tool in fertility work-up. This study aims to investigate the safety of contrast media used during HSG by evaluating the long-term effects on the neurodevelopment of offspring 6-8 years after exposure to iodinated contrast media.

Background: Iodinated contrast is commonly used in hysterosalpingography (HSG), a diagnostic tool in fertility work-up. Yet excessive iodine may pool for a long time in the body, crosses the placenta easily, and can induce hypothyroidism in both mothers and foetuses. Inadequate supplies of thyroid hormones have previously been associated with neurocognitive impairments in offspring. Considering the widespread use of iodinated contrast during fertility work-up, the potential iatrogenic effect of preconceptional iodine exposure on the brain development of the offspring needs to be addressed urgently.

Objectives: This project aims to investigate the safety of contrast media used during HSG by evaluating the long-term effects on the neurodevelopment of offspring 6-8 years after exposure to iodinated contrast media. To do this, the investigators will follow up on a cohort of offspring conceived during the H2Oil randomised controlled trial (NTR 3270), which was set up to evaluate the effect of using water- or oil-based media during HSG on pregnancy rates.

Methods: The study team have previously obtained parental permission for follow-up research in 140 children conceived during the H2Oil study <6 months after exposure to iodine during the HSG. The investigators will conduct comprehensive an in-depth outcome assessment of intelligence, neurocognitive development, school performance, and behavioural functioning.

Relevance: Using this diverse range of methods, the investigators expect to be the first to shed light on the long-term iatrogenic consequences of using iodinated contrast just before conception on the neurodevelopment of their offspring. The findings of this study will have implications for current clinical practice, where HSG is readily used in subfertile women, and will be used to inform the Dutch guidelines for fertility work-up.

Inclusion Criteria:

• Children conceived after the mother underwent HSG procedure in the context of the H2Oil trial (2012-2014)
• Children must be conceived <6 months after the HSG procedure
• Parents must have given consent for recontacting for follow up research

Exclusion Criteria:

• Children conceived after the mother underwent HSG procedure that was not part of the H2Oil trial
• Children conceived >6 months after the HSG procedure
• Children whose parents did not give permission to be recontacted for follow up research
• Children that are not able to comprehend the instructions at the time of assessment
• Absence or withdrawal of written informed consent
• Inability to comprehend testing instructions at time of assessment
• Severe motor disability that interferes with outcome assessment at time of assessment
• Documented and/or parent-reported diagnosis of a neurological disorder
• Somatic disorders known to affect the outcome assessments at time of assessment

Children born to mothers who participated in the original H2Oil study (NTR3270), a multicentre randomised controlled trial on oil- versus water-based HSG in 2012-2014 whose parents gave consent to be contacted for follow up studies (n=140).