Letter to the editor: Safety of contrast-enhanced ultrasound using microbubbles in human pregnancy: A scoping review

Dear Editor,

We would like to comment Dassen et al. [1] for the recent scoping review of the safety of ultrasound and contrast agents during pregnancy. As the first literature review on this crucial topic, their study provides an important and valuable contribution to the field of medical imaging.

The review offers a comprehensive summary of the available evidence, which will undoubtedly serve as a valuable reference for healthcare professionals, researchers, and policymakers concerned with pregnant patient safety. However, despite its strengths, we have some concerns regarding the methodology employed in the review, which we believe may limit the reliability and applicability of the findings.

While the methodology follows the principles of a scoping review, it would be beneficial to explain why this approach was selected over a systematic review. A systematic review could provide a more in-depth assessment of the quality of evidence, and clarifying this decision would strengthen the understanding of the research objectives [2].

One of the key methodological concerns with this review lies in the inclusion criteria for the studies. Notably, case reports were included without any assessment of their quality. While case reports can provide valuable anecdotal evidence, their methodological rigor is often limited, and they should be interpreted with caution, especially in the context of a scoping review aimed at synthesizing reliable evidence on safety [3]. Additionally, the inclusion of studies where only the abstract was available is problematic. Abstracts typically provide a limited amount of information and may omit critical details regarding study design, patient outcomes, and potential complications. This lack of complete data makes it challenging to accurately assess the overall safety of contrast agents used in ultrasound, particularly in terms of rare or delayed adverse events. Drawing conclusions about the absence of complications based on such limited evidence is risky, especially when these studies do not explicitly state that no complications occurred. Without clear documentation of safety outcomes, it is difficult to determine whether the absence of reported complications truly reflects the safety of the procedures or simply incomplete reporting. These factors highlight the need for a more rigorous approach to study selection, ensuring that the evidence base is both robust and transparent when evaluating the safety profile of contrast-enhanced ultrasound.

A third significant concern relates to the way certain studies have reported safety outcomes, focusing primarily on the mode and term of delivery as key indicators. While these are undoubtedly important aspects of pregnancy outcomes, their interpretation as safety data is problematic, particularly in the context of major maternal pathologies. For instance, in cases where the mother presents with severe medical conditions, the mode and timing of delivery may be influenced more by the underlying maternal pathology than by the use of contrast agents during ultrasound. Therefore, these outcomes cannot reliably be considered as direct indicators of the safety of contrast agents, and drawing conclusions about safety based on these factors is highly questionable. Furthermore, there is a noticeable gap in the review regarding neonatal and fetal safety outcomes, which should ideally be described in relation to the gestational age at which the contrast agent was administered. The timing of exposure to contrast agents could have significant implications for fetal development and neonatal outcomes, and this critical factor is largely overlooked in the included studies. A more thorough and nuanced analysis of fetal and neonatal safety, taking into account gestational age and other relevant factors, is necessary to provide a comprehensive understanding of the risks associated with the use of contrast agents in ultrasound. Thus, relying solely on delivery mode and term without considering these broader safety outcomes limits the applicability of the review's conclusions.

In conclusion, while Dassen et al.’s review [1] provides valuable insight into the safety of ultrasound and contrast agents, several methodological issues limit the reliability of its findings. Including studies without explicit safety outcomes creates a misleading impression of a more robust evidence base than actually exists. A more rigorous study selection and comprehensive analysis of neonatal and fetal safety would strengthen the review's conclusions and provide clearer guidance regarding the use of contrast agents in clinical practice. We hope that future research will address these limitations and build upon the foundation provided by this review.

Publication History

Received: 22 October 2024

Accepted: 13 November 2024

Article published online:
13 December 2024

• References

• 1 Dassen S, Monen L, Oei G. et al. Safety of contrast-enhanced ultrasound using microbubbles in human pregnancy: A scoping review. Ultraschall in Med
• 2 Page M, Moher D, Bossuyt P. et al. PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160
• 3 Gagnier JJ, Kienle G, Altman DG. et al. The CARE guidelines: consensus-based clinical case reporting guideline development. Journal of Medical Case Reports 2013; 7 (01) 223