Department of Reproductive Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1118, 1081 HV, Amsterdam, the Netherlands.
Department of Obstetrics and Gynaecology, Máxima MC, De Run 4600, 5504 DB, Veldhoven, the Netherlands.
Hum Reprod. 2020 May 1;35(5):1159-1167. doi: 10.1093/humrep/deaa049.
Does exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast?
Preconceptional HSG with iodinated contrast did not influence the neonatal thyroid function.
HSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG.
STUDY DESIGN, SIZE, DURATION: This is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of ≤ -0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups.
Data were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0-96.0] in the oil group and 90.0 nmol/l [78.0-106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH.The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0-11.8] in the oil-group and 10.0 ml [IQR, 7.5-14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37).
LIMITATIONS, REASONS FOR CAUTION: A relatively small sample size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking.
As HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment.
STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (Academic Medical Center and VU University Medical Center) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and intrepretation of the data. I.R. reports receiving travel fee from Guerbet. C.B.L. reports speakers fee from Ferring in the past and research grants from Ferring, Merck and Guerbet. K.D. reports receiving travel fee and speakers fee from Guerbet. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. V.M. reports receiving travel fee and speakers fee as well as research grants from Guerbet. The other authors do not report conflicts of interest.
Netherlands Trial Register NTR 7526 (Neonates born after the H2Oil study), NTR 3270 (original H2Oil study), www.trialregister.nl.
与碘水基造影剂相比，碘油基造影剂在受孕前的子宫输卵管造影（HSG）中是否会影响新生儿甲状腺功能？
受孕前使用碘造影剂不会影响新生儿的甲状腺功能。
HSG 是生育检查中常用的一种输卵管通畅性测试方法，可使用油基或水基造影剂。油基造影剂含有的碘比水基造影剂多。先前在东亚人群中的一项研究发现，与 HSG 期间使用油基造影剂的女性相比，在 HSG 期间接触高剂量油基造影剂的母亲所生的新生儿患先天性甲状腺功能减退症（CH）的风险增加。
研究设计、规模、持续时间：这是 H2Oil 研究的回顾性数据分析，这是一项随机对照试验（RCT），比较了生育检查中使用油基与水基造影剂进行 HSG。与油基 HSG 后，214 名女性在 6 个月内继续妊娠并分娩活产儿，而与水基 HSG 后，155 名女性继续妊娠并分娩活产儿。
参与者/材料、设置、方法：在 369 名活产婴儿中，有 208 名同意接受未来研究，138 名提供了同意收集其子女甲状腺功能检查数据的知情同意书（n=140）。这些儿童的甲状腺功能检查结果从荷兰新生儿筛查计划中获得，该计划包括对所有新生儿进行总甲状腺素（T4）评估，随后仅对 T4 水平≤-0.8 SD 评分的婴儿进行促甲状腺激素检测。此外，还比较了两组研究中使用的造影剂量和 HSG 与受孕之间的时间间隔。
从接受油基（n=76）或水基（n=64）造影剂 HSG 后的 140 名新生儿中收集了数据。油组的中位 T4 浓度为 87.0 nmol/l [76.0-96.0]，水组为 90.0 nmol/l [78.0-106.0]（P=0.13）。没有新生儿出现 CH 的阳性筛查结果。油组使用的造影剂中位数为 9.0 ml [四分位距（IQR），6.0-11.8]，水组为 10.0 ml [IQR，7.5-14.0]（P=0.43）。没有发现造影剂量对 T4 浓度的造影剂组效应的影响（交互作用 P 值，0.37）。
局限性、谨慎原因：样本量相对较小和随访时可能存在流失是这项研究的局限性。尽管我们的结果表明，碘造影剂用于 HSG 对后代是安全的，但不能排除碘造影剂对母体甲状腺功能的影响对后代神经发育的影响，因为缺乏 HSG 后和受孕期间母体甲状腺功能的数据。
由于油基 HSG 不会影响后代的甲状腺功能，因此没有理由拒绝为接受 HSG 的不孕女性使用这种造影剂。未来的研究应调查碘造影剂是否会影响受孕前的母体甲状腺功能，进而影响后代的神经发育。
研究资金/利益冲突：这项研究没有获得资金。原始的 H2Oil RCT 是一项由两个学术机构（阿姆斯特丹大学医学中心和 VU 大学医学中心）发起的研究，由这两个学术机构资助。资助者在研究设计、数据收集、分析和解释方面没有作用。IR 报告曾收到来自 Guerbet 的旅行费用。CBL 报告过去曾收到过来自 Ferring 的演讲费和研究资助，现在收到过来自 Ferring 和 Guerbet 的研究资助。KD 报告收到来自 Guerbet 的旅行费和演讲费。BWM 得到了 NHMRC 从业者奖学金（GNT1082548）的支持。BWM 报告与 ObsEva、Merck KGaA 和 Guerbet 有咨询关系，并从 Merck KGaA 和 Guerbet 获得旅行和研究资助。其他作者没有利益冲突。
荷兰试验登记处 NTR 7526（H2Oil 研究后出生的新生儿），NTR 3270（原始 H2Oil 研究），www.trialregister.nl。
