Evaluating the Long-term Neurocognitive Effects of Preconceptional Exposure to Iodinated Contrast on the Offspring

Neurocognitive Disorders Clinical Trial

— Neuro-H2Oil  

Official title:

Evaluating the Long-term Neurocognitive Effects of Preconceptional Exposure to Iodinated Contrast During Hysterosalpingography (HSG) on the Offspring of the H2Oil Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05168228
• Other study ID #: 2021.0448
• Status: Active, not recruiting
• Start date: January 26, 2022
• Est. completion date: August 1, 2022

Study information

• Verified date: January 2022
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: August 1, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Neurocognitive Disorders

Intervention

Procedure:
• Oil- versus waterbased contrast in hysterosalpingography (HSG)
The Neuro-H2Oil study looks at the offspring of the H2Oil study, a randomized controlled trial (RCT) comparing hysterosalpingography (HSG) with oil- versus water-based contrast during fertility work-up. For more information please see NTR 3270 (original H2Oil study), www.trialregister.nl. The control group is the Database for Controls in Neuroscience Studies (D-CNS), registered as NL9574 (https://www.trialregister.nl/trial/9574).

Locations

Country	Name	City	State
Netherlands	Emma Kinderziekenhuis	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
VU University Medical Center	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

Dreyer K, van Rijswijk J, Mijatovic V, Goddijn M, Verhoeve HR, van Rooij IAJ, Hoek A, Bourdrez P, Nap AW, Rijnsaardt-Lukassen HGM, Timmerman CCM, Kaplan M, Hooker AB, Gijsen AP, van Golde R, van Heteren CF, Sluijmer AV, de Bruin JP, Smeenk JMJ, de Boer JAM, Scheenjes E, Duijn AEJ, Mozes A, Pelinck MJ, Traas MAF, van Hooff MHA, van Unnik GA, de Koning CH, van Geloven N, Twisk JWR, Hompes PGA, Mol BWJ. Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women. N Engl J Med. 2017 May 25;376(21):2043-2052. doi: 10.1056/NEJMoa1612337. Epub 2017 May 18. — View Citation

Königs M, Verhoog EM, Oosterlaan J. Exploring the neurocognome: Neurocognitive network organization in healthy young adults. Cortex. 2021 Oct;143:12-28. doi: 10.1016/j.cortex.2021.06.011. Epub 2021 Jul 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	School performance	Longitudinal data on school performance will be collected using standardised tests from the pupil monitoring system developed by the Dutch National Institute for Educational Measurement (CITO-test). CITO-tests are used to assess children's academic performance (reading comprehension, spelling, and arithmetic performance) in primary schools in the Netherlands.	Between the ages of 4-12, up to 12 years
Primary	Intelligence	General intelligence will be assessed using a shortened Fifth version of the Wechsler Intelligence Scale for Children. Full-scale IQ (FSIQ) will be estimated using the subtests Vocabulary, Similarities, Matrix Reasoning, and Block Design.	1 Day
Primary	Behavioural functioning evaluated through the Strengths and Difficulties Questionnaire (SDQ).	Behavioural functioning will be evaluated through the Strengths and Difficulties Questionnaire (SDQ). Both parents and teachers will fill in the SDQ.	1 Day
Primary	Behavioural functioning evaluated through the Strengths and Weaknesses of ADHD Symptoms And Normal behaviour (SWAN) scale.	Behavioural functioning will be evaluated will be evaluated using the Strengths and Weaknesses of ADHD Symptoms And Normal behaviour (SWAN) scale. Both parents and teachers will fill in the SWAN scale.	1 Day
Secondary	Visuomotor integration	Visuomotor integration will be assessed using a Track & Trace task of the Emma Toolbox for Neurocognitive Functioning, which is an in-house designed battery of computerised tests for assessing different neurocognitive domains.	1 Day
Secondary	Processing & Control	Processing & Control will be assessed using an Attention Network Test of the Emma Toolbox for Neurocognitive Functioning, which is an in-house designed battery of computerised tests for assessing different neurocognitive domains.	1 Day
Secondary	Visual Memory	Visual Memory will be assessed using an Location Learning Test of the Emma Toolbox for Neurocognitive Functioning, which is an in-house designed battery of computerised tests for assessing different neurocognitive domains.	1 Day
Secondary	Verbal Memory	Verbal Memory will be assessed using a Rey Auditory Verbal Learning Test (Dutch Version) of the Emma Toolbox for Neurocognitive Functioning, which is an in-house designed battery of computerised tests for assessing different neurocognitive domains.	1 Day
Secondary	Visual Working Memory	Visual Working Memory will be assessed using a Klinberg task of the Emma Toolbox for Neurocognitive Functioning, which is an in-house designed battery of computerised tests for assessing different neurocognitive domains.	1 Day
Secondary	Verbal Working Memory	Verbal Working Memory will be assessed using a Digit Span task of the Emma Toolbox for Neurocognitive Functioning, which is an in-house designed battery of computerised tests for assessing different neurocognitive domains.	1 Day