目的:在子宫输卵管造影术(HSG)中,与暴露于水性替代药物相比,先入性暴露于油碘造影剂是否会影响儿童的神经发育?
结论:我们的研究发现,与水性替代药物相比,在HSG中,先入性暴露于油碘造影剂对儿童的神经发育没有大的影响。
背景:HSG在女性生育力检查中被广泛用作诊断工具。油基碘化对比剂的输卵管冲洗已被证明可以提高不明原因不孕症夫妇的生育结果,与水基替代方案相比,增加了怀孕和活产的机会。然而,油基造影剂含有较高剂量的碘,半衰期较长,人们担心碘化造影剂会影响女性的碘状况,并导致母亲和/或胎儿的暂时性(亚)临床甲状腺功能减退症。考虑到甲状腺激素对胚胎和胎儿大脑发育至关重要,使用油基造影剂可能会增加HSG后不久受孕儿童神经发育受损的风险.在这里,我们研究了HSG后受孕的学龄儿童的神经发育结果。
方法:这是H2Oil试验的长期随访,该试验在HSG期间使用油基或水基造影剂(荷兰;2012-2014;NTR3270)。在研究中,在HSG后6个月出生的369名儿童中,我们联系了140名儿童的母亲,他们同意接受随访。后续研究于2022年1月至7月进行(NCT05168228)。
方法:该研究包括69名年龄在6-9岁之间的儿童,他们在HSG后使用油基(n=42)或水基对比剂(n=27)受孕。评估有针对性的智力(韦克斯勒儿童智力量表),神经认知结果(计算机化神经认知测试),行为功能(家长和教师问卷),和学习成绩。线性回归模型,根据年龄调整,性别,和父母的教育程度被用来比较群体。
结果:油性造影剂HSG后母亲所生的学龄儿童与水性造影剂HSG后母亲所生的儿童没有显着差异,关于智力,神经认知功能,行为功能,或者学业成绩,除了暴露于基于油的对比先入为主的儿童的视觉运动整合功能表现更好。在对多重比较进行探索性校正后,组间差异无统计学意义。
结论:这项随访研究的样本量小限制了统计能力。这项研究提供了证据,证明了两种造影剂类型的先入性暴露之间没有大的差异,但与没有先入性暴露于HSG的自然受孕儿童相比,不排除对神经发育的更微妙的影响。
结论:这项研究有助于我们了解不同类型的碘化造影剂在生育检查中的长期影响,这表明选择油基而不是水基碘化造影剂不太可能对HSG后不久受孕的儿童的长期神经发育结局产生重大影响。然而,进一步的研究应集中在HSG期间碘暴露的整体安全性,将HSG后受孕的儿童与自然受孕的儿童进行比较,因为这两种类型的造影剂都含有大量的碘。
背景:最初的H2Oil随机对照试验是一项由研究者发起的研究,该研究由两家学术医院资助,现在合并为阿姆斯特丹大学医学中心。当前的后续研究(Neuro-H2Oil)由阿姆斯特丹生殖与发展(AR&D)研究所授予作者的研究资助资助。S.K.由阿姆斯特丹UMC的AMCMD/博士奖学金资助。S.K.报告在民间社会组织“基本药物和人民健康运动联盟大学”中担任自愿角色。V.M.报告收到Guerbet的差旅费和演讲者费以及研究补助金,默克和费林。K.D.报告收到了Guerbet的差旅费和演讲费以及研究补助金。BWM由NHMRC调查员资助(GNT1176437)和报告咨询公司支持,默克公司的旅行支持和研究经费,Organon和Norgine的顾问,并持有ObsEva的股票。其他作者报告没有利益冲突。
背景:NCT05168228。
OBJECTIVE: Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children\'s neurodevelopment compared with exposure to water-based alternatives?
CONCLUSIONS: Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives.
BACKGROUND: HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women\'s iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG.
METHODS: This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012-2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228).
METHODS: The study included 69 children aged 6-9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups.
RESULTS: School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant.
CONCLUSIONS: The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG.
CONCLUSIONS: This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine.
BACKGROUND: The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People\'s Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest.
BACKGROUND: NCT05168228.