P-756 Neurodevelopmental outcomes at school-age after conception with hysterosalpingography using iodinated contrast media - follow-up of the nationwide multicentre H2Oil trial
Authors: Keestra S , Kooper C , Van Welie N , Dreyer K , Van Eekelen R , Roseboom T , Oosterlaan J , Mol B  W , Finken M  J J , Mijatovic V , Königs M 
Published: July 2024

Abstract

Study question
How does conception &lt;6 months after hysterosalpingography (HSG) with iodinated contrast media affect the neurodevelopment of the offspring compared to naturally-conceived peers at a school-age?

Summary answer
Children conceived &lt;6 months after HSG with iodinated contrast media perform lower on intelligence tests and information processing and attention control compared to naturally-conceived peers.

What is known already
Tubal patency in subfertile women is commonly assessed using hysterosalpingography (HSG), but the potential risks of exposure to high iodine content in contrast media used remains unknown. Exposure to iodine excess can cause transient reduction in thyroid hormone synthesis due to the Wolff-Chaikoff effect. Thyroid hormone sufficiency in early pregnancy is vital for children’s neurodevelopment. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone supply could jeopardize children’s neurodevelopment.

Study design, size, duration
We evaluated neurodevelopmental outcomes of 6–9-year-old children conceived &lt;6 months after HSG with oil-based (iodine content: 480mg/ml) or water-based contrast (iodine content: 240-300mg/ml) in a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). Naturally-conceived children (n = 44) with similar age, sex and parental education were used as a comparison group (NTR9574). We also compared children conceived &lt;4w, 4-12w, &gt;12w after HSG with those conceived naturally. The study took place January 2022 until November 2023.

Participants/materials, setting, methods
We contacted 140 mothers from the H2Oil trial, 69 children conceived &lt;6m after HSG participated, and parallelly we recruited 44 naturally-conceived children. Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behavioural functioning (SDQ and SWAN, administered to parents and teachers), and academic performance. Secondary outcomes were neurocognitive function assessed by a battery of computerized tests. We used linear regression adjusted for age, sex, and parental education and applied FDR correction.

Main results and the role of chance
Compared to naturally conceived children, children conceived &lt;6m after HSG had lower performance on intelligence tests (-6.81; 95%CI-10.97 to -2.65; p = 0.02) and the neurocognitive domain Processing & Control (-0.52; 95%CI-0.84 to -0.19; p = 0.02), with functions relating to information processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. Considering time between HSG and conception, intelligence scores were lower for children conceived &lt;4w after HSG compared to naturally-conceived peers (-11.47; 95%CI-17.98 to -4.95; p = 0.03), while no significant differences were found for the groups of children conceived 4-12 weeks after HSG (-7.17; 95%CI -12.28 to -2.06; p = 0.10) or &gt; 12 weeks after HSG (-4.20; 95%CI -9.33 to 0.94; p = 0.52). The findings of this study warrant replication in larger independent samples in order to evaluate the long-term neurodevelopment of children conceived after HSG with iodinated contrast media.

Limitations, reasons for caution
We aimed to recruit 64 children for each group, but our study was not sufficiently powered for small- and medium-sized differences. We did not collect information on the thyroid or iodine status of the mothers following HSG, and there is limited knowledge about pharmacokinetics of iodinated contrast media in humans.

Wider implications of the findings
Replication studies with are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children’s neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted.

Trial registration number
NCT05168228